BACKGROUND: Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. METHODS: The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. RESULTS: A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. CONCLUSIONS: In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy.

Center for Behavioral Health Cleveland Clinic Cleveland OH USA

Dalhousie University Halifax Canada

Department of Clinical Medicine Faculty of Medicine and Dentistry University of Bergen and Division of Psychiatry Haukeland University Hospital Bergen Norway

Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Psychiatry and Behavioral Sciences The Johns Hopkins School of Medicine Baltimore MD USA

Department of Psychiatry Case Western Reserve University Cleveland OH USA

Department of Psychiatry Indiana University Indianapolis IN USA

Department of Psychiatry Massachusetts General Hospital and Harvard University Boston MA USA

Department of Psychiatry University of California San Diego La Jolla CA USA

Department of Psychiatry VA San Diego Healthcare System La Jolla CA USA

Division of Mental Health and Addiction Oslo University Hospital Oslo Norway

Division of Psychiatry Faculty of Medicine and Dentistry Stavanger University Hospital University of Bergen Stavanger Norway

Division of Psychiatry Haukeland University Hospital Bergen Norway

Division of Psychiatry St Olav University Hospital of Trondheim and Department of Neuroscience Faculty of Medicine Norwegian University of Science and Technology Trondheim Norway

Mayo Clinic Rochester MN USA

National Institute of Alcohol Abuse and Alcoholism NIH Bethesda MD USA

National Institute of Mental Health Klecany Czech Republic

Norwegian Centre for Mental Disorders Research Institute of Clinical Medicine University of Oslo Oslo Norway

University of Chicago Chicago IL USA

University of Iowa Iowa City IA USA

University of Michigan Ann Arbor MI USA

University of Pennsylvania Perelman School of Medicine Philadelphia PA USA

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