Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial

Psychiatry Clin Neurosci. 2014 Jun;68(6):432-40. doi: 10.1111/pcn.12150. Epub 2014 Feb 18.

Abstract

Aims: Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA.

Methods: Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects.

Results: Analysis was by linear mixed model. Fifty-two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.

Conclusions: Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.

Keywords: clinical trial; pregnenolone; recent-onset schizophrenia; schizoaffective disorder.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antipsychotic Agents / therapeutic use
  • Diagnostic and Statistical Manual of Mental Disorders
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Pregnenolone / adverse effects
  • Pregnenolone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antipsychotic Agents
  • Pregnenolone