Cariprazine − a Cardiometabolically Friendly Antipsychotic

Introduction

In his introduction to the topic of antipsychotic treatment and the use of cariprazine, the lecturer reminded the audience that patients with severe psychiatric disorders, including schizophrenia, have a 2−3× higher mortality rate, partly due to cardiometabolic and respiratory diseases. It is therefore essential to monitor both personal and family history of cardiometabolic conditions, medication, body weight, blood pressure, and to regularly conduct various laboratory tests in patients with schizophrenia. Cardiovascular risk assessment (e.g., using the SCORE system), patient education, and collaboration with general practitioners should not be neglected either.

In cases of weight gain and cardiometabolic issues following the initiation of antipsychotic treatment, which can occur shortly after starting therapy, it is entirely appropriate to switch to a metabolically friendly antipsychotic, particularly in the early stages of the illness after the acute phase has subsided.

Metabolic Side Effects and Differences in Antipsychotic Safety

The side effects of antipsychotic treatment form a very heterogeneous group, and individual medications vary significantly in how they affect, for example, glucose and lipid metabolism or the QTc interval. In this context, the lecturer mentioned a meta-analysis evaluating 18 antipsychotics and their impact on metabolic functions in patients with schizophrenia. The results indicate significant differences in metabolic side effects among antipsychotics – partial agonists of dopamine receptors, such as cariprazine, have a better cardiometabolic profile compared to, for instance, olanzapine and clozapine.

Cariprazine's metabolically friendly profile is contributed to by its receptor profile – its effect on serotonin 5-HT_2C receptors and histamine H₁ receptors is very weak, and weight gain with this antipsychotic is rare. This is also evidenced by a series of case reports presented by the lecturer.

The Issue of Akathisia and Its Management

While treating with cariprazine, it is important to consider the possible occurrence of extrapyramidal symptoms and akathisia, particularly during the titration of cariprazine. If akathisia occurs in schizophrenic patients on this therapy, several approaches can be taken: discontinuation of co-medication contributing to akathisia, dose reduction of cariprazine or moving the dose to the nighttime, addition of medication to reduce akathisia (such as beta-blockers, mirtazapine, mianserin, anticholinergics, or adding benzodiazepine to the medication regimen), or changing the antipsychotic.

Cariprazine Titration

On the topic of cariprazine titration, Prof. Masopust also provided several practical tips. When switching from another antipsychotic, it is important to be wary of the rebound effect, hence the transition should occur slowly with a cross-titration strategy. First, the cariprazine dose should be titrated, and only then should the dose of the initial antipsychotic be gradually reduced until its complete discontinuation. The duration of the transition period depends, among other things, on the acuteness of symptoms and the type of initial antipsychotic. The slower the change, the more certain the result, and the safer it is for the patient, also considering the possible occurrence of akathisia.

The recommended dose of cariprazine is 1.5−6 mg per day, based on the expected impact on pathopsychology and possible side effects at higher than recommended doses.

Conclusion

Cardiometabolic risks are inherently associated with schizophrenia and its treatment, and this fact must be recognized even at the first onset of the disease before starting antipsychotic treatment. It is essential to regularly monitor the overall physical health and the occurrence of side effects in all patients with schizophrenia, and to take early intervention if necessary, including possible medication changes. With regard to cardiometabolic risks, cariprazine has proven to be an effective and well-tolerated antipsychotic with a very favorable cardiometabolic profile in the treatment of schizophrenia.

(pak)

Source: Masopust J. Cariprazine: a Cardiometabolically Friendly Antipsychotic. 63rd Czech-Slovak Psychopharmacological Conference, January 15−16, 2021.