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Effects of antidepressant medicines on preventing relapse of unipolar depression: a pooled analysis of parametric survival curves

Published online by Cambridge University Press:  05 June 2020

Dongdong Zhou
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Zhen Lv
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Lei Shi
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Xiaoxin Zhou
Affiliation:
Medical Department, University-Town Hospital of Chongqing Medical University, Chongqing, China
Qingxia Lin
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China
Xiaorong Chen
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Liyang Wan
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Yao Li
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Liuyi Ran
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Yan Huang
Affiliation:
GCP Office, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
Gaomao Wang
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Daqi Li
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Wo Wang
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Chuan Liu*
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China
Li Kuang*
Affiliation:
Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
*
Authors for correspondence: Li Kuang, E-mail: [email protected]; or Chuan Liu, E-mail: [email protected]
Authors for correspondence: Li Kuang, E-mail: [email protected]; or Chuan Liu, E-mail: [email protected]

Abstract

Background

Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs).

Methods

PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months.

Results

Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an ‘enriched’ randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization.

Conclusions

The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.

Type
Original Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

Contributed equally to this manuscript.

References

Amsterdam, J. D., & Bodkin, J. A. (2006). Selegiline transdermal system in the prevention of relapse of major depressive disorder: A 52-week, double-blind, placebo-substitution, parallel-group clinical trial. Journal of Clinical Psychopharmacology, 26(6), 579586. doi: 10.1097/01.jcp.0000239794.37073.70.CrossRefGoogle ScholarPubMed
Baethge, C., Assall, O. P., & Baldessarini, R. J. (2013). Systematic review of blinding assessment in randomized controlled trials in schizophrenia and affective disorders 2000–2010. Psychotherapy and Psychosomatics, 82(3), 152160. doi: 10.1159/000346144.CrossRefGoogle ScholarPubMed
Bauer, M., Severus, E., Moller, H. J., & Young, A. H., & WFSBP Task Force on Unipolar Depressive Disorders. (2017). Pharmacological treatment of unipolar depressive disorders: Summary of WFSBP guidelines. International Journal of Psychiatry in Clinical Practice, 21(3), 166176. doi: 10.1080/13651501.2017.1306082.CrossRefGoogle ScholarPubMed
Bialos, D., Giller, E., Jatlow, P., Docherty, J., & Harkness, L. (1982). Recurrence of depression after discontinuation of long-term amitriptyline treatment. American Journal of Psychiatry, 139(3), 325329. doi: 10.1176/ajp.139.3.325.Google ScholarPubMed
Boulenger, J. P., Loft, H., & Florea, I. (2012). A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder. Journal of Psychopharmacology, 26(11), 14081416. doi: 10.1177/0269881112441866.CrossRefGoogle ScholarPubMed
Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., … Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet (London, England), 391(10128), 13571366. doi: 10.1016/S0140-6736(17)32802-7.CrossRefGoogle ScholarPubMed
Conradi, H. J., Ormel, J., & de Jonge, P. (2012). Symptom profiles of DSM-IV-defined remission, recovery, relapse, and recurrence of depression: The role of the core symptoms. Depression and Anxiety, 29(7), 638645. doi: 10.1002/da.21960.CrossRefGoogle ScholarPubMed
Cope, S., & Jansen, J. P. (2013). Quantitative summaries of treatment effect estimates obtained with network meta-analysis of survival curves to inform decision-making. BMC Medical Research Methodology, 13, 147. doi: 10.1186/1471-2288-13-147.CrossRefGoogle ScholarPubMed
Coppen, A., Ghose, K., Montgomery, S., Rama Rao, V. A., Bailey, J., & Jorgensen, A. (1978). Continuation therapy with amitriptyline in depression. British Journal of Psychiatry, 133, 2833. doi: 10.1192/bjp.133.1.28.CrossRefGoogle ScholarPubMed
Dalery, J., Dagens-Lafont, V., & De Bodinat, C. (2001). Efficacy of tianeptine vs placebo in the long-term treatment (16.5 months) of unipolar major recurrent depression*. Human Psychopharmacology, 16(S1), S39S47. doi: 10.1002/hup.269.CrossRefGoogle ScholarPubMed
Davidson, J., & Raft, D. (1984). Use of phenelzine in continuation therapy. Neuropsychobiology, 11(3), 191194. doi: 10.1159/000118076.CrossRefGoogle ScholarPubMed
Dias, S., Welton, N. J., Sutton, A. J., & Ades, A. E. (2014). NICE DSU technical support document 2: A generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. London: National Institute for Health and Care Excellence (NICE). Retrieved from https://pubmed.ncbi.nlm.nih.gov/27466657/.Google ScholarPubMed
Dobson, K. S., Hollon, S. D., Dimidjian, S., Schmaling, K. B., Kohlenberg, R. J., Gallop, R. J., … Jacobson, N. S. (2008). Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the prevention of relapse and recurrence in major depression. Journal of Consulting and Clinical Psychology, 76(3), 468477. doi: 10.1037/0022-006X.76.3.468.CrossRefGoogle ScholarPubMed
Durgam, S., Chen, C., Migliore, R., Prakash, C., & Thase, M. E. (2019). Relapse prevention with levomilnacipran ER in adults with major depressive disorder: A multicenter, randomized, double-blind, placebo-controlled study. Depression and Anxiety, 36(3), 225234. doi: 10.1002/da.22872.CrossRefGoogle ScholarPubMed
Durgam, S., Gommoll, C., Migliore, R., Chen, C., Chang, C. T., Aguirre, M., & Thase, M. E. (2018). Relapse prevention in adults with major depressive disorder treated with vilazodone: A randomized, double-blind, placebo-controlled trial. International Clinical Psychopharmacology, 33(6), 304311. doi: 10.1097/YIC.0000000000000236.CrossRefGoogle ScholarPubMed
El-Mallakh, R. S., & Briscoe, B. (2012). Studies of long-term use of antidepressants: How should the data from them be interpreted? CNS Drugs, 26(2), 97109. doi: 10.2165/11599450-000000000-00000.CrossRefGoogle ScholarPubMed
Feiger, A. D., Bielski, R. J., Bremner, J., Heiser, J. F., Trivedi, M., Wilcox, C. S., … Archibald, D. G. (1999). Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression. International Clinical Psychopharmacology, 14(1), 1928. doi: 10.1097/00004850-199901000-00002.CrossRefGoogle ScholarPubMed
Frank, E., Prien, R. F., Jarrett, R. B., Keller, M. B., Kupfer, D. J., Lavori, P. W., … Weissman, M. M. (1991). Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Archives of General Psychiatry, 48(9), 851855. doi: 10.1001/archpsyc.1991.01810330075011.CrossRefGoogle Scholar
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England), 392(10159), 17891858. doi: 10.1016/S0140-6736(18)32279-7.CrossRefGoogle Scholar
Geddes, J. R., Carney, S. M., Davies, C., Furukawa, T. A., Kupfer, D. J., Frank, E., & Goodwin, G. M. (2003). Relapse prevention with antidepressant drug treatment in depressive disorders: A systematic review. Lancet (London, England), 361(9358), 653661. doi: 10.1016/S0140-6736(03)12599-8.CrossRefGoogle ScholarPubMed
Ghaemi, S. N., & Selker, H. P. (2017). Maintenance efficacy designs in psychiatry: Randomized discontinuation trials – enriched but not better. Journal of Clinical and Translational Science, 1(3), 198204. doi: 10.1017/cts.2017.2.CrossRefGoogle Scholar
Gilaberte, I., Montejo, A. L., de la Gandara, J., Perez-Sola, V., Bernardo, M., Massana, J., … Fluoxetine Long-Term Study Group. (2001). Fluoxetine in the prevention of depressive recurrences: A double-blind study. Journal of Clinical Psychopharmacology, 21(4), 417424. doi: 10.1097/00004714-200108000-00009.CrossRefGoogle ScholarPubMed
Goodwin, G. M., Boyer, P., Emsley, R., Rouillon, F., & de Bodinat, C. (2013). Is it time to shift to better characterization of patients in trials assessing novel antidepressants? An example of two relapse prevention studies with agomelatine. International Clinical Psychopharmacology, 28(1), 2028. doi: 10.1097/YIC.0b013e32835b0814.CrossRefGoogle ScholarPubMed
Guyot, P., Ades, A. E., Ouwens, M. J., & Welton, N. J. (2012). Enhanced secondary analysis of survival data: Reconstructing the data from published Kaplan-Meier survival curves. BMC Medical Research Methodology, 12, 9. doi: 10.1186/1471-2288-12-9.CrossRefGoogle ScholarPubMed
Higgins, J. P.T., & Green, S. (2011) Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration. Retrieved from http://handbook-5-1.cochrane.org/.Google Scholar
Hochstrasser, B., Isaksen, P. M., Koponen, H., Lauritzen, L., Mahnert, F. A., Rouillon, F., … Nil, R. (2001). Prophylactic effect of citalopram in unipolar, recurrent depression: Placebo-controlled study of maintenance therapy. British Journal of Psychiatry, 178, 304310. doi: 10.1192/bjp.178.4.304.CrossRefGoogle ScholarPubMed
Jansen, J. P., & Cope, S. (2012). Meta-regression models to address heterogeneity and inconsistency in network meta-analysis of survival outcomes. BMC Medical Research Methodology, 12, 152. doi: 10.1186/1471-2288-12-152.CrossRefGoogle ScholarPubMed
Kamijima, K., Burt, T., Cohen, G., Arano, I., & Hamasaki, T. (2006). A placebo-controlled, randomized withdrawal study of sertraline for major depressive disorder in Japan. International Clinical Psychopharmacology, 21(1), 19. doi: 10.1097/01.yic.0000182118.57510.d1.CrossRefGoogle ScholarPubMed
Kasper, S., Volz, H. P., Moller, H. J., Dienel, A., & Kieser, M. (2008). Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression – a double-blind, randomized, placebo controlled long-term trial. European Neuropsychopharmacology, 18(11), 803813. doi: 10.1016/j.euroneuro.2008.06.006.CrossRefGoogle ScholarPubMed
Keller, M. B., Kocsis, J. H., Thase, M. E., Gelenberg, A. J., Rush, A. J., Koran, L., … Harrison, W. (1998). Maintenance phase efficacy of sertraline for chronic depression: A randomized controlled trial. JAMA, 280(19), 16651672. doi: 10.1001/jama.280.19.1665.CrossRefGoogle ScholarPubMed
Keller, M. B., Ruwe, F. J., Janssens, C. J., Sitsen, J. M., Jokinen, R., & Janczewski, J. (2005). Relapse prevention with gepirone ER in outpatients with major depression. Journal of Clinical Psychopharmacology, 25(1), 7984. doi: 10.1097/01.jcp.0000150221.53877.d9.CrossRefGoogle ScholarPubMed
Keller, M. B., Trivedi, M. H., Thase, M. E., Shelton, R. C., Kornstein, S. G., Nemeroff, C. B., … Ninan, P. T. (2007). The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the 2-year and combined maintenance phases. Journal of Clinical Psychiatry, 68(8), 12461256. doi: 10.4088/jcp.v68n0812.CrossRefGoogle ScholarPubMed
Kocsis, J. H., Thase, M. E., Trivedi, M. H., Shelton, R. C., Kornstein, S. G., Nemeroff, C. B., … Keller, M. B. (2007). Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT Study. Journal of Clinical Psychiatry, 68(7), 10141023. doi: 10.4088/jcp.v68n0706.CrossRefGoogle Scholar
Kupfer, D. J., Frank, E., Perel, J. M., Cornes, C., Mallinger, A. G., Thase, M. E., … Grochocinski, V. J. (1992). Five-year outcome for maintenance therapies in recurrent depression. Archives of General Psychiatry, 49(10), 769773. doi: 10.1001/archpsyc.1992.01820100013002.CrossRefGoogle ScholarPubMed
Kuyken, W., Hayes, R., Barrett, B., Byng, R., Dalgleish, T., Kessler, D., … Byford, S. (2015). Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): A randomised controlled trial. Lancet (London, England), 386(9988), 6373. doi: 10.1016/s0140-6736(14)62222-4.CrossRefGoogle ScholarPubMed
Liebowitz, M., Lam, R. W., Lepola, U., Datto, C., Sweitzer, D., & Eriksson, H. (2010). Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: A randomized, placebo-controlled trial. Depression and Anxiety, 27(10), 964976. doi: 10.1002/da.20740.CrossRefGoogle ScholarPubMed
McGrath, P. J., Stewart, J. W., Quitkin, F. M., Chen, Y., Alpert, J. E., Nierenberg, A. A., … Petkova, E. (2006). Predictors of relapse in a prospective study of fluoxetine treatment of major depression. American Journal of Psychiatry, 163(9), 15421548. doi: 10.1176/ajp.2006.163.9.1542.CrossRefGoogle Scholar
Montgomery, S. A., Dufour, H., Brion, S., Gailledreau, J., Laqueille, X., Ferrey, G., … Pierredon, M. A. (1988). The prophylactic efficacy of fluoxetine in unipolar depression. British Journal of Psychiatry, 153(suppl. 3), 6976. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/3150694.10.1192/S0007125000297328CrossRefGoogle Scholar
Montgomery, S. A., & Dunbar, G. (1993). Paroxetine is better than placebo in relapse prevention and the prophylaxis of recurrent depression. International Clinical Psychopharmacology, 8(3), 189195. doi: 10.1097/00004850-199300830-00009.CrossRefGoogle ScholarPubMed
Montgomery, S. A., Entsuah, R., Hackett, D., Kunz, N. R., & Rudolph, R. L., & Venlafaxine 335 Study Group. (2004). Venlafaxine versus placebo in the preventive treatment of recurrent major depression. Journal of Clinical Psychopharmacology, 65(3), 328336. doi: 10.4088/jcp.v65n0307.Google ScholarPubMed
Montgomery, S. A., Rasmussen, J. G., & Tanghoj, P. (1993). A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression. International Clinical Psychopharmacology, 8(3), 181188. doi: 10.1097/00004850-199300830-00008.CrossRefGoogle ScholarPubMed
Ouwens, M. J., Philips, Z., & Jansen, J. P. (2010). Network meta-analysis of parametric survival curves. Research Synthesis Methods, 1(3–4), 258271. doi: 10.1002/jrsm.25.CrossRefGoogle ScholarPubMed
Perahia, D. G., Gilaberte, I., Wang, F., Wiltse, C. G., Huckins, S. A., Clemens, J. W., … Detke, M. J. (2006). Duloxetine in the prevention of relapse of major depressive disorder: Double-blind placebo-controlled study. British Journal of Psychiatry, 188, 346353. doi: 10.1192/bjp.188.4.346.CrossRefGoogle ScholarPubMed
Perahia, D. G., Maina, G., Thase, M. E., Spann, M. E., Wang, F., Walker, D. J., & Detke, M. J. (2009). Duloxetine in the prevention of depressive recurrences: A randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychiatry, 70(5), 706716. doi: 10.4088/jcp.08m04756.CrossRefGoogle ScholarPubMed
Rapaport, M. H., Bose, A., & Zheng, H. (2004). Escitalopram continuation treatment prevents relapse of depressive episodes. Journal of Clinical Psychiatry, 65(1), 4449. doi: 10.4088/jcp.v65n0107.CrossRefGoogle ScholarPubMed
Rickels, K., Montgomery, S. A., Tourian, K. A., Guelfi, J. D., Pitrosky, B., Padmanabhan, S. K., … Brisard, C. (2010). Desvenlafaxine for the prevention of relapse in major depressive disorder: Results of a randomized trial. Journal of Clinical Psychopharmacology, 30(1), 1824. doi: 10.1097/JCP.0b013e3181c94c4d.CrossRefGoogle ScholarPubMed
Robert, P., & Montgomery, S. A. (1995). Citalopram in doses of 20-60 mg is effective in depression relapse prevention: A placebo-controlled 6 month study. International Clinical Psychopharmacology, 10(Suppl. 1), 2935. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/7622809.10.1097/00004850-199503001-00006CrossRefGoogle ScholarPubMed
Robinson, D. S., Lerfald, S. C., Bennett, B., Laux, D., Devereaux, E., Kayser, A., … Albright, D. (1991). Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine: A double-blind placebo-controlled discontinuation study. Psychopharmacology Bulletin, 27(1), 3139. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1862204.Google ScholarPubMed
Rosenthal, J. Z., Boyer, P., Vialet, C., Hwang, E., & Tourian, K. A. (2013). Efficacy and safety of desvenlafaxine 50 mg/d for prevention of relapse in major depressive disorder: A randomized controlled trial. Journal of Clinical Psychiatry, 74(2), 158166. doi: 10.4088/JCP.12m07974.CrossRefGoogle ScholarPubMed
Rouillon, F., Warner, B., Pezous, N., & Bisserbe, J. C. (2000). Milnacipran efficacy in the prevention of recurrent depression: A 12-month placebo-controlled study. Milnacipran recurrence prevention study group. International Clinical Psychopharmacology, 15(3), 133140. doi: 10.1097/00004850-200015030-00002.CrossRefGoogle ScholarPubMed
Shiovitz, T., Greenberg, W. M., Chen, C., Forero, G., & Gommoll, C. P. (2014). A randomized, double-blind, placebo-controlled trial of the efficacy and safety of levomilnacipran ER 40–120 mg/day for prevention of relapse in patients with major depressive disorder. Innovations in Clinical Neuroscience, 11(1–2), 1022. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24653937.Google Scholar
Sim, K., Lau, W. K., Sim, J., Sum, M. Y., & Baldessarini, R. J. (2015). Prevention of relapse and recurrence in adults with major depressive disorder: Systematic review and meta-analyses of controlled trials. International Journal of Neuropsychopharmacology, 19(2), 113. doi: 10.1093/ijnp/pyv076.Google ScholarPubMed
Simon, J. S., Aguiar, L. M., Kunz, N. R., & Lei, D. (2004). Extended-release venlafaxine in relapse prevention for patients with major depressive disorder. Journal of Psychiatric Research, 38(3), 249257. doi: 10.1016/j.jpsychires.2003.10.004.CrossRefGoogle ScholarPubMed
Terra, J. L., & Montgomery, S. A. (1998). Fluvoxamine prevents recurrence of depression: Results of a long-term, double-blind, placebo-controlled study. International Clinical Psychopharmacology, 13(2), 5562. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9669185.10.1097/00004850-199803000-00001CrossRefGoogle Scholar
Thase, M. E., Nierenberg, A. A., Keller, M. B., Panagides, J., & Relapse Prevention Study Group. (2001). Efficacy of mirtazapine for prevention of depressive relapse: A placebo-controlled double-blind trial of recently remitted high-risk patients. Journal of Clinical Psychiatry, 62(10), 782788. doi: 10.4088/jcp.v62n1006.CrossRefGoogle ScholarPubMed
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., … Team, S. D. S. (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. American Journal of Psychiatry, 163(1), 2840. doi: 10.1176/appi.ajp.163.1.28.CrossRefGoogle ScholarPubMed
Versiani, M., Mehilane, L., Gaszner, P., & Arnaud-Castiglioni, R. (1999). Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. Journal of Clinical Psychiatry, 60(6), 400406. doi: 10.4088/jcp.v60n0610.CrossRefGoogle ScholarPubMed
Viguera, A. C., Baldessarini, R. J., & Friedberg, J. (1998). Discontinuing antidepressant treatment in major depression. Harvard Review of Psychiatry, 5(6), 293306. doi: 10.3109/10673229809003578.CrossRefGoogle ScholarPubMed
Warner, C. H., Bobo, W., Warner, C., Reid, S., & Rachal, J. (2006). Antidepressant discontinuation syndrome. American Family Physician, 74(3), 449456. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16913164.Google ScholarPubMed
Weihs, K. L., Houser, T. L., Batey, S. R., Ascher, J. A., Bolden-Watson, C., Donahue, R. M., & Metz, A. (2002). Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Biological Psychiatry, 51(9), 753761. doi: 10.1016/s0006-3223(01)01317-8.CrossRefGoogle ScholarPubMed
Williams, N., Simpson, A. N., Simpson, K., & Nahas, Z. (2009). Relapse rates with long-term antidepressant drug therapy: A meta-analysis. Human Psychopharmacology, 24(5), 401408. doi: 10.1002/hup.1033.CrossRefGoogle ScholarPubMed
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