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Metabolic and Endocrine Disturbances in Psychiatric Disorders: A Multidisciplinary Approach to Appropriate Atypical Antipsychotic Utilization

Published online by Cambridge University Press:  07 November 2014

Prakash S. Masand ,
Larry Culpepper ,
David Henderson ,
Scott Lee ,
Kimberly Littrell ,
John W. Newcomer  and
Natalie Rasgon
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Abstract

Patients with psychiatric disorders have an increased rate of cardiovascular morbidity and mortality compared with the general population. Metabolic issues such as weight gain, dyslipidemia, diabetes mellitus, diabetic ketoacidosis, and pancreatitis have been reported with the use of antipsychotic agents. Although atypical antipsychotics have not been linked directly to the development of metabolic syndrome, these medications have been shown to increase risk factors that can lead to metabolic and endocrine disturbances. Therefore, clinicians should provide ongoing monitoring for patients who are being treated for psychiatric disorders with these agents. According to the 2004 Consensus Report on Antipsychotics, screening measures should include baseline and follow-up monitoring of personal/family histories, weight (body mass index), waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile.

Type
Clinical Information Monograph
Information
CNS Spectrums , Volume 10 , Issue 10 , October 2005 , pp. 819a - 819l
Copyright
Copyright © Cambridge University Press 2005

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References

1.Ten, S, Maclaren, N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004;89(6):2526–2539.Google Scholar
2.Bonow, RO, Gheorghiade, M. The diabetes epidemic: a national and global crisis. Am J Med. 2004;116(suppl 5A):2S–10S.Google Scholar
3.Hu, FB, Stampfer, MJ, Haffner, SM, Solomon, CG, Willen, WC, Manson, JE. Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes. Diabetes Care. 2002;25(7):1129–1134.Google Scholar
4.Haffner, SM, Lento, S, Ronnemaa, T, Pyorala, K, Laakso, M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229–234.CrossRefGoogle ScholarPubMed
5.Reaven, GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–1607.Google Scholar
6.Schinner, S, Scherbaum, WA, Bornstein, SR, Barthel, A. Molecular mechanisms of insulin resistance. Diabet Med. 2005;22(6):674–682.CrossRefGoogle ScholarPubMed
7.The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20:1183–1197.CrossRefGoogle Scholar
8.World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva: World Health Organization; 1999.Google Scholar
9.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005;28(suppl 1):S37–42.CrossRefGoogle Scholar
10.Orchard, TJ, Temprosa, M, Goldberg, R, et al.The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005;142(8):611–619.Google Scholar
11.Grundy, SM, Cleeman, JI, Daniels, SR. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;09 12: [Epub ahead of print].Google Scholar
12.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Trearment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421.Google Scholar
13.Goodpaster, BH, Krishnaswami, S, Harris, TB, et al.Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med. 2005;165(7):777–783.CrossRefGoogle ScholarPubMed
14.Park, YW, Zhu, S, Palaniappan, L, Heshka, S, Carnechon, MR, Heymsfield, SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Intern Med. 2003;163(4):427–436.Google Scholar
15.Nasrallah, HA, Newcomer, JW. Atypical antipsychotics and metabolic dysregulation: evaluating the risk/benefit equation and improving the standard of care. J Clin Psychopharmacol. 2004;24:S7–S14.CrossRefGoogle ScholarPubMed
16.American Diabetes Association, American Psychiattic Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care. 2004;27:596–601.Google Scholar
17.Sokal, J, Messias, E, Dickerson, FB, et al.Comorbidity of medical illnesses among adults with serious mental illness who are receiving community psychiatric services. J Nerv Ment Dis. 2004;192:421–427.Google Scholar
18.Einhorn, D, Reaven, GM, Cobin, RH, et al.American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. 2003;9:237–252.Google Scholar
19.Harris, EC, Barraclough, B. Excess mortality of mental disorder. Br J Psychiatry. 1998;173:11–53.Google Scholar
20.Newman, SC, Bland, RC. Mortality in a cohort of patients with schizophrenia: a record linkage study. Can J Psychiatry. 1991;36(4):239–245.CrossRefGoogle Scholar
21.Osby, U, Correia, N, Brandt, L, Ekbom, A, Sparen, P. Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Schizophr Res. 2000;45(1–2):21–28.Google Scholar
22.Osby, U, Correia, N, Brandt, L, Ekbom, A, Sparen, P. Time trends in schizophrenia mortality in Stockholm county, Sweden: cohort study. BMJ. 2000;321(7259):483–484.Google Scholar
23.Osby, U, Brandt, L, Correia, N, Ekbom, A, Sparen, P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58(9):844–850.Google Scholar
24.Goff, DC, Cather, C, Evins, AE, et al.Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists. J Clin Psychiatry. 2005;66:183–194.CrossRefGoogle ScholarPubMed
25.Enger, C, Weatherby, L, Reynolds, RF, Glasser, DB, Walker, AM. Serious cardiovascular events and mortality among patients with schizophrenia. J Nerv Ment Dis. 2004;192(1):19–27.CrossRefGoogle ScholarPubMed
26.Brown, S, Birtwistle, J, Roe, L, Thompson, C. The unhealthy lifestyle of people with schizophrenia. Psychol Med. 1999;29(3):697–701.Google Scholar
27.Dixon, L, Postrado, L, Delahanty, J, Fischer, PJ, Lehman, A. The association of medical comorbidity in schizophrenia with poor physical and mental health. J Nerv Ment Dis. 1999;187(8):496–502.CrossRefGoogle ScholarPubMed
28.Holmberg, SK, Kane, C. Health and self-care practices of persons with schizophrenia. Psychiatr Serv. 1999;50(6):827–829.Google Scholar
29.Lyons, MJ, Bar, JL, Kremen, WS, Toomey, R, et al.Nicotine and familial vulnerability to schizophrenia: a discordant twin study. J Abnorm Psychol. 2002;111(4):687–693.Google Scholar
30.Druss, BG, Bradford, WD, Rosenheck, RA, Radford, MJ, Krumholz, HM. Quality of medical care and excess mortality in older patients with mental disorders. Arch Gen Psychiatry. 2001;58(6):565–572.Google Scholar
31.Koro, CE, Fedder, DO, L'Italien, GJ, et al.Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-conttol study. BMJ. 2002;325:243.CrossRefGoogle ScholarPubMed
32.Gianfrancesco, FD, Grogg, AL, Mahmoud, RA, Wang, RH, Nasrallah, HA. Differential effects of risperidone, olanzapine, clozapine, and convenrional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002;63:920–930.Google Scholar
33.Gianfrancesco, F, White, R, Wang, RH, Nasrallah, HA. Antipsychotic-induced type 2 diabetes: evidence from a large health plan database. J Clin Psychopharmacol. 2003;23:328–335.Google Scholar
34.Sernyak, MJ, Leslie, DL, Alarcon, RD, Losonczy, MF, Rosenheck, R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002;159:561–566.Google Scholar
35.Lund, BC, Perry, PJ, Brooks, JM, Arndt, S. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry. 2001;58:1172–1176.Google Scholar
36.Wang, PS, Glynn, RJ, Ganz, DA, Schneeweiss, S, Levin, R, Avorn, J. Clozapine use and risk of diabetes mellitus. J Clin Psychopharmacol. 2002;22:236–243.Google Scholar
37.Fuller, MA, Shermock, KM, Secic, M, Grogg, AL. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2003;23:1037–1043.CrossRefGoogle ScholarPubMed
38.Caro, JJ, Ward, A, Levinton, C, Robinson, K. The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis. J Clin Psychiatry. 2002;63:1135–1139.Google Scholar
39.Newcomer, JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19:(suppl 1):1–93.Google Scholar
40.Buse, JB, Cavazzoni, P, Hornbuckle, K, Hutchins, D, Breier, A, Jovanovic, L. A retrospective cohott study of diabetes mellitus and antipsychotic treatment in the United States. J Clin Epidemiol. 2003;56(2):164–170.Google Scholar
41.Ability (package insert). Otsuka Pharmaceutical Co, Ltd (Tokyo) and Bristol-Myers Squibb (Princeton, NJ); 2002.Google Scholar
42.Geodon (package insert). New York, NY: Pfizer, Inc.; 2002.Google Scholar
43.Simpson, GM, Glick, ID, Weiden, PJ, Romano, SJ, Siu, CO. Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Am J Psychiatry. 2004;161(10):1837–1847.Google Scholar
44.Baptista, T, Kin, NM, Beaulieu, S, de Baptista, EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 2002;35(6):205–219.Google Scholar
45.Allison, DB, Mentore, JL, Heo, M, et al.Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1000; 156:1686–1696.Google Scholar
46.Leiberman, JA, Stroup, TS, McEvoy, JT, et al.Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New Engl J Med. 2005; 09 19, 2005 (10.1056/NEJMoa05 1688).Google Scholar
47.Weiden, PJ, Mackwell, JA, McDonnelll, DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res. 2004;66:51–57.Google Scholar
48.Ratzoni, G, Gothelf, D, Brand-Gothelf, A, et al.Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. J Am Acad Child Adolesc Psychiatry. 2002;41(3):337–343.Google Scholar
49.Delbello, MP, Schwiers, ML, Rosenberg, HL, Strakowski, SM. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2002;41(10):1216–1223.CrossRefGoogle ScholarPubMed
50.Tohen, M, Chengappa, KN, Suppes, T, et al.Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproare or lithium monotherapy. Arch Gen Psychiatry. 2002;59(1):62–69.Google Scholar
51.Lindenmayer, JP, Czobor, P, Volavka, J, et al.Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical ot atypical antipsychotics. Am J Psychiatry. 2003;160(2):29O–296.Google Scholar
52.Citrome, LL, Jaffe, AB. Relationship of atypical antipsychotics with development of diabetes mellitus. Ann Pharmacother. 2003;37:1849–1857.Google Scholar
53.Fleischhacker, WW, Nasrallah, H, Newcomer, JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19(suppl 1):1–93.Google Scholar
54.Koller, E, Schneider, B, Bennett, K, Dubitsky, G. Clozapine-associated diabetes. Am J Med. 2001;111:716–723.Google Scholar
55.Koller, EA, Doraiswamy, PM. Olanzapine-associated diabetes mellitus. Pharmacotherapy. 2002;22:841–52.Google Scholar
56.Koller, EA, Cross, JT, Doraiswamy, PM, Schneider, BS. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy. 2003;23:735–44.Google Scholar
57.Koller, EA, Weber, J, Doraiswamy, PM, Schneider, BS. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004;65(6):857–863.CrossRefGoogle ScholarPubMed
58.Henderson, DC, Cagliero, E, Copeland, PM, et al.Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis. Arch Gen Psychiatry. 2005;62(1):19–28.Google Scholar
59.Newcomer, JW, Haupt, DW, Fucetola, R, et al.Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002;59(4):337–345.Google Scholar
60.Henderson, DC, Cagliero, E, Gray, C, et al.Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000;157(6):975–981.CrossRefGoogle ScholarPubMed
61.Henderson, DC, Nguyen, DD, Copeland, PM, et al.Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study. J Clin Psychiatry. 2005;66:1116–1121.Google Scholar
62.Curtis, V. Women are not the same as men: specific clinical issues for female patients with bipolar disorder. Bipolar Disord. 2005;7(suppl 1):16–24.CrossRefGoogle Scholar
63.Leibenluft, E. Women with bipolar illness: clinical and research issues. Am J Psychiatry. 1996;153(2):163–173.Google Scholar
64.Leibenluft, E. Women and bipolar disorder: an update. Bull Menninger Clin. 2000;64(1):5–17.Google Scholar
65.Rasgon, N, Bauer, M, Glenn, T, Elman, S, Whybrow, PC. Menstrual cycle related mood changes in women with bipolar disorder. Bipolar Disord. 2003;5(1):48–52.Google Scholar
66.Kessler, RC, McGonagle, KA, Zhao, S, et al.Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51(1):8–19.Google Scholar
67.Tondo, L, Baldessarini, RJ. Rapid cycling in women and men with bipolar manic-depressive disorders. Am J Psychiatry. 1998;155(10):1434–1436.Google Scholar
68.McElroy, SL, Strakowski, SM, Keck, PE Jr, Tugrul, KL, West, SA, Lonczak, HS. Differences and similarities in mixed and pure mania. Compr Psychiatry. 1995;36(3):187–194.Google Scholar
69.Benazzi, F. Gender differences in bipolar II and unipolar depressed outpatients: a 557-case study. Ann Clin Psychiatry. 1999;11(2):55–59.Google Scholar
70.Rasgon, N, Bauer, M, Grof, P, Gyulai, L, et al.Sex-specific self-reported mood changes by patients with bipolar disorder. J Psychiatr Res. 2005;39(1):77–83.CrossRefGoogle ScholarPubMed
71.Blehar, MC, DePaulo, JR Jr, Gershon, ES, Reich, T, Simpson, SG, Nurnberger, JI Jr. Women with bipolar disorder: findings from the NIMH Genetics Initiative sample. Psychopharmacol Bull. 1998;34(3):239–243.Google Scholar
72.Parry, BL, Hauger, R, LeVeau, B, et al.Circadian rhythms of prolactin and thyroid-stimulating hormone during the menstrual cycle and early versus late sleep deprivation in premenstrual dysphoric disorder. Psychiatry Res. 1996;62(2):147–160.Google Scholar
73.Bauer, M, London, ED, Silverman, DH, Rasgon, N, Kirchheiner, J, Whybrow, PC. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging. Pharmacopsychiatry. 2003;36(suppl 3):S215–S221.Google Scholar
74.Polycystic ovarian syndrome. The National Women's Health Center, US Department ot Health and Human Services. Available at: www.women-shealth.gov. Accessed 09 2005.Google Scholar
75.Franks, S. Polycystic ovary syndrome. N Engl J Med. 1995;333(13):853–861.Google Scholar
76.Bauer, J, Jarre, A, Klingmuller, D, Elger, CE. Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women. Epilepsy Res. 2000;41(2):163–167.Google Scholar
77.Duncan, S. Polycystic ovarian syndrome in women with epilepsy: a review. Epilepsia. 2001;42(suppl 3):60–65.Google Scholar
78.Rasgon, NL, Altshuler, LL, Fairbanks, L, et al.Reproductive function and risk for PCOS in women treated for bipolar disorder. Bipolar Disord. 2005;7(3):246–259.Google Scholar
79.Hopkinson, ZE, Sattar, N, Fleming, R, Greer, IA. Polycystic ovarian syndrome: the metabolic syndrome comes to gynecology. BMJ. 1998;317(7154):329–332.CrossRefGoogle Scholar
80.Lobo, RA, Carmina, E. The importance of diagnosing the polycystic ovary syndrome. Ann Intern Med. 2000;132(12):989–993.Google Scholar
81.Halbreich, U, Kinon, BJ, Gilmore, JA, Kahn, LS. Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects. Psychoneuroendocrinology. 2003;28(suppl 1):53–67.Google Scholar
82.Kinon, BJ, Gilmore, JA, Liu, H, Halbreich, UM. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology. 2003;28(suppl 2):55–68.Google Scholar
83.Melkerrson, K. Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry. 2005;66:761–767.Google Scholar
84.Halbteich, U, Shen, J, Panaro, V. Are chronic psychiatric patients at increased risk for developing breast cancer? Am J Psychiatry. 1996;153(4):559–560.Google Scholar
85.Stahl, SM. Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 2: illustrating their mechanism of action. J Clin Psychiatry. 2001;62(12):923–924.Google Scholar
86.lnoue, A, Nakata, Y. Strategy for modulation of central dopamine transmission based on the partial agonist concept in schizophrenia therapy. Jpn J Pharmacol. 2001;86(4):376–380.Google Scholar
87.Liu-Seifert, H, Kinon, BJ, Ahl, J, Lamberson, S. Osteopenia associated with increased prolactin and aging in psychiatric patients treated with prolactinelevating antipsychotics. Ann N Y Acad Sci. 2004;1032:297–298.Google Scholar
88.Shaarawy, M, Nafei, S, Abul-Nasr, A, el-Sharkawy, S, Younis, A. Circulating nitric oxide levels in galactorrheic, hyperprolactinemic, amenorrheic women. Fertil Steril. 1997;68(3):454–459.Google Scholar
89.Wallaschofski, H, Kobsar, A, Koksch, M, et al.Prolactin receptor signaling during platelet activation. Prolactin receptor signaling during platelet activation. Horm Metab Res. 2003;35(4):228–235.Google Scholar
90.Wallaschofski, H, Eigenthaler, M, Kiefer, M, et al.Hyperprolactinemia in patients on antipsychotic drugs causes ADP-stimulated platelet activation that might explain the increased risk for venous thromboembolism: pilot study. J Clin Psychopharmacol. 2003;23(5):479–483.Google Scholar
91.Dickson, RA, Glazer, WM. Neuroleptic-induced hyperprolactinemia. Schizophr Res. 1999;35(suppl):S75–S86.Google Scholar
92.Ahl, J, Kinon, BJ, Liu-Seifert, H. Sexual dysfunction associated with neuroleptic-induced hyperprolactinemia improves with reduction in prolactin levels. Ann N Y Acad Sci. 2004;1032:289–290.Google Scholar
93.American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Washington, DC: American Psychiatric Association; 2004.Google Scholar
94.American Urological Association, Inc. The Management of Benign Prostatic Hyperplasia. Baltimore, MD: American Urological Association; 2003.Google Scholar
95.Druss, BG, Rohrbaugh, RM, Levinson, CM, Rosenheck, RA. Integrated medical care for patients with serious psychiatric illness: a randomized trial. Arch Gen Psychiatry. 2001;58(9):861–868.Google Scholar
96.Katzelnick, D, Simon, G, Pearson, S, Manning, W, Kobak, K. Depression management programs. Arch Fam Med. 2000;9(8):689–770.Google Scholar
97.Katon, WJ, Von Korff, M, Lin, EH, et al.The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression. Arch Gen Psychiatry. 2004;61(10):1042–1049.Google Scholar
98.Katon, WJ, Roy-Byrne, P, Russo, J, Cowley, D. Cost-effectiveness and cost offset of a collaborative care intervention for primary care patients with panic disorder. Arch Gen Psychiatry. 2002;59(12):1098–1104.Google Scholar
99.Druss, BG, Rosenheck, RA. Locus of mental health treatment in an integrated service system. Psychiatr Serv. 2000;51(7):890–892.Google Scholar
100.Druss, BG, Rosenheck, RA. Mental disorders and access ro medical care in the United States. Am J Psychiatry. 1998;155(12):1775–777.Google Scholar
101.Druss, BG, Rosenheck, RA, Desai, MM, Perlin, JB. Quality of preventive medical care for patients with mental disorders. Med Care. 2002;40(2):129–136.Google Scholar
102.Newcomer, JW, Nasrallah, HA, Loebel, AD. The Atypical Antipsychotic Therapy and Metabolic Issues National Survey: Practice Patterns and Knowledge of Psychiatrists. J Clin Psychopharmacol. 2004;24(suppl):S1–S6.Google Scholar
103.Stroup, TS, McEvoy, JP, Swartz, MS, et al.The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29(1):15–31.Google Scholar
104.Sachs, GS, Thase, ME, Otto, MW, et al.Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003;53(11):1028–1042.Google Scholar