Drug therapy is integral to the management of acute psychotic episodes in patients with schizophrenia and generally is required for long-term stabilization to sustain symptom remission or control and to minimize the risk of relapse. Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia. Patient response and tolerance to antipsychotic agents are variable, and patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.
Cariprazine hydrochloride is an atypical antipsychotic that is administered orally in the treatment of schizophrenia. Schizophrenia is a major psychotic disorder that frequently has devastating effects on various aspects of the patient's life and carries a high risk of suicide and other life-threatening behaviors. Manifestations of schizophrenia involve multiple psychologic processes, including perception (e.g., hallucinations), ideation, reality testing (e.g., delusions), emotion (e.g., flatness, inappropriate affect), thought processes (e.g., loose associations), behavior (e.g., catatonia, disorganization), attention, concentration, motivation (e.g., avolition, impaired intention and planning), and judgment. The principal manifestations of this disorder usually are described in terms of positive and negative (deficit) symptoms and, more recently, disorganized symptoms. Positive symptoms include hallucinations, delusions, bizarre behavior, hostility, uncooperativeness, and paranoid ideation, while negative symptoms include restricted range and intensity of emotional expression (affective flattening), reduced thought and speech productivity (alogia), anhedonia, apathy, and decreased initiation of goal-directed behavior (avolition). Disorganized symptoms include disorganized speech (thought disorder) and behavior and poor attention.
Short-term efficacy of cariprazine monotherapy in the treatment of schizophrenia has been established in 3 randomized, multicenter, double-blind, placebo-controlled studies of 6 weeks' duration (studies 1, 2, and 3) in adults who met DSM-IV-TR criteria for schizophrenia and were experiencing an acute exacerbation of psychotic symptoms. The primary and secondary efficacy end points in these studies were the change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total score and the Clinical Global Impressions-Severity (CGI-S) score, respectively. Studies 1 and 2 included an active control arm (risperidone and aripiprazole, respectively) to assess assay sensitivity. Study 1 evaluated 3 fixed dosages of cariprazine (1.5, 3, or 4.5 mg daily), study 2 evaluated 2 fixed dosages of cariprazine (3 or 6 mg daily), and study 3 evaluated flexible dosages of cariprazine in the range of 3-6 or 6-9 mg daily. In all 3 studies, cariprazine was found to be more effective than placebo in improving the PANSS total score and CGI-S score at week 6. Antipsychotic efficacy was demonstrated at cariprazine dosages ranging from 1.5-9 mg daily, and a modest dose-response relationship for efficacy was observed. However, there was a dose-related increase in certain adverse effects, particularly at dosages above 6 mg daily; therefore, the manufacturer states that the maximum recommended dosage of cariprazine for the treatment of schizophrenia is 6 mg daily. An examination of population subgroups did not reveal any clear evidence of differential responsiveness to the drug based on age (there were few patients over 55 years of age), gender, or race.
The American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for the management of the acute phase of schizophrenia (including first psychotic episodes), principally because of the decreased risk of adverse extrapyramidal effects and tardive dyskinesia, with the understanding that the relative advantages, disadvantages, and cost-effectiveness of conventional and atypical antipsychotic agents remain controversial. The APA states that, with the possible exception of clozapine for the management of treatment-resistant symptoms, there currently is no definitive evidence that one atypical antipsychotic agent will have superior efficacy compared with another agent in the class, although meaningful differences in response may be observed in individual patients. Conventional antipsychotic agents also may be an appropriate first-line option for some patients, including those who have been treated successfully in the past with or who prefer conventional agents. The choice of an antipsychotic agent should be individualized, considering past response to therapy, current symptomatology, concurrent medical conditions, other medications and treatments, adverse effect profile, and the patient's preference for a specific drug, including route of administration.
For additional information on the symptomatic management of schizophrenia, including treatment recommendations, .
Cariprazine hydrochloride is used orally for the acute treatment of manic or mixed episodes associated with bipolar I disorder.
Efficacy of cariprazine in the acute treatment of bipolar mania was established in 3 double-blind, placebo-controlled studies of 3 weeks' duration (studies 1, 2, and 3) in adults who met DSM-IV-TR criteria for bipolar I disorder with manic or mixed episodes with or without psychotic features. The principal rating instrument used for assessing psychiatric signs and symptoms in these studies was the Young Mania Rating Scale (YMRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score). The main secondary rating instrument used in these trials was the CGI-S scale. The primary and secondary end points in these studies was the change from baseline to the end of week 3 on the YMRS and the CGI-S scores, respectively.
Study 1 evaluated flexible dosages of cariprazine in the ranges of 3-6 and 6-12 mg daily; studies 2 and 3 evaluated flexible dosages of cariprazine in the range of 3-12 mg daily. In all 3 studies, cariprazine was found to be more effective than placebo on the primary and secondary end points. Efficacy was demonstrated at daily cariprazine dosages ranging from 3-12 mg; however, no additional benefit was demonstrated at dosages above 6 mg daily and there was a dose-related increase in certain adverse effects. Therefore, the maximum recommended dosage of cariprazine in the acute treatment of manic or mixed episodes associated with bipolar I disorder is 6 mg daily. An examination of population subgroups did not reveal any clear evidence of differential responsiveness to the drug based on age (there were few patients over 55 years of age), gender, or race.