Efficacy and safety of cariprazine in the treatment of bipolar disorder

Saraf, Gayatri; Pinto, Jairo Vinícius; Yatham, Lakshmi N.

doi:10.1080/14656566.2019.1660319

Cited by 13 publications

(9 citation statements)

References 60 publications

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“…Some research data have indicated that both low and high doses of cariprazine are effective and well tolerated as a drug treatment for mania, depression, and psychosis [343][344][345]. RCTs of BD-I patients in manic and mixed episodes found the greatest treatment benefit when cariprazine was provided in the range of 3 to 12 mg [346,347]. Placebo-controlled studies of bipolar depression have indicated that 1.5 to 3 mg/d of cariprazine monotherapy is a competent treatment for acute depression in BD [346].…”

Section: Cariprazinementioning

confidence: 99%

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Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

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Section: Cariprazinementioning

confidence: 99%

“…RCTs of BD-I patients in manic and mixed episodes found the greatest treatment benefit when cariprazine was provided in the range of 3 to 12 mg [346,347]. Placebo-controlled studies of bipolar depression have indicated that 1.5 to 3 mg/d of cariprazine monotherapy is a competent treatment for acute depression in BD [346].…”

Section: Cariprazinementioning

confidence: 99%

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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“…More recently and based on the proposed neurobiological aberration in SUD and BD, D2/D3 receptor partial agonists attract attention as a possible medication of interest. A recent case report on cariprazine an effective medication in BD [53]-in methamphetamine use disorder [54] argues for further evaluation in RCTs.…”

Section: Pharmacotherapies Of Comorbid Bd and Illicit Substance Usementioning

confidence: 99%

Bipolar Disorder and Comorbid Use of Illicit Substances

et al. 2021

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Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

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“…Following oral administration, cariprazine is rapidly absorbed and reaches peak concentrations within 3–5 h ( 28 ). It has a large volume of distribution and is extensively distributed in tissues ( 29 ). Cariprazine is primarily metabolized by the CYP3A4 isoenzyme and to a lesser extent, by CYP2D6 into two major active metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR) ( 30 ).…”

Section: Overview Of Cariprazinementioning

confidence: 99%

“…According to a 12-week study, steady-state plasma concentrations were reached within 1–2 weeks for cariprazine and DCAR, and within 4 weeks for DDCAR due to its slow elimination ( 33 ). Cariprazine and its metabolites are minimally excreted in urine ( 29 ). Cariprazine itself is a weak inhibitor of CYP3A4 and CYP2D6 with no significant induction effects in human hepatocytes ( 30 ).…”

Section: Overview Of Cariprazinementioning

confidence: 99%

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials

Keramatian

Schaffer

et al. 2021

Front. Psychiatry

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Bipolar disorder (BD) is chronic psychiatric disorder associated with significant impairment in psychosocial functioning and quality of life. Although current pharmacological treatments for BD have improved its clinical management, many patients do not achieve remission, particularly those suffering from bipolar depression. In addition, available treatments are associated with a myriad of potential adverse effects, which highlights the need for novel therapeutic agents that can be effective for both phases of the illness with a reduced side effect burden. Cariprazine is a novel antipsychotic that is a dopamine D2/D3 partial agonist with a preference for D3 receptors. In this review, we examine the pharmacological properties, clinical efficacy and tolerability profile of cariprazine in patients with BD, taking into account the latest clinical trials data. We also review post hoc analyses addressing clinically relevant subgroups and symptom domains in BD. Current evidence suggests efficacy for cariprazine 3–12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the efficacy of cariprazine appears to be dose-related, with doses of 1.5–3 mg/day beneficial as monotherapy. Cariprazine is overall well-tolerated by patients in both manic and depressive episodes. Its most common side effects relative to placebo include akathisia, extrapyramidal symptoms and nausea. There are no metabolic concerns reported with cariprazine use. In summary, the latest evidence suggests that cariprazine is an effective and safe treatment option for BD.

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Efficacy and safety of cariprazine in the treatment of bipolar disorder

Cited by 13 publications

References 60 publications

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Bipolar Disorder and Comorbid Use of Illicit Substances

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials

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