OJPsych  Vol.2 No.3 , July 2012
Adjunctive pharmacotherapy and treatment patterns among initiators of SSRI therapy for major depressive disorder: A cohort study using a primary care database
Abstract: Objective: Adjunctive therapy is often used for treatment of major depressive disorder (MDD) following an inadequate response to an antidepressant. However, there is little information regarding its practice within primary care in the United Kingdom (UK). Objectives of the study were to examine incidence and predictors of adjunctive pharmacotherapy among patients with MDD treated with selective serotonin reuptake inhibitors (SSRIs) by UK general practitioners (GPs). Methods: The General Practice Research Database was used to identify 15,274 MDD patients prescribed first-line treatment with SSRIs from 2006-2008 (latest patient follow-up towards end of 2010). Treatment trajectories were identified and classified as adjunctive therapy, combination therapy, drug switches, dose increases, and restart of therapy. Incidence and predictors of adjunctive therapy were assessed, and healthcare resource utilization was evaluated. Results: Overall incidence of adjunctive therapy was 3.07/100 person years (95% CI 2.90-3.25). Patients prescribed adjunctive therapy were more likely to be female (IRR 1.15, p = 0.03), of higher age (IRRs 1.51-2.60, p ≤ 0.001), and had a greater depression severity score (IRR 1.02, p = 0.003). Presence of irritable bowel syndrome (IRR 1.53, p = 0.001), and an increasing Charlson Comorbidity Index (IRR 1.15, p = 0.01) were associated with a higher incidence of adjunctive therapy. MDD-related general practitioner consultations among patients who received adjunctive therapy was lower compared with patients receiving other treatment interventions (IRRs 0.79 - 0.87, p ≤ 0.001). Conclusions: Adjunctive therapy is infrequently utilized relative to other treatment options for management of MDD among patients who are inadequate responders to their SSRI treatments in UK primary care; however some groups are more likely to receive adjunctive therapy than others.
Cite this paper: Classi, P. , Ball, S. , Davé, S. , Maguire, A. and Le, T. (2012) Adjunctive pharmacotherapy and treatment patterns among initiators of SSRI therapy for major depressive disorder: A cohort study using a primary care database. Open Journal of Psychiatry, 2, 211-219. doi: 10.4236/ojpsych.2012.23028.

[1]   NICE (2009) Depression. The treatment and management of depression in adults. NICE clinical guideline 90. National Institute for Health and Clinical Excellence, 2010.

[2]   Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D., Niederehe, G., Thase, M.E., Lavori, P.W., Lebowitz, B.D., McGrath, P.J., Rosenbaum, J.F., Sackeim, H.A., Kupfer, D.J., Luther, J. and Fava, M. (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163, 1905-1917. doi:10.1176/appi.ajp.163.11.1905

[3]   Judd, L.L., Akiskal, H.S., Maser, J.D., Zeller, P.J., Endicott, J., Coryell, W., Paulus, M.P., Kunovac, J.L., Leon, A.C., Mueller, T.I., Rice, J.A. and Keller, M.B. (1998) Major depressive disorder: A prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. Journal of Affective Disorders, 50, 97-108. doi:10.1016/S0165-0327(98)00138-4

[4]   Judd, L.L., Akiskal, H.S., Zeller, P.J., Paulus, M., Leon, A.C., Maser, J.D., Endicott, J., Coryell, W., Kunovac, J.L., Mueller, T.I., Rice, J.P. and Keller, M.B. (2000) Psychosocial disability during the long-term course of unipolar major depressive disorder. Archives of General Psychiatry, 57, 375-380. doi:10.1001/archpsyc.57.4.375

[5]   Kennedy, S., McIntyre, R., Fallu, A. and Lam, R. (2002) Pharmacotherapy to sustain the fully remitted state. Journal of Psychiatry and Neuroscience, 27, 269-280.

[6]   Thase, M.E., Simons, A.D., McGeary, J., Cahalane, J.F., Hughes, C., Harden, T. and Friedman, E. (1992) Relapse after cognitive behavior therapy of depression: Potential implications for longer courses of treatment. American Journal of Psychiatry, 149, 1046-1052.

[7]   Keller, M.B. (2004) Remission versus response: The new gold standard of antidepressant care. Journal of Clinical Psychiatry, 65, 53-59.

[8]   Chisholm, J. (1990) The Read clinical classification. British Medical Journal, 300, 1092. doi:10.1136/bmj.300.6732.1092

[9]   Dave, S., Petersen, I., Sherr, L. and Nazareth, I. (2010) Incidence of maternal and paternal depression in primary care: A cohort study using a primary care database. Archives of Pediatrics & Adolescent Medicine, 164, 1038-1044. doi:10.1001/archpediatrics.2010.184

[10]   Joling, K.J., Van Marwijk, H.W., Piek, E., Van der Horst, H.E., Penninx, B.W., Verhaak, P. and Van Hout, H.P. (2011) Do GPs’ medical records demonstrate a good recognition of depression? A new perspective on case extraction. Journal of Affective Disorders, 133, 522-527. doi:10.1016/j.jad.2011.05.001

[11]   Kroenke, K., Spitzer, R.L. and Williams, J.B. (2001) The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine, 16, 606-613. doi:10.1046/j.1525-1497.2001.016009606.x

[12]   Zigmond, A.S. and Snaith, R.P. (1983) The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67, 361-370. doi:10.1111/j.1600-0447.1983.tb09716.x

[13]   Beck, A.T., Steer, R.A. and Brown, G.K. (1996) Manual for the beck depression inventory-II. Psychological Corporation, San Antonio.

[14]   Charlson, M.E., Pompei, P., Ales, K.L. and MacKenzie, C.R. (1987) A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. Journal of Chronic Diseases, 40, 373-383. doi:10.1016/0021-9681(87)90171-8

[15]   Khan, N.F., Perera, R., Harper, S. and Rose, P.W. (2010) Adaptation and validation of the Charlson index for Read/OXMIS coded databases. BMC Family Practice, 11, 1. doi:10.1186/1471-2296-11-1

[16]   Bauer, M., Monz, B.U., Montejo, A.L., Quail, D., Dantchev, N., Demyttenaere, K., Garcia-Cebrian, A., Grassi, L., Perahia, D.G., Reed, C. and Tylee, A. (2008) Prescribing patterns of antidepressants in Europe: Results from the Factors Influencing Depression Endpoints Research (FINDER) study. European Psychiatry, 23, 66-73. doi:10.1016/j.eurpsy.2007.11.001

[17]   Martin-Lopez, L.M., Rojo, J.E., Gibert, K., Martin, J.C., Sperry, L., Duno, L., Bulbena, A. and Vallejo, J. (2011) The strategy of combining antidepressants in the treatment of major depression: Clinical experience in spanish outpatients. Depression Research and Treatment, 2011, 140194. doi:10.1155/2011/140194

[18]   Gregor, K.J., Riley, J.A. and Downing, D.K. (1996) Concomitant use of anxiolytics and hypnotics with selective serotonin reuptake inhibitors. Clinical Therapeutics, 18, 521-527. doi:10.1016/S0149-2918(96)80034-8

[19]   McManus, P., Mant, A., Mitchell, P., Birkett, D. and Dudley, J. (2001) Co-prescribing of SSRIs and TCAs in Australia: How often does it occur and who is doing it? British Journal of Clinical Pharmacology, 51, 93-98. doi:10.1046/j.1365-2125.2001.01319.x

[20]   Classi, P., Ball, S. and Le, T.K. (2011) What happens next? Pharmacological Prescription patterns in patients with major depressive disorder who initiate selective serotonin reuptake inhibitor therapy. American Psychiatric Association Annual Conference, Honolulu.

[21]   Weissman, M.M., Bland, R.C., Canino, G.J., Faravelli, C., Greenwald, S., Hwu, H.G., Joyce, P.R., Karam, E.G., Lee, C.K., Lellouch, J., Lepine, J.P., Newman, S.C., Rubio-Stipec, M., Wells, J.E., Wickramaratne, P.J., Wittchen, H. and Yeh, E.K. (1996) Cross-national epidemiology of major depression and bipolar disorder. Journal of the American Medical Association, 276, 293-299. doi:10.1001/jama.1996.03540040037030

[22]   Angst, J., Gamma, A., Gastpar, M., Lepine, J.P., Mendlewicz, J. and Tylee, A. (2002) Gender differences in depression. Epidemiological findings from the European DEPRES I and II studies. European Archives of Psychiatry and Clinical Neuroscience, 252, 201-209. doi:10.1007/s00406-002-0381-6

[23]   Hall, R.H. (2003) Promoting men’s health. Australian Family Physician, 32, 401-407.

[24]   Thorogood, M., Coulter, A., Jones, L., Yudkin, P., Muir, J. and Mant, D. (1993) Factors affecting response to an invitation to attend for a health check. Journal of Epidemiology & Community Health, 47, 224-228. doi:10.1136/jech.47.3.224

[25]   Cole, M.G., Bellavance, F. and Mansour, A. (1999) Prognosis of depression in elderly community and primary care populations: A systematic review and meta-analysis. American Journal of Psychiatry, 156, 1182-1189.

[26]   Sable, J.A., Dunn, L.B. and Zisook, S. (2002) Late-life depression. How to identify its symptoms and provide effective treatment. Geriatrics, 57, 18-19.

[27]   NHS (2009) Trends in consultation rates in general practice 1995/1996 to 2008/2009: Analysis of the QResearch database. The Health and Social Care Information Centre.

[28]   Leo, R.J. (2005) Chronic pain and comorbid depression. Current Treatment Options in Neurology, 7, 403-412. doi:10.1007/s11940-005-0032-0

[29]   Koike, A.K., Unutzer, J. and Wells, K.B. (2002) Improving the care for depression in patients with comorbid medical illness. American Journal of Psychiatry, 159, 1738-1745. doi:10.1176/appi.ajp.159.10.1738

[30]   Agius, M., Murphy, C.L. and Zaman, R. (2010) Does shared care help in the treatment of depression? Psychiatria Danubina, 22, S18-S22.