Remission of Persistent Negative Symptoms and Psychosocial Consequences by Combined Clozapine and Cariprazine Treatment in a Patient With Long-Standing Treatment-Resistant Schizoaffective Disorder

Abstract

This patient case report describes a 45-year old white unmarried man with disability pension due to schizoaffective disorder, diagnosed at the age of 24. He lives in an apartment and has housing support. Retrospectively, the patient displayed prodromal markers of a disorder within the schizophrenia spectrum many years before the onset of frank psychosis, indeed since childhood. Over the years several symptoms and signs across schizophrenia domains have been manifest: positive, negative, cognitive, and affective, among which the negative and affective symptoms and signs were the earliest to appear. While the positive, disorganized, and catatonic symptoms responded to treatment – when duly tested and complied with – the negative and affective symptoms have been notoriously difficult to handle. We now report on the successful introduction of cariprazine (CAR) to his ongoing clozapine (CLZ) medication, the result of which has been a near-complete remission of his persistent negative and psychosocial issues. We interpret this remarkable alleviation of the patient's disease – and concomitant improvement of his quality of life – in terms of neuroreceptor target complementarity between CLZ and CAR, with particular emphasis on the contributions from the D3 and D2 receptor partial agonist components of the latter agent.

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

“…In a 45-year-old man diagnosed with treatment-resistant schizoaffective disorder and presenting a long history of treatment resistance, clozapine administered at 600 mg/day did not succeed in controlling negative symptoms and obsessive thoughts, which severely impacted his daily functioning ( 58 ). A trial with cariprazine was initiated in a slow titration regimen, up to 4.5 mg/day in combination with clozapine 450 mg/day ( 58 ). No tolerability difficulties were observed during the 9 months of monitored, combined treatment, and the functionality gradually improved ( 58 ).…”

“…A trial with cariprazine was initiated in a slow titration regimen, up to 4.5 mg/day in combination with clozapine 450 mg/day ( 58 ). No tolerability difficulties were observed during the 9 months of monitored, combined treatment, and the functionality gradually improved ( 58 ). The clozapine dose decreased to 275 mg/day, which led to an improvement of the general status by the disappearance of several adverse events, e.g., constipation or hypersalivation ( 58 ).…”

“…No tolerability difficulties were observed during the 9 months of monitored, combined treatment, and the functionality gradually improved ( 58 ). The clozapine dose decreased to 275 mg/day, which led to an improvement of the general status by the disappearance of several adverse events, e.g., constipation or hypersalivation ( 58 ). The CGI-S scores improved following the introduction of cariprazine in the treatment regimen ( 58 ).…”

“…The clozapine dose decreased to 275 mg/day, which led to an improvement of the general status by the disappearance of several adverse events, e.g., constipation or hypersalivation ( 58 ). The CGI-S scores improved following the introduction of cariprazine in the treatment regimen ( 58 ).…”

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

“…Cariprazine acts as an antagonist when dopamine activity is normal and as partial agonist when the activity is low, depending on the available dopamine ( 63 ). 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 ).…”