Eighteen studies were included in the review. Sample size ranged from 58 to 1,293 patients. Six studies evaluated SGAs as monotherapy and 12 studies evaluated SGAs as adjunctive therapy.
Quetiapine monotherapy: Two eight-week placebo-controlled studies each found a statistically significant greater mean change in MADRS total score from baseline to endpoint with 50mg (mean change from baseline -13.6, p<0.05 versus placebo), 150mg (-14.8, p<0.01) and 300mg (-15.3, p<0.01) of quetiapine extended release compared with placebo.
Sulpiride and amisulpride monotherapy: One study found a statistically significant greater mean change in the 21-item Hamilton Depression Rating Scale with 150mg to 300mg sulpiride compared with placebo (-10 versus -8, p<0.01). One study for amisulpride found a statistically significant greater mean change in MADRS with 50mg amisulpride compared with placebo (-12.7 versus -7.6, p<0.01) and with 100mg imipramine compared with placebo (-12.2 versus -7.6, p<0.05).
Results for other outcomes and for studies without placebo groups were reported.
Quetiapine adjunctive therapy: One study in treatment-resistant depressed patients found a statistically significant greater mean change in MADRS total score with 150mg and 300mg extended release quetiapine combined with antidepressants compared with placebo combined with antidepressants (-15.3/ -14.9 versus -12.2, p<0.01). A second study found a statistically significant greater mean change in MADRS total score with 300mg extended release quetiapine combined with antidepressants compared with placebo combined with antidepressants (-14.7 versus -11.7, p<0.01), but found no difference between 150mg extended release quetiapine combined with antidepressants compared with placebo combined with antidepressants.
Aripiprazole adjunctive therapy: Three studies all found statistically significant greater mean change in MADRS total score from baseline to endpoint with 2mg to 20mg aripiprazole combined with SSRIs/SNRIs compared with placebo combined with SSRIs/SNRIs (-10.1 versus -6.4, p<0.01, -8.5 versus -5.7, p<0.01 and -8.8 versus -5.8, p<0.01)
Olanzapine in combination with fluoxetine: One study of olanzapine in combination with fluoxetine showed a statistically significant greater mean change in MADRS total score from baseline to endpoint compared with olanzapine alone or fluoxetine alone (-12.6 versus -8.9/-9.2, p<0.01). One RCT that compared olanzapine in combination with fluoxetine to venlafaxine and one study that compared olanzapine in combination with fluoxetine with nortriptyline found greater mean change in MADRS total score in the course of the trials, but no difference by the endpoints.
Risperidone: One study found a statistically significant greater mean change in the 17-item Hamilton Depression Rating Scale with risperidone 1mg to 2mg combined with antidepressants compared with placebo combined with antidepressants (-10.8 versus -8.2, p<0.01)
Results for other outcomes were reported.
Safety/withdrawal due to adverse events was one- to three-fold higher with SGA than with placebo. Discontinuations were dose related. This was especially so in quetiapine trials, where patients who took lower doses withdrew less frequently. The most common events for withdrawal were sedation/somnolence (quetiapine, aripiprazole, risperidone, sulpiride), akathisia/restlessness (aripiprazole) and weight gain/increased appetite (olanzapine-fluoxetine combination, risperidone).