Cariprazine for late-life psychiatric illness

Abstract

Clinicians often face many challenges in the pharmacological treatment of late-life psychiatric illness especially while choosing an antipsychotic drug. The choice of antipsychotic is mostly guided by the extension of evidence from the adult population and tolerability. In India, based on evidence commonly prescribed antipsychotic drugs for older adults are quetiapine (QTP) followed by olanzapine (OLZN) and risperidone. Cariprazine is a newer antipsychotic that was recently launched in India. It is a novel mechanism of action at D3 receptors is known to have antidepressant and procognitive action in addition to the antipsychotic effects which is desirable in geriatric population. It can be a potential option as an add-on drug in late-life depression in addition to the existing aripiprazole and OLZN. The treatment of late-life mania and very late-onset schizophrenia is limited by the paucity of studies, with randomized control studies done only on QTP and amisulpride, respectively. Cariprazine can be considered in late-life psychotic disorders with the evidence available from its efficacy studies in adult patients. Merits of cariprazine are favorable metabolic profile, cardiac safety, and procognitive action. Demerits include extrapyramidal symptoms and fluctuations in blood pressure. Slower titration and monitoring for akathisia are recommended. There is a need for controlled studies in older adults with cariprazine to get better informed about its efficacy and safety.

A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia

“…First generation antipsychotics exhibits narrow efficacy spectrum in managing negative symptoms of schizophrenia ( 7 ). Second generation antipsychotics were introduced in the late 80s ( 24 ) with a promise to yield higher treatment efficacy, better receptor binding properties and lower side effects compared to FGAs ( 36 ).…”

“…Cariprazine was approved in 2015 by the US FDA and later in 2018 in the UK ( 5 , 7 ). The antipsychotic is approved in the US for treatment of schizophrenia, mania or mixed episodes, and depressive episodes related to bipolar I disorder and as adjunctive therapy to anti-depressants for the treatment of major depressive disorders, whereas in Europe it is approved for treatment of schizophrenia ( 26 ).…”

“…This feature of cariprazine is proven effective for treatment of predominant primary negative symptoms of schizophrenia ( 24 , 64 ). It is especially recommended for elder patients, as cariprazine results in procognitive and antidepressant effects due to its partial agonism towards D2/D3 receptors ( 7 ). Cariprazine also acts as an antagonist to 5-HT 2B and a partial agonist to 5-HT 1A .…”

“…Likewise, the European Psychiatric Association guidelines recommended switching to SGA in patients not responding to FGA, along with social skill training and psychosocial rehabilitation (20). First generation antipsychotics exhibits narrow efficacy spectrum in managing negative symptoms of schizophrenia (7). Second generation antipsychotics were introduced in the late 80s (24) with a promise to yield higher treatment efficacy, better receptor binding properties and lower side effects compared to FGAs (36).…”

“…The mechanism of action of first generation antipsychotics (FGAs) lack preference-based blocking of dopamine pathway, resulting in extrapyramidal symptoms (dyskinesia, akathisia and tremors), hyperprolactinemia-associated sexual dysfunction and aggravation of negative symptoms ( 6 ). The second generation antipsychotics (SGAs) are combined D2 and serotonin 5-HT 2A receptor antagonists with lower risk for developing extrapyramidal symptoms (EPS) ( 7 ). Second generation antipsychotics are effective for negative symptoms, but result in several treatment-emergent side effects including diabetes, ketoacidosis, weight gain, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension and metabolic syndrome ( 6 , 8 , 9 ).…”