Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder

J Clin Psychopharmacol. 2024 Sep-Oct;44(5):481-491. doi: 10.1097/JCP.0000000000001889.

Abstract

Background: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo.

Methods: We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures.

Results: Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups.

Conclusions: This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.

Trial registration: ClinicalTrials.gov NCT02466685.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Bipolar Disorder* / complications
  • Bipolar Disorder* / drug therapy
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / etiology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Receptors, Serotonin / drug effects
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology
  • Treatment Outcome

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • serotonin 7 receptor

Associated data

  • ClinicalTrials.gov/NCT02466685