Atypical antipsychotics in primary generalized anxiety disorder or comorbid with mood disorders

Abstract

Generalized anxiety disorder (GAD) is a chronic, highly prevalent and debilitating disorder that commonly co-occurrs with mood disorders. Current available agents for GAD are limited either by their slow onsets of actions, unsatisfactory anxiolytic effects or potential for abuse/dependence. Atypical antipsychotics have been studied as alternatives. Olanzapine, risperidone and quetiapine immediate release have been explored in the treatment of refractory GAD and risperidone in bipolar anxiety with randomized, double-blind, placebo-controlled trials, but the results were not consistent. By contrast, quetiapine extended release (quetiapine-XR) 150 mg/day monotherapy yielded consistent anxiolytic effects across three studies that were superior to placebo and as effective as paroxetine 20 mg/day and escitalopram 10 mg/day but with an earlier onset of action. In a 52-week treatment of GAD, quetiapine-XR was superior to placebo in the prevention of anxiety relapses. Overall, atypical antipsychotics were relatively well tolerated, with common side effects of somnolence and sedation. However, in contrast to antidepressants and benzodiazepines, the long-term risk and benefit of atypical antipsychotics in the treatment of GAD is yet to be determined.

Keywords::

• atypical antipsychotics
• diagnosis
• efficacy
• generalized anxiety disorder
• impact
• mood disorder
• prevalence
• safety

Financial & competing interests disclosure

Supported in part by the P20 MH-66054 (Joseph R Calabrese, Keming Gao) and John C and Sally S Morley Family Foundation (Keming Gao).

Joseph R Calabrese has also received grant support and/or honoraria from Abbott, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, Janssen, and NIMH.

Keming Gao has received grant support from AstraZeneca and NARSAD, and acted as a consultant and received honoraria from Schering-Plough.

David V Sheehan has received grant funding support, or been affiliated or received honoraria and travel expenses related to lectures/presentations or consultant activities from the following organizations: Abbott Laboratories, Ad Hoc Committee, Treatment Drug & Assessment Research Review, Alexa, Alza Pharmaceuticals, Palo Alto, California, American Medical Association, American Psychiatric Association Task Force on Benzodiazepine Dependency, American Psychiatric Association Task Force on Treatments of Psychiatric Disorders, American Psychiatric Association Working Group to revise DSM III Anxiety Disorders Section, Anclote Foundation, Anxiety Disorders Resource Center, Anxiety Drug Efficacy Case, USFDA, Applied Health Outcomes/XCENDA, AstraZeneca, Avera Pharmaceuticals, Boehringer Ingelheim, Boots Pharmaceuticals, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Charter Hospitals, Ciba Geigy, Committee (RRC) of NIMH, on Anxiety and Phobic Disorder Projects, Connecticut & Ohio Academies of Family Physicians, Cortex Pharmaceutical, Council on Anxiety Disorders, CPC Coliseum Medical Center, Cypress Bioscience, Dista Products Company, Division of Drugs & Technology, American Medical Association, EISAI, Eli Lilly, Excerpta Medica Asia, Faxmed, Inc. Forest Laboratories, Glaxo Pharmaceuticals, GlaxoSmithKline, Glaxo-Wellcome, Hospital Corporation of America, Humana, ICI, INC Research, International Clinical Research (ICR), International Society for CNS Drug Development (ISCDD), Janssen Pharmaceutica, Jazz Pharmaceuticals, Kali-Duphar, Labopharm, Layton Bioscience, Lilly Research Laboratories, Lundbeck, Denmark, Marion Merrill Dow, McNeil Pharmaceuticals, Mead Johnson, Medical Outcome Systems, MediciNova, Merck Sharp & Dohme, National Anxiety Awareness Program, National Anxiety Foundation, National Depressive & Manic Depressive Association, National Institute of Drug Abuse, NIH, Novartis Pharmaceuticals Corp., Novo Nordisk, Organon, Orion Pharma, Parexel International Corporation, Parke-Davis, Pfizer, Pharmacia, Pharmacia & Upjohn, Philadelphia College of Pharmacy & Science, Pierre Fabre, France, Quintiles, Rhone Laboratories, Rhone-Poulenc Rorer Pharmaceuticals, Roche, Roerig, Sandoz Pharmaceuticals, Sanofi-Aventis, Sanofi-Synthelabo Recherche, Schering Corporation, Sepracor Shire Laboratories, Inc. SmithKlineBeecham, Solvay Pharmaceuticals, Takeda Pharmaceuticals Tampa General Hosp. University of South Florida Psychiatry Center, University of South Florida College of Medicine, TAP Pharmaceuticals, Targacept, TGH-University Psychiatry Center, Tikvah Therapeutics, Titan Pharmaceuticals, United Bioscience, The Upjohn Company, US Congress-House of Representatives Committee, USF Friends of Research in Psychiatry, Board of Trustees, Warner Chilcott, World Health Organization, Worldwide Clinical Trials, Wyeth-Ayerst, ZARS, Zeneca Pharmaceuticals.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.