Tolerability and Safety Profile of Cariprazine in Treating Psychotic Disorders, Bipolar Disorder and Major Depressive Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Lao, Kim S. J.; He, Ying; Wong, Ian C. K.; Besag, Frank; Chan, Esther Wai Yin

doi:10.1007/s40263-016-0382-z

Cited by 39 publications

(18 citation statements)

References 48 publications

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“…Cariprazine improved PANSS total-psychiatric scale used for measuring symptom severity in patients with psychosis along with improving anxiety and depressed mood. Cariprazine also showed significant improvements in CGI-S, YMRS, MADRS and HAM-D. As far as our awareness, this is the first meta-analysis that covered the role of cariprazine in the different psychiatric conditions, our results are in consistency with a previous meta-analysis that focused on the tolerability of cariprazine and showed statistically significant higher risk of EPS-related AEs (Lao et al 2016). These results confirm similar results in another meta-analysis that studied cariprazine in psychotic disorders such as schizophrenia, but not including recent trials especially in the field of cariprazine role in the management of bipolar depression and major depressive disorder (Chhatlani et al 2018).…”

Section: Discussionsupporting

confidence: 90%

Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: A Meta-Analysis of Randomized Controlled Trials

et al. 2020

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Background: Cariprazine is a new atypical antipsychotic drug approved for the treatment of schizophrenia and bipolar disorders. Methods: we searched the published randomized controlled-trials (RCT) to review cariprazine efficacy and tolerability using the databases (PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials) for cariprazine role in managing the following psychiatric conditions (schizophrenia, bipolar mania, bipolar depression and major depressive disorder). A meta-analysis was conducted using the identified 13 clinical trials to assess efficacy using with the outcomes: positive and negative syndrome scale (PANSS), clinical global impressions -severity of Illness (CGI-S), young mania rating scales (YMRS), Montgomery Asberg depression rating scale (MADRS) and Hamilton rating scale for depression (HAM-D). The risk of discontinuation due to adverse effects and common side effects were examined.Results: The mean difference in change from baseline for PANSS was -6.23 (95% Confidence Interval (CI) -7.18, -5.28) favoring cariprazine treatment (p<0.00001). Similarly, mean difference for CGI-S was -0.36 (95% CI -0.41, -0.30), , ) and . The risk ratio (RR) of discontinuing due to adverse events was 1.18 (95% CI 1.01, 1.38) meaning risk increased by 18% in cariprazine group with RR for EPS related side effects 2. 82 (95% CI 2.47, 3.22) reflecting an increased risk of experiencing EPS related side effects by 182%. Cariprazine was also associated with an increased incidence of side effects such as akathisia, nausea and insomnia.Conclusion: Cariprazine demonstrates significant improvements in symptom intensity control in patients suffering from psychiatric conditions including schizophrenia, bipolar disorders and depression and is considered well-tolerated with similar rates of trials discontinuation; however, cariprazine was associated with a higher risk of EPS side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting psychiatric patients care.

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Section: Discussionsupporting

confidence: 90%

Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: A Meta-Analysis of Randomized Controlled Trials

et al. 2020

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“…According to several meta-analyses,28,75 the highest incidence of EPS in patients with schizophrenia occurs with HAL, with moderate EPS being observed with RIS, PALI, and LUR, down to CPZ; milder EPS being observed with ASE, ZIP, AMI, ILO, and ARI; and still milder EPS being observed with QUE, OLA, SER, and CLO. Although CAR is a partial D2 agonist, it seems to increase the risk of EPS according to a recent meta-analysis across SMI,76 perhaps due to relatively weak 5HT2A antagonism (or more antagonism than agonism). Perhaps because of illness-induced serotonin disturbance, BD patients, especially in depression, have been found in one meta-analysis to be more vulnerable to acute movement disorders secondary to antipsychotics than patients with schizophrenia 77…”

Section: Methodsmentioning

confidence: 99%

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Solmi

Murru

Pacchiarotti

et al. 2017

TCRM

335

244

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Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis.

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“…Three meta-analyses were found that focused on cariprazine and included data for the treatment of schizophrenia. 62 – 64 …”

Section: Literature Searchmentioning

confidence: 99%

Cariprazine for acute and maintenance treatment of adults with schizophrenia: an evidence-based review and place in therapy

Citrome¹

2018

NDT

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Cariprazine is an oral antipsychotic approved in the US and EU for the treatment of schizophrenia. Cariprazine differs from other antipsychotics in that it is a dopamine D3- and D2-receptor partial agonist, with tenfold higher affinity for D3 receptors than for D2 receptors. Cariprazine is metabolized in two steps by CYP3A4 to didesmethyl-cariprazine (DDCAR). DDCAR has a long half-life of 1–3 weeks and is the predominant circulating active moiety. Efficacy and safety in persons with acute schizophrenia were assessed in four similarly designed, short-term, randomized, placebo-controlled clinical trials in nonelderly adults, with three studies considered positive and yielding a number needed to treat vs placebo for response (change from baseline ≥30% in Positive and Negative Syndrome Scale total score) of ten for the approved dose range of cariprazine 1.5–6 mg/day. The most common adverse reactions were extrapyramidal symptoms (15% and 19% for 1.5–3 and 4.5–6 mg/day, respectively, vs 8% for placebo) and akathisia (9% and 12.5% for 1.5–3 and 4.5–6 mg/day, respectively, vs 4% for placebo). For the approved dose range, rates of discontinuation because of an adverse event were lower overall for patients receiving cariprazine vs placebo (9% vs 12%). Weight and metabolic profile appear favorable. Cariprazine does not increase prolactin levels or prolong the electrocardiographic QT interval. Cariprazine has also been found to be effective for the maintenance treatment of schizophrenia by delaying time to relapse when compared with placebo (HR 0.45). A 26-week randomized clinical trial evidenced superiority of cariprazine over risperidone for the treatment of predominantly negative symptoms in patients with schizophrenia. Cariprazine is also approved in the US for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and is being studied for the treatment of bipolar I depression and major depressive disorder.

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Tolerability and Safety Profile of Cariprazine in Treating Psychotic Disorders, Bipolar Disorder and Major Depressive Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Cited by 39 publications

References 48 publications

Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: A Meta-Analysis of Randomized Controlled Trials

Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: A Meta-Analysis of Randomized Controlled Trials

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Cariprazine for acute and maintenance treatment of adults with schizophrenia: an evidence-based review and place in therapy

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