Maintenance or Discontinuation of Antidepressants in Primary Care

Bethie Seay — Sun, 03 Oct 2021 05:00:00 +0000

Date Added:

October 3, 2021

Journal/Publication:

The New England Journal of Medicine

Publication Date:

September 30, 2021

Type:

Clinical Research Results

DOI (1):

10.1056/NEJMoa2106356

In patients whose depression resolved on antidepressants, discontinuation of the antidepressant is associated with a significantly higher rate of depression reoccurrence vs. maintenance antidepressant therapy over a one year period.

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BACKGROUND
Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.

METHODS
We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.

RESULTS
A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.

CONCLUSIONS
Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)

Author/s:

Lewis, G., Marston, L., Duffy, L., Freemantle, N., Gilbody, S., Hunter, R., Kendrick, T., Kessler, D., Mangin, D., King, M., Lanham, P., Moore, M.

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

John Bayhi — Fri, 17 Apr 2020 17:32:46 +0000

Date Added:

April 17, 2020

Journal/Publication:

AHRQ Publication No. 20-EHC005-EF

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 10, 2020

URL:

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER224

Keywords

cognitive behavioral therapy

selective serotonin reuptake inhibitors

MeSH

serotonin uptake inhibitors

paroxetine

Depressive Disorder

depressive disorder, major

united states food and drug administration

risk

Inpatients

Confidence Intervals

antidepressive agents

Cognitive Behavioral Therapy

The key findings are listed on the third page (page ii). James W. Mold, MD, MPH

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Background. Depressive disorders can affect long-term mental and physical health functioning among children and adolescents, including increased risk of suicide. Despite access to several nonpharmacological, pharmacological, and combined treatment options for childhood depression, clinicians contend with sparse evidence and are concerned about harms associated with treatment.

Methods. We conducted a systematic review to evaluate the efficacy, comparative effectiveness, and moderators of benefits and harms of available nonpharmacological and pharmacological treatments for children and adolescents with a confirmed diagnosis of a depressive disorder (DD)—major depressive disorder (MDD), persistent depressive disorder (previously termed dysthymia) or DD not otherwise specified. We searched five databases and other sources for evidence available from inception to May 29, 2019, dually screened the results, and analyzed eligible studies.

Results. We included in our analyses data from 60 studies (94 articles) that met our review eligibility criteria. For adolescents (study participants’ ages range from 12 to 18 years) with MDD, cognitive behavioral therapy (CBT), fluoxetine, escitalopram, and combined fluoxetine and CBT may improve depressive symptoms (1 randomized controlled trial [RCT] each, n ranges from 212 to 311); whether the magnitude of improvement is clinically significant is unclear. Among adolescents or children with MDD, CBT plus medications (8–17 years) may be associated with lower rates of relapse (1 RCT [n = 121]). In the same population (6–17 years), selective serotonin reuptake inhibitors (SSRIs) may be associated with improved response (7 RCTs [n = 1,525]; risk difference [RD], 72/1,000 [95% confidence interval (CI), 2 to 24], I2 = 9%) and functional status (5 RCTs [n = 941]; standardized mean difference, 0.16 [95% CI, 0.03 to 0.29]; I2 = 0%). For adolescents or children with any DD (7–18 years), CBT or family therapy may be associated with improvements in symptoms, response, or functional status (1 RCT each, n ranges from 64 to 99). Among children with any DD (7–12 years), family-based interpersonal therapy may be associated with improved symptoms (1 RCT, n = 38). Psychotherapy trials did not report harms. SSRIs may be associated with a higher risk of serious adverse events among adolescents or children with MDD (7–18 years; 9 RCTs [n = 2,206]; RD, 20/1,000 [95% CI, 1 to 440]; I2, 4%) and with a higher risk of withdrawal due to adverse events among adolescents with MDD (12–18 years; 4 RCTs [n = 1,296], RD, 26/1,000 [95% CI, 6 to 45]; I2, 0%). Paroxetine (1 RCT [n = 180]) may be associated with a higher risk of suicidal ideation or behaviors among adolescents with MDD (12–18 years). Evidence was insufficient to judge the risk of suicidal ideation or behavior for other SSRIs for adolescents and children with MDD or other DD (7–18 years) (10 RCTs [n = 2,368]; relative risk, 1.14 [95% CI, 0.89 to 1.45]; I2, 8%). However, this report excluded data on inpatients and those without depressive disorders, whom the Food and Drug Administration included in finding an increased risk of suicidality for all antidepressants across all indications.

Conclusion. Efficacious treatments exist for adolescents with MDD. SSRIs may be associated with increased withdrawal and serious adverse events. No evidence on harms of psychotherapy were identified.

Author/s:

Viswanathan, M, Kennedy, SM, McKeeman, J, Christian, R, Coker-Schwimmer, Cook Middleton, Bann, C, Lux, L, Randolph, Forman-Hoffman, V