Clinical briefing: Stopping antidepressants

More people are taking antidepressants for longer — but as many as 30 to 50 per cent of patients derive no benefit from them or do not have an evidence-based reason to continue them long-term.^1,2 

Many patients are “deeply apprehensive” about stopping antidepressants, while doctors may be concerned about disturbing a patient’s “equilibrium”.³ Nevertheless, many people still want to stop taking these medications. 

Some feel well enough, such as after a change in personal circumstances or an important positive life event, to stop antidepressants. Some stop because of side-effects, including weight gain, lethargy, gastrointestinal changes, light headedness, sexual dysfunction and lost “clarity of thought”.¹ 

Many people find that antidepressants suppress positive as well as negative emotions, sometimes leaving them feeling numb.⁴ Other people want to try to recover without medication or have concerns about addiction and other long-term effects1 but, when they stop, many people experience antidepressant discontinuation symptoms (ADS).³ 

Doctors and patients worry that ADS may herald a relapse so they restart antidepressants...which perpetuates long-term use.⁵

FINISHing ADS

The FINISH mnemonic offers an aide-mémoire for ADS: Flu-like symptoms; Insomnia; Nausea; Imbalance; Sensory disturbances; and Hyperarousal, including anxiety and agitation.⁶ Tapering the dose over several weeks seems to reduce ADS frequency and severity.⁷ Nevertheless, some people experience ADS despite dose tapering.⁶

A recent meta-analysis looking at ADS included 79 studies involving 21,002 patients. Thirty-one per cent of patients stopping antidepressants experienced at least one ADS compared with 17 per cent of those stopping placebo – so about 14 per cent of patients have ADS directly attributable to discontinuation. 

Severe ADS was experienced by 2.8 per cent of patients stopping antidepressants compared with 0.6 per cent of those who stopped taking placebo. The risk seemed highest with imipramine (44 per cent experienced ADS), desvenlafaxine and venlafaxine (40 per cent), escitalopram (39 per cent), fluvoxamine (38 per cent), paroxetine (32 per cent) and duloxetine (32 per cent).³

The study is “the first meta-analytic assessment of the incidence of [ADS] and of placebo effects”.³ An accompanying editorial notes that discontinuation symptoms after stopping placebo underscore that healthcare professionals “must be careful when we infer that any symptom is causally related to stopping the medication” and “discuss the possibility that [patients’] symptoms might not be due to the discontinuation of antidepressants”.⁷

Giving up is hard to do...

ADS are one reason why stopping anti-depressants can be tough. A recent study enrolled 330 people who wanted to stop their medication. The patients could consult their GP or nurse practitioner to review their antidepressants. In addition to active review, 178 of the patients received augmented care, where GPs, nurses and patients could access internet support. Patients could arrange up to three telephone calls with a NHS Talking Therapies psychological well-being practitioner.²

After six months, 41.9 per cent of control patients had stopped antidepressants. It is worth noting, however, that controls received current best practice, rather than usual care, which may be no active review² – so the discontinuation rates among controls may be better than in day-to-day practice.

At six months, 45.5 per cent of the intervention arm discontinued antidepressants. The difference between groups was not statistically significant. ADS were less severe and mental well-being was significantly better in the intervention group compared with controls. The differences were, however, small.²

“Evidence that about one in 35 patients suffers from severe [ADS] must be considered preliminary, but caution towards severe [ADS] seems to be warranted when discontinuing imipramine, paroxetine, or desvenlafaxine and venlafaxine,” the authors conclude.³ 

One in 35 may not sound like a particularly high risk but the editorial points out that because “many millions” of patients take antidepressants, “relatively uncommon severe withdrawal symptoms will still affect a substantial number of people”.⁷

For some, antidepressants are life-savers, countering suicidality and other high-risk behaviours. They help people cope with enduring, intractable social and personal problems. Nevertheless, further research needs to find the best way to support patients to stop antidepressants and manage ADS. 

<sup>References
1.    Primary Health Care Research & Development 2023; 24:e16
2.    JAMA Network Open 2024; 7:e2418383
3.    Lancet Psychiatry 2024; 11:526-535
4.    Nutt D Psychedelics. Yellow Kite
5.    Davies J Sedated: How Modern Capitalism Created Our Mental Health Crisis. Atlantic Books
6.    European Neuropsychopharmacology 2023; 66:1-10
7.    Lancet Psychiatry 2024; 11:485-486</sup>