Abstract
Eric F. C. Cheung, Department of Psychiatry, Queen Mary Hospital, Pokfulam, Hong Kong:
Clozapine is an atypical antipsychotic that has been shown to be effective in treatment-refractory schizophrenia. However, treatment with clozapine is not uncommonly complicated by obsessive–compulsive (OC) symptoms [1]. We report the emergence and the successful treatment with clomipramine of OC symptoms in a patient receiving clozapine treatment for refractory schizophrenia.
Miss A, a 19-year-old Hong Kong Chinese woman, had suffered from hebephrenic schizophrenia since she was 14. She presented with an insidious onset of disorganized behaviour and general decline in psychosocial functioning which was associated with distressing visual and somatic hallucination. Negative symptoms such as personal neglect and blunting of affect were also prominent. Miss A's illness was unresponsive to various conventional antipsychotic medications in both oral and depot form. Clozapine was started and both her positive and negative symptoms improved. However, at 400 mg/day of clozapine, Miss A began to have recurrent intrusive ego-dystonic impulses of suicide or violent acts, which she recognized as her own thoughts and was trying hard to resist them. Clomipramine was started and at 100 mg/day, these OC symptoms subsided and remained so despite the further increase in clozapine dosage to 600 mg/day that was eventually needed to achieve satisfactory control of her positive psychotic symptoms.
This case report illustrates a not uncommon adverse effect of clozapine. A retrospective study reported that OC symptoms were present in 20.6% of clozapinetreated psychotic patients compared with 1.3% in patients treated with conventional antipsychoticmedications [2]. In most reported cases, as in Miss A's case, the emergence of OC symptoms accompanied the improvement of psychotic symptoms and a dose–response relationship has been reported between clozapine and OC symptoms [3].
Clozapine's antiserotonergic property has been implicated as the underlying mechanism for causing OC symptoms and the co-administration of serotonin reuptake inhibitors (SRIs) may be effective in abating clozapine-induced OC symptoms. Concomitant use of SRIs with clozapine also seems to be safe and does not compromise its effect [4].
In Miss A's case, OC symptoms occurred at a clozapine dosage of 400 mg/day and it is reasonable to believe that further increase in dosage would bring about worsening of her OC symptoms. It would not have been possible to further increase the dosage of her clozapine if her OC symptoms were not controlled by the addition of clomipramine. The addition of an SRI provides a safe and viable option for patients who otherwise would not benefit from clozapine because of the emergence of OC symptoms.