March 2025
Antidepressants reduce generalised anxiety disorder symptoms, finds Cochrane review
By Rebecca Jenkins
Antidepressants effectively reduce symptoms in patients with generalised anxiety disorder (GAD) compared with placebo, a Cochrane review finds.
Researchers said the review aimed to provide an updated summary of all the evidence available on antidepressants compared with placebo in GAD, including the efficacy and acceptability of the pharmacotherapy.
They included 37 unique randomised controlled trials with 12,226 participants, who were all adults with moderate-to-severe GAD and without any serious medical comorbidities.
The double-blind treatment duration of the included trials ranged from four weeks to 28 weeks, they noted.
Antidepressants were more effective than placebo in reducing anxiety symptoms, measured as a reduction of at least 50% on the Hamilton Anxiety Rating Scale (HAM-A; risk ratio [RR], 1.41).
The magnitude of effect corresponded to a number needed to treat for an additional beneficial (NNTB) outcome of 7.
The research also showed antidepressants had no difference in acceptability compared with placebo, as measured by the number of participants who dropped out of trials early.
Fewer people in the antidepressant group dropped out of the studies early due to the antidepressant being considered ineffective compared with placebo (RR, 0.41) with an NNTB of 27.
More participants dropped out due to adverse effects in the antidepressant group compared with placebo (RR, 2.18), with a number needed to treat for an additional harmful outcome of 17.
Professor Lisa Lampe, Conjoint Associate Professor in Psychiatry at the University of Newcastle, NSW, welcomed the findings and said the study helped to quantify the effectiveness of antidepressants over placebo.
‘The quality of the evidence is high and gives a high level of confidence in the findings,’ she told Medicine Today.
‘I think it is possible that clinicians may have had a more pessimistic view of how helpful antidepressants can be in GAD.’
However, Professor Lampe noted the main limitation with the review was the short duration of some of the included studies, which might have underestimated the treatment effect.
‘This is an important issue, and one very relevant to clinical practice, because it is now well established that response in anxiety disorders is typically slow, much slower than that seen in depression,’ she said.
The most commonly reported adverse events with antidepressants were sleepiness/drowsiness, she added, and, notably, there was no difference from placebo in the number reporting suicidal ideation.
The available data did not permit questions to be answered about which selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) to use.
‘It would also have been helpful to have reporting on doses used, even if this was just expressed as a ratio of the average dose to a therapeutic minimum dose,’ she said.
Overall, the review provided strong support for the current Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines, Professor Lampe concluded.
‘SSRIs and SNRIs remain the option of first choice, with a lack of robust evidence to support choice of any particular agent,’ she said.