Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-25T10:10:34.278Z Has data issue: false hasContentIssue false
  • English
  • Français

Critical analysis and comparison of the side-effect and safety profiles of the new antipsychotics*

Published online by Cambridge University Press:  06 August 2018

Thomas R. E. Barnes  and
Mike A. McPhillips
Thomas R. E. Barnes*
Affiliation:
Division of Neuroscience and Physiological Medicine, Imperial College School of Medicine, London
Mike A. McPhillips
Affiliation:
Division of Neuroscience and Physiological Medicine, Imperial College School of Medicine, London
*
Correspondence: Professor T. R. E. Barnes, Ealing, Hammersmith and Fulham NHS Trust, Academic Centre, Trust Headquarters, Uxbridge Road, Ealing UBI 3EU
Get access Rights & Permissions [Opens in a new window]

Extract

The conventional antipsychotic drugs are associated with a wide range of unwanted effects (Barnes & Guy Edwards, 1993; Guy Edwards & Barnes, 1993). These side-effects represent part of the burden of patients given antipsychotic medication, affect compliance with treatment, and contribute to the prescribing clinician's weigh-ing-up of the risks and benefits of a particular antipsychotic in an individual case. The conventional drugs show differences in their side-effect profiles, particularly with regard to sedation and extrapyramidal problems, and it is probably a reasonable generalisation to state that these have largely governed clinicians' choice. The newer ‘atypical’ antipsychotics (such as clozapine, risperidone, sertindole, olanzapine, quetiapine and amisulpride) are less liable to cause extrapyramidal symptoms than the conventional antipsychotics. However, this advantage is greater for some of the new drugs than for others, and their safety profiles also differ in other key respects. Thus, in terms of side-effects and safety, each of these newer drugs must be evaluated individually.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 174 , Issue S38: New antipsychotics - preclinical and clinical comparisons , May 1999 , pp. 34 - 43
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

∗

Author's note: During the interval between completion of this paper and its publication, the availability of sertindole was voluntarily suspended by the manufacturer, Lundbeck Ltd, because of concerns about cardiotoxicity.

References

Aizenberg, D., Zemishlany, Z., Dorfman-Etrog, P., et al (1995) Sexual dysfunction in male schizophrenic patients. Journal of Clinical Psychiatry, 56, 137–141.Google ScholarPubMed
Alvir, J. M. J., Lieberman, J. A., Safferman, A. Z., et al (1993) Clozapine-induced agranulocytosis: Incidence and risk factors in the United States. New England Journal of Medicine, 329, 162–167.CrossRefGoogle ScholarPubMed
Anon (1993) Risperidone and remoxipride for schizophrenia. Drug and Therapeutics Bulletin, 31, 101–102.CrossRefGoogle Scholar
Anon (1997) Olanzapine, sertindole and schizophrenia. Drug and Therapeutics Bulletin, 35, 81–83.CrossRefGoogle Scholar
Arvanitis, L. A., Miller, B. G. & the Seroquel Trial 13 Study Group (1997) Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biological Psychiatry, 42, 233–246.CrossRefGoogle ScholarPubMed
Atkin, K., Kendall, F., Gould, D., et al (1996) Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. British Journal of Psychiatry, 169, 483–488.CrossRefGoogle ScholarPubMed
Aunsholt, N. A. (1989) Prolonged QT interval and hypokalaemia caused by haloperidol. Acta Psychiatrica Scandinavica, 79, 411–412.CrossRefGoogle ScholarPubMed
Awad, A. G. & Hogan, T. P. (1994) Subjective response to neuroleptics and quality of life-implications for treatment outcome. Acta Psychiatrica Scandinavica, 89 (suppl. 380), 27–32.CrossRefGoogle Scholar
Barnes, T. R. E. (1989) A rating scale for drug-induced akathisia. British Journal of Psychiatry, 154, 672–676.CrossRefGoogle ScholarPubMed
Barnes, T. R. E. (1992) Neuromuscular effects of neuroleptics: Akathisia. In Adverse Effects of Psychotropic Drugs (eds Kane, J. M. & Lieberman, J. A.), pp. 201–217. New York: Guilford Press.Google Scholar
Barnes, T. R. E. & Guy Edwards, J. (1993) The side-effects of antipsychotic drugs. I. CNS and neuromuscular effects. In Antipsychotic Drugs and Their Side-Effects (ed. Barnes, T. R. E.), pp. 213–247. London: Academic Press.CrossRefGoogle Scholar
Barnes, T. R. E. & Harvey, C. A. (1993) Psychiatric drugs and sexuality. In Sexual Pharmacology (eds Riley, A. J., Peet, M. & Wilson, C.), pp. 176–196. Oxford: Oxford Medical Publications.CrossRefGoogle Scholar
Barnes, T. R. E. & McPhillips, M. A. (1995) How to distinguish between the neuroleptic-induced deficit syndrome, depression and disease-related negative symptoms in schizophrenia. International Clinical Psychopharmacology, 10, 115–121.Google ScholarPubMed
Barnes, T. R. E. & McPhillips, M. A. (1996) Antipsychotic-induced extrapyramidal symptoms: Role of anticholinergic drugs in treatment. CNS Drugs, 6, 315–330.CrossRefGoogle Scholar
Beasley, C. M. (1997) Safety of olanzapine. Journal of Clinical Psychiatry, 15, 19–21.Google Scholar
Beasley, C. M., Sanger, T., Satterlee, W., et al (1996a) Olanzapine versus placebo: acute phase results of a double-blind, fixed dose olanzapine trial. Psychopharmacology, 124, 159–167.CrossRefGoogle ScholarPubMed
Beasley, C. M., Tollefson, G., Tran, P., et al (1996b) Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology, 14, 111–123.CrossRefGoogle ScholarPubMed
Bhavnani, S. M. & Levin, G. M. (1996) Antipsychotic agents: a survey of the prevalence, severity and burden of side-effects. International Clinical Psychopharmacology, 11, 1–12.CrossRefGoogle ScholarPubMed
Bollen, C. A., De Cuyper, C. H., Eneman, H., et al (1992) Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study. Acta Psychiatrica Scandinavica, 85, 295–305.Google Scholar
Boyer, P., Lecrubier, Y., Peuch, A. J., et al (1995) Treatment of negative symptoms in schizophrenia with amisulpride. British Journal of Psychiatry, 166, 68–72.CrossRefGoogle ScholarPubMed
Brecher, M. (1996) Long-term safety of risperidone (abstract P-15–1). European Neuropsychopharmacology, 6 (suppl. 3), 170.CrossRefGoogle Scholar
Casey, D. E. (1996) Side effect profiles of new antipsychotic agents. Journal of Clinical Psychiatry, 57 (suppl. 11), 40–45.Google ScholarPubMed
Casey, D. E. (1997) The relationship of pharmacology to side effects. Journal of Clinical Psychiatry, 58 (suppl. 10), 55–62.Google ScholarPubMed
Ceskova, E. & Svetska, J. (1996) Efficacy and tolerance of risperidone in various doses. Ceska a Slovenska Psychiatrie, 92, 50–56.Google ScholarPubMed
Chengappa, K. N., Shelton, M. D., Baker, R. W., et al (1994) The prevalence of akathisia in patients receiving stable doses of clozapine. Journal of Clinical Psychiatry, 55, 142–145.Google ScholarPubMed
Chouinard, G. (1990) A placebo-controlled clinical trial of remoxipride and chlorpromazine in newly-admitted schizophrenic patients with acute exacerbation. Acta Psychiatrica Scandinavica, 82 (suppl. 358), 111–119.CrossRefGoogle Scholar
Chouinard, G., Ross-Chouinard, A., Annable, L., et al (1980) The extrapyramidal symptom rating scale. Canadian Journal of Neurological Science, 7, 233.Google Scholar
Chouinard, G., Jones, B., Remington, G., et al (1993) A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Journal of Clinical Psychopharmacology, 13, 25–40.CrossRefGoogle ScholarPubMed
Claghorn, J., Honigfeld, G., Abuzzahab, F. S., et al (1987) The risks and benefits of clozapine versus chlorpromazine. Journal of Clinical Psychopharmacology, 7, 377–384.CrossRefGoogle ScholarPubMed
Claus, A., Bollen, J., Cuyper, H., et al (1992) Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study. Acta Psychiatrica Scandinavica, 85, 295–305.CrossRefGoogle ScholarPubMed
Cohen, B. M., Keck, P. E., Satlin, A., et al (1991) Prevalence and severity of akathisia in patients on clozapine. Biological Psychiatry, 29, 1215–1219.CrossRefGoogle ScholarPubMed
Coukell, A. J., Spencer, C. M. & Benfield, P. (1996) Amisulpride: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of schizophrenia. CNS Drugs, 6, 237–256.CrossRefGoogle Scholar
Daniel, D., Goldberg, T. E., Weinberger, D. R., et al (1996) Different side-effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: A pilot study. American Journal of Psychiatry, 153, 417–419.Google ScholarPubMed
Devinsky, O. & Pacia, S. V. (1994) Seizures during clozapine therapy. Journal of Clinical Psychiatry, 55(B): 153–156.Google ScholarPubMed
Factor, S. A. & Friedman, J. H. (1997) The emerging role of clozapine in the treatment of movement disorders. Movement Disorders, 12, 483–496.CrossRefGoogle ScholarPubMed
Fleischhacker, W. W., Meise, U., Gunther, V., et al (1994) Compliance with antipsychotic drug treatment: influence of side-effects. Acta Psychiatrica Scandinavica, 89 (suppl. 382), 11–15.Google Scholar
Franz, M., Lis, S., Pluddemann, K., et al (1997) Conventional versus atypical antipsychotics: subjective quality of life in schizophrenic patients. British Journal of Psychiatry, 170, 422–425.CrossRefGoogle ScholarPubMed
Freeman, H. L. (1997) Amisulpride compared with standard neuroleptics in acute exacerbations of schizophrenia. International Clinical Psychopharmacology, 12 (suppl. 2), 11–17.CrossRefGoogle ScholarPubMed
Fuller, M. A., Borovicka, M. C., Jaskiw, G. E., et al (1996) Clozapine-induced urinary incontinence: incidence and treatment with ephedrine. Journal of Clinical Psychiatry, 57, 514–518.CrossRefGoogle ScholarPubMed
Gerlach, J. & Peacock, L. (1995) Intolerance to neuroleptic drugs: the art of avoiding extrapyramidal syndromes. European Psychiatry, 10 (suppl. 1), 27–31.CrossRefGoogle ScholarPubMed
Grohmann, R., Schmidt, L. G., Speiss-Kiefer, C., et al (1989) Agranulocytosis and significant leucopenia with neuroleptic drugs: results from the AMUP program. Psychopharmacology, 99 (suppl.), 109–112.CrossRefGoogle ScholarPubMed
Guy Edwards, J. & Barnes, T. R. E. (1993) The side-effects of antipsychotic drugs II. Effects on other physiological systems. In Antipsychotic Drugs and Their Side-Effects (ed. Barnes, T. R. E.), pp. 249–275. London: Academic Press.CrossRefGoogle Scholar
Hale, A. S. (1998) A review of the safety and tolerability of sertindole. International Clinical Psychopharmacology, 13 (suppl. 3), 65–70.CrossRefGoogle ScholarPubMed
Halstead, S. M., Barnes, T. R. E. & Speller, J. C. (1994) Akathisia: prevalence and associated dysphoria in an in-patient population with chronic schizophrenia. British Journal of Psychiatry, 164, 177–183.CrossRefGoogle Scholar
Heimberg, C., Gallacher, F., Gur, R. C., et al (1995) Diet and gender moderate clozapine-related weight gain. Human Psychopharmacology, 10, 367–71.CrossRefGoogle Scholar
Jensen, V. E. & Gotzsche, O. (1994) Allergic myocarditis in clozapine treatment. Ugeskrift for Laeger (Copenhagen), 156, 4151–4152.Google ScholarPubMed
Josefson, D. (1997) Hay fever drug to be banned by the FDA. British Medical Journal, 314, 248.CrossRefGoogle ScholarPubMed
Jurivich, D. A., Hanlon, J. & Andolsek, K. (1987) Neuroleptic-induced neutropenia in the elderly. Journal of the American Geriatrics Society, 35, 248–250.CrossRefGoogle ScholarPubMed
Kane, J. M. (1994) Risperidone (editorial). American Journal of Psychiatry, 151, 802–803.Google Scholar
Kane, J. M., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic. Archives of General Psychiatry, 45, 789–796.CrossRefGoogle ScholarPubMed
Kerwin, R. W. (1994) The new atypical antipsychotics: a lack of extrapyramidal side-effects and new routes in schizophrenia research. British Journal of Psychiatry, 164, 141–148.CrossRefGoogle ScholarPubMed
Klieser, E., Lehmann, E., Kinzler, E., et al (1995) Randomised, double-blind controlled trial of risperidone versus clozapine in patients with chronic schizophrenia. Journal of Clinical Psychopharmacology, 15 (suppl. I), 45–51.CrossRefGoogle ScholarPubMed
Krahenbuhl, S., Sauter, B., Kupferschmidt, H., et al (1995) Case report: reversible QT prolongation with torsade de pointes in a patient with pimozide intoxication. American Journal of Medical Science, 309, 315–316.CrossRefGoogle Scholar
Kuchenhoff, B. (1993) Die wichtigsten Nebenwirkungen unter Clozapin (Leponex) und ihre Behandlung. Psychiatrische Praxis, 20, 201–206.Google Scholar
Kurz, M., Hummer, M., Oberhauer, H., et al (1995) Extrapyramidal side-effects of clozapine and haloperidol. Psychopharmacology, 118, 52–56.CrossRefGoogle ScholarPubMed
Lader, M. H. (1993) Neuroleptic-induced deficit syndrome: old problem, new challenge. Journal of Psychopharmacology, 7, 392–393.CrossRefGoogle ScholarPubMed
Lamberti, J. S., Bellnier, T. & Schwarzkopf, S. B. (1992) Weight gain among schizophrenic patients treated with clozapine. American Journal of Psychiatry, 149, 689–690.Google ScholarPubMed
Lamberti, J. S., Bellnier, T. (1993) Clozapine and tardive dyskinesia. Journal of Nervous and Mental Disease, 181, 137–138.CrossRefGoogle Scholar
Lande, G., Drouin, E., Gauthier, C., et al (1992) Effets arythmogènes du chlorydrate de sultopride: corrélation clinique et électrophysiologique cellulaire. Annales Françaises d'Anesthésie et de Réanimation, 11, 629–635.CrossRefGoogle Scholar
Lewander, T., Westerbergh, S.-E. & Morrison, D. (1990) Clinical profile of remoxipride – a combined analysis of a comparative double-blind multicentre trial programme. Acta Psychiatrica Scandinavica, 82, 92–98.CrossRefGoogle Scholar
Lilleng, P., Morild, I. & Hope, M. (1995) Clozapine and myocarditis. Tidsskrift for den Norske Laegeforening, 115, 3026–3027.Google ScholarPubMed
Linzasoro, G., Marti-Masso, J. F. & Suarez, J. A. (1993) Nocturnal akathisia in Parkinson's disease: treatment with clozapine. Movement Disorders, 8, 171–174.CrossRefGoogle Scholar
Lingjaerde, O., Ahlfors, U., Bech, P., et al (1987) The UKU Side Effect Rating Scale: a new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side-effects in neuroleptic-treated patients. Acta Psychiatrica Scandinavica, 76, 1–100.CrossRefGoogle Scholar
Loo, H., Poirier-Littré, M-F., Théron, M., et al (1997) Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia. British Journal of Psychiatry, 170, 18–22.CrossRefGoogle ScholarPubMed
Marder, S. R. & Meibach, R. C. (1994) Risperidone in the treatment of schizophrenia. American Journal of Psychiatry, 151, 825–835.Google ScholarPubMed
Mekker, J. E., Herrmann, P. W., Som, C. W., et al (1992) Clozapine tissue concentrations following an apparent suicidal overdose of Clozaril. Journal of Analytical Toxology, 16, 54–56.CrossRefGoogle Scholar
Merschel, A., Oberlé, J. & Rangoni, F. (1993) La clozapine: effets indésirables: Etude dans les CHS de la région Alsace. Pharmacie Hospitalière Française, 106, 231–242.Google Scholar
Moller, H.-J. (1996) Extrapyramidal side-effects of neuroleptic medication: Focus on risperidone. In Serotonin in Antipsychotic Treatment: Mechanisms and Clinical Practice (eds Kane, J. M., Moller, H-J. & Awouters, F.), pp. 345–356. New York: Marcel Dekker.Google Scholar
Monteiro, W. O., Noshirvani, H. F., Marks, I. M., et al (1987) Anorgasmia from clomipramine in obsessive compulsive disorder: a controlled trial. British Journal of Psychiatry, 151, 107–112.CrossRefGoogle ScholarPubMed
Mortimer, A. & Barnes, T. R. E. (1996) The treatment of schizophrenia: Comparative studies with placebo, haloperidol and risperidone. In Serotonergic Mechanisms in Antipsychotic Treatment (eds Kane, J. M., Moller, H-J. & Awouters, F.), pp. 311–330. New York: Marcel Dekker.Google Scholar
Owens, D. G. C. (1996) Adverse effects of antipsychotic agents: Do newer agents offer advantages? Drugs, 51, 895–930.CrossRefGoogle ScholarPubMed
Peuskens, J. (1995) Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multicentre, double-blind, parallel-group study versus haloperidol. British Journal of Psychiatry, 166, 712–726.CrossRefGoogle ScholarPubMed
Pisciotta, A. V. (1978) Drug-induced agranulocytosis. Drugs, 15, 132–143.CrossRefGoogle ScholarPubMed
Pollack, M. H., Reiter, S. & Hammerness, P. (1992) Genitourinary and sexual adverse effects of psychotropic medication. International Journal of Psychiatry in Medicine, 22, 305–327.CrossRefGoogle ScholarPubMed
Ramirez, L., Silber, C. & Mack, R. (1997) The long-term cardiovascular safety of sertindole (abstract). Schizophrenia Research, 24, 202.CrossRefGoogle Scholar
Royal College of Psychiatrists (1997) The Association Between Antipsychotic Drugs and Sudden Death. Council Report CR57. London: Royal College of Psychiatrists.Google Scholar
Safferman, A. Z., Lieberman, J. A., Pollack, S., et al (1993) Akathisia and clozapine treatment. Schizophrenia Research, 9, 248–249.CrossRefGoogle Scholar
Simpson, G. M. & Angus, J. W. S. (1970) A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica Supplementum, 212, 11–19.CrossRefGoogle ScholarPubMed
Small, J. G., Hirsch, S. R., Arvanitis, L. A., et al and the Seroquel Study Group (1997) Quetiapine in patients with schizophrenia. Archives of General Psychiatry, 54, 549–557.CrossRefGoogle ScholarPubMed
Song, F. (1997) Risperidone in the treatment of schizophrenia: a meta-analysis of randomized, controlled trials. Journal of Psychopharmacology, 11, 65–71.CrossRefGoogle ScholarPubMed
Speller, J. C., Barnes, T. R. E., Curson, D. A., et al (1997) One-year, low-dose neuroleptic study of inpatients with chronic schizophrenia characterised by persistent negative symptoms. Amisulpride v. haloperidol. British Journal of Psychiatry, 171, 564–568.CrossRefGoogle ScholarPubMed
Stanton, J. M. (1995) Weight gain associated with neuroleptic medication: A review. Schizophrenia Bulletin, 21, 463–472.CrossRefGoogle ScholarPubMed
Tamminga, C. A., Mack, R. J., Grannerman, G. R., et al (1997) Sertindole in the treatment of psychosis in schizophrenia: efficacy and safety. International Clinical Psychopharmacology, 12 (suppl. 1), 29–35.CrossRefGoogle ScholarPubMed
Thomas, S. H. L. (1994) Drugs, QT interval abnormalities and ventricular arrhythmias. Adverse Drug Reactions & Toxicological Reviews, 13, 77–102.Google ScholarPubMed
Tollefson, G. D., Tran, P. V., Hamilton, S., et al (1997) Olanzapine versus risperidone in the treatment of psychosis: Preliminary report (abstract). Schizophrenia Research, 24, 191–192.Google Scholar
Tollefson, G. D., Beasley, C. M., Tamura, R. N., et al (1997b) Blind, controlled, long-term study of the comparative incidence of treatment-emergent tardive dyskinesia with olanzapine or haloperidol. American Journal of Psychiatry, 154, 1248–1254.Google ScholarPubMed
Umbricht, D. & Kane, J. M. (1996a) Understanding the relationship between extrapyramidal side-effects and tardive dyskinesia. In Serotonergic Mechanisms in Antipsychotic Treatment (eds Kane, J. M., Moller, H-J. & Awouters, E.), pp. 221–251. New York: Marcel Dekker.Google Scholar
Umbricht, D. & Kane, J. M. (1996b) Medical complications of new antipsychotic drugs. Schizophrenia Bulletin, 22, 475–483.CrossRefGoogle ScholarPubMed
Van Kammen, D. P., McEvoy, J. P., Targum, S. D., et al (1996) A randomized, controlled, dose-ranging trial of sertindole in schizophrenia. Psychopharmacology, 124, 168–175.CrossRefGoogle ScholarPubMed
Van Putten, T. & May, P. R. A. (1978) Akinetic depression in schizophrenia. Archives of General Psychiatry, 35, 1101–1107.CrossRefGoogle ScholarPubMed
Warner, J. P., Harvey, C. & Barnes, T. R. E. (1996) Clozapine and enuresis. International Clinical Psychopharmacology, 9, 207–209.CrossRefGoogle Scholar
Wehnert, A., Hale, A., Kasper, S., et al (1997) EPOS: Increasing our understanding of the treatment of schizophrenia. International Journal of Psychiatry in Clinical Practice, 1, 197–202.CrossRefGoogle ScholarPubMed
Wirshing, W. C., Phelan, C. K., Van Putten, T., et al (1990) Effects of clozapine on treatment-resistant akathisia and concomitant tardive dyskinesia. Journal of Clinical Psychopharmacology, 10, 371–373.CrossRefGoogle ScholarPubMed
Zehender, M., Hohnloser, S. & Just, H. (1991) QT-interval prolonging drugs: mechanisms and clinical relevance of their arrhythmogenic hazards. Cardiovascular Drugs and Therapy, 5, 515–530.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.