This entire article is available in PDF format to paid subscribers (certain restrictions apply).
If you have not already registered for Full Text Access to The Journal, then visit our registration page.

Comparing Acute Toxicity of First-and Second-Generation Antipsychotic Drugs: A 10-Year, Retrospective Cohort Study

Michael A. Ciranni, M.D., Ph.D.; Thomas E. Kearney, Pharm.D.; and Kent R. Olson, M.D.

Objective: Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied.

Method: A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity.

Results: Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR=1.71, 95% CI=1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR=2.39, 95% CI=1.09 to 5.26), coma (OR=2.18, 95% CI=1.30 to 3.65), and hypotension (OR=1.80, 95% CI=1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR=0.12, 95% CI=0.08 to 0.19) or rigidity (OR=0.30, 95% CI=0.10 to 0.90).

Conclusion: SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.


(J Clin Psychiatry 2009;70(1):122-129. Online Ahead of Print January 13, 2009. doi:10.4088/JCP.08m04315)

Received April 22, 2008; accepted Nov. 4, 2008. From the Department of Psychiatry, New York University (Dr. Ciranni); California Poison Control System, San Francisco Division, and the Department of Clinical Pharmacy, University of California, San Francisco (Drs. Kearney and Olson); and the Division of Clinical Pharmacology, University of California, San Francisco (Dr. Olson).

Dr. Ciranni has previously received an American Psychiatric Association (APA)/Bristol-Myers Squibb fellowship in public psychiatry and an APA/Lilly resident research award. Drs. Kearney and Olson report no financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Michael Ciranni, M.D., Ph.D., Department of Psychiatry, New York University, 462 1st Ave., NBV 20N11, New York, NY 10016 (e-mail: