Cariprazine add-on in inadequate clozapine response: another case study
Clozapine is the gold standard in treating treatment resistant schizophrenia, but several patients do not respond adequately or develop adverse effects. This report by De Berardis et al. summarizes a case of treatment resistant schizophrenia with comorbid substance abuse, successfully treated with clozapine and cariprazine.
Descripción del caso
Antecedentes de la paciente / Diagnóstico y síntomas
This is a 35-year-old, unmarried, male diagnosed with schizophrenia at age 24. Substance abuse (mainly cocaine and cannabis) accompanied the onset, which was characterized by positive symptoms, marked impulse dyscontrol and hostility, as well as negative symptoms (blunted affect, poor rapport, social withdrawal). Haloperidol, olanzapine, and paliperidone long-acting were all tried for treatment, but without response and a considerable problem in functioning (the patient lost his job). He took clozapine 350 mg/day for almost one and a half years, with a functional improvement on hostility and uncooperativeness, but without any significant effects on other symptoms. When tried on clozapine 400 mg/day, the patient developed marked sedation.
Tratamiento
Upon examination at the outpatient facility at the Hospital of Teramo, he was symptomatic and his PANSS scores were clinically significant (total score=121, positive=27, negative=34, general=70). The patient was 95 kg, with a BMI of 28.4 kg/m2. He was offered aripiprazole but refused it because a friend told him that it has unknown “adverse effects”. He agreed to 1.5 mg/day cariprazine treatment.
Three weeks later, there was a slight improvement on the patient’s PANSS score (total score=101, positive=20, negative=30, general=61) and he reported feeling better, especially cognitively and functionally, without adverse effects. It was agreed to titrate cariprazine up to 3 mg/day. After two months, there was an improvement in both PANSS (total score=77, positive=13, negative=15, general=49) and BMI (26.9 kg/m2), while clozapine was reduced to 300 mg/day. It was a constant improvement, and the patient was able to find a job in a brick factory, stating, “my mind and thoughts are more clear”.
After three more months of clozapine 300 mg/day and cariprazine 3 mg/day combination therapy, PANSS scores improved even more (total score=57, positive=9, negative=12, general=29), as did his BMI (25.6 kg/m2). There were no adverse effects observed or reported.
Discusión
At the clinic, to date, this was one among the first two cases of using cariprazine in combination with clozapine, after there was an inadequate response to clozapine monotherapy. The combination was very efficacious, as shown by the improvement in PANSS scores over time. Along with the improvement in all the PANSS subscales, negative symptoms also improved noticeably. This can be connected to cariprazine’s partial agonism on D3 receptors, as several studies suggest that its affinity and action on D3 could explain its efficacy on negative symptoms, executive deficits, as well as cognitive and mood impairment.
The reduction in weight and BMI may be attributed to the physical activity the patient started doing, as a potential consequence of cariprazine’s pro-cognitive and negative symptom effects. Overall, this case also showed that the combination of clozapine and cariprazine is highly efficacious, without any adverse effects, in treating treatment-resistant schizophrenia.
COD. 300020/R43. Submitted to AIFA on 12 October 2020.
Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases
„In conclusion, cariprazine add-on to clozapine showed remarkable and relatively rapid efficacy in the treatmentof subjects with inadequate response to clozapine. The tolerability of this association was excellent without reported adverse effects.”
