Anxiety Medications Ranked, With Surprising Winner

Lavender oil is available by prescription outside the US as Silexan and Lasea. The same manufacturer sells it over-the-counter in the US as CalmAid.

Most anxiety drugs beat placebo, but only one also beats it on side effects

STUDY: Müller TJ et al, European Archives of Psychiatry and Clinical Neuroscience 2026

STUDY TYPE: Network meta-analysis (systematic review)

FUNDING: Schwabe Pharma AG (manufacturer of silexan)

Background

Generalized anxiety disorder (GAD) and related anxiety conditions are usually treated with SSRIs or SNRIs, but side effects and dependency concerns with benzodiazepines push many patients toward alternatives. In the past 15 years, Silexan, an oral lavender oil capsule, has emerged as a viable alternative.

The Study

• 100 randomized trials, 28,637 adults with GAD or another anxiety disorder
• Compared 20 drugs, including SSRIs, SNRIs, benzodiazepines, a tricyclic, an atypical antipsychotic, and silexan, against placebo and each other
• Average treatment length was about 10 weeks
• Outcomes: anxiety scale (HAM-A) change, all-cause discontinuation, and adverse events

Nearly every drug beat placebo on the anxiety scale (HAM-A) except the benzo clobazam. Clomipramine had the best efficacy but the worst acceptability, with the highest dropout rate. Silexan (lavender oil) ranked sixth of 19 drugs for efficacy and was just as acceptable as placebo for dropouts.

Only four treatments caused fewer side effects than placebo on any measure: diazepam, agomelatine, clobazam, and silexan. When plotting efficacy against moderate side effects specifically, silexan was the only one of the thirteen most effective drugs to land in the good-efficacy, good-safety zone.

Comparison to Guidelines

The research on lavender is relatively new, and some guidelines are catching up with it, with recommendation second-line by the Psychopharmacology Algorithm Project for generalized anxiety disorder (GAD) and endorsement by the World Federation of Biological Psychiatry and Canadian CANMAT guidelines for supplements (for both GAD and major depression).

However, most guidelines recommend SSRIs first-line for GAD, with heavy influence from the pharmaceutical industry, while this one arrives at Silexan, with direct funding from the manufacturer.

It’s no surprise that a Cochrane review of 21 studies concluded that financial conflicts of interest are associated with favorable recommendations in clinical guidelines.

Limitations

Industry funded studies and review. Heterogeneity between studies was substantial, reporting gaps blocked analysis of response and remission rates.

Practice Implications

1. There are a few examples where natural therapies surpass the effect size of medications. Silexan in GAD is one (marketed in the US as Calm Aid, 80 mg bid), confirmed by head-to-head trials and meta-analyses (in practice, I’ve seen a difference with it). It also has a tolerability advantage.
2. The caveat is industry funding, a problem shared by pharmaceuticals.

—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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