Ten randomised controlled trials (RCTs; n=2,344) were included, of which 7 were published (n=1,619). Five included adolescents only (range: 12 to 18 years; n=1,273)
Eight studies reported baseline patient demographics by treatment group. Five studies reported similar demographics between the treatment groups, 2 studies reported a difference in history of depression or anxiety between the treatment groups, and 1 study reported a difference in the gender distribution of participants between the treatment groups.
Efficacy.
Three (n=754) out of 4 RCTs of fluoxetine versus placebo showed statistically significant improvements in depression scores in the intervention group, using the CGI and the CDRS-R scales. There was no statistically significant difference between the groups in the fourth RCT (n=40).
One RCT (n=275) found a statistically significant difference between paroxetine and placebo, measured using the HAM-D, K-SADS-L and CGI scales. There was no difference between imipramine and placebo on any measures in the same study. Two other (unpublished) RCTs of paroxetine versus placebo (n=792) found no statistically significant difference between the groups. One RCT (n=174) of citalopram found a statistically significant benefit for citalopram in remission rates, measured by CDRS-R response. A second (unpublished) study (n=233) found no significant difference in depression scores between the citalopram and placebo groups.
A single study of sertraline (n=376) showed a statistically significant benefit for sertraline compared with placebo, using the CDRS-R and CGI subscale scores.
Tolerability and safety.
Where reported, study withdrawal rates due to adverse events ranged from nil to 9.7% and were highest for paroxetine. Seven studies described adverse events, commonly dry mouth, vomiting, nausea, diarrhoea, somnolence, insomnia, dizziness, tremor and agitation. Adverse events were more common in the SSRI group than in the placebo group, though this was rarely reported to reach statistical significance.
Serious adverse events (significant psychiatric symptoms or requirement for hospitalisation) were also more common in the intervention groups. The largest study (n=439) reported a significantly increased risk of harm to self or others associated with fluoxetine, with an apparent protective effect conferred by concurrent CBT.
The authors noted that potentially relevant unpublished data on safety were not available to them for the review, and cited other publications indicating increased risk of suicidal ideation or attempt associated with the use of SSRIs in young people (see Other Publications of Related Interest nos.1-2).