The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.
Using the intent to treat sample, 27 [56%] of those receiving fluoxetine and 16 [33%] receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit [Chi-squared=5.1, df=1, P=.02]. Significant differences were also noted in weekly ratings of the Children’s Depression Rating Scale-Revised after 5 weeks of treatment [using last observation carried forward]. Equivalent response rates were found for patients aged 12 years and younger [n=48] and those aged 13 years and older [n=48]. However, complete symptom remission [Children's Depression Rating Scale-Revised] occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients.
Significantly more fluoxetine treated patients [41.3%] than placebo-treated patients [19.8%] met the prospectively defined criteria for remission [p < .01].
The rate of remitted subjects at the end of treatment, based on the dichotomized CDRS-R, was 102 of 439, or 23%. There was a significant overall treatment [Wald x2= 17.08, df = 3, p = .0007] and site [Wald x2 = 21.5, df =12, p = .04] effect. More specifically, the COMB group with a 37% remission rate was superior to all of the other treatment conditions [FLX: 23%, p = .02; CBT: 16%, p = .0004; PBO: 17%, p = .0009]. However, the FLX, CBT, and PBO rates were not statistically different from one another [p 9 .05]….
The overall rate of response, defined as a CGI-I score of 1 or 2 in the intention-to-treat sample was 229 of 439, or 52% [TADS, 2004]. As previously reported, response rates by treatment arm were as follows: 71.0% [COMB], 60.6% [FLX], 43.2% [CBT], and 34.8% [PBO].
GIBBONS et al
|Youth Studies of Fluoxetine
In youth studies of fluoxetine, the estimated average rates of change over 6 weeks were −15.96 CDRS-R units for placebo and −20.58 CDRS-R units for fluoxetine [MMLE=−4.62; SE=1.26; P<.001], indicating 29.0% greater improvement for fluoxetine. The estimated response rates were 29.8% for fluoxetine vs 5.7% for placebo [OR=6.66; 95% CI, 3.07- 14.48; P<.001; NNT=4.16]. Remission rates were 46.6% vs 16.5% for fluoxetine and placebo, respectively [OR=4.23; 95% CI, 2.64-6.77; P<.001;NNT=3.33]. The finding of higher remission rates than response rates questions the validity of the CDRS-R remission threshold score of 28. No effect of baseline severity on treatment efficacy was found [P=.90]. For patients with low severity, the rates of change in symptoms were −17.60 CDRS-R units for fluoxetine vs −12.56 CDRS-R units for placebo. For patients with high severity, the rates of change were −28.86 CDRS-R units for fluoxetine vs −24.40 CDRS-R units for placebo. The estimated differences were 5.04 CDRS-R units [95% CI, 2.56 to 7.52] for low severity and 4.45 CDRS-R units [95% CI, −0.58 to 9.49] for high severity. Estimated response rates for treated vs placebo receiving patients were 23.0% vs 3.2% [difference of 19.8%], respectively, for low severity and 40.2% vs 17.2% [difference of 23.0%], respectively, for high severity. Estimated remission rates for treated vs placebo-receiving patients were 54.1% vs 19.4% [difference of 34.7%], respectively, for low severity and 28.9% vs 7.5% [difference of 21.4%], respectively, for high severity.
The outcome criteria for Gibbons et al are:
Using the values from above, we can construct the following table comparing the reported results between the pertinent input studies [X065, HCEJ, and TADS] and Gibbons’ outcome for the meta-analysis of all four studies. Recall that the lower the Number Needed to Treat, the more efficacious the treatment [NNT = 1 ÷ diff]. And it all comes down to the red numbers in the table below – the outcome variables [NNT] from the original studies that fit the same criteria used by Gibbons:
As I said, there was no way for me to adjust the number to make up for the fact that Gibbons didn’t use all the data, but I still think if anything it would decrease efficacy. For the numbers I could compute, Gibbon’s outcome was better that any of the studies he used for his meta-analysis. And that’s before the decrease from the negative study LYAQ and whatever efficacy he lost by cutting off the end of the others. I find that
remarkable impossible. How can the meta-analysis be better than any of the pieces used to derive it? better for remission in all cases? better in the one case where we can make direct response rate comparisons? better absent the effect of a large negative study with 24% of the overall subject pool?