Maintenance or Discontinuation of Antidepressants in Primary Care

Abstract

BACKGROUNDPatients 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. METHODSWe 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-toevent 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. RESULTSA 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. CONCLUSIONSAmong 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.

A Patient Stratification Approach to Identifying the Likelihood of Continued Chronic Depression and Relapse Following Treatment for Depression

“…Although many patients do not want long-term treatment with antidepressants [11], there is an increasing trend for them to be maintained on antidepressants for two years or more [12,13], and the use of antidepressants has greatly increased over the last three decades [14]. Although pharmacogenetics may hold promise for personalizing antidepressant treatments [15,16], it is becoming increasingly common that antidepressants are prescribed indefinitely for all patients with a history of previous relapses, to mitigate the risks of chronic illness and relapse [11,12,17,18]. This is despite evidence of the waning effectiveness of medications over time [19][20][21][22], and even increased risk of relapse and other harmful outcomes for those remaining on medications after several years [17,23].…”

Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT

“…The mechanistic outcomes are not reported in the report or in the main trial paper that reports the clinical outcomes; they will be reported in separate paper(s). 34 However, we provide their description below.…”

Tackling overprescribing

“…Equally pressing is the need for more evidence and guidance on how best to withdraw inappropriate medication (deprescribing) 1314. Clinical trials have already shown that it is safe and even beneficial for patients to stop some long term drugs such as antidepressants and statins towards the end of life 1516…”