Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study

Am J Psychiatry. 2002 Oct;159(10):1777-9. doi: 10.1176/appi.ajp.159.10.1777.


Objective: Posttraumatic stress disorder (PTSD), particularly in combat veterans with chronic illness, is often refractory to standard pharmacological interventions. There is a need to test adjunctive treatments to boost response.

Method: Subjects were 19 patients with PTSD who were minimally responsive to 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) at maximum tolerated dose. Outcomes were compared among subjects whose treatment was augmented with 8 weeks of double-blind olanzapine or placebo administration.

Results: Olanzapine augmentation was associated with statistically significantly greater reduction than placebo in specific measures of posttraumatic stress, depressive, and sleep disorder symptoms. Clinician-rated global response rates did not, however, significantly differ between groups.

Conclusions: This is most likely the first double-blind, placebo-controlled study of an adjunct to SSRIs for PTSD. Despite the small group size, the findings suggest a role for olanzapine or other atypical antipsychotics in treating SSRI-resistant PTSD. Sleep symptoms may especially benefit.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines
  • Combat Disorders / drug therapy*
  • Combat Disorders / psychology
  • Depressive Disorder / drug therapy
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Paroxetine / therapeutic use
  • Pirenzepine / analogs & derivatives
  • Pirenzepine / therapeutic use*
  • Placebos
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sertraline
  • Sleep Wake Disorders / drug therapy
  • Sleep Wake Disorders / psychology
  • Treatment Outcome


  • Antipsychotic Agents
  • Placebos
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Benzodiazepines
  • Pirenzepine
  • Paroxetine
  • Olanzapine
  • Sertraline