engleski

Treatment of de novo obsessive compulsive symptoms with fluoxetine in shizophrenics after clozapine treatment

Several reports have associated clozapine treatment with de novo or exacerbated obsessive-compulsive symptoms in schizophrenic patients (1, 2, 3, 4, 5). Similar phenomena have been described during risperidone treatment (6, 7). The data suggest that the effects of clozapine and risperidone on serotonin neurotransmission account of these symptoms, as serotoninergic dysfunction has been implicated in obsessive- compulsive disorder (8, 9, 10). The data from literature about these phenomena are different. Coexistence of psychotic and obsessive-compulsive symptoms is common, perhaps more so among chronically symptomatic patients, including most of those treated with clozapine (11, 12). Therefore, reports from literature may be more reflective of a common coincidence than an etiologic relationship. Buttressing the notion that clozapine does not cause obsessive or compulsive symptoms are reports of two patients whose obsessive-compulsive disorder improved on clozapine despite previous failure to respond to treatment with SSRIs. (13> In another open label study 21 patients were treated with risperidone as an adjunct to conventional SRI therapy, 16 experienced a substantial reduction of obsessive-compulsive symptoms (14). On other hand, reports of remission of obsessive-compulsive symptoms after clozapine or risperidone reduction suggest a cause and effect relationship, but also that drug-induced obsessive-compulsive symptoms may be dose related (3, 4, 7). Studies demonstrating the exacerbation and reduction of obsessive-compulsive symptoms in response to serotonin agonists and antagonists provider further support for the serotoninergic hypotesis. The apparent superiority of SSRIs over agents lacking potent effects on serotonin reuptake inhibition provides support for role of serotonin in the etiology of obsessive-compulsive symptoms too. But inhibition of serotonin reuptake occurs within minutes of the first dose of drug, yet symptoms only respond after several weeks of treatment, maybe because of some undiscovered compensatory changes in both presynaptic and postsynaptic neurons following chronic reuptake inhibition. We assessed de novo obsessive-compulsive symptom occurred in schizophrenic patients during clozapine treatment and its course after fluoxetine application. PATIENTS AND METHODS The prospective follow up included 8 patients with schizophrenia according to DSM IV. Five female and three male patients were enrolled: 1 patient with Undifferentiated Type, 2 with Disorganised Type and 5 patients with Paranoid Type of schizophrenia. Average age was 31.7+5.90. Obsessions and compulsion were measured before and during fluoxetine treatment in 24-week trial. Efficacy measures were the Yale- Brown Obsessive Compulsive Scale, CGI Obsessive Compulsive Scale, Hamilton Rating Scale for Anxiety. The patients, after one week wash-out, were treated with 40-60 mg daily doses of fluoxetine. RESULTS In analysing of the results we used paired t-test. Statistically significant improvement was observed on Y- BOCS between 3 and 6 weeks of trial, which was eith'er shovved in additional 18 weeks as a sustained improvement (PcO.Ol). The corresponding results was also observed in CGI Obsessive Compulsive Scale. On HAMS statistically significant improvement was observed after 3 weeks of therapy, which was either showed in additional part of trial as a sustained improvement. CONCLUSION Results support efficacy, safety and tolerability of fluoxetine 40- 60 mg daily doses in the acute and maintenance treatment of that particular group of schizophrenic patients. REFERENCES 1. Allen L & Tejera C: Treatment of clozapine-induced obsessive- compulsive symptoms with sertraline. Am J Psychiatry 151:1096- 97, 1994. 2. Baker RW, Chengappa KNR, Baird JW, Steingard S, Christ, MA & Schooler NR: Emergance of obsessive compulsive symptoms during treatment wilh clozapine. J Clin Psychiatry 53:439-42, 1992. 3. Eales MJ & Rasmunssen SA: Obsessive compulsive disorder with psychoticfeatures. J Clin Psychiatry 54:373-79, 1993. 4. Levkovitch Y, Kronnenberg Y & Gaoni B: Can clozapine trigger OCD? J Am Acad Adoles Psychiatry 34:263, 1995. 5. Patel B & Tandon R: Development of obsessive- compulsive symptoms during clozapine treatment. Am J Psychiatry 150:836. 1993. 6. Kopala L & Honer WG: Risperidone, serotonergic mechanisms, and obsessive-compulsive symptoms in schizophrenia. Am J Psychiatry 151:1714-15, 1994. 7. Remington G & Adams M: Risperidone and obsessive- compulsive svmptoms. J Clin Psychopharmacol 14:258-359, 1994. 8. Barr LC, Goodman WK, Priče LH, McDougle CJ & Chamey DS: The serotonin hypotesis of obsessive compulsive disorder. Implications of pharmacologic challenge studies. J Clin Psychiatry 53(4, Suppl.): 17-28, 1992. 9. Winslow JT & Insel TR: Neurobiologv of obsessive-compulsive disorder. A possible role of serotonin. J Clin Psychiatry 51(8, Suppl.):27-31, 1990. 10. Murphy DL, Žohar J, Benkelfat C, Pato MT, Pigott TA & Insel TR: Obsessive- compulsive disorder as a 5-HT subsystem- related behevioural disorder. Br J Psychiatry 155(8, Suppl.): 15-24, 1989. 11. Eisen JL & Rasmunssen SA: Obsessive compulsive disorder with psychoticfeatures. J Clin Psychiatry 54:373-379, 1993. 12. Berman 1, Kalinowski A, Berman SM, Lengua J & Green AI: Obsessive and compulsive symptoms in chronic schizophrenia. Comprenhensive Psychiatry 36(1):6-10, 1995. 13. LaPorta LD: More on obsessive-compulsive svmptoms and clozapine. J Clin Psychiatry 55:312, 1994. 14. Saxena S, Wang D, Bystritsky A & Baxter LR: Risperidone augmentation of 'SRI treatment for refractory obsessive- compulsive disorder. J Clin Psychiatry 57(7):303-306, 1996.

schoizophrenia ; obsessive compulsive symptoms ; treatment ; clozapine ; fluoxetine

Rad je prezentiran na skupu 18th Danube Symposion of Psychiatry, održanom 04.-06.06.1998.g., Zagreb, Hrvatska.