Discontinuation of antidepressant therapy among patients with major depressive disorder


Objective: Patients with major depressive disorder (MDD) often discontinue antidepressant therapy pre- maturely risking relapse, despite United Kingdom (UK) guidelines recommending therapy for up to at least six months after remission. More information is needed on the patterns of antidepressant discontinuation in UK primary care. Objectives of the study were to assess the patterns, incidence and predictors of therapy discontinuation among MDD patients initiating treatment with selective serotonin reuptake inhibitors (SSRIs). Methods: This was a retrospective cohort study using general practices registered with the General Practice Research Database (GPRD). 15,274 patients with MDD receiving a first ever prescription (index) for an SSRI between 2006-2008 were identified in GPRD. Discontinuation (including temporary gaps) and cessation of antidepressant therapy were examined over follow-up. Predictors of incidence of discontinuation in the six months after index were assessed. Results: Incidence of discontinuation of antidepressant therapy over follow-up was 80.05 per 100 person years (95% CI 78.94 - 81.17). At six months after index 42% of patients had discontinued and 33% had ceased therapy altogether. Lower discontinuation of index SSRI therapy in the first six months after initiation was associated with higher age, higher body mass index (BMI), and comorbid irritable bowel syndrome. Higher discontinuation was associated with paroxetine or fluoxetine at index, and a more recent index calendar year. Conclusions: There is a significant risk of discontinuation of antidepressant therapy in the 6 months after initiation of treatment for MDD. This finding requires awareness by the general practitioner (GP) to ensure implementation of optimal treatment regimens, and minimization of therapy non-compliance among MDD patients.

Share and Cite:

Davé, S. , Classi, P. , Kim Le, T. , Maguire, A. and Ball, S. (2012) Discontinuation of antidepressant therapy among patients with major depressive disorder. Open Journal of Psychiatry, 2, 272-280. doi: 10.4236/ojpsych.2012.24038.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] King, M., Nazareth, I., Levy, G., Walker, C., Morris, R., Weich, S., Bellon-Saameno, J.A., Moreno, B., Svab, I., Rotar, D., Rifel, J., Maaroos, H.I., Aluoja, A., Kalda, R., Neeleman, J., Geerlings, M.I., Xavier, M., de Almeida, M.C., Correa, B. and Torres-Gonzalez, F. (2008) Prevalence of common mental disorders in general practice attendees across Europe. The British Journal of Psychiatry, 192, 362-367. doi:10.1192/bjp.bp.107.039966
[2] NICE (2009) Depression: The treatment and management of depression in adults (Clinical Guideline 90). National Institute for Health and Clinical Excellence, London.
[3] Claxton, A.J., Li, Z. and McKendrick, J. (2000) Selective serotonin reuptake inhibitor treatment in the UK: Risk of relapse or recurrence of depression. The British Journal of Psychiatry, 177, 163-168. doi:10.1192/bjp.177.2.163
[4] Judd, L.L., Paulus, M.J., Schettler, P.J., Akiskal, H.S., Endicott, J., Leon, A.C., Maser, J.D., Mueller, T., Solomon, D.A. and Keller, M.B. (2000) Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? American Journal of Psychiatry, 157, 1501-1504. doi:10.1176/appi.ajp.157.9.1501
[5] 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
[6] Mitchell, A.J. and Selmes, T. (2007) Why don’t patients take their medicine? Reasons and solutions in psychiatry. Advances in Psychiatric Treatment, 13, 336-346. doi:10.1192/apt.bp.106.003194
[7] Fortney, J.C., Pyne, J.M., Edlund, M.J., Stecker, T., Mittal, D., Robinson, D.E. and Henderson, K.L. (2011) Reasons for antidepressant nonadherence among veterans treated in primary care clinics. Journal of Clinical Psychiatry, 72, 827-834. doi:10.4088/JCP.09m05528blu
[8] 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
[9] Anderson, H.D., Pace, W.D., Libby, A.M., West, D.R. and Valuck, R.J. (2012) Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: A retrospective US claims study. Clinical Therapeutics, 34, 113-123. doi:10.1016/j.clinthera.2011.11.024
[10] Kikuchi, T., Suzuki, T., Uchida, H., Watanabe, K. and Kashima, H. (2011) Subjective recognition of adverse events with antidepressant in people with depression: A prospective study. Journal of Affective Disorders, 135, 347-353. doi:10.1016/j.jad.2011.07.011
[11] Moore, M., Yuen, H.M., Dunn, N., Mullee, M.A., Maskell, J. and Kendrick, T. (2009) Explaining the rise in antidepressant prescribing: A descriptive study using the general practice research database. British Medical Journal, 339, b3999. doi:10.1136/bmj.b3999
[12] Wade, A.G., Saragoussi, D., Despiegel, N., Francois, C., Guelfucci, F. and Toumi, M. (2010) Healthcare expenditure in severely depressed patients treated with escitalopram, generic SSRIs or venlafaxine in the UK. Current Medical Research & Opinion, 26, 1161-1170. doi:10.1185/03007991003738519
[13] Kurd, S.K., Troxel, A.B., Crits-Christoph, P. and Gelfand, J.M. (2010) The risk of depression, anxiety, and suicidality in patients with psoriasis: A population-based cohort study. Archives of Dermatology, 146, 891-895. doi:10.1001/archdermatol.2010.186
[14] Becker, C., Brobert, G.P., Johansson, S., Jick, S.S. and Meier, C.R. (2011) Risk of incident depression in patients with Parkinson disease in the UK. European Journal of Neurology, 18, 448-453. doi:10.1111/j.1468-1331.2010.03176.x
[15] Lewis, J.D., Bilker, W.B., Weinstein, R.B. and Strom, B.L. (2005) The relationship between time since registration and measured incidence rates in the General Practice Research Database. Pharmacoepidemiology and Drug Safety, 14, 443-451. doi:10.1002/pds.1115
[16] Chisholm, J. (1990) The Read clinical classification. British Medical Journal, 300, 1092. doi:10.1136/bmj.300.6732.1092
[17] Kroenke, K., Spitzer, R.L. and Williams, J.B.W. (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
[18] 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
[19] Beck, A.T., Steer, R.A. and Brown, G.K. (1996) Manual for the Beck Depression Inventory-II. Psychological Corporation, San Antonio.
[20] Gilbody, S., Richards, D., Brealey, S. and Hewitt, C. (2007) Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): A diagnostic meta-analysis. Journal of General Internal Medicine, 22, 1596-1602. doi:10.1007/s11606-007-0333-y
[21] Elliott, W.J., Plauschinat, C.A., Skrepnek, G.H. and Gause, D. (2007) Persistence, adherence, and risk of discontinuation associated with commonly prescribed antihypertensive drug monotherapies. The Journal of the American Board of Family Medicine, 20, 72-80. doi:10.3122/jabfm.2007.01.060094
[22] 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
[23] 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
[24] Warner-Schmidt, J.L., Vanover, K.E., Chen, E.Y., Marshall, J.J. and Greengard, P. (2011) Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by anti-inflammatory drugs in mice and humans. Proceedings of the National Academy of Sciences of the United States of America, 108, 9262-9267. doi:10.1073/pnas.1104836108
[25] Lee, Y.M. and Lee, K.U. (2011) Time to discontinuation among the three second-generation antidepressants in a naturalistic outpatient setting of depression. Psychiatry and Clinical Neurosciences, 65, 630-637. doi:10.1111/j.1440-1819.2011.02275.x
[26] Olfson, M., Marcus, S.C., Tedeschi, M. and Wan, G.J. (2006) Continuity of antidepressant treatment for adults with depression in the United States. American Journal of Psychiatry, 163, 101-108. doi:10.1176/appi.ajp.163.1.101
[27] Simon, G.E., Von Korff, M., Wagner, E.H. and Barlow, W. (1993) Patterns of antidepressant use in community practice. General Hospital Psychiatry, 15, 399-408. doi:10.1016/0163-8343(93)90009-D
[28] Hansen, D.G., Vach, W., Rosholm, J.U., Sondergaard, J., Gram, L.F. and Kragstrup, J. (2004) Early discontinuation of antidepressants in general practice: Association with patient and prescriber characteristics. The Journal of Family Practice, 21, 623-629. doi:10.1093/fampra/cmh608
[29] Rait, G., Walters, K., Griffin, M., Buszewicz, M., Petersen, I. and Nazareth, I. (2009) Recent trends in the incidence of recorded depression in primary care. The British Journal of Psychiatry, 195, 520-524. doi:10.1192/bjp.bp.108.058636
[30] Demyttenaere, K., Enzlin, P., Dewe, W., Boulanger, B., De, B.J., De, T.W. and Mesters, P. (2001) Compliance with antidepressants in a primary care setting, 1: Beyond lack of efficacy and adverse events. Journal of Clinical Psychiatry, 62 Suppl 22, 30-33.
[31] Lin, E.H., Von, K.M., Katon, W., Bush, T., Simon, G.E., Walker, E. and Robinson, P. (1995) The role of the primary care physician in patients’ adherence to antidepressant therapy. Medical Care, 33, 67-74. doi:10.1097/00005650-199501000-00006
[32] Lewis, E., Marcus, S.C., Olfson, M., Druss, B.G. and Pincus, H.A. (2004) Patients’ early discontinuation of antidepressant prescriptions. Psychiatric Services, 55, 494. doi:10.1176/appi.ps.55.5.494
[33] Serna, M.C., Cruz, I., Real, J., Gasco, E. and Galvan, L. (2010) Duration and adherence of antidepressant treatment (2003-2007) based on prescription database. European Psychiatry, 25, 206-213. doi:10.1016/j.eurpsy.2009.07.012
[34] Mabotuwana, T., Warren, J., Orr, M., Kenealy, T. and Harrison, J. (2011) Using primary care prescribing data to improve GP awareness of antidepressant adherence issues. Informatics in Primary Care, 19, 7-15.
[35] Aikens, J.E., Kroenke, K., Swindle, R.W. and Eckert, G.J. (2005) Nine-month predictors and outcomes of SSRI antidepressant continuation in primary care. General Hospital Psychiatry, 27, 229-236. doi:10.1016/j.genhosppsych.2005.04.001
[36] Meijer, W.E., Heerdink, E.R., Leufkens, H.G., Herings, R.M., Egberts, A.C. and Nolen, W.A. (2004) Incidence and determinants of long-term use of antidepressants. European Journal of Clinical Pharmacology, 60, 57-61. doi:10.1007/s00228-004-0726-3
[37] Horne, R. (1999) Patients’ beliefs about treatment: The hidden determinant of treatment outcome? Journal of Psychosomatic Research, 47, 491-495. doi:10.1016/S0022-3999(99)00058-6
[38] Aikens, J.E., Nease, D.E., Jr. and Klinkman, M.S. (2008) Explaining patients’ beliefs about the necessity and harmfulness of antidepressants. The Annals of Family Medicine, 6, 23-29. doi:10.1370/afm.759
[39] Hirschfeld, R.M. (2003) Long-term side effects of SSRIs: Sexual dysfunction and weight gain. Journal of Clinical Psychiatry, 64 Suppl 18, 20-24.
[40] Fakhoury, W.K., Wright, D. and Wallace, M. (2001) Prevalence and extent of distress of adverse effects of antipsychotics among callers to a United Kingdom National Mental Health Helpline. International Clinical Psychopharmacology, 16, 153-162. doi:10.1097/00004850-200105000-00004
[41] Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J. and Johnson, B.T. (2008) Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLOS Medicine, 5, e45. doi:10.1371/journal.pmed.0050045
[42] Kirsch, I. (2009) Antidepressants and the placebo response. Epidemiologia e psichiatria sociale, 18, 318-322.
[43] Thase, M.E., Ferguson, J.M., Lydiard, R.B. and Wilcox, C.S. (2002) Citalopram treatment of paroxetine-intolerant depressed patients. Depression and Anxiety, 16, 128-133. doi:10.1002/da.10055
[44] Rambelomanana, S., Depont, F., Forest, K., Hebert, G., Blazejewski, S., Fourrier-Reglat, A., Molimard, M. and Moore, N. (2006) Antidepressants: General practitioners’ opinions and clinical practice. Acta Psychiatrica Scandinavica, 113, 460-467. doi:10.1111/j.1600-0447.2006.00793.x
[45] Edwards, J.G. and Anderson, I. (1999) Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs, 57, 507-533. doi:10.2165/00003495-199957040-00005

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.