Sustaining remission of psychotic depression: rationale, design and methodology of STOP-PD II

BMC Psychiatry. 2013 Jan 25:13:38. doi: 10.1186/1471-244X-13-38.

Abstract

Background: Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder.

Methods/design: The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.

Discussion: This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.

Trial registration: ClinicalTrials.gov NCT01427608.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Affective Disorders, Psychotic / drug therapy*
  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use*
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Middle Aged
  • Olanzapine
  • Remission Induction / methods
  • Secondary Prevention
  • Sertraline / administration & dosage
  • Sertraline / therapeutic use
  • Young Adult

Substances

  • Antidepressive Agents
  • Antipsychotic Agents
  • Benzodiazepines
  • Olanzapine
  • Sertraline

Associated data

  • ClinicalTrials.gov/NCT01427608