In this study, we report on later remission rates in pediatric depression. Earlier we reported on acute remission outcomes for the TADS sample,6
with 23% of patients having achieved remission. Although this rate was relatively low, the present report found that later remission rates are considerably better. By week 36 the overall estimated remission rate is around 60%, more than doubling the rate found at week 12. This remission rate is comparable to the overall cumulative remission rate found in the STAR*D trial, which was 67%.39
These findings highlight the importance of continuation and maintenance phase treatments, as the rates of remission improve with time and continued treatment. While the outcome for the majority of patients who continue in treatment is promising, it is important to recognize that a substantial number of patients who undergo nine months of treatment fail to achieve remission.
Combination treatment and fluoxetine monotherapy achieved significantly higher rates of remission early in treatment (Week 6), compared to CBT (only 4%). The combination of fluoxetine and CBT was superior to both monotherapies at weeks 12 and 18. By week 24 all active treatment conditions converged on rates of remission. The superiority of combination treatment over both monotherapies at week 18 is especially important to note, as all treatment conditions were open label beginning at week 12. Thus, selecting a monotherapy treatment could mean a delay of remission for a substantial number of depressed adolescent patients by two to three months. These findings mirrored the longer-term outcomes recently reported on response rates.32
Between 65 and 72% of adolescents who reached remission during acute treatment maintained it through continuation and maintenance therapies. Thus, these adolescents had recovered from their depression as defined by the ACNP definition of recovery, which is sustained remission for four months.12
No differences were found on rates of recovery across treatment groups. This recovery rate was similar to the rates of sustained remission as reported in the adult literature (67 – 86%).9–11
While not statistically significant, it does appear that those remitters who received CBT monotherapy had slightly higher rates of recovery (ranging from 77.8 to 87.5%), which is consistent with findings in the adult depression CBT outcome literature.40
Conversely, one third of patients achieving remission did not maintain remission during continuation and maintenance treatments. This finding has important clinical implications, as it highlights the need to continue to monitor patients even after they have reached remission status. Furthermore, the loss of remission status in one third of patients may have methodological implications in future studies of remission. For example, a last observation carried forward (LOCF) approach to this missing data in analyses of remission may be misleading, as it may not capture variations in remission rates over time.
The presence of residual symptoms provided important prognostic information on later remission achievement. Greater numbers of symptoms remaining at the end of 12 weeks of treatment were predictive of later remission status. This was true at both 18 and 36 weeks.
Finally, participants assigned to combination treatment tended to stay in TADS COMB. However, those assigned to a TADS monotherapy tended to augment with either medication (in the case of CBT) and with psychosocial treatment (in the case of FLX) in later stages of treatment. It is unclear if this was based on a clinician decision or a patient decision, but it suggests that there is a belief that combination treatment is preferable.
These findings should be evaluated in light of the adopted definitions of remission and recovery, possible influence of mere passage of time, and experimental sample size. An accepted definition of remission, based on normative data (i.e., CDRS-R ≤ 28) was used for these analyses; however a different definition might result in different findings. In addition, we were restricted to measuring remission according to a set assessment schedule, and thus were not able to capture or properly analyze timing of remission.
Although we found that remission rates improved over time and concluded that this was related to continued treatment, it is possible that the mere passage of time contributed partially or fully to higher remission rates. Studies of depressed youth which include long term follow-up assessments frequently find that experimental groups and control groups converge on later outcomes.41
Furthermore, Kovacs has reported that the length of an episode is typically 9 months with most youth having recovered by one year.14–15
It is possible, that at 36 weeks, our patients were out of their episode as a result of time and not treatment. However, the mean episode duration in the study was greater than one year and more than half the sample had received prior treatment, yet these participants continued to meet criteria for depression (i.e., had not recovered).33
Thus, in our sample, spontaneous remission is unlikely, due to the illness severity of these patients and past treatment of this sample.33
Our study is also limited by the design in which all participants were in open treatment after week 12. For ethical reasons, we could not create and follow an untreated group of depressed adolescents for nine months. To truly evaluate the effects on continuation treatment, one would need to conduct an RCT of continuation care versus a control condition, such that of Emslie and colleagues.25
Finally, the smaller sample sizes at subsequent weeks due to attrition and removal of the PBO arm may have limited our ability to adequately investigate questions of treatment group differences and their impact on the achievement and maintenance of remission.
Despite the early low remission rates, the majority of depressed adolescents go on to achieve remission after nine months of treatment. Methods of achieving higher or more rapid remission rates are still needed. A better understanding of which remitted patients will fail to maintain their recovery and how to better assist them is also necessary. Clinicians should be particularly attentive to the presence of residual symptoms remaining after initial treatment response.