Psychopharmacology Bulletin
March 4, 2024
Timothy Whitaker, Kimberly F Farrand, Michael E. Thase
249 citations
No approved therapy exists for suicidal ideation and behavior (SI/B) in Major Depressive Disorder (MDD), though ketamine shows rapid antidepressant effects. While FDA-approved esketamine reduced suicidality indicators, its effects did not significantly surpass placebo. Racemic ketamine, a mixture of esketamine and arketamine, may better alleviate SI/B. In an open-label study, 17 hospitalized MDD patients with acute SI/B received intranasal racemic ketamine (SLS-002). Treatment significantly reduced depression and suicidality scores on four clinical scales, including the Montgomery-Åsberg Depression Rating Scale and Sheehan-Suicidality Tracking Scale. SLS-002 was well tolerated with an acceptable safety profile, supporting continued development.
Psychopharmacology Bulletin
April 8, 2025
Keming Gao, Buket Koparal, Evrim Bayrak Oruc et al.
99 citations
A patient with treatment-resistant depression and multiple comorbid conditions (generalized anxiety disorder, eating disorder, post-traumatic stress disorder, and borderline personality disorder) experienced some short-term benefit from electroconvulsive therapy and ketamine infusion. Over a ten-year period from adolescence to adulthood, she had two separate periods of two-year stability, first with compounded ketamine intranasal spray and later with intranasal esketamine. She has been relatively stable without hospitalization or suicide attempt for more than two years on esketamine, suggesting that patients with complex treatment-resistant depression may benefit from ketamine-based treatments at different developmental stages.
Psychopharmacology Bulletin
July 8, 2024
Justin Faden, Leslie Citrome
29 citations
Several new psychiatric medications have recently been approved or are nearing approval. Auvelity, a combination of bupropion and dextromethorphan, is a novel antidepressant that speeds up response and remission compared to bupropion alone. Zuranolone, an oral medication for postpartum depression, works in just 14 days and shows improvement lasting 45 days. Gepirone, a 5HT1a receptor partial agonist, was approved for major depression with a favorable side effect profile. Cariprazine was approved as an adjunctive treatment for resistant depression, with easy dosing and lower metabolic side effects.
Psychopharmacology Bulletin
August 12, 2025
Alan F. Schatzberg, D Charles
15 citations
Several innovative psychiatric drugs have recently been approved or are nearing approval. Auvelity (bupropion/dextromethorphan) speeds antidepressant response and remission more than bupropion alone. Zuranolone, a 14-day oral treatment for postpartum depression, improves symptoms at day 15 and through day 45. Gepirone, a 5HT1a partial agonist, was approved for major depression based on positive trials and a favorable side effect profile. Cariprazine was approved as an adjunctive treatment for resistant major depression at 1.5 mg daily. MDMA-assisted psychotherapy for PTSD led to over 70% of subjects no longer meeting PTSD criteria, compared to 46% with psychotherapy and placebo. Xenomeline/tropsium (KarXT), a muscarinic M1M4 agonist, effectively treats positive and negative schizophrenia symptoms without dopamine antagonism. Lecanemab, a monoclonal antibody targeting beta-amyloid, slowed cognitive decline by 27% in early Alzheimer's disease.
Psychopharmacology Bulletin
August 12, 2025
Dustin Latimer, Michael D. Stocker, Kia Sayers et al.
10 citations
Post-traumatic stress disorder (PTSD) is common among U.S. veterans. Standard treatments include trauma-focused psychotherapies and antidepressant medications such as SSRIs and SNRIs. MDMA, a psychoactive compound classified as a Schedule I controlled substance since the 1980s, has reemerged as a potential therapy. Before prohibition, psychotherapists used it for various psychiatric conditions. Recent randomized, controlled trials support MDMA as an effective pharmacological adjunct to psychotherapy for PTSD.
Psychopharmacology Bulletin
February 3, 2025
Anna Mori-Kreiner, Arpit Aggarwal, Meelie Bordoloi
8 citations
Hallucinogen-persisting perception disorder (HPPD) is rare in adolescents. A 16-year-old male with major depressive disorder and polysubstance use (LSD, MDMA, psilocybin, cannabis, benzodiazepines) experienced auditory hallucinations and heightened hearing between MDMA use for eight months, plus auditory and visual hallucinations during a five-day inpatient admission. Treatment with aripiprazole 5 mg led to gradual improvement but not complete resolution. First-line treatments include clonidine and benzodiazepines; second-generation antipsychotics are generally less effective except aripiprazole. The diagnosis was complicated by polysubstance use, requiring distinction from non-substance-induced psychotic disorders.
Psychopharmacology Bulletin
August 12, 2025
Anna Mori-Kreiner, Arpit Aggarwal, Meelie Bordoloi
1 citation
Hallucinogen-Persisting Perception Disorder (HPPD) is rare in adolescents. A 16-year-old male with major depressive disorder and polysubstance use (LSD, MDMA, psilocybin, cannabis, benzodiazepines) experienced auditory hallucinations and heightened hearing between MDMA use for eight months, plus auditory and visual hallucinations during a five-day inpatient stay. Treatment with aripiprazole 5 mg led to gradual symptom improvement, though symptoms did not fully resolve. Literature review indicates first-line treatments include clonidine and benzodiazepines; second-generation antipsychotics are generally less effective except aripiprazole. Diagnosis was complicated by polysubstance use, requiring distinction from non-substance-induced psychotic disorders.
Psychopharmacology Bulletin
August 12, 2025
Priyanka Ghosh, Omar Viswanath
1 citation
A CNN article described a man with a 35-year history of severe refractory depression and suicidal ideation who was successfully treated with ketamine after failing numerous other medications. Seven placebo-controlled randomized clinical trials have shown beneficial effects of ketamine infusion therapy for refractory depression. However, ketamine therapy remains limited as an off-label use, with no large-scale randomized controlled trials demonstrating its safety or durability. Patient selection criteria are limited to major depressive disorder without psychotic features, with effects lasting up to one week. Evidence suggests other patients and repeated dosing could be beneficial, but clinical trials are lacking, and the FDA has not approved ketamine for psychiatric illness.
Psychopharmacology Bulletin
June 5, 2026
Michael E. Thase, Brian Brennan, Rachael Macisaac et al.
In patients with treatment-resistant depression, a single-day individualized dosing regimen of inhaled GH001 (synthetic mebufotenin) produced rapid and large improvements in depressive symptoms compared with placebo in a Phase 2b trial, with 57.5% achieving remission at Day 8 versus 0% on placebo. A post hoc analysis of 40 patients who received GH001 found no meaningful correlation between the number of prior lifetime antidepressant treatment failures and improvement on the Montgomery-Åsberg Depression Rating Scale at Day 8 or among 6-month open-label extension completers. Remission rates at Day 8 were similar across subgroups with 2, 3, 4, or 5 or more prior failures (range 53.9%-63.6%) and were maintained at Month 6 (range 61.5%-85.7%). The efficacy of GH001 appears largely independent of how many prior antidepressant treatments a patient has tried.
Psychopharmacology Bulletin
June 5, 2026
Keming Gao, Evrim Bayrak Oruc, Heather Wobbe et al.
Among six patients with bipolar depression who received both electroconvulsive therapy (ECT) and ketamine infusion (KET-IFU) in routine care, most responded well to ECT, with four showing at least 50% improvement on a depression self-report scale. Half of those who responded to ECT also responded to KET-IFU, though the onset of antidepressant effect differed between treatments. One patient did not respond to either treatment. Subjective memory concerns led five patients to try KET-IFU after ECT, though their cognitive test scores were normal. No patient stopped KET-IFU due to side effects. The findings suggest that some patients with bipolar depression may benefit similarly from both treatments, but head-to-head randomized studies are needed.
Psychopharmacology Bulletin
August 12, 2025
Bridgette Martinak, Ramy A Bolis, J. Black et al.
Dextromethorphan (DXM), a common over-the-counter cough suppressant, can cause psychosis when abused at high doses (over 1500 mg/day), producing delusions, hallucinations, and paranoia similar to phencyclidine (PCP). A case of severe DXM use disorder with psychotic disorder in a 40-year-old woman resolved only after treatment with an antipsychotic and mood stabilizer. DXM is not detected on standard urine drug screens, and its abuse may be an under-recognized cause of substance-induced psychosis. Clinicians should be aware of these psychiatric risks.
Psychopharmacology Bulletin
August 12, 2025
Patrick J Beck, Abhishek Reddy
An adolescent female presented to the emergency department with acute psychosis after using a cannabis vape pen. Her symptoms were self-limited and resolved without significant intervention, leading to a diagnosis of cannabis-induced psychosis (CIP). Cannabis vaping is growing in popularity among adolescents due to ease of concealment and lack of odor, and vape products often contain higher THC concentrations than traditional cannabis leaf, potentially increasing the risk for adverse effects including dysphoria and psychosis. The case is used to discuss CIP symptomatology and treatment, and the broader implications of cannabis vaping for adolescent neurodevelopment, substance use, and psychiatric comorbidities.
Psychopharmacology Bulletin
August 15, 2016
Edward C Lauterbach
Dextromethorphan (DM) can produce a rapid-acting antidepressant effect in treatment-resistant unipolar major depressive disorder (MDD), similar to ketamine. In a patient who had failed adequate trials of citalopram and vortioxetine and lost response to fluoxetine and bupropion, a 300 mg oral loading dose of DM followed by 60 mg twice daily led to improvement within 48 hours that lasted 7 days and was sustained up to 20 days with daily administration, after which the response gradually waned over 7 days. The effect is thought to involve mTOR activation, NMDA receptor antagonism, sigma-1 and beta adrenergic receptor stimulation, and serotonin transporter inhibition.