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Background: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) may increase the risk of suicide among children and youth, although the association between suicide risk and the combination of SSRIs with other medication such as stimulants in this population remains unclear. This study explored whether the combination of SSRIs with stimulants influenced suicide risk. Methods: A retrospective cohort study was conducted at a single children's hospital campus-based ambulatory psychiatric clinic between September 1, 2017, and September 30, 2020. Subjects were 6-21 years of age and prescribed either stimulants or stimulants and SSRIs only. The primary outcome was suicidal thoughts and behaviors (STB), defined by documented suicidal thoughts, plans, or behaviors. Firth logistic regression evaluated associations between medication class and STB. Results: Among 349 patients, the prevalence of STB was 5.7% ( n  = 20). In unadjusted model, patients prescribed SSRIs and stimulants had a 2.9-fold increase of STB compared to patients prescribed stimulants only, along with increasing age, male sex, and the diagnoses of anxiety and/or depression. In the final model adjusted for each of these factors, the observed association of medication regiment with STB was attenuated (odds ratio [OR]: 1.3, confidence interval [CI]: 0.3-4.9, p  = 0.7). The magnitude of the adjusted association between depressive diagnosis and STB was notable (OR: 3.6, CI: 1.0-12.6, p  = 0.049). Conclusions: Among patients followed in a children's hospital-based ambulatory psychiatric clinic, a combination medication regimen of SSRIs and stimulants after adjusting for genetic sex, age, anxiety diagnosis, and depression diagnosis, the observed association between STB and combination stimulant and SSRI treatment was attenuated. This finding suggests that other factors, including depression, may have contributed to the association between SSRI treatment and STB. Larger, prospective studies of the relationship between combination pharmacotherapy and suicide risk are warranted to guide clinical/pharmacological decision making and to better clarify these relationships.

Objective: The purpose of this article is to review the literature on hypothesized behavioral correlates of pharmacotherapy treatment response. A particular focus is placed on what have been referred to as "common factors" across mental health treatments, including medication adherence, therapeutic alliance, motivation for behavior change, and expectancies for positive treatment outcomes. These understudied factors may provide unique explanations for mechanisms of symptom change, patient risk as a result of protocol deviation, and attenuated treatment outcomes., Method: A literature search was conducted to evaluate the relationship between treatment processes in pediatric psychiatry and medication adherence, therapeutic alliance, motivation for behavior change, and expectancies for positive treatment outcomes., Results: Substantial variability and room for improvement was identified for each common factor. Behavioral protocols have already been developed to address many aspects of common factors in pediatric psychiatric treatment, but are not yet a part of many practice parameters., Conclusion: Interventions to improve common factors can be used immediately in tandem with psychopharmacological interventions to provide increased symptom relief and reduce patient risk. Furthermore, incorporating instruction in common factors interventions can positively affect training of future providers and enhance understanding of the mechanisms of effect of medications. An increased focus on common factors, with a particular emphasis on quantifying the magnitude and mechanisms of their effects on psychopharmacological interventions stand to benefit child patients, their families, treatment providers, training facilities, and pharmaceutical manufacturers.