Table 1.
Summary of the studies about augmentation with other ADs and buspirone in TRD.
| Reference | n | Age (Years) | Design | Augmentation Molecule | Dosage | AD | Duration | Primary Outcome Measures | Results |
|---|---|---|---|---|---|---|---|---|---|
| RCTs | |||||||||
| Altamura et al. [13] | 22 | 18–65 | Single-blind Comparison IV CIT/pcb | Citalopram | 10 mg/d (IV) | Paroxetine, Sertraline or Escitalopram | 5 days | HAM-D, MADRS | ↓ HAM-D: CIT > pcb (p < 0.01) ↓ MADRS: CIT > pcb (p < 0.05) |
| Licht and Qvitzau [16] | 253 | Mean (SD): 39 (±12) | Multicenter, double-blind Comparison SER100 + pcb/SER200 + pcb/SER100 + MIA | Mianserin | 30 mg/d | Sertraline | 5 weeks | HAM-D | ↓ HAM-D: - SER100 = SER100 + MIA (p = 0.85) - Both > SER200 (p < 0.05) |
| Kessler et al. [17] | 431 | 18–65 | Multicenter, double-blind Comparison mirtazapine/pcb | Mirtazapine | 30 mg/d | SSRIs or SNRIs | 1 year | BDI-II at week 12 | ↓ BDI-II: mirtazapine = pcb (p = 0.09) |
| Altamura et al. [18] | 54 | 18–65 | Head-to-head Single-blind Comparison IV CIT/CLO/pcb | Citalopram/clomipramine | CIT: 10 mg/d CLO: 25 mg/d | SSRIs | 5 days | HAM-D melancholy and anxiety-somatization scores | ↓ HAM-D: - CIT and CLO > pcb (p < 0.01) CIT = CLO on melancholy (p = 0.73) CIT > CLO on anxiety/somatization (p = 0.027) |
| Fava et al. [19] | 41 | Mean (SD): 39.6 (±9.9) | Head-to-head Double-blind Comparison FLU/FLU + Li/FLU + DES | Desipramine | FLU: 40–60 mg/d FLU 20 mg/d + Li: 300–600 mg/d FLU 20 mg/d + DES: 25–50 mg/d | Fluoxetine | 4 weeks | HAM-D | ↓ HAM-D: Whole sample: FLU > FLU + Li/FLU + DES (p = 0.05) Non-responders: FLU/FLU + Li > FLU + DES (p = 0.04) |
| Fava et al. [20] | 101 | Mean (SD): 41.6 (±10.6) | Head-to-head Double-blind Comparison FLU/FLU + Li/FLU + DES/pcb | Desipramine | ≈ | Fluoxetine | 4 weeks | HAM-D | FLU = FLU + Li = FLU + DES = pcb (p = 0.20) |
| Open studies | |||||||||
| Joffe and Schuller [14] | 25 | Range: 22–56 Mean: 40.2 | Open-label | Buspirone | Range: 20–50 mg/d Mean: 31.2 mg/d | Fluoxetine or Fluvoxamine | 3 weeks | CGI | Response rate: 68% Remission rate: 32% |
| Taylor and Prather [15] | 11 | Mean (SD): 53 (±10.5) | Open-label | Nefazodone | 50–300 mg/d Mean (SD): 200 (±134.2) mg/d | Various ADs | 9 months | Presence/absence anxiety/depression symptoms CGI | Depression remission (p < 0.005) Anxiety remission (p < 0.0005) |
| Navarro et al. [21] | 104 | Mean (SD): 47.9 (±8.4) | Head-to-head Open-label Comparison CIT/Li | Citalopram | CIT: 30 mg/d Li: 600 mg/d | Imipramine | 10 weeks | HAM-D | Remission: CIT > Li (p = 0.034) ↓ HAM-D: CIT > Li (p = 0.005) |
Key: ≈ = same as above; AD = antidepressant; BDI-II = Beck Depression Inventory—II; CGI = Clinical Global Impression; CIT = citalopram; CLO = clomipramine; d = day; DES = desipramine; FLU = fluoxetine; HAM-D = Hamilton Depression Rating Scale; IV = intravenous; Li = lithium; MADRS = Montgomery and Åsberg Depression Rating Scale; MIA = mianserin; pcb = placebo; RCT = randomized controlled trial; SD = standard deviation; SER = sertraline; SER100 = sertraline at 100 mg/d; SER200 = sertraline at 200 mg/d; SNRI = Serotonin and Norepinephrine Reuptake Inhibitor; SSRI = Selective Serotonin Reuptake Inhibitor.