While methylphenidate possesses structural similarities to amphetamine, and both agents target the dopamine transporter, subtle pharmacological differences exist, such as amphetamines being dopamine transport substrates whereas methylphenidate is a dopamine transport blocker (Sulzer et al. ![]() amphetamines, methylphenidate, modafinil, armodafinil) with diverse chemical composition and biological functions. Stimulants include a heterogeneous group of medications (e.g. Some of these compounds may even have cognition enhancing actions (Turner et al. Stimulants and related stimulant-like compounds such as modafinil and armodafinil (hereafter referred to collectively as stimulants) can promote alertness and wakefulness, reduce fatigue, attenuate excessive appetite, and perhaps even improve mood through a variety of mechanisms of action distinctive from those of mood stabilizers, second-generation antipsychotics, and antidepressants (Connolly & Thase, 2011). For these reasons, there is a compelling need for additional treatment options with proven efficacy and safety/tolerability in bipolar depression. Moreover, antidepressants may be less effective in bipolar compared to unipolar depression, and may induce mania, rapid cycling, mood destabilization, and increased suicidality (Ghaemi et al. In addition, treating bipolar depression is particularly challenging, with mood stabilizers and second-generation antipsychotics commonly yielding inadequate efficacy and safety/tolerability, respectively. While mood stabilizers (lithium, divalproex, carbamazepine, lamotrigine) and second-generation antipsychotics can effectively and rapidly overcome the core symptoms of mania, bipolar depression remains the major source of suffering for most patients, being the most pervasive illness phase, and associated with the greatest symptom burden and disability (Judd et al. 2007), severe, disabling and chronic illness that profoundly adversely impacts the lives of patients and their families (Judd et al. The present review aims to provide an updated perspective on the use of stimulants and stimulant-like medications in adult bipolar depression, considering not only recent randomized controlled trials, but also open naturalistic studies, in order to clarify the strengths and limitations of using these agents.Īrmodafinil, bipolar depression, methylphenidate, modafinil, stimulants Introductionīipolar disorder (BD) is a common (Merikangas et al. Stimulants and related compounds such as modafinil and armodafinil have on occasion been used as adjuncts in bipolar depressed patients with encouraging results, but their use is limited by the paucity of systematic evidence of efficacy and safety. Moreover, the use of antidepressants in bipolar depression is controversial due to concerns regarding the risks of inefficacy or switching to mood elevation. Mood stabilizers and second-generation antipsychotics for bipolar depression are commonly only partially effective, and their side-effects may overlap with depressive symptoms such as hypersomnia, daytime drowsiness, fatigue, psychomotor retardation, and weight gain. ![]() ![]() ![]() Bipolar depression represents a high priority research field, due to its pervasiveness, and high economic and personal (suicidality, impaired function, quality of life) costs, and the limited evidence base to inform therapeutics.
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