Good News in Psychiatry

Concern over withdrawal of antidepressant is common. A new study suggests this concern is not supported by empirical data.

The journal JAMA Psychiatry has published a systematic review and meta-analysis of studies looking at discontinuation of antidepressant medications. I cover this study because antidepressants are one of the most commonly used medications in the US.

For instance, one recent estimate has 24 percent of women in the United States currently having or being treated for depression, compared to 11 percent of men. That is a lot of people.

Antidepressant medication often comes up in the arrhythmia clinic because of drug-drug interactions. Of course, I would normally be quite anxious about stopping an antidepressant.

But perhaps I should be less worried. Led by a team at Imperial College London, the authors analyzed 50 studies including 17,828 participants (67% female, mean age 44 years) with follow-up ranging from 1 day to 52 weeks.

The question was to sort out the incidence and nature of antidepressant discontinuation symptoms. They used something called the DESS—Discontinuation Emergent Signs and Symptoms—as a primary endpoint.

There were two comparisons: one was the difference in symptoms between patients who stopped vs continued an antidepressant and the other was to compare symptoms in those who stopped an antidepressant vs stopping a placebo.

The main results did find statistical differences. Patients were about 70% more likely to have one or more DESS symptom. (standardized mean difference, 0.31; 95% CI, 0.23-0.39; number of studies [k] = 11; n = 3915 participants. The authors provide a translation of what this “standardized mean difference” means clinically: it is estimated to be equivalent to 1 more symptom on the DESS.

Discontinuation of antidepressants was associated with increased odds of dizziness (OR, 5.52; 95% CI, 3.81-8.01), nausea (OR, 3.16; 95% CI, 2.01-4.96), vertigo (OR, 6.40; 95% CI, 1.20-34.19), and nervousness (OR, 3.15; 95% CI, 1.29-7.64) compared to placebo discontinuation.

The main finding: Discontinuation was not associated with depression symptoms, despite being measured in people with major depressive disorder (k = 5).

The authors concluded:

This systematic review and meta-analysis indicated that the mean number of discontinuation symptoms at week 1 after stopping antidepressants was below the threshold for clinically significant discontinuation syndrome. Mood worsening was not associated with discontinuation; therefore, later presentation of depression after discontinuation is indicative of depression relapse.

Comments

The strengths include the fact that systematic reviews and meta-analyses are the highest form of medical evidence. The studies included patients with diverse conditions including major depression (28), anxiety (9), panic (4) and even fibromyalgia, among others. The authors also included 11 unpublished studies.

Weaknesses, as noted by the authors, were short treatment duration, though 6 studies had treatment periods ranging from 36 weeks to 4.5 years. There was also a short follow up duration of 2 weeks. and some studies reported only symptoms that were statistically different from placebo, which may have inflated the apparent incidence in the antidepressant groups.

Finally, not all antidepressants were included. For instance, the commonly used fluoxetine was underrepresented. And there were no available studies on newer FDA-approved antidepressants (gepirone, dextromethorphan-bupropion).

It’s important to list a crucial caveat: while this meta-analysis finds no average signal of major harm from stopping antidepressants, it does not translate to every single patient and situation.

Studies provide average effects; specific situations deserving of more careful titration surely exist within the realm of average effects.

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Yet I find it remarkable that something that induces huge amounts of worry (antidepressant withdrawal) was not borne out when studied systematically.

This phenomenon—of things thought but not confirmed empirically—is one of the driving forces of Sensible Medicine.

This study-of-the-week supports the clear benefits of empirical study, especially of commonly-held beliefs.

Doctors and patients alike can take from this analysis less fear of stopping an antidepressant medication.

I am happy to report good news in the field of psychiatry.