Treating schizophrenia with cariprazine: from clinical research to clinical practice. Real world experiences and recommendations from an International Panel

Abstract

Background Management of schizophrenia is sub-optimal in many patients. Targeting negative symptoms, among the most debilitating aspects of schizophrenia, together with positive symptoms, can result in significant functional benefits and dramatically improve quality of life for patients and their carers. Cariprazine, a partial agonist of the dopamine receptors D2/D3 has demonstrated effectiveness across symptom domains in clinical trials, particularly on negative symptoms. Objective To obtain a broader insight from clinicians with specific experience with cariprazine, on how it affects patient populations outside the clinical trial setting. Methods The panel addressed a series of psychopharmacologic topics not comprehensively addressed by the evidence-based literature, including characteristics of patients treated, dosing and switching strategies, duration of therapy, role of concomitant medications and tolerability as well as recommendations on how to individualize cariprazine treatment for patients with schizophrenia. Results Patients recommended for cariprazine treatment are those with first episodes of psychosis, predominant negative symptoms (maintenance/acute phase) and significant side effects (metabolic side effects, hyperprolactinemia, sedation) with other antipsychotics. When the long-term treatment of a lifetime illness is adequately weighted, cariprazine becomes one of the first-line medications, not only for patients with predominant negative symptoms but also for those with relatively severe positive symptoms, especially if they are at the first episodes and if a specific medication is added for symptoms such as agitation or insomnia. For instance, patients with agitation may also benefit from the combination of cariprazine and a benzodiazepine or another sedating agent. Cariprazine may be prescribed as add-on to medications such as clozapine, when that medication alone is ineffective for negative symptoms, and sometimes the first may be discontinued or its dose lowered, after a period of stability, leaving the patient on a better tolerated antipsychotic regimen. Conclusions Based on real-world clinical experience, the panel considered that cariprazine, with its distinct advantages including pharmacokinetics/pharmacodynamics, good efficacy and tolerability, represents a drug of choice in the long-term management of schizophrenia not only for patients with predominant negative symptoms but also for those with positive symptoms.

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

“…For these reasons, cariprazine is judged to be an advantageous treatment option for patients with schizophrenia and, although treatment decisions need to be made with individual patient characteristics in mind, cariprazine is among the safest antipsychotic treatment options available [90,95]. In most cases, cariprazine-related AEs can be successfully managed by dose reduction; akathisia may be managed by lower doses or a combination of dose reduction and rescue medication [90]. This is a narrative review that has some inherent limitations related to the studies and analyses that were selected for inclusion.…”

“…Although predominant positive symptoms may be the focus of clinical attention during an acute exacerbation of schizophrenia, addressing negative symptoms and cognitive symptoms is additionally important [ 90 ]. Across a spectrum of presenting symptom scenarios, cariprazine is considered a drug of choice for treating patients with schizophrenia and acute positive symptoms, first episode psychosis, predominant negative symptoms, and metabolic syndrome [ 90 ]. Once acute symptoms are stabilized, long-term treatment of schizophrenia is required to ensure symptom control and prevent relapse [ 91 ].…”

“…Finally, long-term efficacy for cariprazine versus the active comparator risperidone has been shown in patients with persistent and predominant negative symptoms of schizophrenia, a domain with few proven treatments and considerable unmet need. As such, patients with negative symptoms are considered a target treatment group for cariprazine owing to its clinical and pharmacological advantages over other antipsychotics in terms of negative symptom efficacy [ 90 ]. In fact, in an attempt to provide an algorithm for negative symptom treatment, Cerveri et al have proposed cariprazine as first-line treatment for this patient population, followed by amisulpride, quetiapine, and olanzapine [ 52 ].…”

“…Across studies and post hoc analyses, cariprazine has been shown to be safe and generally well tolerated in patients with schizophrenia, with a neutral metabolic profile, clinically nonsignificant cardiac changes, no prolactin level increase, and small body weight increases. For these reasons, cariprazine is judged to be an advantageous treatment option for patients with schizophrenia and, although treatment decisions need to be made with individual patient characteristics in mind, cariprazine is among the safest antipsychotic treatment options available [ 90 , 95 ]. In most cases, cariprazine-related AEs can be successfully managed by dose reduction; akathisia may be managed by lower doses or a combination of dose reduction and rescue medication [ 90 ].…”

Case Report: Cariprazine Efficacy in Young Patients Diagnosed With Schizophrenia With Predominantly Negative Symptoms

“…If the weight is placed on the long-term efficacy and tolerability, cariprazine may become one of the first-line medications in schizophrenia, not only for prominent negative symptoms, but also for relatively severe positive symptoms (9). An overlap of at least 2-3 weeks is usually recommended in clinical practice when switching from other antipsychotics to cariprazine, in order to avoid a dopaminergic, antihistaminergic and/or muscarinic rebound (9). This case series presents three young adults with persistent negative symptoms during treatment with an atypical antipsychotic, administered in stable doses within the therapeutic range and for at least 4 weeks, prior to the cariprazine switch.…”