An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression

Durgam, Suresh; Earley, Willie; Lipschitz, Alan; Guo, Hua; Laszlovszky, István; Németh, György; Vieta, Eduard; Calabrese, Joseph R.; Yatham, Lakshmi N.

doi:10.1176/appi.ajp.2015.15020164

Cited by 159 publications

(130 citation statements)

References 6 publications

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“…Data support efficacy for brief pulse right unilateral placement, although there are insufficient data to guide the decision of unilateral or bilateral placement for bipolar depression 261. Additional second‐line options include cariprazine, with efficacy demonstrated through a large RCT262 and a pooled analysis of a failed RCT and a positive RCT263 (level 2), although there is less clinical experience supporting its use. Olanzapine‐fluoxetine combination (level 2)264, 265 is effective and is also recommended as a second‐line option.…”

Section: Acute Management Of Bipolar Depressionmentioning

confidence: 99%

“…We do not provide specific recommendations for the use of cariprazine, as there is currently only evidence for efficacy in acute manic and depressive episodes262, 392 and not yet for maintenance treatment (level 4). While a small RCT suggests a lack of efficacy for flupenthixol as maintenance treatment, larger studies are needed before definite conclusions can be drawn (level 3 negative) 393.…”

Section: Maintenance Therapy For Bipolar Disordermentioning

confidence: 99%

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Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

et al. 2018

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The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

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Section: Acute Management Of Bipolar Depressionmentioning

confidence: 99%

Section: Maintenance Therapy For Bipolar Disordermentioning

confidence: 99%

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

et al. 2018

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“…Among six second-generation antipsychotics in the acute treatment of bipolar depression [72][73][74][75][76][77][78][79][80][81][82], three had significantly higher rates of somnolence relative to placebo; quetiapine-XR had the highest rate of somnolence (29.2 %) [81], the largest ARI (23.4 %), and the smallest NNH (4; 95 % CI 3-7) ( Table 4). The rates of somnolence from ziprasidone were positively correlated to dosing [82].…”

Section: Acute Active Treatment Versus Placebomentioning

confidence: 99%

Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

et al. 2016

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Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to develop over at least 4 weeks is reasonable before discontinuing an antipsychotic.

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“…The recently published results of a randomized, double-blind, placebocontrolled study suggests that adjunctive cariprazine 2-4.5 mg/d is effective and generally well tolerated in adults with major depressive disorder who had inadequate responses to standard antidepressants (Durgam et al, 2016a). Positive results have been also obtained from phase II and III clinical trials for bipolar mania (Calabrese et al, 2015;Durgam et al, 2016b;Sachs A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT et al, 2015) leading to approval by the FDA of cariprazine also for the treatment of manic or mixed episodes associated with bipolar disorder (McCormack, 2015). Table S3 reports clinical trials currently running or recently completed regarding cariprazine in different CNS diseases.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Current drug treatments targeting dopamine D3 receptor

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Pharmacology & Therapeutics

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An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression

Abstract: Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression.

Cited by 159 publications

References 6 publications

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

Current drug treatments targeting dopamine D3 receptor

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