Antidepressants may improve treatment response in generalized anxiety disorder vs. placebo

Key takeaways:

• Treatment of generalized anxiety disorder with an antidepressant increased the treatment response rate by 41%.
• Fewer patients who received antidepressants dropped out due to lack of efficacy.

Antidepressants were more effective than placebo in reducing anxiety symptoms among adults with moderate to severe generalized anxiety disorder, according to a review published in Cochrane Database of Systematic Reviews.

“The research shows that antidepressants are highly effective at treating generalized anxiety disorder, at least in the specific circumstances seen in trials,” Giuseppe Guaiana, MD, MSc, PhD, FRCPC, associate professor of psychiatry in the Schulich School of Medicine & Dentistry at Western University in London, Ontario, Canada, and chief of psychiatry at St. Thomas Elgin General Hospital in St. Thomas, Canada, said in a press release. “For people with generalized anxiety disorder and no other conditions, we have good evidence that antidepressants lead to clinically meaningful improvements over a 1- to 3-month period compared to placebo.”

Guaiana and colleagues searched the CENTRAL, MEDLINE, Embase and PsycINFO databases, the Cochrane Common Mental Health Disorders register and two trial registers to perform a systematic review and meta-analysis of 37 randomized controlled trials including 12,226 adults aged 18 years or older with moderate to severe generalized anxiety disorder and no serious medical comorbidities.

Patients were randomly assigned to receive an antidepressant or placebo; double-blind treatment duration ranged from 4 to 28 weeks.

The researchers observed that treatment with an antidepressant increased the rate of treatment response — as measured by a 50% or greater reduction on the Hamilton Anxiety Rating Scale — by 41% vs. treatment with placebo (RR = 1.41; 95% CI, 1.29-1.55).

They found no significant difference in dropout rates between patients who received antidepressants and those who received placebo (RR = 1.03; 95% CI, 0.93-1.14).

Additionally, they found that patients assigned antidepressants were less likely to drop out due to a lack of efficacy (RR = 0.41; 95% CI, 0.33-0.5) but more likely to drop out due to adverse effects (RR = 2.18; 95% CI, 1.81-2.61) compared with the placebo groups.

The researchers acknowledged several study limitations, including the exclusion of patients with generalized anxiety disorder and other co-occurring medical conditions.

“We don’t have enough evidence to say how effective [antidepressants] may be in patients with generalized anxiety disorder alongside other mental health conditions, which is much more common in clinical practice,” Guaiana said in the release. “Most of the patients I see with generalized anxiety disorder also have other mental health conditions, so future trials should investigate the effects of different treatment strategies on patients with multiple conditions.”

They also noted that most trials included in the analysis lacked long-term follow-up data.

“We don’t have enough information on the potential long-term benefits and harms of antidepressants, even though people often taken them for years,” lead study author Katarina Kopcalic, MS, of the department of epidemiology and biostatistics at Western University, said in the release. “This is an area that needs further exploration in future trials.”

Reference:

• Antidepressants reduce anxiety, but long-term impact remains unclear. https://www.cochrane.org/news/antidepressants-reduce-anxiety-long-term-impact-remains-unclear. Published Jan. 29, 2025. Accessed Feb. 11, 2025.