Article

Risk of Switch in Mood Polarity to Hypomania or Mania in Patients With Bipolar Depression During Acute and Continuation Trials of Venlafaxine, Sertraline, and Bupropion as Adjuncts to Mood Stabilizers

University of Texas at Dallas, Richardson, Texas, United States
American Journal of Psychiatry (Impact Factor: 12.3). 02/2006; 163(2):232-9. DOI: 10.1176/appi.ajp.163.2.232
Source: PubMed

ABSTRACT

The authors examined the comparative risks of switches in mood polarity into hypomania or mania during acute and continuation trials of adjunctive antidepressant treatment of bipolar depression.
One hundred fifty-nine patients with bipolar I disorder or bipolar II disorder participated in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an adjunct to a mood stabilizer. Patients in 87 of these trials entered continuation treatment for up to 1 year. Antidepressant response and the occurrence of subthreshold brief hypomania (emergence of brief hypomania [at least 1 but <7 days] or recurrent brief hypomania) and threshold switches (emergence of full-duration hypomania [> or =7 days] or mania) were blindly assessed by using clinician-rated daily reports of mood-associated dysfunction on the National Institute of Mental Health Life Chart Method.
Threshold switches into full-duration hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold brief hypomanias was higher in both the acute (ratio=3.60) and continuation trials (ratio=3.75) of venlafaxine than in the acute and continuation trials of bupropion (ratios=0.85 and 1.17, respectively) and sertraline (ratios=1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant trials, or in only 23.3% of the patients, was there a sustained antidepressant response in the continuation phase in the absence of a threshold switch.
Adjunctive treatment with antidepressants in bipolar depression was associated with substantial risks of threshold switches to full-duration hypomania or mania in both acute and long-term continuation treatment. Of the three antidepressants included in the study, venlafaxine was associated with the highest relative risk of such switching and bupropion with the lowest risk.

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Available from: Heinz Grunze, Dec 21, 2015
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    • "Concerns about inducing mania surely contribute to the routine exclusion of patients with identified BD from controlled trials of antidepressant drugs, contributing to the dearth of investigations of bipolar depression. Evidence of long-term, prophylactic benefit of antidepressants is even more limited, with greater concerns about increased long-term risk of mania, emotional destabilization or more rapid cycling of mood-states (Ghaemi et al., 2003, 2008, 2010 ; Leverich et al., 2006 ; Post et al., 2006 ; Pacchiarotti et al., 2011b ; Sussman et al., 2012 ; Valentí et al., 2012). One meta-analysis of 12 heterogeneous , short-term trials that included both BD I and II patients in acute depression found that antidepressants of various types yielded a rather large apparent superiority in pooled response-rates vs. placebo or other control treatments, averaging 86 % [95 % confidence intervals (CI) 49–130] and for remission rates, 41 % (95 % CI 11–80 ; Gjisman et al., 2004). "

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    • "Furthermore, changes in mood after sleep deprivation share several phenomenological similarities with hypomania, and the risk of hypomanic switch is elevated during and after sleep deprivation (Wehr et al., 1982; Colombo et al., 1999). Interestingly, antidepressants that do not suppress REM sleep (e.g., bupropion) (Nofzinger et al., 1995; Ott et al., 2004), have the least risk to induce a hypomanic switch in a depressed person (Leverich et al., 2006). This latter observation is consistent with the proposal that REM suppression is one of the main mechanisms by which most antidepressants and sleep deprivation induce hypomanic/manic symptoms (Salvadore et al., 2010). "
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    • "Concerns about inducing mania surely contribute to the routine exclusion of patients with identified BD from controlled trials of antidepressant drugs, contributing to the dearth of investigations of bipolar depression. Evidence of long-term, prophylactic benefit of antidepressants is even more limited, with greater concerns about increased long-term risk of mania, emotional destabilization or more rapid cycling of mood-states (Ghaemi et al., 2003, 2008, 2010 ; Leverich et al., 2006 ; Post et al., 2006 ; Pacchiarotti et al., 2011b ; Sussman et al., 2012 ; Valentí et al., 2012). One meta-analysis of 12 heterogeneous , short-term trials that included both BD I and II patients in acute depression found that antidepressants of various types yielded a rather large apparent superiority in pooled response-rates vs. placebo or other control treatments, averaging 86 % [95 % confidence intervals (CI) 49–130] and for remission rates, 41 % (95 % CI 11–80 ; Gjisman et al., 2004). "

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