children and young people
NNTB/NNTH Remission (or NNTB 9 (NNTB 4 – –
7.5 Antidepressant drug versus psychological therapies, and the combination
7.5.1 Introduction
Little research has focused on the direct comparison of antidepressants with
trial, conducted by the Treatment for Adolescents With Depression Study (TADS) team, is the largest community sampled trial of depression in young people. The first stage of the study assessed the safety and effectiveness of fluoxetine, CBT, and their combination when compared with placebo in 439 young people (12–17 years) with moderate to severe depression. It is important to note that while the group receiving fluoxetine alone or placebo were blind to treatment, those in the combined treatment group were
informed they were receiving fluoxetine, and those receiving CBT were by necessity unblind to treatment.
There is also at least one ongoing study, the Treatment Of Resistant Depression In Adolescents (TORDIA), which aims to recruit 400 boys and girls aged 12–18 years, who are currently prescribed an SSRI, to a 12-week RCT. There are four conditions: (1) switching to an alternative SSRI, (2) switching to a different non-SSRI antidepressant, (3) switching to an alternative SSRI and receiving CBT, or (4) switching to a different non-SSRI antidepressant and receiving CBT. More information can be found through the following website: http://clinicaltrials.gov/show/NCT00018902.
7.5.2 Treatment included
The following treatments were included:
G Fluoxetine
G CBT.
7.5.3 Studies considered
The review team conducted a new systematic search for RCTs that assessed the efficacy of an antidepressant versus a psychological intervention and/or the combination.
One trial (TADS200416) met the eligibility criteria set by the GDG, providing data on 439
participants. TADS2004 randomised participants to fluoxetine alone (n 109), CBT alone
(n 111), fluoxetine with CBT (n 107), or placebo (n 112). The duration of the study was 12 weeks. All participants were diagnosed with major depressive disorder
by DSM-IV and were aged 12–17 years. Based on the Children’s Depression Rating Scale – Revised (CDRS-R), participants had moderate to severe depression, with 27% having at least minimal suicidal ideation at baseline. Those randomised to fluoxetine alone or placebo were blind to treatment, whereas those receiving the combination of fluoxetine and CBT were not.
A further study (MANDOKI1997), randomised 40 participants with depression
aged 8–18 years to venlafaxine with psychotherapy (n 20) or psychotherapy
alone (n 20). However, this study was excluded from the analysis because it provided no information about the type of psychotherapy used or whether it was manualised.
16This study was also included in the analysis of antidepressants versus placebo and the analysis of
7.5.4 Fluoxetine alone versus CBT alone
Table 19:Evidence summary table for fluoxetine alone/Fluoxetine combined with CBT versus CBT alone/Placebo/Fluoxetine alone
Fluoxetine Fluoxetine Fluoxetine Fluoxetine
alone vs. with CBT with CBT with CBT vs.
CBT alone vs. placebo vs. fluoxetine CBT alone
alone
Published Published Published Published
only only only only
Total no. of 1 RCT (220) 1 RCT (219) 1 RCT (216) 1 RCT (218)
trials (total no. of participants) Depressive symptoms Clinician completed CDRS-R G G 䊊 G K 1; N 220 K 1; N 219 K 1; N 216 K 1; N 218 Clinical Improvement Clinician completed CGI-I 䊊 G 䊊 䊊 K 1; N 220 K 1; N 219 K 1; N 216 K 1; N 218 Harms Harm-related ? adverse event K 1; N 220 K 1; N 219 K 1; N 216 K 1; N 218 Suicide attempts K 1; N 220 K 1; N 219 K 1; N 216 K 1; N 218 Suicide-related 䊊 events K 1; N 220 K 1; N 219 K 1; N 216 K 1; N 218 Suicide ideation 䊊 (SIQ) K 1; N 220 K 1; N 219 K 1; N 216 K 1; N 218 NNTB/NNTH Clinical NNTB 6 NNTB 3 NNTB 10 NNTB 4 improvement (CGI) (4 to 25) (2 to 5) (5 to 50) (3 to 7) Harm-related 11.9% vs. 8.4% vs. 5.4%: 8.4% vs. 11.9% vs. adverse event 4.5%: NNTH NNTH 33 11.9%: NNTB 4.5%: NNTH 14 (7 to 455) (NNTH 11 to 29 (NNTB 9 to 14 (7 to 455) to NNTB 28) to NNTH 23) Suicide attempts 1.8% vs. 0.9%: 3.7% vs. 0%: 3.7% vs. 1.8%: 1.8% vs. NNTH 108 NNTH 27 NNTH 53 0.9%: (NNTH 25 to (NNTH 13 to (NNTH 16 to NNTH 108 to NNTB 47) to NNTB 455) to NNTB 42) (NNTH 25 to to NNTB 47) Continued
7.5.5 Clinical summary
For individual outcomes, the quality of the evidence was moderate, reflecting the fact only one study was included in the review.
Fluoxetine alone versus CBT
Fluoxetine (up to 40 mg/day for 12 weeks) alone showed evidence of a reduction in depressive symptoms and limited evidence of global clinical improvement
when compared with CBT (15 sessions of between 50 and 60 minutes for 12 weeks) alone.
There is limited evidence favouring CBT in relation to harm-related adverse events, suicide attempts, suicide-related events and suicidal ideation.
Fluoxetine plus CBT versus placebo
There is evidence that fluoxetine (up to 40 mg/day for 12 weeks) in combination with CBT (15 sessions of between 50 and 60 minutes for 12 weeks) reduces depressive symptoms and produces global clinical improvement when compared with placebo.
There is limited evidence that fluoxetine in combination with CBT is more likely to bring about increases in harm-related adverse events, suicide attempts and suicide-related events than placebo. However, this was not confirmed by a self-report measure of suicidal ideation, which suggested no increase in risk.
Fluoxetine plus CBT versus fluoxetine alone
There is limited evidence that fluoxetine in combination with CBT reduces depressive symptoms and produces global clinical improvement when compared with fluoxetine alone. Table 19: (Continued) Suicide-related 5.6% vs. 4.5%: 5.6% vs. 3.6%: 5.6% vs. 8.3%: 5.6% vs. 4.5%: events NNTH 91 NNTH 50 NNTB 38 NNTH 91 (NNTH 15 to (NNTH 14 to (NNTB 11 to (NNTH 15 to to NNTB 22) to NNTB 29) to NNTH 25) to NNTB 22)
Note. G evidence of a clinically important effect favouring treatment A; 䊊 limited evidence of a clinically
important effect favouring treatment A; limited evidence of clinically important effect favouring treatment B; there is unlikely to be a clinically important difference between groups; ? the evidence is inconclusive.
Fluoxetine Fluoxetine Fluoxetine Fluoxetine
alone vs. with CBT with CBT with CBT vs.
CBT alone vs. placebo vs. fluoxetine CBT alone
alone
Published Published Published Published
only only only only
Total no. of 1 RCT (220) 1 RCT (219) 1 RCT (216) 1 RCT (218)
trials (total no. of participants)
There is limited evidence that fluoxetine in combination with CBT is less likely to bring about suicide-related events and suicidal ideation but more likely to bring about suicidal attempts. Evidence regarding harm-related adverse events is inconclusive.
Fluoxetine plus CBT versus CBT alone
Fluoxetine in combination with CBT showed evidence of a reduction in depressive symptoms and limited evidence of global clinical improvement when compared with CBT alone.
There is limited evidence that fluoxetine in combination with CBT is more likely to bring about increases in harm-related adverse events, suicide attempts and suicide-related events than CBT alone. There is evidence that fluoxetine in combination with CBT produces no difference in suicidal ideation when compared with CBT alone.
Conclusion
Fluoxetine in combination with CBT is more effective in reducing depressive symptoms and producing global clinical improvement. The effect is strongest when compared with placebo and weakest when compared with fluoxetine alone.
There is limited evidence suggesting that the fluoxetine may increase suicidal ideation and /or behaviour but that the addition of CBT may reduce this risk.