Switching Clozapine to Cariprazine in Three Patients with Persistent Symptoms of Schizophrenia: A Case Series

Abstract

Despite many available treatments for schizophrenia, several unmet needs persist in treating individuals with this disorder, and the response rate to first-line antipsychotics remains relatively low. Clozapine has shown efficacy in treating schizophrenia patients who failed to respond to previous antipsychotics. However, side effects and the need for routine blood tests have limited its use as a first-line treatment. Cariprazine is a D 2 /D 3 partial agonist antipsychotic with a mechanism of action that differs from other antipsychotics due to its higher affinity for D 3 receptors. Several trials have demonstrated the efficacy of cariprazine on positive and negative symptoms of schizophrenia and have shown that it is a well-tolerated treatment. In this series, we present 3 cases of patients diagnosed with schizophrenia who were initially under treatment with clozapine. Despite some initial improvement, the patients showed persisting positive and negative symptoms or developed limiting side effects while in treatment with clozapine. Cariprazine treatment was titrated concurrently with clozapine tapering until its discontinuation. Significant improvement in both positive and negative symptoms was observed up to 14 months after starting cariprazine, and resolution of side effects was reported in all cases. Our case series supports cariprazine as an effective treatment for positive and negative symptoms in patients who failed to adequately respond or poorly tolerated treatment with clozapine, as well as a potential treatment in dual disorders, specifically psychotic disorders and cocaine use disorder.

Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

“…The treatment adherence was confirmed, with the plasma level of clozapine ranging between 375 and 415 ng/ml ( 59 ). Cariprazine was added to clozapine and gradually increased to 6 mg/day, while the clozapine dose was reduced starting from week 2 until discontinued ( 59 ). Four months after cross-titration, the positive symptoms and mannerisms decreased significantly, together with disorganization symptoms; the overall functionality increased ( 59 ).…”

“…The effects of switching from clozapine to cariprazine were also explored in case of intolerable adverse events or partial responsivity. A 29-year-old woman diagnosed with schizophrenia presented only partial remission and multiple adverse events–“sedation,” “cognitive blurring,” and “apathy,” after 1 year of clozapine treatment (maximum dose reached 400 mg/day) ( 59 ). The treatment adherence was confirmed, with the plasma level of clozapine ranging between 375 and 415 ng/ml ( 59 ).…”

“…A 29-year-old woman diagnosed with schizophrenia presented only partial remission and multiple adverse events–“sedation,” “cognitive blurring,” and “apathy,” after 1 year of clozapine treatment (maximum dose reached 400 mg/day) ( 59 ). The treatment adherence was confirmed, with the plasma level of clozapine ranging between 375 and 415 ng/ml ( 59 ). Cariprazine was added to clozapine and gradually increased to 6 mg/day, while the clozapine dose was reduced starting from week 2 until discontinued ( 59 ).…”

“…Cariprazine was added to clozapine and gradually increased to 6 mg/day, while the clozapine dose was reduced starting from week 2 until discontinued ( 59 ). Four months after cross-titration, the positive symptoms and mannerisms decreased significantly, together with disorganization symptoms; the overall functionality increased ( 59 ). At the 12-month-follow-up, the treatment adherence was adequate, and the psychotic symptoms were remitted, while the functionality was preserved (data confirmed by a family member) ( 59 ).…”

“…A 45-year-old male with a long history of schizophrenia (25 years) presented persistent positive, behavioral, cognitive, and negative symptoms, although his treatment adherence to clozapine (500 mg/day) was confirmed by blood concentrations (387 ng/mL) for at least 1 year ( 59 ). The medication was cross-titrated to cariprazine for 6 weeks, up to 6 mg/day, with a favorable evolution- a gradual decrease of positive symptoms, reduced psychomotor retardation, and improvement in speech content and quality for the next 6 months ( 59 ). After 1 year, negative symptoms were improved, and functionality also increased (by self-report and caregiver reports) ( 59 ).…”