Effects of stimulants and atomoxetine on emotional lability in adults: A systematic review and meta-analysis
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Background: Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms. Methods: A systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline ® and the clinicaltrials.gov website. We included randomised, double-blind, placebo-controlled trials of stimulants and atomoxetine in adults aged 18–60 years, with any mental health diagnosis characterised by emotional or mood instability, with at least one outcome measure of EL. All identified trials were on adults with ADHD. A random-effects meta-analysis with standardised mean difference and 95% confidence intervals was used to investigate the effect size on EL and compare this to the effect on core ADHD symptoms. Results: Of the 3,864 publications identified, nine trials met the inclusion criteria for the meta-analysis. Stimulants and atomoxetine led to large mean weighted effect-sizes for on ADHD symptoms ( n = 9, SMD = −0.8, 95% CI:−1.07 to −0.53). EL outcomes showed more moderate but definite effects ( n = 9, SMD = −0.41, 95% CI:−0.57 to −0.25). Conclusions: In this meta-analysis, stimulants and atomoxetine were moderately effective for EL symptoms, while effect size on core ADHD symptoms was twice as large. Methodological issues may partially explain the difference in effect size. Reduced average effect size could also reflect heterogeneity of EL with ADHD pharmacotherapy responsive and non-responsive sub-types. Our findings indicate that EL may be less responsive than ADHD symptoms overall, perhaps indicating the need for adjunctive psychotherapy in some cases. To clarify these questions, our findings need replication in studies selecting subjects for high EL and targeting EL as the primary outcome.
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Several meta-analyses and reviews assessing double-blind randomized control trials describe positive emotional outcomes for treatments such as atomoxetine, lisdexamfetamine, methylphenidate transdermal system, and OROS-MPH versus placebo in adults with ADHD.
“several meta-analyses and reviews assessing the results of double-blind randomized control trials describe positive emotional outcomes for treatments such as atomoxetine, lisdexamfetamine, methylphenidate transdermal system, and OROS-MPH versus placebo in adults with ADHD (Lenzi et al., 2017; Moukhtarian et al., 2017; C. B. H. Surman & Walsh, 2022)”
From A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials (2024) · cites this paper as Moukhtarian et al., 2017
Several meta-analyses and reviews of clinical trials for stimulant and non-stimulant treatments have demonstrated improvements in EL.
“These reports have been further demonstrated by several meta-analyses and reviews of clinical trials for stimulant and non-stimulant treatments (Lenzi et al., 2017; Moukhtarian et al., 2017; C. B. H. Surman & Walsh, 2022).”
From A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials (2024) · cites this paper as Moukhtarian et al., 2017
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Kiefer, F., Hoffmann, S., Arens, J., Beutel, M., Bilke-Hentsch, O., Bischof, G., Bonnet, U., Bumb, J. M., Demmel, R., Diestelkamp, S., et al. (2022) · Springer eBooks · doi:10.1007/978-3-662-63677-0_3
Moukhtarian, T. R. (2018) · PsyPag Quarterly · doi:10.53841/bpspag.2018.1.107.20
Self-citationLee, D., & Espiridion, E. D. (2025) · Journal of Advances in Medicine and Medical Research · doi:10.9734/jammr/2025/v37i15704
Moukhtarian, T. R., Reinhard, I., Moran, P., Ryckaert, C., Skirrow, C., Ebner-Priemer, U., & Asherson, P. J. (2021) · Figshare · doi:10.6084/m9.figshare.13979096
Self-citationGao, Y., Wu, Z.-M., 杨斌让, Chen, W., Dang, C., Zhu, Y., Pan, M., Dong, M., Li, H., Zhao, M., et al. (2026) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.70217
Medication Treatment for Children, Adolescents, and Adults with ADHD
Kennedy, R. J. (2026) · Springer eBooks · doi:10.1007/978-3-032-24171-9_7
- Authors
- Moukhtarian, T. R., Cooper, R. E., Vassos, E., Moran, P., & Asherson, P.
- Affiliations
- King's College London (GB)
- Queen Mary University of London (GB)
- University of Bristol (GB)
- Corresponding author
- Moukhtarian, T.R.
- Venue
- European Psychiatry
- Publisher
- Cambridge University Press (CUP)
- Published
- 2017-07
- Volume
- 44
- Pages
- 198-207
- ISSN
- 0924-9338 (ISSN-L)
- 1778-3585
- OpenAlex
- W2617656397
- Cited by
- 56
- References
- 39
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 1
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- European Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Greenwich Academic Literature Archive (University of Greenwich) (acceptedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, cc-by-nc-nd)
- Explore Bristol Research (acceptedVersion, cc-by-nc-nd)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute for Health and Care Research (NF-SI-0616-10040, EME/14/23/17, 14/23/17)
- King's College London
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- emotional lability, adult ADHD, stimulants, atomoxetine, ADHD medication, mood instability, treatment response heterogeneity, adjunctive psychotherapy
- MeSH terms
- Atomoxetine Hydrochloride, Adult, Affective Symptoms, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Emotions, Female, Humans, Methylphenidate, Middle Aged, Mood Disorders, Young Adult
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