Initial severity and antidepressant efficacy for anxiety disorders, obsessive‐compulsive disorder, and posttraumatic stress disorder: An individual patient data meta‐analysis

BACKGROUND: It has been suggested that antidepressant benefits are smaller for mild than severe depression. Because antidepressants are also used for anxiety disorders, obsessive‐compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), we examined the influence of severity for these disorders. METHODS: We used individual patient data of eight trials (3,430 participants) for generalized anxiety disorder (GAD); four trials (1,195 participants) for social anxiety disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071 participants) for PTSD; and 10 trials (2,151 participants) for panic disorder (PD). Mixed‐effects models were used to investigate an interaction between severity and treatment group. RESULTS: For GAD and PD, severity moderated antidepressant efficacy. The antidepressant–placebo difference was 1.4 (95% CI: 0.4–2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM‐A) points for participants with mild GAD (baseline HAM‐A = 10), increasing to 4.0 (3.4–4.6; SMD: 0.45) or greater for severely ill participants (HAM‐A ≥ 30). For PD, the difference was 0.4 (0.3–0.6) panic attacks/2 weeks for participants with 10 panic attacks/2 weeks at baseline, increasing to 4.7 (3.0–6.4) for participants with 40. For SAD, OCD, and PTSD, no interaction was found. Across severity levels, the differences were 16.1 (12.9–19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5–4.4, SMD: 0.39) Yale–Brown Obsessive‐Compulsive Scale points, and 10.3 (6.9–13.6; SMD: 0.41) Clinician‐Administered PTSD Scale points. CONCLUSIONS: Antidepressants are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and PD, however, benefits are small at low severity, and the benefit–risk ratio may be unfavorable for these patients.