Combining selective serotonin reuptake inhibitors and cognitive behavioral therapy in youth with depression and anxiety
Open accessAbstract
Background Treatment studies of children and adolescents with internalizing disorders suggest that the combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone. We sought to determine how response to combined treatment varies across disorders (anxiety versus depression), and by specific patient characteristics. Methods Three large National Institutes of Health-funded trials of children and adolescents with major depression (n = 2) and anxiety disorders (n = 1) were evaluated, each comparing CBT + SSRI to SSRI only, Bayesian Hierarchical Models (BHMs) were used, for endpoint response, time course of response and predictors of response in participants who received SSRI or SSRI+CBT. Results SSRI+CBT significantly decreased symptoms by week 4 (p<0.001) across disorders. This improvement continued at week 8 and 12 (p<0.001); however, the additive benefit of CBT over SSRI monotherapy was not statistically significant until week 12 (p<0.001). The fastest response to SSRI+CBT was for patients who were younger, with milder baseline anxiety/depression symptoms and depressive disorders. The slowest response for SSRI+CBT was for boys, adolescents, minoritized children, those with severe symptoms and externalizing disorders. Limitations Limitations included inconsistent moderators, variation in the number of observations over time and a lack of genetic or pharmacokinetic variables related to SSRI exposure across studies. Conclusions The superiority of SSRI+CBT for youth with depression and anxiety is further supported. For purposes of rapid and greater relief, combination treatment is the superior approach across anxiety and depression and is robust to a range of participant characteristics. However, the added value of CBT (with an SSRI) occurs late in treatment. These findings represent a step towards understanding heterogeneity of treatment response and raise the possibility that interventions could be better tailored or adapted based on patient characteristics.
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Combining SSRIs with cognitive-behavioral therapy yields better outcomes than medication alone, particularly in reducing symptom severity and preventing relapse.
“Studies indicate that combining SSRIs with cognitive-behavioral therapy (CBT) yields better outcomes than medication alone, particularly in reducing symptom severity and preventing relapse (Strawn et al.) A growing body of research supports the combination of SSRIs and CBT as the most effective treatment for both depression and anxiety in youth [117].”
From The Impact of Social Media & Technology on Child and Adolescent Mental Health (2025) · cites this paper as [117]
The Results (Time course of CBT+SSRI benefit relative to SSRI benefit; page unavailable) report greater symptom improvement with combined treatment than with SSRI alone by week 12. The paper examines treatment response through week 12, but the passages found do not support the claim that the combination prevents relapse. (LLM, conf=0.89)
Experimental — accuracy not yet measuredThe benefits of CBT become more pronounced over time, with significant symptom reduction by the 12-week mark of treatment.
“The benefits of CBT become more pronounced over time, with studies showing significant symptom reduction by the 12-week mark of treatment [117].”
From The Impact of Social Media & Technology on Child and Adolescent Mental Health (2025) · cites this paper as [117]
The Results (‘Time course of CBT+SSRI benefit relative to SSRI benefit’; page not provided) show that the added benefit of CBT became statistically significant at week 12, while symptoms in the combined-treatment group had already decreased significantly by week 4. The claim omits that this finding concerns CBT added to an SSRI in youth with depression or anxiety, not CBT treatment on its own. (LLM, conf=0.86)
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The Impact of Social Media & Technology on Child and Adolescent Mental Health
Masri-zada, T., Martirosyan, S., Abdou, A., Barbar, R., Kades, S., Makki, H., Haley, G., & K Agrawal, D. (2025) · Journal of Psychiatry and Psychiatric Disorders · doi:10.26502/jppd.2572-519x0242 · Cited by 45 · see citing works
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Self-citationFlores-Sandoval, C., Teasell, R., MacKenzie, H. M., McIntyre, A., Barua, U., Mehta, S., Bayley, M., & Bateman, E. A. (2024) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000984 · Cited by 16 · see citing works
“…the 2 different treatment options, in particular, CBT and antidepressants for the treatment of depression and anxiety in people with chronic conditions 123 and nonpatient population, 124–126 conclusions cannot be drawn about using these drug classes as co-interventions in a population with MSTBI.”
- Authors
- Strawn, J. R., Mills, J. A., Suresh, V., Peris, T. S., Walkup, J. T., & Croarkin, P. E.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Cincinnati (US)
- University of California, Los Angeles (US)
- Northwestern University (US)
- Mayo Clinic (US)
- Corresponding author
- Strawn, Jeffrey R.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 298
- Issue
- Pt A
- Pages
- 292-300
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC8674898
- OpenAlex
- W3208333533
- Cited by
- 49
- References
- 8
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 7 · 2023: 10 · 2022: 8
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD098757, R01HD099775)
- National Institute of Mental Health
- Chinese Academy of Medical Sciences
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- selective serotonin reuptake inhibitors, cognitive behavioral therapy, combined psychotherapy and pharmacotherapy, childhood depression, adolescent anxiety disorders, internalizing disorders, predictors of treatment response, Bayesian hierarchical model, treatment moderators, externalizing disorders, minority children
- MeSH terms
- Adolescent, Anxiety, Anxiety Disorders, Bayes Theorem, Child, Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Male, Cognitive Behavioral Therapy, Treatment Outcome, Selective Serotonin Reuptake Inhibitors
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