Cariprazine efficacy in bipolar I depression with and without concurrent manic symptoms: post hoc analysis of 3 randomized, placebo-controlled studies

Abstract

Objective. Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms. Methods. Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Results. Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of −2.5 (p = .0033) and −2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (−3.3; p = .0008), but not for 3 mg/day (−1.9; p = .0562). Conclusion. The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.

Cariprazine as a treatment across the bipolar I spectrum from depression to mania: mechanism of action and review of clinical data

“…In a post hoc analysis of all three of these studies pooled together to investigate cariprazine’s efficacy in depression with symptoms of mania, it was determined that 58.4% of the 1483 patients randomized to treatment had concurrent manic symptoms (YMRS score ⩾4 but <10 (1 study) or 12 (2 studies) (Table 4). 31 Both patients with and without manic symptoms showed significant improvement in MADRS score from baseline compared with placebo, but for patients with manic symptoms, both 1.5 mg/day and 3.0 mg/day were significant but only 1.5 mg/day was significant for patients without manic symptoms (Table 4). 31…”

“…31 Both patients with and without manic symptoms showed significant improvement in MADRS score from baseline compared with placebo, but for patients with manic symptoms, both 1.5 mg/day and 3.0 mg/day were significant but only 1.5 mg/day was significant for patients without manic symptoms (Table 4). 31…”

“…The side effect profile of cariprazine is different in patients with bipolar depression compared with patients with manic or mixed episodes, probably because of the differences in dosing and titration between the two sets of studies (Table 5). [23][24][25][26][27][28][29][30][31][32][33] That is, the most common adverse reactions in the manic/mixed patients, extrapyramidal symptoms and akathisia, were present in a greater percentage of patients than in the bipolar depressed group, likely because the dose was lower and the titration much slower in the bipolar depressed group. The proportion of patients with metabolic shifts of fasting glucose, total cholesterol, and fasting triglycerides was similar to placebo and there was no meaningful increase in mean prolactin levels from baseline to endpoint.…”

Diagnosing and treating major depressive episodes that lie along the mood disorders spectrum: focus on depression with mixed features

“…Post-hoc analyses of a number of positive randomized, placebocontrolled trials of second-generation antipsychotics in bipolar depression have explored response of depression with hypo/manic symptoms vs pure depression (ie, bipolar depression with no hypo/manic symptoms). These studies found that olanzapine (with and without fluoxetine), 50,51 lurasidone, 52 and cariprazine 53 were as effective in mixed depression as in pure depression. A similar analysis showed that lurasidone reduced mixed features in children with bipolar depression.…”

Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine

“…Furthermore, incidence of suicidality was low in cariprazine group ( 73 ). Finally, a post-hoc analysis of three randomized, placebo-controlled studies showed that cariprazine is effective in treating bipolar I depression with mixed features in the doses of 1.5 and 3.0 mg per day ( 74 ).…”