As this chapter has attempted to illustrate, the data sources, capacities and roles for psychopharmacoepi- demiology have all expanded. Given the centrality of psychotropic medications in the current treatment of mental disorders, psychopharmacoepidemiologic studies remain essential to ensuring that such use is safe, effective and cost-beneficial. If history is any guide, investigators can anticipate a steady stream of new hypotheses concerning unanticipated effects of both established and new psychotropic medica- tions. Likewise, tracking how psychiatric medica- tions are used, by whom, and the outcomes from use is imperative to identify unmet needs for effec- tive treatment and new intervention targets. And as constraints on health care resources and reliance on psychotropic medications increase, so too will the need for evaluations of the relative value obtained from psychopharmacologic regimens. Psychophar- macoepidemiologists should anticipate a growing need to evaluate a wide range of interventions that could have important impacts on patients’ use of psy- chotropic medications and their clinical outcomes.
To meet all of these future demands, advances will also be needed in the data, methods and resources available for conducting psychopharmacoepidemio- logic studies. Recognising the need for new data sources and analyses, the Food and Drug Admin- istration Amendments Act (FDAAA) of 2007 calls for a marked expansion in the current system of monitoring the performance of approved medica- tions [63]. Part of this new capacity for conducting active surveillance will include the Sentinel Initiative, a national electronic system of linked healthcare datasources for monitoring medical product safety.
The FDAAA legislation sets as targets that data on 25 million patients and 100 million patients be acces- sible by 1 July 2010 and 2012, respectively. Parallel methodologic and analytic developments will also be needed to ensure that queries of these expanded data- sources can be implemented and yield valid answers.
Another important potential future role that psy- chopharmacoepidemiology could play is in facilitat- ing health care reform. Experts and opinion leaders have emphasised the need for rigorous data on the comparative effectiveness of medical treatments to both inform practice decisions and improve health
care quality, outcomes and value [38]. Bodies such as the Congressional Budget Office and Institute of Medicine have joined in these calls for new research shedding light on the relative benefits, risks and costs of medical therapies [64, 65] and US Congres- sional legislation [66] has been introduced that would establish an independent, non-governmental Health- care Comparative Effectiveness Research Institute.
Generating some of this data will certainly involve conducting large comparative effectiveness trials.
However the costs, time required and other chal- lenges of conducting large practical clinical trials make it clear that additional means will also be needed. As covered in this chapter, the range of data sources, study methods and analytic approaches now available to psychopharmacoepidemiologists leave them well poised to answer questions regarding the comparative effectiveness, safety and value of psy- chotropic medications in the future.
Acknowledgements
The views and opinions expressed are those of the authors and should not be construed to represent the views of any sponsoring organisation, agencies or the US Government.
The views expressed do not necessarily represent the views of the National Institute of Mental Health, the National Institutes of Health, the Department of Health and Human Services or the United States government.
References
[1] Schatzberg, A. and Nemeroff, C. (2006) Essentials of Clinical Psychopharmacology, 2nd edn, American Psychiatric Publishing, Inc.
[2] Leucht, S., Pitschel-Walz, G., Abraham, D. et al.
(1999) Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperi- done, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr. Res., 35, 51–68.
[3] Wang, P.S., West, J.C., Tanielian, T. et al. (2000) Recent patterns and predictors of antipsychotic medi- cation regimens used to treat schizophrenia and other psychotic disorders.Schizophr. Bull.,26, 451–457.
[4] Lieberman, J.A., Stroup, T.S., McEvoy, J.P. et al.
(2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.N. Engl. J. Med.,353, 1209–1223.
[5] Honer, W.G., Thornton, A.E., Chen, E.Y.et al. (2006) Clozapine alone versus clozapine and risperidone with refractory schizophrenia.N. Engl. J. Med.,354, 472–482.
[6] U.S. Congressional Budget Office (2007) Research on the Comparative Effectiveness of Medical Treat- ments: Issues and Options for an Expanded Federal Role, Congressional Budget Office, Washington, DC.
December.
[7] Polinski, J.M., Wang, P.S. and Fischer, M.A. (2007) Medicaid’s prior authorization program and access to atypical antipsychotic medications.Health Aff., 26, 750–760.
[8] Fischer, M.A., Servi, A.D., Polinski, J.M.et al. (2007) Restrictions on antidepressant medications for chil- dren: a review of medicaid policy. Psychiatr. Serv., 58, 135–138.
[9] Wang, P.S., Aguilar-Gaxiola, S., Alonso, J., et al.
The WHO World Mental Health Survey Consor- tium (2007) Worldwide use of mental health services for anxiety, mood, and substance disorders: results from 17 countries in the WHO World Mental Health (WMH) surveys.Lancet,370, 841–850.
[10] Wang, P.S., Demler, O., Olfson, M. et al. (2006) Changing profiles of service sectors used for mental health care in the United States.Am. J. Psychiatry, 163, 1187–1198.
[11] Kessler, R.C., Demler, O., Frank, R.G.et al. (2005) Prevalence and treatment of mental disorders, 1990 to 2003.N. Engl. J. Med.,352, 2515–2523.
[12] Kessler, R.C., Berglund, P., Borges, G.et al. (2005) Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990–1992 to 2001–
2003.J. Am. Med. Assoc.,293, 2487–2495.
[13] Strom, B.L. (1994) What is pharmacoepidemiology?
inPharmacoepidemiology, 2nd edn (ed B.L. Strom), John Wiley & Sons, Inc., New York, pp. 3–13.
[14] McBride, W.G. (1961) Thalidomide and congenital abnormalities.Lancet,ii, 1358.
[15] Wilholm, B.E., Onsson, S., Moore, N.,et al. (1994) Spontaneous reporting system outside the United States, inPharmacoepidemiology, 2nd edn (ed. B.L.
Strom), John Wiley & Sons, Inc., New York, pp. 139–155.
[16] Baum, C., Kweder, S.L. and Anello, C. (1994) The spontaneous reporting system in the United States, inPharmacoepidemiology, 2nd edn (ed B.L. Strom), John Wiley & Sons, Inc., New York, pp. 125–137.
[17] Mattison, N. and Richard, B.W. (1987) Postapproval research requested by the FDA at the time of NCE approval, 1970–1984.Drug Inf. J.,21, 309–329.
[18] Cole, J.O. (1988) Where are those new antidepres- sants we were promised?Arch. Gen. Psychiatry,45, 193–197.
[19] Morris, H.H. and Estes, M. (1987) Traveler’s amnesia:
transient global amnesia secondary to triazolam. J.
Am. Med. Assoc.,258, 945–946.
[20] Maclure, M. (1991) The case-crossover design: a method for studying transient effects of the risk of acute events.Am. J. Epidemiol.,113, 144–153.
[21] Suissa, S. (1995) The case-time-control design.Epi- demiology,6, 248–253.
[22] Wang, P.S., Schneeweiss, S., Glynn, R.J.et al. (2004) Use of the case-crossover design to study prolonged drug exposures and insidious outcomes. Ann. Epi- demiol.,14, 296–303.
[23] Schneeweiss, S., Maclure, M., Walker, A.M. et al.
(2001) On the evaluation of drug benefits policy changes with longitudinal claims data: the policy maker’s versus the clinician’s perspective.Health Pol- icy,55, 97–109.
[24] Gold, M.R., Siegel, J.E. and Russell, L.B. (1996) Cost-Effectiveness in Health and Medicine, Oxford University Press, New York.
[25] Eddy, D.M. (2007) Linking electronic medical records to large-scale simulation models: can we put rapid learning on turbo?Health Aff.,26, w125–w136.
[26] Rosenbaum, P.R. and Rubin, D.B. (1983) Assessing sensitivity to an unobserved binary covariate in an observational study with binary outcome.J. R. Stat.
Soc. B,45, 212–218.
[27] Schneeweiss, S. (2007) Developments in post- marketing comparative effectiveness research. Clin.
Pharmacol. Ther.,82, 143–156.
[28] Seeger, J.D., Kurth, T. and Walker, A.M. (2007) Use of propensity score technique to account for exposure related covariates.Med. Care,45, S143–S148.
[29] Schneeweiss, S., Patrick, A.R., St ¨urmer, T. et al.
(2007) Increasing levels of restriction in pharmacoepi- demiologic database studies of elderly and compar- ison with randomized trial results. Med. Care, 45, S131–S142.
[30] St ¨urmer, T., Glynn, R.J., Rothman, K.J.et al. (2007) Adjustments for unmeasured confounders in phar- macoepidemiologic database studies using external information.Med. Care,45, S158–S165.
[31] Brookhart, M.A., Rassen, J.A., Wang, P.S. et al.
(2007) Evaluating the validity of an instrumental variable study of neuroleptics: can between-physician differences in prescribing patterns be used to estimate treatment effects?Med. Care,45, S116–S122.
[32] Strom, B.L. (1994b) How should one perform phar- macoepidemiology studies?: Choosing among the available alternatives, inPharmacoepidemiology, 2nd edn (ed B.L. Strom), John Wiley & Sons, Inc., New York, pp. 337–350.
[33] Bright, R.A., Avorn, J. and Everitt, D.E. (1989) Med- icaid data as a resource for epidemiologic studies:
strengths and limitations. J. Clin. Epidimiol., 42, 937–945.
[34] Lessler, J.T. and Harris, B.S.H. (1984) Medicaid Data as a Source for Postmarketing Surveillance Infor- mation, Final Report, Research Triangle Institute, Research Triangle Park, NC.
[35] Roos, L.L., Sharp, S.M. and Cohen, M.M. (1991) Comparing clinical information with claims data:
some similarities and differences.J. Clin. Epidemiol., 44, 881–888.
[36] Trivedi, M.H., Fava, M., Wisniewski, S.R. et al.
(2006) Medication augmentation after the failure of SSRIs for depression. N. Engl. J. Med., 354, 1243–1252.
[37] Sachs, G.S., Nierenberg, A.A., Calabrese, J.R.et al.
(2007) Effectiveness of adjunctive antidepressant treatment for bipolar depression. N. Engl. J. Med., 356, 1711–1722.
[38] March, J.S., Silva, S.G., Compton, S.et al. (2005) The case for practical clinical trials in psychiatry.Am. J.
Psychiatry,162, 836–846.
[39] McGrath, P.J., Kahn, A.Y., Trivedi, M.H.et al. (2008) Response to a selective serotonin reuptake inhibitor (citalopram) in major depressive disorder with melan- cholic features: a STAR*D report.J. Clin. Psychiatry, 69, 1847–1855.
[40] Dennehy, E.B., Bauer, M.S., Perlis, R.H.et al. (2007) Concordance with treatment guidelines for bipo- lar disorder: data from the Systematic Treatment Enhancement Program for Bipolar Disorder. Psy- chopharmacol. Bull.,40, 72–84.
[41] US Food and Drug Administration (2004) Center for Drug Evaluation and Research: FDA Public Health Advisory: Worsening Depression and Suicidality in Patients Being Treated with Antidepressant Medica- tions, March 22, 2004. Available at: http://www.fda.
gov/Drugs/DrugSafety/PostmarketDrugSafetyInforma tionforPatientsandProviders/DrugSafetyInformation forHeathcareProfessionals/PublicHealthAdvisories/
ucm161696.htm (accessed 29 November 2010).
[42] US Food and Drug Administration (2004) Sum- mary Minutes of the September 13–14, 2004 Cen- ter for Drug Evaluation and Research Pharma- chopharmacologic Drugs Advisory Committee and the FDA Pediatric Advisory Committee. Available at: http://www.fda.gov/ohrms/dockets/ac/04/minutes/
2004-4065M1_Final.htm. (accessed 27 September 2010).
[43] Jick, H., Kaye, J. and Jick, S. (2004) Antidepressants and the risk of suicidal behaviors.J. Am. Med. Assoc., 292, 338–343.
[44] Martinez, C., Rietbrock, S., Wise, L. et al. (2005) Antidepressant treatment and the risk of fatal and
non-fatal self-harm in the first episode of depression.
Br. Med. J.,330, 389.
[45] Simon, G.E., Savarino, J., Operskalski, B.et al. (2006) Suicide risk during antidepressant treatment.Am. J.
Psychiatry,163, 41–47.
[46] Olfson, M. and Marcus, S.C. (2008) A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes.J.
Clin. Psychiatry,69, 425–432.
[47] US Food and Drug Administration (2006) Overview for December 13 Meeting of Psychopharmaco- logic Drugs Advisory Committee (PDAC). Available at: http://www.fda.gov/ohrms/dockets/ac/06/briefing/
2006-4272b1-01-FDA.pdf. (accessed 27 September 2010).
[48] US Food and Drug Administration (2005) FDA Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances.
Available at: http://www.fda.gov/Drugs/DrugSafety/
PostmarketDrugSafetyInformationforPatientsandPro viders/DrugSafetyInformationforHeathcareProfession als/PublicHealthAdvisories/ucm053171.htm (accessed 29 November 2010).
[49] Wang, P.S., Schneeweiss, S., Avorn, J.et al. (2005) Risk of death in elderly users of conventional vs.
atypical antipsychotic medications.N. Engl. J. Med., 353, 2335–2341.
[50] Schneeweiss, S., Setoguchi, S., Brookhart, A.et al.
(2007) Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. Can. Med. Assoc. J., 176, 627–632.
[51] Gill, S.S., Bronskill, S.E., Normand, S.L.et al. (2007) Antipsychotic drug use and mortality in older adults with dementia.Ann. Intern. Med.,146, 775–786.
[52] US Food and Drug Administration (2008) FDA alert.
Cent. Drug Eval. Res., Available at: http://www.fda.
gov/Safety/MedWatch/SafetyInformation/SafetyAlerts forHumanMedicalProducts/ucm110212.htm (accessed 29 November 2010).
[53] Collins, J.C. and McFarland, B.H. (2008) Divalproex, lithium and suicide among Medicaid patients with bipolar disorders.J. Affect Disord.,107, 23–28.
[54] Olfson, M., Blanco, C., Liu, L.et al. (2006) National trends in outpatient treatment of children and adoles- cents with antipsychotic drugs.Arch. Gen. Psychiatry, 63, 679–685.
[55] Moreno, C., Laje, G., Blanco, C.et al. (2007) National trends in the outpatient diagnosis and treatment of bipolar disorder in youth.Arch. Gen. Psychiatry,64, 1032–1039.
[56] Wang, P.S., Lane, M., Olfson, M.et al. (2005) Twelve- month use of mental health services in the United States.Arch. Gen. Psychiatry,62, 629–640.
[57] Wang, P.S., Schneeweiss, S., Brookhart, M.A.et al.
(2005) Suboptimal antidepressant use in the elderly.
J. Clin. Psychopharmacol.,25, 118–126.
[58] Simon, G.E., Katon, W.J., VonKorff, M.et al. (2001a) Cost-effectiveness of a collaborative care program for primary care patients with persistent depression.Am.
J. Psychiatry,158, 1638–1644.
[59] Simon, G.E., Manning, W.G., Katzelnick, D.J.et al.
(2001) Cost-effectiveness of systematic depression treatment for high utilizers of general medical care.
Arch Gen. Psychiatry,58, 181–187.
[60] Schoenbaum, M., Unutzer, J., Sherbourne, C.et al.
(2001) Cost-effectiveness of practice-initiated quality improvement for depression: results of a randomized controlled trial.J. Am. Med. Assoc.,286, 1325–1330.
[61] Wang, P.S., Patrick, A.R., Avorn, J.et al. (2006) The costs and benefits of enhanced depression care to employers.Arch. Gen. Psychiatry,63, 1345–1353.
[62] Wang, P.S., Patrick, A.R., Dormuth, C.et al. (2008) The impact of cost-sharing on antidepressant use among older adults in British Columbia.Psychiatr.
Serv.,59, 377–383.
[63] US Food and Drug Administration Amendments Act of 2007. Public Law 110-85, September (2007). Title IX, Section 905.
[64] Clancy, C.M. (2006) Getting to ‘smart’ health care.
Health Aff.,25(6), w589–w592.
[65] Wilensky, G.R. (2006) Developing a center for com- parative effectiveness information. Health Aff., 25, w572–w585.
[66] US Senate (2008) Comparative Effectiveness Research Act of 2008. United States Senate Bill S. 3408, July 31.
11 Peering into the future
of psychiatric epidemiology
Michaeline Bresnahan,
1,2Ezra Susser,
1,2Dana March
1,2and Bruce Link
1,21Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA
2New York State Psychiatric Institute, NY, USA