Cariprazine for the treatment of bipolar mania with mixed features: A post hoc pooled analysis of 3 trials

McIntyre, Roger S.; Masand, Prakash S.; Earley, Willie; Patel, Mehul

doi:10.1016/j.jad.2019.07.020

Cited by 26 publications

(19 citation statements)

References 44 publications

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“…A number of observational studies have suggested that the efficacy of lithium declines with successive episodes. A similar pattern appears to occur with atypical antipsychotics in the treatment of bipolar disorder, with data for both olanzapine and cariprazine. Lamotrigine is less effective as a function of the number of prior depressive episodes, and so is treatment in general.…”

Section: What Is the Evidence Supporting Staging?mentioning

confidence: 91%

Staging in bipolar disorder: from theoretical framework to clinical utility

et al. 2017

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Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an atrisk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.

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Section: What Is the Evidence Supporting Staging?mentioning

confidence: 91%

Staging in bipolar disorder: from theoretical framework to clinical utility

et al. 2017

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“…three or more symptoms of depression), 15% had two or more depressive symptoms, and 44% had a Montgomery Asberg Depression Rating Scale (MADRS) Score of 10 or more at baseline (Table 2). 27 In each of these groups, cariprazine significantly reduced manic symptoms (Young Mania Rating Scale, YMRS), compared with placebo and numerically reduced depressive symptoms in all groups and significantly so in the MADRS 10 or more subgroup (Table 2).…”

Section: Efficacy In Mania: Acute Bp Mania Dsm-iv Mixed Episodes (Full Criterion Mania Plus Full Criterion Depression) and Dsm5 Manic Epimentioning

confidence: 95%

“…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.…”

Section: Tolerabilitymentioning

confidence: 99%

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

Stahl

Laredo

Morrissette

2020

Therapeutic Advances in Psychopharmacology

204

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Cariprazine is one of the newest dopamine-serotonin partial agonists, also known as ‘atypical’ second generation antipsychotics. Originally approved for acute and maintenance treatment of schizophrenia as well as for acute mania and mixed mania/depression, cariprazine has now been approved for bipolar I depression. Additionally, post hoc analyses of bipolar I depressed subjects show that both those with and those without concurrent manic features were improved following treatment with cariprazine. Maintenance studies are in progress in bipolar disorder, as are studies to augment antidepressants in unipolar major depressive episodes insufficiently responsive to treatment. Here, we review specifically the efficacy and safety data of cariprazine in bipolar I disorder and discuss the hypothesized mechanism of action of cariprazine and how it could theoretically be linked to caprazine’s broad therapeutic actions across the mood disorder spectrum.

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“…Double-blind, placebo-controlled studies have demonstrated the efficacy of cariprazine in low doses (3-6 mg/day) and high doses (6-12 mg/day) in the treatment of manic and mixed episodes of bipolar I disorder (63)(64)(65)(66). Importantly, cariprazine was well-tolerated with non-significant changes in prolactin levels, QT intervals and metabolic parameters [with the exception for fasting glucose in the study by Durgam et al (64)].…”

Section: Cariprazine Efficacy Across the Wide Range Of Symptoms Of Bipolar Disordermentioning

confidence: 99%

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

et al. 2021

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Cariprazine is currently approved for the treatment of patients with schizophrenia (USA and EU), and for manic, depressive, and episodes with mixed features in bipolar I disorder (USA): several randomized controlled studies have also explored its efficacy in patients with major depressive disorder. This review summarizes its current therapeutic uses and potential advantages for treating the main symptoms of schizophrenia, bipolar I and major depressive disorder, considering its pharmacodynamic properties, efficacy, and tolerability. Its predominantly D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, contributes to its efficacy across a wide array of psychopathological symptoms (including reality distortion, disorganized thought, negative symptoms, mood disturbance, anhedonia, and cognitive impairment), and to a favorable side effect profile. Cariprazine may be a “drug of choice” in patients with predominant negative and cognitive symptoms of schizophrenia, as well as those with metabolic syndrome. Further investigation of its relative efficacy when compared to aripiprazole or other active comparators is warranted. Its effectiveness in the treatment of bipolar mania, bipolar I depression and bipolar I episodes with mixed features, with minimal accompanying metabolic changes is well-established. The longer half-life and delayed time to relapse in patients diagnosed with schizophrenia when compared to other second-generation antipsychotics represent other advantages, given the high rates of non-adherence and frequent relapses seen in clinical practice. Its efficacy in overlapping symptom domains in other major psychiatric disorders appears promising.

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Cariprazine for the treatment of bipolar mania with mixed features: A post hoc pooled analysis of 3 trials

Cited by 26 publications

References 44 publications

Staging in bipolar disorder: from theoretical framework to clinical utility

Staging in bipolar disorder: from theoretical framework to clinical utility

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

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

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