Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-11T04:19:03.889Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of stimulants and atomoxetine on emotional lability in adults: A systematic review and meta-analysis

Published online by Cambridge University Press:  23 March 2020

T.R. Moukhtarian ,
R.E. Cooper ,
E. Vassos ,
P. Moran  and
P. Asherson
T.R. Moukhtarian*
Affiliation:
King's College London, MRC social, genetic and developmental psychiatry centre, Institute of psychiatry, psychology and neuroscience, SE5 8AFLondon, UK
R.E. Cooper
Affiliation:
King's College London, MRC social, genetic and developmental psychiatry centre, Institute of psychiatry, psychology and neuroscience, SE5 8AFLondon, UK Newham centre for mental health, unit for social and community psychiatry, Queen Mary University of London, UK
E. Vassos
Affiliation:
King's College London, MRC social, genetic and developmental psychiatry centre, Institute of psychiatry, psychology and neuroscience, SE5 8AFLondon, UK
P. Moran
Affiliation:
Centre for academic mental health, School of social & community medicine, University of Bristol, UK
P. Asherson
Affiliation:
King's College London, MRC social, genetic and developmental psychiatry centre, Institute of psychiatry, psychology and neuroscience, SE5 8AFLondon, UK
*
* Corresponding author. E-mail address:[email protected] (T.R. Moukhtarian).
Get access

Abstract

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.

Keywords

Attention-deficit/hyperactivity disorderEmotional labilityStimulantsAtomoxetineSystematic reviewMeta-analysis
Type
Review
Information
European Psychiatry , Volume 44 , July 2017 , pp. 198 - 207
Copyright
Copyright © European Psychiatric Association 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

1

Co-first authors.

References

Polanczyk, GDe Lima, MSLessa Horta, BBiederman, JRohde, LAThe worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007; 164(6): 942–948.CrossRefGoogle ScholarPubMed
Faraone, SVBiederman, JMick, EThe age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 2006; 36(2): 159–165.CrossRefGoogle ScholarPubMed
Cheung, CHMRijsdijk, FMcLoughlin, GBrandeis, DBanaschewski, TAsherson, P, et al.Cognitive and neurophysiological markers of ADHD persistence and remission. Br J Psychiatry 2016; 208(6): 548–555.10.1192/bjp.bp.114.145185CrossRefGoogle ScholarPubMed
Fayyad, JDe Graaf, RKessler, RAlonso, JAngermeyer, MDemyttenaere, K, et al.Cross–national prevalence and correlates of adult attention–deficit hyperactivity disorder. Br J Psychiatry 2007; 190(5): 402–409.CrossRefGoogle ScholarPubMed
Posner, JKass, EHulvershorn, LUsing stimulants to treat ADHD-related emotional lability. Curr Psychiatry Rep 2014; 16(10): 478CrossRefGoogle ScholarPubMed
Association AP Diagnostic and statistical manual of mental disorders, 5th edition, VA: Arlington; 2013.Google Scholar
Skirrow, CAsherson, PEmotional lability, comorbidity and impairment in adults with attention-deficit hyperactivity disorder. J Affect Disord 2013; 147(1–3): 80–86.CrossRefGoogle ScholarPubMed
Barkley, RAFischer, MThe unique contribution of emotional impulsiveness to impairment in major life activities in hyperactive children as adults. J Am Acad Child Adolesc Psychiatry 2010; 49(5): 503–513.Google ScholarPubMed
Rosler, MRetz, WFischer, ROse, CAlm, BDeckert, J, et al.Twenty-four-week treatment with extended release methylphenidate improves emotional symptoms in adult ADHD. World J Biol Psychiatry 2010; 11(5): 709–718.CrossRefGoogle ScholarPubMed
Asherson, PStes, SNilsson Markhed, MBerggren, LSvanborg, PKutzelnigg, A, et al.The effects of atomoxetine on emotional control in adults with ADHD: an integrated analysis of multicenter studies. Eur Psychiatry 2015; 30(4): 511–520.CrossRefGoogle ScholarPubMed
Wender, PHAttention-deficiti hyperactivity disorder in adults. Psychiatr Clin North Am 1998; 21: 761–774.CrossRefGoogle ScholarPubMed
Wood, DRReimherr, FWWender, PHJohnson, GEDiagnosis and treatment of minimal brain dysfunction in adults: a preliminary report. Arch Gen Psychiatry 1976; 33: 1453–1460.CrossRefGoogle ScholarPubMed
Asherson, PBuitelaar, JFaraone, SVRohde, LAAdult attention-deficit hyperactivity disorder: key conceptual issues. The lancet Psychiatry 2016; 3(6): 568–578.CrossRefGoogle ScholarPubMed
Asherson, PYoung, AHEich-Hochli, DMoran, PPorsdal, VDeberdt, WDifferential diagnosis, comorbidity, and treatment of attention-deficit/hyperactivity disorder in relation to bipolar disorder or borderline personality disorder in adults. Curr Med Res Opin 2014; 30(8): 1657–1672.CrossRefGoogle ScholarPubMed
Skirrow, CHosang, GMFarmer, AEAsherson, PAn update on the debated association between ADHD and bipolar disorder across the lifespan. J Affect Disord 2012; 141(2–3): 143–159.CrossRefGoogle ScholarPubMed
Skirrow, CMcLoughlin, GKuntsi, JAsherson, PBehavioral, neurocognitive and treatment overlap between attention-deficit/hyperactivity disorder and mood instability. Expert Rev Neurother 2009; 9(4): 489–503.CrossRefGoogle ScholarPubMed
Reimherr, FWMarchant, BKStrong, REHedges, DWAdler, LSpencer, TJ, et al.Emotional dysregulation in adult ADHD and response to atomoxetine. Biol Psychiatry 2005; 58(2): 125–131.CrossRefGoogle ScholarPubMed
Retz, WRosler, MOse, CScherag, AAlm, BPhilipsen, A, et al.Multiscale assessment of treatment efficacy in adults with ADHD: a randomized placebo-controlled, multi-centre study with extended-release methylphenidate. World J Biol Psychiatry 2012; 13(1): 48–59.CrossRefGoogle ScholarPubMed
Marchant, BKReimherr, FWRobison, RJOlsen, JLKondo, DGMethylphenidate transdermal system in adult ADHD and impact on emotional and oppositional symptoms. J Atten Disord 2011; 15(4): 295–304.CrossRefGoogle ScholarPubMed
Reimherr, FWMarchant, BKGift, TESteans, TAWender, PHTypes of adult attention-deficit hyperactivity disorder (ADHD): baseline characteristics, initial response, and long-term response to treatment with methylphenidate. Atten Defic Hyperact Disord 2015; 7(2): 115–128.CrossRefGoogle ScholarPubMed
Moher, DLiberati, ATetzlaff, JAltman, DGPreferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Journal of Clinical Epidemiology, 2009;62(10):1006–12.CrossRefGoogle ScholarPubMed
Higgins, JPTGreen, SCochrane handbook for systematic reviews of interventions Hoboken: Wiley; 2008, http://www.kcl.eblib.com/patron/FullRecord.aspx?p=366838.CrossRefGoogle Scholar
Roth, RMIsquith, PKGioia, GABehavior rating inventory of executive function–adult version (BRIEF-A). Parinc; 2000.Google Scholar
Conners, CKErhardt, DSparrow, MAConners’ adult ADHD rating scales (CAARS). New York; 1999.Google Scholar
Corp, SStata statistical software., 11 ed., College Station, TX: STATACorp LP; 2009.Google Scholar
Morris, SBEstimating effect sizes from pretest-posttest-control group designs. Organizational Research Methods 2008; 11(2): 364–386.CrossRefGoogle Scholar
Cohen, JA power primer. Psychol Bull 1992; 112(1): 155–159.10.1037/0033-2909.112.1.155CrossRefGoogle ScholarPubMed
Field, APGillett, RHow to do a meta-analysis. Br J Math Stat Psychol 2010; 63(3): 665–694.CrossRefGoogle Scholar
Adler, LAClemow, DBWilliams, DWDurell, TMAtomoxetine effects on executive function as measured by the BRIEF--a in young adults with ADHD: a randomized, double-blind, placebo-controlled study. PLoS One 2014;9(8):e104175.CrossRefGoogle ScholarPubMed
Reimherr, FWWilliams, EDStrong, REMestas, RSoni, PMarchant, BKA double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. J Clin Psychiatry 2007; 68(1): 93–101.10.4088/JCP.v68n0113CrossRefGoogle ScholarPubMed
Adler, LADirks, BDeas, PFRaychaudhuri, ADauphin, MRLasser, RA, et al.Lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2013; 74(7): 694–702.10.4088/JCP.12m08144CrossRefGoogle ScholarPubMed
Goto, THirata, YTakita, YTrzepacz, PTAllen, AJSong, DH, et al. Efficacy and safety of atomoxetine hydrochloride in Asian adults with ADHD: a multinational 10-week randomized double-blind placebo-controlled Asian study. J Atten Disord 2013Google Scholar
Wender, PHReimherr, FWMarchant, BKSanford, MECzajkowski, LATomb, DAA one year trial of methylphenidate in the treatment of ADHD. J Atten Disord 2011; 15(1): 36–45.CrossRefGoogle ScholarPubMed
Castells, XRamos-Quiroga, JARigau, DBosch, RNogueira, MVidal, X, et al.Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder. CNS Drugs 2011; 25(2): 157–169.CrossRefGoogle ScholarPubMed
Cunill, RCastells, XTobias, ACapellà, DAtomoxetine for attention deficit hyperactivity disorder in the adulthood: a meta-analysis and meta-regression. Pharmacoepidemiol Drug Saf 2013; 22(9): 961–969.Google ScholarPubMed
Adler, LMDTanaka, YPWilliams, DMTrzepacz, PTMDGoto, TMDPAllen AJMDP, , et al.Executive function in adults with attention-deficit/hyperactivity disorder during treatment with atomoxetine in a randomized, placebo-controlled, withdrawal study. J Clin Psychopharmacol 2014; 34(4): 461–466.CrossRefGoogle Scholar
Ortego, CBotella, JThe hard but necessary task of gathering order-one effect size indices in meta-analysis. Psicológica 2010; 31(2): 291–315.Google Scholar
Stoffers, JMVöllm, BARücker, GTimmer, AHuband, NLieb, K Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev) 2012;(8). http://dx.doi.org/10.1002/14651858.CD005652.pub2 [Art. No.: CD005652].CrossRefGoogle Scholar
Philipsen, ARichter, HPeters, JAlm, BSobanski, EColla, M, et al.Structured group psychotherapy in adults with attention deficit hyperactivity disorder: results of an open multicentre study. J Nerv Ment Dis 2007; 195(12): 1013–1019.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.