ADHD is often treated with medications that target neurotransmitter systems in the brain, particularly dopamine and norepinephrine.
Stimulant medications, such as methylphenidate and amphetamines, are the most commonly prescribed and have been shown to be effective in reducing core ADHD symptoms of inattention, hyperactivity, and impulsivity.
Non-stimulant medications, like atomoxetine and alpha-2 agonists, are also used to treat ADHD, particularly when stimulants are not well-tolerated or effective. These medications are believed to work by enhancing the availability and balance of neurotransmitters involved in attention, motivation, and self-regulation.
Medication management is often combined with behavioral and psychosocial interventions for optimal outcomes.
It is advisable to speak to a medical professional about ADHD medication and the risks involved. This article is meant to serve as a review of clinical research only.
Boland, H., DiSalvo, M., Fried, R., Woodworth, K. Y., Wilens, T., Faraone, S. V., & Biederman, J. (2020). A literature review and meta-analysis on the effects of ADHD medications on functional outcomes. Journal of psychiatric research, 123, 21-30. https://doi.org/10.1016/j.jpsychires.2020.01.006
Key Points
- This systematic review and meta-analysis of 40 studies from large databases and registries found that ADHD medications, particularly stimulants, are associated with decreased risks for a wide range of adverse functional outcomes, including mood disorders, suicidality, criminality, substance use disorders, accidents and injuries, traumatic brain injury, automobile crashes, and academic impairments.
- Within-individual analyses showed that protective effects were particularly strong during periods of medication adherence compared to non-adherence.
- While the findings strongly support the benefits of stimulants in mitigating serious risks associated with ADHD, the research has some limitations, such as relying on coded diagnoses and treatments that may not include all affected subjects.
- Given the high prevalence and morbidity associated with ADHD, these findings have significant clinical and public health implications for early diagnosis and treatment.
Rationale
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobiological disorder affecting up to 11% of children and 5% of adults, and is associated with high rates of adverse functional outcomes (Faraone et al., 2003; Polanczyk et al., 2014).
While stimulant medications have been shown to improve ADHD core symptoms (Faraone et al., 2006), less is known about their effects on ADHD-associated functional impairments (Faraone & Glatt, 2010).
A recent qualitative review suggested beneficial effects of ADHD medication on several functional outcomes (Chang et al., 2019), but did not include a meta-analysis.
Therefore, this systematic review and meta-analysis aimed to quantitatively assess the effects of ADHD medications, particularly stimulants, on a wide range of ecologically valid functional outcomes using data from large databases and registries.
Method
The authors conducted a systematic literature search of PubMed, PsycINFO, MEDLINE, and Web of Science for studies published before January 2019 that examined the effects of ADHD medications on functional outcomes using population-wide or large insurance claims databases.
Of the 40 articles meeting inclusion criteria, 21 had extractable data for meta-analysis.
Procedure
This was a systematic review and meta-analysis of observational studies using population-based and insurance claims databases.
Sample
The included studies had sample sizes ranging from 5718 to over 146,000,000 individuals with ADHD. Most studies were from non-U.S. countries.
Measures
Functional outcomes examined included mood disorders, suicidality, criminality, substance use disorders, accidents/injuries, traumatic brain injury, motor vehicle crashes, and academic outcomes. Medication adherence was also assessed.
Statistical Analysis
Random-effects meta-analyses were conducted using odds ratios for dichotomous outcomes and hazard ratios for time-to-event data. Heterogeneity was assessed with the I2 statistic.
Results
The systematic review and meta-analyses found that ADHD medication treatment, mostly with stimulants, was associated with significantly decreased risks for:
- Mood disorders (OR=0.69)
- Accidents and injuries (OR=0.72; HR=0.77)
- Poor academic outcomes (OR=0.80)
Non-significant protective effects were also seen for:
- Suicidality (HR=0.65)
- Substance use disorders (HR=0.79)
- Criminality (HR=0.87)
- Traumatic brain injury (HR=0.68)
Within-individual analyses consistently showed larger protective effects during periods of medication adherence vs non-adherence.
Insight
This comprehensive review provides strong evidence that ADHD medications, especially stimulants, can mitigate a wide range of serious and costly adverse outcomes associated with the disorder.
The findings underscore the importance of early diagnosis and treatment, as well as promoting medication adherence.
Future studies should examine potential moderators and mediators of these protective medication effects. Given that most studies focused on stimulants, more research is needed on long-term functional outcomes with non-stimulants.
Strengths
This review has several methodological strengths:
- Systematic review and meta-analysis of a large number of population-based studies with very large sample sizes, enhancing generalizability
- Examined a broad range of ecologically valid functional outcomes, providing a comprehensive assessment of medication effects
- Many studies compared periods of medication adherence vs non-adherence within individuals, providing stronger causal evidence
- Included studies from multiple countries, increasing global relevance of findings
- Analyzed both qualitative review and quantitative meta-analytic results, allowing for a thorough evaluation of the evidence
- Assessed heterogeneity and publication bias, strengthening the reliability of the findings
Limitations
Despite several strengths, there are some notable limitations of this review:
- Most studies relied on coded diagnoses and treatments in databases that may not capture all affected individuals, potentially leading to selection bias
- Limited data on effects of non-stimulant ADHD medications, restricting conclusions about their long-term functional outcomes
- Potential confounding cannot be fully ruled out in observational studies, although within-individual designs mitigate this concern
- Some meta-analyses had high heterogeneity, suggesting potential moderators of medication effects that require further investigation
- Variability in how medication adherence was defined across studies may have influenced the consistency of findings
- Lack of randomized controlled trials limits causal inferences, although ethical and practical considerations preclude long-term RCTs for many functional outcomes
- The duration of follow-up varied across studies, and longer-term outcomes of childhood treatment remain an important research gap
- Most studies focused on children and adolescents, highlighting the need for more research on functional outcomes of adult ADHD treatment
Implications
The accumulating evidence that medication treatment of ADHD reduces the risks of highly impairing and costly outcomes has major clinical and societal implications. Clinicians should prioritize early identification and evidence-based management of ADHD.
Promoting long-term medication adherence appears critical for maintaining therapeutic benefits.
At a policy level, improving access to ADHD care and supports may yield significant returns in helping individuals achieve better functional outcomes while reducing societal costs and burdens associated with untreated ADHD.
References
Primary reference
Boland, H., DiSalvo, M., Fried, R., Woodworth, K. Y., Wilens, T., Faraone, S. V., & Biederman, J. (2020). A literature review and meta-analysis on the effects of ADHD medications on functional outcomes. Journal of psychiatric research, 123, 21-30. https://doi.org/10.1016/j.jpsychires.2020.01.006
Other references
Chang, Z., Ghirardi, L., Quinn, P. D., Asherson, P., D’Onofrio, B. M., & Larsson, H. (2019). Risks and benefits of attention-deficit/hyperactivity disorder medication on behavioral and neuropsychiatric outcomes: a qualitative review of pharmacoepidemiology studies using linked prescription databases. Biological psychiatry, 86(5), 335-343. https://doi.org/10.1016/j.biopsych.2019.04.009
Faraone, S. V., Biederman, J., Spencer, T. J., & Aleardi, M. (2006). Comparing the efficacy of medications for ADHD using meta-analysis. MedGenMed: Medscape General Medicine, 8(4), 4.
Faraone, S. V., & Glatt, S. J. (2009). A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes. The Journal of clinical psychiatry, 71(6), 3475.
Faraone, S. V., Sergeant, J., Gillberg, C., & Biederman, J. (2003). The worldwide prevalence of ADHD: is it an American condition?. World psychiatry, 2(2), 104.
Polanczyk, G. V., Willcutt, E. G., Salum, G. A., Kieling, C., & Rohde, L. A. (2014). ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. International journal of epidemiology, 43(2), 434-442. https://doi.org/10.1093/ije/dyt261
Keep Learning
Here are some suggested Socratic questions for students to critically analyze and discuss this research paper further:
- How might the long-term benefits of ADHD medication on functional outcomes compare to non-pharmacological treatments?
- What factors contribute to poor ADHD medication adherence and how can adherence be better supported?
- Given that most studies focused on children and adolescents, what additional research is needed on functional outcomes of adult ADHD treatment?
- How can mental health disparities in ADHD diagnosis and treatment access be reduced?
