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Treatment of HIV-related psychotic disorders with risperidone: A series of 21 cases
Journal oft~ychosomatic Research, Vol. 42, No. 5, pp. 489493, 1997 Copyright © 1997 Elsevier Science Inc. All rights reserved. 0022-3999/97 $17.00 + .00
ELSEVIER
S0022-3999(96)00373-X
T R E A T M E N T OF H I V - R E L A T E D PSYCHOTIC D I S O R D E R S WITH RISPERIDONE: A SERIES OF 21 CASES A S H O K N. S I N G H , * H E L E N G O L L E D G E
and JOSI~ C A T A L A N
(Received 29 October 1996; accepted 13 November 1996) Abstract--We describe a consecutive series of 21 patients with HIV or AIDS who received risperidone for psychotic disorders. Of these, 13 became symptom-free, 7 showed substantial improvement, and 1 had no response. Most responded to low doses of risperidone (mean maximum dose 3.3 mg) and needed only a short course of treatment (mean 6.4 weeks). The 12 manic patients did particularly well: 9 became symptom-free and the mean Young mania rating scale fell from 28.36 to 3.91. No serious adverse effects were reported. Three patients became drowsy and two experienced drooling, but these resolved after dose reductions or at the end of treatment. No adverse hematological effects were observed. We suggest that risperidone may be the treatment of choice for patients with HIV-related psychotic disorders. © 1997 Elsevier Science Inc.
Keywords:
AIDS; HIV infection; Psychosis; Antipsychotic agents; Risperidone.
INTRODUCTION Psychotic disorders and mania are not u n c o m m o n in patients with the acquired imm u n e deficiency s y n d r o m e ( A I D S ) [1-4]. H o w e v e r , these patients are particularly sensitive to the e x t r a p y r a m i d a l side-effects (EPS) of conventional neuroleptic agents and, already having extremely c o m p r o m i s e d white blood cell levels, should not be exposed to an additional hematological risk [5-8]. Risperidone causes fewer extrapyramidal side-effects than haloperidol in patients with schizophrenia [9, 10], and, unlike clozapine, has not b e e n associated with serious hematological effects. W e previously r e p o r t e d four cases [11] and n o w have experience with a further 17 which tend to confirm our view that risperidone m a y be the drug of choice for such patients.
CASE HISTORY SERIES Outlines of the 21 cases are shown in Table I. T h e y represent a consecutive series of cases referred to the Psychological Medicine Unit b e t w e e n mid-1994 and mid1996 requiring treatment for HIV-related psychosis. All but one were male, the m e a n age was 39 years. F o u r patients had a previous history of psychiatric illness, 1 admitPsychological Medicine Unit, South Kensington & Chelsea Mental Health Centre, London, UK. *Address correspondence to: Dr. Singh, Beaconfield Mental Health Resource Centre, Beacon Lane, Grantham, Lincolnshire, NG31 9DF, UK; Phone: (44) 1476-591233;Fax: (44) 1476-591739. 489
490
A.N. SINGH et al.
ted to using recreational drugs, and 12 had predominantly manic symptoms at presentation.
Response to risperidone Thirteen patients (62%) became completely symptom-flee, seven showed significant improvement, and one showed no response after treatment with risperidone. Those with manic symptoms responded particularly well, with 9 of 12 (75%) becoming symptom-flee compared with 4 of 9 (44%) of those with schizophrenialike psychoses. Of the 14 patients who had stopped treatment at the time of this survey, the average length of treatment was 6.4 weeks. The mean time to a clinically significant response was 4.1 weeks. Five patients received longer term maintenance treatment with risperidone of 1 mg o.d. (2 cases), 1 mg b.d. (2 cases), or 3 mg b.d. The mean maximum daily dose of risperidone was 3.29 mg, the mean minimum dose was 1.76 mg. At doses above 1 mg o.d., risperidone was usually given in divided doses. Only one patient (with a previous history of psychiatric illness) required 4 mg b.d. One patient was switched to haloperidol liquid because of severe esophageal candidiasis; a liquid preparation of risperidone has since become available. Another patient was switched to haloperidol after a poor response to risperidone but died 2 weeks later of AIDS-related disease.
Safety and adverse effects' No serious adverse reactions were observed, although two patients had previously developed severe EPS with conventional neuroleptic agents. Three patients complained of mild or moderate drowsiness, one of drooling saliva and one of drooling, slight stiffness, and drowsiness. These symptoms resolved completely after dose reductions (in three cases) or when risperidone was stopped following a good response (in two cases). No adverse hematological effects were associated with risperidone.
DISCUSSION
Previous investigators have noted that AIDS patients are particularly susceptible to the side-effects of conventional neuroleptic drugs [8] and have suggested that treatment "should be based primarily on the side effect profile" [12]. In our series, only one patient developed anything approaching recognizable EPS and this was mild and transient. Although previous publications have not stated the proportion of patients who experienced EPS with other neuroleptic agents, statements such as "the development of both anticholinergic and extrapyramidal side-effects limited the dose of neuroleptic that could be used" [8] and "AIDS patients have been regarded as susceptible to extrapyramidal side effects of antipsychotic drugs" [3] suggest that side-effects are more frequent and more severe in patients receiving conventional neuroleptic drugs. The cause of drooling saliva is unclear, because risperidone has little affinity for muscarinic receptors which mediate this effect in clozapine. A direct comparison of
Risperidone in HIV-related psychosis
491
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risperidone and clozapine in schizophrenic patients found that risperidone caused less hypersalivation than clozapine [13]. Patients with HIV infection appear to be very sensitive to antipsychotic treatments, not only in terms of susceptibility to side-effects, but also in the rapid response seen to very low doses. Most of our cases responded to 2 m.g.b.d, of risperidone. Patients with schizophrenia, who have often received long-term treatment with other agents, tend to require daily doses of 4-8 mg with a recent study showing a mean of 7.5 mg [14]. Hematological safety is of particular importance in patients with compromised leukocyte numbers and low CD4 counts are usually taken as a contraindication for clozapine treatment [15]. Similarly, although remoxipride was effective in HIVrelated mania, it was withdrawn because of aplastic anaemia [16]. Some of our patients had rapidly falling CD4 counts, but risperidone appeared safe in all cases. Our cases show several characteristic features of AIDS-related psychosis, such as acute onset of symptoms, rapid response to treatment, and short duration of psychosis [8, 12]. Lyketsos et al. observed that patients without a family or personal history of affective disorder presented later in the course of HIV infection [2]. Only four of our patients had a previous history of psychiatric illness and there was no correlation with the stage of presentation. Many patients with HIV/AIDS have a history of drug abuse which may affect their mental state or prognosis: recreational drug use was admitted by one patient in the current series. However, risperidone has been used in drug-induced psychoses and may be appropriate even in dual-diagnosis cases [17].
CONCLUSION
Risperidone was effective and well-tolerated and may cause fewer side-effects than conventional neuroleptic drugs in patients with HIV infection. Randomized controlled trials are needed to confirm the superior efficacy and safety of risperidone, but our experience suggests that it is particularly suitable for the treatment of HIV-related psychoses. A c k n o w l e d g m e n t - - W e thank Elizabeth Wager for her help during the development of this article.
REFERENCES 1. Kieburtz K, Zettelmaier A, Ketonen L, et al. Manic syndrome in AIDS. Am J Psychiatry 1991; 148:1068-1070. 2. Lyketsos C, Hanson A, Rishman M, et al. Manic syndrome early and late in the course of HIV. Am J Psychiatry 1993;150:326-327. 3. Maj M. Psychiatric aspects of HIV-1 infection and AIDS. Psychol Med 1990;20:547-563. 4. Catalan J, Burgess A, Klimes I, eds. Psychological medicine of HIV infection. Oxford: Oxford Medical Publications 1995. 5. Edelstein H, Knight R. Severe parkinsonism in two AIDS patients taking prochlorperazine. Lancet 1987;2:341-342. 6. Maecario M, Scharre D. HIV and acute onset of psychosis. Lancet 1987;2:342. 7. Breitbart W, Marotta R, Call P. AIDS and the neuroleptie malignant syndrome. Lancet 1988; 2:1488-1489. 8. Sewell D, Jeste D, Atkinson J, et al. HIV-associated psychosis: a study of 20 cases. Am J Psychiatry 1994;151:237-242.
Risperidone in HIV-related psychosis
493
9. 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. 10. Owens D. Extrapyramidal side effects and tolerability of risperidone: a review. J Clin Psychiatry 1994;55(suppl 5):29-53. 11. Singh A, Catalan J. Risperidone in HIV-related manic psychosis. Lancet 1994;344:1029-103(I. 12. Harris M, Jeste D, Gleghorn A, Sewell D. New-onset psychosis in HIV-infected patients. J Clin Psychiatry 1991;52:369-376. 13. Heinrich K, Kleiser E, Lehmann E. Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial. Prog Neuropsychobiol Psychiatry 1994;18:129-137. 14. Kirov G, Murray R, Seth R, Feeney S. Observations on switching patients with schizophrenia to risperidone treatment. Acta Psychiatr Scand (in press). 15. Krupp P, Barnes P. Clozapine-associated agranulocytosis: risk and aetiology. Br J Psychiatry 1992;160(suppl 17):38-40. 16. Scurlock H, Singh A, Catalan J. Atypical antipsychotic drugs in the treatment of manic syndromes in patients with HIV-1 infection. J Psychopharmacol 1995;9:151-154. 17. Moslehuddin K. Treatment of psychoses in substance abusers: four case histories of the use of risperidone. J Drug Devel (Case History Series) 1994;1:13-14.
ELSEVIER
S0022-3999(96)00373-X
T R E A T M E N T OF H I V - R E L A T E D PSYCHOTIC D I S O R D E R S WITH RISPERIDONE: A SERIES OF 21 CASES A S H O K N. S I N G H , * H E L E N G O L L E D G E
and JOSI~ C A T A L A N
(Received 29 October 1996; accepted 13 November 1996) Abstract--We describe a consecutive series of 21 patients with HIV or AIDS who received risperidone for psychotic disorders. Of these, 13 became symptom-free, 7 showed substantial improvement, and 1 had no response. Most responded to low doses of risperidone (mean maximum dose 3.3 mg) and needed only a short course of treatment (mean 6.4 weeks). The 12 manic patients did particularly well: 9 became symptom-free and the mean Young mania rating scale fell from 28.36 to 3.91. No serious adverse effects were reported. Three patients became drowsy and two experienced drooling, but these resolved after dose reductions or at the end of treatment. No adverse hematological effects were observed. We suggest that risperidone may be the treatment of choice for patients with HIV-related psychotic disorders. © 1997 Elsevier Science Inc.
Keywords:
AIDS; HIV infection; Psychosis; Antipsychotic agents; Risperidone.
INTRODUCTION Psychotic disorders and mania are not u n c o m m o n in patients with the acquired imm u n e deficiency s y n d r o m e ( A I D S ) [1-4]. H o w e v e r , these patients are particularly sensitive to the e x t r a p y r a m i d a l side-effects (EPS) of conventional neuroleptic agents and, already having extremely c o m p r o m i s e d white blood cell levels, should not be exposed to an additional hematological risk [5-8]. Risperidone causes fewer extrapyramidal side-effects than haloperidol in patients with schizophrenia [9, 10], and, unlike clozapine, has not b e e n associated with serious hematological effects. W e previously r e p o r t e d four cases [11] and n o w have experience with a further 17 which tend to confirm our view that risperidone m a y be the drug of choice for such patients.
CASE HISTORY SERIES Outlines of the 21 cases are shown in Table I. T h e y represent a consecutive series of cases referred to the Psychological Medicine Unit b e t w e e n mid-1994 and mid1996 requiring treatment for HIV-related psychosis. All but one were male, the m e a n age was 39 years. F o u r patients had a previous history of psychiatric illness, 1 admitPsychological Medicine Unit, South Kensington & Chelsea Mental Health Centre, London, UK. *Address correspondence to: Dr. Singh, Beaconfield Mental Health Resource Centre, Beacon Lane, Grantham, Lincolnshire, NG31 9DF, UK; Phone: (44) 1476-591233;Fax: (44) 1476-591739. 489
490
A.N. SINGH et al.
ted to using recreational drugs, and 12 had predominantly manic symptoms at presentation.
Response to risperidone Thirteen patients (62%) became completely symptom-flee, seven showed significant improvement, and one showed no response after treatment with risperidone. Those with manic symptoms responded particularly well, with 9 of 12 (75%) becoming symptom-flee compared with 4 of 9 (44%) of those with schizophrenialike psychoses. Of the 14 patients who had stopped treatment at the time of this survey, the average length of treatment was 6.4 weeks. The mean time to a clinically significant response was 4.1 weeks. Five patients received longer term maintenance treatment with risperidone of 1 mg o.d. (2 cases), 1 mg b.d. (2 cases), or 3 mg b.d. The mean maximum daily dose of risperidone was 3.29 mg, the mean minimum dose was 1.76 mg. At doses above 1 mg o.d., risperidone was usually given in divided doses. Only one patient (with a previous history of psychiatric illness) required 4 mg b.d. One patient was switched to haloperidol liquid because of severe esophageal candidiasis; a liquid preparation of risperidone has since become available. Another patient was switched to haloperidol after a poor response to risperidone but died 2 weeks later of AIDS-related disease.
Safety and adverse effects' No serious adverse reactions were observed, although two patients had previously developed severe EPS with conventional neuroleptic agents. Three patients complained of mild or moderate drowsiness, one of drooling saliva and one of drooling, slight stiffness, and drowsiness. These symptoms resolved completely after dose reductions (in three cases) or when risperidone was stopped following a good response (in two cases). No adverse hematological effects were associated with risperidone.
DISCUSSION
Previous investigators have noted that AIDS patients are particularly susceptible to the side-effects of conventional neuroleptic drugs [8] and have suggested that treatment "should be based primarily on the side effect profile" [12]. In our series, only one patient developed anything approaching recognizable EPS and this was mild and transient. Although previous publications have not stated the proportion of patients who experienced EPS with other neuroleptic agents, statements such as "the development of both anticholinergic and extrapyramidal side-effects limited the dose of neuroleptic that could be used" [8] and "AIDS patients have been regarded as susceptible to extrapyramidal side effects of antipsychotic drugs" [3] suggest that side-effects are more frequent and more severe in patients receiving conventional neuroleptic drugs. The cause of drooling saliva is unclear, because risperidone has little affinity for muscarinic receptors which mediate this effect in clozapine. A direct comparison of
Risperidone in HIV-related psychosis
491
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A.N. SINGH et al.
risperidone and clozapine in schizophrenic patients found that risperidone caused less hypersalivation than clozapine [13]. Patients with HIV infection appear to be very sensitive to antipsychotic treatments, not only in terms of susceptibility to side-effects, but also in the rapid response seen to very low doses. Most of our cases responded to 2 m.g.b.d, of risperidone. Patients with schizophrenia, who have often received long-term treatment with other agents, tend to require daily doses of 4-8 mg with a recent study showing a mean of 7.5 mg [14]. Hematological safety is of particular importance in patients with compromised leukocyte numbers and low CD4 counts are usually taken as a contraindication for clozapine treatment [15]. Similarly, although remoxipride was effective in HIVrelated mania, it was withdrawn because of aplastic anaemia [16]. Some of our patients had rapidly falling CD4 counts, but risperidone appeared safe in all cases. Our cases show several characteristic features of AIDS-related psychosis, such as acute onset of symptoms, rapid response to treatment, and short duration of psychosis [8, 12]. Lyketsos et al. observed that patients without a family or personal history of affective disorder presented later in the course of HIV infection [2]. Only four of our patients had a previous history of psychiatric illness and there was no correlation with the stage of presentation. Many patients with HIV/AIDS have a history of drug abuse which may affect their mental state or prognosis: recreational drug use was admitted by one patient in the current series. However, risperidone has been used in drug-induced psychoses and may be appropriate even in dual-diagnosis cases [17].
CONCLUSION
Risperidone was effective and well-tolerated and may cause fewer side-effects than conventional neuroleptic drugs in patients with HIV infection. Randomized controlled trials are needed to confirm the superior efficacy and safety of risperidone, but our experience suggests that it is particularly suitable for the treatment of HIV-related psychoses. A c k n o w l e d g m e n t - - W e thank Elizabeth Wager for her help during the development of this article.
REFERENCES 1. Kieburtz K, Zettelmaier A, Ketonen L, et al. Manic syndrome in AIDS. Am J Psychiatry 1991; 148:1068-1070. 2. Lyketsos C, Hanson A, Rishman M, et al. Manic syndrome early and late in the course of HIV. Am J Psychiatry 1993;150:326-327. 3. Maj M. Psychiatric aspects of HIV-1 infection and AIDS. Psychol Med 1990;20:547-563. 4. Catalan J, Burgess A, Klimes I, eds. Psychological medicine of HIV infection. Oxford: Oxford Medical Publications 1995. 5. Edelstein H, Knight R. Severe parkinsonism in two AIDS patients taking prochlorperazine. Lancet 1987;2:341-342. 6. Maecario M, Scharre D. HIV and acute onset of psychosis. Lancet 1987;2:342. 7. Breitbart W, Marotta R, Call P. AIDS and the neuroleptie malignant syndrome. Lancet 1988; 2:1488-1489. 8. Sewell D, Jeste D, Atkinson J, et al. HIV-associated psychosis: a study of 20 cases. Am J Psychiatry 1994;151:237-242.
Risperidone in HIV-related psychosis
493
9. 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. 10. Owens D. Extrapyramidal side effects and tolerability of risperidone: a review. J Clin Psychiatry 1994;55(suppl 5):29-53. 11. Singh A, Catalan J. Risperidone in HIV-related manic psychosis. Lancet 1994;344:1029-103(I. 12. Harris M, Jeste D, Gleghorn A, Sewell D. New-onset psychosis in HIV-infected patients. J Clin Psychiatry 1991;52:369-376. 13. Heinrich K, Kleiser E, Lehmann E. Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial. Prog Neuropsychobiol Psychiatry 1994;18:129-137. 14. Kirov G, Murray R, Seth R, Feeney S. Observations on switching patients with schizophrenia to risperidone treatment. Acta Psychiatr Scand (in press). 15. Krupp P, Barnes P. Clozapine-associated agranulocytosis: risk and aetiology. Br J Psychiatry 1992;160(suppl 17):38-40. 16. Scurlock H, Singh A, Catalan J. Atypical antipsychotic drugs in the treatment of manic syndromes in patients with HIV-1 infection. J Psychopharmacol 1995;9:151-154. 17. Moslehuddin K. Treatment of psychoses in substance abusers: four case histories of the use of risperidone. J Drug Devel (Case History Series) 1994;1:13-14.