A 2026 dose-informed network meta-analysis of 92 RCTs in 14,510 patients with panic disorder found that alprazolam, fluvoxamine, and fluoxetine most consistently beat placebo for anxiety symptoms, while fluvoxamine and alprazolam sustained-release also lowered weekly panic attacks. The study also found that the biggest apparent effect, brofaromine (SMD -2.47), came from lower-quality evidence, a reminder that your frontline judgment matters as much as the ranking table.

Why It Matters To Your Practice

• NPs and PAs are often the first clinicians patients trust when panic symptoms hit, and this analysis reinforces that your medication choices can quickly shape symptom control and follow-up success.

• This was the first dose-accounting network meta-analysis for panic disorder, with and without agoraphobia, comparing 36 treatment combinations across a large RCT evidence base.

• The most credible signal: several familiar agents outperformed placebo, but not all “top” results were equally trustworthy once study quality was considered.

Clinical Benefits

• For anxiety symptom reduction, the strongest supported options versus placebo were alprazolam (SMD -0.66), sublingual alprazolam (SMD -0.61), fluvoxamine (SMD -0.53), fluoxetine (SMD -0.52), and alprazolam sustained-release (SMD -0.41).

• For treatment response, imipramine, alprazolam, and brofaromine outperformed placebo.

• For reducing weekly panic attacks, fluvoxamine (SMD -0.33) and alprazolam sustained-release (SMD -0.30) outperformed placebo.

• Practical takeaway: if you need a medication with evidence across both symptom burden and attack frequency, fluvoxamine and alprazolam sustained-release stand out.

Managing Risks

• Don’t over-read the largest effect size: brofaromine looked best numerically, but stronger effects tracked with lower study quality in meta-regression.

• Benzodiazepines may help quickly, but they still require the kind of careful monitoring, dependence-risk counseling, and reassessment that experienced NPs and PAs routinely do well.

• Match the drug to the patient in front of you: comorbid depression, substance use risk, sedation concerns, adherence barriers, and need for rapid relief should drive selection.

• The analysis also assessed tolerability, remission, acceptability, and specific adverse events, so medication choice should balance efficacy with real-world staying power.

The Bottom Line

• Your role is not “backup” to physician care here, it is central: panic disorder is frontline medicine, and your prescribing decisions can change the trajectory fast.

• Best-supported everyday options from this review include fluvoxamine, fluoxetine, and alprazolam formulations, with fluvoxamine and alprazolam sustained-release showing added benefit on panic-attack frequency.

• Use the rankings intelligently, not blindly: the flashiest result came from weaker-quality evidence, so the highest-value care still depends on your clinical read, follow-up plan, and patient partnership.

Reference: Efficacy and safety of pharmacological interventions for panic disorder with or without agoraphobia: A systematic review and network meta-analysis, accounting for dose.