Improvement in Psychotic Symptoms and Social Functioning After Augmentation of Paliperidone With Clozapine in a Patient With Schizoaffective Disorder

To the Editor: “Mrs. B,” who had significant depression symptoms and psychotic symptoms with significant exacerbations of self-care in the past 7 months, was diagnosed with schizoaffective disorder, depressed subtype, because of persistent psychotic symptoms even after response of her depression with mirtazapine 60 mg/day. She still had significant psychotic symptoms even after several kinds of antipsychotics, such as risperidone 8 mg/day, olanzapine 30 mg/day, and aripiprazole 30 mg/day during her 1-month hospitalization (Brief Psychiatric Rating Scale−18 items [BPRS−18] scores: 56, especially in items of uncooperativeness [6 points], hallucinatory behaviors [7 points], hostility [6 points] and suspiciousness [6 points]). Because of apparent treatment-resistance, the antipsychotic was switched to clozapine 200 mg/day gradually, with excessive salivation side effects. The responses of her psychotic symptoms still remained limited after using clozapine (BPRS−18 scores: 53). Her self-care, social, and occupational functioning also did not improve (Social and Occupational Function Assessment Scale [SOFA] score: 20].

Because of the persistence of psychotic symptoms even under clozapine, we added paliperidone 9 mg/day to assist the control of psychotic symptoms. She had significant improvement of psychotic symptoms (BPRS scores: 53 > 38; items of uncooperativeness [6 > 2], hallucinatory behaviors [7 > 3], hostility [6 > 3] and suspiciousness [6 > 3]) after augmentation of paliperidone for 1 month. No significant side effects after combinations of clozapine and paliperidone were observed. After discharge, she could go to market to buy commodities and had better ability for self-care. Her social functioning also showed significant improvement (SOFA score: 20 > 55).

Discussion

This patient had significant improvements of treatment-resistant psychotic symptoms after augmentation of paliperidone with clozapine. It might be related to the serotonin 5-HT_2A antagonism and dopamine D₂ antagonism effects of paliperidone. Besides, paliperidone is effective in the treatment of schizoaffective disorder.¹ Paliperidone has been reported to improve personal and social functioning in schizophrenia patients.² Paliperidone also has a better profile of side effects and less harm.³ Healthy volunteers using paliperidone had better performance on Stroop Word–Color tests than on risperidone or placebo. This suggests that paliperidone might improve cognitive functioning.⁴ Kim et al.’s report on schizophrenia patients also supports the role of paliperidone in the improvement of neurocognitive and social functioning.⁵ In this patient, I hypothesized that paliperidone augmentation might enhance the clozapine’s 5HT_2A antagonism with better results in social and occupational functions. Also, paliperidone might enhance D₂ antagonism effects of clozapine because of paliperidone’s higher affinity for D₂ receptors, which will decrease psychotic symptoms.⁶ To my knowledge, this is first case report about clozapine and paliperidone combination therapy in schizoaffective disorder. This combination might be an alternative for treatment-resistant schizoaffective patients.