Table 3 Study characteristics and main results

Beasley 2000 (1) [28]

TCAs vs Flx (doses 20–80 mg/die): greatest incidence of cholinergic ADEs (dry mouth, constipation, abnormal vision), sedation (somnolence), orthostatic (dizziness) and paresthesia in TCAs group.

Flx (doses 20–80 mg/die) vs pla: greatest incidence of gastrointestinal ADEs (dyspepsia, nausea, anorexia, diarrhea), sedating (somnolence, asthenia), activation (insomnia, nervousness, anxiety), tremor, sweating, dizziness in Flx group.

Flx 20 mg die vs pla: nervousness, tremor, dizziness, dyspepsia no more common than pla.

Total drop-out: flx (20–80) 35.2%, TCAs 47.9% (p < 0.001.); total drop-out: flx (20–80) 37.7%, pla 38.2% (p = n.s.); total drop-out: flx (20) 29.0%, pla 27.5% (p = n.s.);

Drop-out for ADE: flx (20–80) 16.4%, TCAs 31.4% (p < 0.001); drop-out for ADE: flx (20–80) 13.7%, pla 6.0% (p < 0.001); drop-out for ADE: flx (20) 9.0%, pla 7.7% (p = n.s.);

Drop-out for lack of efficacy: flx (20–80) 9.5%, TCAs 7.8% (p = n.s.); drop-out for lack of efficacy: flx (20–80) 10.6%, pla 22.3% (p < 0.001); drop-out for lack of efficacy: flx (20) 8.8%, pla 11.3% (p = 0.029);

Beasley 2000 (2)[29]

For minimal therapeutic exposure HDRS-17 responders flx v pla: +24.8%; p < 0.01; HDRS-17 remitters (HDRS ≤ 7 at last visit) flx v pla: +17.5%; p < 0.01.

For intent-to-treat responders flx v pla: +20.5%; p < 0.01; remitters flx v pla: +13.3%; p < 0.01.

Bech 2000[31]

HDRS-17 responders flx v pla: +21.4% (efficacy analysis); +13.6% intention to treat analysis. Overall Odds ratio = 2.22 (95% CI: 1.83–2.70; p < 0.01).

CGI responders flx v pla: +24.3% (efficacy analysis); +14.3% (intention to treat analysis). Overall Odds ratio = 2.20 (95% CI: 1.83–2.66; p < 0.01).

Total drop-out: Odds ratio flx vs TCAs: 0.75 (95% CI: 0.62–0.90; p < 0.01).

Drop-out for adverse event: Odds ratio flx vs TCAs: 0.53 (95% CI: 0.42–0.67; p < 0.01).

Tollefson 1994[34]