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


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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    • "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). "
    03/2015; 13(1):102-112. DOI:10.1176/appi.focus.130119
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    • "This is particularly important because the presence of subthreshold bipolarity in patients with misdiagnosed unipolar major depression is one of the most common causes for the potential lack of antidepressant response and worsening of the affective disorder (Rihmer et al., 2013). It has been demonstrated that the presence of (hypo)manic symptoms in patients with major depressive episodes could predispose to a higher risk for developing an antidepressant induced manic switch (Tondo et al., 2010). Besides the current controversies over their short-term efficacy (Vazquez et al., 2013), a panel of experts has recently recommended to avoid the use of antidepressants (AD) for acute depressive patients with high mood instability, a history of rapid cycling, and psychomotor agitation (Pacchiarotti et al., 2013). "
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    ABSTRACT: Background: Mood disorders (MD) are disabling conditions throughout the world associated with significant psychosocial impairment. Affective temperaments, as well as hopelessness, may play a significant role in the pathophysiology of MD. The present study was designed to characterize patients with MD for their prevalent affective temperament and level of hopelessness. Methods: Five hundred fifty-nine (253 men and 306 women) consecutive adult inpatients were assessed using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version (TEMPS-A), the Gotland Scale for Male Depression (GSMD), the Beck Hopelessness Scale (BHS) and the Mini International Neuropsychiatric Interview (MINI). Results: Higher cyclothymia and irritable temperaments were found in bipolar disorder-I (BD-I) patients compared to those with other Axis I diagnoses. Major depressive disorder (MDD) patients had lower hyperthymia than BD-I and BD-II patients and higher anxiety than patients with other Axis I diagnoses. Severe "male" depression was more common in BD-II patients compared to BD-I and MDD patients. BD-I patients and those with other axis I diagnoses reported lower BHS Z 9 scores than those with BD-II and MDD. Limitations: The study had the limitations of all naturalistic designs, that is, potentially relevant variables were not addressed. Furthermore, the cross-sectional nature of the study did not allow conclusions about causation, and the use of self-report measures could be potentially biased by social desirability. Conclusion: MDD patients were more likely to have higher anxious temperament, higher hopelessness and lower hyperthymic temperament scores, while BD-I patients more often had cyclothymic and irritable temperaments than patients with other Axis I diagnoses. The implications of the present results were discussed.
    Journal of Affective Disorders 06/2014; 166:285-291. DOI:10.1016/j.jad.2014.05.018 · 3.38 Impact Factor
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    • "The use of antidepressants for bipolar depression is still controversial. The major criticism regarding use of antidepressants in instances of bipolar depression is based on the risk of destabilizing mood, switching into mania or hypomania [54-56] or increasing the cycle frequency [57,58]. Such negative effects appear to be limited to certain classes of antidepressants [59-61]. "
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    ABSTRACT: Many new approaches have been adopted for the treatment of bipolar disorder (BD) in the past few years, which strived to produce more positive outcomes. To enhance the quality of care, several guideline recommendations have been developed. For study purposes, we monitored the prescription of psychotropic drugs administered to bipolar patients who had been referred to tertiary care services, and assessed the degree to which treatment met specific guidelines. Between December 2006 and February 2009, we assessed 113 individuals suffering from BD who had been referred to the Royal Ottawa Mental Health Centre (ROMHC) Mood Disorders Program by physicians within the community, mostly general practitioners. The Structured Clinical Interview for DSM-IV-TR was used to assess diagnosis. The prescribed treatment was compared with specific Canadian guidelines (CANMAT, 2009). Univariate analyses and logistic regression were used to assess the contribution of demographic and clinical factors for concordance of treatment with guidelines. Thirty-two subjects had BD type I (BD-I), and 81 subjects had BD type II (BD-II). All subjects with BD-I, and 90% of the BD-II group were given at least one psychotropic treatment. Lithium was more often prescribed for subjects with BD-I (62%) than those with BD-II (19%). Antidepressants were the most frequently prescribed class of psychotropics. Sixty-eight percent of subjects received treatment concordant with guidelines by medication and dose. The presence of a current hypomanic episode was independently associated with poorer concordance to guidelines. In more than half the cases, the inappropriate use of antidepressants was at the origin of the non concordance of treatment with respect to guidelines. Absence of psychotropic treatment in bipolar II patients and inadequate dosage of mood stabilizers were the two other main causes of non concordance with guidelines. The factors related to treatment not concordant with guidelines should be further explored to determine appropriate strategies in implementing the use of guidelines in clinical practice.
    BMC Psychiatry 08/2013; 13(1):211. DOI:10.1186/1471-244X-13-211 · 2.21 Impact Factor
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