Cariprazine add-on in inadequate clozapine response: a case study
This article by De Berardis et al. presents a case of schizophrenia successfully treated with cariprazine as an add-on therapy in inadequate clozapine response. Clozapine is the gold standard in treating treatment resistant schizophrenia, but several patients do not respond adequately or develop adverse effects. The presented case illustrates the benefits of cariprazine as an add-on treatment to clozapine in treatment resistant schizophrenia, while decreasing adverse effects.
Case description
Patient history / Diagnosis and symptoms
This case is of a 29-year-old, unmarried, unemployed female who was diagnosed with schizophrenia at 19 years of age with an acute episode, which included mixed positive and negative symptoms, with marked hostility. She was treated with oral (haloperidol, olanzapine, and paliperidone), as well as long-acting antipsychotics (haloperidol decanoate and aripiprazole long-acting) over the years, “with no effects on psychopathology”. Afterwards, clozapine 450 mg/day was tried, with limited success even after augmentation with amisulpride 800 mg/day.
When arriving to the outpatient facility of the Hospital of Teramo, Italy after a GP referral, she was symptomatic and her Positive and Negative Symptoms Scale (PANSS) scores were clinically significant (total score=113, positive=22, negative=33, general=58). She had also gained weight while being treated with clozapine (weight was 84 kg and BMI 26.8 kg/m2 at arrival).
Treatment
Since there was no response to aripiprazole previously, cariprazine combination treatment was started at 1.5 mg/day, which was titrated to 3 mg/day without adverse effects. PANSS score improvement (total score=89, positive=18, negative=27, general=44) was seen after 30 days of cariprazine combination treatment. After 3 months of therapy, the PANSS scores improved markedly (total score=74, positive=14, negative=20, general=40) and no adverse effects were reported. There was also a significant improvement in weight (79 kg, BMI 25.1 kg/m2).
After another 4 months, the PANSS scores improved once again (total score=57, positive=10, negative=14, general=33), as did her BMI (24.6 kg/m2). The patient found a part-time job and was doing physical activity three times a week. She was taking clozapine 400 mg/day and cariprazine 3 mg/day.
Discussion
At the clinic, this case was the first time cariprazine was used in combination with clozapine, after there was an inadequate response to clozapine monotherapy. The combination proved to be 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, the case demonstrated that the combination of clozapine and cariprazine was 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.”
