Rates of relapse and recurrence in recent clinical trials of antidepressant therapy for depression
| Study | Prereatment | Groups to which patients were randomly assigned, n values | No. (and %) of patients who relapsed 3–6 mo after full remission | No. (and %) of patients who relapsed 7–10 mo after full remission | No. (and %) of patients with recurrence of depression after sustained remission for 4–6 mo | Patient types, definitions | |
|---|---|---|---|---|---|---|---|
| Patients in full remission before randomization | |||||||
| Reimherr et al (54) | 12- to 14-wk acute FLX | 6 mo | 9.5 mo | 62 wk | Outpatients with depression > 1 mo 86.6% rated as high probability of relapse MDD relapse criteria ×2 wk or HAM-D17 > × 14 × 3 wk Randomized as follows: FLX 20 mg/d ×14 wk, n = 97 FLX 20 mg/d ×38 wk, n = 100 FLX 20 mg/d ×50 wk, n = 102 Placebo ×50 wk, n = 95 | ||
| FLX 20 mg/d, n = 299 | 78 (26) | 9/105 (9) | 3/28 (11) | ||||
| Placebo, n = 95 | 46 (48) | 12/52 (23) | 5/34 (15) | ||||
| p < 0.001 | p < 0.04 | p = ns | |||||
| Montgomery and Dunbar (58) | 8-wk acute PRX | 4 mo | 12 mo | Recurrent depression (≥2 previous episodes) Relapse: CGI ≤4 or decline in CGI ≥2 or depressive symptoms ≥7 days or investigator opinion to treat Completers and dropouts not reported | |||
| PRX 20–30 mg, n = 68 | 2 (3) | 9/66 (14) | |||||
| Placebo, n = 67 | 13 (19) | 16/54 (30) | |||||
| p < 0.01 | p < 0.05 | ||||||
| Keller et al (59) | 12-wk acute SRT (sustained for 4 mo) | 76 wk | Chronic depression Response: 85% had HAM-D24 ≤ 10 Re-emergence of depression by consensus assessment Completers: SRT, n = 35; placebo, n = 24 | ||||
| SRT 200 mg/d, n = 77 | 20 (26) | ||||||
| Placebo, n = 84 | 42 (50) | ||||||
| p = 0.001 | |||||||
| Franchini et al (60), (61) | Remission with antidepressant therapy (sustained for 4 mo) | 2 yr | 4 yr | Recurrent depression (≥1 previous episodes) Remission: HAM-D < 8 Antidepressant therapy (77% tricyclics) Recurrence: clinical worsening, HAM-D > 15 All 64 patients completed study | |||
| SRT 100–200 mg/d, n = 32 | 7 (22) | 3/22 (14) | |||||
| FLV 200–300 mg/d, n = 32 | 6 (19) | 5/25 (20) | |||||
| p = ns | p = ns | ||||||
| Robert and Montgomery (62) | 8-week CTL | 6 mo | Patients with depression > 3 mo were excluded Relapse: both MADRS > 25 and clinical judgment of investigator | ||||
| CTL 20–60 mg, n = 152 | 21 (14) | ||||||
| Placebo, n = 74 | 18 (24) | ||||||
| p = 0.04 | |||||||
| Entsuah et al (66) | 8-wk acute VFX | 6 mo | Recurrent depression Remission: HAM-D21 ≤ 10 and CGI ≤3 Relapse: CGI > 4 or 2 CGI ≥4 or final CGI > 4 for any patient who withdrew for any reason | ||||
| VFX 75–225 mg/d, n = 161 | 45 (28) | ||||||
| Placebo, n = 157 | 82 (52) | ||||||
| p ≤0.05 | |||||||
| Thase et al (68) | 8- to 12-wk MTZ | 10 mo | Not reported Relapse: 1 HAM-D17 > 18 or 2 HAM-D17 = 15–17 | ||||
| MTZ | 19.7% | ||||||
| Placebo | 43.8% | ||||||
| n = 156 | p = ? | ||||||
| Patients with a response before randomization | |||||||
| Lonnqvist et al (65) | 6-wk acute therapy | 3 mo | 66% of patients first depressive episode Response: HAM-D17 ≤16 Relapse: both HAM-D17 > 16 and CGI > 3 Dropouts: MCL, 7/29; FLX, 3/30 | ||||
| MCL 300–450 mg/d, n = 29 | 2 (7) | ||||||
| FLX 20–40 mg/d, n = 30 | 1 (3) | ||||||
| Versiani et al (63) | 6-wk acute RBX | 6 mo | 12 mo | Recurrent MDD Response: > 50% decrease in HAM-D, Remission: HAM-D < 10 (66% of patients) Relapse: > 50% increase in HAM-D or HAM-D21> 18 Dropouts: RBX, 64/143; placebo, 75/140 | |||
| RBX 8 mg/d, n = 145 | 52/133 (39) | 9/75 (12) | |||||
| Placebo, n = 141 | 79/132 (60) | 20/49 (41) | |||||
| p ≤0.001 | p = 0.001 | ||||||
Note: CGI = Clinical Global Impressions; CTL = citalopram; FLV = fluvoxamine; MADRS = Montgomery–Asberg Depression Rating Scale; MTZ = mirtazapine; NFZ = nefazodone; ns = not significant. See Table 1 footnote for other abbreviations.