Childhood and adolescence are vulnerable periods for the development of mental health problems, which are also associated with mental health and physical problems in adulthood. There are a range of different psychological therapies and medications available to choose from, but how can clinicians, parents, and young people best be guided to choose the treatment that is right for them?
The National Institute of Health and Care Excellence (NICE) recommends psychotherapy over medication for young people’s depression treatment in the UK. However, the evidence that informs this recommendation is derived from separate meta-analyses of psychotherapy and medication trials; head-to-head trials that directly compare the two are uncommon. Recently, network meta-analyses (NMA) have been used to directly compare the efficacy of psychotherapy and medication for young people’s depression (Zhou et al., 2020). However, Stringaris et al. (2025) highlight differences in characteristics related to participants (e.g., populations sampled between psychotherapy and medication trials; self-selection biases in psychotherapy versus medication trials; clinical characteristics like baseline depression severity, sex, and age) and trial design (e.g., blinding in medication trials versus generally unblinded psychotherapy trials; comparability of control conductions in medication vs psychotherapy trials), meaning that direct comparison of these trials may not be appropriate.
To investigate this further, Stringaris and colleagues (2025) undertook a quantitative critique of the literature to see whether we really can compare psychotherapy and medication trials for young people’s depression, or if it is a case of comparing apples with oranges.
Deciding whether psychological therapy or medication should be prescribed for depression in young people can be challenging because of the difficulty in comparing the available trial efficacy evidence.
Methods
Stringaris et al. conducted a random-effects meta-analysis of psychotherapy and antidepressant medication randomised controlled trials (RCTs) for depression in young people (4-18 years old). The authors extracted data used in previous meta-analyses of psychotherapy (Cuijpers et al., 2023), antidepressants (Cipriani et al., 2016) and the network meta-analysis that compared psychotherapy and medication RCTs (Zhou et al., 2020). They tested subgroup differences between trial types focusing on depression severity, sex, age, and trial design.
Within the 92 RCTs identified, there were 48 active medication arms, 36 medication control arms, 67 active psychotherapy arms, and 62 psychotherapy control arms. Pill placebo was the control for all medication trials. Psychotherapy controls included waitlists (n = 14), treatment-as-usual (n = 28), and other control conditions (n = 20).
Results
Participant characteristics
When comparing medication and psychotherapy RCTs, baseline depression severity in medication trials were statistically significantly higher than in psychotherapy trials for the young people (p = .033). Some of the RCTs included patients who were on a waitlist control and individuals with subclinical depression symptoms. Sensitivity analyses exploring whether excluding these individuals made a difference to the pattern of results, showed they did not.
When looking at sex differences between trial types, two RCTs that focused on female young people were excluded. Overall, psychotherapy trials had a higher number of young female participants than medication trials. Within psychotherapy trials, 61.36% (SE = 2.31) of participants were female, compared to 53.72% (SE = 2.33) of females in medication trials, which was statistically significant (p = .020). Similar sex differences were observed when excluding subclinical and waitlist controls.
Age was not statistically significant between trial types, and this did not change when excluding waitlist controls and those with subclinical depression.
Trial design characteristics
The meta-regression found there were within-group differences between the four arms of the meta-analysis. The most substantial difference was between the medication control (within-group standardised mean difference (SMD) = 1.89, 95% CI [-2.1 to 1.67]) compared to the psychotherapy control condition (SMD = -0.62, 95% CI [-0.9 to -0.34]).
When looking at other design related characteristics between RCTs, it was found that there were significantly more trial sites involved in medication (M = 35.96, SD = 25.16) compared with psychotherapy (M = 3.04, SD = 3.13) RCTs (p<.001 wp_automatic_readability="225.18641603489">
There were also differences when comparing the nature and intensity of the active compared to the control conditions in psychotherapy trials. Within the active psychotherapy conditions, there were more treatment sessions (d = 0.76, p <.001>which were often longer (d = 1.10, p <.001>and more frequent (d = 1.02, p <.001>than in the control psychotherapy conditions. The control psychotherapy conditions were often poorly described and sometimes their intensity could not be characterised.
In this meta-analysis of treatments for depression in young people, several key differences between psychotherapy and medication trials were found relating to symptom severity, sex, and number of trial sites.
Conclusions
Stringaris and colleagues (2025) conclude that the existing evidence comparing psychotherapy and medication treatment for depression in young people is akin to comparing apples and oranges because of the stark differences between participant and trial design characteristics within the available meta-analyses that inform this guidance.
Clinicians, parents, and young people should be aware of the limitations of the evidence-base behind these guidelines. The authors recommend that value-based judgements should be used within practice, rather than relying solely on the quantitative data to support treatment decision-making for depression in young people.
The current quantitative evidence we have for the efficacy of psychotherapy or medication for treating young people’s depression is akin to comparing apples and oranges – they are too dissimilar to be properly compared.
Strengths and limitations
This study importantly highlights difficulties in comparing RCT evidence between medication and psychotherapy trials. These findings provoke important discussions in the field about the appropriateness and rigour of our evidence-base, and the claims we are making in the context of design limitations. This is the paper’s key strength. Other strengths include comparing psychotherapy and medication RCT populations for adolescent depression and the utilisation of meta-analytic data from 92 RCTs with heterogeneous samples.
There are a range of other factors that may also influence the comparability of medication and psychotherapy RCT evidence that were not examined in the Stringaris et al. paper, which may be helpful to guide treatment choice decision making:
- Within the paper, Stringaris and colleagues examine differences in the number of sites between medication and psychological therapy RCTs, but context of the site is not considered. Antidepressant medication administered by a General Practitioner or Psychiatrist in primary care or hospital settings, are unlikely to be comparable to a Psychological Wellbeing Practitioner or Clinical Psychologist in Child and Adolescent Mental health Services (CMAHS) with regards to the setting, person prescribing/delivering therapy, and time spent with the young person.
- Another example is the dose of medication or psychological therapy were not considered and is a factor that is not easily comparable between treatments (e.g., comparing a 10mg dose of Fluoxetine, versus 6-sessions of guided self-help cognitive behavioural therapy). This is further complicated by the type of antidepressant medication or psychological therapy.
- Further differences include potential side effects of treatments (Linden & Schermuly-Haupt, 2014; Strawn et al., 2023) which may (e.g., deterioration of depression symptoms) or may not (nausea from antidepressants, compared with ruptures of therapeutic alliance in psychologic therapy) be comparable, and side effects are important considerations in guiding treatment choice for young people with depression (Hickie et al., 2007).
As is the case with all meta-analyses, the analysis is only as good as the quality and rigour of the RCTs conducted. This analysis highlights the complexity and interplay of factors affecting the comparability of antidepressant medication and psychological therapy trials and we need more studies with larger and diverse samples to support guidance of young people’s depression treatment choice.
More high-quality studies are needed to help support evidence-informed guidance on young people’s treatment choices between antidepressant medication and psychological therapy for depression.
Implications for practice
Taken together, the main message from this paper is clear: guidelines on treatment choice between medication and psychotherapy for depression in young people should not rest upon meta-analyses of trial evidence alone. Medication and psychotherapy RCTs vary too much to be directly compared, both in relation to the young people who are taking part in these trials, but also the designs of the trials themselves. Instead, as Stringaris and colleagues note, value-based judgments should be key to supporting treatment decision-making, alongside NICE guidelines and meta-analytic evidence.
Collaborative models that consider perspectives from the young people themselves, carers/parents and clinicians are really important for treatment choice and personalised care. We know that experiences of adolescent depression are different from adult depression, and young people value having their voice heard in their treatment choice (Wells et al., 2020). Encouragingly, within both the medical and psychological therapy fields, there is an increased focus on treatment personalisation (e.g., Li et al., 2024) and identifying what treatment works best for whom, when under which circumstances, which can help to guide decision-making. Ultimately, in practice the best way forward is to have that open and honest discussion, taking into account the evidence behind the guidelines and the young person’s preferences.
Rather than relying on the meta-analytic evidence alone, clinicians should use value-based judgements in decision-making to guide young people’s depression treatment choice.
Statement of interests
None.
Links
Primary paper
Stringaris, A., Burman, C., Delpech, R., Uher, R., Bhudia, D., Miliou, D., … & Krebs, G. (2025). Comparing apples and oranges in youth depression treatments? A quantitative critique of the evidence base and guidelines. BMJ Mental Health, 28(1).
Other references
Cipriani, A., Zhou, X., Del Giovane, C., Hetrick, S. E., Qin, B., Whittington, C., … & Xie, P. (2016). Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. The Lancet, 388(10047), 881-890.
Cuijpers, P., Karyotaki, E., Ciharova, M., Miguel, C., Noma, H., Stikkelbroek, Y., Weisz, J. R., & Furukawa, T. A. (2023). The effects of psychological treatments of depression in children and adolescents on response, reliable change, and deterioration: a systematic review and meta-analysis. European Child and Adolescent Psychiatry, 32(1), 177–192.
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Hickie, I. B., Luscombe, G. M., Davenport, T. A., Burns, J. M., & Highet, N. J. (2007). Perspectives of young people on depression: awareness, experiences, attitudes and treatment preferences. Early Intervention in Psychiatry, 1(4), 333–339.
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Liang, J. H., Li, J., Wu, R. K., Li, J. Y., Qian, S., Jia, R. X., … & Xu, Y. (2021). Effectiveness comparisons of various psychosocial therapies for children and adolescents with depression: a Bayesian network meta-analysis. European Child & Adolescent Psychiatry, 30, 685-697.
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Wells, H., Crowe, M., & Inder, M. (2020). Why people choose to participate in psychotherapy for depression: A qualitative study. Journal of Psychiatric and Mental Health Nursing, 27(4), 417-424.
Zhou, X., Teng, T., Zhang, Y., Del Giovane, C., Furukawa, T. A., Weisz, J. R., … & Xie, P. (2020). Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis. The Lancet Psychiatry, 7(7), 581-601.
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