Non-adherence to medication is common, and appears to be associated with a number of adverse clinical outcomes, including increased severity of depression, and increased risk of relapse and hospitalisation. One half or more of patients receiving antidepressants fail to take them at an adequate dose for an adequate duration.[479]Ho SC, Chong HY, Chaiyakunapruk N, et al. Clinical and economic impact of non-adherence to antidepressants in major depressive disorder: a systematic review. J Affect Disord. 2016 Mar 15;193:1-10.
http://www.ncbi.nlm.nih.gov/pubmed/26748881?tool=bestpractice.com
[480]Holvast F, Oude Voshaar RC, Wouters H, et al. Non-adherence to antidepressants among older patients with depression: a longitudinal cohort study in primary care. Fam Pract. 2019 Jan 25;36(1):12-20.
http://www.ncbi.nlm.nih.gov/pubmed/30395196?tool=bestpractice.com
During the 8- to 12-week initiation and titration phase, the first 2 weeks of drug therapy has the greatest discontinuation risk.
Help patients to continue medicine therapy by offering a timely response to adverse effects and by maintaining close contact. Beyond their utility in the diagnostic work-up, features of the history, examination, and laboratory studies can prove vital in monitoring for, and preventing adverse effects from, treatment.[481]Dodd S, Mitchell PB, Bauer M, et al. Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: An international consensus statement. World J Biol Psychiatry. 2018 Aug;19(5):330-48.
http://www.ncbi.nlm.nih.gov/pubmed/28984491?tool=bestpractice.com
Follow up with patients, in person or by telephone, within the first 2 weeks to address adverse effects, suicidality, and acceptance of medication taking, and to reinforce educational messages. Telephone follow-up by a trained nurse is also effective, as is text messaging.[482]Wells KB, Sherbourne C, Schoenbaum M, et al. Impact of disseminating quality improvement programs for depression in managed primary care: a randomized controlled trial. JAMA. 2000 Jan 12;283(2):212-20.
http://www.ncbi.nlm.nih.gov/pubmed/10634337?tool=bestpractice.com
[483]Simon GE, Ralston JD, Savarino J, et al. Randomized trial of depression follow-up care by online messaging. J Gen Intern Med. 2011 Jul;26(7):698-704.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138593
http://www.ncbi.nlm.nih.gov/pubmed/21384219?tool=bestpractice.com
Depending on the speed, stability, and adequacy of response, treatment of depression may require close follow-up for up to 1 year in order to adjust or augment therapy.
During the maintenance phase, monitor patients monthly in person or by telephone. It is important to continue assessing adherence, suicidality, and adverse effects.
Use the Patient Health Questionnaire-9 (PHQ-9) to assess changes in symptom severity objectively. A 50% decrease in symptom score constitutes an adequate response, and a 25% to 50% change in symptom score may indicate the need to modify treatment.
Collaborative care models and digital interventions (e.g., iCBT) may facilitate monitoring. See Management approach.
Duration of treatment following the remission of symptoms depends on the prior course of illness. Data on treatment outcomes beyond the initial weeks of treatment are limited, although one systematic review suggests that the efficacy of antidepressants compared with placebo is stable over at least the first 6 months of treatment.[320]Henssler J, Kurschus M, Franklin J, et al. Long-term acute-phase treatment with antidepressants, 8 weeks and beyond: a systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Psychiatry. 2018 Jan/Feb;79(1).
http://www.ncbi.nlm.nih.gov/pubmed/28068463?tool=bestpractice.com
In general there appears to be a reduced risk of relapse when antidepressants are continued for 6 months or over.[321]Baldessarini RJ, Lau WK, Sim J, et al. Duration of initial antidepressant treatment and subsequent relapse of major depression. J Clin Psychopharmacol. 2015 Feb;35(1):75-6.
http://www.ncbi.nlm.nih.gov/pubmed/25502491?tool=bestpractice.com
[322]Kato M, Hori H, Inoue T, et al. Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis. Mol Psychiatry. 2021 Jan;26(1):118-33.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815511
http://www.ncbi.nlm.nih.gov/pubmed/32704061?tool=bestpractice.com
[323]Zhou D, Lv Z, Shi L, et al. Effects of antidepressant medicines on preventing relapse of unipolar depression: a pooled analysis of parametric survival curves. Psychol Med. 2022 Jan;52(1):48-56.
http://www.ncbi.nlm.nih.gov/pubmed/32501194?tool=bestpractice.com
Continue successful antidepressant treatment for 6-12 months following remission.[165]National Institute for Health and Care Excellence. Depression in adults: treatment and management. Jun 2022 [internet publication].
https://www.nice.org.uk/guidance/ng222
[322]Kato M, Hori H, Inoue T, et al. Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis. Mol Psychiatry. 2021 Jan;26(1):118-33.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815511
http://www.ncbi.nlm.nih.gov/pubmed/32704061?tool=bestpractice.com
Discontinuation of antidepressant treatment has consistently been associated with a greater risk of relapse than does continuing treatment, and is therefore a complex clinical decision.[324]Van Leeuwen E, van Driel ML, Horowitz MA, et al. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database Syst Rev. 2021 Apr 15;4(4):CD013495.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013495.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/33886130?tool=bestpractice.com
[325]Lewis G, Marston L, Duffy L, et al. Maintenance or discontinuation of antidepressants in primary care. N Engl J Med. 2021 Sep 30;385(14):1257-67.
https://www.nejm.org/doi/10.1056/NEJMoa2106356
http://www.ncbi.nlm.nih.gov/pubmed/34587384?tool=bestpractice.com
[326]Donald M, Partanen R, Sharman L, et al. Long-term antidepressant use in general practice: a qualitative study of GPs' views on discontinuation. Br J Gen Pract. 2021 Jul;71(708):e508-16.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074642
http://www.ncbi.nlm.nih.gov/pubmed/33875415?tool=bestpractice.com
For some people at increased risk of relapse, continuation of treatment beyond this period may be required. Shared decision-making is recommended.
The World Federation of Societies of Biological Psychiatry (WFSBP) supports the use of maintenance treatment for recurrent depression in some circumstances; WFSBP recommends maintenance treatment for 5-10 years, or indefinitely, for those people at greater risk of recurrent depression, particularly when two or three attempts to withdraw medication have been followed by another episode within a year.[332]Bauer M, Severus E, Köhler S, et al.; World Federation of Societies of Biological Psychiatry (WFSBF) Task Force on Treatment Guidelines for Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 2: maintenance treatment of major depressive disorder - update 2015. World J Biol Psychiatry. 2015 Feb;16(2):76-95.
https://wfsbp.org/wp-content/uploads/2023/02/Bauer_et_al_2015.pdf
http://www.ncbi.nlm.nih.gov/pubmed/25677972?tool=bestpractice.com
For patients established on pharmacological treatment for depression, regularly review their antidepressant use to assess efficacy and the presence of any adverse effects, and to ensure that long-term use remains clinically indicated.[272]Royal College of Psychiatrists. Position statement on antidepressants and depression. May 2019 [internet publication].
https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/position-statements/ps04_19---antidepressants-and-depression.pdf?sfvrsn=ddea9473_5
If discontinuation of a selective serotonin-reuptake inhibitor (SSRI) or a serotonin-noradrenaline reuptake inhibitor (SNRI) is required, slowly decrease the dose to reduce the risk of unpleasant withdrawal symptoms; this may need to take place over several months or longer, and should be done at a rate that is tolerable to the patient.[324]Van Leeuwen E, van Driel ML, Horowitz MA, et al. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database Syst Rev. 2021 Apr 15;4(4):CD013495.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013495.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/33886130?tool=bestpractice.com
[328]Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry. 2019 Jun;6(6):538-46.
http://www.ncbi.nlm.nih.gov/pubmed/30850328?tool=bestpractice.com
Drugs with shorter half-lives (e.g., paroxetine, venlafaxine) require longer periods of taper.[329]Palmer EG, Sornalingam S, Page L, et al. Withdrawing from SSRI antidepressants: advice for primary care. Br J Gen Pract. 2023 Mar;73(728):138-40.
https://bjgp.org/content/73/728/138
http://www.ncbi.nlm.nih.gov/pubmed/36823051?tool=bestpractice.com
A proportionate method of tapering is recommended by some treatment guidelines; this involves reductions as a proportion of the previous dose (e.g., 25%) rather than reducing the dose by a fixed increment each time.[165]National Institute for Health and Care Excellence. Depression in adults: treatment and management. Jun 2022 [internet publication].
https://www.nice.org.uk/guidance/ng222
If the required dose is not available in tablet form, a liquid preparation may be required (if available). Be aware that people’s experiences of withdrawal symptoms can vary substantially from mild and transient to longer-lasting and more severe. Anticipatory discussion with the patient is important, including when and how to seek support from a healthcare professional in the event of withdrawal symptoms.[329]Palmer EG, Sornalingam S, Page L, et al. Withdrawing from SSRI antidepressants: advice for primary care. Br J Gen Pract. 2023 Mar;73(728):138-40.
https://bjgp.org/content/73/728/138
http://www.ncbi.nlm.nih.gov/pubmed/36823051?tool=bestpractice.com
Closely monitor the patient to ensure that any apparent emerging withdrawal symptoms do not in fact represent a relapse of their depression.[272]Royal College of Psychiatrists. Position statement on antidepressants and depression. May 2019 [internet publication].
https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/position-statements/ps04_19---antidepressants-and-depression.pdf?sfvrsn=ddea9473_5
[330]National Institute for Health and Care Excellence. Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults. Apr 2022 [internet publication].
https://www.nice.org.uk/guidance/ng215
There is a growing body of evidence supporting the use of psychological therapy for prevention of relapse and recurrence, both when used alone and in combination with pharmacotherapy.[175]Furukawa TA, Shinohara K, Sahker E, et al. Initial treatment choices to achieve sustained response in major depression: a systematic review and network meta-analysis. World Psychiatry. 2021 Oct;20(3):387-96.
https://onlinelibrary.wiley.com/doi/10.1002/wps.20906
http://www.ncbi.nlm.nih.gov/pubmed/34505365?tool=bestpractice.com
[333]Guidi J, Fava GA. Sequential combination of pharmacotherapy and psychotherapy in major depressive disorder: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Mar 1;78(3):261-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689568
http://www.ncbi.nlm.nih.gov/pubmed/33237285?tool=bestpractice.com
Specific modalities with demonstrated efficacy for relapse prevention include preventive CBT, mindfulness-based CBT, and interpersonal therapy (IPT).[334]Clarke K, Mayo-Wilson E, Kenny J, et al. Can non-pharmacological interventions prevent relapse in adults who have recovered from depression? a systematic review and meta-analysis of randomised controlled trials. Clin Psychol Rev. 2015 Jul;39:58-70.
http://www.ncbi.nlm.nih.gov/pubmed/25939032?tool=bestpractice.com
There is evidence that switching in the maintenance phase from pharmacotherapy to psychotherapy can be at least as effective in preventing relapse as staying with pharmacotherapy.[333]Guidi J, Fava GA. Sequential combination of pharmacotherapy and psychotherapy in major depressive disorder: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Mar 1;78(3):261-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689568
http://www.ncbi.nlm.nih.gov/pubmed/33237285?tool=bestpractice.com
[339]Breedvelt JJF, Warren FC, Segal Z, et al. Continuation of antidepressants vs sequential psychological interventions to prevent relapse in depression: an individual participant data meta-analysis. JAMA Psychiatry. 2021 Aug 1;78(8):868-75.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135055
http://www.ncbi.nlm.nih.gov/pubmed/34009273?tool=bestpractice.com