REVIEW OF: Munkholm K et al, Eur Arch Psychiatry Clin Neurosci 2024;274(3):475–486

STUDY TYPE: Meta-analysis of placebo-controlled trials

Patients often ask for rapid-acting medications for the short-term treatment of anxiety, but how safe and effective are the options?

Researchers reviewed randomized controlled trials (RCTs) that examined benzodiazepines, sedating antipsychotics and antidepressants, antihistamines, melatonin, Z-drugs, and pregabalin for treating acute stress disorder, adjustment disorder, mild to moderate depression, and anxiety. Primary outcomes were the Hamilton Rating Scale for Anxiety (HAM-A), daily functioning, and serious adverse events. 

Their search yielded 34 RCTs involving 7,044 patients. Benzodiazepines, quetiapine, and pregabalin significantly reduced anxiety compared to placebo. Compared to placebo, the standardized mean differences on the HAM-A after one to four weeks of treatment were -0.58 (95% confidence interval [CI]: -0.77 to -0.40) for benzodiazepines, -0.51 (95% CI: -0.90 to -0.13) for quetiapine, and -0.58 (95% CI: -0.87 to -0.28) for pregabalin. Notably, no significant differences in symptom reduction were found between them. However, the authors rated the certainty of this evidence as low to very low. Only a handful of trials reported symptom chronicity—a significant absence, as the focus of this review was on acute symptoms. Adverse side effects were inconsistently reported, and thus researchers did not draw conclusions regarding tolerability.

CARLAT TAKE

In this study, quetiapine and pregabalin are viable alternatives to benzodiazepines for treating new-onset acute anxiety over short time periods. When choosing among them, consider cardiac history, as quetiapine is associated with the risk of arrhythmia, as well as metabolic side effects and tardive dyskinesia. Generally, aim for quetiapine ≤ 150 mg daily, starting as low as 12.5 mg every eight hours as needed. When dosing pregabalin, consider chronic kidney disease due to its renal excretion. For most patients, start at 75 mg twice daily.