cariprazine and Depressive-Disorder

Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States. We systematically reviewed the literature on the efficacy and safety of cariprazine.. We performed a literature search of the PubMed, MEDLINE, PsycINFO, EMBASE, and Cochrane collaboration databases through August 31, 2016. The search was not restricted by patient age. Articles published in English or official English translations were included.. Eleven articles that evaluated the use of cariprazine in the treatment of psychiatric disorders were identified. Four trials evaluated the safety and efficacy of cariprazine in bipolar disorder. One trial investigated its use as an adjunct to antidepressants in major depressive disorder. Three trials evaluated its use in the treatment of acute exacerbations of schizophrenia. Two studies used risperidone or aripiprazole as comparators. Both low- and high-dose cariprazine were more effective than placebo in the treatment of acute mania, mixed episodes, and acute psychosis. Additionally, cariprazine showed efficacy as an adjunctive treatment for depression.. Our review indicates that cariprazine demonstrates superior efficacy and good tolerability, both at low and high doses, in the treatment of individuals with psychosis, mania, and depression.

Topics: Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder; Humans; Piperazines; Risperidone; Schizophrenia

Cariprazine is a novel drug with partial agonist activity at dopamine D2/3 receptors and six- to eightfold higher affinity for human dopamine D3 over D2 receptors. Results from several placebo-controlled Phase II/III trials in patients with a The Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of schizophrenia or bipolar I disorder suggest that cariprazine is superior to placebo with respect to antipsychotic and antimanic activity. Reports concerning safety and tolerability of cariprazine are mainly favorable, although the rates of treatment-associated adverse events, which most commonly included akathisia and extrapyramidal symptom, are rather high. However, only minor alterations of clinical laboratory values, prolactin concentrations and ECG parameters are reported in cariprazine-treated patients. A new drug application to the U.S. F DA for cariprazine for the treatment of both schizophrenia and manic or mixed episodes associated with bipolar I disorder was submitted in November 2012. A more precise assessment of the clinical properties of this new drug will require additional studies, aimed to compare and contrast cariprazine with other antipsychotic agents.

Topics: Administration, Oral; Animals; Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Dopamine Agonists; Drug Partial Agonism; Humans; Piperazines; Receptors, Dopamine D2; Receptors, Dopamine D3; Schizophrenia; Schizophrenic Psychology

Rates of response and remission are measures that endorse the clinical significance of treatment. Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults. Post hoc analyses of pooled data from 3 pivotal trials of cariprazine in manic/mixed episodes associated with bipolar I disorder were conducted to investigate the effect of cariprazine on various criteria of response and remission.. The constituent studies were 3-week randomized, double-blind, placebo-controlled, multicenter, parallel-group phase II/III studies in adult patients (age 18-65 years) with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668). Post hoc analyses included Young Mania Rating Scale (YMRS) outcomes for response (≥50% decrease in score), remission (total score ≤12 and ≤8), cumulative remission, and global improvement. Additionally, composite remission (YMRS total score ≤12 plus Montgomery-Åsberg Depression Rating Scale total score ≤12) and worsening/switch to depression (MADRS total score ≥15) by week were investigated.. Rates of response and remission were significantly greater for cariprazine versus placebo on every measure evaluated (P < .01 all analyses); the estimated number needed to treat for each measure was ≤10. There was no evidence of worsening/switch to depression.. Post hoc analyses, short treatment duration, no active comparator.. Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Depression; Depressive Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Piperazines; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to evaluate whether chronic treatment with cariprazine, a dopamine D2 and D3 receptor partial agonist with preferential binding to D3 receptors, shows antidepressant-like effects in the chronic mild stress (CMS)-induced anhedonia model. Male Wistar rats were subjected to the CMS procedure for 7 weeks; nonstressed animals served as controls. For the last 5 weeks of the CMS procedure, rats were injected once daily with vehicle, imipramine (10 mg/kg), aripiprazole (1 and 5 mg/kg), or cariprazine (0.01, 0.03, 0.065, 0.25, and 1.0 mg/kg). Activity in reversing CMS-induced decreases in consumption of 1% solution of sucrose was measured. CMS significantly reduced sucrose intake. Imipramine, and both doses of aripiprazole and cariprazine 0.03, 0.065, and 0.25 mg/kg significantly attenuated CMS-induced reductions in sucrose intake; the lowest and highest cariprazine doses (0.01 and 1 mg/kg) did not have this effect. Cariprazine showed greater potency (ED50=0.052) relative to aripiprazole (ED50=4.4) in this model. Thus, in the rat CMS model, cariprazine showed antidepressant-like action with greater potency than aripiprazole. These results suggest that cariprazine may have clinical utility in the treatment of depression and the negative symptoms of schizophrenia.

Topics: Anhedonia; Animals; Antidepressive Agents; Aripiprazole; Chronic Disease; Depressive Disorder; Dietary Sucrose; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking Behavior; Imipramine; Male; Piperazines; Quinolones; Rats, Wistar; Stress, Psychological