The Journal of clinical psychiatry
March 3, 2025
Guy M Goodwin, Ania Nowakowska, Merve Atli et al.
14 citations
A single 25 mg dose of the synthetic psilocybin formulation COMP360 showed a longer time before depressive events recurred over 52 weeks compared with 1 mg and 10 mg doses in people with treatment-resistant depression. In the full group of 233 participants, the median time to a depressive event was 92 days for the 25 mg group, 83 days for the 10 mg group, and 62 days for the 1 mg group. Most participants had a depressive event by 12 weeks. Adverse events were rare; one case of mild suicidal ideation in the 1 mg group was considered possibly related to the drug. Larger long-term studies are needed to confirm these results.
The Journal of clinical psychiatry
April 24, 2024
Gregory H Jones, Courtney M Vecera, Ana C Ruiz et al.
13 citations
A single dose of intranasal ketamine (50 mg) produced rapid antidepressant effects compared to placebo in unmedicated inpatients with major depression and current suicidal ideation, but did not significantly reduce suicidal thoughts. Patients with comorbid alcohol use disorder showed a statistical trend toward greater improvement in suicidality, though the primary outcome was not met. The treatment was well tolerated. The antidepressant benefit was largely unaffected by the presence of alcohol use disorder or the type of mood disorder (unipolar or bipolar). Among those receiving ketamine, improvement in depression correlated with reduced suicidal ideation only in patients without alcohol use disorder.
The Journal of clinical psychiatry
October 2, 2024
Mia C Santucci, Mina Ansari, Sina Nikayin et al.
12 citations
In a real-world clinical setting, 45 patients with treatment-resistant bipolar depression received intravenous ketamine or intranasal esketamine. Among 38 who completed an acute series (twice-weekly treatments for up to four weeks), 39% achieved a clinical response (at least 50% improvement on the Montgomery-Asberg Depression Rating Scale) and 13.2% achieved remission (score of 10 or lower). Mean depression scores dropped from 31.1 to 19.2, a 38.3% improvement. No manic or hypomanic episodes occurred during the acute phase. However, during maintenance treatment, 28.9% of patients experienced hypomanic or manic symptoms, with one severe event requiring hospitalization.
The Journal of clinical psychiatry
August 14, 2023
Michael E. Thase
9 citations
After decades of limited progress in treating major depressive disorder (MDD), especially for patients unresponsive to standard antidepressants, the serendipitous discovery of ketamine's antidepressant effects has renewed optimism. This has spurred development of related drugs like S-ketamine and oral NMDA antagonists showing promise in late-stage trials. An extended-release combination of bupropion (105 mg) and dextromethorphan (45 mg) reduced MADRS total scores in recipients. Neurosteroids such as brexanolone and zuranolone represent another class, modulating GABA neurotransmission, a pathway long used for insomnia and anxiety. Psychedelic drugs, after nearly 50 years of legal restrictions, are also being investigated, with psilocybin under study for treatment-resistant depression.
The Journal of clinical psychiatry
August 26, 2024
Rachel M Pacilio, Juan F Lopez, Sagar V Parikh et al.
7 citations
Many women who could become pregnant receive ketamine for psychiatric conditions, but risks to a developing fetus are frequently overlooked. A survey of U.S. outpatient ketamine clinics found that fewer than half discuss pregnancy-related risks during informed consent, only 20% require pregnancy tests before treatment, and just 13.7% recommend or require contraception. A record review at one academic medical center showed all patients were tested weekly for pregnancy, but only half used contraception. The findings indicate a need for greater attention to reproductive health in ketamine treatment protocols.
The Journal of clinical psychiatry
May 26, 2025
Rachel M Pacilio, Sagar V Parikh, Jamarie Geller
4 citations
Ketamine is increasingly used for psychiatric disorders outside academic settings, but little is known about real-world practices. A survey of U.S. community-based ketamine clinics and a review of their websites found that all clinics use ketamine for treatment-resistant depression, and many also prescribe it for treatment-naive depression (72.3%), bipolar depression (78.9%), and subclinical depression (59.7%). Over 80% of clinics offer maintenance treatment, often for prolonged periods, and over 40% provide ketamine for at-home use. Fewer than 30% of clinics are run by psychiatric physicians, and over 25% by nonphysician providers. The findings indicate significant variability in indications, duration, formulations, and settings, highlighting a need for increased oversight and specific practice guidelines.
The Journal of clinical psychiatry
July 8, 2024
Wei-Chen Lin, Mu-Hong Chen, Tung-Ping Su et al.
4 citations
A single low-dose infusion of ketamine (0.5 mg/kg) briefly reduces hopelessness and later lowers suicidal ideation in people with treatment-resistant depression and strong suicidal thoughts. In a randomized trial of 84 patients, those receiving ketamine showed significantly less hopelessness four hours after infusion compared with those receiving a control drug (midazolam). Two days after infusion, the ketamine group had more positive and fewer negative suicidal thoughts. The early drop in hopelessness predicted the later antisuicidal effect. The antihopelessness effect lasted only about four hours, while the antisuicidal effect appeared on the second day.
The Journal of clinical psychiatry
February 5, 2025
David A Bender, Sandeep M Nayak, Joshua S Siegel et al.
3 citations
Practitioners who oversee psychedelic therapy sessions slightly prefer an 'emotive' approach—one that emphasizes human and spiritual elements—over a 'neuromodulatory' approach that focuses on biological drug effects. A survey of 40 qualified respondents from at least 4 countries, 11 U.S. states, and 16 institutions found no consensus on many psychological support strategies. Four key themes emerged: the importance of trust, the role of spirituality, creating an emotional setting, and conceptualizing negative experiences. Practitioners trained at the Multidisciplinary Association for Psychedelic Studies or the California Institute of Integral Studies showed a significantly stronger emotive preference than those trained elsewhere.
The Journal of clinical psychiatry
July 7, 2025
Angela T H Kwan, Moiz Lakhani, Joshua D Rosenblat et al.
2 citations
In a global pharmacovigilance analysis of adverse event reports from the World Health Organization's VigiBase database, esketamine was associated with higher reporting odds for suicidal ideation compared to lithium (5.13 times) and fluoxetine (3.34 times), while ketamine showed lower reporting odds for suicidal ideation, suicide attempt, and completed suicide relative to both reference drugs. Both drugs had lower reporting odds for suicide attempts and completed suicides. The authors caution that causality cannot be determined from these observational data.
The Journal of clinical psychiatry
January 27, 2025
Kristin Clemens, Amanda Teeple, Maryia Zhdanava et al.
2 citations
Among employed adults with treatment-resistant depression, esketamine nasal spray plus an oral antidepressant led to larger reductions in work productivity loss and related costs than quetiapine extended release plus an oral antidepressant. By week 8, total work productivity loss decreased by 30.3 percentage points with esketamine versus 17.3 with quetiapine, a difference of 13.0 percentage points. Weekly cost savings were $363 for esketamine and $207 for quetiapine. By week 32, reductions were 45.3 and 32.5 percentage points, respectively, with weekly cost savings of $543 versus $390. The results suggest greater benefits for both patient well-being and employer perspectives.
The Journal of clinical psychiatry
January 8, 2025
Ali Abdolizadeh, Brett D M Jones, Maryam Hosseini Kupaei et al.
2 citations
A systematic review of treatments for suicidality among psychiatric inpatients aged 18–65 found that intravenous ketamine produced the most consistent rapid reduction in suicidality among 14 pharmacologic trials. Among 35 nonpharmacologic trials—including chronotherapy, neurostimulation, and psychotherapies—results were mixed, with some interventions showing potential benefit, especially for mood, personality, and trauma-related disorders. Many studies had methodological limitations such as nonrandomized designs and lack of control groups. The review calls for larger, well-designed trials to confirm effectiveness.
The Journal of clinical psychiatry
January 21, 2026
Matheus G Marques, Aysegul Özerdem, Simon Kung et al.
1 citation
For treatment-resistant depression (TRD), a panel of 10 psychiatrists reached strong consensus on recommending augmentation with second-generation antipsychotics, transcranial magnetic stimulation, and ketamine/esketamine as next-step treatments after three failed antidepressant trials. Treatment preferences shifted to include nonaugmentative antidepressants and electroconvulsive therapy depending on patient characteristics such as metabolic disease and age. The findings underscore the importance of tailoring TRD treatment strategies to individual patient factors beyond conventional guideline tiers.
The Journal of clinical psychiatry
June 10, 2026
Jacob T Steinle, Suraj Shankar, Joshua S Siegel et al.
After adjusting for preexisting psychiatric conditions, the link between hallucinogen use and psychosis disappears. Among 273,466 people with substance-related hospital admissions, psychosis diagnoses were more common after hallucinogen-related admissions (16.4%) than after other substance admissions (6.6%). However, once clinical characteristics were accounted for, the increased risk became nonsignificant (hazard ratio 0.97). This suggests that observed associations between hallucinogens and psychosis are largely due to underlying mental health vulnerabilities, not a direct causal effect. The findings inform psychedelic policy by indicating that population-level data on hallucinogen safety may reflect preexisting risk factors.
The Journal of clinical psychiatry
June 3, 2026
Martin Johnson, Pau Aceves Baldo, Emilio Arbe et al.
In a small open-label trial, ten women with postpartum depression received up to three escalating doses of inhaled GH001 (a synthetic form of 5-MeO-DMT) on a single day. Depressive symptoms, measured on the Montgomery-Asberg Depression Rating Scale, dropped by an average of 35.4 points from a baseline of 36.7 by day 8, and all participants met criteria for both response and remission. Improvements were first noted two hours after the final dose. The treatment was well tolerated, with only mild to moderate side effects, most commonly headache. These preliminary findings suggest GH001 may produce rapid and substantial antidepressant effects in postpartum depression, but larger controlled trials are needed.
The Journal of clinical psychiatry
May 13, 2026
Andrew van der Vaart, Jeffrey LaPratt, Kimberly Swartz et al.
A single 25-mg dose of a synthetic psilocybin formulation, combined with psychological support, rapidly and durably reduced chronic suicidal ideation and depressive symptoms in 20 adults with major depressive disorder who had not responded to at least two prior antidepressant treatments. Suicidal ideation scores dropped significantly by week 1, remained reduced at week 3 (the primary endpoint), and were still lower at week 12, when 70% of participants had minimal or no suicidal ideation. Depressive symptoms also improved substantially. No serious adverse events occurred. The findings are preliminary and require confirmation in larger randomized trials.
The Journal of clinical psychiatry
May 4, 2026
Samuel T Wilkinson, Brandon M Kitay, Matthew Macaluso et al.
Adding cognitive behavioral therapy to esketamine treatment reduces suicidal ideation more than esketamine alone in people with major depression and suicidal thoughts. In a randomized trial of 93 patients, 72% completed the study, meeting feasibility goals. Those who received 16 weeks of CBT plus esketamine showed greater improvement on three measures of suicidal ideation than those receiving esketamine with usual care: a mean difference of -1.91 on the Beck Scale for Suicidal Ideation, -0.33 on the Clinician Global Improvement Scale for Suicide Severity, and -3.77 on the depression rating scale. No difference was found on the Columbia-Suicide Severity Rating Scale or in suicide-related events.
The Journal of clinical psychiatry
April 2, 2025
Adriana Feder, Oneysha Brown, Sarah B Rutter et al.
Combining six ketamine infusions with a brief exposure-based psychotherapy, written exposure therapy (WET), produced large and durable reductions in PTSD symptoms for patients with chronic, severe PTSD. In an open-label trial, 13 of 14 patients completed treatment. PTSD symptom severity, measured by the CAPS-5, dropped from an average of 41.6 before treatment to 20.8 at 12 weeks, a large-magnitude improvement. Nine patients (69%) were treatment responders, and eight (61.5%) maintained improvement up to six months. The authors suggest the combined treatment may be effective but call for larger randomized controlled trials to confirm efficacy and synergy.
The Journal of clinical psychiatry
February 11, 2025
correction
This is a correction notice for a previously published article. It identifies the original article by its DOI but provides no new findings, arguments, or data.