ISSN 0160-6689
46 papers in the library · 3,272 citations · publishing 2004-2026
The Journal of Clinical Psychiatry November 15, 2006 Francisco Moreno, Christopher B. Wiegand, E. Keolani Taitano et al. 786 citations
In a controlled clinical setting, psilocybin was safely administered to individuals with obsessive-compulsive disorder (OCD) and was linked to immediate decreases in core OCD symptoms in several participants.
The Journal of Clinical Psychiatry July 13, 2010 Nancy Diazgranados, Lobna Ibrahim, Nancy E. Brutsché et al. 563 citations
A single infusion of ketamine (0.5 mg/kg) rapidly reduced suicidal thoughts in people with treatment-resistant major depression. Suicidal ideation scores dropped significantly within 40 minutes and remained lower for at least 4 hours. Among the 10 participants who had a score of 4 or higher on the Scale for Suicide Ideation at the start, all dropped below 4—9 within 40 minutes and 1 by 80 minutes. Depression, anxiety, and hopelessness also improved substantially at all measured time points. The findings suggest ketamine may offer a fast-acting intervention for suicidal ideation, a medical emergency with few pharmacologic options.
The Journal of Clinical Psychiatry May 11, 2020 Dong-Jing Fu, Dawn F. Ionescu, Xiang Li et al. 367 citations
In adults hospitalized for major depressive disorder with active suicidal thoughts, adding esketamine nasal spray to standard treatment (antidepressants and hospitalization) reduced depression symptoms more than placebo plus standard treatment within 24 hours, with benefits persisting over four weeks. The difference in suicidal ideation severity between groups was not statistically significant. Common side effects of esketamine included dizziness, dissociation, headache, nausea, and drowsiness.
The Journal of Clinical Psychiatry April 20, 2020 Ewa Wajs, Leah Aluisio, Richard Holder et al. 288 citations
In a year-long open-label study of 802 adults with treatment-resistant depression, esketamine nasal spray combined with a new oral antidepressant showed a manageable safety profile and sustained improvement in depressive symptoms. Common side effects included dizziness, dissociation, nausea, and headache, mostly mild or moderate and resolving the same day. Two deaths occurred, neither linked to the drug. Cognitive performance remained stable or improved. Depression scores dropped during the first four weeks and stayed lower through the maintenance phase.
The Journal of Clinical Psychiatry September 2, 2014 Le-Ben Wan, Cara F. Levitch, Andrew M. Perez et al. 232 citations
Ketamine given intravenously at 0.5 mg/kg over 40 minutes was safe and well tolerated in a large group of patients with treatment-resistant depression. Across 205 infusions in 97 participants, the antidepressant response rate was 67%. Only about 2% of infusions were stopped due to adverse effects, and the overall dropout rate was 3%. Common temporary side effects in the first four hours included drowsiness, dizziness, poor coordination, blurred vision, and feeling strange or unreal. About one third of participants had changes in blood pressure or heart rate. There were small but significant increases in psychotomimetic and dissociative symptoms, but no lasting psychotic effects, medical complications, or increased substance use among those followed long-term.
The Journal of Clinical Psychiatry May 15, 2014 Mark J. Niciu, David A. Luckenbaugh, Dawn F. Ionescu et al. 167 citations
Higher body mass index and a family history of alcohol use disorder in a first-degree relative were associated with greater improvement in depression symptoms after a single ketamine infusion. Patients with no prior suicide attempts also showed greater improvement, but only at day 7. The analysis combined data from four studies of treatment-resistant inpatients with major depressive disorder or bipolar depression who received a single 0.5 mg/kg ketamine infusion over 40 minutes. The findings suggest that certain clinical characteristics may help predict who benefits most from ketamine's rapid antidepressant effects, though the analysis was post hoc and the models explained only 13% to 36% of the variation in symptom improvement.
The Journal of Clinical Psychiatry September 8, 2009 Rodrigo Machado‐Vieira, Peixiong Yuan, Nancy E. Brutsché et al. 154 citations
Ketamine produces rapid antidepressant effects in people with treatment-resistant major depressive disorder, but these effects are not linked to changes in brain-derived neurotrophic factor (BDNF) levels. In 23 adults aged 18 to 65, a single intravenous infusion of ketamine (0.5 mg/kg) significantly improved depression scores on the Montgomery-Asberg Depression Rating Scale within 230 minutes. However, BDNF levels measured at the same time points did not change from baseline, and no association appeared between antidepressant response and BDNF. The findings indicate that ketamine's initial antidepressant action operates through mechanisms other than BDNF.
The Journal of Clinical Psychiatry April 15, 2019 Joshua D. Rosenblat, André F. Carvalho, Madeline Li et al. 111 citations
Oral ketamine shows significant antidepressant effects with good tolerability, but its effects are not as rapid as intravenous ketamine. In two randomized controlled trials, significant reductions in depressive symptoms were observed only after 2-6 weeks of treatment. Rapid antidepressant effects within 24 hours, antisuicide effects, and efficacy in treatment-resistant depression were reported only in retrospective studies. Dosages ranged from 0.5 to 7.0 mg/kg, with most studies using 1-2 mg/kg every 1-3 days. No clinically significant adverse effects were reported. The review concludes that antisuicide effects and efficacy in treatment-resistant depression have yet to be demonstrated in well-designed trials.
The Journal of Clinical Psychiatry September 25, 2014 Dawn F. Ionescu, David A. Luckenbaugh, Mark J. Niciu et al. 111 citations
Patients with treatment-resistant major depressive disorder who also have high anxiety (anxious depression) responded better to a single infusion of ketamine than those without high anxiety, contrary to expectations based on traditional antidepressants. Over 28 days of follow-up, the anxious group showed significantly fewer depression symptoms at multiple time points and relapsed much later (median 19 days versus 1 day). No significant differences in side effects were observed. These results suggest that ketamine, an NMDA receptor antagonist, may be especially effective for the anxious depression subtype, which is typically difficult to treat with standard antidepressants.
The Journal of Clinical Psychiatry May 26, 2020 George I. Papakostas, Naji C. Salloum, Rebecca S. Hock et al. 107 citations
Adjunctive intranasal esketamine is more effective than placebo for treating major depressive disorder. Pooling five randomized, double-blind trials with 774 patients, esketamine outperformed placebo on depression rating scale score change, response, and remission. The effect was statistically significant across different study samples and baseline antidepressant regimens. Esketamine appears to be an effective treatment strategy for patients who are treatment-resistant or acutely suicidal.
The Journal of Clinical Psychiatry July 23, 2018 Samuel T. Wilkinson, Rachel B. Katz, Mesut Toprak et al. 88 citations
In a clinical setting, ketamine infusions for severe, treatment-resistant mood disorders showed lower response and remission rates than those in research protocols. Of 44 patients starting a four-infusion protocol, 45.5% responded and 27.3% remitted by the fourth infusion. A small long-term subsample (n=14) received 12 to 45 total treatments over 14 to 126 weeks with no observed cognitive decline, increased delusions, or cystitis symptoms. The treatment was generally well tolerated, but the small maintenance group limits conclusions about long-term safety.
The Journal of Clinical Psychiatry December 6, 2016 Jennifer L. Vande Voort, Elizabeth D. Ballard, David A. Luckenbaugh et al. 67 citations
People with depression who had a reduction in suicidal thoughts after a single ketamine infusion also showed less nighttime wakefulness, measured by EEG, the night after the infusion compared to those whose suicidal thoughts did not improve. The level of wakefulness in responders was similar to that of healthy controls. This suggests that ketamine's effect on suicidal ideation may involve changes in sleep-wake regulation.
The Journal of Clinical Psychiatry May 4, 2023 Sandeep M. Nayak, Melissa Bradley, Bethea A Kleykamp et al. 38 citations
A systematic review of randomized trials of psychedelics in humans found that most studies use inert placebos rather than active comparators, and very few assess whether blinding was successful. Of 86 unique studies, 61.2% used an inert placebo, 20.0% used active comparators, and only 17.3% included any assessment of blinding; when assessed, blinding success was generally poor. Only 3 of 21 therapeutic trials compared psychological support to a minimally supportive condition. The review concludes that randomized psychedelic trials underutilize blind assessment, active drug controls, and adequate control conditions for psychological support, and recommends improvements to trial methods.
The Journal of Clinical Psychiatry October 15, 2004 Nicholas Weiss, Lee Jones, John Chamberlain 33 citations
A case of prolonged psychosis and sleep deprivation triggered by peyote, a hallucinogen containing mescaline, was resolved by initiating sleep. While peyote's effects typically subside within 10 to 12 hours, this instance involved extended symptoms. The report highlights that sleep deprivation may contribute to psychosis beyond the direct drug effects.
The Journal of Clinical Psychiatry September 30, 2008 Michael Paulzen, Gerhard Gründer 32 citations
The hallucinogenic sage Salvia divinorum, known by many names including ska Maria and ska Pastora, was first identified in 1962 by Wasson and Hofmann among the Mazatec people of Oaxaca, Mexico, who recognized its psychoactive properties. In recent years, the plant has become widely available globally through internet suppliers, sold as leaves or concentrated extracts.
The Journal of Clinical Psychiatry July 16, 2021 Ibrahim Turkoz, Ella Daly, Jaskaran Singh et al. 21 citations
For patients with treatment-resistant depression who did not show a response within the first week of treatment, a full four-week induction course of esketamine nasal spray plus an oral antidepressant may still provide benefit. In a pooled analysis of two phase 3 trials, among those not meeting early response criteria at day 2 or days 2 and 8, the odds of a response by day 28 were about 1.6 times higher with esketamine plus antidepressant compared to antidepressant plus placebo. The findings suggest that lack of early improvement does not preclude later benefit from the full induction course.
The Journal of Clinical Psychiatry January 13, 2022 Richard J. Zeifman, Dengdeng Yu, Nikhita Singhal et al. 18 citations
A meta-analysis of 7 psychedelic therapy clinical trials found that, relative to baseline, psychedelic therapy was associated with large decreases in suicidality acutely (80–240 minutes) and at 1 day, 1–8 weeks, and 3–4 months (standardized mean differences ranging from −1.48 to −2.36). At 6 months, the effect was medium (SMD = −0.65). Reductions were significant at all time points except 7–8 weeks. Acute and post-acute elevations in suicidality were rare (6.5% and 3.0%, respectively). The authors note limitations including heterogeneous samples and interventions, and suggest that controlled trials specifically evaluating psychedelic therapy for suicidality may be warranted.
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 November 14, 2022 Anna Feeney, Bettina B. Hoeppner, Marlene P. Freeman et al. 9 citations
Among people with treatment-resistant depression, those taking oral benzodiazepines alongside a single intravenous infusion of ketamine showed less improvement in depression scores 24 hours later if they were on higher benzodiazepine doses. The same pattern was not seen in those who received a midazolam placebo. By day 3 after the infusion, benzodiazepine use no longer affected depression scores. The findings suggest that higher doses of benzodiazepines may temporarily weaken ketamine's rapid antidepressant effect.
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.