Question 1

Which anxiety medication class should I try first, and how do they compare head-to-head?

Accepted Answer

The 2025 Cochrane review of 37 RCTs (12,226 adults with generalized anxiety disorder [GAD]) found antidepressants produce number needed to treat (NNT) 7 for response and number needed to harm (NNH) 17 for adverse events — a favorable benefit-to-harm ratio (Kopcalic et al., 2025; ch03/lesson-01, Section 1.2). SSRIs are first-line across all major guidelines (CANMAT, WFSBP, NICE, APA). SSRIs and SNRIs are largely equivalent in anxiolytic efficacy (aggregate standardized mean difference [SMD] -0.56, medium effect, vs placebo; Gosmann et al., 2021); the differential is safety and tolerability. TCAs show comparable efficacy (pre-post d=1.83, large effect, Bandelow 2015; pre-post effect size, not directly comparable to placebo-controlled SMD) but are third-line due to narrow therapeutic index and overdose lethality (Buckley & McManus, 2002). Buspirone is FDA-approved for GAD (d=0.17, small effect; Hidalgo 2007) with good tolerability and no dependence risk. Benzodiazepines provide rapid anxiolysis (NNT 4 for panic response, Breilmann 2019 Cochrane; note: NNT values from different disorders/populations, not directly comparable) but are not first-line monotherapy due to dependence risk.

Question 2

What are the effect sizes for SSRIs vs SNRIs vs TCAs vs benzodiazepines?

Accepted Answer

The 2025 Cochrane review of 37 RCTs (12,226 adults with generalized anxiety disorder [GAD]) found antidepressants produce number needed to treat (NNT) 7 for response and number needed to harm (NNH) 17 for adverse events — a favorable benefit-to-harm ratio (Kopcalic et al., 2025; ch03/lesson-01, Section 1.2). SSRIs are first-line across all major guidelines (CANMAT, WFSBP, NICE, APA). SSRIs and SNRIs are largely equivalent in anxiolytic efficacy (aggregate standardized mean difference [SMD] -0.56, medium effect, vs placebo; Gosmann et al., 2021); the differential is safety and tolerability. TCAs show comparable efficacy (pre-post d=1.83, large effect, Bandelow 2015; pre-post effect size, not directly comparable to placebo-controlled SMD) but are third-line due to narrow therapeutic index and overdose lethality (Buckley & McManus, 2002). Buspirone is FDA-approved for GAD (d=0.17, small effect; Hidalgo 2007) with good tolerability and no dependence risk. Benzodiazepines provide rapid anxiolysis (NNT 4 for panic response, Breilmann 2019 Cochrane; note: NNT values from different disorders/populations, not directly comparable) but are not first-line monotherapy due to dependence risk.

Question 3

If SSRIs and SNRIs have similar efficacy, why are SSRIs preferred?

Accepted Answer

The 2025 Cochrane review of 37 RCTs (12,226 adults with generalized anxiety disorder [GAD]) found antidepressants produce number needed to treat (NNT) 7 for response and number needed to harm (NNH) 17 for adverse events — a favorable benefit-to-harm ratio (Kopcalic et al., 2025; ch03/lesson-01, Section 1.2). SSRIs are first-line across all major guidelines (CANMAT, WFSBP, NICE, APA). SSRIs and SNRIs are largely equivalent in anxiolytic efficacy (aggregate standardized mean difference [SMD] -0.56, medium effect, vs placebo; Gosmann et al., 2021); the differential is safety and tolerability. TCAs show comparable efficacy (pre-post d=1.83, large effect, Bandelow 2015; pre-post effect size, not directly comparable to placebo-controlled SMD) but are third-line due to narrow therapeutic index and overdose lethality (Buckley & McManus, 2002). Buspirone is FDA-approved for GAD (d=0.17, small effect; Hidalgo 2007) with good tolerability and no dependence risk. Benzodiazepines provide rapid anxiolysis (NNT 4 for panic response, Breilmann 2019 Cochrane; note: NNT values from different disorders/populations, not directly comparable) but are not first-line monotherapy due to dependence risk.

Question 4

Is there any scenario where a TCA should be first-line over an SSRI?

Accepted Answer

The 2025 Cochrane review of 37 RCTs (12,226 adults with generalized anxiety disorder [GAD]) found antidepressants produce number needed to treat (NNT) 7 for response and number needed to harm (NNH) 17 for adverse events — a favorable benefit-to-harm ratio (Kopcalic et al., 2025; ch03/lesson-01, Section 1.2). SSRIs are first-line across all major guidelines (CANMAT, WFSBP, NICE, APA). SSRIs and SNRIs are largely equivalent in anxiolytic efficacy (aggregate standardized mean difference [SMD] -0.56, medium effect, vs placebo; Gosmann et al., 2021); the differential is safety and tolerability. TCAs show comparable efficacy (pre-post d=1.83, large effect, Bandelow 2015; pre-post effect size, not directly comparable to placebo-controlled SMD) but are third-line due to narrow therapeutic index and overdose lethality (Buckley & McManus, 2002). Buspirone is FDA-approved for GAD (d=0.17, small effect; Hidalgo 2007) with good tolerability and no dependence risk. Benzodiazepines provide rapid anxiolysis (NNT 4 for panic response, Breilmann 2019 Cochrane; note: NNT values from different disorders/populations, not directly comparable) but are not first-line monotherapy due to dependence risk.

PsychHQ

First-Line Medication for Anxiety: Why SSRIs Win and When to Consider Alternatives