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Medication-Free Minors With Schizophrenia

To the Editor: In their conclusions on schizophrenia research with medication-free minors, Sanjiv Kumra, M.D., F.R.C.P., and colleagues (1) may have underestimated the clinical impact of the speed of tapering neuroleptic medications in children and adolescents, who are usually more sensitive to the adverse effects of psychotropics. The authors stated that the subjects were tapered "over 1 to 2 weeks." Whether or not this schedule conforms to routine clinical practice, common sense and guidelines for the tapering of most psychotropics taken for prolonged periods suggest that this schedule be considered an abrupt withdrawal.

And contrary to what the authors implied in their article, the study they cited (2) and another meta-analysis of neuroleptic withdrawal (3, 4) actually show that abrupt withdrawal increases the probability of recurrence of psychotic symptoms. In that light, the "rapid and severe deterioration" of symptoms that followed drug discontinuation in 26% of their subjects points to a withdrawal reaction, as psychotic relapses rarely occur during the first weeks of withdrawal (5). Withdrawal reactions appear to be especially common when atypical neuroleptics are abruptly withdrawn (6, 7). Until the authors provide additional data (e.g., on concomitant medications prescribed and withdrawn, on withdrawal-emergent extrapyramidal symptoms, on speed of response to reinstitution of neuroleptics), their study underscores the clinical need for gradual, patient-centered drug withdrawal and the scientific need to distinguish between neuroleptic withdrawal reactions and psychotic relapses.

References

1. Kumra S, Briguglio C, Lenane M, Goldhar L, Bedwell J, Venuchekov J, Jacobsen LK, Rapoport JL: Including children and adolescents with schizophrenia in medication-free research. Am J Psychiatry 1999; 156:1065–1068
2. Viguera AC, Baldessarini RJ, Hegarty JD, van Kammen DP, Tohen M: Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry 1997; 54:49–55[Abstract/Free Full Text]
3. Gilbert PL, Harris J, McAdams LA, Jeste DV: Neuroleptic withdrawal in schizophrenic patients: a review of the literature. Arch Gen Psychiatry 1995; 52:173–188[Abstract/Free Full Text]
4. Baldessarini RJ, Viguera AC: Neuroleptic withdrawal in schizophrenic patients. Arch Gen Psychiatry 1995; 52:189–192[Abstract/Free Full Text]
5. Perenyi A, Frecska E, Bagdy G, Revai K: Changes in mental condition, hyperkinesias and biochemical parameters after withdrawal of chronic neuroleptic treatment. Acta Psychiatr Scand 1985; 72:430–435[CrossRef][Medline]
6. Shiovitz TM, Welke TL, Tigel PD, Anamd R, Hartman RD, Sramek JJ, Kurtz NM, Cutler NR: Clozapine rebound and rapid onset psychosis following abrupt clozapine withdrawal. Schizophr Bull 1996; 22:591–595
7. Goudie AJ, Smith JA, Robertson A, Cavanagh C: Clozapine as a drug of dependence. Psychopharmacology 1999; 142:369–374[CrossRef][Medline]

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