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{"Image DocumentName": "Bipolar Disorders: Scope of the Problem", "Image ImageDescription": "Bipolar I and II disorders occur in up to 4% of the population 1,2. frequently begin in the mid to late-teens 3,4. cause chronic disability 5-7. characterized by recurrent and chronic symptoms with associated multiple psychiatric and medical comorbid conditions 1,2. also excess and premature mortality and suicide Bipolar disorder has been listed among the top 10 causes of disability worldwide 7. estimated to cost about  70 billion/year in 2008 dollars 11,12,15. Editorial \u2013 CNS Spectrums, Something Borrowed, Something Blue: Why is Bipolar Disorder an Orphan? Andrew A. Nierenberg, MD (http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=2552) Bipolar disorders (bipolar I disorder and bipolar II disorder) occur in up to 4% of the population,1,2 frequently begin in the mid to late-teens,3,4 and cause chronic disability.5-7 Bipolar I disorder and bipolar II disorder are characterized by recurrent and chronic symptoms with associated multiple psychiatric and medical comorbid conditions,1,2 as well as excess and premature mortality and suicide.8-10 Bipolar disorder has been listed among the top 10 causes of disability worldwide7 and is estimated to cost about  70 billion/year in 2008 dollars.11,12 Yet, since the advent of lithium over 60 years ago, not a single medication has been specifically developed for bipolar disorder. Every modern medication approved or studied for bipolar disorder has been derived from existing anticonvulsants,13-18 antipsychotics,19-22 antidepressants,23 wakefulness medications,24 and antiglutaminergic agents,25 all approved for other disorders. Thus, the paradox exists that one of the most common psychiatric disorders is an orphan. One possible reason for the lack of specific drug development could be the perceived success of lithium. Lithium recently enjoyed the 60th anniversary of its formal debut into psychiatry.26 John Cade published his remarkable study in 1949 and it is worth reading for Cade\u2019s insightful observations.27,28 Through the work of Morgans Schou,29 Sam Gershon,30,31 and others, the clinical database for the efficacy of lithium grew. It took until the early 1970\u2019s for lithium to enter the market in the United States, partially because of toxicity concerns left over from its use as a salt substitute. Lithium continues to be one of the mainstays of bipolar treatment and is recommended by multiple treatment guidelines.32 Paradoxically, its use has been declining while studies of the mechanisms of action of lithium and lithium response are starting to unlock important clues to bipolar pathophysiology Another problem in the bipolar field that may have blocked drug development comes from the surprising controversy in the use of antidepressants. On one hand, a meta-analysis strongly supported the use of antidepressants with antimanic medications for bipolar depression.37 On the other hand, the largest placebo-controlled study of an antidepressant added to a mood stabilizer found no benefit from bupropion or paroxetine, and no short-term harm with switching from depression to mania.23 Thus, the problem. Dr. Nierenberg is professor of psychiatry at Harvard Medical School, co-director of the Bipolar Clinic and Research Program, and associate director of the Depression Clinical and Research Program at Massachusetts General Hospital (MGH) in Boston. Faculty Disclosures: Dr. Nierenberg consulted to or served on the advisory boards of Abbott, Appliance Computing, Inc., Brain Cells, Inc., Bristol-Myers Squibb, Eli Lilly, EpiQ, Forest, GlaxoSmithKline, Janssen, Jazz, Merck, Novartis, Pamlab, Pfizer, PGx Health, Pharmaceutica, Schering-Plough, Sepracor, Shire, Somerset, Takeda, and Targacept; he has received research support from Cederroth, Cyberonics, Forest, Medtronics, NARSAD, the NIMH, Ortho-McNeil-Janssen, Pamlab, Pfizer, Shire, and the Stanley Foundation through the Broad Institute; he has received past support from Bristol-Myers Squibb, Cederroth, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Pfizer, Lictwer Pharma, and Wyeth; he has received honoraria from the MGH Psychiatry Academy (MGHPA activities are supported through Independent Medical Education grants from AstraZeneca, Eli Lilly, and Janssen; he earns fees for editorial functions for CNS Spectrums through MBL Communications, Inc., and Psychiatric Annals through Slack, Inc.; he receives honoraria as a CME Executive Director for the Journal of Clinical Psychiatry through Physicians Postgraduate Press; he has been on the speaker\u2019s bureaus of Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, and Wyeth; he has received royalties from Cambridge University Press and Belvoir Publishing; he owns stock options in Appliance Computing, Inc.; and owns the copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale, exclusively licensed to the MGH Clinical Trials Network and Institute. CNS Spectr 15:1 \u00a9 MBL Communications Inc. January is that bipolar depression may (or may not) be responsive to antidepressants. As an alternative to antidepressants, studies have shown the efficacy of a combination of olanzapine and fluoxetine21 or quetiapine.38 The problem here is that we lack effectiveness studies that include a broad, representative bipolar population and integrate tolerability, attrition, and efficacy. Only by conducting effectiveness studies will we know how these treatments perform in the real world. Where does this leave the bipolar orphan? It might be time to consider that while people with bipolar disorder can become psychotic, bipolar disorder is not schizophrenia. While depression is a prominent component of bipolar disorder, antidepressants may not be the answer. While bipolar patients have mood episodes, it is insufficient to just treat the episodes; they have a chronic disorder and we need to find new treatments to improve the course of the disorder. It is time to develop drugs specific to bipolar disorder, informed by our growing understanding of pathophysiology and genetics. Then we won\u2019t have to borrow and be so blue. CNS. REFERENCES. 1. Grant BF, Stinson FS, Hasin DS, et al. Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2005;66: Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2007;64: Perlis RH, Miyahara S, Marangell LB, et al. 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Antidepressants for bipolar depression: A systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161: Thase ME. Efficacy of quetiapine monotherapy in bipolar I and II depression: A double-blind, placebo-controlled study (The BOLDER II study). J Clin Psychopharmacol. 2006;26: Editorial. 16.", "Image XResolution": "37", "Image YResolution": "37", "Image ResolutionUnit": "Pixels/Centimeter", "Image Software": "SlidePlayer", "Image YCbCrPositioning": "Centered"}