Transition to Mania During Treatment of Bipolar Depression

Abstract

Some individuals with bipolar disorder transition directly from major depressive episodes to manic, hypomanic, or mixed states during treatment, even in the absence of antidepressant treatment. Prevalence and risk factors associated with such transitions in clinical populations are not well established, and were examined in the Systematic Treatment Enhancement Program for Bipolar Disorder study, a longitudinal cohort study. Survival analysis was used to examine time to transition to mania, hypomania, or mixed state among 2166 bipolar I and II individuals in a major depressive episode. Cox regression was used to examine baseline clinical and sociodemographic features associated with hazard for such a direct transition. These features were also examined for interactive effects with antidepressant treatment. In total, 461/2166 subjects in a major depressive episode (21.3%) transitioned to a manic/hypomanic or mixed state before remission, including 289/1475 (19.6%) of those treated with antidepressants during the episode. Among the clinical features associated with greatest transition hazard were greater number of past depressive episodes, recent or lifetime rapid cycling, alcohol use disorder, previous suicide attempt, and history of switch while treated with antidepressants. Greater manic symptom severity was also associated with risk for manic transition among both antidepressant-treated and antidepressant-untreated individuals. Three features, history of suicide attempt, younger onset age, and bipolar subtype, exhibited differential effects between individuals treated with antidepressants and those who were not. These results indicate that certain clinical features may be associated with greater risk of transition from depression to manic or mixed states, but the majority of them are not specific to antidepressant-treated patients.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

“…Patients with BD II in this trial showed similar benefits to those with BD I, with no increase in hypo ⁄ manic switch. Similarly, in the entire STEP-BD sample (n = 3640; 30.7% with BD II), there was no increased frequency of switch from depression to hypo ⁄ mania without an intervening period of wellness in antidepressant-treated patients (19.6%) compared to patients receiving non-antidepressant treatments (24.9%) (353). Consistent with previous studies (354), the risk of antidepressant-associated switch was lower in BD II than BD I.…”

Mixed Depression: Clinical Features and Predictors of Its Onset Associated with Antidepressant Use

“…Sensitivity and specificity of our model for antidepressant-association predictors were high. Some studies indicated that a BDI diagnosis [37,38,39], a positive history of suicide attempts possibly related to patient impulsiveness [37], higher YMRS scores on the disruptive behavior item [37], and excitatory symptoms (motor activation, pressured speech, and racing thoughts) [40] increase antidepressant-associated switch-risk. There is contrasting evidence about the role of age [37,38,41].…”

“…However, data on this topic are limited [7,33,34,35,36]. Furthermore, few studies have focused on characteristics that make patients more susceptible to antidepressant-associated MxD (AD-MxD) [37,38,39,40,41,42]; finally, no study heretofore has investigated the antidepressant-associated transition from depression to MxD.…”

State-Dependent Differences in Emotion Regulation Between Unmedicated Bipolar Disorder and Major Depressive Disorder

“…[1][2][3] Patients with MDD show lateral PFC hyperfunction or hypofunction (during automatic or voluntary emotion regulation, respectively), while BD is associated with VLPFC and ventromedial PFC hypofunction. Furthermore, both disorders are characterized by predominantly decreased frontolimbic connectivity.…”