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Adding cognitive behaviour therapy to SSRIs is unlikely to improve outcomes
Around 3-5% of adolescents are affected by clinical depression worldwide.1 2 3 4 Although specific data on depression are not available, an Australian survey found 26% of adolescents with mental disorders were treated in general or paediatric practice, while only 9% received care from specialist mental health services.3
Episodes of depression generally last about seven to nine months. Probability of relapse is 40% within two years and 70% after five years.5 Depression can be devastating to a young person's academic and social development and can adversely affect family relationships, especially if the problems are misunderstood.
Optimal treatment for depression in adolescents is unclear. Concern about an increased rate of suicidal behaviours with antidepressants in trials in adolescents has led to safety warnings about their use in Europe, North America, and Australasia.6 Should adolescents with depression be prescribed antidepressants, and if so, should they be given only with psychotherapy?
In this week's BMJ, a randomised controlled trial (adolescent depression antidepressant and psychotherapy trial; ADAPT) by Goodyer and colleagues compares a selective serotonin reuptake inhibitor (SSRI) alone and with cognitive behaviour therapy in 208 people aged 11-17 years with depression.7 In these adolescents, depression had not responded to a brief psychosocial intervention or was severe at the outset. The investigators tried hard to reflect “real world” conditions—the participants were heterogeneous for previous treatment exposure, self harm, suicidal thoughts, subtype of depression, and comorbidity. The primary outcome was a change in score on the Health of the Nation outcome scales for children and adolescents from baseline. They conducted assessments at six, 12, and 28 weeks, so that follow-up extended beyond that usually seen in trials of antidepressants. The trial found no significant difference in treatment effect between groups at any time point.
The trial reported a 40% treatment response in both groups at 12 weeks, which is somewhat lower than that seen in other treatment studies for depression in adolescents. This may have been due to the exclusion of adolescents who had already responded to the brief psychosocial intervention. By 28 weeks the response rate had increased to nearly 60%.
The improvement in response rate from 12 to 28 weeks is noteworthy, as most treatment trials have been shorter in duration,8 and they may have underestimated the treatment response. The conclusion challenges the recommendation by the National Institute for Health and Clinical Excellence (NICE) and other bodies that SSRIs should be given to moderate and severely depressed adolescents only, in combination with a psychological therapy.8 9
ADAPT is the fourth study to assess the combination of SSRI and cognitive behaviour therapy over monotherapy for depression in adolescents. The treatment for adolescents with depression study (TADS) found that the combination of fluoxetine and cognitive behaviour therapy was better than fluoxetine or behaviour therapy alone in reducing depressive symptoms. Combined treatment and fluoxetine alone were equally effective in achieving a clinical response and superior to cognitive behaviour therapy alone.10 The most recent trial found no advantage of sertraline plus cognitive behaviour therapy over monotherapy in rates of remission or moderation of depressive symptoms after 12 weeks of treatment, and at follow-up after nine months.11 The third trial also found that the addition of cognitive behaviour therapy to SSRIs had no significant effect on symptoms of depression.12
The results of the ADAPT trial suggest a further trend away from the positive findings of TADS. Differences in the dose and duration of treatment and in the choice of primary outcome measure may have contributed to the variation in study outcomes, but the data suggest that combining cognitive behaviour therapy with an SSRI had only a modest advantage over an SSRI alone in treating depression in adolescents.
Combining cognitive behaviour therapy with an SSRI may have other advantages, such as reducing suicidal thoughts and prolonging the benefit of treatment, but evidence for this across the four trials is equivocal. Suicidal thinking was lowest in the group receiving combined treatment in one study,10 but two studies found no significant difference.7 11 Suicidal thinking was not measured in the fourth study,12 which found higher remission rates after 52 weeks for combined treatment than for SSRI monotherapy.12 In contrast, the ADAPT study found no significant differences between groups in remission rates after 28 weeks.7
What does this mean for clinicians managing adolescents with depression? Contrary to the NICE guidelines,8 evidence suggests that monotherapy with an SSRI is a reasonable treatment option for moderate to severe depression in adolescents, particularly if access to cognitive behaviour therapy may be delayed. The SSRI must be given at a high enough dose and for an adequate amount of time, as some patients take 12 weeks or longer to respond.
Of note, people randomised to monotherapy with an SSRI in the ADAPT and other trials received a high level of clinical care, with frequent clinical reviews and rigorous monitoring of the benefit of treatment and adverse events. The implication for clinical practice is that good quality pharmacological treatment involves more than simply writing the prescription.
Competing interests: PH (or his employer) received fees for participating in advisory boards from Lilly, Novartis, and Shire; fees for speaking from Lilly, Janssen-Cilag, and Pfizer; and payment for conducting clinical trials from Lilly and Celltech.
Provenance and peer review: Commissioned; not externally peer reviewed.