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December 1995, Vol 52, No. 12 >
Article | December 1995

Conversions From Clozapine to Other Antipsychotic Drugs

Ross J. Baldessarini, MD; David M. Gardner, BSPharm; David L. Garver, MD, PhD
Arch Gen Psychiatry. 1995;52(12):1071-1072. doi:10.1001/archpsyc.1995.03950240089014
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Conversions between dissimilar antipsychotic agents can be problematic. Agents of low potency present risks of central depressant and autonomic side effects, whereas agents of high potency carry a higher risk of inducing acute extrapyramidal effects. Conversions between clozapine and other more typical antipsychotic drugs, including the new agent risperidone,1 are increasingly common and may cause special problems. For example, over a dozen cases of worsening of psychotic symptoms after abrupt withdrawal from clozapine therapy have been reported2-7 and at least five additional similar cases have been observed recently at our centers (D.M.G and R.J.B., unpublished data, June 1995). These reactions often evolved over several days and so were much more rapid than relapses after stopping treatment with standard agents, which average 50% risk over a 3- to 4-month period.8,9 Moreover, several case reports6,10,11 and cases observed at our centers (by D.M.G., D.L.G., and R.J.B. May 1995)

REFERENCES

1 +
Marder SR, Meibach RC.  Risperidone in the treatment of schizophrenia . Am J Psychiatry . 1994;;151:825-835.
2 +
Ekblom B, Eriksson K, Lindstrom LH.  Supersensitivity psychosis in schizophrenic patients after sudden clozapine withdrawal . Psychopharmacology . 1984;;83:293-294.
3 +
Perenyi A, Kuncz E, Bagdy G.  Early relapse after sudden withdrawal or dose reduction of clozapine . Psychopharmacology . 1986;;86:244.
4 +
Eklund K.  Supersensitivity and clozapine withdrawal . Psychopharmacology . 1987;;90:135.
5 +
Alphs LD, Lee HS.  Comparison of withdrawal of typical and atypical antipsychotic drugs: a case study . J Clin Psychiatry . 1991;;52:346-348.
6 +
Parsa MA, Al-Lahham YH, Ramirez JF, Meltzer HY.  Prolonged psychotic relapse after abrupt clozapine withdrawal . J Clin Psychopharmacol . 1993;;13:154-155.
7 +
Abuzzahab FS, Gillund JM. Clozapine and risperidone in schizophrenia. In: ACNP Annual Meeting Abstracts. Nashville, Tenn: American College of Neuropsychopharmacology;1994;33:225.
8 +
Gilbert PL, Harris MJ, Jeste DV.  Neuroleptic withdrawal in schizophrenic patients: a review of the literature . Arch Gen Psychiatry . 1995;;52:173-188.
9 +
Baldessarini RJ, Viguera AC.  Neuroleptic withdrawal in schizophrenic patients . Arch Gen Psychiatry . 1995;;52:189-192.
10 +
Dickson R, Williams R, Dalby JT.  Dystonic reaction and relapse with clozapine discontinuation and risperidone initiation . Can J Psychiatry . 1994;;39:184.
11 +
Mok H, Yatham LN.  Response to clozapine as a predictor of risperidone response in schizophrenia . Am J Psychiatry 1994;;151:1393-1394.
12 +
Baldessarini RJ, Frankenburg FR.  Clozapine: a novel antipsychotic agent . N Engl J Med 1991;;324:746-754.
13 +
Cohen BM, Tsuneizumi T, Baldessarini RJ, Campbell A, Babb SM.  Differences between antipsychotic drugs in persistence of brain levels and behavioral effects . Psychopharmacology . 1992;;108:338-344.
14 +
Baldessarini RJ, Centorrino F, Flood JG, Volpicelli SA, Huston-Lyons D, Cohen BM.  Tissue concentrations of clozapine and its metabolites in the rat . Neuropsychopharmacology . 1993;;9:117-124.
15 +
Van Tol HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli D.  Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine . Nature . 1991;;350:610-614.
16 +
O'Malley KL, Harmon S, Tang L, Todd RD.  The rat D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system . New Biologist . 1992;;4:137-146.
17 +
Kimmel SE, Calabrese JR, Woyshville MJ, Meltzer HY.  Clozapine in treatmentrefractory mood disorders . J Clin Psychiatry . 1994;;55( (suppl B) ):91-93.
18 +
Leysen JE, Janssen PMF, Megens AAHP, Schotte A.  Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism: receptor occupancy profile and pharmacologic activity . J Clin Psychiatry . 1994;;55( (suppl 5) ):5-12.
19 +
Wolf ME, Roth RH.  Autoreceptor regulation of dopamine synthesis . Ann N Y Acad Sci . 1990;;604:323-342.
20 +
Ichikawa J, Meltzer HY.  Differential effects of repeated treatment with haloperidol and clozapine and dopamine release and metabolism in the striatum and the nucleus accumbens . J. Pharmacol Exp Ther . 1991;;256:348-357.
21 +
Suppes T, Baldessarini RJ, Faedda GL, Tondo L, Tohen M.  Discontinuation of maintenance treatment in bipolar disorder: risks and implications . Harvard Rev Psychiatry . 1993;;1:131-144.

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1 +
Marder SR, Meibach RC.  Risperidone in the treatment of schizophrenia . Am J Psychiatry . 1994;;151:825-835.
2 +
Ekblom B, Eriksson K, Lindstrom LH.  Supersensitivity psychosis in schizophrenic patients after sudden clozapine withdrawal . Psychopharmacology . 1984;;83:293-294.
3 +
Perenyi A, Kuncz E, Bagdy G.  Early relapse after sudden withdrawal or dose reduction of clozapine . Psychopharmacology . 1986;;86:244.
4 +
Eklund K.  Supersensitivity and clozapine withdrawal . Psychopharmacology . 1987;;90:135.
5 +
Alphs LD, Lee HS.  Comparison of withdrawal of typical and atypical antipsychotic drugs: a case study . J Clin Psychiatry . 1991;;52:346-348.
6 +
Parsa MA, Al-Lahham YH, Ramirez JF, Meltzer HY.  Prolonged psychotic relapse after abrupt clozapine withdrawal . J Clin Psychopharmacol . 1993;;13:154-155.
7 +
Abuzzahab FS, Gillund JM. Clozapine and risperidone in schizophrenia. In: ACNP Annual Meeting Abstracts. Nashville, Tenn: American College of Neuropsychopharmacology;1994;33:225.
8 +
Gilbert PL, Harris MJ, Jeste DV.  Neuroleptic withdrawal in schizophrenic patients: a review of the literature . Arch Gen Psychiatry . 1995;;52:173-188.
9 +
Baldessarini RJ, Viguera AC.  Neuroleptic withdrawal in schizophrenic patients . Arch Gen Psychiatry . 1995;;52:189-192.
10 +
Dickson R, Williams R, Dalby JT.  Dystonic reaction and relapse with clozapine discontinuation and risperidone initiation . Can J Psychiatry . 1994;;39:184.
11 +
Mok H, Yatham LN.  Response to clozapine as a predictor of risperidone response in schizophrenia . Am J Psychiatry 1994;;151:1393-1394.
12 +
Baldessarini RJ, Frankenburg FR.  Clozapine: a novel antipsychotic agent . N Engl J Med 1991;;324:746-754.
13 +
Cohen BM, Tsuneizumi T, Baldessarini RJ, Campbell A, Babb SM.  Differences between antipsychotic drugs in persistence of brain levels and behavioral effects . Psychopharmacology . 1992;;108:338-344.
14 +
Baldessarini RJ, Centorrino F, Flood JG, Volpicelli SA, Huston-Lyons D, Cohen BM.  Tissue concentrations of clozapine and its metabolites in the rat . Neuropsychopharmacology . 1993;;9:117-124.
15 +
Van Tol HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli D.  Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine . Nature . 1991;;350:610-614.
16 +
O'Malley KL, Harmon S, Tang L, Todd RD.  The rat D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system . New Biologist . 1992;;4:137-146.
17 +
Kimmel SE, Calabrese JR, Woyshville MJ, Meltzer HY.  Clozapine in treatmentrefractory mood disorders . J Clin Psychiatry . 1994;;55( (suppl B) ):91-93.
18 +
Leysen JE, Janssen PMF, Megens AAHP, Schotte A.  Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism: receptor occupancy profile and pharmacologic activity . J Clin Psychiatry . 1994;;55( (suppl 5) ):5-12.
19 +
Wolf ME, Roth RH.  Autoreceptor regulation of dopamine synthesis . Ann N Y Acad Sci . 1990;;604:323-342.
20 +
Ichikawa J, Meltzer HY.  Differential effects of repeated treatment with haloperidol and clozapine and dopamine release and metabolism in the striatum and the nucleus accumbens . J. Pharmacol Exp Ther . 1991;;256:348-357.
21 +
Suppes T, Baldessarini RJ, Faedda GL, Tondo L, Tohen M.  Discontinuation of maintenance treatment in bipolar disorder: risks and implications . Harvard Rev Psychiatry . 1993;;1:131-144.

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