Medications used to manage ADHD symptoms include stimulants (methylphenidate, amphetamines) and non-stimulants (atomoxetine, guanfacine, clonidine). Managing ADHD is crucial for improving functioning and long-term outcomes.
Side effects may include decreased appetite, sleep disturbances, and cardiovascular effects. Medication selection must be individualized considering factors like symptom severity, comorbidities, and patient preferences.
Disclaimer: This review article is for informational purposes only and should not be taken as medical advice. Treatment decisions should be made in consultation with a qualified healthcare provider.
Mechler, K., Banaschewski, T., Hohmann, S., & Häge, A. (2022). Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacology & Therapeutics, 230, 107940. https://doi.org/10.1016/j.pharmthera.2021.107940
Key Points
The key points from this review on evidence-based pharmacological treatment options for ADHD in children and adolescents are:
- Current pharmacological treatments for ADHD include stimulants (methylphenidate, amphetamines) and non-stimulants (atomoxetine, guanfacine, clonidine). Stimulants are recommended as first-line treatment.
- While current medications show relatively large short-term effect sizes and good tolerability, there is a need for improvement of pharmacotherapeutic strategies and development of novel medications.
- Factors like age, severity of symptoms, comorbidities, and individual needs significantly affect treatment decisions. An individualized, multimodal approach combining pharmacological and non-pharmacological interventions is recommended.
- The research has limitations, including a lack of long-term efficacy data, underrepresentation of age and gender differences, and limited generalizability of study populations. Further studies are needed comparing medications head-to-head and with non-pharmacological options.
- Optimizing pharmacological treatment of ADHD is universally important given the high prevalence, persistence into adulthood, and negative impacts on functioning and outcomes if undertreated.
Rationale
ADHD is a prevalent neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity that often persists into adulthood.
Extensive research has revealed a multifactorial etiology, high heritability, and executive deficits in several cognitive domains substantiated by abnormal brain imaging findings (Faraone et al., 2015).
ADHD frequently co-occurs with other psychiatric and somatic conditions, and insufficient treatment is associated with adverse long-term academic, occupational, social, and health outcomes (Arnold et al., 2020; Cortese, 2019).
While the short-term efficacy and safety of stimulant and non-stimulant medications have been well-established (Cortese et al., 2018), evidence gaps remain regarding long-term effects, head-to-head comparisons, and their combination with non-pharmacological treatments (Wong et al., 2019).
Optimizing safe and effective pharmacotherapy as part of a multimodal, individualized treatment plan is crucial.
This review aims to summarize the current state of evidence for the pharmacological treatment of pediatric ADHD, identify research gaps, and provide an overview of novel medications under development.
Method
This paper provides a narrative review of evidence-based pharmacological treatments for ADHD in children and adolescents.
It summarizes key information about currently approved stimulant and non-stimulant medications, including mechanisms of action, formulations, efficacy, tolerability, treatment strategies, and current issues in research.
A systematic cross-sectional analysis of the ClinicalTrials.gov registry was also conducted to identify novel medications currently under development.
Results
- Stimulants (methylphenidate, amphetamines) are considered first-line treatment for ADHD. They have relatively large effect sizes for reducing core symptoms and are available in various short-acting and long-acting formulations. Common adverse effects include decreased appetite, sleep disturbances, headaches, and cardiovascular effects.
- Non-stimulants (atomoxetine, guanfacine, clonidine) have smaller effect sizes than stimulants but offer potential advantages like longer duration of action and utility in certain comorbid conditions. They differ in terms of mechanisms, dosing, onset of effects, and adverse effect profiles.
- Treatment selection should consider factors like symptom severity, comorbidities, individual needs, and patient preference. Using stimulants as first-line and non-stimulants as second-line is generally recommended, but must be individualized. Ongoing monitoring and adjustments are important.
- Several novel medications with potential for treating ADHD are in various stages of clinical development. These include viloxazine, centanafadine, and mazindol. However, none represent distinctly novel mechanisms of action and further research is needed to establish their efficacy, safety and role in treatment.
Insight
This review provides a helpful synthesis of current evidence-based pharmacological treatment options for ADHD in pediatric populations.
The key insights are:
- Stimulants remain the first-line treatment based on effect sizes, but non-stimulants have a role for certain patients or as adjunctive agents;
- Multiple factors must be weighed to individualize medication selection and treatment plans;
- Pharmacotherapy should be delivered as part of a multimodal treatment approach;
- Notable evidence gaps exist regarding head-to-head comparisons, long-term effects, and combination treatment;
- Some novel agents are in the pipeline but do not yet represent major advances in treatment.
The findings highlight the importance of a patient-centered, evidence-based approach to optimizing pharmacotherapy for ADHD and the need for further research to inform clinical practice, especially comparative effectiveness trials and studies in real-world populations.
Strengths
The review provides a comprehensive overview of current pharmacological treatment options for ADHD, with helpful details on mechanisms, formulations, efficacy, and safety.
Summarizing the evidence for both stimulant and non-stimulant options, as well as discussing factors influencing treatment selection, provides useful guidance for clinicians.
The cross-sectional analysis of medications in development is a relative strength. The review appropriately highlights key evidence gaps and areas for further research.
Limitations
As a narrative review, the article is prone to selection bias in terms of which studies are included and emphasized.
It does not appear to be a fully systematic review and lacks explicit search criteria.
Meta-analytic results are presented for some but not all medication classes.
The cross-sectional analysis of novel medications relies only on a ClinicalTrials.gov search and does not capture drugs in earlier stages of development.
The article is focused specifically on children and adolescents, without fully discussing the adult ADHD population.
Finally, non-pharmacological treatment modalities are mentioned but not discussed in any depth.
Implications
The review emphasizes that while current pharmacotherapies for ADHD are relatively effective and safe, clinical practice must focus on optimizing individual treatment plans through a multimodal approach.
Medication selection remains more of an art than a science, drawing upon a combination of research evidence, clinical expertise, and patient values. More personalized prescribing approaches may be possible in the future with advances in pharmacogenomics and biomarker development.
At the health systems level, quality metrics and incentives should promote measurement-based, multimodal ADHD care. In terms of treatment development, novel delivery systems for existing medications should be pursued in parallel with identifying new molecular entities with distinct mechanisms of action.
Comparative effectiveness research, including head-to-head medication trials, long-term studies, and real-world evidence, is a priority to guide treatment optimization.
Finally, research must examine medication effects in understudied populations and consider a full range of functional outcomes beyond symptom control.
Policy implications include ensuring affordable access to a range of medication options and supporting research to modernize the ADHD pharmacotherapy evidence base.
References
Primary reference
Mechler, K., Banaschewski, T., Hohmann, S., & Häge, A. (2022). Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacology & Therapeutics, 230, 107940. https://doi.org/10.1016/j.pharmthera.2021.107940
Other references
Arnold, L. E., Hodgkins, P., Kahle, J., Madhoo, M., & Kewley, G. (2020). Long-term outcomes of ADHD: Academic achievement and performance. Journal of Attention Disorders 24 (1), 73–85. https://doi.org/10.1177/108705471456607
Cortese, S. (2019). The association between ADHD and obesity: Intriguing, progressively more investigated, but still puzzling. Brain Sciences, 9(10), 256. https://doi.org/10.3390/brainsci9100256
Cortese, S., Adamo, N., Del Giovane, C., Mohr-Jensen, C., Hayes, A. J., Carucci, S., … & Cipriani, A. (2018). Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry, 5(9), 727-738. https://doi.org/10.1016/S2215-0366(18)30269-4
Faraone, S. V., Asherson, P., Banaschewski, T., Biederman, J., Buitelaar, J. K., Ramos-Quiroga, J. A., … & Franke, B. (2015). Attention-deficit/hyperactivity disorder. Nature Reviews Disease Primers, 1(1), 1-23.
Wong, I. C., Banaschewski, T., Buitelaar, J., Cortese, S., Döpfner, M., Simonoff, E., & Coghill, D. (2019). Emerging challenges in pharmacotherapy research on attention-deficit hyperactivity disorder—outcome measures beyond symptom control and clinical trials. The Lancet Psychiatry, 6(6), 528-537. https://doi.org/10.2147/JEP.S256586
Keep Learning
Some Socratic questions for a college class to discuss based on this review paper could include:
- How do the key decision points in selecting an ADHD medication for a pediatric patient align with the principles of evidence-based practice and shared decision-making? What additional information would be most helpful to guide treatment personalization?
- To what extent do you think novel medications with distinct mechanisms of action are needed to address current gaps in ADHD pharmacotherapy? What would be the most important attributes of an “ideal” new pharmacotherapy?
- How could researchers, clinicians, patients/families, policymakers and other stakeholders work together to efficiently generate and apply real-world evidence to optimize ADHD treatment and outcomes at both the individual and population level?
- What do you see as the most significant barriers to implementing measurement-based, multimodal ADHD care in routine clinical practice? How could health professions education, care delivery models, and payment structures be reformed to enable a more integrated, patient-centered approach?
- In what ways could a better understanding of the underlying neurobiology and heterogeneity of ADHD inform a more personalized approach to pharmacotherapy? How might advances in pharmacogenomics, neuroimaging, and digital phenotyping be leveraged to guide treatment selection and monitoring?
