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Supplements Trends in Managed Behavioral Healthcare: A Focus on Improving Depression Outcomes

Depression: The Benefits of Early and Appropriate Treatment

Aron Halfin, MD
Phase 1 results (n = 2876) indicated that only approximately 30% of patients met the criteria for remission during initial citalopram treatment. Response rates did not differ between patients treated in primary and psychiatric care settings. Remission, when it occurred, did so only after 8 weeks or more of treatment.32 In phase 2, augmentation of citalopram with sustained-release bupropion or buspirone led to similar rates of remission (39.0% and 32.9%, respectively). In those patients switched to another antidepressant therapy, approximately 25% had remission of symptoms after switching to sustained-release bupropion, sertraline, or extended-release venlafaxine, a serotonin norepinephrine reuptake inhibitor (SNRI).33

There are economic implications to switching between antidepressants. An analysis of a national pharmacy claims database indicated that switching from a failed antidepressant to another agent with a different mechanism of action (eg, SSRI to SNRI) resulted in reduced total healthcare costs, regardless of which drug class was attempted first.34 Costs declined after switching, but SSRI to SNRI switchers experienced a greater decline in total cost compared with SNRI to SSRI switchers.

To help clarify the selection of antidepressants in a managed care setting, Dunn and Tierney developed a step-therapy algorithm modeled partially after the STAR*D trial and based on trial data and the consensus statements of a panel of clinical and managed care professionals (Figure 3).25 The algorithm begins with the trial of an initial agent, followed by observation to determine the patient's response. If an inadequate response is achieved or if intolerable adverse events occur, options exist for dose escalation and/or augmentation as well as switching and/or discontinuation.20 In keeping with the body of evidence in depression treatment, remission is the end goal of the treatment outlined in the algorithm. Frequent follow-up visits or calls are promoted in the algorithm to continuously monitor progress in patients being treated for depression. When switching is deemed appropriate following 1 or 2 therapeutic failures in the same class, the panel recommends switching to an agent from a different class than the initial agent, in keeping with the body of evidence.20

Depression is a long-term and progressive condition that when not treated adequately can lead to severe morbidity and mortality and increased costs for payers, employers, and patients. Despite the significant burden of depression, the majority of patients do not receive treatment adequate enough to achieve remission. While remission is the primary goal of treatment, it is sometimes the most difficult to achieve. Effective strategies to achieve remission include an increase in dose, augmentation of medication, combination of psychotherapy and antidepressant treatments, or using medications with more than 1 mechanism of action. These strategies may be most easily applied through the use of a treatment algorithm. Patients who do not achieve remission, including those cycling on ineffective therapies, are at greater risk for relapse and recurrence, more long-term depressive episodes, and a shorter duration between depressive episodes. SSRIs are widely used first-line agents for the treatment of depression because of their efficacy, tolerability, and generic status, but when treatment fails, another class of antidepressants, such as an SNRI, should be attempted. Clinical trials provide good evidence to show that achieving and sustaining the fully remitted state is an attainable goal in the management of patients with depression.


Address correspondence to: Aron Halfin, MD, 3350 Peachtree Rd NE, Mail Stop G005-0001, Atlanta, GA 30326. E-mail:

1. National Institute of Mental Health. Pathways to Health: Charting the Science of Brain, Mind, Behavior. A Research Strategic Plan for the National Institute of
Mental Health Fiscal Year
2000–2001. Bethesda, MD: National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services. Available at: Accessed October 7, 2007.
2. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry. 1998; 55:580-592.
3. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW. Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation. 1996;94:3123-3129.
4. Greenberg PE, Kessler RC, Birnbaum HG, et al. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry. 2003;64:1465-1475.
5. Rice DP, Miller LS. Health economics and cost implications of anxiety and other mental disorders in the United States. Br J Psychiatry Suppl. 1998:4-9.
6. Simon GE, VonKorff M. Recognition, management, and outcomes of depression in primary care. Arch Fam Med. 1995;4:99-105.
7. Henk HJ, Katzelnick DJ, Kobak KA, Greist JH, Jefferson JW. Medical costs attributed to depression among patients with a history of high medical expenses in a health maintenance organization. Arch Gen Psychiatry. 1996;53:899-904.
8.Von Korff M, Katon W, Unutzer J, Wells K, Wagner EH. Improving depression care: barriers, solutions, and research needs. J Fam Pract. 2001;50:E1.
9. Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D. Cost of lost productive work time among US workers with depression. JAMA. 2003;289:3135-3144.
10. Pincus HA, Pettit AR. The societal costs of chronic major depression. J Clin Psychiatry. 2001;62(suppl 6): 5-9.
11. Greden JF. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry. 2001;62(suppl 22):5-9.
12. Judd LL, Paulus MP, Wells KB, Rapaport MH. Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am J Psychiatry. 1996;153:1411-1417.
13. Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry. 1992;14:237-247.
14. Regier DA, Narrow WE, Rae DS, Manderscheid RW, Locke BZ, Goodwin FK. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50:85-94.
15. Callahan EJ, Bertakis KD, Azari R, Robbins J, Helms LJ, Miller J. The influence of depression on physicianpatient interaction in primary care. Fam Med. 1996;28:346-351.
16. Coyne JC, Fechner-Bates S, Schwenk TL. Prevalence, nature, and comorbidity of depressive disorders in primary care. Gen Hosp Psychiatry. 1994;16:267-276.
17. Coulehan JL, Schulberg HC, Block MR, Madonia MJ, Rodriguez E.Treating depressed primary care patients improves their physical, mental, and social functioning. Arch Intern Med. 1997;157:1113-1120.
18. Rost K, Smith JL, Dickinson M. The effect of improving primary care depression management on employee absenteeism and productivity. A randomized trial. Med Care. 2004;42:1202-1210.
19. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry. 2000;157:1-45.
20. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry. 1991;52(suppl):28-34.
21. Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995;25:1171-1180.
22. Mueller TI, Leon AC, Keller MB, Solomon DA, Endicott J, Coryell W. Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. Am J Psychiatry. 1999;156:1000-1006.
23. Judd LL, Paulus MJ, Schettler PJ, Akiskal HS, Endicott J, Leon AC. Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry. 2000;157:1501-1504.
24. Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry. 1990;47:1093-1099.
25. Dunn JD, Tierney JG. A step therapy algorithm for the treatment and management of chronic depression. Am J Manag Care. 2006;12(suppl 12):S335-S343.
26. Judd LL, Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W. Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. J Affect Disord. 1998;50:97-108.
27. Greenberg P, Corey-Lisle PK, Birnbaum H, Marynchenko M, Claxton A. Economic implications of treatmentresistant depression among employees. Pharmacoeconomics. 2004;22:363-373.
28. Simon GE, Revicki D, Heiligenstein J, Grathaus L, Vonkorff M, Katon WJ, et al. Recovery from depression, work productivity, and health care costs among primary care patients. Gen Hosp Psychiatry. 2000;22:153-162.
29. Corey-Lisle PK, Nash R, Stang P, Swindle R. Response, partial response, and nonresponse in primary care treatment of depression. Arch Intern Med. 2004;164:
30. Nelson JC. Managing treatment-resistant major depression. J Clin Psychiatry. 2003;64(suppl 1):5-12.
31. Souery D, Papakostas GI, Trivedi MH. Treatment-resistant depression. J Clin Psychiatry. 2006;67(suppl 6):16-22.
32. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28-40.
33. Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354:1231-1242.
34. Kruzikas D, Khandker RK, McLaughlin T, Tedeschi M. Patterns of antidepressant use and cost implications of product switching. Presented at: the Academy of Managed Care Pharmacy Educational Meeting. Nashville, TN, October 5-8, 2005.
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