Skip to main content Accessibility help

Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics

  • Robert A. Rosenheck (a1)



Second-generation antipsychotics may have few advantages over older, cheaper drugs, except for possibly reduced risk of tardive dyskinesia.


To evaluate the cost-effectiveness of second-generation antipsychotics with regard to reducing tardive dyskinesia.


Literature was reviewed on risk of tardive dyskinesia with second-generation antipsychotics; on severity duration and impairment of tardive dyskinesia; and on the relationship of this disorder to quality of life and quality-adjusted life-years (QALYs). Diverse cost and benefit assumptions and of 1-year and 5-year planning horizons were examined in a deterministic sensitivity analysis.


Estimating 0.143 QALYs lost per case of severe tardive dyskinesia, 1-year cost-effectiveness estimates for second-generation antipsychotics ranged from $185 000 ($370 000) to $850 000 ($1.7 million) per QALY, and 5-year cumulative estimates ranged from $74 000 ($ 149 000) to $342 000 ($683 000) per QALY, all above the conventional policy threshold of $25 000 ($50 000).


Reduction of tardive dyskinesia with second-generation antipsychotics appears unlikely to meet standards for cost-effectiveness.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics
      Available formats


Corresponding author

Dr R. Rosenheck, Northeast Program Evaluation Center (182), VA Connecticut Health Care System, 950 Campbell Avenue, West Haven, CT 06516, USA. Tel: +1 203 937 3850; fax: + 1 203 937 3433; e-mail: Robert.Rosenheck@Yale.Edu


Hide All

Declaration of interest

R.A.R. has received research support from and/or been a consultant to Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmith Kline, Janssen Pharmaceutica and Wyeth.



Hide All
American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, et al (2004) Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care, 27, 596601.
Arato, M., O'Connor, R. & Meitzer, H. Y. (2002) A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) Study. International Journal of Clinical Psychopharmacology, 17, 207215.
Basil, B., Mathews, M., Adetunji, B., et al (2001) The CATIE Study. American Journal of Psychiatry, 163, 555.
Beasley, C. M., Dellva, M. A., Tamura, R. N., et al (1999) Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol. British Journal of Psychiatry, 174, 2330.
Bekelman, J. E., Li, Y. & Gross, C. P. (2003) Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA, 289, 454465.
Briggs, A. (2005) Probabilistic analysis of cost-effectiveness models: statistical representation of parameter uncertainty. Value in Health, 8, 12.
Browne, S., Roe, M., Lane, A., et al (1996) Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia. Acta Psychiatrica Scandinavica, 94, 118124.
Casey, D. E. (2001) Implications of the CATIE Trial on Treatment: extrapyramidal symptoms. CNS Spectrums, 11 (suppl. 7), 2531.
Chakos, M. H., Alvir, J. M., Woerner, M. G., et al (1996) Incidence and correlates of tardive dyskinesia in first episode of schizophrenia. Archives of General Psychiatry, 53, 313319.
Chouinard, G., Annable, L., Mercier, P., et al (1986) A five year follow-up study of tardive dyskinesia. Psychopharmacology Bulletin, 22, 259263.
Claxton, K., Sculpher, M., McCabe, C., et al (2005) Probabilistic sensitivity analysis for NICE technology assessment: not an optional extra. Health Economics, 14, 339347.
Correll, C. U., Leucht, S. & Kane, J. M. (2004) Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. American Journal of Psychiatry, 161, 414425.
Csernansky, J. G., Mahmoud, R. & Brenner, R. (2002) A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. New England Journal of Medicine, 346, 1622.
Daniels, N. & Sabin, J. (2002) Setting Limits Fairly: Can We Learn to Share Medical Resources? Oxford University Press.
Davis, J. M. (2006) The choice of drugs for schizophrenia (letter). New England Journal of Medicine, 354, 518520.
Davis, J. M., Chen, N. & Glick, I. D. (2003) A metaanalysis of the efficacy of second-generation antipsychotics. Archives of General Psychiatry, 60, 553564.
Duggan, M. (2005) Do new prescription drugs pay for themselves? The case of second-generation antipsychotics. Journal of Health Economics, 24, 131.
Fenton, W. (2000) Prevalence of spontaneous dyskinesias in schizophrenia. Journal of Clinical Psychiatry, 61 (suppl. 4), 1014.
Gardos, G. & Cole, J. O. (1983) Tardive dyskinesia and anticholinergic drugs. American Journal of Psychiatry, 140, 200202.
Geddes, J. R., Freemantle, N., Harrison, P., et al (2000) Atypical antipsychotics in the treatment of schizophrenia – systematic overview and metaregression analysis. BMJ, 321, 13711376.
Glazer, W. M., Morgenstern, H. & Doucette, J. T. (1993) Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications. Journal of Clinical Psychiatry, 54, 133139.
Gold, M. R., Siegel, J. E., Russell, L. B., et al (1996) Cost Effectiveness in Health and Medicine. Oxford University Press.
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). National Institute for Mental Health.
Halliday, J., Farrington, S., Macdonald, S., et al (2002) Nithsdale Schizophrenia Surveys 23: movement disorders: 20-year review. British Journal of Psychiatry, 181, 422427.
Hamilton, S. H., Revicki, D. A., Edgell, E. T., et al (1999) Clinical and economic outcomes of olanzapine compared with haloperidol for schizophrenia – results from a randomized clinical trial. Pharmacoeconomics, 15, 469480.
Heinrichs, D. W., Hanlon, E. T. & Carpenter, W. T. (1984) The quality of life scale: an instrument for rating the schizophrenic deficit syndrome. Schizophrenia Bulletin, 10, 388398.
Heres, S., Davis, J., Maino, K., et al (2006) Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. American Journal of Psychiatry, 163, 185194.
Hugenholtz, G. W. K., Heerdink, E. R., Stolker, J. J., et al (2006) Haloperidol dose when used as active comparator in randomized controlled trials with atypical antipsychotics in schizophrenia: comparison with officially recommended doses. Journal of Clinical Psychiatry, 67, 897903.
Jeste, D. V., Caliguri, M. P., Paulsen, J. S., et al (1995) Risk of tardive dyskinesia in older patients: a prospective longitudinal study of 266 outpatients. Archives of General Psychiatry, 52, 756765.
Jones, P. B., Barnes, T. R. E., Davies, L., et al (2006) Randomized controlled trial of the effect on quality of life of second-vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASSI). Archives of General Psychiatry, 63, 10791087.
Kane, J. M. (2006) Tardive dyskinesia circa 2006. American Journal of Psychiatry, 163, 13161318.
Kane, J. M., Woerner, M., Weinhold, P., et al (1984) Incidence of tardive dyskinesia: five-year data from a prospective study. Psychopharmacology Bulletin, 20, 387389.
Kay, S. R., Fiszbein, A. & Opler, L. (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261276.
Kinon, B. J., Jeste, D. V., Kollack-Walker, S., et al (2004) Olanzapine treatment for tardive dyskinesia in schizophrenia patients: a prospective clinical trial with patients randomized to blinded dose reduction periods. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28, 985996.
Lee, P. E., Sykora, K., Gill, S. S., et al (2005) Antipsychotic medication and drug-induced movement disorder: a population-based cohort study in older adults. Journal of the American Geriatrics Society, 53, 13741379.
Lenert, L., Sturly, A. P. & Rupnow, M. (2003) Toward improved methods for measurement of utility: automated repair of errors in utility elicitations. Medical Decision-Making, 23, 19.
Lenert, L., Sturley, A. P., Rapaport, M. H., et al (2004) Public preferences for health states with schizophrenia and a mapping function to estimate utilities from positive and negative syndrome scale scores. Schizophrenia Research, 71, 155165.
Leslie, D. & Rosenheck, R. A. (2005) Pharmacotherapy and healthcare costs among patients with schizophrenia and newly diagnosed diabetes. Psychiatric Services, 56, 803810.
Leucht, S., Wahlbeck, K., Hamann, J., et al (2003) New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet, 361, 15811589.
Lexchin, J., Bero, L. A., Djulbegovic, B., et al (2003) Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ, 326, 11671170.
Lieberman, J. A., Stroup, S., McEvoy, J., et al (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: primary efficacy and safety outcomes of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. New England Journal of Medicine, 353, 12091223.
Mohr, P. E., Cheng, C. M., Claxton, K., et al (2004) The heterogeneity of schizophrenia in disease states. Schizophrenia Research, 71, 8395.
Montgomery, J. H., Byerly, M., Carmody, T., et al (2004) An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia. Controlled Clinical Trials, 25, 598612.
Neumann, P. J. (2005) Using Cost-Effectiveness Analysis to Improve Health Care. Oxford University Press.
Rochon, P. A., Stukel, T. A., Sykora, K., et al (2005) Atypical antipsychotics and parkinsonism. Archives of Internal Medicine, 165, 18821888.
Rosack, J. (2006) Drug firms vie to develop more effective antipsychotics. Psychiatric News, 41, 2529.
Rosenheck, R. A. (2005) Effectiveness versus efficacy of second-generation antipsychotics: haloperidol without anticholinergics as a comparator. Psychiatric ervices, 56, 8592.
Rosenheck, R. A., Cramer, J., Xu, W., et al (1997) A comparison of clozapine and haloperidol in the treatment of hospitalized patients with refractory schizophrenia. New England Journal of Medicine, 337, 809815.
Rosenheck, R. A., Perlick, D., Bingham, S., et al (2003) Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia. JAMA, 290, 26932702.
Rosenheck, R. A., Leslie, D., Sindelar, J., et al (2006) Cost-effectiveness of second generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia. American Journal of Psychiatry, 163, 20802089.
Schneider, L. S., Tariot, P. N., Dagerman, K. S., et al (2006) Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. New England Journal of Medicine, 355, 15251538.
Schooler, N. R. & Kane, J. M. (1982) Research diagnosis for tardive dyskinesia. Archives of General Psychiatry, 39, 486487.
Schooler, N., Rabinowitz, J., Davidson, M., et al (2005) Early Psychosis Global Working Group. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. American Journal of Psychiatry, 162, 947953.
Swartz, M., Perkins, D., Stroup, S., et al (2007) Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. American Journal of Psychiatry, 164, 428436.
Tamminga, C. & Woerner, M. G. (2002) Clinical course and cellular pathology of tardive dyskinesia. In Neuropsychopharmacology: The Fifth Generation of Progress (eds K. L. Davis, D. S. Charney, J. T. Coyle, et al), pp. 18311842. Baltimore, MD: Lippincott/Williams & Wilkins.
Tamminga, C. A., Thaker, G. K., Moran, M., et al (1994) Clozapine in tardive dyskinesia: observations from human and animal model studies. Journal of Clinical Psychiatry, 55 (suppl. B), 102106.
Tandon, R. & Constantine (2006) Avoiding EPS is key to realizing ‘atypical benefits'. Current Psychiatry, 5, 3545.
Tarsy, D. & Baldessarini, R. J. (2006) Epidemiology of tardive dyskinesia: is risk declining with modern antipsychotics?. Movement Disorders, 21, 589598.
Tenback, D. E., van Harten, P. N., Slooff, C. J., et al (2006) Evidence that early extrapyramidal symptoms predict later tardive dyskinesia: a prospective analysis of 10 000 patients in the European Schizophrenia Outpatient Health Outcomes (SOHO) study. American Journal of Psychiatry, 163, 14381440.
Ubel, P. A. (2000) Pricing Life: Why It's Time for Health Care Rationing. MIT Press.
Woods, S. W. (1999) Olanzapine and tardive dyskinesia. British Journal of Psychiatry, 175, 391392.


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics

  • Robert A. Rosenheck (a1)
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *