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Ziprasidone Augmentation of SSRI Antidepressants in Posttraumatic Stress Disorder

A Randomized, Placebo-Controlled Pilot Study of Augmentation Therapy

Hamner, Mark B., MD*†; Hernandez-Tejada, Melba A., DHA, PhD*‡; Zuschlag, Zachary D., DO†§; Agbor-Tabi, Deborah, MPH*†; Huber, Michael, MD*†; Wang, Zhewu, MD*†

Journal of Clinical Psychopharmacology: March/April 2019 - Volume 39 - Issue 2 - p 153–157
doi: 10.1097/JCP.0000000000001000
Brief Reports

Background Posttraumatic stress disorder (PTSD) is often a chronic, disabling illness for which antidepressant medications (ie, SSRI) are considered the primary psychopharmacological treatment. However, many patients remain refractory to antidepressants alone or in combination with psychotherapy. Safe and effective treatments for individuals with refractory PTSD are needed. This study aimed to examine ziprasidone augmentation of SSRI treatment of PTSD.

Methods This was a 2-phase study. In phase 1, subjects were treated with paroxetine or sertraline for 8 weeks. Individuals refractory to the SSRI treatment then entered into phase II of the study and were randomized, in a double-blind fashion, to 8 weeks of treatment with either ziprasidone or placebo. The primary outcome measure was change in Clinician Administered PTSD Scale total scores with the intent-to-treat sample. Secondary outcome measures included Positive and Negative Syndrome Scale scores, measures of depression and anxiety, and safety measures.

Results No significant differences were observed on the Clinician Administered PTSD Scale, Positive and Negative Syndrome Scale, or other outcome measures between ziprasidone and placebo groups. No significant differences were observed for safety measures including metabolic profiles, extrapyramidal symptoms/movement disorder rating scales, nor study dropout.

Conclusions Although no significant differences were noted in efficacy or safety measures between ziprasidone and placebo in this pilot study, the small sample size prevents definitive conclusions.

From the *Ralph H. Johnson VA Medical Center;

Department of Psychiatry and Behavioral Sciences, and

College of Nursing, Medical University of South Carolina, Charleston, SC; and

§James A. Haley Veterans' Hospital, Tampa, FL.

Received July 11, 2018; accepted after revision November 20, 2018.

Reprints: Zachary D. Zuschlag, DO, James A. Haley Veterans' Hospital, 13000 Bruce B. Downs Blvd, Tampa, FL 33612 (e-mail:;

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