OPEN Foundation

J. Wang

Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials

February 6, 2022 / Depression, Ketamine, Papers / Leave a Comment / By / , , , , , , ,

Abstract

Esketamine is a promising drug which can induce antidepressant effects in Major Depression Disorder (MDD). Several randomized controlled trials (RCTs) have been implemented to assess the efficacy and safety of esketamine for the treatment of MDD. Therefore, we carried out a meta-analysis to assess adverse effect profiles of esketamine for the treatment of MDD. We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase and Cochrane Library databases. Finally, four RCTs with 551 patients were included in our study. We pooled 551 patients from 4 RCTs. Compared with placebo, an increased risk of adverse effects was observed in our analysis. After using esketamine, the risk of nausea (RR = 2.34, 95% CI, 1.04 to 5.25, P = 0.04), dissociation (RR = 4.54, 95% CI, 2.36 to 8.73, P < 0.00001), dizziness (RR = 3.00, 95% CI, 1.80 to 5.00, P < 0.0001), vertigo (RR = 7.47, 95% CI, 2.55 to 21.86, P = 0.0002), hypoesthesia (RR = 5.68, 95% CI, 2.06 to 15.63, P = 0.0008), sedation (RR = 3.96, 95% CI, 1.29 to 12.15, P = 0.02) and paresthesia(RR = 3.05, 95% CI, 1.07 to 8.65, P = 0.04)were significantly increased compared with placebo. Our synthesized data analysis revealed drug specific risk profiles. The most frequent adverse effects under treatment with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia,sedation and paresthesia.

Yang, S., Wang, J., Li, X., Wang, T., Xu, Z., Xu, X., Zhou, X., & Chen, G. (2021). Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials. The Psychiatric quarterly, 10.1007/s11126-020-09871-x. Advance online publication. https://doi.org/10.1007/s11126-020-09871-x

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MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study

January 6, 2022 / End of Life Anxiety, MDMA, Papers, Psychotherapy / Leave a Comment / By / , , , , , , , , , , , ,

Abstract

The success of modern medicine creates a growing population of those suffering from life-threatening illnesses (LTI) who often experience anxiety, depression, and existential distress. We present a novel approach; investigating MDMA-assisted psychotherapy for the treatment of anxiety in people with an LTI. Participants with anxiety from an LTI were randomized in a double-blind study to receive MDMA (125 mg, n = 13) or placebo (n = 5) in combination with two 8-h psychotherapy sessions. The primary outcome was change in State-Trait Anxiety Inventory (STAI) Trait scores from baseline to one month post the second experimental session. After unblinding, participants in the MDMA group had one open-label MDMA session and placebo participants crossed over to receive three open-label MDMA sessions. Additional follow-up assessments occurred six and twelve months after a participant’s last experimental session. At the primary endpoint, the MDMA group had a greater mean (SD) reduction in STAI-Trait scores, – 23.5 (13.2), indicating less anxiety, compared to placebo group, – 8.8 (14.7); results did not reach a significant group difference (p = .056). Hedges’ g between-group effect size was 1.03 (95% CI: – 5.25, 7.31). Overall, MDMA was well-tolerated in this sample. These preliminary findings can inform development of larger clinical trials to further examine MDMA-assisted psychotherapy as a novel approach to treat individuals with LTI-related anxiety.Trial Registration: clinicaltrials.gov Identifier: NCT02427568, first registered April 28, 2015.

Wolfson, P. E., Andries, J., Feduccia, A. A., Jerome, L., Wang, J. B., Williams, E., Carlin, S. C., Sola, E., Hamilton, S., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2020). MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Scientific reports, 10(1), 20442. https://doi.org/10.1038/s41598-020-75706-1

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Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials

January 3, 2022 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychotherapy / Leave a Comment / By / , , , , , , ,

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.

Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.

Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.

Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = – 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = – 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.

Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2020). Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology, 237(8), 2485–2497. https://doi.org/10.1007/s00213-020-05548-2

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Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials

May 11, 2020 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.
Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.
Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.
Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = – 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = – 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.
Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., … & Doblin, R. (2020). Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology., https://doi.org/10.1007/s00213-020-05548-2
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Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents

July 1, 2016 / Ayahuasca, Medicine, Other subjects, Papers, Publications / By / , , , , ,

Abstract

A series of N(9)-substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N(9)-substituted harmine derivatives had anticancer effects. In particular, N(9)-haloalkyl derivatives 9a-9c and N(9)-acyl harmine derivatives 11c and 11d, with IC50 values less than 1μM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure-activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N(9)-position of harmine could significantly increase the anticancer activity. The most active compound (11d) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner.
Du, H., Tian, S., Chen, J., Gu, H., Li, N., & Wang, J. (2016). Synthesis and biological evaluation of N 9-substituted harmine derivatives as potential anticancer agents. Bioorganic & medicinal chemistry letters, 26(16), 4015-4019. 10.1016/j.bmcl.2016.06.087
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30 April - Q&A with Rick Strassman

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