Article

Mania associated with antidepressant treatment: Comprehensive meta-analytic review

Department of Psychiatry and Neuroscience Program, Harvard Medical School and McLean Division of Massachusetts General Hospital, Boston, MA, USA.
Acta Psychiatrica Scandinavica (Impact Factor: 5.61). 12/2009; 121(6):404-14. DOI: 10.1111/j.1600-0447.2009.01514.x
Source: PubMed

ABSTRACT

To review available data pertaining to risk of mania-hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers.
Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use.
The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients.
Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers.

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    • "without; χ 2 ¼5.29, p ¼0.02), consistent with confounding by indication (Tondo et al., 2010). Among BD patients, switching risk was somewhat, but nonsignificantly, greater if an antidepressant was used (31.4% vs. 21.3%; "
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    • "Many clinicians rely on plausibly expected, protective effects of ongoing mood-stabilizing treatments to limit risks of mood-switching when an antidepressant is given to a BD patient. However, evidence concerning putative protective effects of mood-stabilizers against mania or hypomania during treatment with antidepressants remains inconclusive and the point requires further, randomized-controlled trials (Licht et al., 2008 ; Tondo et al., 2010). Additional treatments for bipolar depression are being considered, but most remain experimental (Table 3). "

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    • "In summary, we believe that this patient had an antidepressant-induced mania due to excessively prolonged use of a substance with antidepressant properties and his bipolar disorder. There are studies that suggest a 4.58% (Tondo et al. 2010) to 15% (Pickar 1982) risk of switch to mania in bipolar patients treated with MAO inhibitors. According to DSM 5, 'a manic episode that emerges during antidepressant treatment but persists beyond the physiological effect of treatment is sufficient evidence of manic episode and therefore a bipolar disorder type I' (American Psychiatric Association 2013); given that for high doses of β-carbolines the half-life is 1 to 5 h (Riba et al. 2003), we believe this is the case of the patient presented. "
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