Abstract
Bipolar depression is considered the most difficult-to-treat phase of bipolar disorder, in relation to its pervasiveness and efficacy and/or tolerability limitations of available treatments. Indeed, most mood stabilizers and atypical antipsychotics are not as effective in ameliorating depressive compared with manic symptoms, and entail substantial tolerability limitations. However, the use of antidepressants is highly controversial, as their efficacy appears less robust in bipolar compared with unipolar depression. In addition, antidepressants, in spite of generally having adequate somatic tolerability, in BD may be associated with a higher risk of manic/hypomanic switch, suicidality and rapid cycling. Among alternative pharmacological strategies, compounds with stimulant and pro-dopaminergic effects, such as methylphenidate, modafinil, armodafinil and pramipexole, have showed potential antidepressant activity, even though their use in clinical practice has been limited by the paucity of controlled evidence. This article seeks to review available evidence about the use of the aforementioned compounds in the treatment of bipolar depression. Findings from reviewed studies suggested that pro-dopaminergic compounds, such as pramipexole and stimulants/stimulant-like agents, deserve consideration as adjunctive therapies in bipolar depressed patients, at least in some subgroups of patients. Nevertheless, caution regarding their use is recommended as further clinical trials with larger samples and longer follow-up periods are necessary to clarify the roles of these medications in bipolar depression.
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Conflict of Interest
Bernardo Dell’Osso has served on speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Eli Lilly, Pfizer, GlaxoSmithKline, Lundbeck, Cyberonics and Italfarmaco.
Terence A. Ketter has received grant/research support from AstraZeneca, Cephalon, Eli Lilly and Company, Pfizer and Sunovion Pharmaceuticals; has served as a consultant for Allergan, Avanir Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Forest Pharmaceuticals, Janssen Pharmaceutica Products, Merck & Co., Sunovion Pharmaceuticals and Teva Pharmaceuticals; has received lecture honoraria from Abbott Laboratories, AstraZeneca, GlaxoSmithKline and Otsuka Pharmaceuticals; and has received royalties from American Psychiatric Publishing. In addition, Dr. Ketter’s spouse is an employee of and holds stock in Janssen Pharmaceuticals.
Laura Cremaschi and Gregorio Spagnolin declare that they have no conflict of interest.
A. Carlo Altamura has served as a consultant for Roche, Merck, AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Lundbeck, Sanofi, Eli Lilly and Pfizer.
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Dell’Osso, B., Ketter, T.A., Cremaschi, L. et al. Assessing the Roles of Stimulants/Stimulant-like Drugs and Dopamine-agonists in the Treatment of Bipolar Depression. Curr Psychiatry Rep 15, 378 (2013). https://doi.org/10.1007/s11920-013-0378-z
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DOI: https://doi.org/10.1007/s11920-013-0378-z