TO THE EDITOR: Obsessive-compulsive symptoms, documented in as many as 25% of schizophrenic patients, pose a substantial therapeutic challenge. The addition of clomipramine to the neuroleptic regimen has alleviated both schizophrenic and obsessive-compulsive symptoms (R1557291A). In some patients with obsessive-compulsive disorder (OCD), intravenous administration is superior to the oral administration of clomipramine (R1557292A). We report on the beneficial effects of adding intravenous clomipramine to a regimen of neuroleptics for a stabilized schizophrenic patient with severe obsessive-compulsive symptoms.
Ms. A, a 25-year-old woman who had had schizophrenic disorder, paranoid type (according to DSM-IV), since the age of 17 years, was hospitalized twice because of acute psychotic exacerbation. After treatment with various antipsychotics, she was stabilized with perphenazine (8 mg/day). Ms. A also manifested ego-dystonic checking and cleaning rituals related to an obsessive fear of contamination. The subsequent addition of fluvoxamine (250 mg/day for 12 weeks) and fluoxetine (40 mg/day for 8 weeks) to the neuroleptic treatment failed to control her obsessive-compulsive symptoms. Further deterioration of the compulsive behavior resulted in her rehospitalization. At this point, in addition to the previously observed rituals, Ms. A was exercising compulsively for 12–14 hours per day. Despite her awareness of the irrationality of her behavior, our attempts to stop the exercising caused her severe anxiety. We initiated a course of intravenous clomipramine (75 mg in 1500 cc of normal saline) in addition to the ongoing perphenazine (8 mg/day); we repeated the 4-hour infusion procedure 24 hours later. Five days after the second infusion, Ms. A's score on the Yale-Brown Obsessive Compulsive Scale dropped from 19 to 4, an indication that her compulsive behavior had almost completely disappeared. This was the first notable improvement since the onset of her obsessive-compulsive symptoms. In addition, Ms. A's score on the Brief Psychiatric Rating Scale dropped from 41 to 29, and her monitored ECG, pulse, and blood pressure were within normal limits. The only side effect was mild sedation. We subsequently gave Ms. A prescriptions for oral clomipramine (150 mg/day) and perphenazine (8 mg/day) and discharged her from the hospital. We observed no recurrence of her obsessive-compulsive or schizophrenic symptoms during a 6-month follow-up.
The combination of clomipramine and neuroleptics has been recommended as a first-line treatment in schizophrenia with comorbid OCD (R1557293A). In the case described here, intravenous clomipramine was effective and well tolerated in a stabilized schizophrenic patient with refractory obsessive-compulsive symptoms who was receiving concurrent neuroleptic treatment. Our observation is consistent with the recently documented beneficial effect of pulse loading intravenous clomipramine in treatment-resistant OCD (R1557292A). However, we used a lower dose (75 mg/day versus 150–200 mg/day) and a slower rate of administration (4 hours versus 90 minutes). The robust and rapid therapeutic response to intravenous clomipramine pulse loading has been explained by immediate achievement of the therapeutic plasma or brain concentration, with subsequent effect on gene expression (R1557292A). If these findings are confirmed under placebo-controlled conditions, intravenous clomipramine may expand our options for treating obsessive-compulsive symptoms in schizophrenic patients.