To examine the causative agents, clinical characteristics, management, risk factors, and neurochemical mechanism of the antidepressant-associated mania, MEDLINE searches were conducted. Mania can occur by chance during antideressant treatment or withdrawal, particularly in patients predisposed to mood disorder. Antidepressant-associated mania, especially withdrawal mania, appears to be milder and a more time-limited syndrome than a spontaneous mania and may represent a distinct clinical entity. MAOI, especially RIMA, or bupropion may be associated with milder and less manic inductions than either TCA or SSRI. The possible risk factors for antidepressant-induced mania are female, mood disorder, especially bipolar type Ⅰ, past and family history of mood disorder, especially bipolar type Ⅰ, long-term treatment, high dose, and combined therapy in treatment-resistant depression, the possible for withdrawal mania are female, mood disorder, especially major depressive disorder, past and family history of mood disorder, especially major depressive disorder, long-term treatment, high dose, abrupt discontinuation or dose reduction, TCA or MAO(except RIMA?). Antidepressantinduced mania can result from dysfunction of mechanisms that maintain noradrenaline/acetylcholine balance associated with the antidepressant-induced activation of noradrenaline system. The mechanism of withdrawal mania with TCA is cholinergic-monoaminergic interaction theory, and with MAOI is related a hyperdopaminergic state due to loss of drug-induced subsensitivity of dopamine autoreceptors. The prevention of these side effects will require further well-designed study on risk factors.
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