Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial.

Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.

Psychiatric risks for worsened mental health after psychedelic use.

BACKGROUND: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies. METHODS: A "bottom margin analysis" approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies (N = 807). We define "negative response" by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses. RESULTS: We find that 16% of the cohort falls into the "negative responder" subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample (b = 1.425, p < 0.05). CONCLUSION: We infer that the presence of a personality disorder may represent an elevated risk for psychedelic use and hypothesize that the importance of psychological support and good therapeutic alliance may be increased in this population.

Effects of DMT on mental health outcomes in healthy volunteers.

Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.

Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder.

Background: MDMA-assisted psychotherapy (MDMA-AP) is a combined psychotherapeutic and pharmacologic intervention that shows promise in the treatment of posttraumatic stress disorder (PTSD). Although therapeutic alliance has been established as a key predictor across psychotherapies and is emphasised within MDMA-AP treatment manuals, research has not yet examined the relationship between therapeutic alliance and MDMA-AP treatment outcomes.Objective: Examine whether therapeutic alliance predicts changes in PTSD symptoms following MDMA-AP.Method: Twenty-three individuals with chronic PTSD participated in a MDMA-AP clinical trial that included a randomised (MDMA vs. placebo) and open-label phase. The present analyses focused on participants who were administered MDMA over the course of the randomised and open-label phases (n = 22). Therapeutic alliance was assessed using the Working Alliance Inventory at sessions baseline (pre-session 3) and sessions 4 and 9. PTSD symptoms were assessed using the Clinician Administered PTSD Scale and the Impact of Events Scale-Revised.Results: Controlling for baseline clinician-assessed PTSD severity, therapeutic alliance at sessions 4 and 9 (but not baseline) significantly predicted post-MDMA-AP clinician-assessed PTSD severity. Controlling for baseline self-reported PTSD severity, therapeutic alliance at baseline (although this did not survive correction for multiple comparisons) and sessions 4 and 9 predicted post-MDMA-AP self-reported PTSD severity.Conclusions: The present results provide the first preliminary evidence for the relationship between the therapeutic alliance and treatment outcomes within MDMA-AP for PTSD. These findings highlight the important role of psychotherapy, and common psychotherapeutic factors, within MDMA-AP. Replication in studies with larger and more diverse clinical samples remain necessary.Trial registration: ClinicalTrials.gov identifier: NCT00090064.

Among individuals with chronic posttraumatic stress disorder, therapeutic alliance predicted changes in posttraumatic stress disorder severity following MDMA-assisted psychotherapy.Therapeutic alliance may play a key role in facilitating therapeutic improvement within MDMA-assisted psychotherapy.Further research remains necessary to confirm these preliminary findings and the role of therapeutic alliance in MDMA-assisted psychotherapy.

Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences.

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.

Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3-4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression or provide substantial clinical benefit. Furthermore, despite psychological distress being highly prevalent in ALS patients, psychological treatments remain understudied. Psychedelics (i.e., serotonergic psychedelics and related compounds like ketamine) have seen a resurgence of research into therapeutic applications for treating a multitude of neuropsychiatric conditions, including psychiatric and existential distress in life-threatening illnesses. Methods: We conducted a narrative review to examine the potential of psychedelic assisted-psychotherapy (PAP) to alleviate psychiatric and psychospiritual distress in ALS. We also discussed the safety of using psychedelics in this population and proposed putative neurobiological mechanisms that may therapeutically intervene on ALS neuropathology. Results: PAP has the potential to treat psychological dimensions and may also intervene on neuropathological dimensions of ALS. Robust improvements in psychiatric and psychospiritual distress from PAP in other populations provide a strong rationale for utilizing this therapy to treat ALS-related psychiatric and existential distress. Furthermore, relevant neuroprotective properties of psychedelics warrant future preclinical trials to investigate this area in ALS models. Conclusion: PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should rigorously explore this therapy for ALS in future trials.

How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change.

BACKGROUND: Psilocybin therapy is receiving attention as a mental health intervention with transdiagnostic potential. In line with psychotherapeutic research, qualitative research has highlighted the role of reductions in experiential avoidance (and increases in connectedness) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism underlying psilocybin therapy's therapeutic effects. METHOD: Data was used from a double-blind randomized controlled trial that compared psilocybin therapy (two 25 mg psilocybin session plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among individuals with major depressive disorder (N = 59). All participants received psychological support. Experiential avoidance, connectedness, and treatment outcomes were measured at pre-treatment and at a 6 week primary endpoint. Acute psilocybin experiences and psychological insight were also measured. RESULTS: With psilocybin therapy, but not escitalopram, improvements in mental health outcomes (i.e., well-being, depression severity, suicidal ideation, and trait anxiety) occurred via reductions in experiential avoidance. Exploratory analyses suggested that improvements in mental health (except for suicidal ideation) via reduction in experiential avoidance were serially mediated through increases in connectedness. Additionally, experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance following psilocybin therapy. LIMITATIONS: Difficulties inferring temporal causality, maintaining blindness to condition, and reliance upon self-report. CONCLUSIONS: These results provide support for the role of reduced experiential avoidance as a putative mechanism underlying psilocybin therapy's positive therapeutic outcomes. The present findings may help to tailor, refine, and optimize psilocybin therapy and its delivery.

Posttraumatic stress disorder treatment preference: Prolonged exposure therapy, cognitive processing therapy, or medication therapy?

To investigate preferences for evidence-based treatments for posttraumatic stress disorder (PTSD) and the role of likely PTSD in those preferences. Undergraduate students (N = 119) and participants recruited from trauma support groups (N = 126) read descriptions of front-line recommended treatments for PTSD, including prolonged exposure therapy (PE), cognitive-processing therapy (CPT), and medication therapy (MT). Participants selected their treatment of choice and provided ratings of the credibility and their personal reactions to each treatment. Participants generally preferred psychotherapeutic treatments (CPT and PE) over MT, and this finding persisted when considering likely PTSD. Trauma support group participants and students with no likely PTSD showed preference towards CPT over PE, and students with likely PTSD preferred both CPT and PE over MT. In both groups, credibility and personal reaction ratings were also generally higher for the psychotherapeutic treatments than MT, with the highest ratings of credibility and personal reactions for CPT. There was a significant interaction between treatment type and likely PTSD for credibility and personal reaction ratings among students, such that students with likely PTSD had lower credibility and personal reaction ratings to MT. Determining preference for PTSD treatment has important implications for maximizing treatment efficacy, adherence, and engagement. Our results indicate that individuals generally prefer psychotherapeutic treatments, highlighting the need to increase the availability and utilization of evidence-based psychotherapeutic treatments for PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Subjective distress, self-harm, and suicidal ideation or behavior throughout trauma-focused cognitive-behavioral therapy in transitional age youth.

OBJECTIVE: Elevations in distress, self-harm, and suicidal ideation or behavior are of significant concern in clinical practice. We examined these in a pilot trial of Trauma Focused-Cognitive Behavioral Therapy (TF-CBT) for transitional age youth (aged 15-25 years) with histories of interpersonal trauma and symptoms of posttraumatic stress disorder. METHOD: Participants were 20 young people (13 females, M = 19.5 years) from a pilot study of TF-CBT. Frequencies of elevated distress, self-harm, and suicidal ideation or behavior were measured throughout treatment sessions and across the treatment phases of TF-CBT. RESULTS: Across the 279 sessions of TF-CBT (m = 15.5 sessions), there were 16 incidents of elevated distress in seven participants (i.e., six in Phase I and five each in Phases II and III); 15 incidents of self-harming behavior in seven participants (five incidents in each of the three phases) and one incident of both elevated distress and suicide ideation (Phase I). CONCLUSION: Findings indicate that there may be a relationship between the experience of in session distress and self-harming behaviors. The importance of safety planning and coping skills (acquired in Phase 1) is stressed to ensure the effective implementation of TF-CBT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Correction to "On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review".

[This corrects the article DOI: 10.1021/acsptsci.1c00024.].

Decreases in Suicidality Following Psychedelic Therapy: A Meta-Analysis of Individual Patient Data Across Clinical Trials.

Objective: Suicide is a global health concern, and innovative interventions that target suicidality are needed. While psychedelic therapy shows promise for a range of mental health concerns, including suicidality, not all psychedelic therapy trials have published their suicidality results and no meta-analysis has been published on the topic. Therefore, we completed the first meta-analysis of patient-level data on the effects of psychedelics on suicidality.Data Sources: We conducted a systematic search of MEDLINE, PsycINFO, and PubMed for all psychedelic therapy clinical trials (last search: November 5, 2020).Study Selection: We identified all psychedelic therapy trials that included a measure or measure-item that assesses suicidality.Data Extraction: Suicidality data were requested from study authors and extracted using a data extraction form developed for this study.Results: We identified 8, and successfully collected data from 7, relevant trials. Analysis of standardized mean differences (SMDs) indicated that, relative to baseline, psychedelic therapy was associated with large effect sizes for acute (80-240 min) and sustained (1 day, 1-8 weeks, and 3-4 months) decreases in suicidality (SMD range = -1.48 to -2.36; 95% CI range, -4.30 to 0.23). At 6 months, the effect size was medium (SMD = -0.65; 95% CI, -1.14 to -0.16). Reductions in suicidality were significant at all time points except for 7-8 weeks. Acute and post-acute elevations in suicidality were rare (6.5% and 3.0%, respectively).Conclusions: Limitations include heterogeneous samples and interventions, as well as limited sample size and number of studies. Results provide preliminary support for the safety of psychedelic therapy and its positive effect on suicidality. Controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality may be warranted.

Evaluation of a decision aid for the treatment of depression among college students.

Objective: Depression, and its treatment, is a concern among college students. Research indicates decision aids (DA) improve patients' treatment knowledge, decision making, and decisional conflict; however, it is unknown whether they are helpful for disseminating depression treatment information to college students. This study evaluated a DA for depression and its impact on college students' knowledge and treatment decision making. Methods: College students (N = 144) completed questionnaires pre-, post-, and at 1-month follow-up after reviewing an evidence-based DA for depression. Results: Participants rated the DA as highly acceptable and useful, and their knowledge increased at post-treatment and follow-up. However, treatment option presentation order influenced decision making. Conclusions: This DA is a useful and acceptable decision-making tool, and increased knowledge of depression and its treatment among college students. This study proposes a novel tool for educating college students about depression treatment, furthering our understanding of factors influencing treatment preferences.

On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review.

Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly, further understanding of the relationship between classic psychedelics and suicidality is needed. Therefore, we conducted a systematic review of the relationship between classic psychedelics (both non-clinical psychedelic use and psychedelic therapy) and suicidality. We identified a total of 64 articles, including 41 articles on the association between non-clinical classic psychedelic use and suicidality and 23 articles on the effects of psychedelic therapy on suicidality. Findings on the association between lifetime classic psychedelic use and suicidality were mixed, with studies finding positive, negative, and no significant association. A small number of reports of suicide and decreased suicidality following non-clinical classic psychedelic use were identified. Several cases of suicide in early psychedelic therapy were identified; however, it was unclear whether this was due to psychedelic therapy itself. In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment. We identify some remaining questions and provide suggestions for future research on the association between classic psychedelics and suicidality.

Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer.

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained improvements in depression, demoralization, and hopelessness in people with cancer. Converging epidemiologic and clinical trial findings suggests a potential antisuicidal effect of this treatment. To probe our hypothesis that PAP relieves SI through its beneficial impacts on depression and demoralization (LoM in particular), we performed secondary analyses assessing within- and between-group differences with regard to LoM and an SI composite score. Among participants with elevated SI at baseline, PAP was associated with within-group reductions in SI that were apparent as early as 8 h and persisted for 6.5 months postdosing. PAP also produced large reductions in LoM from baseline that were apparent 2 weeks after treatment and remained significant and robust at the 6.5 month and 3.2 and 4.5 year follow-ups. Exploratory analyses support our hypothesis and suggest that PAP may be an effective antisuicidal intervention following a cancer diagnosis due to its positive impact on hopelessness and demoralization and its effects on meaning-making in particular. These preliminary results implicate psilocybin treatment as a potentially effective alternative to existing antidepressant medications in patients with cancer that are also suicidal, and warrant further investigation in participants with elevated levels of depression and suicidality.

Optimizing treatment for comorbid borderline personality disorder and posttraumatic stress disorder: A systematic review of psychotherapeutic approaches and treatment efficacy.

Comorbid borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) is a severe and complicated clinical presentation characterized by especially high rates of suicide, healthcare utilization, and psychosocial impairment. Although guidelines exist for treating each of these disorders alone, there remains limited guidance on the optimal treatment in cases where BPD and PTSD co-occur. Therefore, this systematic review synthesizes the existing research on the treatment of BPD-PTSD with the aim of optimizing treatment for this population. First, the prevalence and clinical severity of comorbid BPD-PTSD is reviewed. Next, we describe the results of our systematic review, which identified 21 articles that examined treatment outcomes in the context of BPD-PTSD or subclinical BPD-PTSD. Based on our results, we describe existing psychotherapeutic approaches, including BPD-specific treatments, trauma-focused and non-trauma-focused treatments for PTSD, and stage-based treatments for BPD-PTSD. We also summarize BPD-PTSD treatment outcomes, including whether each disorder interferes with treatment and recovery of the other. Results related to treatment safety and concerns regarding conducting trauma-focused treatment for BPD-PTSD are addressed. We end by highlighting important gaps in the literature and provide recommendations for further research.

The moderating effects of anger suppression and anger expression on cognitive behavioral group therapy and mindfulness-based stress reduction among individuals with social anxiety disorder.

BACKGROUND: . Cognitive-behavioral therapy and mindfulness-based stress reduction (MBSR) are two prominent evidence-based treatments for social anxiety disorder (SAD). It is not clear, however, whether outcomes of these two treatments are moderated by similar factors. For example, whereas anger suppression and anger expression each predict outcomes in cognitive- behavioral group therapy (CBGT), it is unknown whether they differentially influence outcomes in CBGT versus MBSR. METHODS: . One hundred eight participants with SAD were randomized to CBGT, MBSR or Waitlist (WL). WL participants were later randomized to CBGT or MBSR, and their data were combined with data from those originally randomized to CBGT or MBSR. Anger suppression and anger expression were assessed at pre-treatment, and social anxiety was assessed at pre-treatment, post-treatment, and every 3 months throughout a 12-month follow-up period. RESULTS: . From pre- to post-treatment, higher anger suppression was associated with significantly greater reduction in social anxiety in CBGT compared with MBSR. From post-treatment through follow-up, higher anger expression was associated lesser reduction in social anxiety in MBSR but not in CBGT. LIMITATIONS: . Data are limited by sole reliance on self-report and it is unclear whether these findings generalize beyond group-based interventions. CONCLUSIONS: . Individuals with SAD who are higher in anger suppression and/or expression might be better suited to CBGT than MBSR.

On loving thyself: Exploring the association between self-compassion, self-reported suicidal behaviors, and implicit suicidality among college students.

OBJECTIVE: Suicide is a major public health concern. It is unknown whether self-compassion is associated with suicide risk above and beyond suicide risk factors such as self-criticism, hopelessness, and depression severity. Participants: Participants were 130 ethnically diverse undergraduate college students. Methods: Participants completed self-report measures of self-compassion, self-criticism, hopelessness, depression severity, and suicidal behaviors, as well as an implicit measure of suicidality. Results: Self-compassion was significantly associated with self-reported suicidal behaviors, even when controlling for self-criticism, hopelessness, and depression severity. Self-compassion was not significantly associated with implicit suicidality. Conclusions: The findings suggest that self-compassion is uniquely associated with self-reported suicidal behaviors, but not implicit suicidality, and that self-compassion is a potentially important target in suicide risk interventions. Limitations and future research directions are discussed.

Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial.

RATIONALE: Suicidality is a major public health concern with limited treatment options. Accordingly, there is a need for innovative interventions for suicidality. Preliminary evidence indicates that treatment with the psychedelic ayahuasca may lead to decreases in depressive symptoms among individuals with major depressive disorder (MDD). However, there remains limited understanding of whether ayahuasca also leads to reductions in suicidality. OBJECTIVE: To examine the acute and post-acute effect of ayahuasca on suicidality among individuals with MDD. METHODS: We conducted a secondary analysis of an open-label trial in which individuals with recurrent MDD received a single dose of ayahuasca (N = 17). Suicidality was assessed at baseline; during the intervention; and 1, 7, 14, and 21 days after the intervention. RESULTS: Among individuals with suicidality at baseline (n = 15), there were significant acute (i.e., 40, 80, 140, and 180 min after administration) and post-acute (1, 7, 14, and 21 days after administration) decreases in suicidality following administration of ayahuasca. Post-acute effect sizes for decreases in suicidality were large (Hedges' g = 1.31-1.75), with the largest effect size 21 days after the intervention (g = 1.75). CONCLUSIONS: When administered in the appropriate context, ayahuasca may lead to rapid and sustained reductions in suicidality among individuals with MDD. Randomized, double-blind studies with larger sample sizes are needed to confirm this early finding.