Scientific research and medical studies

Medical studies and literature about the therapies we use in the Treatment of severe depression, anxieties, obsessive-compulsive disorder, neurological disorders, Alzheimers and more. Studies about Ketaminetherapy for depression, rTMS during pregnancy and other therapy methods like EMDR, virtual reality, HRV Biofeedback, tDCS and Neurofeedback.

Studies about the use of Ketamine

Background. There are few studies on ketamine and its properties to work with addiction (alcohol, opioid, cannabis, and cocaine use disorder). The studies show that ketamine treatment can help reduce craving and support abstinence [14]. Hypnotherapy is an evidence-based treatment gaining popularity for treating addiction, but not everybody can be hypnotized due to different levels of suggestibility. Our clinical practice has observed that people who are not highly hypnotizable, such as patients with obsessive-compulsive disorders, become more suggestible accompanied by our newly developed method called “Ketamine-Hypnosis package” (KHP). In this case report and study, we want to explore and evaluate the potential of KHP in working with addiction. Diagnostic and a qualitative content analysis should give profound insights into the treatment process and method.

Case Report. The subject is a 48-year-old male German Social Worker with treatment-resistant depression, suicidal thoughts, obsessive behavior, and several forms of addiction. The patient received a 10-day treatment at Instituto Dr. Scheib, with Diagnostic, rTMS, neurofeedback, and four sessions of KHP. Every Ketamine infusion remained with a standard dose of 0.5 mg/kg R-Ketamine for about 45 minutes.

Results. Primary outcome measures included change in depression as measured by the BDI-II with a reduction from 44, highly depressed, to a score of 3, no depression, and change of symptoms measured by the SCL-90 R that showed a clear reduction in almost every factor vs. baseline. The qualitative content analysis of the KHP sessions identified nine categories; Setting, Intervention, Body, Control, Feelings, Insights/Realizations, Addiction, Depression and Imagery. QEEG measurements before and after treatment showed a pattern of over-representation of slow brain activity with closed eyes, which can be observed in fluctuating concentration and volatile impulse control. Follow-Up Data with BDI-II one week after treatment showed factor 3 and 5 weeks after treatment factor 15.

Conclusions. The 10-day-treatment program improved numerous important treatment outcomes in one substance-dependent adult engaged in hypnotherapeutic modification, including promoting less substance abuse, diminishing craving, and reducing the risk of relapse. Further research is needed to replicate these promising results in a larger sample.

READ THE COMPLETE STUDY

Basant Pradhan, Garrett Rossi



Abstract

Opioid addiction in the United States currently presents a national crisis despite availability of different treatments. Prior findings suggest that both repetitive transcranial magnetic stimulation (rTMS) and subanesthetic dose of ketamine are efficacious in patients with opioid use disorders (OUD) when administered in isolation. However, their therapeutic value may be undermined by varying clinical responses that tend to dissipate with treatment cessation. There has been no study to date that has used a combination of both for OUD, and there are still many unanswered questions with respect to both. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation of memories) therapy attempts to alter the expression of emotionally charged memories such as traumatic memories, and has been successfully tried in chronic post-traumatic stress disorder (PTSD) and in combination with memory-altering pharmacotherapy like ketamine infusion. By a combination of extinction and reconsolidation of memory approaches, TIMBER works to not over-flood and/or retraumatize as is seen in other treatment approaches. TIMBER involves a balanced combination of both the memory extinction and memory reconsolidation approaches (rather than extinction-only approaches) which explains its superior efficacy in PTSD and benefit in substance use disorders.

Introduction

Opioid addiction in the United States (US) currently presents a national crisis despite availability of different treatments. Over 2.1 million people were diagnosed with opioid use disorder (OUD) in 2016 [1]. Prior findings suggest that both repetitive transcranial magnetic stimulation (rTMS) and subanesthetic dose of ketamine are efficacious in patients with OUD when administered in isolation [1-4]. However, their therapeutic value may be undermined by varying clinical responses that tend to dissipate with treatment cessation. There has been no study to date that has used a combination of both for OUD, and there are still many unanswered questions with respect to both. Trauma Interventions using Mindfulness Based Extinction and Reconsolidation of memories (TIMBER) attempts to alter the expression of emotionally charged memories such as traumatic memories, and has been successfully tried in chronic post-traumatic stress disorder (PTSD) alone, or in combination with memory-altering pharmacotherapy like ketamine infusion [5-7]. By a combination of extinction and re-consolidation of memory approaches, TIMBER works to not over-flood and/or re-traumatize as is seen in other treatment approaches. At the present time, TIMBER has been shown to be efficacious in targeting trauma memories and their expressions in PTSD patients [6]

TIMBER uses all eight limbs of Yoga including the focused attention meditation and mindfulness meditation, the five-factor model of trauma or addiction experience, and integrates the principles of cognitive behavioral therapy (CBT) (mindfulness-based graded exposure therapy: MB-GET) with the neurobiology of emotionally charged traumatic or addiction memories. With respect to applying the translational model of TIMBER for drug addiction, the key steps are:

1. Inducing a mindful state (calm, alert but non-reactive) by use of a standardized meditation protocol (StaMP).

2. Creating drug-cues evoked controlled arousal response using a scripted brief narrative of the addiction experience by using the Buddha’s Five Factor Model (thoughts, feelings, memories, sensations/perceptions, and urges/impulses related to the addiction experience).

3. Using the mindfulness-based graded exposure therapy (MB-GET) and the TIMBER methods to decrease the arousal responses.

4. Using the already created mindful state to cognitively reprocess and reappraise the drug-related emotionally charged memories so that the drug-related emotionally charged memories are extinguished and de-conditioned from the cues and re-consolidated/updated as new memories.

TIMBER involves a balanced combination of both the memory extinction and memory reconsolidation approaches (rather than extinction only approaches) which likely explains its superior efficacies in PTSD and possibly in our future studies on drug addiction as well. The case series presented here is the extended application of the proof of concept model of TIMBER in three patients with chronic OUD.

Materials & Methods

The study is an open-label proof of concept study designed to test the feasibility and efficacy of ketamine, rTMS, and TIMBER in patients with OUD. The study included three patients all with a diagnosis of OUD. The primary outcome measure was percent reduction in cravings using the opiate use craving scale from baseline to the fifth rTMS session.

The following interventions were used:

1. Ketamine was given as a single infusion of 0.75 mg/kg weight-based dose capped at 745 mg total, administered over a 45 minute period. A one week washout period followed prior to the start of rTMS.

2. rTMS was performed for five sessions of 10 Hz and 3000 stimulation pulses applied to the right dorsolateral pre-frontal cortex (DLPFC) over one to two weeks.

3. Five sessions of TIMBER mindfulness-based therapy was carried out during the same two weeks period that rTMS was performed.

4. Home practice was then carried out two times daily with additional sessions on an as-needed basis whenever cravings were present.

Cravings were measured using the Opiate Craving Scale. Arousal responses were measured by a multi-system biofeedback bundle that comprised of real-time electroencephalogram (EEG), heart rate variability, and breath response pattern guided focused attention and mindfulness meditation practice (three minutes before rTMS, 21 minutes during, and three minutes after administration of rTMS).

Results

In our open-label pilot study sample that consisted of three subjects with opiate use disorder (two with heroin use disorder and one with oxycodone use disorder), the participants rated their craving on the Opiate Craving Scale (OCS: scores range 0-30), five minutes before and five minutes after the rTMS stimulation [8]. They rated their level of mindfulness pre-infusion baseline and after completing five sessions of TMS+mindfulness using the Assessment Scale for Mindfulness Interventions (ASMI) [6,7].

In these three subjects, at baseline, the mean OCS was 23.6 (SD 4.2), which indicates a high level. The OCS reduced to 8.2 (SD 2.7) after five sessions of TMS and mindfulness. Similarly, at baseline, their mean ASMI was 28.45 (SD 9.61). After five sessions of TMS and mindfulness, the mean ASMI was 49. 67 (SD 7.72) indicating a significant increase in mindfulness (Table 1).

Patient ProfileCravings at BaselineCravings at session FiveCraving Percent Decrease After 5 SessionsMindfulness at BaselineMindfulness at Session 5Mindfulness percent Increase After 5- sessionst-test P-Value (2-tailed), and 95% CI
Combined Patient DataOCS: 23.66 +/- 3.21OCS: 8.33 +/- 2.565.7%ASMI: 29 +/- 3.6ASMI: 49.33 +/- 7.3741.21%For OCS: P=0.002, t=6.5, 95% CI=8.8 to 21.85   For ASMI: P=0.01 T= 4.2, 95% CI= 33.48 to 7.18
 

Discussion

Collectively all of these therapeutic interventions show promise as individual treatments for maintenance of abstinence in OUD, particularly improvement in cravings and increased motivation to quit. Significant long-term improvements in complete abstinence have been demonstrated with the use of ketamine following extended inpatient treatment [3,4], and ketamine reduced physiological response during opioid withdrawal [9]. However, these studies on the use of ketamine are limited by their use of low-dose ketamine as the comparison group rather than a true placebo. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique currently approved for major depressive disorder. rTMS is currently being pursued as a treatment for substance use disorder. Preliminary data looking at treatment with rTMS to the dorsolateral pre-frontal cortex (DLPFC) has shown reduction in cravings in alcohol, cocaine, and nicotine use disorders [2]. Single session rTMS studies have demonstrated that applying excitatory rTMS to the DLPFC can decrease cue-induced craving in nicotine, cocaine, and alcohol use disordered populations. The mechanism of rTMS success in treating addiction is thought to involve increased dopamine function in the shell region of the nucleus accumbuns [10].

Single session studies have only found small temporary reductions in craving, however more frequent sessions could lead to longer durations and greater reductions in cravings. The largest such clinical trial (n=130 smokers) demonstrated that 13 sessions of DLPFC rTMS resulted in six month tobacco abstinence rates of 33% [2]. Trauma memories lay at the core of the pathogenesis of PTSD. TIMBER therapy attempts to alter the expression of emotionally charged memories such as traumatic memories, and has been successfully tried in chronic PTSD alone or in combination with memory altering pharmacotherapy like ketamine infusion [5,7]. There are many similarities between the emotionally charged memories common in PTSD, and the emotionally charged memories associated with addiction. Exposure to environmental cues such as people, places, or drug paraphernalia lead to a state of arousal and strong emotional response that often results in relapse for patients attempting to maintain sobriety. The use of mindfulness-based graded exposure therapy (MB-GET) and the TIMBER methods to decrease the arousal responses will extinguish drug-related emotionally charged memories while replacing them with new more adaptive memories. TIMBER aims to restructure cognitions and emotions, which prevents reactivity of the underlying memories in trauma [5].

A number of important questions remain. It is unclear how each of these modalities will function in combination and in comparison to a true placebo group. It is unclear what role baseline levels of desire to quit, motivation for treatment, and prior periods of abstinence have on the achievement and maintenance of abstinence. The groups chosen for the ketamine studies were treatment-seeking and completed three months of residential treatment prior to treatment with ketamine infusion [3,4]. The abstinence rates at one- and two-year follow-up for ketamine are promising; unique genetic and socioeconomic factors must be considered [3,4]. To date there is limited work examining the effect of rTMS on craving in OUD. However, preliminary data indicates significant possibility of reduced craving with multiple sessions of rTMS. While TIMBER methods have been successfully used to treat PTSD, this method has yet to be applied to substance use disorders on a mass scale. TIMBER involves a balanced combination of both the memory extinction and memory reconsolidation approaches (rather than extinction only approaches) and has possible implications for substance use disorder. 

Conclusions

Combination therapy with ketamine, rTMS and TIMBER is feasible in patients with OUD. Although an open-label proof of concept study, the data suggests that the combination therapy reduces craving, promotes abstinence, and reduces the amount used in patients with OUD. Combination therapy allows patients to be actively involved in their care by engaging in meditative therapy-based techniques that directly result in a calmer state of mind. This protocol allows concurrent implementation of three individually effective interventions in combination for a compounding synergistic effect. 

Link to publication: https://europepmc.org/article/pmc/pmc7779150#free-full-text

Journal of Psychiatric Research

Available online 11 December 2020

Authors: Jiaqi Xiong1 Orly LipsitzDavid Chen-LiJoshua  D.Rosenblat123 Nelson  B.RodriguesIsabelle CarvalhoLeanna M.W. LuiHartej Gill34 Flora NarsiRodrigo B. MansurYena LeeRoger S. McIntyre1234

https://doi.org/10.1016/j.jpsychires.2020.12.038Get rights and content

Highlights

• Single-dose intravenous ketamine/intranasal esketamine has rapid and robust acute effects in reducing suicidal ideation (SI).

• Future high-quality research on the anti-SI efficacy of alternative administration routes (i.e. intramuscular, subcutaneous, oral/sublingual) and formulations of ketamine is needed.

• Dosage, routes of administration, and formulations are factors to be considered for optimizing SI treatment using ketamine.

Abstract

The efficacy of ketamine in reducing suicidal ideation (SI) has been previously reported. We aimed to evaluate acute anti-SI effects of single-dose ketamine in different formulations/routes of administration by pooling results from randomized controlled trials (RCTs). A systematic search was conducted on Cochrane, Embase, Medline, and PubMed from inception to July 1st, 2020. Studies were selected based on pre-determined eligibility criteria. Effect sizes of different formulations/routes at various time points were computed using random-effects models. With data from nine eligible RCTs (n=197), the pooled effect size for anti-SI effects at 24-hour time point was 1.035 (N=6, CI: 0.793 to 1.277, p<0.001) for intravenous (IV) racemic ketamine and 1.309 (N=1, CI: 0.857 to 1.761, p<0.001) for intranasal (IN) esketamine. An additional five RCTs were available for qualitative analysis. RCTs were identified for oral/sublingual ketamine for depression, however, none of these trials reported anti-SI effects preventing quantitative analysis for these routes of delivery. No RCTs for intramuscular (IM) ketamine were identified. The findings suggest that single-dose IV ketamine/IN esketamine is associated with robust reductions in suicidal thoughts at 2-hour, 4-hour, and 24-hour post-intervention. In addition, future studies on IM/oral/sublingual ketamine and comparative studies are warranted to evaluate the anti-SI efficacy of distinct formulations and routes of administration.

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 105, 8 March 2021, 110126

Authors: Orly Lipsitzab Roger  S.McIntyreabcd Nelson  B.Rodriguesab Tyler S. Kasterdh Danielle  S. Chaab Elisa Brietzkejk Hartej Gillab Flora NasriKangguang Linef Mehala Subramaniapillaiab Kevin KratiukKayla TeopizLeanna M.W. LuiYena Leeab Roger HoMargarita Shekotikhinaabi Rodrigo B. Mansurad Joshua  D. Rosenblatabcd

https://doi.org/10.1016/j.pnpbp.2020.110126Get rights and content

Highlights

• Early symptom improvement was associated with greater antidepressant effects following four ketamine infusions.

• ~40% of individuals with early improvement responded to the full treatment course versus 14–19% in non-early improvers.

• 58% of individuals who did not experience early improvement experienced a partial to full response after the fourth infusion.

Abstract

Background

Early symptomatic improvement with monoamine-based antidepressants is predictive of treatment response. The objective of this study was to determine if early symptomatic improvements with intravenous (IV) ketamine predicted treatment response to an acute course of four infusions.

Method

134 adults with treatment resistant depression (TRD) received four ketamine infusions over one to two weeks. Depressive symptoms were measured using the Quick Inventory for Depressive Symptomatology Self-Report16 (QIDS-SR16) at baseline and post-infusions 1, 2, 3, and 4. Early improvement was defined as ≥20% reduction in QIDS-SR16 scores after the first or second infusion. Linear models were used to determine whether early improvement was associated with post-infusion 4 QIDS-SR16 scores after controlling for baseline characteristics.

Results

Early improvement post-infusion 1 (β = −3.52, 95% BCa CI [−5.40, −1.78]) and 2 (β = −3.16, 95% BCa CI [−5.75, −1.59]) both significantly predicted QIDS-SR16scores post-infusion 4. Early improvers had significantly lower QIDS-SR16 scores at post-infusion 4 (post-infusion 1 improvers: M = 9.8, SD = 4.5; post-infusion 2 improvers: M = 10.6, SD = 5.7) compared to non-early improvers (post-infusion 1 non-improvers: M = 13.7, SD = 5.8; post-infusion 2 non-improvers: M = 14.1, SD = 5.3) when controlling for baseline characteristics. The majority (58%) of individuals who did not improve post-infusions 1 or 2 still experienced an antidepressant response or partial response (≥20% reduction in QIDS-SR16) post-infusion 4.

Limitations

This is a post-hoc analysis of an open-label study.

Conclusion

Early improvement was associated with greater antidepressant effects following a course of four ketamine infusions. However, individuals who did not show early improvements still had a high likelihood of experiencing clinically significant symptom reduction after the fourth infusion, suggesting that completing four infusions, regardless of early symptom changes, is appropriate and merited.

Steven R.D. Best a,*, Dan G. Pavel b, Natalie Haustrup c

a The Neuroscience Center, Deerfield, IL, USA
b PathFinder, Brain SPECT Imaging, Deerfield, IL, USA
c Haustrup Scientific Consulting, Cambridge, UK

A R T I C L E  I N F O

Keywords: Psychiatry, Neurology, TMS, Depression, Ketamine, Comorbidity, Biomarker, Combination

A B S T R A C T

Background: Both transcranial magnetic stimulation (TMS) and infused ketamine are recognized treatments for patients suffering from major depressive disorder (MDD). A novel therapy named combination TMS with ketamine (CTK) is introduced. This retrospective review examined the safety and clinical benefits of CTK in patients suffering from treatment-resistant depression (TRD) during the routine practice of psychiatry in a private clinic.

Methods: TRD patients (N . 28) received a coincident application of high-output TMS (30 minutes) with biomarker-determined ketamine infusions (20 minutes). Frequency of treatment was dependent on patient responsiveness (10–30 sessions). Clinical global impression (CGI) data was collected pre- and post-treatment and then two years later.

Results: The mean reduction in CGI severity for the patient group following CTK was 4.46 0.54 at a 99% confidence interval and was deemed statistically significant using a paired t-test (α . 0.01, t . 22.81 p < 0.0001).
This reduction was sustained for two years following treatment completion and this remission was deemed statistically significant by a second paired t-test (α . 0.01, t . 27.36, p < 0.0001).

Limitations: Retrospective review of a limited number of patients undergoing CTK in a clinical practice.

Conclusions: This clinical review indicated that CTK is an effective, long-term therapy (after two years) and can be used for TRD patients. The coincident administration of ketamine allowed for higher TMS intensities than otherwise would be tolerated by patients. Further studies for optimization of CTK are warranted.

1. Introduction

Treatment-resistant depression refers to a major depressive disorder (MDD) with a lack of clinically meaningful improvement to an appropriate course (adequate dose over 6–8 weeks) of at least two antidepressants from different pharmacological classes, prescribed for adequate duration, with adequate affirmation of treatment adherence (Little, 2009; EMA Guidelines, 2013). It is estimated that between 15% and 33% of patients will not respond to multiple interventions and therefore be classed as suffering from treatment-resistant depression (Little, 2009).

The sequenced treatment alternatives to relieve depression (STAR*D) trial explored the effectiveness of alternative treatments for treatment-resistant depression patients and predicted that only a third of the 20 million Americans suffering from MDD would achieve remission (Warden et al., 2007). Continued depressive symptoms have been linked to social issues, a greater risk of suicide and mortality and ultimately results in increased health-care costs (Lepine and Briley, 2011; Kellar et al., 2016).

The cause of such depressive disorders remains unclear. However, it is commonly agreed that it relates to a system disorder affecting pathways between cortical, subcortical and limbic sites, along with the neurotransmitter and molecular mediators (Mayberg et al., 2005). Patients with unipolar depression have been shown to have prefrontal abnormalities, predominantly on the left and decreased neuronal activities in the dorsolateral prefrontal cortex (PFC) regions, as well as in the rostral anterior cingulate cortex (ACC) areas, closely connected to the dorsolateral PFC (Baeken and De Raedt, 2011).

Research has shown a strong negative correlation between the ACC

* Corresponding author.

E-mail address: srdbest@neuroscience.md (S.R.D. Best).

Contents lists available at ScienceDirect

Heliyon

journal homepage: www.heliyon.com

https://doi.org/10.1016/j.heliyon.2019.e02187

Received 28 February 2019; Received in revised form 31 May 2019; Accepted 26 July 2019

2405-8440/© 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Published: 29 August 2017

  • Jerome H Taylor,
  • Angeli Landeros-Weisenberger,
  • Catherine Coughlin,
  • Jilian Mulqueen,
  • Jessica A Johnson,
  • Daniel Gabriel,
  • Margot O Reed,
  • Ewgeni Jakubovski&
  • Michael H Bloch

Neuropsychopharmacology  volume 43, pages325–333(2018) Cite this article

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Abstract

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

 

Paul GluepastedGraphic.png, Shona Neehoff, Amandine Sabadel, …

First Published September 17, 2019 Research Article Find in PubMed

https://doi.org/10.1177/0269881119874457

Article information 

Abstract

Background:

We previously reported that ketamine has anxiolytic effects in patients with treatment-resistant generalized anxiety and social anxiety disorders.

Aims:

The purpose of this study was to replicate our earlier report about ketamine‘s anxiolytic activity, using a more robust study design.

Methods:

This was a double-blind, psychoactive-controlled ascending dose study in 12 patients with treatment-resistant generalized anxiety and social anxiety disorders who were not currently depressed. Ascending doses of ketamine (0.25, 0.5, 1 mg/kg) were administered at weekly intervals, and midazolam 0.01 mg/kg, the control, was randomly inserted into the ketamine dose sequence. Assessments included ratings of anxiety and dissociation, safety and tolerability, and blood samples for ketamine pharmacokinetics and BDNF concentrations.

Results:

Improvements in anxiety ratings occurred within an hour of ketamine dosing, and persisted for up to 1 week. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate after ketamine dosing. Midazolam had minor brief effects on anxiety ratings. Ketamine was safe and well tolerated. Ketamine pharmacokinetics were correlated with dissociation ratings. Serum BDNF concentrations declined over time and were similar for all treatments.

Conclusions:

Ketamine may be a potential therapeutic option for patients with treatment-resistant generalized anxiety and social anxiety disorders.

Jennifer L. Phillips1,2, Sandhaya Norris1,2, Jeanne Talbot1,2, Taylor Hatchard1, Abigail Ortiz 1, Meagan Birmingham1, Olabisi Owoeye1,2, Lisa A. Batten1 and Pierre Blier1,2,3

Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P < 0.001, Cohen’s d = 0.83). Participants had cumulative reductions in MADRS-SI scores with repeated infusions (P < 0.001), and no further change with maintenance infusions (P = 0.94). QIDS-SI results were consistent with MADRS-SI. Overall, 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions. This study adds to the growing body of research suggesting ketamine as a possible novel treatment strategy for SI in mood disorders.

Neuropsychopharmacology (2019) 0:1–7; https://doi.org/10.1038/s41386-019-0570-x

 

Muris Humoa, Beyza Ayazgökab, Léa J.Beckera, Elisabeth Waltispergera, Tomi Rantamäkicd, Ipek Yalcina

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 100, 8 June 2020,

https://doi.org/10.1016/j.pnpbp.2020.109898

Abstract

Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions of individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, is shown to be efficient in treating both pain and depression-related symptoms. However, the molecular characteristics of its role in chronic pain-induced depression remain largely unexplored. Hence, we studied the behavioral and molecular effects of a single systemic administration of ketamine (15 mg/kg, i.p.) on mechanical hypersensitivity and depressive-like consequences of chronic neuropathic pain. We showed that ketamine transiently alleviated mechanical hypersensitivity (lasting <24 h), while its antidepressant effect was observed even 72 h after administration. In addition, ketamine normalized the upregulated expression of the mitogen activated protein kinase (MAPK) phosphatase 1 (MKP-1) and the downregulated phosphorylation of extracellular signal-regulated kinase (pERK) in the anterior cingulate cortex (ACC) of mice displaying neuropathic pain-induced depressive-like behaviors. This effect of ketamine on the MKP-1 was first detected 30 min after the ketamine administration and persisted until up to 72 h. Altogether, these findings provide insight into the behavioral and molecular changes associated with single ketamine administration in the comorbidity of chronic pain and depression.

 

Aust N Z J Psychiatry. 2020 Jan;54(1):29-45. doi: 10.1177/0004867419883341. Epub 2019 Nov 15.

Witt K1Potts J2,3Hubers A1,4Grunebaum MF5Murrough JW6Loo C7Cipriani A2,3Hawton K1,2.

Author information

Abstract

OBJECTIVE: 

Ketamine may reduce suicidal ideation in treatment-resistant depression. But it is not known how quickly this occurs and how long it persists. We undertook a systematic review and meta-analysis to determine the short- and long-term effectiveness of ketamine for suicidality.

METHOD: 

CENTRAL, EMBASE, Medline, and PsycINFO were searched until 12 December 2018. Randomised controlled trials of ketamine or esketamine reporting data on suicidal ideation, self-harm, attempted or completed suicide in adults diagnosed with any psychiatric disorder were included. Two reviewers independently extracted data, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Standardised mean difference was used for continuous outcomes.

RESULTS: 

Twenty-five reports from 15 independent trials, with a total of 572 participants diagnosed with predominately affective disorders, were included. The evidence was rated moderate to low. In most trials, ketamine was administered at 0.5 mg/kg via a single intravenous infusion over a 30- to 45-minute period. Only a single trial of intranasal esketamine was identified. At 4 hours post-infusion, treatment with ketamine was associated with a significant reduction in suicidal ideation scores (standardised mean difference = -0.51, 95% confidence interval = [-1.00, -0.03]), which persisted until 72 hours post-infusion (time points between 12 and 24 hours: standardised mean difference = -0.63, 95% confidence interval = [-0.99, -0.26]; between 24 and 72 hours: standardised mean difference = -0.57, 95% confidence interval = [-0.99, -0.14]), but not thereafter. However, there was marked heterogeneity of results. In a single trial of esketamine, marginal effects on suicidal ideation were observed. In terms of actual suicidal behaviour, there were virtually no data on effects of ketamine or esketamine.

CONCLUSION: 

A single infusion of ketamine may have a short-term (up to 72 hours) beneficial impact on suicidal thoughts. While confirmation of these results in further trials is needed, they suggest possible use of ketamine to treat acute suicidality. Means of sustaining any anti-suicidal effect need to be found.

Abstract

Steven Richard Devore Best & Brian Griffin

Pages 232-234 | Received 19 Aug 2013, Accepted 09 Jun 2014, Accepted author version posted online: 13 Jun 2014, Published online: 23 Jul 2014

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In the present article, we report on the case of a 23-year-old woman with a history of treatment-resistant depression who achieved significant symptom improvement with a novel treatment consisting of ketamine, a dissociative anesthetic, and external neuromodulation with transcranial magnetic stimulation (TMS). This case highlights the need for further investigation of treatments pairing external neuromodulation with dissociative anesthetics.

Despite advances in pharmacological treatment, approximately half of patients fail to achieve full remission, prompting researchers to look beyond conventional antidepressant medications [1]. Recent research has examined transcranial magnetic stimulation (TMS and its variant rTMS), in which an electromagnetic stimulator positioned at the scalp induces a change in local and distant electric field conditions and may cause an associated depolarization of neurons [2]. When used to stimulate the dorsolateral prefrontal cortex, rTMS has been associated with significant antidepressant effects [3], and is an FDA-approved treatment for depression. However, it is difficult to achieve remission with rTMS alone. A separate body of research has investigated intravenous ketamine, an N-methyl-D-aspartate (NMDA) antagonist [4–8]. In contrast to typical antidepressant medications that take effect within several weeks, ketamine provides relief within 2 h and lasts between four and seven days, after which relapse is common [4,5]. To date, little is known about the possible synergistic effects of combined rTMS/ketamine treatment for depression.

One study found that a factor underlying treatment resistance in depression is abnormal function in a thalamocortical circuit involving the anterior cingulate cortex (ACC), among other areas [9,11]. Accordingly, the first author hypothesized stimulating the ACC with TMS would restore normal functioning in the relevant circuit, thereby improving response to ketamine. We report on a depressed patient treated with a novel combined ketamine/TMS technique who showed substantial improvement in depression symptomatology at the end of treatment, and again at follow-up 483 days later. An IRB exemption was obtained from an independent accredited agency.

Case Report. Patient X is a 23-year-old woman who presented with a 9-year history of depression that did not respond to treatment with sertraline, buprorion, paroxetine, or stimulants. She also presented with attention deficit disorder that was treated with amphetamine from intake through follow-up. Her past history included diagnoses of anorexia nervosa and substance abuse (cocaine) that were in full remission at intake. Patient X was systematically assessed for psychopathology by an independent licensed psychologist at the outset of treatment. The primary assessment instruments were the Beck Depression Inventory-II (BDI-II) and the Personality Assessment Inventory (PAI). PAI subscale scores greater than 70 indicate clinically significant difficulties. Results of this assessment suggested that Patient X exhibited moderate levels of depression (BDI-II = 17, PAI DEP T = 84) consisting predominantly of depressed mood (PAI DEP-A T = 83), low self-esteem (PAI DEP-C T = 87), and suicidal ideation (PAI SUI T = 62). In addition, the initial assessment suggested significant difficulties in developing and maintaining a sense of life purpose and self-identity (PAI BOR-I T = 80), problematic alcohol use (PAI ALC = 66), and concentration difficulties (PAI SCZ-T T = 73). After this comprehensive assessment, Patient X’s mood was assessed during each treatment by the first author using a visual analog scale. In this measure, Patient X indicated where her mood fell along a continuum from “the worst I can imagine feeling” to “the best I can imagine feeling.”

Prior to beginning combined treatment, Patient X was given 2 days of rTMS pretreatment (four treatments per day of 30 min with 45 min of rest between treatments). Combined ketamine/TMS treatment began the following day and continued at weekly intervals for 13 weeks. Fifteen years of observational evidence from our clinic suggested that this duration produced clinically significant results. Combined treatment consisted of 40 min of 1 Hz continuous TMS with an intravenous ketamine infusion administered concurrent to and bracketed within the middle 30 min of TMS, resulting in 5 min of TMS pre- and postinfusion. The dosage of infused ketamine increased gradually from 30 mg at the first treatment to 100 mg at the last treatment. During combined treatment, the TMS head coil (manufactured by Neotonus) was positioned at the midline of the scalp to achieve maximal stimulation of the medial prefrontal area that overlays the anterior cingulate, a region implicated in depression [10]. While direct stimulation of the anterior cingulate is not likely given its subcortical position and the limited electromagnetic field penetration of TMS coils [4], we hypothesized that indirect stimulation of the anterior cingulate via TMS applied to the overlaying scalp region would result in a beneficial effect.

Baseline brain scans were used to ensure accurate coil positioning at each treatment. TMS treatments were administered at 115% of motor threshold at 1 Hz continuous pulsation given that these settings were within safety guidelines and consistent with previous research. Using this method, we hypothesized that the dissociative effects of ketamine along with TMS activation of the anterior cingulate would help reestablish normal oscillatory rhythms in this region, leading to a decrease in depression symptoms.

After the treatment on week three, Patient X reported a substantial improvement in mood and energy levels. Patient X noted that these gains were maintained over the duration of treatment with some fluctuation in mood due to relationship difficulties. Soon after the last combined treatment, Patient X reported a nondepressed mood with increased motivation and diminished attention difficulties. Combined treatment was followed by regular psychiatric visits 1–2× /month for 14 months. Gains were generally maintained over this span, with Patient X reporting that she was able to begin graduate studies and sustain an intimate relationship. Four hundred and eighty three days after her initial assessment, Patient X was again systematically assessed for psychopathology by an independent licensed psychologist. Results showed substantial decreases in depression (BDI-II = 0, PAI DEP T = 41), suicidal ideation (PAI SUI T = 45), alcohol use (PAI ALC T = 49), and concentration difficulties (PAI SCZ T = 49), along with increased sense of self-purpose (PAI BOR-I T = 56).

Discussion. This case report adds to the literature on improving the efficacy of brain electromagnetic stimulation by administering pharmacological agents that modulate glutamatergic transmission. Whereas previous research suggests that rTMS is somewhat effective in treating depression [3], and that subanesthetic doses of ketamine are temporarily helpful with depression [5–9]; the present case report is the first to suggest that a combined ketamine/rTMS treatment may be a more efficacious treatment for refractory depression than either infused ketamine or rTMS alone. Future research should examine combined ketamine/TMS treatment in a randomized controlled trial.

Declaration of Interest

Dr. Best reports no biomedical financial interests or potential conflicts of interest. Brian Griffin reports no biomedical financial interests or potential conflicts of interest. The authors alone are responsible for the content and writing of this paper.

References

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The fast-acting nasal spray esketamine, marketed as SpravatoTM, was recently approved by the Food and Drug Administration (FDA) to treat depression in individuals whose depression has been resistant to at least two medications. Structurally, esketamine is an enantiomer, or mirror image, of ketamine and works by a similar mechanism.1 The antidepressant response is evident within a few days of administration, unlike traditional antidepressants that often take weeks for the patient to feel any improvement in mood. This is particularly advantageous for patients who have suicidal thoughts and need quick resolution of depression symptoms.

While an old anesthetic drug, this new formulation has yet to be explored extensively through clinical studies in the pregnant and breastfeeding population. Interestingly, animal studies conducted don’t seem to produce promising results. A new study conducted in 2017 found that offspring of pregnant rats treated with ketamine had impaired learning and memory.2 Another study found that offspring of rats treated with ketamine during the second trimester had long-term neurocognitive dysfunction.3 A study in 2016 found that ketamine exposure during pregnancy in rats resulted in reduced development of certain brain regions in the offspring.4 Thus, at this time, ketamine’s effects in pregnancy are concerning and it is not recommended for use during pregnancy. Although the FDA has not assigned a pregnancy category to esketamine, the pharmaceutical provider suggests that SpravatoTM may cause fetal toxicity and should be avoided in pregnant and breastfeeding women.5

This is not to say that women shouldn’t seek treatment for depression during pregnancy, however. It is instead recommended that pregnant or potentially soon-to-be pregnant women turn to older antidepressants, such as select serotonin reuptake inhibitors (SSRIs). The more popular antidepressants used during pregnancy include sertraline, escitalopram, or fluoxetine.6 Paroxetine has been associated with an increased risk of cardiac defects in exposed infants with exposure in the 1st trimester.Bupropion is another alternative treatment for depression in pregnant mothers. Treatment should be initiated on a case-by-case basis depending on severity of symptoms and personal history. All of these aspects should be discussed with a physician before initiating therapy. Medication changes should ideally be made prior to pregnancy.6

Common antidepressants in pregnancy:

MedicationDescription
BupropionAnimal studies revealed no evidence of harm6
CitalopramPossible SSRI withdrawal syndrome6
EsketamineNew to the market
EscitalopramPossible SSRI withdrawal syndrome6
FluoxetinePossible SSRI withdrawal syndrome6
ParoxetineStudies in pregnant women suggested some risk to fetus6

 

Conclusions

  • Esketamine has not been studied extensively in pregnant women, but has shown negative effects on exposed offspring in rats.
  • Esketamine is not currently recommended for pregnant women.
  • Other antidepressants, such as an SSRI or bupropion, should be considered for depression in pregnancy.
  • Medication changes should ideally be made before pregnancy and should be initiated on case-by-case basis with individualized treatment.
  • An appropriate dose for an adult is 56 mg (2 sprays total intranasally) administered on day 1 of treatment, then 56-84 mg (2-3 sprays total) twice weekly for 4 weeks.5
  • It is important to remember that untreated depression during pregnancy is very risky and mothers should seek treatment for depression during pregnancy.

 

Erika Anderson MS4

Thomas W. Hale, Ph.D.

Teresa Baker MD

Infantrisk Center

Resources:

  1. Paddock, Catharine. “The FDA Approve Esketamine Nasal Spray for Severe Depression.” Medical News Today, MediLexicon International, 8 Mar. 2019, www.medicalnewstoday.com/articles/324656.php.
  2. Li, Xinran, et al. “Ketamine Administered Pregnant Rats Impair Learning and Memory in Offspring via the CREB Pathway.” Oncotarget, vol. 8, no. 20, 2017, doi:10.18632/oncotarget.15405.
  3. Li, Yanan, et al. “Long-Term Neurocognitive Dysfunction in Offspring via NGF/ ERK/CREB Signaling Pathway Caused by Ketamine Exposure during the Second Trimester of Pregnancy in Rats.” Oncotarget, vol. 8, no. 19, 2017, doi:10.18632/oncotarget.16042.
  4. Dong, C., et al. “Ketamine Exposure during Embryogenesis Inhibits Cellular Proliferation in Rat Fetal Cortical Neurogenic Regions.” Acta Anaesthesiologica Scandinavica, vol. 60, no. 5, 2016, pp. 579–587., doi:10.1111/aas.12689.
  5. “SPRAVATO™ Treatment Center.” Spravato Esketomine, www.spravatotreatmentcenter.com/.
  6. Payne, Jennifer L., and Samantha Meltzer-Brody. “Antidepressant Use During Pregnancy: Current Controversies and Treatment Strategies.” Clinical Obstetrics and Gynecology, vol. 52, no. 3, 2009, pp. 469–482., doi:10.1097/grf.0b013e3181b52e20.

 

Adriana Feder M.D., Sara Costi, M.D., Sarah B. Rutter, M.A., Abigail B. Collins, B.S., Usha Govindarajulu, Ph.D., Manish K. Jha, M.D., Sarah R. Horn, M.A., Marin Kautz, M.A., Morgan Corniquel, M.A., Katherine A. Collins, Ph.D., M.S.W., Laura Bevilacqua, M.D., Ph.D., Andrew M. Glasgow, M.D., Jess Brallier, M.D., Robert H. Pietrzak, Ph.D., M.P.H., James W. Murrough, M.D., Ph.D.,Dennis S. Charney, M.D.

Published Online: American Journal of Psychiatry, 5 Jan 2021 https://doi.org/10.1176/appi.ajp.2020.20050596

Abstract

 

Objective:

Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors’ previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD.

 

Methods:

Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale–Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures.

 

Results:

The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events.

 

Conclusions:

This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine’s full potential as a treatment for chronic PTSD.

Deborah Brauser, January 18, 2021Repeated intravenous infusions of ketamine provide rapid relief for patients with posttraumatic stress disorder (PTSD), new research suggests.

In what investigators are calling the first randomized controlled trial of repeated ketamine administration for chronic PTSD, 30 patients received six infusions of ketamine or midazolam (used as a psychoactive placebo) over 2 consecutive weeks.

No serious TRAE were reported. Some dissociative symptoms occurred during the ketamine infusion, with the highest levels toward the end of the infusion, but these had resolved by the time of the next assessment 2 hours after infusion.

The most commonly reported adverse event in the ketamine group compared with midazolam after the start of the infusion was blurred vision (53% vs. 0%), followed by dizziness (33% vs. 13%), fatigue (33% vs. 87%), headache (27% vs. 13%), and nausea or vomiting (20% vs. 7%).

“Widespread improvement”
“Overall, the results in this patient population indicate that repeated ketamine infusions over 2 weeks are associated with marked, clinically significant improvement in PTSD symptomatology,” the investigators write, and Feder found them “very satisfactory.”

“It was also encouraging to hear what some of the participants had to say. For example, some reported how their symptoms and feelings had changed over the course of ketamine treatment, with them feeling stronger and better able to cope with their trauma and memories.”

She added, however, that the study was not specifically designed to evaluate ketamine for treatment-resistant PTSD. “Some patients had already had several unsuccessful treatments, while others had never been treated. Efficacy in treatment-resistant PTSD is an important question for future investigation,” Feder said.

Overall, the results in this patient population show that repeated ketamine infusions over 2 weeks are associated with marked, clinically significant improvement in PTSD symptomatology. Dr. Adriana Feder and colleagues
Other areas worth exploring in the future would be the efficacy of the treatment in patients with different forms of trauma and whether the results lasted longer in patients receiving ketamine plus psychotherapy, she noted.

“I don’t want to ignore the fact that the treatments currently available work for a number of people with chronic PTSD. But since there are many more people for whom these treatments do not help or do not help enough, this is certainly a potentially very promising approach to add to a clinician’s treatment repertoire,” Feder said.

Continue reading at Medscape

Studies about Neurofeedback

  • Ashlie N. Bell, PhDSaybrook University / NeuroGrove, P.C. / Integrative Neurotherapy Center of Colorad
  • Donald Moss, PhDSaybrook University
  • Robert J. Kallmeyer, PhDSaybrook University
Keywords: Traumatic stress, PTSD, EEG biofeedback, LORETA, Z-score neurofeedback, Neurophysiology
 

ABSTRACT

Introduction: Posttraumatic stress disorder (PTSD) has been linked to abnormalities within three neural networks: default mode (DMN), salience (SN), and central executive (CEN).  This study examined the effectiveness of LORETA z-score neurofeedback (LZNF) training for altering current source within these networks and reducing symptoms associated with PTSD.  Methods: Twenty-three adults with chronic PTSD were randomly assigned to 15 sessions of either LZNF (n= 12) or heart rate variability biofeedback (HRVB; n = 11).  Psychosocial and physiological assessments were completed at baseline and postintervention.  Results: The LZNF group showed very large, statistically significant decreases in symptoms on the PTSD Checklist for DSM-V (PCL-5; p = .003, d = 2.09) and Beck Anxiety Inventory (BAI; p = .003, d = 2.13).  The HRVB group also showed very large decreases on the PCL-5 (p = .006, d = 1.40) and medium effects on the BAI (p = .018, d = 0.76).  Between-group comparisons showed medium to large effects of group type in favor of LZNF (PCL-5 d = 0.57; BAI d = 0.94), although not statistically significant.  LZNF Responders (n = 9) demonstrated very large, statistically significant decreases in abnormal z-scores within all targeted networks (DMN p = .012, d = 0.96; SN p = .008, d = 1.32; CEN p = .008, d = 1.33).  Conclusion: The positive outcomes of this study provide preliminary evidence to support LZNF training as a specific, effective, and tolerable intervention for adults with chronic PTSD.

Zahra Kosari1 pastedGraphic.png,  Mohsen Dadashi * pastedGraphic.png 2Mahdi Maghbouli3 pastedGraphic.png , Hossin Mostafavi4 pastedGraphic.png

1- Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran.
2- Department of Clinical Psychology, Social Determinants of Health Research Center, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
3- Department of Neurology, Faculty of Medicine, Vali Asr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran.
4- Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. 

Basic and Clinical Neuroscience, 2020

Abstract:

Introduction: Migraine is considered one of the most common primary headache disorders. Migraine attacks may occur due to a lack of sleep. Furthermore, sleep is regarded as one of the smoothing factors of migraine pain. Patients with sleep disorders often suffer from headaches when they wake up compared with healthy individuals.
Methods: This research was a quasi-experimental study with a pretest-posttest design and a 2-month follow-up. The samples included 20 migraine patients within the age range of 15 to 55 years who were selected as volunteers for treatment by the neurologists and psychiatrists during 2017. The initial evaluation was then conducted based on the inclusion and exclusion criteria and using the Ahvaz migraine questionnaire, and Pittsburgh sleep quality index. The patients were randomly assigned to two neurofeedback (n=10) and transcranial direct current stimulation (tDCS) (n=10) groups and evaluated three times. The obtained data were analyzed by the repeated measures ANCOVA and Chi-square test in SPSS.
Results: Based on the scores of both groups, no significant difference was observed between neurofeedback and tDCS groups. However, based on the results, neurofeedback decreased sleep latency, whereas tDCS increased sleep efficiency. Overall, these two treatments were effective in improving subjective sleep quality and sleep quality.
Conclusion: Both neurofeedback and tDCS treatments could significantly enhance sleep quality of the patients in the posttest and 2-month follow-up. Given the effectiveness of both treatments, neurofeedback and tDCS are recommended to be used for improving the sleep status of patients with migraine.

 

Martijn Arns · C. Richard Clark · Mark Trullinger · Roger deBeus · Martha Mack · Michelle Aniftos

© The Author(s) 2020

Abstract

Stimulant medication and behaviour therapy are the most often applied and accepted treatments for Attention-Deficit/ Hyperactivity-Disorder (ADHD). Here we explore where the non-pharmacological clinical intervention known as neuro- feedback (NFB), fits on the continuum of empirically supported treatments, using standard protocols. In this quantitative review we utilized an updated and stricter version of the APA guidelines for rating ‘well-established’ treatments and focused on efficacy and effectiveness using effect-sizes (ES) and remission, with a focus on long-term effects. Efficacy and effec- tiveness are compared to medication and behaviour therapy using benchmark studies. Only recent systematic reviews and meta-analyses as well as multi-centre randomized controlled trials (RCT’s) will be included. Two meta-analyses confirmed significant efficacy of standard neurofeedback protocols for parent and teacher rated symptoms with a medium effect size, and sustained effects after 6–12 months. Four multicenter RCT’s demonstrated significant superiority to semi-active control groups, with medium-large effect sizes end of treatment or follow-up and remission rates of 32–47%. Effectiveness in open- label studies was confirmed, no signs of publication bias were found and no significant neurofeedback-specific side effects have been reported. Standard neurofeedback protocols in the treatment of ADHD can be concluded to be a well-established treatment with medium to large effect sizes and 32–47% remission rates and sustained effects as assessed after 6–12 months.

 

Studies about repetitive transcranial magnetic stimulation (rTMS)

Amin et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2020) 56:19

The Egyptian Journal of Neurology, https://doi.org/10.1186/s41983-019-0140-5 Psychiatry and Neurosurgery

RESEARCH

Randa Amin1, Tamer Emara1*, Samia Ashour1, Mahmoud Hemeda1, Nahed Salah Eldin1, Salma Hamed1, Sara Shouman2 and Mohamed Shouman3

Abstract

Objective: The aim of the study was to examine the prophylactic role of repetitive transcranial magnetic stimulation (rTMS) on the frequency, and severity of migraine attacks in episodic migraineurs who failed medical treatment.

Methods: A randomized double-blinded placebo-controlled study was designed to assess the effect of 5 Hz rTMS applied over the left dorsolateral prefrontal cortex (LDLPFC ) in 33 migraineurs. Patients were followed up for 1 month before receiving rTMS, and for another month after the sessions by a headache diary. The primary outcome measure was the achievement of 50% reduction in the number of migraine attacks. Secondary outcome measures included migraine days, assessment of migraine attack severity, disability by HIT-6, and side-effects to the procedure.

Results: The study revealed that 69.2% of the active treatment group achieved 50% or more reduction in the number of migraine attacks versus 25% of cases in the control group (p = 0.02). The absolute number of migraine attacks was reduced by 3.1 vs 1.5 in the active and control group, respectively. The number of cases with severe HIT-6 scores was reduced by 46.2% in active treatment group versus a 7.1% reduction in the control group (p = 0.02).

Conclusion: High-frequency rTMS applied to LDLPFC can reduce the number of migraine attacks by 50% or more in almost 70% of a sample of episodic migraineurs with a concomitant decrease in functional disability.

Trial registration: ClinicalTrials.gov, Identifier: NCT04031781. Registered 23 July 2019—retrospectively registered at https://clinicaltrials.gov/ct2/show/NCT04031781?term=Migraine+Prophylaxis&recrs=ce&type=Intr&cond=Migraine&rank=9

 

Ying-hui Chouab Viet Ton Thata MarkSundmana

https://doi.org/10.1016/j.neurobiolaging.2019.08.020

 

Abstract

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5–30 consecutive rTMS sessions could last for 4–12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.

us leo.

Jean-Pascal Lefaucheur et al (2020)

Abstract

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcra- nial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150–206]. These updated recommendations take into account all rTMS publications, includ- ing data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralat- eral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respec- tively, in Parkinson’s disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spas- ticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recom- mendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

! 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

 

Nervenheilkunde 2020; 39(04): 213-221
DOI: 10.1055/a-1113-0084

Schwerpunkt

© Georg Thieme Verlag KG Stuttgart · New York

Transkranielle Magnetstimulation zur Behandlung von Depressionen bei Schwangeren Eine Übersicht

Transcranial magnetic stimulation in the treatment of depression during pregnancy  A review

Tobias Hebel, Martin Schecklmann, Berthold Langguth

Zusammenfassung

Gegenstand und Ziel In dieser Übersichtsarbeit sollen die Wirksamkeit und Sicherheit der repetitiven transkraniellen Magnetstimulation (rTMS) für die Patientengruppe depressiv erkrankter Schwangerer evaluiert werden.

Material und Methoden Es wurde eine Datenbankrecherche auf Pubmed durchgeführt, um alle relevanten Original- und Übersichtsarbeiten zu dem Thema zu identifizieren und zu analysieren

Ergebnisse Zusätzlich zu einer Reihe von Fallberichten existieren 3 kontrollierte Studien zur Behandlung depressiver Schwangerer mittels rTMS. Der Datenlage nach scheint die rTMS sowohl für die schwangeren Patientinnen als auch ihre ungeborenen Kinder sicher zu sein. Es wurden keine postnatalen negativen Wirkungen auf die Kindesentwicklung berichtet.

Schlussfolgerung rTMS stellt eine vielversprechende Behandlungsoption dar. Weitere Studien mit größeren Teilnehmerzahlen sind notwendig, um den Stellenwert der rTMS in einer multimodalen Depressionsbehandlung in der Schwangerschaft zu klären.

 

Arch Womens Ment Health. 2014 Aug;17(4):311-5. doi: 10.1007/s00737-013-0397-0. Epub 2013 Nov 20.

Hızlı Sayar G1Ozten ETufan ECerit CKağan GDilbaz NTarhan N.

Abstract

The aim of the present study was to assess the safety and effectiveness of high-frequency repetitive transcranial magnetic stimulation (rTMS) in pregnant patients with depression. Thirty depressed pregnant patients received rTMS over the left prefrontal cortex for 6 days in a week, from Monday to Saturday for 3 weeks. The rTMS intensity was set at 100% of the motor threshold. A 25-Hz stimulation with a duration of 2 s was delivered 20 times with 30-s intervals. A session comprised 1,000 magnetic pulses. Depression was rated using the 17-item Hamilton depression rating scale (HAMD) before and after treatment. Response was defined as a 50% reduction of the HAMD score. Patients with HAMD scores less than 8 were considered to be in remission. The mean HAMD score for the study group decreased from 26.77 ± 5.58 to 13.03 ± 6.93 (p < 0.001) after 18 sessions of rTMS. After the treatment period, 41.4% of the study group demonstrated significant mood improvements as indexed by a reduction of more than 50% on the HAMD score. In addition, 20.7% attained remission (HAMD score < 8), 34.5% achieved a partial response, and 3.4% had worsening in HAMD scores at the end of treatment. Treatment was well tolerated, and no significant adverse effects were reported. rTMS was well tolerated and found to be statistically and clinically effective in pregnant patients with treatment-resistant depression. This study contributed to the existing evidence of the antidepressant effect of rTMS in the treatment of depression in pregnancy.

PMID: 24248413

DOI: 10.1007/s00737-013-0397-0

 

Studies about the use of Virtual Reality (German)

Behaviour Change (2018), 35, 152–166 doi:10.1017/bec.2018.15

STANDARD PAPER

Rachel K. Chesham, John M. Malouff* and Nicola S. Schutte
University of New England, Armidale, New South Wales, Australia
*Corresponding author. John M. Malouff, University of New England, School of Psychology, Armidale NSW 2351, Australia. Email: jmalouff@une.edu.au

Abstract

Social anxiety is a common, debilitating psychological problem. In the present study, two meta-analyses examined the efficacy of virtual reality exposure therapy for social anxiety. The first meta-analysis tested whether virtual reality exposure therapy reduces social anxiety more than a waitlist control condition. The results of the first meta-analysis, consisting of six studies and 233 participants, showed a significant overall effect size, indicating that virtual reality exposure therapy was effective in reducing social anxiety. The second meta-analysis tested whether the standard treatment for social anxiety, which includes in vivo or imaginal exposure, leads to greater effects than virtual reality exposure therapy. The second meta-ana- lysis, consisting of seven studies and 340 total participants, showed essentially no difference in effect sizes between virtual reality exposure and in vivo or imaginal exposure. The results of the two meta-analyses support the use of virtual reality in the treatment of social anxiety.
Keywords: exposure therapy; meta-analysis; social anxiety; virtual reality

Social anxiety is characterised by fear of social situations and of interactions with others. Individuals experiencing social anxiety frequently avoid social situations due to fear of public scrutiny and negative evaluation (Hofmann & DiBartolo, 2014). Research findings indicate that public speaking is the most prevalent social fear (Furmark, 2002; Ruscio et al., 2008). Other common social fears include interact- ing with strangers, dating, and going to parties (Hofmann, Heinrichs, & Moscovitch, 2004). Research findings show that these fears can cause impairments in social functioning and are associated with lower levels of educational attainment, higher risk of unemployment, and difficulties in forming intim- ate relationships (Crome et al., 2015; Fehm, Pelissolo, Furmark, & Wittchen, 2005).
Despite the various harmful impacts of high social anxiety, few individuals with social anxiety seek professional help (Crome et al., 2015; Fehm et al., 2005). One possible reason for the low rate of help seeking might be that social anxiety leads these individuals to avoid interactions with mental health care providers, just as they avoid interactions with others.
Socially anxious individuals may meet criteria for a diagnosis of social anxiety disorder, as described by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). According to the DSM-5, a diagnosis of social anxiety disorder (also known as social phobia) reflects clinically significant levels of social anxiety. Furthermore, the DSM-5 includes a ‘performance only’ specifier for individuals fearing only public speaking or performance situations.
Anxiety in social situations is a common human experience (Ruscio, 2010). Therefore, some experts argue it is best to conceptualise social anxiety as existing along a continuum ranging from fears that are adaptive to those that cause substantial impairment (Hofmann & DiBartolo, 2014). Ruscio (2010) suggested that all levels of social anxiety are important to consider and that researchers may overlook important information by excluding milder cases that fall below the diagnostic threshold.
© The Author(s) 2018
Behaviour Change 153

Theoretical and Treatment Models of Social Anxiety

Cognitive behaviour therapy (CBT) is the first-line treatment for social anxiety (Pilling et al., 2013). While the main evidence-based CBT tools for social anxiety include exposure, cognitive restructuring, social skills training and relaxation training, standard treatment almost always includes exposure as a key component (Heimberg, 2002).
The therapist and the client typically generate a hierarchy of social situations to use in gradual in vivo or imaginal exposure (Deacon & Abramowitz, 2004; Rodebaugh, Holaway, & Heimberg, 2004). In vivo exposure involves direct confrontation of actual feared stimuli, whereas imaginal exposure involves visualising feared situations (Olatunji, Cisler, & Deacon, 2010). The client gradually confronts each situation, from least to most feared, and engages with each item until anxiety decreases (Rodebaugh et al., 2004).
There are two prevailing theoretical models related to learning that explain how exposure therapy reduces anxiety (Abramowitz, 2013). Emotional processing theory (Foa & Kozak, 1986) and the inhibi- tory learning model (Craske et al., 2008) both postulate that exposure allows individuals to learn cor- rective information about a feared stimulus. Emotional processing theory specifically postulates that feared stimuli activate a fear structure (Foa & Kozak, 1986). When corrective information is incom- patible with this fear structure, it is replaced with a new, non-fear structure (Foa & Kozak, 1986). However, the inhibitory learning model emphasises tolerating rather than replacing fear (Craske et al., 2008). It posits that while old, fear-based learning is not erased by extinction, new learning can inhibit its expression (Craske et al., 2008).
A large body of research supports the efficacy of in vivo and imaginal exposure treatments for redu- cing symptoms of social anxiety, although the methods do not work for all individuals with social anx- iety (e.g., Acarturk, Cuijpers, van Straten, & de Graaf, 2009; Feske & Chambless, 1995; Gould, Buckminster, Pollack, Otto, & Massachusetts, 1997; Powers, Sigmarsson, & Emmelkamp, 2008; Turner, Beidel, & Jacob 1994).

Virtual Reality Exposure Therapy

In recent years, exposure therapy through virtual reality has gained substantial attention as an inter- vention for social anxiety (Powers & Emmelkamp, 2008; Wallach, Safir, & Bar-Zvi, 2009). Virtual reality technology integrates computer graphics, visual displays, motion tracking and other sensory devices to give the user a multisensory and realistic experience (Bush, 2008; Krijn, Emmelkamp, Olafsson, & Biemond, 2004; Powers & Emmelkamp, 2008). A head-mounted display is typically used to immerse clients in the virtual environment (Krijn et al., 2004).
During virtual reality exposure therapy (VRET), the client confronts computer-generated simula- tions of feared situations (Anderson et al., 2013). Trained therapists conduct the treatment in a private, safe, and controlled environment (Bush, 2008). Virtual technology is programmable, and environ- ments can be customised to clients’ specific social anxieties, in accordance with their fear and avoid- ance hierarchy (Krijn et al., 2004; Vanni et al., 2013).
VRET may be useful in addressing the shortcomings of established methods of exposure, particu- larly in relation to cost-effectiveness, convenience, treatment acceptability, treatment availability, and difficulties with clients visualising scenes during imaginal exposure (Anderson et al., 2013; Choy, Fyer, & Lipsitz, 2007; Krijn et al., 2004). Furthermore, VRET offers an appealing and novel treatment approach, and may be useful for those who show reluctance toward participating in vivo or imaginal exposure (Benedek & Wynn, 2016; Bush, 2008). Because of these advantages, VRET might have the potential to lead individuals to seek treatment who otherwise might not do so (Powers & Emmelkamp, 2008).

The Efficacy of Virtual Reality Exposure Therapy for Social Anxiety

To date, three meta-analyses have explored the efficacy of VRET for a range of anxiety disorders (Opriş et al., 2012; Parsons & Rizzo, 2008; Powers & Emmelkamp, 2008). One other meta-analysis
154 Rachel K. Chesham et al.

(Kampmann, Emmelkamp, & Morina, 2016) investigated the efficacy of treating social anxiety with a variety of technological interventions, including VRET.
Parsons and Rizzo (2008) investigated the pre-post effects of VRET for social phobia and reported a meta-analytic effect size of 0.96, 95% CI [0.34, 1.59], indicating a reduction in anxiety symptoms follow- ing VRET. However, the authors only analysed results for VRET conditions and did not compare their findings to waitlist control groups or standard treatments, making it difficult to determine the relative efficacy of VRET. In contrast, Powers and Emmelkamp (2008) did make a comparison between VRET and control conditions for two social phobia studies. They reported a between-groups, meta-analytic Hedges’ g of 0.73 (no reported confidence interval), indicating that VRET was more efficacious than con- trol conditions in the treatment of social anxiety. The meta-analysis combined waitlist control conditions and standard exposure control conditions in one meta-analysis, making the results hard to interpret.
More recently, Opriş et al. (2012) and Kampmann, Emmelkamp, and Morina (2016) examined the efficacy of VRET compared to waitlist controls. Opriş et al. (2012) reported a d of 1.01, 95% CI [0.69, 1.33] across three social phobia studies, indicating VRET outperformed waitlist on outcome measures of social anxiety. Kampmann, Emmelkamp, and Morina (2016) reported a similarly large and signifi- cant effect size across three studies, with g = 0.82, 95% CI [0.13, 1.51]. Both authors also compared VRET to standard, empirically supported treatments for social anxiety, including in vivo and imaginal exposure. Opriş et al. (2012) reported a non-significant effect size in favour of in vivo and imaginal exposure (d = 0.13, 95% CI [−0.11, 0.38] for three social phobia studies, suggesting that VRET and standard treatments had comparable efficacy. Kampmann, Emmelkamp, and Morina (2016) reported similar non-significant findings in favour of VR in comparison to empirically supported treatments across three studies, with g = −0.24, 95% CI [−0.71, 0.23]. A difference between these two meta-analyses was that Kampmann, Emmelkamp, and Morina (2016) restricted their analysis to ran- domised control trials and participants with diagnosed social anxiety disorder, whereas Opriş et al. (2012) did not require participants to have a clinical diagnosis and included studies with various meth- odological designs (e.g., non-random, quasi-random).
In each of these meta-analyses, researchers examined the efficacy of VRET for social anxiety by including it as a subcategory of a larger analysis. Within these subanalyses, the number of studies on social anxiety ranged from two to four, and the total number of participants ranged from 50 to
216. Moreover, the researchers included some small studies with low participant numbers. When com- pared to bigger studies, smaller studies often show larger and different treatment effects (Sterne, Gavaghan, & Egger, 2000). Further, small studies are regularly selected for publication because of their statistically significant results (Sterne et al., 2000). This phenomenon contributes to publication bias (publishing only favourable results) and can therefore affect the generalisability of effect sizes in meta-analysis (Sterne et al., 2000). Although Kampmann, Emmelkamp, and Morina (2016) acknowl- edged the issue of publication bias in the report of their meta-analysis, they could not examine its influence on effect sizes in their VRET analysis because of the low number of studies included.
Individual studies considered in the reviewed meta-analyses investigated the efficacy of VRET for social anxiety by assessing participants’ social anxiety symptomatology with various outcome mea- sures, such as the Liebowitz Social Anxiety Scale (Liebowitz, 1987), which has high levels of reliability and validity (Heimberg et al., 1999), and behavioural measures, such as total time speaking, which have face validity.
In sum, previous meta-analytic studies of the effects of VRET for social anxiety have had two main deficiencies: a very low number of studies and a lack of evaluation of publication bias. While a meta-analysis only requires a minimum of two studies (Valentine, Pigott, & Rothstein, 2010), increas- ing this number tends to enhance the generalisability of results (Schmidt & Hunter, 2014).

Aims and Hypotheses of the Present Study

The overall objective of the present study was to examine, through two meta-analyses, the efficacy of VRET for reducing symptoms of social anxiety. We aimed to improve on prior analyses by employing a more methodologically rigorous design. We further aimed to consider the impact of publication bias in order to improve the precision of effect size estimates. First, we assessed the efficacy of VRET com- pared to a waitlist control. Second, we compared the efficacy of VRET to the standard treatments of in vivo or imaginal exposure. We tested the following hypotheses in two separate meta-analyses:

H1: Virtual reality exposure therapy would demonstrate greater efficacy in reducing social anxiety than a waitlist control condition.

H2: The standard treatments of in vivo or imaginal exposure would demonstrate greater efficacy in reducing social anxiety when compared to virtual reality exposure therapy.

Method

Literature Search
We searched the electronic databases PubMed, EBSCOhost, Proquest Central, PsychINFO and Proquest Dissertations and Theses in July 2017 for published and unpublished studies. We searched the databases using Boolean operators to link the search terms and phrases ‘virtual reality exposure therapy’ or ‘VRET’ or ‘virtual reality therapy’ or ‘VRT’ and ‘social anxiety’ or ‘social phobia’. We sought studies in Google Scholar by searching in the title using the exact phrases ‘virtual reality expos- ure therapy’ or ‘virtual reality therapy’, ‘VRT’, or ‘VRET’, and at least one of the terms ‘social’, ‘anxiety’, or ‘phobia’. There were no date limits set on the search. Articles had to be in English. We sought further studies from reference lists of retrieved articles. We wrote to authors of studies included in the meta-analysis to enquire after unpublished studies investigating the effects of VRET on social anxiety. We evaluated studies for inclusion by systematically analysing the title and abstract and then the full text. Figure 1 provides a summary of the search process.

Inclusion Criteria and Evaluation Process

Studies had to meet the following criteria for inclusion in the meta-analysis: (1) The study must be a well-controlled trial with random assignment, quasi-random assignment or participant matching pro- cedures that minimise bias. (2) The study must not use the same sample as another study. (3) The study report must be in English. (4) The study must have a VRET condition and at least one compari- son condition, which is a waitlist or an exposure treatment using in vivo or imaginal exposure. (5) Comparison treatments must not include VRET. (6) The article must provide treatment assessment data for social anxiety symptomatology, such as appropriate reporting of means and standard devia- tions. (7) Social anxiety must be the main target of the intervention.
We excluded measures not relating directly to social anxiety, such as depression, general anxiety, and quality-of-life scales. Excluding these measures maintained the focus on social anxiety. We used outcome-measure totals rather than subscale values, if researchers reported both. Two studies used the Self-Statements During Public Speaking (Hofmann & DiBartolo, 2000) scale, which contains positive and negative subscales. The negative subscale is a direct measure of social anxiety, shows more sensitivity to change than the positive scale, is more highly correlated with social anxiety, and is better able to differentiate between individuals with and without social anxiety (Hofmann & DiBartolo, 2000). As a result, we included only the negative subscale in the analysis.
The time of final comparison for each of the two meta-analysis was the latest measured time point during which participants remained in their originally allocated conditions, unless more than half the participants were lost by that time point. If available, we used carry-forward intention-to-treat (ITT) data because it offers a more conservative estimate of treatment outcomes (Gupta, 2011). In ITT, the pretreatment scores of participants who do not complete the postassessment are carried forward to serve as their post-intervention scores.

The authors Heuett and Heuett (2011) informed us, upon our contacting them, that they randomly assigned participants in their study to treatment conditions but not to the waitlist. The waitlist was comprised of individuals who filled out pretest forms incorrectly or were absent during the baseline assessment. There was evident systematic bias in the participant assignment to this condition. Therefore, we excluded the waitlist conditions from the meta-analysis. Furthermore, the data reported for two of the outcome measures at pretreatment in Heuett and Heuett’s imaginal exposure condition were implausible in an absolute sense and inconsistent with the other conditions, likely due to printing errors in the article. Therefore, we excluded from the analysis the results reported for the Willingness to Communicate scale and the Self-Perceived Communication Competence scale.
The results reported in Safir, Wallach, and Bar-Zvi (2012) are the follow-up assessment for Wallach et al. (2009). We used the 1-year data in Safir et al. (2012) for the comparison of VRET and standard treatments. Since the researchers did not assess waitlist at 1 year, we used the 12-week time point for the VRET and waitlist comparison.
We included two studies that used quasi-random assignment to condition and one study that used matching of participants prior to assignment to condition. Wallach et al. (2009) allocated participants to conditions by order of arrival, which is not true random assignment (Torgerson & Torgerson, 2008). Further, Wallach et al. (2009) used weighted assignment later in the study due to sample attrition, which allowed the researchers to maintain groups of equal size. Harris, Kemmerling, and North (2002) allocated four counsellor-referred participants straight to the waitlist and randomly assigned the remaining participants. Klinger et al. (2005) matched participants on key variables (e.g., age, gender) before assignment to conditions. Despite the lack of random assignment, we con- sidered this a well-controlled trial and included it in the meta-analysis.

Study Coding and Intercoder Agreement

Two of us jointly coded the following information for each study: publication characteristics (author and year of publication); age of participants; nature of the comparison group (treatment with exposure or waitlist); nature of participant assignment; outcome measures for assessing social anxiety symp- toms; time from baseline to final comparison of conditions; number of treatment sessions; study results (sample size, pre- and postassessment means and standard deviations); and the effect direction (positive or negative).
The third author independently checked the coding by randomly selecting four studies, which included 25 lines of data (out of a total of 50 lines) and 275 entries. For continuous data entries, we considered an agreement to be a variance of anything less than 5% of the original coded value. The agreement rate was 96%. Where there were disagreements, we made final decisions by consensus.

Statistical Procedure and Data Analysis

We calculated effect sizes using the coded values of the included studies, such as pre- and postassess- ment means and standard deviations for conditions. We used Hedges’ g, which is closely related to Cohen’s (1988) d, as the unbiased estimate of effect size. We used a random-effects model in the ana- lysis to allow for the possibility that effect sizes between studies differ (Borenstein, Hedges, Higgins, & Rothstein, 2010). The Q-value and I2 assessed heterogeneity across studies. While the Q-value is a sig- nificance test, I2 reports what percentage of total variability across studies in meta-analysis is due to between-study variability rather than to chance. Higgins and Thompson (2002) suggested tentative values of I2 in which 30% is mild, and exceeding 50% is large. A 95% confidence interval and a p value were computed for each model. We assessed the impact of publication bias using Orwin’s (1983) failsafe N, Duvall and Tweedie’s (1998) trim and fill method, and by viewing funnel plots. Negative values of g suggested results favoured standard treatment efficacy, whereas positive values indicated results favoured VRET efficacy. We conducted all analyses using Comprehensive Meta-Analysis (Version 3.3.070, 2014).
We first performed analyses with all studies relevant to each analysis. However, not every study used random assignment. Lacking randomisation makes these studies more susceptible to confound- ing bias (see Faber, Ravaud, Riveros, Perrodeau, & Dechartres, 2016). Randomised control trials are considered the gold standard in research design and provide the best evidence for assessing the efficacy of treatment (Faraoni & Schaefer, 2016). Further, randomised trials increase the statistical power and precision of estimated effects in meta-analysis (Wetterslev, Thorlund, Brok, & Gluud, 2008). So, we conducted a second set of analyses including only trials using random assignment.

Results

The search strategy resulted in nine relevant studies, with a total of 573 participants. The meta-analysis data file can be obtained by contacting the corresponding author. Table 1 provides a summary of the key characteristics of the included studies. Figure 2 shows: (1) the studies used in the comparison of VRET and waitlist control conditions analysis, and (2) the studies used in the comparison of VRET and in-vivo or imaginal exposure therapy analysis and a forest plot of the effect sizes.

LINK TO COMPLETE STUDY


Emily Carla,⁎, Aliza T. Steina, Andrew Levihn-Coonb,c, Jamie R. Pogued, Barbara Rothbaume,
Paul Emmelkampf, Gordon J.G. Asmundsong, Per Carlbringh,i, Mark B. Powersa,d
a Department of Psychology, The University of Texas at Austin, Austin, TX, United States‌
b San Francisco Veterans Affairs Medical Center, San Francisco, CA, United States
c Northern California Institute for Research and Education, San Francisco, CA, United States
d Baylor University Medical Center, Dallas, TX, United States
e Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, United States f Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands g Department of Psychology, University of Regina, Regina, SK, Canada‌‌
h Department of Psychology, Stockholm University, Stockholm, Sweden
i University of Southern Denmark, Odense, Denmark

A R T I C L E I N F O

Keywords:
Meta-Analysis Virtual reality VR
Virtual reality exposure therapy VRET
A B S T R A C T


Trials of virtual reality exposure therapy (VRET) for anxiety-related disorders have proliferated in number and diversity since our previous meta-analysis that examined 13 total trials, most of which were for specific phobias (Powers & Emmelkamp, 2008). Since then, new trials have compared VRET to more diverse anxiety and related disorders including social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), and panic disorder (PD) with and without agoraphobia. With the availability of this data, it is imperative to re-examine the efficacy of VRET for anxiety. A literature search for randomized controlled trials of VRET versus control or in vivo exposure yielded 30 studies with 1057 participants. Fourteen studies tested VRET for specific phobias, 8 for SAD or performance anxiety, 5 for PTSD, and 3 for PD. A random effects analysis estimated a large effect size for VRET versus waitlist (g = 0.90) and a medium to large effect size for VRET versus psychological placebo conditions (g = 0.78). A comparison of VRET and in vivo conditions did not show significantly different effect sizes (g = −0.07). These findings were relatively consistent across disorders. A meta-regression analysis revealed that larger sample sizes were associated with lower effect sizes in VRET versus control comparisons (β = −0.007, p < 0.05). These results indicate that VRET is an effective and equal medium for exposure therapy.

LINK TO FULL STUDY

Studies about HRV Biofeedback

Applied Psychophysiology and Biofeedback
https://doi.org/10.1007/s10484-020-09458-z

Marcos Economides · Paul Lehrer · Kristian Ranta · Albert Nazander · Outi Hilgert · Anu Raevuori · Richard Gevirtz · Inna Khazan · Valerie L. Forman‐Hoffman

© The Author(s) 2020

Abstract

A rise in the prevalence of depression underscores the need for accessible and effective interventions. The objectives of this study were to determine if the addition of a treatment component showing promise in treating depression, heart rate variability-biofeedback (HRV-B), to our original smartphone-based, 8-week digital intervention was feasible and whether patients in the HRV-B (“enhanced”) intervention were more likely to experience clinically significant improvements in depressive symptoms than patients in our original (“standard”) intervention. We used a quasi-experimental, non-equivalent (matched) groups design to compare changes in symptoms of depression in the enhanced group (n = 48) to historical out- come data from the standard group (n = 48). Patients in the enhanced group completed a total average of 3.86 h of HRV-B practice across 25.8 sessions, and were more likely to report a clinically significant improvement in depressive symptom score post-intervention than participants in the standard group, even after adjusting for differences in demographics and engagement between groups (adjusted OR 3.44, 95% CI [1.28–9.26], P = .015). Our findings suggest that adding HRV-B to an app-based, smartphone-delivered, remote intervention for depression is feasible and may enhance treatment outcomes.

Clin Psychopharmacol Neurosci. 2019 Mar; 17(2): 222–232.

Published online 2019 Apr 30. doi: 10.9758/cpn.2019.17.2.222

PMCID: PMC6478078

PMID: 30905122

I-Mei Lin,1,* Sheng-Yu Fan,,* Cheng-Fang Yen, Yi-Chun Yeh, Tze-Chun Tang, Mei-Feng Huang, Tai-Ling Liu, Peng-Wei Wang, Huang-Chi Lin, Hsin-Yi Tsai, and Yu-Che Tsai” src=”blob:https://www.psychosomatik.com/61724f14-b840-4c3c-bf1c-de47cbec0d0e” alt=”corresponding author” border=”0″ class=”Apple-web-attachment Singleton” style=”width: 0.0729in; height: 0.0937in; opacity: 1;”>

Abstract

Objective

Autonomic imbalance is considered a psychopathological mechanism underlying major depressive disorder (MDD). Heart rate variability (HRV) is an index for autonomic activation. Poor sleep quality is common among patients with MDD. HRV biofeedback (BF) has been used for regulating autonomic balance among patients with physical illness and mental disorders. The purpose of present study was to examine the effects of HRV-BF on depressive symptoms, sleep quality, pre-sleep arousal, and HRV indices, in patients with MDD and insomnia.

Methods

In this case-controlled study, patients with MDD and Pittsburgh Sleep Quality Index (PSQI) score higher than 6 were recruited. The HRV-BF group received weekly 60-minute protocol for 6 weeks, and the control group who have matched the age and sex received medical care only. All participants were assessed on Beck Depression Inventory-II, Back Anxiety Inventory, PSQI, and Pre-Sleep Arousal Scale. Breathing rates and electrocardiography were also performed under resting state at pre-testing, and post-testing conditions and for the HRV-BF group, also at 1-month follow-up.

Results

In the HRV-BF group, symptoms of depression and anxiety, sleep quality, and pre-sleep arousal were significantly improved, and increased HRV indices, compared with the control group. Moreover, in the HRV-BF group, significantly improved symptoms of depression and anxiety, decreased breathing rates, and increased HRV indices were detected at post-testing and at 1-month follow-up, compared with pre-testing values.

published: 08 May 2020

Abstract

We performed a systematic and meta analytic review of heart rate variability biofeedback (HRVB) for various symptoms and human functioning. We analyzed all problems addressed by HRVB and all outcome measures in all studies, whether or not relevant to the studied population, among randomly controlled studies. Targets included various biological and psychological problems and issues with athletic, cognitive, and artistic performance. Our initial review yielded 1868 papers, from which 58 met inclusion criteria. A significant small to moderate effect size was found favoring HRVB, which does not differ from that of other effective treatments. With a small number of studies for each, HRVB has the largest effect sizes for anxiety, depression, anger and athletic/artistic performance and the smallest effect sizes on PTSD, sleep and quality of life. We found no significant differences for number of treatment sessions or weeks between pretest and post-test, whether the outcome measure was targeted to the population, or year of publication. Effect sizes are larger in comparison to inactive than active control conditions although significant for both. HRVB improves symptoms and and functioning in many areas, both in the normal and pathological ranges. It appears useful as a complementary treatment. Further research is needed to confirm its efficacy for particular applications.

 

Studies about transcranial direct current stimulation (tDCS)

Eman M. Khedr, MD, Ragaa H. Salama, MD, Mohamed Abdel Hameed, MD, …

First Published April 3, 2019

https://doi.org/10.1177/1545968319840285

Abstract

Objective

To explore the neuropsychological effects and levels of tau protein (TAU), amyloid β 1-42 (Aβ 1-42), and lipid peroxidase after 10 sessions of anodal transcranial direct current stimulation (tDCS) in patients with mild to moderate Alzheimer disease (AD). Patients and methods. A total of 46 consecutive patients with probable AD participated in this study. They were classified randomly into 2 equal groups: active versus sham. Each patient received 10 sessions of anodal tDCS over the left and right temporoparietal region for 20 minutes for each side with the cathode on the left arm. Patients were assessed using the Modified Mini Mental State Examination (MMMSE), clock drawing test, Montreal Cognitive Scale (MoCA), and the Cornell Scale for depression. Serum TAU, Aβ 1-42, and lipid peroxidase were measured before and after the 10th session. Results. There was a significant improvement in the total score of each cognitive rating scale (MMMSE, clock drawing test, and MoCA) in the real group, whereas no such change was observed in the sham group. The Cornell depression score improved significantly in both groups. There was a significant increase in serum Aβ 1-42 (P = .02) in the real but not in the sham group, with a significant Treatment condition × Time interaction (P = .009). There was no significant effect on tau or lipid peroxidase in either group but a significant positive correlation between changes of Aβ1-42 and MMMSE (P = .005) and MoCA (P= .02). Conclusion. The observed cognitive improvements were complemented by parallel changes in serum levels of Aβ 1-42.

 

Lais B. Razza

Priscila Palumbo

Adriano H. Moffa

Andre F. Carvalho

Marco Solmi

Colleen K. Loo

Andre Russowsky Brunoni

First published: 26 February 2020

https://doi.org/10.1002/da.23004

 

Abstract

Background

Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment.

Objective

To perform a systematic review and meta‐analysis of trials using tDCS to improve depressive symptoms.

Methods

A systematic review was performed from the first date available to January 06, 2020 in PubMed, EMBASE, Cochrane Library, and additional sources. We included randomized, sham‐controlled clinical trials (RCTs) enrolling participants with an acute depressive episode and compared the efficacy of active versus sham tDCS, including association with other interventions. The primary outcome was the Hedges’ g for continuous depression scores; secondary outcomes included odds ratios (ORs) and number needed to treat (NNT) for response, remission, and acceptability. Random effects models were employed. Sources of heterogeneity were explored via metaregression, sensitivity analyses, subgroup analyses, and bias assessment.

Results

We included 23 RCTs (25 datasets, 1,092 participants), most (57%) presenting a low risk of bias. Active tDCS was superior to sham regarding endpoint depression scores (k = 25, g = 0.46, 95% confidence interval [CI]: 0.22–0.70), and also achieved superior response (k = 18, 33.3% vs. 16.56%, OR = 2.28 [1.52–3.42], NNT = 6) and remission (k = 18, 19.12% vs. 9.78%, OR = 2.12 [1.42–3.16], NNT = 10.7) rates. Moreover, active tDCS was as acceptable as sham. No risk of publication bias was identified. Cumulative meta‐analysis showed that effect sizes are basically unchanged since total sample reached 439 participants.

Conclusions

TDCS is modestly effective in treating depressive episodes. Further well‐designed, large‐scale RCTs are warranted.

 

Personalized Medicine in Psychiatry

Volumes 17–18, November–December 2019, Pages 17-22

Mayank V.Jogab Danny J.J.Wangb Katherine L.Narrac

https://doi.org/10.1016/j.pmip.2019.03.001Get rights and content

Highlights

  • TDCS may be less suited for treatment-resistant depression.
  • Combining tDCS with pharmaco- or psychotherapies may enhance therapeutic outcomes.
  • Optimizing tDCS parameters to individual patients can improve physiological response.

Abstract

Transcranial direct current stimulation (tDCS) is a low intensity neuromodulation technique shown to elicit therapeutic effects in a number of neuropsychological conditions. Independent randomized sham-controlled trials and meta- and mega-analyses demonstrate that tDCS targeted to the left dorsolateral prefrontal cortex can produce a clinically meaningful response in patients with major depressive disorder (MDD), but effects are small to moderate in size. However, the heterogeneous presentation, and the neurobiology underlying particular features of depression suggest clinical outcomes might benefit from empirically informed patient selection. In this review, we summarize the status of tDCS research in MDD with focus on the clinical, biological, and intrinsic and extrinsic factors shown to enhance or predict antidepressant response. We also discuss research strategies for optimizing tDCS to improve patient-specific clinical outcomes. TDCS appears suited for both bipolar and unipolar depression, but is less effective in treatment resistant depression. TDCS may also better target core aspects of depressed mood over vegetative symptoms, while pretreatment patient characteristics might inform subsequent response. Peripheral blood markers of gene and immune system function have not yet proven useful as predictors or correlates of tDCS response. Though further research is needed, several lines of evidence suggest that tDCS administered in combination with pharmacological and cognitive behavioral interventions can improve outcomes. Tailoring stimulation to the functional and structural anatomy and/or connectivity of individual patients can maximize physiological response in targeted networks, which in turn could translate to therapeutic benefits.

Studies about EMDR

Patricia Novo Navarroa,b,c, Ramón Landin-Romerod,e,f,g, Rocio Guardiola-Wanden-Bergheb,c, Ana Moreno-Alcázarc,d, Alicia Valiente-Gómezc,d, Walter Lupoh, Francisca Garcíai, Isabel Fernándezj, Víctor Pérezb,c
y Benedikt L. Amannc,d,∗

Abstract

Eye movement desensitization and reprocessing (EMDR) is a relatively new psychot- herapy that has gradually gained popularity for the treatment of post-traumatic stress disorder. In the present work, the standardised EMDR protocol is introduced, along with current hypot- heses of its mechanism of action, as well as a critical review of the available literature on its clinical effectiveness in adult post-traumatic stress disorder. A systematic review of the published literature was performed using PubMed and PsycINFO databases with the keywords «eye movement desensitization and reprocessing» and «post-traumatic stress disorder» and its abbreviations «EMDR» and «PTSD». Fifteen randomised controlled trials of good methodologi- cal quality were selected. These studies compared EMDR with unspecific interventions, waiting lists, or specific therapies. Overall, the results of these studies suggest that EMDR is a useful, evidence-based tool for the treatment of post-traumatic stress disorder, in line with recent recommendations from different international health organisations.

© 2016 SEP y SEPB. Published by Elsevier España, S.L.U. All rights reserved.

Journal of EMDR Practice and Research

 Volume 13, Issue 4

  • de Jongh, Ad
  • Amann, Benedikt L.
  • Hofmann, Arne
  • Farrell, Derek
  • Lee, Christopher W.

Journal of EMDR Practice and Research

Vol 13Issue 4

DOI: 10.1891/1933-3196.13.4.261

Abstract

Given that 2019 marks the 30th anniversary of eye movement desensitization and reprocessing (EMDR) therapy, the purpose of this article is to summarize the current empirical evidence in support of EMDR therapy as an effective treatment intervention for posttraumatic stress disorder (PTSD). Currently, there are more than 30 randomized controlled trials (RCT) demonstrating the effectiveness in patients with this debilitating mental health condition, thus providing a robust evidence base for EMDR therapy as a first-choice treatment for PTSD. Results from several meta-analyses further suggest that EMDR therapy is equally effective as its most important trauma-focused comparator, that is, trauma-focused cognitive behavioral therapy, albeit there are indications from some studies that EMDR therapy might be more efficient and cost-effective. There is emerging evidence showing that EMDR treatment of patients with psychiatric disorders, such as psychosis, in which PTSD is comorbid, is also safe, effective, and efficacious. In addition to future well-crafted RCTs in areas such as combat-related PTSD and psychiatric disorders with comorbid PTSD, RCTs with PTSD as the primary diagnosis remain pivotal in further demonstrating EMDR therapy as a robust treatment intervention.

Journal of EMDR Practice and Research Volume 13, Issue 4

  • Tesarz, Jonas
  • Wicking, Manon
  • Bernardy, Kathrin
  • Seidler, Günter H.

Journal of EMDR Practice and Research Vol 13 Issue 4 DOI:

10.1891/1933-3196.13.4.337

Abstract

Chronic pain is the most common global cause of functional and quality of life limitations. Although there are many effective therapies for the treatment of acute pain, chronic pain is often unsatisfactory. Against this background, there is currently an urgent need to develop innovative therapies that enable more efficient pain relief. Psychosocial factors play an important role in the development and persistence of chronic pain. Especially in patients with high levels of emotional stress, significant anxiety, or relevant psychological comorbidity, classical pain therapy approaches often fail. This is in line with the results of recent pain research, which has shown that dysfunctions in emotion processing have a significant influence on the persistence of pain symptoms. The recognition that pain can become chronic through maladaptive emotional processing forms the pathophysiological basis for the application of eye movement desensitization and reprocessing (EMDR) in the treatment of chronic pain. In this sense, EMDR can be used as an established method for desensitizing and processing of emotional distress from trauma therapy specifically for processing emotional stress in patients with chronic pain. Against this background, it is not surprising that the implementation of EMDR for patients with chronic pain is expanding. However, the increasing clinical use of EMDR in the treatment of chronic pain has also led to a reputation to test the efficacy of EMDR in pain management through randomized clinical trials. In addition to numerous case control studies, there are now also six randomized controlled clinical trials available that demonstrate the efficacy and safety of EMDR in the treatment of different pain conditions. However, in order to overcome several methodological limitations, large multicenter studies are needed to confirm the results.

Marianne Littel* , Marcel A. van den Hout and Iris M. Engelhard

Clinical Psychology, Utrecht University, Utrecht, Netherlands

Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During this treatment, patients recall traumatic memo- ries while making horizontal eye movements (EM). Studies have shown that EM not only desensitize negative memories but also positive memories and imagined events. Substance use behavior and craving are maintained by maladaptive memory associa- tions and visual imagery. Preliminary findings have indicated that these mental images can be desensitized by EMDR techniques. We conducted two proof-of-principle studies to investigate whether EM can reduce the sensory richness of substance-related mental representations and accompanying craving levels. We investigated the effects of EM on (1) vividness of food-related mental imagery and food craving in dieting and non-dieting students and (2) vividness of recent smoking-related memories and cigarette craving in daily smokers. In both experiments, participants recalled the images while making EM or keeping eyes stationary. Image vividness and emotionality, image-specific craving and general craving were measured before and after the intervention. As a behavioral outcome measure, participants in study 1 were offered a snack choice at the end of the experiment. Results of both experiments showed that image vividness and crav- ing increased in the control condition but remained stable or decreased after the EM intervention. EM additionally reduced image emotionality (experiment 2) and affected behavior (experiment 1): participants in the EM condition were more inclined to choose healthy over unhealthy snack options. In conclusion, these data suggest that EM can be used to reduce intensity of substance-related imagery and craving. Although long-term effects are yet to be demonstrated, the current studies suggest that EM might be a useful technique in addiction treatment.

Front. Psychiatry 7:14. doi: 10.3389/fpsyt.2016.00014

Hwallip Bae • Changwoo Han • Daeho Kim

Ó Springer Science+Business Media New York 2013

Abstract

This case series introduces the desensitization of triggers and urge reprocessing (DeTUR), as a promising adjunctive therapy in addition to comprehensive treatment package for pathological gambling. This addiction protocol of eye movement desensiti- zation and reprocessing was delivered to four male inpatients admitted to a 10-week inpatient program for pathological gambling. The therapist gave three 60-min weekly sessions of the DeTUR using bilateral stimulation (horizontal eye movements or alterna- tive tactile stimuli) focusing on the hierarchy of triggering situations and the urge to initiate gambling behaviors. After treatment, self-reported gambling symptoms, depression, anx- iety, and impulsiveness were all improved, and all the participants reported satisfaction with the therapy. They were followed up for 6 months and all maintained their abstinence from gambling and their symptomatic improvements. Given the efficiency (i.e., brevity and efficacy) of the treatment, a controlled study to confirm the effects of the DeTUR on pathological gambling would be justified.

Open Access Original
Article DOI:
10.7759/cureus.3250

Received 08/27/2018
Review began 08/31/2018
Review ended 08/31/2018
Published 09/04/2018

Ali M. Khan 1 , Sabrina Dar 2 , Rizwan Ahmed 3 , Ramya Bachu 4 , Mahwish Adnan 5 , Vijaya Padma Kotapati 6

1. Psychiatry Resident, University of Texas Rio Grande Valley, Harlingen, Texas, USA 2. Psychiatry, Saint Elizabeth’s Medical Center, Boston, MA, USA 3. Psychiatry, Liaquat College, Karachi, PAK 4. Psychiatry, Northwell Zucker Hillside Hospital, New York, USA 5. Center for Addiction and Mental Health, University of Toronto, Toronto, CAN 6. Psychiatry, Manhattan Psychiatric Center, New York, USA

Corresponding author: Vijaya Padma Kotapati, padmakotapati89@gmail.com Disclosures can be found in Additional Information at the end of the article

Abstract

Background

Post-traumatic stress disorder (PTSD) is prevalent in children, adolescents and adults. It can occur alone or in comorbidity with other disorders. A broad range of psychotherapies such as cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) have been developed for the treatment of PTSD.

Aim

Through quantitative meta-analysis, we aimed to compare the efficacy of CBT and EMDR: (i) relieving the post-traumatic symptoms, and (ii) alleviating anxiety and depression, in patients with PTSD.

Methods

We systematically searched EMBASE, Medline and Cochrane central register of controlled trials (CENTRAL) for articles published between 1999 and December 2017. Randomized clinical trials (RCTs) that compare CBT and EMDR in PTSD patients were included for quantitative meta- analysis using RevMan Version 5.

Results

Fourteen studies out of 714 were finally eligible. Meta-analysis of 11 studies (n = 547) showed that EMDR is better than CBT in reducing post-traumatic symptoms [SDM (95% CI) = -0.43 (- 0.73 – -0.12), p = 0.006]. However, meta-analysis of four studies (n = 186) at three-
month follow-up revealed no statistically significant difference [SDM (95% CI) = -0.21 (-0.50 – 0.08), p = 0.15]. The EMDR was also better than CBT in reducing anxiety [SDM (95% CI) = -0.71 (-1.21 – -0.21), p =0.005]. Unfortunately, there was no difference between CBT and EMDR in reducing depression [SDM (95% CI) = -0.21 (-0.44 – 0.02), p = 0.08].

Conclusion

The results of this meta-analysis suggested that EMDR is better than CBT in reducing post- traumatic symptoms and anxiety. However, there was no difference reported in reducing depression. Large population randomized trials with longer follow-up are recommended to build conclusive evidence.

Serkan Basmanpsychotherapie Berlin

Specialist in psychiatry and psychotherapy
Languages: German | Turkish | English

Clinical activities

  • 2021 Senior physician at the Center for Transcultural Psychiatry
  • 2020 Specialist in Psychiatry and Psychotherapy
  • 2018-2019 Asisstence physician in neurology at TWW Hospital Berlin- focus on Parkinson's disease and pain therapy
  • 2015- 2020 Training in depth psychological psychotherapy
  • 2014 German license to practice
  • 2013- 2020 Resident in psychiatry and psychotherapy in Germany
  • 2012 Specialist in anesthesia and intensive care medicine
  • 2008-2012 Residency in anesthesiology in Istanbul
  • 1997-2005 Faculty of Medicine, Istanbul Cerrahpasa

Academic studies

  • Comparison of actual mortality and morbidity with predicted modified APACHE-II and risk scoring prism in pediatric patients after arterial switch surgery (2012).
  • Comparison of neostigmine and sugammadex to assess the effect of rocuronium on neuromuscular blockade in patients undergoing pulmonary resection surgery (2011)
  • Poster presentation at the 45th National Congress of the Turkish Society of Anesthesiology and Critical Care Medicine (2011).

 

Psychologist (M.Sc.) | Brain stimulation methods (NFB, rTMS) | Relaxation methods
languages: German | English | Spanish

Professional background

Studies of psychology at the Julius-Maximilians University of Würzburg with focus on clinical psychology, intervention psychology and clinical neuroscience.
Erasmus semester at the Universitat de les Illes Balears, Spain
Research assistant at the Department of General Psychology in the area of motivation and emotion, University of Würzburg, Germany
Internship at the Milton Erikson Institute, Rottweil, Germany
Internship at the Practice for Forensic Psychology, Würzburg
Short internship at the Bürgerhospital, Klinikum Stuttgart, Center for Mental Health, Department: Addictive Disorder
Since 2018 member of the team Dr. Scheib

Further education:

Autogenic training
Behavioral therapy
Repetitive transcranial magnetic stimulation
Systemic consultant in further education

"You have to keep finding your way through the little thoughts that annoy you to the big thoughts that strengthen you." (Dietrich Bonhoeffer)

Julia Stumpp

Human Medicine
Languages: German | English

University studies

2009 - 2015 Study of human medicine at the LMU Munich
Since 19.11.2015 Approbation granted by the government of Upper Bavaria

Professional experience

  • 2008-2010 Nursing assistant, Seniorenzentrum Pichlmayr, Aschheim
  • 2010-2015 Student assistant in the area of telephone coordination of organ donations in Bavaria South, German Foundation for Organ Transplantation Bavaria South, Munich
  • 2011-2015 Promoter in the field of organ donation, Fürs Leben e.V.
  • 2012 - 2016 Working student in the field of OR organization and coordination of organ offers, Transplant Center Munich of the Ludwig-Maximilians-University.
  • 06/2016 - 05/2019 Resident in internal medicine within the framework of further training in general medicine, Ebersberg District Hospital
  • 08/2019 - 07/2020 Resident physician in further training to become a general practitioner, Practice for General Medicine, Dr. med. Stephanie

Advanced training

Since 2018 advanced training in basic psychosomatic care.

Dr. med. Maksym YarmolenkoMaxim Yarmolenko psychosomatische Medizin und Psychotherapie berlin

Specialist in psychosomatic medicine and psychotherapy
Languages: German, Russian, Ukrainian, English

Clinical activity

  • 2014 University Hospital Erlangen, Department of Psychosomatic Medicine
  • 2017 Psychiatric work at the Center for Affective Disorders and Center for Transcultural Psychiatry (Humboldt-Klinikum Vivantes)
  • 2019 Internal Medicine (Clinics at the Theodor-Wenzel-Werk)
  • 2020 Specialist in psychosomatic medicine and psychotherapy, functional senior physician at the psychosomatic day clinic Sonnenallee (Vivantes Neukölln). Clinical focus: Affective disorders, anxiety and obsessive-compulsive disorders, trauma sequelae disorders, pain disorders, eating disorders, transcultural psychotherapy.

Scientific activity, studies

  • 2006-2013 Medical studies at the University of Duisburg-Essen
  • 2010-2014 Research in neuropathology (University of Essen), PhD on the topic: "Running during pregnancy attenuates neuroinflammation and oxidative stress of the offspring in a transgenic mouse model of Alzheimer's disease"
  • 2015 Junior Researcher Support Program "Posttraumatic Disorders" (Lindau Psychotherapy Weeks).

Dipl. med. Ralph GötzDr Ralph Götz psychotherapie München

Specialist in psychiatry and psychotherapy
Languages: German | English

Professional background:

  • Medical studies in Leipzig until 1989
  • Residency in Lower Saxony and Bavaria
  • Specialist certification by the Bavarian Medical Association in 1997
  • Psychotherapist since 1993
  • Diving physician (GTÜM)
  • Specialized knowledge/qualifications: Addiction medicine, rescue service,
  • Balint group leader (DBG); NLP master, traffic medicine
  • In private practice since 1995

 

Agne Brand

Agne Brand Psychotherapie auf MallorcaPsychologist | Psychotherapist | Behavioral Therapy | EMDR |
Gestalt therapy | crisis intervention | trauma | pain

Languages: German | Lithuanian | Russian | English | Spanish | Catalan
Núm. Colegiado: B-02812

Active in the fields of internal medicine, general medicine and psychiatry, as well as an emergency physician.Dr Mario Scheib, Ketamintherapie in Berlin

1984 GP practice in Frankfurt with psychosomatic orientation.

1988 Practice for psychotherapy in Frankfurt am Main.

Organization and realization of training doctors in the area of transcultural psychosomatic and traditional medicine in Sri Lanka and Peru. Scientific work on the South American psychoanalysis history.

Education as leader of “balintguppen” and lecturer in autogenic training.

Since 1995, courses for basic psychosomatic care for doctors
with recognition by the medical associations in Germany and the Ministry of Health of the Balearic Islands.

Since 2001 practice and beds for psychotherapy treatment and addiction treatment in Palma de Mallorca, associated with Palmaclinic and the Hospital Quirón Palmaplanas

Organization and management of medical training in Spain, Germany and the United Arab Emirates,
inter alia, in the areas of Psychotherapy and Psychosomatics, Addiction Medicine, Pain Therapy, relaxation techniques, hypnosis, sexual medicine.

Memberships

  • International College of Psycosomatic Medicine (ICPM)
  • Deutsche Gesellschaft für psychosomatische Medizin (DGPM)
  • Deutsche Gesellschaft für ärztliche Hypnose und Autogenes Training
  • Deutsche Gesellschaft für Biofeedback (DGBfb)
  • Deutsche Balintgesellschaft (DBG)
  • Gründungsmitglied und Vorsitzender der Hellenic Balint Society (www.hellenicbalintsociety.gr)

Psychologist | Clinical Hypnotherapist | Coach | Scientific Associate
Languages: English | German

hypnose Berlin Sophie Adler

Career 

  • Studied psychology in Berlin and in Innsbruck with a focus on clinical psychology and psychoanalysis.
  • Student assistant in the research project “Psychoanalytic case-related supervision in youth welfare” with Prof. Dr. Andreas Hamburger at the IPU Berlin.
  • Mentoring activity at the IPU Berlin.
  • Co-foundation and development of the Student Council at IPU Berlin.
  • Department for matters of trust.
  • Day clinic for anxiety disorders and depression VIVANTES Klinikum Spandau, Berlin.
  • Tutor “Clinical Psychology and Psychotherapy” with Prof. Dr. biol. hum. Anna Buchheim.
  • Psychologist at the Children and Youth Home JUGENDLAND, Innsbruck.
  • Training in hypnosis, hypnotherapy and hypnosis coaching at TherMedius Institute.
  • Psychologist, hypnosis therapist and research assistant to Dr. Mario Scheib.
  • Kundalini Yoga Teacher Training at RaMa-Institute Mallorca
  • Training “The MIND Integration Program”
  • Member of the first KRIYA-Consultation Group (California)

Professional characteristics / Memberships

  • Specialization in working with altered states of consciousness and their integration
  • Research and work on “Substance-assisted therapy”
  • Development and exploration of the “Ketamine Hypnosis Package”
  • MIND European Foundation for Psychedelic Science

Karin Svabik

Karin Svabik psychologic Praxis Dr Scheib berlin

Psychologist | Behavioural Therapist  | Mediator | Relationship Counsellor | Coach | Psychologic Councelling | Equine therapy | Awareness teacher | Mental trainer | Relaxation Therapist

Education:

    • 1992 - 1998 study of psychology at the Free University of Berlin with a degree in psychology
    • 1987 - 1991 apprenticeship as a goldsmith's assistant, master craftsman goldsmith Diehl, Berlin with qualification as goldsmith's assistant
    • In-service training 2020 Training as a hypnotherapist, Hypnose Siegrist, Zurich
    • 2016 - 2017 certified equine therapist, Centro Hippico, Oberkrämer
    • 2011 certified stress management trainer, relaxation therapist, AT, PMR, IEK-Berlin
    • 2006 psychological coach, Dr. Wolff coaching
    • 01/2000 - 10/2000 mediator and couple counselor at the Institute for Dispute Culture, Berlin
    • 09/1998 - 09/1999 behavioral talk therapist at the trainer and therapist community, Berlin

Professional activities:

  • Since 2018 until today: Psychological therapist, Clinica Dr. Scheib/ Clinica Luz Mallorca
  • Since 2017 until today: Lecturer and equine therapist with own therapy horse, Centro Hipico, Oberkrämer
  • From 2011 to 2018: Psychological therapist in her own practice, Institut Aus-Zeit
  • Since 2011 - 2017: Lecturer for stress management, resilience, PMR and AT, IEK-Berlin
  • Since 2011 - 2020: Individual case assistant at the Social Psychiatric Service Berlin
  • 1/2003 - 12/2011: Head of Personnel Development Department at Regiocom GmbH, Halle
  • Since 2001 continuously until today: Business partner of graduate business economist Kaj-Arne-Hennig from Phone Service, focus on management training, Hanover
  • 07/2003 - 05/2004: Evaluation of network projects in cooperation with Prof. Dr. Rolf U. Sprenger, Ifo Institute Munich
  • 08/2001 - 04/2002: research assistant with teaching activity at the Freie Universität Berlin, in the field of economic and organizational psychology, Prof. Dr. Detlev Liepmann
  • 05/2001 - 5/2006: Conception and moderation of the start-up workshops of the Association of Young Entrepreneurs
  • 07/1999 - 01/2001: personnel and organisational developer, ÖKOTEC Management GmbH, Berlin, Dr. Zschocke
  • 1998 - 2001: Work and organizational psychologist at the Institute for Personnel Development, Prof. Dr. Hans Gerhard Sack

Susanne Maus

Dr Susanne Maus Berlin

Specialist in rehabilitative and physical medicine

Languages: German | Spanish | French | English

Professional background

  • Study of modern foreign languages and philologies
  • Study of human medicine 1989-1998 at the Freie University of Berlin
  • Practical doctor in neurology, Sophie and Hufeland Clinic Weimar
  • Doctorate at the University of Marburg on RTMS on the premotor dorsal cortex to improve motor hand function after a stroke
  • Completion of the specialist examination for rehabilitative and physical medicine

Advanced training

  • Knowledge of radiation protection and teleradiology
  • Basic course autogenic training
  • In training for manual therapy

Professional Activities:

  • Assistant doctor in the Bavaria Clinic for Neurorehabilitation Dresden / Kreischa
  • Activity in a life insurance risk assessment Assistant doctor in orthopedics, LVA Klinik Hohenelse / Rheinsberg
  • Assistant doctor in orthopedics, Rehabilitation Clinic Bad Heilbrunn
  • Resident in Neurologie und Orthopädie Rehazentrum Ingolstadt
  • Assistant doctor at the Neurologie Klinikum Ingolstadt
  • Assistant doctor in geriatrics, orthopedics and neurology, Passauer Wolf Bad Gögging
  • Resident physician in the geriatrics KMG Klinikum Pritzwalk
  • Activity in traffic medicine and video consultation
  • Since 2021: Freelance employee in the practice of Dr Scheib Berlin

 

My Motto:
Treat others as you wish to be treated

 

 

Tobias Müller

Doctor | Engineer (B.Sc. Medical Technology) | scientific AssociateTobias Müller, Arzt Praxis dr Scheib Berlin

Languages: German, English

Academic education:

    • 2014 - 2020: Study of human medicine in Erlangen
    • 2010 - 2013: Study of medical technology (Bachelor of Science) in Erlangen with focus on medical electronics and medical image and data processing

Practical experience:

    • Practical year:  Ear, nose and throat medicine - Plastic surgery (Park-Klinik Weißensee, Berlin)
    •  Internal and emergency medicine (Bürgerspital Solothurn, Switzerland)
    • Surgery (Munich Clinic Bogenhausen)

Internships:

    • Neurosurgery (Charité Campus Benjamin-Franklin)
    • Anaesthesiology and operative intensive care medicine (Charité Campus Mitte)
    • Child and adolescent psychiatry (University Hospital Erlangen)

Publications since 2017:

  • PhD at the Psychiatric and Psychotherapeutic Clinic in Erlangen with the topic "The role of Bassoon in glutamatergic neurons of the forebrain in the amplifying effects of alcohol in the animal model on the mouse"
  • 2013: Lecture at the First Russian German Conference on Biomedical Engineering in Hanover with the topic "EEG Monitoring During General Anesthesia"

Anja Frank

Childhood Educator | Apparative methods (rTMS, qEEG, Neurofeedback, HRV) | Hypnosis Coach | Scientific Associate Languages: German | EnglishAnja Frank Praxis dr Scheib Berlin

Professional background

● Studied psychology and psychoanalysis in Berlin and childhood education, as well as early childhood educational research (M.A.) in Potsdam, both with a focus on psychoanalysis
● Consultation assistant in the ophthalmological practice of Dr. Frank
● Internship in the psychiatric sanatorium SHG Klinikum Sonnenberg in Saarbrücken; closed station
● Work as an individual case helper and integration helper for hard of hearing children (CI) with a focus on learning to hear and use sign language (Jugendamt & Albert-Schweitzer-KiTa Reinickendorf)
● Internship in the Trilingual Crèche & KiTa Cheburashka Prenzlauer Berg
● Internship in the emergency accommodation for refugees Cyclopstraße, Wittenau
● Internship at the Trenkle organization for the ,, 3rd Parts Therapy Conference ”in Heidelberg
● Seminar assistant at Conflict House e.V.
● Since 2018: Pedagogical and psychological care for young adults with diagnoses from the schizophrenic group of forms (transitional residence of the support group for mental health e.V.)
● Since 2020: Research internship at SKKIPPI, the effectiveness study on psychodynamic / psychoanalytic parent-infant-toddler therapy (International Psychoanalytic University)
● Privatpraxis  Dr. Scheib

Advanced training
● Training in hypnosis, hypnotherapy and hypnosis coaching (96 hours; TherMedius Institute)
● Training in mediation & conflict management (120 hours; Conflict House e.V. & FH Potsdam)
● Advanced training in ketamine hypnosis based on the Sophie Adler approach (Instituto Dr. Scheib)
● Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder and depression (neuroCare Group)
● SCP-Neurofeedback (neuroCare Group)
● In further training: Assessment method Emotional Availability Scale for quantitative assessment of the quality of dyadic relationships (International Center for Excellence in Emotional Availability in Boulder, USA)
● Certified rater for the Attachment-Q-Sorts method for determining attachment styles (University of Vienna) ● In further training: Metacognitive training in psychosis (MKT +) (University Hospital Hamburg-Heppenheim)

Research interests & memberships
● Consciousness and hypnosis research
● Psychosis and schizophrenia research
● Parent-Infant-Toddler Therapy
● Member of the MIND European Foundation for Psychedelic Science

"If you touch the emptiness in your life,  flowers will bloom in its place. "
-Buddhist wisdom

Chiara Rolle

Psychologic Psychotherapist | vast experience in NeuropsychologyPsychologische Psychotherapeutin München Chiara Rolle
Languages: Italian, German, English

Professional education:

  • 01.01.2021-01.02.2021: Licence to practice repetitive Transcranial Magnetic Stimulation (rTms)
  • 18.11.2020: Master's degree in Advanced Studies Psychotherapy with focus on behaviour therapy MASPTVT from the University of Bern
  • 18.11.2020: License to practice as a psychological psychotherapist specialising in behavioural therapy
  • 10.03.2018 - present: Further training as a clinical neuropsychologist GNP-School for clinical Neuropsychology.
  • 01.04.2016-17.09.2020: DGVT - Training Center Munich / Bad Tölz - 4 Year education in psychological psychotherapy with focus on behaviour therapy.
  • 10.07.2013: License to practice as a psychologist-University of Turin.
  • 29.10.2012: Master's Degree in Clinical Psychology with 110/110 points- University of Turin- Italy
  • 01.10.2010 - 29.10.2012: Master’s Studies in clinical psychology and neuropsychology. - University of Turin, Italy.
  • 14.07.2010: Bachelor's Degree in neuropsychology (Faculty of Psychology) with 105/110 points.
  • 01.10.2007 - 14.07.2010: Bachelor Degree Studies in Neuropsychology (Faculty of Psychology) - University of Turin, Italy.

Berufserfahrung:

  • 01.01.2021- present: Private practice Dr. Scheib: Practice for hypnosis, neurofeedback, biofeedback, virtual reality, psychotherapy with a focus on behavior therapy, rTMS, ketamine infusions to treat depression, anxiety, obsessive-compulsive disorder, burn-out, neurological disorders, trauma-related disorders, addictions, etc. Part-time psychotherapist 20 hours / week
  • 01.06.2017- present:Benedictus Hospital Feldafing neurological, orthopedic and geriatric, rehabilitation center. Psychologist M.Sc. part-time 19 hours / week.
  • 01.07.2017 - 20.04.2020: DGVT Psychotherapy School in Munich: 600 hours of patient treatment as a Psychotherapist in education.
  • 01.10.2016 - 31.05.2017: District Hospital Landshut - Clinic for Psychiatry, Psychotherapy, Psychosomatic Psychologist MSc in internship.
  • 01.06.2014 - 30.09.2016: Asklepios Klinik Schaufling - Rehabilitation Center for patients with neurological, orthopedic, geriatric, cardiological and psychosomatic diseases. MSc psychologist in the neurological department full-time
  • 10.03.2014 - 30.05.2014: Klinikum Bogenhausen- Munich- Neurocenter Clinic for Neurology and Neuropsychology. Internship.
  • 02.09.2013 - 28.02.2014: Schön Klinik Bad Aibling- Specialized hospital for neurology. Internship
  • 18.07.2011 - 03.06.2013: Klinik „Puzzle“, Rehabilitation center for people with acquired brain damage- Turin (Italy). Internship.
  • 01.03.2010 - 30.05.2010: Presidio Ospedaliero Riabilitativo Beata Vergine Consolata – Specialist Clinic for Mental Disorders - S. Maurizio Canavese (Turin) - Italy. Internship

Frauke D. NeesPsychologin Berlin. ketamintherapie

Dipl.- Psychologist | Person-Centered Psychotherapy (GwG, HPG) | Psychodynamic Imaginative Trauma Therapy (PITT according to Reddemann) | Attachment-Based Therapy (Brisch, Munich) | "Traumatic Stress Studies" with Bessel van der Kolk in Boston | Clinical Hypnosis and Hypnotherapy (DGH) | Inner Parts Work IFS (Internal Family System, Schwartz, USA, in advanced training Ketamine Assisted Therapy (Polarisinsight, San Francisco) | Certified Practitioner with AIN (Applied Improvisation Network) | Lecturer | Trainer | Coaching

Languages: German, English, Spanish

She is also an experienced improvisation actress, tango dancer and clown.

Since 2008 she has been giving workshops in further education institutes as well as at congresses for psychotherapists, psychologists and doctors with elements of improvisational theater, acting and tango on the topics of resilience, change processes, creativity, humor.

Conception and leadership of professional excursions to Argentina, Cuba and Colombia on the topic of psychology/psychotherapy in the context of history and politics.

For many years her second center of life was in Buenos Aires. She combines in a unique way the analytical and empathic skills of a psychologist with the power of improvisation and her intercultural experience.

www.frauke-nees.de

Publications:

Nees, F. (2019). Self-strengthening: 80 creative experiential exercises for psychotherapy. With 20-page booklet. Beltz Verlag, Weinheim.

 

 

Hiba Abdelgalil

Languages: English, German, Arabic

 Professional Career

Hiba abdelgalil Ärztin in der Privatpraxis Dr Scheib in Berlin

  • 02 / 2020—03 / 2020  Clinic Dahme Spreewald (Lübben)  
  • 10/2014 - 02/2016 Medical coordinator, Health attaché
    of the Saudi Embassy in Berlin
  • 10/2009 - 02/2012  Scientific Associate, University of Khartoum, Pathology program part 1
  • 01/2007 - 01/2008 Assistant doctor Omdurman Military Hospital, Hematology and oncology
  • 04/2005 - 10/2006 Medical intern
    Internal Medicine- Chest Center- Khartoum Learning Hospital
    Internal medicine-Soba Hospital
    Pediatric Academy Learning Hospital
    Obstetrics and Gynecology- Omdurman Saudi hospital Orthopedic Omdurman Military Hospital

 Education

  •  04/1998 - 04.2004 Study of Human Medicine Ahfad University for Women, Faculty of Medicine, Omdurman / Sudan Major fields of study: Human Medicine, Surgery
    Degree: MBBs