Psychiatric Quarterly

, Volume 73, Issue 4, pp 297–311 | Cite as

Safety and Tolerability: How Do Newer Generation “Atypical” Antipsychotics Compare?

  • Rajiv Tandon


Previously, clinicians worked with antipsychotic drugs that almost invariably caused extrapyramidal side effects (EPS) at the dose at which they were clinically effective. By definition, all newer generation atypical antipsychotic agents are significantly better than conventional agents with regard to EPS; i.e., they are clinically effective at doses at which they do not cause EPS. This EPS advantage of atypical antipsychotics translates into several important clinical benefits, including better negative symptom efficacy, lesser dysphoria, less impaired cognition, and a lower risk of tardive dyskinesia; in fact, this “EPS advantage” is the principal basis of the many clinical advantages provided by the class of atypical antipsychotics. While all atypical agents share this “EPS advantage,” there are important differences between these agents with regard to the ease and consistency with which this EPS advantage can be realized. Pharmacologically, different atypical antipsychotics differ; these differences translate into differences in their side effect profiles. Five atypical antipsychotics are currently available: clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. Meaningful differences between these agents with regard to weight gain, sedation, anticholinergic side effects, cardiovascular issues, endocrine side effects, hepatic and sexual issues, will be considered and their clinical implications discussed.

antipsychotics side effects treatment schizophrenia pharmacology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tandon R, Jibson M, Taylor SF, DeQuardo JR: The pathophysiology of positive and negative symptoms in schizophrenia. In: Shriqui C, Nasrallah HA, eds, Contemporary Issues in the Treatment of Schizophrenia., Washington, DC, American Psychiatric Press, 1995, pp. 109-124.Google Scholar
  2. 2.
    Andrew H: Clinical relationship of extrapyramidal symptoms and tardive dyskinesia. Canadian Journal of Psychiatry 39(Suppl 2):76-80, 1994.Google Scholar
  3. 3.
    Casey DE: Motor and mental aspects of EPS. International Clinical Psychopharmacology 10:105-114, 1995.Google Scholar
  4. 4.
    Harvey PD, Keefe RSE: Cognitive impairment in schizophrenia and implications of atypical neuroleptic treatment. CNS Spectrums 2:41-52, 1997.Google Scholar
  5. 5.
    DeQuardo JR, Tandon R: Do atypical antipsychotic medications favorably alter the long-term course of schizophrenia? Journal of Psychiatric Research 32:229-242, 1998.Google Scholar
  6. 6.
    Kane J, Honigfeld G, Singer J, Meltzer HY: Clozapine for the treatment-resistant schizophrenic: A double-blind comparison with chlorpromazine. Archives of General Psychiatry 45:789, 1988.Google Scholar
  7. 7.
    Meltzer HY: Treatment-resistant schizophrenia: The role of clozapine. Current Medical Research and Opinion 14:1-20, 1997.Google Scholar
  8. 8.
    Chakos M, Lieberman J, Hoffman E: Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia. American Journal of Psychiatry 155:914-920, 2001.Google Scholar
  9. 9.
    Jibson MD, Tandon R: New atypical antipsychotic medications. Journal of Psychiatric Research 32:215-228, 1998.Google Scholar
  10. 10.
    Maixner SM, Mellow AM, Tandon R: The efficacy, safety, and tolerability of antipsychotics in the elderly. Journal of Clinical Psychiatry 60(Suppl 8):29-41, 1999.Google Scholar
  11. 11.
    Tandon R: Antipsychotic agents. In: Quitkin FM, Adams DC, Bowden CL, et al., eds., Current Psychotherapeutic Drugs, Washington, DC, American Psychiatric Press, 1998, pp. 120-154.Google Scholar
  12. 12.
    Tandon R, Milner K, Jibson MD: Antipsychotics from theory to practice: Integrating clinical and basic data. Journal of Clinical Psychiatry 60(Suppl 8):21-28, 1999.Google Scholar
  13. 13.
    Jibson MD, Tandon R: Treatment of schizophrenia. Psychiatric Clinics of North America, Annual of Drug Therapy 7:83-113, 2000.Google Scholar
  14. 14.
    Tandon R, Jibson MD: How do atypical antipsychotics compare? Psychoneuroendocrinology, in press.Google Scholar
  15. 15.
    Meltzer HY: Clinical studies on the mechanism of action of clozapine: The dopamine serotonin hypothesis of schizophrenia. Psychopharmacology (Suppl.):S18-S27, 1991.Google Scholar
  16. 16.
    Richelson E: Receptor pharmacology of neuroleptics: Elation to clinical effects. Journal of Clinical Psychiatry 60:5-14, 1999.Google Scholar
  17. 17.
    Nordstrom AL, Farde L: Plasma prolactin and central D2 receptor occupancy in antipsychotic drug-treated patients. Journal of Clinical Psychopharmacology 18:305-310, 1998.Google Scholar
  18. 18.
    Kapur S, Seeman P: Antipsychotic agents differ in how fast they come off the dopamine D2 receptors: Implications for atypical antipsychotic action. Journal of Psychiatry and Neuroscience 25:161-166, 2000.Google Scholar
  19. 19.
    Allison DB, Mentore JL, Heo M: Antipsychotic weight gain:A comprehensive research synthesis. American Journal of Psychiatry 156:1686-1696, 1999.Google Scholar
  20. 20.
    Ganguli R: Weight gain associated with antipsychotic drugs. Journal of Clinical Psychiatry 60:20-24, 1999.Google Scholar
  21. 21.
    Wirshing DA, Wirshing WC, Kysar L: Novel antipsychotics: Comparison of weight gain liabilities. Journal of Clinical Psychiatry 60:358-363, 1999.Google Scholar
  22. 22.
    Welch R, Chue P: Antipsychotic agents and QT changes. Journal of Psychiatry and Neuroscience 25:154-160, 2000.Google Scholar
  23. 23.
    Malik M, Camm AJ: Evaluation of drug-induced QT interval prolongation: Implications for drug approval and labeling. Drug Safety 24:323-351, 2001.Google Scholar
  24. 24.
    Kleinberg DL, Davis JM, de Coster R: Prolactin levels and adverse events in patients treated with risperidone. Journal of Clinical Psychopharmacology 19:57, 1999.Google Scholar
  25. 25.
    Milner K, Tomori O, Florence T, Tandon R: Psychotropic medications and sexual dysfunction. In: P.F. Buckley, ed., Sexuality Among Patients With Serious Mental Illness, American Psychological Association Press, 1998.Google Scholar
  26. 26.
    Tandon R, Taylor SF, DeQuardo JR: The cholinergic system in schizophrenia reconsidered. Neuropsychopharmacology 22:S189-S202, 1999.Google Scholar
  27. 27.
    Tandon R: Cholinergic aspects of schizophrenia. British Journal of Psychiatry 173 (Suppl. 37):7-11, 1999.Google Scholar

Copyright information

© Human Sciences Press, Inc. 2002

Authors and Affiliations

  • Rajiv Tandon
    • 1
  1. 1.University of Michigan Medical CenterAnn Arbor

Personalised recommendations