Efficacy of Typical and Atypical Antipsychotics for Primary and Comorbid Anxiety Symptoms or Disorders: A Review

Keming Gao, M.D., Ph.D.; David Muzina, M.D.; Prashant Gajwani, M.D.; and Joseph R. Calabrese, M.D.

Objective: The efficacy of antipsychotics in the treatment of primary or comorbid anxiety disorders or anxiety symptoms in major depressive disorder or bipolar disorder was reviewed.

Data Sources: English-language literature cited in MEDLINE from January 1, 1968, to December 31, 2005, was searched with the keywords anxiety disorder, anxiety symptoms, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, bipolar disorder, major depressive disorder, Hamilton Rating Scale for Anxiety, antipsychotics, typical antipsychotics, atypical antipsychotics, fluphenazine, haloperidol, perphenazine, pimozide, thiothixene, trifluoperazine, loxapine, molindone, chlorpromazine, mesoridazine, thioridazine, fluspirilene, penfluridol, pipothiazine, flupenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, amisulpride, and clinical trial. Randomized, double-blind, placebo-controlled trials and open-label studies with a minimum of 20 subjects with a DSM-III/IV or ICD-10 diagnosis of anxiety disorder and studies without a DSM-III/IV or ICD-10 diagnosis of anxiety disorder but with Hamilton Rating Scale for Anxiety (HAM-A) scores as an outcome were prioritized. Studies on bipolar disorder or major depressive disorder with the analysis of changes in anxiety symptoms were reviewed. Early studies on neurosis/anxiety or anxious depression without a HAM-A component were also reviewed.

Data Synthesis: Six trials in primary generalized anxiety disorder (GAD), 15 in refractory obsessive-compulsive disorder (OCD), 8 in posttraumatic stress disorder (PTSD), 6 in neurosis with the HAM-A, 1 in social phobia, and 2 in anxiety symptoms in bipolar depression were identified. Low doses of trifluoperazine were superior to placebo in the treatment of GAD. Most of the less well-designed studies showed that other typical antipsychotics might be superior to placebo or as effective as benzodiazepines in the treatment of GAD and other anxiety conditions. In most studies, risperidone, olanzapine, and quetiapine augmentation to antidepressants was superior to placebo in treating refractory OCD and PTSD. Both olanzapine and quetiapine significantly reduced anxiety compared to placebo in studies of bipolar depression.

Conclusion: Except for trifluoperazine, there is no large, well-designed study of antipsychotics in the treatment of primary or comorbid anxiety symptoms or disorders. The efficacy of these agents in various anxiety conditions needs to be further investigated with large, well-designed comparison studies.

(J Clin Psychiatry 2006;67:1327-1340)

Received Sept. 6, 2005; accepted Feb. 6, 2006. From the Department of Psychiatry, the Bipolar Disorders Research Center, University Hospitals of Cleveland/Case Western Reserve University, School of Medicine, Cleveland, Ohio (Drs. Gao, Gajwani, and Calabrese); and the Department of Psychiatry and Psychology, Cleveland Clinic Foundation, Cleveland Clinic, Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio (Dr. Muzina).

Support for this manuscript included National Institute of Mental Health grant #P20 MH-66054 (Dr. Calabrese).

Dr. Gao reports no financial or other affiliation relevant to the subject of this article. Dr. Muzina has served as a consultant for AstraZeneca and GlaxoSmithKline; has served on the speakers or advisory boards of and received honoraria from AstraZeneca, GlaxoSmithKline, Eli Lilly, Pfizer, and Shire; and has received grant/research support from Eli Lilly, AstraZeneca, GlaxoSmithKline, and Abbott. Dr. Gajwani has received grant/research support from Pfizer, Bristol-Myers Squibb, and Otsuka and honoraria from AstraZeneca and has served on the speakers or advisory boards of AstraZeneca, Pfizer, Forest, Bristol-Myers Squibb, Cyberonics, Abbott, and GlaxoSmithKline. Dr. Calabrese has received grant support and honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Pfizer, Janssen, and Merck and has served as a consultant for or on the advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Otsuka, Eli Lilly, GlaxoSmithKline, Janssen, and Teva.

Corresponding author and reprints: Keming Gao, M.D., Ph.D., 11400 Euclid Ave., Suite 200, Cleveland, OH 44106 (e-mail: keming.gao@uhhs.com).