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Maund, 2019 Managing Antidepressant Discontinuation: A Systematic Review.

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Ann Fam Med. 2019 Jan;17(1):52-60. doi: 10.1370/afm.2336.

Managing Antidepressant Discontinuation: A Systematic Review.

Maund E1, Stuart B1, Moore M1, Dowrick C2, Geraghty AWA1, Dawson S3, Kendrick T4.


Abstract at https://www.ncbi.nlm.nih.gov/pubmed/30670397  Free full text at http://www.annfammed.org/content/17/1/52.long



We aimed to determine the effectiveness of interventions to manage antidepressant discontinuation, and the outcomes for patients.



We conducted a systematic review with narrative synthesis and meta-analysis of studies published to March 2017. Studies were eligible for inclusion if they were randomized controlled trials, quasi-experimental studies, or observational studies assessing interventions to facilitate discontinuation of antidepressants for depression in adults. Our primary outcomes were antidepressant discontinuation and discontinuation symptoms. Secondary outcomes were relapse/recurrence; quality of life; antidepressant reduction; and sexual, social, and occupational function.



Of 15 included studies, 12 studies (8 randomized controlled trials, 2 single-arm trials, 2 retrospective cohort studies) were included in the synthesis. None were rated as having high risk for selection or detection bias. Two studies prompting primary care clinician discontinuation with antidepressant tapering guidance found 6% and 7% of patients discontinued, vs 8% for usual care. Six studies of psychological or psychiatric treatment plus tapering reported cessation rates of 40% to 95%. Two studies reported a higher risk of discontinuation symptoms with abrupt termination. At 2 years, risk of relapse/recurrence was lower with cognitive behavioral therapy plus taper vs clinical management plus taper (15% to 25% vs 35% to 80%: risk ratio = 0.34; 95% CI, 0.18-0.67; 2 studies). Relapse/recurrence rates were similar for mindfulness-based cognitive therapy with tapering and maintenance antidepressants (44% to 48% vs 47% to 60%; 2 studies).



Cognitive behavioral therapy or mindfulness-based cognitive therapy can help patients discontinue antidepressants without increasing the risk of relapse/recurrence, but are resource intensive. More scalable interventions incorporating psychological support are needed.


From the paper:



Discontinuation Symptoms

One RCT and 1 retrospective cohort study reported on discontinuation symptoms (Table 2).38,53 The RCT compared abrupt discontinuation of desvenlafaxine 50 mg/day vs tapering using 25 mg/day for 1 week.38 There was significantly lower risk of discontinuation-emergent adverse events with the 1-week taper (RR = 0.76; 95% CI, 0.58–0.98) but no statistically significant difference in the risk of discontinuation syndrome. The study may have been underpowered to detect a difference, however, with 140 patients in the tapering arm and 148 patients in the abrupt discontinuation arm.


The retrospective cohort study assessed outcomes among 385 patients treated with paroxetine for a single episode of major depressive disorder.53 Discontinuation syndrome occurred significantly less frequently in patients who discontinued gradually, with a 10-mg reduction every 2 weeks, compared with patients who discontinued abruptly (5% vs 34%; RR = 0.14; 95% CI, 0.07–0.25). Patients experiencing discontinuation syndrome were significantly younger (P = .02), but more young patients discontinued abruptly. Of 41 patients experiencing discontinuation syndrome, 36 were restarted on paroxetine and subsequently tapered off at 5 mg every 2 to 4 weeks, with no recurrence of discontinuation syndrome. As 10-mg tablets were the only form available, however, patients had to split them.


Summary of Main Findings

We found discontinuation rates varied from only 6% to 7% for prompted primary care clinician patient review and guided tapering, to 40% to 95% for specialist psychological or psychiatric interventions. Merely 2 studies reported on discontinuation symptoms. One RCT38 found a lower risk of serious adverse events with 1-week taper vs abrupt discontinuation of desvenlafaxine, whereas a retrospective cohort study53 found discontinuation syndrome significantly more common after abrupt paroxetine cessation.


Rates of relapse/recurrence were low in primary care (13% to 26%) compared with psychiatric or psychological therapy settings (15% to 90%), presumably related to the larger proportion of patients with multiple recurrences, partial remissions on antidepressants, or both in specialist settings, but there has been very little research in primary care. A primary care placebo-controlled trial of maintenance SSRI treatment to prevent depression recurrence (excluded from this review) found similar recurrence rates: 10% in the continuation arm and 23% in the taper arm over 18 months.58


The risk of relapse/recurrence was significantly reduced with the combination of CBT and tapering vs clinical management and tapering alone. MBCT with tapering enabled high rates of discontinuation without increasing relapse/recurrence rates, as compared with maintenance antidepressants.




ADMIN NOTE This paper contains no information about tapering techniques or their comparison.


Exactly two of the 15 studies reported withdrawal symptoms:



One RCT and 1 retrospective cohort study reported on discontinuation symptoms (Table 2).


Table 2:


Khan et al, 2014 -- one-week taper, appears to have resulted in 22% incidence of withdrawal symptoms vs "abrupt discontinuation" 21%-51%

Himei and Okamura, 2006 -- 8-week taper, "A 10-mg reduction every 2 weeks", 5% incidence of withdrawal symptoms vs "abrupt withdrawal" 34%


The rest reported varying rates of "relapse."


As it appears most of the studies, as usual, contained no protocols for distinguishing withdrawal symptoms, it's quite possible many more patients experienced withdrawal symptoms than were reported, particularly in the primary care studies. The high rate of "relapse" in specialist settings may indicate more eagerness among mental health "specialists" to diagnose psychiatric conditions and re-medicate, while the low rate among primary care physicians may be simply lack of follow up or inclination among patients to ask for more drugs from their doctors.


The recommended CBT may very well have helped patients cope with withdrawal symptoms rather than forestall "relapse."


I believe what this study found was inattention to distinguishing withdrawal symptoms from "relapse."


This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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