Cited by 385Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

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A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

Spencer, Thomas, Biederman, Joseph, Wilens, Timothy, Doyle, Robert, Surman, Craig, Prince, Jefferson, Mick, Eric, Aleardi, Megan, Herzig, Kathleen, Faraone, Stephen·2005·Biological Psychiatry

DOI 10.1016/j.biopsych.2004.11.043

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Abstract

Background The few controlled studies of methylphenidate (MPH) in adults with attention deficit/hyperactivity disorder (ADHD) have reported equivocal results. A previous, pilot study by our group suggested that these results were due to inadequate dosing. Method We conducted a randomized, 6-week, placebo-controlled, parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized instruments for diagnosis, separate assessments of ADHD, depressive and anxiety symptoms, and a robust average oral daily dose of 1.1 mg/kg/day. Results We found a marked therapeutic response for the MPH treatment of ADHD symptoms that exceeded the placebo response (76% vs. 19%). Treatment was safe and well tolerated. Response to MPH was independent of socioeconomic status, gender, and lifetime history of psychiatric comorbidity. Conclusions These results confirm that robust doses of MPH are effective in the treatment of adult ADHD.

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Background
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Torgersen, T., Gjervan, B., & Rasmussen, K. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s1223 · Cited by 60
“…in adults with ADHD, including one study with dexmethylphenidate (Wood et al 1976; Mattes et al 1984; Gualtieri et al 1985; Wender et al 1985; Spencer et al 1995, 2005, 2006; Kuperman et al 2001; Levin et al 2001, 2006, 2007; Schubiner et al 2002; Tenenbaum et al 2002; Bouffard et al 2003;…”
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Long-Term Safety of OROS Methylphenidate in Adults With Attention-Deficit/Hyperactivity Disorder: An Open-Label, Dose-Titration, 1-Year Study
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“Clinician-assessed response rates for ADHD symptom reduction with these agents have been reported in clinical trials and prospective community studies to be between 69% and 81%.(31,32) A recent review of the literature assessing results of studies conducted to date found that LA stimulants were shown to be superior to…”
Background
Emotion dysregulation in attention-deficit/hyperactivity disorder and borderline personality disorder
Moukhtarian, T. R., Mintah, R. S., Moran, P., & Asherson, P. J. (2018) · Borderline Personality Disorder and Emotion Dysregulation · doi:10.1186/s40479-018-0086-8 · Cited by 54
Comorbidity of migraine with ADHD in adults
Hansen, T. F., Hoeffding, L. K., Kogelman, L., Haspang, T. M., Ullum, H., Sørensen, E., Erikstrup, C., Pedersen, O. B., Nielsen, K. R., Hjalgrim, H., et al. (2018) · BMC Neurology · doi:10.1186/s12883-018-1149-6 · Cited by 46
Agreement Rates Between Parent and Self-Report on Past ADHD Symptoms in an Adult Clinical Sample
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“Such criteria have been used in large treatment studies with adults (Spencer et al., 2005).”
Method
Attention Deficit/Hyperactivity Disorder in Adults
Moss, S. B., Nair, R. J., Vallarino, A., & Wang, S. (2007) · Primary Care Clinics in Office Practice · doi:10.1016/j.pop.2007.05.005 · Cited by 45
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“…intervention in the treatment of ADHD for children, adolescents (Multidisciplinaire Richtlijn ADHD 2005), and adults (Kooij 2003; Spencer et al. 2005), it can also be prescribed to adults for somatic problems such as a delirium or during the palliative phase of a somatic…”
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“Findings have revealed comparable ef fects of MPH in adults as those observed in children and adolescents [116, 120, 123].”
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Methylphenidate HCl: therapy for attention deficit hyperactivity disorder
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“To this end, different techniques and methodologies have been used to demonstrate that childhood and adult ADHD have etiological similarities (Murphy & Barkley, 1996 ; Seidman et al. 1998 ; Barkley et al. 2004 ; Hervey et al. 2004 ; Spencer et al. 2005 ; Turner et al. 2005 ; Biederman et al. 2006).”
Method
Is emotion recognition the only problem in ADHD? effects of pharmacotherapy on face and emotion recognition in children with ADHD
Demi̇rci̇, E., & Erdoğan, A. (2016) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-016-0201-x · Cited by 45
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Frölich, J., Banaschewski, T., Döpfner, M., & Görtz‐Dorten, A. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.922542 · Cited by 40
“In adults, a similar positive response to MPH has been observed [79-81] with a similar safety profile [82].”
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Less discontinuation of ADHD drug use since the availability of long-acting ADHD medication in children, adolescents and adults under the age of 45 years in the Netherlands
van den Ban, E. F., Souverein, P. C., Swaab, H., van Engeland, H., Egberts, T. C. G., & Heerdink, E. R. (2010) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-010-0044-9 · Cited by 40
“…Parameter for the use of stimulant medications in the treatment of children, adolescents and adults 2002; Multidisciplinaire Richtlijn ADHD 2005) and adults (Kooij 2003; Spencer et al. 2005), it can also be prescribed to adults for somatic problems (Donker et al. 2005; Gagnon et al. 2005).”
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Method
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Clarke, S. P., Heussler, H., & Kohn, M. R. (2005) · Internal Medicine Journal · doi:10.1111/j.1445-5994.2005.00987.x · Cited by 43
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Background
Predictors of treatment outcome in adults with ADHD treated with OROS® methylphenidate
Buitelaar, J. K., Kooij, J. J. S., Ramos‐Quiroga, J. A., Dejonckheere, J., Casas, M., van Oene, J. C., Schäuble, B., & Trott, G.-E. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.12.016 · Cited by 39
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BackgroundResultInfluential
Correlates of physical activity with intrusive thoughts, worry and impulsivity in adults with attention deficit/hyperactivity disorder: a cross-sectional pilot study.
Amitai Abramovitch, A., Goldzweig, G., & Schweiger, A. (2013) · PubMed · Cited by 37
Methylphenidate increases cigarette smoking in participants with ADHD
Vansickel, A., Stoops, W. W., Glaser, P., Poole, M. M., & Rush, C. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2328-y · Cited by 41
“Methylphenidate is commonly prescribed and effective for the treatment of attention deficit/hyperactivity disorder (ADHD) symptoms in children and adults (Brown et al. 2005; Faraone et al. 2006; Spencer et al. 2005).”
Background
OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: A randomized, placebo-controlled cross-over study
Bron, T. I., Bijlenga, D., Boonstra, A. M., Breuk, M., Pardoen, W. F. H., Beekman, A. T. F., & Kooij, J. J. S. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.007 · Cited by 38
“Stimulant medications such as methylphenidate are the pharmacological treatment of choice for ADHD (Spencer et al., 2005).”
Background
Nonmedical Use of Prescription ADHD Stimulant Medications Among Adults in a Substance Abuse Treatment Population
Cassidy, T. A., McNaughton, E. C., Varughese, S., Russo, L., Zulueta, M. G., & Butler, S. F. (2013) · Journal of Attention Disorders · doi:10.1177/1087054713493321 · Cited by 37
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Background
Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder
Biederman, J., Mick, E. O., Surman, C. B. H., Doyle, R., Hammerness, P. G., Michel, E., Martin, J., & Spencer, T. J. (2007) · BMC Psychiatry · doi:10.1186/1471-244x-7-49 · Cited by 37
“To this end we used data from two similarly designed, large, randomized, placebo-controlled, six week trials of IR and OROS-MPH in adults with DSM-IV ADHD [11,12].”
InfluentialSelf-citation
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Krause, J., Krause, K., Dresel, S. H. J., la Fougère, C., & Ackenheil, M. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.1/jkrause · Cited by 35
An Open-Label Trial of OROS Methylphenidate in Adults with Late-Onset ADHD
Biederman, J., Mick, E. O., Spencer, T. J., Surman, C. B. H., Hammerness, P. G., Doyle, R., Dougherty, M., Aleardi, M., & Schweitzer, K. (2006) · CNS Spectrums · doi:10.1017/s1092852900014528 · Cited by 37
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Self-citation
Toward Quality Care in ADHD: Defining the Goals of Treatment
Rostain, A., Jensen, P. S., Connor, D. F., Miesle, L. M., & Faraone, S. V. (2015) · Journal of Attention Disorders · doi:10.1177/1087054712473835 · Cited by 33
“…Sinzig et al., 2007; Spencer et al., 1998; Spencer, Biederman, Heiligenstein et al., 2001; Spencer , Biederman, Wilens et al., 2001; Spencer et al., 2002; Spencer et al., 2005; Spencer et al., 2007; Stein et al., 2003; Szobot, Ketzer, Parente, Biederman, & Rohde, 2004; Taylor & Russo, 2000;…”
Self-citation
Attention-deficit/hyperactivity disorder in pregnancy and the postpartum period
Scoten, O. C., Tabi, K., Paquette, V., Carrion, P. B., Ryan, D. M., Radonjić, N. V., Whitham, E. A., & Hippman, C. (2024) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2024.02.297 · Cited by 38
Achieving Remission as a Routine Goal of Pharmacotherapy in Attention-Deficit Hyperactivity Disorder
Ramos-Quiroga, J. A., & Casas, M. (2011) · CNS Drugs · doi:10.2165/11538450-000000000-00000 · Cited by 33
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Oehrlein, E. M., Burcu, M., Safer, D. J., & ZITO, J. M. (2016) · Psychiatric Services · doi:10.1176/appi.ps.201500269 · Cited by 37
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Friedlander, A. H., Yagiela, J. A., Mahler, M. E., & Rubín, R. T. (2007) · The Journal of the American Dental Association · doi:10.14219/jada.archive.2007.0199 · Cited by 34
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Faraone, S. V. (2010) · Journal of Attention Disorders · doi:10.1177/1087054710379738 · Cited by 32
Self-citation
Four-Year Outcome in Psychopharmacologically Treated Adults With Attention-Deficit/Hyperactivity Disorder
Lensing, M. B., Zeiner, P., Sandvik, L., & Opjordsmoen, S. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12m07714 · Cited by 32
Attention‐Deficit/Hyperactivity Disorder
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Castells, X., Cunill, R., & Capellà, D. (2013) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-012-1390-7 · Cited by 41
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Upadhyaya, H., Ramos-Quiroga, J., Adler, L., Williams, D. R., Tanaka, Y., Lane, J. R., Escobar, R., Trzepacz, P., Camporeale, A., & Allen, A. (2013) · The European Journal of Psychiatry · doi:10.4321/s0213-61632013000300004 · Cited by 28
Treatment of adults with attention-deficit/hyperactivity disorder
Hechtman, L. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s1747 · Cited by 31
“Stimulants are the most effective medications for the treatment of ADHD, with responsiveness rates in the 70%–80% range (Spencer et al 2005).”
Background
Further evidence of low adherence to stimulant treatment in adult ADHD: an electronic medical record study examining timely renewal of a stimulant prescription
Biederman, J., Fried, R. S., DiSalvo, M., Woodworth, K. Y., Biederman, I., Driscoll, H., Noyes, E. J., Faraone, S. V., & Perlis, R. H. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05576-y · Cited by 37
“At the same time, ADHD is among the most treatable psychiatric disorders due to the well-documented safety and efficacy of stimulants (Spencer et al. 2005; Spencer et al. 2007; Spencer et al. 2013; Biederman et al. 2006a; Medori et al. 2008; Faraone and Glatt 2009; Canadian ADHD Resource Alliance 2008; Kendall et al.…”
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Effect of acute and repeated treatment with desipramine or methylphenidate on serial reversal learning in rats
Seu, E., & Jentsch, J. D. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.007 · Cited by 32
“Multiple clinical reports suggest that repeated dosing with these agents is required before a significant improvement in ADHD behavioral symptoms can be measured (Spencer et al., 2005; Spencer et al., 1998), suggesting that chronic treatment with these drugs may be necessary to relieve behavioral symptoms.”
BackgroundInfluential
The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder
Ashton, H., Gallagher, P., & Moore, B. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106061710 · Cited by 31
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El ASRS v.1.1. como instrumento de cribado del trastorno por déficit de atención e hiperactividad en adultos tratados por conductas adictivas: propiedades psicométricas y prevalencia estimada
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Self-citation
Efficacy and safety of prolonged-release OROS methylphenidate in adults with attention deficit/hyperactivity disorder: A 13-week, randomized, double-blind, placebo-controlled, fixed-dose study
Casas, M., Rösler, M., Sandra Kooij, J. J., Ginsberg, Y., Ramos-Quiroga, J. A., Heger, S., Berwaerts, J., Dejonckheere, J., van der Vorst, E., & Schäuble, B. (2013) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.600333 · Cited by 38
“In short-term ( 7-week) clinical trials, methylphenidate (MPH) is an effective treatment for adults with ADHD (Bouffard et al. 2003; Kooij et al. 2004; Spencer et al. 2005).”
Background
A pilot clinical trial of oxcarbazepine in adults with attention-deficit hyperactivity disorder
Davids, E., Kis, B., Specka, M., & Gastpar, M. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.03.035 · Cited by 28
A Randomized, Single-Blind, Substitution Study of OROS Methylphenidate (Concerta) in ADHD Adults Receiving Immediate Release Methylphenidate
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“Recent, separate, large, randomized, placebo-controlled clinical trials have documented that therapeutic daily doses approximating 1 mg/kg of TID immediate-release methylphenidate (IR-MPH) and once-daily extended-release formulation of methylphenidate (OROS-MPH) are each highly effective and well tolerated in the trea…”
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Methylphenidate normalizes emotional processing in adult patients with attention-deficit/hyperactivity disorder: Preliminary findings
Conzelmann, A., Woidich, E., Mucha, R. F., Weyers, P., Jacob, C. P., Lesch, K.-P., & Pauli, P. (2011) · Brain Research · doi:10.1016/j.brainres.2010.12.085 · Cited by 27
Adrenergic α2A receptor gene is not associated with methylphenidate response in adults with ADHD
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“However, many patients still do not show an appropriate clinical response to the MPH treatment [29, 51 , 52].”
Background
Pharmacokinetics, dose‐range, and mutagenicity studies of methylphenidate hydrochloride in B6C3F1 mice
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A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD
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“The use of a 30% reduction in ADHD symptoms is more conservative than recent trials (25% reduction; [26]) and commensurate with previous work [17,28,29].”
Self-citation
Multimodale Therapie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter
Jacob, C., Philipsen, A., Ebert, D., & Deckert, J. (2008) · Der Nervenarzt · doi:10.1007/s00115-008-2510-6 · Cited by 24
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy, Safety, and Tolerability of Extended-Release Metadoxine in Adults With Attention-Deficit/Hyperactivity Disorder
Manor, I., Ben‐Hayun, R., Aharon‐Peretz, J., Salomy, D., Weizman, A., Daniely, Y., Megiddo, D., Newcorn, J. H., Biederman, J., & Adler, L. A. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12m07767 · Cited by 25
Self-citation
Acute effects of methylphenidate on neuropsychological parameters in adults with ADHD: possible relevance for therapy
Kurscheidt, J. C., Peiler, P., Behnken, A., Abel, S., Pedersen, A., Suslow, T., & Deckert, J. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0871-4 · Cited by 25
The Decrease in Human Endogenous Retrovirus-H Activity Runs in Parallel with Improvement in ADHD Symptoms in Patients Undergoing Methylphenidate Therapy
Cipriani, C., Pitzianti, M. B., Matteucci, C., D’Agati, E., Miele, M. T., Rapaccini, V., Grelli, S., Curatolo, P., Paola, S.-V., Pasini, A., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113286 · Cited by 24
Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults
Cândido, R. C. F., de Padua, C. A. M., Golder, S., & Junqueira, D. R. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013011.pub2 · Cited by 35
“Three trials reported data on discontinuation due to adverse events (Kooij 2004; Schubiner 2002; Spencer 2005), with one participant discontinuing treatment with placebo and seven discontinuing treatment while receiving IR methylphenidate.”
BackgroundMethodResultInfluential
Questões atuais no tratamento farmacológico do TDAH em adultos com metilfenidato
Louzã, M. R., & Mattos, P. (2007) · Jornal Brasileiro de Psiquiatria · doi:10.1590/s0047-20852007000500012 · Cited by 22
“O metilfenidato parece ser seguro para utilização em pacientes epilépticos (Schubert, 2005) e bipolares (Wilens et al., 2002), desde que adequadamente tratados e com quadro estável.”
Background
Comparative Efficacy of Methylphenidate and Atomoxetine on Emotional and Behavioral Problems in Youths with Attention-Deficit/Hyperactivity Disorder
Shih, H.-H., Shang, C., & Gau, S. S. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2018.0076 · Cited by 23
“Some trials showed a signiﬁcant reduction in anxiety and depression after treatment with methylphenidate in patients with ADHD (Bouffard et al. 2003); others found no change (Kuperman et al. 2001), and still others demonstrated an increase in anxiety and depressive symptoms (Spencer et al. 2005).”
History of attention-deficit hyperactivity disorder (ADHD)
Conners, C. K. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781139035491.002 · Cited by 22
The Cochrane Collaboration withdraws a review on methylphenidate for adults with attention deficit hyperactivity disorder
Boesen, K., Saiz, L. C., Erviti, J., Storebø, O. J., Gluud, C. N., Gøtzsche, P. C., & Jørgensen, K. J. (2017) · BMJ Evidence-Based Medicine · doi:10.1136/ebmed-2017-110716 · Cited by 22
Developmental and Behavioral Disorders Grown Up: Attention Deficit Hyperactivity Disorder
Antshel, K. M., & Barkley, R. A. (2009) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e31819359ea · Cited by 24
Cardiovascular Safety of Stimulant Medications for Pediatric Attention-Deficit Hyperactivity Disorder
Silva, R. R., Skimming, J. W., & Muniz, R. (2010) · Clinical Pediatrics · doi:10.1177/0009922810368289 · Cited by 22
“MAS 30 mg 2% (2/123) Wilens et al15 (13-17) ≥ 25 bpm Increase in baseline pulse Placebo 1% (1/69) MAS-XR (10-60 mg/d) 2% (6/258)”
Attention deficit hyperactivity disorder in children
Зиновьева, О. Е., Rogovina, E. G., & Tyrinova, E. A. (2014) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2014-1-4-8 · Cited by 24
Comorbidity and its Impact in Adult Patients with Attention-Deficit/Hyperactivity Disorder: A Primary Care Perspective
Babcock, T., & Ornstein, C. S. (2009) · Postgraduate Medicine · doi:10.3810/pgm.2009.05.2005 · Cited by 23
“Moreover, there were no changes in measures of anxiety and depression in patients treated with methylphenidate compared with those who had received placebo.(42) Results from another study of 40 adult ADHD patients with and without comorbid depression found that both groups benefi ted equally from treatment with methyl…”
Result
Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults
Cândido, R. C. F., Menezes de Padua, C. A., Golder, S., & Junqueira, D. R. (2021) · White Rose Research Online (University of Leeds, The University of Sheffield, University of York) · Cited by 20
Translating Attention-Deficit/Hyperactivity Disorder Rating Scale-5 and Weiss Functional Impairment Rating Scale-Parent Effectiveness Scores into Clinical Global Impressions Clinical Significance Levels in Four Randomized Clinical Trials of SPN-812 (Viloxazine Extended-Release) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder
Nasser, A. F., Kosheleff, A. R., Hull, J. T., Liranso, T., Qin, P., Busse, G. D., O’Neal, W., D, M. F. M., Faraone, S. V., & Rubin, J. S. (2021) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2020.0148 · Cited by 22
“It is reported ubiquitously in clinical trials treating children and adults for a variety of disorders, including ADHD (Wilens et al. 1999, 2001; Spencer et al. 2005; Safren et al. 2010; Sprich et al. 2016; Nasser et al. 2020).”
BackgroundSelf-citation
Drug Class Review on Pharmacologic Treatments for ADHD
McDonagh, M. S., Peterson, K., & Thakurta, S. (2005) · Cited by 21
The Black Book of Psychotropic Dosing and Monitoring
DeBattista, C., & Schatzberg, A. F. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4493 · Cited by 23
Professionally successful adults with attention-deficit/hyperactivity disorder (ADHD): Compensation strategies and subjective effects of pharmacological treatment
Palmini, A. (2008) · Dementia & Neuropsychologia · doi:10.1590/s1980-57642009dn20100013 · Cited by 20
Is Response to OROS‐Methylphenidate Treatment Moderated by Treatment with Antidepressants or Psychiatric Comorbidity? A Secondary Analysis from a Large Randomized Double Blind Study of Adults with ADHD
Biederman, J., Mick, E., Spencer, T., Surman, C., & Faraone, S. V. (2012) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00233.x · Cited by 20
“[14], for long-acting MPH delivered via an osmotic release oral system (OROS) [15,16], for IR dextroamphetamine, for dexmethylphenidate extended release [17], and for lisdexamfetamine dimesylate [18].”
Self-citation
Attention-deficit/hyperactivity disorder (ADHD) in the course of life
Trott, G. (2006) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-006-1003-5 · Cited by 20
Reasons for Pretreatment Attrition and Dropout From Methylphenidate in Adults With Attention-Deficit/Hyperactivity Disorder
Victor, M. M., Grevet, E. H., Salgado, C. A. I., Silva, K. L., Sousa, N. O., Karam, R. G., Vitola, E. S., Picon, F. A., Zeni, G. D., Contini, V., et al. (2009) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181c00b1e · Cited by 20
Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder
Farhat, L. C., Flores, J. M., Avila-Quintero, V. J., Polanczyk, G. V., Cipriani, A., Furukawa, T. A., Bloch, M. H., & Cortese, S. (2023) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2023.3985 · Cited by 20
Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults
Mueller, L., de Jesus, J. S., Schmid, Y., Müller, F., Becker, A., Klaiber, A., Straumann, I., Luethi, D., Haijen, E. C. H. M., Hurks, P. P. M., et al. (2025) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2025.0044 · Cited by 21
Management of attention-deficit hyperactivity disorder in adults: focus on methylphenidate hydrochloride
Moss, S. B. (2009) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s4101 · Cited by 19
“38,40,54 In a study comparing the efficacy of OROS MPH (72 mg), extended-release amphetamine salts (30 mg) and placebo in improving simulated driving performance among 35 adolescent drivers with ADHD, OROS MPH resulted in a significant improvement in driving performance among adolescents with ADHD.”
Long-Term (1 Year) Safety and Efficacy of Methylphenidate Modified-Release Long-Acting Formulation (MPH-LA) in Adults with Attention-Deficit Hyperactivity Disorder: A 26-Week, Flexible-Dose, Open-Label Extension to a 40-Week, Double-Blind, Randomised, Placebo-Controlled Core Study
Ginsberg, Y., Arngrim, T., Philipsen, A., Gandhi, P., Chen, C.-W., Kumar, V., & Huss, M. (2014) · CNS Drugs · doi:10.1007/s40263-014-0180-4 · Cited by 20
“Methylphenidate remains one of the most commonly prescribed medications for the treatment of ADHD in adults because of availability of efficacy and safety data [5–16].”
Background
Adult attention‐deficit/hyperactivity disorder: A survey of diagnosis and treatment practices
Knutson, K. C., & O’Malley, M. (2010) · Journal of the American Academy of Nurse Practitioners · doi:10.1111/j.1745-7599.2010.00546.x · Cited by 18
“Psychostimulant medication is considered to be firstline treatment for ADHD, and has been shown to be safe and effective for adult patients (Medori et al., 2008; Spencer et al., 2005; Wilens, Spencer, & Biederman, 2002).”
Background
Practice Parameter for the Assessment and Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
assessment, I. A. M. H., (inattention, T. C. S. S. F. A. B. S. A. Q. R. T. M. S. D. O. A., impulsivity, the, A. H. A. A. W. S. S. C. I. T. S. Q. S. B. A. R. O. T. N. O. T. C. C. R. S. O. S. Q. C., symptoms of ADHD can also be included in clinic/office registration materials to be completed by parents before visits or in the waiting room before the evaluation. If a parent reports that the patient suffers from any symptoms of ADHD that induce impairment or if the patient scores in the clinical range for ADHD symptoms on a rating scale, & indicated., T. A. F. E. F. A. A. S. O. I. T. N. R. I. (2008) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/foc.6.3.foc401 · Cited by 18
Primer consenso latinoamericano de trastorno por déficit de atención e hiperactividad
Barragán-Pérez, E., de la Peña, F. R., León, S. O., Ruíz-Garcìa, M., Hernández-Aguilar, J., Palacios‐Cruz, L., & Suárez-Reynaga, A. (2007) · Boletín Médico del Hospital Infantil de México · Cited by 17
Long-term outcomes of stimulant medication in attention-deficit hyperactivity disorder
Poulton, A. S. (2006) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.6.4.551 · Cited by 19
Information for Physicians and Pharmacists About Drugs That Might Cause Dry Mouth: A Study of Monographs and Published Literature
Nguyen, C. T., MacEntee, M. I., Mintzes, B. J., & Perry, T. L. (2013) · Drugs & Aging · doi:10.1007/s40266-013-0141-5 · Cited by 17
Zur Wirksamkeit pharmakologischer und psychotherapeutischer Therapien bei Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Erwachsenenalter: Eine empirische Metaanalyse
Linderkamp, F., & Lauth, G. W. (2011) · Verhaltenstherapie · doi:10.1159/000332429 · Cited by 18
Severity But Not Comorbidities Predicts Response to Methylphenidate in Adults With Attention-Deficit/Hyperactivity Disorder
Victor, M. M., Rovaris, D. L., Salgado, C. A. I., Silva, K. L., Karam, R. G., Vitola, E. S., Picon, F. A., Contini, V., Guimarães-da-Silva, P. O., Blaya‐Rocha, P., et al. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000091 · Cited by 17
“The improvement of ADHD symptoms in our sample was comparable with those previously reported in randomized clinical trials.(44) To our knowledge, our study is the first one to assess clinical and sociodemographic predictors of IR-MPH treatment response in adults with ADHD from a sample collected outside the United Sta…”
Result
Long-Term Treatment of ADHD With Stimulants
Powell, S. G., Thomsen, P. H., Frydenberg, M., & Rasmussen, H. (2010) · Journal of Attention Disorders · doi:10.1177/1087054710368486 · Cited by 18
“For adults with ADHD the optimal dose may be as high as 1.1 mg/kg/day (Spencer et al., 2005).”
BackgroundInfluential
Arousal Regulation in Affective Disorders
Hegerl, U., Sander, C., & Hensch, T. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802456-0.00012-1 · Cited by 19
A candidate gene investigation of methylphenidate response in adult attention-deficit/hyperactivity disorder patients: results from a naturalistic study
Hegvik, T., Jacobsen, K. K., Fredriksen, M., Zayats, T., & Haavik, J. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1540-7 · Cited by 17
Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate
Kluge, M., Hegerl, U., Sander, C., Dietzel, J., Mergl, R., Bitter, I., Demyttenaere, K., Gusmão, R. M., González-Pinto, A. M., Pérez, V., et al. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-71 · Cited by 16
“In ADHD, a disease with high comorbidity and a broad symptom overlap with mania [21,22], psychostimulants effectively reduce attention deficits, sensation seeking behaviour and hyperactivity, symptoms which are also present in mania [23,24].”
Background
Attribution and Self-Evaluation of Continuous Performance Test Task Performance in Medicated and Unmedicated Adults With ADHD
Barrilleaux, K., & Advokat, C. D. (2008) · Journal of Attention Disorders · doi:10.1177/1087054708314604 · Cited by 16
“Numerous studies show at least short-term improvement of symptoms with medication (Dodson, 2005), although there is evidence that adults require larger doses than children for maximum efficacy (Spencer et al., 2005).”
Background
The Risk of Methylphenidate Pharmacotherapy for Adults with ADHD
Bieś, R., Fojcik, J., Warchala, A., Trędzbor, B., Krysta, K., Piekarska-Bugiel, K., & Krzystanek, M. (2023) · Pharmaceuticals · doi:10.3390/ph16091292 · Cited by 16
“Further investigation of cardiovascular parameters showed that people in the MPH population were more likely to have clinically signiﬁcant elevated heart rates than those receiving a placebo [28,30].”
Influential
Long-term relationship between methylphenidate and tobacco consumption and nicotine craving in adults with ADHD in a prospective cohort study.
Bron, T. I., Bijlenga, D., Kasander, M. V., Spuijbroek, A. T., Beekman, A., & Kooij, J. J. S. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.06.004 · Cited by 13
“It is therefore regarded as the drug of choice in the medical treatment for ADHD (Faraone et al., 2002; Kooij, 2010; Spencer et al., 2005).”
Perseveration by NK1R-/- (‘knockout’) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test
Pillidge, K., Porter, A. J., Young, J. W., & Stanford, S. C. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116642541 · Cited by 17
“Despite the undisputed benefits of methylphenidate in treating ADHD (Epstein et al., 2014; Faraone et al., 2006; Grizenko et al., 2013; Spencer et al., 2005), approximately 35% of patients do not respond to this drug (Hodgkins et al.”
Background
Safety and tolerability of atomoxetine hydrochloride in a long-term, placebo-controlled randomized withdrawal study in European and non-European adults with attention-deficit/hyperactivity disorder
Camporeale, A., Upadhyaya, H. P., Ramos‐Quiroga, J. A., Williams, D. W., Tanaka, Y., Lane, J. R., Escobar, R., Trzepacz, P. T., & Allen, A. J. (2013) · The European Journal of Psychiatry · doi:10.4321/s0213-61632013000300005 · Cited by 15
Diagnóstico y tratamiento del trastorno por déficit de atención/hiperactividad en adultos
Ramos-Quiroga, J., Chalita, P. J., Vidal, R., Bosch-Munso, R., Brugué, M. C., Palomar, G., & Prats, L. (2012) · Revista de Neurología · doi:10.33588/rn.54s01.2012009 · Cited by 3
Effects of a 6 Week Yoga Intervention on Executive Functioning in Women Screening Positive for Adult ADHD: A Pilot Study
Fritz, K., & O’Connor, P. J. (2022) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2022.746409 · Cited by 16
Feasibility and tolerability of moderate intensity regular physical exercise as treatment for core symptoms of attention deficit hyperactivity disorder: a randomized pilot study
Svedell, L. A., Lidström-Holmqvist, K., Lindvall, M. A., Cao, Y., & Msghina, M. (2023) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2023.1133256 · Cited by 15
“The majority of patients respond well to pharmacological treatment with stimulant medication, but approximately 30% respond poorly or discontinue treatment because of side effects even when treatment is found to be effective in reducing symptoms (9).”
Background

Authors: Spencer, T., Biederman, J., Wilens, T., Doyle, R., Surman, C., Prince, J., Mick, E., Aleardi, M., Herzig, K., & Faraone, S.
Affiliations: Harvard University (US)
Corresponding author: Spencer, Thomas
ORCID: Spencer, Thomas
Biederman, Joseph
Wilens, Timothy
Surman, Craig
Mick, Eric
Faraone, Stephen
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2005-03
Volume: 57
Issue: 5
Pages: 456-463
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2004.11.043
OpenAlex: W2053924394
Cited by: 385
References: 60
Citations by year: 2026: 6 · 2025: 11 · 2024: 8 · 2023: 16 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 7 · 2017: 15 · 2016: 12 · 2015: 15 · 2014: 16 · 2013: 19 · 2012: 25
FWCI: 21.35
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (R29MH57511, R29MH057511)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: methylphenidate, adult ADHD, ADHD medication, placebo response, dose-response relationship, depressive symptoms, anxiety symptoms, psychiatric comorbidity, treatment safety
MeSH terms: Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Demography, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Methylphenidate, Middle Aged, Neuropsychological Tests, Placebos, Psychiatric Status Rating Scales, Treatment Outcome

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A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

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