Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder.

Abstract

BACKGROUND:

Due to their favorable side-effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Ziprasidone, an atypical antipsychotic agent with strong 5-HT(1A) agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study is to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI).

METHOD:

Twenty patients with major depressive disorder (MDD) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002. MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline to endpoint), as measured by the HAM-D-17 total score.

RESULTS:

Thirteen of 20 patients (65.0%) completed the trial. Using a completer analysis, 8 patients (61.5%) were classified as responders. An intent-to-treat (ITT) analysis resulted in 10 responders (50.0%). The overall proportion of remitters was 5 of 13 (38.5%) using a completer analysis and 5 of 20 (25.0%) using the ITT analysis. Ziprasidone administration appeared to be safe, with no clinically significant QTc prolongation or severe adverse events observed in any of the study participants.

CONCLUSION:

These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD.

• Authors: George I Papakostas, Timothy J Petersen, Andrew A Nierenberg, Jessica L Murakami, Jonathan E Alpert, Jerrold F Rosenbaum, Maurizio Fava
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 65 Issue 2 Pg. 217-21 (Feb 2004) ISSN: 0160-6689 [Print] United States
• PMID: 15003076 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Piperazines
• Serotonin 5-HT1 Receptor Agonists
• Serotonin Uptake Inhibitors
• Thiazoles
• ziprasidone

Topics

• Adult
• Antipsychotic Agents (administration & dosage, adverse effects)
• Depressive Disorder, Major (diagnosis, drug therapy, psychology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Resistance
• Drug Therapy, Combination
• Female
• Humans
• Male
• Middle Aged
• Personality Assessment (statistics & numerical data)
• Personality Inventory (statistics & numerical data)
• Piperazines (administration & dosage, adverse effects)
• Psychometrics
• Serotonin 5-HT1 Receptor Agonists
• Selective Serotonin Reuptake Inhibitors (administration & dosage, adverse effects)
• Thiazoles (administration & dosage, adverse effects)
• Treatment Outcome