Recent Updates in Psychopharmacology: Insights in Schizophrenia, ADHD, and Treatment-Resistant Depression

Travis/AdobeStock

In case you missed any news from the psychopharmacological pipeline, we have briefly compiled some of the most important updates in order to help you stay informed.

Lumateperone for the Prevention of Relapse in Schizophrenia: New sNDA Submitted

Johnson & Johnson recently announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) based on long-term data evaluating the safety and efficacy of lumateperone (Caplyta) for the prevention of relapse in schizophrenia.

Caplyta 42 mg is an oral, once-daily atypical antipsychotic approved for the treatment of adults with schizophrenia and depressive episodes associated with bipolar depression, as both monotherapy and as adjunctive therapy with lithium or valproate.

The sNDA submission is based on positive results from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal trial. Investigators found time to relapse during the 26-week double-blind treatment phase was significantly longer in patients receiving Caplyta compared with those receiving placebo (P=.0002), the primary end point of the study.

Treatment with Caplyta was also associated with a 63% reduction in risk of relapse vs placebo (HR, 0.37; 95% CI, 0.22-0.65). Investigators also found a significantly delayed time to all-cause discontinuation, including relapse, compared with placebo during the double-blind phase (P=.0007), the key secondary end point.

Caplyta’s safety profile was consistent with the existing body of clinical data. No new safety concerns were identified. The most commonly reported adverse event that was observed at a rate greater than or equal to 5% and twice the rate of placebo was headache.

Updated Labeling for Extended-Release Stimulants: Weight Loss Risk in Children Under 6

The FDA announced it will revise the label of all extended-release stimulants indicated to treat attention-deficit/hyperactivity disorder (ADHD), including certain formulations of amphetamine and methylphenidate, to warn about the risk of weight loss and other adverse effects in patients younger than 6 years of age. Although extended-release stimulants are not approved for children younger than 6 years, clinicians occasionally prescribe them off-label to treat ADHD.

According to analysis of data from clinical trials of extended-release formulations of amphetamine and methylphenidate for ADHD treatment, patients younger than 6 years have higher plasma exposures and higher rates of adverse effects than older children taking the same medication at the same dosage. Notably, investigators observed clinically significant weight loss (at least 10% decrease in the Centers for Disease Control and Prevention weight percentile) in both short- and long-term studies with extended-release stimulants. As a result, they believe the benefits of extended-release stimulants may not outweigh the risks of these medications in patients with ADHD who are younger than 6 years. The FDA will thus require a Limitation of Use section in the prescribing information of all extended-release stimulants that includes a statement about the higher plasma exposures and higher rates of adverse reactions in children younger than 6 years.

Positive Phase 2b Results: BPL-003 for Patients With Treatment-Resistant Depression

Positive topline results from atai Life Sciences and Beckley Psytech’s 8-week, quadruple-masked, dose-finding, core stage of the phase 2b clinical trial (NCT05870540) evaluating the efficacy and safety of BPL-003 (intranasal mebufotenin [5-MeO-DMT] benzoate) in patients with treatment-resistant depression (TRD) show that BPL-003 demonstrated rapid, robust, and durable antidepressant effects with a single dose.

The phase 2b clinical study is the largest controlled clinical study to investigate mebufotenin and the only blinded phase 2b study of mebufotenin to include the United States. It was conducted at 38 sites across 6 countries and enrolled a total of 193 participants with moderate to severe TRD (NCT05870540). Participants were randomly assigned to receive a single 12-mg (n=73), 8-mg (n=46), or 0.3-mg comparator (n=74) dose of BPL-003. Investigators followed participants for 8 weeks, conducting efficacy assessments via centralized, blinded raters using the Montgomery- Åsberg Depression Rating Scale (MADRS) at day 2, day 8, day 29 and day 57.

The study met its primary and all key secondary end points, and BPL-003 demonstrated rapid, robust, and durable antidepressant effects with a single dose. For the primary end point, at day 29, a single 12-mg dose of BPL-003 demonstrated a statistically significant reduction in depressive symptoms, as measured by the MADRS, with a mean decrease of 11.1 points from baseline compared with a 5.8-point reduction in the 0.3-mg comparator group (P =.0038).

For the key secondary end points, a single 8-mg dose of BPL-003 also showed significant improvement at day 29, with a mean MADRS score reduction of 12.1 points (P=.0025 for change vs 0.3-mg control). Investigators noted that both the 8-mg and 12-mg doses of BPL-003 showed statistically significant improvements in MADRS scores as early as a single day after dosing and maintained effects until week 8. Follow-up in the 8-week open-label extension stage of the study is ongoing.

Follow us on LinkedIn, Facebook, or X, or subscribe to our eNewsletters to stay up to date. If you are interested in more pharmacological news, be sure to check out our Drug Watch page.