Short-Term Effects of Lisdexamfetamine Dimesylate on Cardiovascular Parameters in a 4-Week Clinical Trial in Adults With Attention-Deficit/Hyperactivity Disorder
Abstract
Objective To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD). Method Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter. Results There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P Conclusions Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as pres…
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Heal, D. J., Smith, S. L., Gosden, J., & Nutt, D. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113482532 · Cited by 622 · see citing works
“The efficacy of lisdexamfetamine has been demonstrated in a number of randomised, double-blind, placebo-controlled clinical trials in ADHD in children, adolescents (Biederman et al., 2007a,b; Lopez et al., 2008; Wigal et al., 2009) and adults (Adler et al., 2008, 2009; Wigal et al., 2010a).”
BackgroundMick, E. O., McManus, D. D., & Goldberg, R. J. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.06.011 · Cited by 134 · see citing works
“Six studies employed optimal response dose titration (Spencer et al., 2005, Adler et al., 2009a, Rosler et al., 2009, Biederman et al., 2010, Retz et al., 2012, Biederman et al., 2012) and four studies employed a forced-dose titration (Weisler et al., 2006, Spencer et al., 2007, Medori et al.,…”
InfluentialMartínez-Raga, J., Knecht, C., Szerman, N., & Martinez, M. I. (2012) · CNS Drugs · doi:10.1007/s40263-012-0019-9 · Cited by 128 · see citing works
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Wilens, T. E., Morrison, N. R., & Prince, J. B. (2011) · Expert Review of Neurotherapeutics · doi:10.1586/ern.11.137 · Cited by 113 · see citing works
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Coghill, D. R., Caballero, B., Sorooshian, S., & Civil, R. (2014) · CNS Drugs · doi:10.1007/s40263-014-0166-2 · Cited by 89 · see citing works
“However, few patients met outlier criteria at more than two study time points (study 303) or at 2 consecutive weeks (study 305) (Table 3), suggesting that the cardiovascular effects of treatment were not sustained [26, 31].”
BackgroundErmer, J., Homolka, R., Martin, P., Buckwalter, M., Purkayastha, J., & Roesch, B. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009357346 · Cited by 72 · see citing works
Drug-related hypertension and resistance to antihypertensive treatment
Rossi, G. P., Seccia, T. M., Maniero, C., & Pessina, A. C. (2011) · Journal of Hypertension · doi:10.1097/hjh.0b013e32834c465d · Cited by 68 · see citing works
Practical Use and Risk of Modafinil, a Novel Waking Drug
Kim, D. (2012) · Environmental Health and Toxicology · doi:10.5620/eht.2012.27.e2012007 · Cited by 75 · see citing works
Santosh, P. J., Sattar, S., & Canagaratnam, M. (2011) · CNS Drugs · doi:10.2165/11593070-000000000-00000 · Cited by 62 · see citing works
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Castells, X., Blanco-Silvente, L., & Cunill, R. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007813.pub3 · Cited by 209 · see citing works
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Castells, X., Ramos-Quiroga, J. A., Bosch, R., Nogueira, M., & Casas, M. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007813.pub2 · Cited by 80 · see citing works
Dolder, P. C., Strajhar, P., Vizeli, P., Hammann, F., Odermatt, A., & Liechti, M. E. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00617 · Cited by 57 · see citing works
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Martı́nez-Raga, J., Ferreros, A., Knecht, C., de Alvaro, R., & Carabal, E. (2016) · Therapeutic Advances in Drug Safety · doi:10.1177/2042098616679636 · Cited by 44 · see citing works
“2013c], as well as in adults with ADHD [Adler et al. 2009; Martinez-Raga et al. 2013c; Mick et al. 2013; Weisler et al. 2005; Weisler et al. 2006].”
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Steer, C., Froelich, J., Soutullo, C. A., Johnson, M., & Shaw, M. (2012) · CNS Drugs · doi:10.2165/11634340-000000000-00000 · Cited by 30 · see citing works
“The initial dosage for lisdexamfetamine is 30mg once daily, taken in the morning up to a maximum of 70mg/day.([62]) Lisdexamfetamine is usually titrated slowly, increasing the dose every 4–7 days (in 20mg increments) until a therapeutic dose is reached.”
BackgroundWard, K., & Citrome, L. (2018) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2018.1420163 · Cited by 32 · see citing works
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Frampton, J. E. (2016) · CNS Drugs · doi:10.1007/s40263-016-0327-6 · Cited by 37 · see citing works
Adult Attention-Deficit/Hyperactivity Disorder Treatment and Cardiovascular Implications
Hammerness, P. G., Surman, C. B. H., & Chilton, A. (2011) · Current Psychiatry Reports · doi:10.1007/s11920-011-0213-3 · Cited by 24 · see citing works
Ermer, J. C., Haffey, M. B., Richards, C., Lasseter, K. C., Roesch, B. G., Purkayastha, J., Corcoran, M., Harlin, B., & Martin, P. T. (2013) · Clinical Drug Investigation · doi:10.1007/s40261-013-0073-1 · Cited by 16 · see citing works
“Increases in pulse rate and blood pressure observed when LDX and VEN were administered alone were consistent with previous studies [11, 13, 17].”
ResultErmer, J., Richards, Lasseter, K., Adeyi, Corcoran, Martin, P., & Stanton, B. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s38377 · Cited by 19 · see citing works
“In a post hoc analysis of that 4-week trial, 18 the proportion of participants who were pulse outliers ( $ 100 beats per minute, any one event) ranged from 3.3% to 8.5% in the LDX groups.”
InfluentialReview of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder
Najib, J., Wimer, D., Zeng, J., Lam, K. W., Romanyak, N., Paige Morgan, E., & Thadavila, A. (2017) · Journal of Central Nervous System Disease · doi:10.1177/1179573517728090 · Cited by 17 · see citing works
Safety of Stimulants Across Patient Populations
Oliva, H. N. P., Prudente, T. P., Mayerson, T. F., Mignosa, M. M., Oliva, I. O., Potenza, M. N., Jegede, O. O., & Angarita, G. A. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.9492 · Cited by 16 · see citing works
Spontaneous Coronary Artery Dissection in a 22-Year-Old Man on Lisdexamfetamine
Afzal, A. M., Sarmast, S., Weber, N., & SCHUSSLER, J. M. (2015) · Baylor University Medical Center Proceedings · doi:10.1080/08998280.2015.11929277 · Cited by 14 · see citing works
Lisdexamfetamine dimesylate: a new option in stimulant treatment for ADHD
Dew, R. E., & Kollins, S. H. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.531009 · Cited by 14 · see citing works
“active treatment group; they therefore recommend that cardiovascular monitoring should be part of standard care with LDX [34].”
BackgroundA cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder
Hammerness, P., Zusman, R., Systrom, D., Surman, C., Baggish, A., Schillinger, M., Shelley-Abrahamson, R., & Wilens, T. E. (2013) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2012.678884 · Cited by 15 · see citing works
“…profi le, numerous, large controlled clinical trials of stimulants in healthy adults with ADHD have rarely identifi ed cardiovascular adverse effects outside of minor mean increases in blood pressure and heart rate (Biederman et al. 2007; Spencer et al. 2007; Wilens et al. 2005; Adler et al. 2009).”
BackgroundAntel, J., Albayrak, Ö., Heusch, G., Banaschewski, T., & Hebebrand, J. (2014) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-014-0522-8 · Cited by 11 · see citing works
Adler, L. A., Frick, G. S., & Yan, B. M. (2017) · Journal of Attention Disorders · doi:10.1177/1087054717696770 · Cited by 9 · see citing works
Self-citationErmer, J. C., Martin, P. T., Corcoran, M., & Matsuo, Y. (2019) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12082 · Cited by 9 · see citing works
Mattos, P. (2014) · Archives of Clinical Psychiatry (São Paulo) · doi:10.1590/0101-60830000000007 · Cited by 7 · see citing works
Frölich, J., Banaschewski, T., Spanagel, R., Döpfner, M., & Lehmkuhl, G. (2012) · Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie · doi:10.1024/1422-4917/a000185 · Cited by 9 · see citing works
Gasior, M., Freeman, J., Zammit, G., Donnelly, P., Gao, J., Ferreira-Cornwell, M., & Roth, T. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000202 · Cited by 4 · see citing works
“Small, subclinical increases in BP and pulse rate with lisdexamfetamine dimesylate and armodafinil are known cardiovascular effects of stimulants and were anticipated.(27,31,32) The population of this study differs from the population included in the approved prescribing information for lisdexamfetamine dimesylate.”
BackgroundResultStimulant Pharmacotherapy for Adults with ADHD
Hammerness, P. G. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-248-3_5 · Cited by 1 · see citing works
Effect of amphetamines on blood pressure
Chan, M., Chan, J. J., & Wright, J. M. (2025) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007896.pub4 · Cited by 4 · see citing works
Clinical Utility of Lisdexamfetamine for the Management of Attention-Deficit Hyperactivity Disorder
Nguyen, M. L., Shapiro, M. A., & Tharani, S. (2012) · Clinical Medicine Insights Therapeutics · doi:10.4137/cmt.s8706 · Cited by 1 · see citing works
Current awareness in human psychopharmacology
(2010) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1063
Current awareness: Pharmacoepidemiology and drug safety
(2010) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1852
- Authors
- Adler, L. A., Weisler, R. H., Goodman, D. W., Hamdani, M., & Niebler, G. E.
- Affiliations
- New York University (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Adler, Lenard A.
- ORCID
- Adler, Lenard A.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2009-12-15
- Volume
- 70
- Issue
- 12
- Pages
- 1652-1661
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2055401851
- Cited by
- 42
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 2 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 8
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- attention deficit hyperactivity disorder, adults, cardiovascular safety, blood pressure, heart rate, electrocardiographic abnormalities, stimulant medication, cardiovascular adverse events, dose-response relationship, pharmacovigilance, ADHD medication, short-term effects
- MeSH terms
- Lisdexamfetamine Dimesylate, Adolescent, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Blood Pressure, Cardiovascular System, Dextroamphetamine, Electrocardiography, Female, Heart Rate, Humans, Male, Middle Aged, Placebos, Prodrugs, Treatment Outcome
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