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Methylphenidate Dosing: Twice Daily Versus Three Times Daily
Abstract
Objective. To evaluate the short-term efficacy and side effects associated with two methylphenidate hydrochloride (MPH) dosing patterns. Methods. Twenty-five boys with attention deficit hyperactivity disorder (ADHD) participated in a 5-week, triple-blind, placebo-controlled, crossover evaluation of MPH administered twice (b.i.d.) versus thrice (t.i.d.) per day (mean dose 8.8 ± 5 mg, .30 ± .1 mg/kg/dose). Four dosing conditions (placebo, titration [gradual increase to target dose], b.i.d., and t.i.d.) were used. Dependent measures obtained on a weekly basis included: parent and teacher ratings of child behavior, parent-child conflicts, parent report of stimulant side effects, child self-report of mood symptoms, a sleep log, laboratory measures of attention, and actigraphic recording of sleep activity. Results. All dosing conditions resulted in significant effects on ADHD symptoms when compared with baseline. Relative to placebo, t.i.d. dosing was characterized by improvement on the greatest number of behavioral measures, and both b.i.d. and t.i.d. were generally more effective than titration. Direct comparisons of b.i.d. and t.i.d. dosing revealed that t.i.d. was associated with greater improvement on the Conners Parent Rating Scale Impulsivity/Hyperactivity factor, with a similar marginally significant effect for the ADD-H Teacher Rating Scale Hyperactivity factor. The analysis of clinically significant change favored a three-times-a-day dosing schedule over placebo on both parent and teacher ratings of impulsivity/hyperactivity and attention. Compared with placebo, appetite suppression was rated, on average, as more severe in the t.i.d. and titration conditions, but not in the b.i.d condition. However, the number of subjects who exhibited any or severe appetite suppression did not differ significantly between the b.i.d. and t.i.d. schedules. Although there was no difference in sleep duration for children on b.i.d. and t.i.d. schedules, total sleep time appeared to decrease slightly on t.i.d. relative to placebo according to both parent ratings and actigraphic assessment. There were no significant differences between b.i.d. and t.i.d. on any other side effects or sleep variables. Conclusions. For many children with ADHD, t.i.d. dosing may be optimal. There are few differences in acute side effects between b.i.d and t.i.d. MPH dosing. The dosing schedule should be selected according to the severity and time course of ADHD symptoms rather than in anticipation of dosing schedule-related side effects.
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“Other studies, however, using a third dose at the end of the day did find a greater sleep-onset delay in children treated with stimulants compared to untreated subjects [7, 137].”
From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [137]
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Sleep Disturbances in Children With Attention‐Deficit/Hyperactivity Disorder
CORKUM, P., TANNOCK, R., & MOLDOFSKY, H. (1998) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199806000-00014 · Cited by 441
Pelham, W. E., Gnagy, E. M., Burrows-Maclean, L., Williams, A., Fabiano, G. A., Morrisey, S. M., Chronis, A. M., Forehand, G. L., Nguyen, C. A., Hoffman, M. T., et al. (2001) · Pediatrics · doi:10.1542/peds.107.6.e105 · Cited by 378
European guidelines on managing adverse effects of medication for ADHD
(for the European Guidelines Group), Graham, J., Banaschewski, T., Buitelaar, J., Coghill, D., Danckaerts, M., Dittmann, R. W., Döpfner, M., Hamilton, R., Hollis, C., et al. (2011) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-010-0140-6 · Cited by 374
“Other studies, however, using a third dose at the end of the day did find a greater sleep-onset delay in children treated with stimulants compared to untreated subjects [7, 137].”
ResultCortese, S., Holtmann, M., Banaschewski, T., Buitelaar, J., Coghill, D., Danckaerts, M., Dittmann, R. W., Graham, J., Taylor, E., Sergeant, J., et al. (2013) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12036 · Cited by 336
“Although there is evidence that a third late afternoon dose of MPH-IR does not disrupt sleep in the majority of children, (Kent, Blader, Koplewicz, Abikoff, & Foley, 1995; Pelham et al., 2001; Stein et al., 1996), MPH may induce problems to fall asleep in individual cases.”
BackgroundMethylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)
Storebø, O. J., Ramstad, E., Krogh, H. B., Nilausen, T. D., Skoog, M., Holmskov, M., Rosendal, S., Groth, C., Magnusson, F. L., Moreira-Maia, C. R., et al. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009885.pub2 · Cited by 347
KRATOCHVIL, C. J., HEILIGENSTEIN, J. H., DITTMANN, R., SPENCER, T. J., BIEDERMAN, J., WERNICKE, J., NEWCORN, J. H., CASAT, C., MILTON, D., & MICHELSON, D. (2002) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200207000-00008 · Cited by 292
“ing (Greenhill et al., 2001; Stein, 1996).”
Konofal, É., Lecendreux, M., & Cortese, S. (2010) · Sleep Medicine · doi:10.1016/j.sleep.2010.02.012 · Cited by 262
“But while some studies have showed that MPH three-times daily does not impact upon sleep [47] or causes only a slight decrease in sleep duration [48], others have reported that a third daily dose of MPH does worsen sleep [49].”
BackgroundResultSpencer, T., Biederman, J., Wilens, T., Faraone, S., Prince, J., Gerard, K., Doyle, R., Parekh, A., Kagan, J., & Bearman, S. K. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.8.775 · Cited by 250
Stein, M. A., Sarampote, C. S., Waldman, I. D., Robb, A. S., Conlon, C. J., Pearl, P. L., Black, D. O., Seymour, K. E., & Newcorn, J. H. (2003) · PEDIATRICS · doi:10.1542/peds.112.5.e404 · Cited by 232
Self-citationDittmann, R., Fouche, D. S., Kratochvil, C. J., Heiligenstein, J. H., Spencer, T. J., & Biederman, J. (2001) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(01)80448-x · Cited by 223
Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate.
Schachar, R., Tannock, R., Cunningham, C. H., & Corkum, P. (1997) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1097/00004583-199706000-00011 · Cited by 202
Treatment of ADHD in neurofibromatosis type 1
Mautner, V., Kluwe, L., Thakker, S. D., & Leark, R. A. (2002) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2002.tb00780.x · Cited by 250
“The test has established normative values (Greenberg and Waldman 1994), has demonstrated reliability (Leark 2000, Llorente 2000), validity (Forbes 1998), and has been used in treatment efficacy studies (Stein et al. 1996, Semrud-Clikeman and Wical 1999).”
MethodCohen-Zion, M., & Ancoli-Israel, S. (2004) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2004.06.002 · Cited by 203
Rendleman, R. L., & Walkup, J. T. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-0435-8.00049-4 · Cited by 197
Purdie, N., Hattie, J., & Carroll, A. (2002) · Review of Educational Research · doi:10.3102/00346543072001061 · Cited by 206
King, S., Griffin, S. C., Hodges, Z., Weatherly, H. L. A., Asseburg, C., Richardson, G. A., Golder, S., Taylor, E., Drummond, M., & Riemsma, R. P. (2006) · Health Technology Assessment · doi:10.3310/hta10230 · Cited by 188
Markowitz, J. S., Straughn, A. B., & Patrick, K. S. (2003) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.23.12.1281.32697 · Cited by 174
Gücüyener, K., Erdemoğlu, A. K., Şenol, S., Serdaroğlu, A., Soysal, Ş., & Koçkar, A. İ. (2003) · Journal of Child Neurology · doi:10.1177/08830738030180020601 · Cited by 165
ADHD Treatments, Sleep, and Sleep Problems: Complex Associations
Stein, M. A., Weiss, M., & Hlavaty, L. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0130-0 · Cited by 165
“[43] utilized actigraphy to measure sleep onset latency (SOL) and duration of sleep in children treated with low to moderate doses of MPH administered twice or three times daily.”
MethodSelf-citationWilens, T. E., McBurnett, K., Bukstein, O., McGough, J., Greenhill, L., Lerner, M., Stein, M. A., Conners, C. K., Duby, J., Newcorn, J., et al. (2006) · Archives of Pediatrics & Adolescent Medicine · doi:10.1001/archpedi.160.1.82 · Cited by 160
“The CCI has been validated in children(38) and has demonstrated clinical usefulness in detecting the effects of methylphenidate use in children.(39) The CCI was administered during telephone interviews.”
BackgroundSelf-citationBoonstra, A. M., Kooij, J. J. S., Oosterlaan, J., Sergeant, J. A., Buitelaar, J. K., & Van Someren, E. J. W. (2007) · Sleep · doi:10.1093/sleep/30.4.433 · Cited by 155
Sobanski, E., Schredl, M., Kettler, N., & Alm, B. (2008) · Sleep · doi:10.1093/sleep/31.3.375 · Cited by 153
WILENS, T., PELHAM, W., STEIN, M., CONNERS, C. K., ABIKOFF, H., ATKINS, M., AUGUST, G., GREENHILL, L., MCBURNETT, K., PALUMBO, D., et al. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000046814.95464.7d · Cited by 148
Self-citationMick, E. O., Biederman, J., Jetton, J. G., & Faraone, S. V. (2000) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/10445460050167331 · Cited by 146
“…Nahas and Krynicki 1977; Puig-Antich et al. 1978; Simonds and Parraga 1984; Tirosh et al. 1993; Trommer et al. 1998) or used psychiatric comorbidity as a criterion for exclusion from the study sample (Busby and Pivik 1985; Kahn 1982; Palm et al. 1992; Ramos Platon et al. 1990; Stein et al. 1996).”
Kaufmann, R., Goldberg‐Stern, H., & Shuper, A. (2009) · Journal of Child Neurology · doi:10.1177/0883073808330165 · Cited by 144
“Methylphenidate resembles amphetamine in central nervous system activity.(38) There is no clear evidence in the literature supporting the possibility that methylphenidate aggravates or induces epilepsy.”
BackgroundPelham, W. E., Gnagy, E. M., Chronis, A. M., Burrows-MacLean, L., Fabiano, G. A., Onyango, A. N., Meichenbaum, D. L., Williams, A., Aronoff, H. R., & Steiner, R. L. (1999) · PEDIATRICS · doi:10.1542/peds.104.6.1300 · Cited by 138
Patrick, K. S., & Markowitz, J. S. (1997) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/(sici)1099-1077(199711/12)12:6 · Cited by 132
ADHD Treatment With Once-Daily OROS Methylphenidate: Final Results From a Long-Term Open-Label Study
Wilens, T. E., McBurnett, K., Stein, M. A., Lerner, M., Spencer, T. J., & Wolraich, M. L. (2005) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000173291.28688.e7 · Cited by 119
Self-citationAbikoff, H. B., Vitiello, B., Riddle, M. A., Cunningham, C., Greenhill, L. L., Swanson, J. M., Chuang, S. Z., Davies, M., Kastelic, E., Wigal, S. B., et al. (2007) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2007.0068 · Cited by 118
“Improved parent–child interactions, decreased negative parenting practices, and improved ratings of parental effectiveness often occur with MPH treatment (Stein et al. 1996; Hecht-man et al. 2004).”
Effects of Modafinil in Children With Attention-Deficit/Hyperactivity Disorder: An Open-Label Study
Rugino, T. A., & COPLEY, T. C. (2001) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200102000-00018 · Cited by 115
“The response rate to these medications ranges from 70% to 90% (Elia et al., 1991; Stein et al., 1996), which suggests that a sizable minority of children are nonresponders.”
BackgroundSleep Disturbances in Children with Attention-Deficit/Hyperactivity Disorder
Ring, A., Stein, D. J., Barak, Y., Teicher, A., Hadjez, J., Elizur, A., & Weizman, A. (1998) · Journal of Learning Disabilities · doi:10.1177/002221949803100607 · Cited by 108
“The findings concerning sleep disturbances in children with ADHD are inconsistent, in that studies relying on parental reports report more disturbances than those using objective measurements of sleep (Greenhill, PuigAntich, Goetz, Hanlon, & Davis, 1983; Stein et al., 1996).”
ResultASSESSMENT AND INTERVENTION FOR ATTENTION-DEFICIT/HYPERACTIVITY DISORDER IN THE SCHOOLS
Swanson, J. M., Lerner, M., March, J. S., & Gresham, F. M. (1999) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70168-1 · Cited by 106
Kirov, R., Kinkelbur, J., Heipke, S., Kostanecka‐Endress, T., Westhoff, M., Cohrs, S., Rüther, E., Hajak, G., Banaschewski, T., & Rothenberger, A. (2004) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2004.00387.x · Cited by 104
“Furthermore, stimulant medication has been demonstrated not to change substantially the PSG-sleep pattern in ADHD patients (Efron et al. 1997; Stein et al. 1996), although increased latency of falling into sleep has been observed.”
BackgroundCohen, S. C., Mulqueen, J. M., Ferracioli-Oda, E., Stuckelman, Z. D., Coughlin, C. G., Leckman, J. F., & Bloch, M. H. (2015) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2015.06.011 · Cited by 105
Sleep Problems in the Child with Attention-Deficit Hyperactivity Disorder
Weiss, M. D., & Salpekar, J. A. (2010) · CNS Drugs · doi:10.2165/11538990-000000000-00000 · Cited by 103
O'Brien, L. (2003) · Sleep Medicine · doi:10.1016/s1389-9457(03)00071-6 · Cited by 97
“The impact of stimulants on sleep in ADHD has been previously examined using objective measures such as polysomnography [9,11,12,16,20–22] or actigraphy [10,23].”
BackgroundMethodCorkum, P. V., Panton, R., Ironside, S., Macpherson, M. J., & Williams, T. (2007) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsm106 · Cited by 98
“Over this same period, standard practice has changed from BID regimes (morning and noon administration to provide coverage during school hours) to three times a day (TID) regimes (including an afterschool dose, in addition to the morning and noon dose), or long-acting sustained-release formulations, to treat ADHD symp…”
BackgroundResultInfluentialSwanson, J. M., Gupta, S., Williams, L., AGLER, D., Lerner, M., & Wigal, S. B. (2002) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200211000-00011 · Cited by 96
“, in press), which is the standard for rapid onset and long duration in the treatment of ADHD symptoms (Greenhill et al., 1996; Kent et al., 1995; MTA Cooperative Group, 1999a,b; Stein et al., 1996).”
BackgroundAttention deficit and hyperactivity disorder, methylphenidate, and epilepsy
Tan, M. (2004) · Archives of Disease in Childhood · doi:10.1136/adc.2003.048504 · Cited by 90
“Both the British National Formulary (BNF, September 2003, pp. 197–8) and the Monthly Index of Medical Specialities (MIMS, October 2003, pp. 122–3) recommend caution when prescribing psychostimulants, including dexamphetamine and methylphenidate, to patients with epilepsy, and discontinuation of…”
BackgroundCoughlin, C. G., Cohen, S. C., Mulqueen, J. M., Ferracioli-Oda, E., Stuckelman, Z. D., & Bloch, M. H. (2015) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0075 · Cited by 86
“Therefore, a total of 23 trials, involving 2959 subjects, were included in our meta-analysis (Gittelman-Klein et al. 1976; Conners and Taylor 1980; Werry et al. 1980; Rapport et al. 1985; Barkley et al. 1990; Ahmann et al. 1993; Buitelaar et al. 1996; Stein et al. 1996; Gillberg et al. 1997; Firestone et al. 1998; Pli…”
BackgroundMethylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)
Storebø, O. J., Storm, M. R. O., Ribeiro, J. P., Skoog, M., Groth, C., Edemann-Callesen, H., Schaug, J. P., Rasmussen, P. D., Huus, C.-M. L., Zwi, M., et al. (2023) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009885.pub3 · Cited by 118
GALLAND, B. C., TRIPP, E. G., & TAYLOR, B. J. (2009) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2009.00795.x · Cited by 85
“, 2006), but others report no differences in sleep quantity (Stein et al., 1996), and even lengthened sleep (recorded by PSG) (Greenhill et al.”
BackgroundResultWang, Y., Zheng, Y., Du, Y., Song, D. H., Shin, Y.-J., Cho, S. C., Kim, B. N., Ahn, D. H., Marquez-Caraveo, M. E., Gao, H., et al. (2007) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/00048670601057767 · Cited by 84
Sleep Characteristics of Children and Adolescents with Attention Deficit-Hyperactivity Disorder
Gruber, R. (2009) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2009.04.011 · Cited by 88
Becker, S. P., Froehlich, T. E., & Epstein, J. N. (2016) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0000000000000285 · Cited by 81
Tamminga, H. G. H., Reneman, L., Huizenga, H. M., & Geurts, H. M. (2016) · Psychological Medicine · doi:10.1017/s0033291716000350 · Cited by 82
“…10 mg Solanto et al. (2009) 25 (44) 8.8 (1.5)/7–12h 16 96 CPT Omissionshh 1.02 (0.20) Fixedb,e 3 d.d. 1 week/ condition IR, 20 mg Mean = 0.59 mg/kg Stein et al. (1996) 25 (100) 8.0 (1.8)/6–12 28 44 TOVA Omissionshh 0.29 (0.20) Fixede 2 d.d. 1 week/ condition IR, mean = 0.3 mg/kg Sunohara…”
InfluentialGarland, E. J. (1998) · Journal of Psychopharmacology · doi:10.1177/026988119801200410 · Cited by 77
“Clinicians have hesitated to consider late-day stimulant dosing due to concerns about insomnia until recent studies (Kent et al., 1995; Stein et al., 1996) have demonstrated the benefits of a third dose of methylphemdate on attention, behavior and even sleep.”
BackgroundKlassen, A. F., Miller, A. R., Raina, P. S., Lee, S. K., & Olsen, L. L. (1999) · The Canadian Journal of Psychiatry · doi:10.1177/070674379904401007 · Cited by 76
Sleep of Children With Attention Deficit Hyperactivity Disorder: Actigraphic and Parental Reports
Moreau, V., Rouleau, N., & Morin, C. M. (2013) · Behavioral Sleep Medicine · doi:10.1080/15402002.2013.764526 · Cited by 80
“Another study found that stimulant use was associated with lower TST, reduced SE, and increased SOL as measured with PSG (Galland, Tripp, & Taylor, 2010).”
ResultInfluentialActigraphic Monitoring During Sleep of Children With ADHD on Methylphenidate and Placebo
SCHWARTZ, G., AMOR, L. B., GRIZENKO, N., LAGEIX, P., BARON, C., BOIVIN, D. B., & JOOBER, R. (2004) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000135802.94090.93 · Cited by 70
“The same group (Stein et al., 1996) exploring the effect of twice-daily and three times daily dosing had previously found no sleep differences on actigraphic recordings of sleep on the two dosing regimens.”
BackgroundPsychostimulants in supportive care
Homsi, J., Walsh, D., & Nelson, K. A. (2000) · Supportive Care in Cancer · doi:10.1007/s005200050007 · Cited by 69
Corkum, P. V., Davidson, F., & MacPherson, M. (2011) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2011.03.004 · Cited by 71
Pozzi, M., Carnovale, C., Peeters, G. G. A. M., Gentili, M., Antoniazzi, S., Radice, S., Clementi, E., & Nobile, M. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.05.021 · Cited by 56
Holmskov, M., Storebø, O. J., Moreira-Maia, C. R., Ramstad, E., Magnusson, F. L., Krogh, H. B., Groth, C., Gillies, D., Zwi, M., Skoog, M., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0178187 · Cited by 58
Lecendreux, M., & Cortese, S. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.12.1799 · Cited by 58
Sleep Disturbances in Adolescents with Symptoms of Attention-Deficit/Hyperactivity Disorder
Stein, D., Pat-Horenczyk, R., Blank, S., Dagan, Y., Barak, Y., & Gumpel, T. P. (2002) · Journal of Learning Disabilities · doi:10.1177/002221940203500308 · Cited by 58
New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder
Patrick, K. S., Ángel-González, M., Straughn, A. B., & Markowitz, J. S. (2005) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2.1.121 · Cited by 61
“00 h) has been reported not to affect sleeping patterns [162], but may significantly diminish appetite [163].”
BackgroundKim, H.-W., Yoon, I.-Y., Cho, S.-C., Kim, B.-N., Chung, S., Lee, H., Kim, C.-W., Park, S.-K., & Yoo, H. J. (2010) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e3283364411 · Cited by 56
Bioavailability of melatonin in humans after day-time administration of D7 melatonin
Fourtillan, J. B., Brisson, A. M., Gobin, P., Ingrand, I., Decourt, J., & Girault, J. (2000) · Biopharmaceutics & Drug Disposition · doi:10.1002/1099-081x(200001)21:1 · Cited by 119
Shader, R. I., Harmatz, J. S., Oesterheld, J. R., Parmelee, D. X., Sallee, F. R., & Greenblatt, D. J. (1999) · The Journal of Clinical Pharmacology · doi:10.1177/00912709922008425 · Cited by 52
“Furthermore, less insomnia and fewer negative emotional symptoms were reported for methylphenidate compared to d-amphetamine.26 Only one study could be located that compared bid and tid dosage schedules for methylphenidate—a triple-blind, placebo-controlled, counterbalanced, crossover study in 25 boys with ADHD.27 The…”
BackgroundInfluentialChronis, A. M., Pelham, W. E., Gnagy, E. M., Roberts, J. E., & Aronoff, H. R. (2003) · Journal of Clinical Child & Adolescent Psychology · doi:10.1207/s15374424jccp3201_11 · Cited by 52
“To date, few studies have evaluated the relative effectiveness of a late-afternoon dose of MPH compared to standard twice-daily dosing (BID; Kent, Blader, Koplewicz, Abikoff, & Foley, 1995; Stein et al., 1996).”
BackgroundMethodResultAbuse-Deterrent and Tamper-Resistant Opioid Formulations
Schneider, J. P., Matthews, M. L., & Jamison, R. N. (2010) · CNS Drugs · doi:10.2165/11584260-000000000-00000 · Cited by 51
Double-blind Methylphenidate Trials
Kent, M. A., Camfield, C., & CAMFIELD, P. R. (1999) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.153.12.1292 · Cited by 50
“Double-blind, placebo-controlled protocols for the use of methylphenidate have been reported previously.(11-19) These studies, in which groups of children with ADD were randomized to 1 of 2 study treatment arms, were designed to compare the efficacy of placebo and of methylphenidate.”
MethodZebrafish models for attention deficit hyperactivity disorder (ADHD)
Fontana, B. D., Franscescon, F., Rosemberg, D. B., Norton, W., Kalueff, A. V., & Parker, M. O. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.02.009 · Cited by 50
The use of actigraphy in the monitoring of methylphenidate versus placebo in ADHD: a meta-analysis
De Crescenzo, F., Armando, M., Mazzone, L., Ciliberto, M., Sciannamea, M., Figueroa, C., Janiri, L., Quested, D., & Vicari, S. (2014) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-013-0122-x · Cited by 48
“2001) or number of times per day administered (Stein et al. 1996), so we did not exclude studies on these bases, but we recorded information on the intervention in the table of included studies.”
BackgroundSTIMULANT MEDICATION FOR THE CHILD WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
Bennett, F. C., Brown, R. T., Craver, J., et al. (1999) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70164-4 · Cited by 47
Optimizing therapy of seizures in children and adolescents with ADHD
Aldenkamp, A. P., Arzimanoglou, A. A., Reijs, R. P., & van Mil, S. (2006) · Neurology · doi:10.1212/wnl.67.12_suppl_4.s49 · Cited by 43
Feltz-Cornelis, C. M. V. D., & Aldenkamp, A. P. (2006) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2006.01.015 · Cited by 44
Evolution of stimulants to treat ADHD: transdermal methylphenidate
Patrick, K. S., Straughn, A. B., Perkins, J. S., & Ángel-González, M. (2008) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.992 · Cited by 42
“This three-times-daily MPH schedule carries with it a higher incidence of appetite suppression and insomnia (Stein et al., 1996).”
Faraone, S. V., Po, M. D., Komolova, M., & Cortese, S. (2019) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.18r12210 · Cited by 49
Yoo, H. K., Park, S., Wang, H., Lee, J. S., Kim, K., Paik, K., Yum, M. S., & Ko, T. (2009) · Epileptic Disorders · doi:10.1684/epd.2009.0278 · Cited by 38
Effect of Lisdexamfetamine Dimesylate on Sleep in Children With ADHD
Giblin, J. M., & Strobel, A. L. (2011) · Journal of Attention Disorders · doi:10.1177/1087054710371195 · Cited by 38
“…methylphenidate on sleep in children with ADHD, sleep-onset latency was significantly increased for children on thricedaily methylphenidate relative to baseline and also when compared with twice-daily atomoxetine based on both objective and subjective measures of sleep (Stein et al., 1996).”
BackgroundResultInfluentialDonnelly, M., Haby, M. M., Donnelly, M., Haby, M. M., Carter, R., Andrews, G., & Vos, T. (2004) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2004.01422.x · Cited by 38
Chin, W., Huang, Y., Chou, Y.-H., Wang, C.-H., Chen, K.-T., Hsu, J. F., & Hsu, S. (2018) · Biomedical Journal · doi:10.1016/j.bj.2018.10.004 · Cited by 40
“Besides, it is important to note that some studies have previously demonstrated no change in sleep quantity [38] and even increased sleep efficiency after MPH use [39].”
BackgroundJohnson, K. A., Barry, E., Lambert, D., Fitzgerald, M., McNicholas, F., Kirley, A., Gill, M., Bellgrove, M. A., & Hawi, Z. (2013) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2013.0032 · Cited by 34
“The most common side effects of MPH are insomnia, decreased appetite, stomachaches, and headaches (Gittelman-Klein et al. 1976; Barkley et al. 1990; Stein et al. 1996; Efron et al. 1997; Schachter et al. 2001).”
Adjei, A. L., Teuscher, N. S., Kupper, R. J., Chang, W.-W., Greenhill, L. L., Newcorn, J. H., Connor, D. F., & Wigal, S. B. (2014) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2013.0135 · Cited by 33
“potential for reducing related adverse events (AEs) (Stein et al. 1996; Greenhill et al. 1999; Markowitz et al. 2003a; Steele et al. 2006; Wigal et al. 2006; Rader et al. 2009).”
New Research on the Complex Interaction of Sleep and ADHD
Weiss, M. D., Craig, S. G., Davies, G., Schibuk, L., & Stein, M. A. (2015) · Current Sleep Medicine Reports · doi:10.1007/s40675-015-0018-8 · Cited by 30
“Early studies showed actigraphic changes in children with ADHD, demonstrating sleep onset insomnia (SOI), decreased sleep duration, sleep variability and sleep efficiency [20, 27, 28].”
BackgroundSelf-citationMorash-Conway, J., Gendron, M. A., & Corkum, P. V. (2016) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-016-0204-7 · Cited by 31
“Of those studies that have, it has been reported that medication significantly increased sleep onset latency (Corkum, Panton, Ironside, MacPherson, & Williams, 2008; Tirosh et al., 1993), and reduced total sleep time compared to placebo (Stein et al., 1996; Tirosh, Sadeh, Munvez, & Lavie, 1993).”
BackgroundGW320659 for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children
DeVeaugh-Geiss, J., Conners, C. K., Sarkis, E. H., Winner, P. K., Ginsberg, L. D., Hemphill, J. M., Laurenza, A., BARROWS, C. F., WEBSTER, C. J., STOTKA, C. J., et al. (2002) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200208000-00009 · Cited by 28
“Although the most commonly used stimulants such as methylphenidate and the amphetamines have efficacy rates as high as 70% in controlled studies, they do not work for all patients with ADHD (Stein et al., 1996).”
BackgroundImmediate-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
Methylphenidate in the treatment of children with attention-deficit hyperactivity disorder.
Vitiello, B. (2001) · Europe PMC (PubMed Central) · Cited by 22
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
Sleep as an outcome measure in ADHD randomized controlled trials: A scoping review
McWilliams, S., Zhou, T., Stöckler, S., Elbe, D., & Ipsiroglu, O. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101613 · Cited by 23
Safety of stimulant treatment in attention deficit hyperactivity disorder: part II
Merkel, R. L. (2010) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2010.503238 · Cited by 21
Can we predict short-term side effects of methylphenidate immediate-release?
Karabekiroğlu, K., Yazgan, Y., & Dedeoğlu, C. (2008) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651500701435954 · Cited by 21
“For decades, stimulant medication, particularly methylphenidate (MPH), is the most frequently recommended medical treatment for ADHD [3].”
BackgroundDrug Class Review on Pharmacologic Treatments for ADHD
McDonagh, M. S., Peterson, K., & Thakurta, S. (2005) · Cited by 21
MANAGEMENT OF STIMULANT MEDICATIONS IN CHILDREN WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
ADESMAN, A. R., & Morgan, A. M. (1999) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70165-6 · Cited by 21
Open-Label Amantadine in Children with Attention-Deficit/Hyperactivity Disorder
Donfrancesco, R., Calderoni, D., & Vitiello, B. (2007) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2006.0128 · Cited by 20
“…disorder (ADHD) is well established, but it is estimated that be-tween 10% and 30% of patients treated with these drugs either do not improve adequately, or are unable to tolerate their side effects (Elia et al. 1991; Spencer et al. 1996; Stein et al. 1996; Pelham et al. 1999).”
Safety of stimulant treatment in attention deficit hyperactivity disorder: part I
Merkel, R. L., & Kuchibhatla, A. (2009) · Expert Opinion on Drug Safety · doi:10.1517/14740330903279956 · Cited by 20
“It is interesting that other studies [5,10,26] have not shown a relation between stimulant dose and reported side effects, but this may relate to lack of power.”
BackgroundSleep Disturbances in Singaporean Children with Attention Deficit Hyperactivity Disorder
Lim, C. G., Ooi, Y. P., Fung, D. S. S., & Kaur, A. (2008) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.v37n8p655 · Cited by 19
Attention-Deficit/Hyperactivity Disorder in Gifted Students
Kaufmann, F. A., & Castellanos, F. X. (2000) · Elsevier eBooks · doi:10.1016/b978-008043796-5/50044-9 · Cited by 20
Solleveld, M. M., Schrantee, A., Baek, H. K., Bottelier, M. A., Tamminga, H. G. H., Bouziane, C., Stoffelsen, R., Lucassen, P. J., Someren, E. J. W. V., Rijsman, R. M., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00082 · Cited by 19
“Indeed, using actigraphy it was already demonstrated that triple dosing vs double dosing with MPH decreases total sleep time in children with ADHD, presumably due to a later dosing in time (30); clearly this is a factor that needs to be taken into account both in clinical studies and clinical practice.”
MethodAdjei, A. L., Kupper, R. J., Teuscher, N. S., Wigal, S. B., Sallee, F. R., Childress, A. C., Kollins, S. H., & Greenhill, L. L. (2014) · Clinical Drug Investigation · doi:10.1007/s40261-014-0234-x · Cited by 17
“Fluctuating plasma methylphenidate concentrations, as produced by IR methylphenidate tablets twice and three times daily, are reported to be less desirable than gradually rising methylphenidate plasma concentrations throughout the day [12, 32, 33].”
BackgroundAttention Deficit Hyperactivity Disorder Medications and Sleep
Stein, M. A., Zulauf-McCurdy, C. A., & DelRosso, L. M. (2022) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2022.03.006 · Cited by 18
Self-citation
Metadata
- Authors
- Stein, M. A., Blondis, T. A., Schnitzler, E. R., O'Brien, T., Fishkin, J., Blackwell, B., Szumowski, E., & Roizen, N. J.
- Affiliations
- University of Chicago (US)
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 1996-10-01
- Volume
- 98
- Issue
- 4
- Pages
- 748-756
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- OpenAlex
- W1521375496
- Cited by
- 151
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PEDIATRICS (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- methylphenidate, dosing frequency, twice-daily dosing, three-times-daily dosing, attention deficit hyperactivity disorder, children, stimulant side effects, appetite suppression, sleep duration, sleep quality, impulsivity, hyperactivity, attention, dose titration, parent and teacher ratings, actigraphy, mood symptoms, parent-child conflict, ADHD medication
- MeSH terms
- Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Capsules, Child, Child Behavior, Cognition, Follow-Up Studies, Humans, Male, Methylphenidate, Sleep, Time Factors
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