Investigation of efficacy of short-acting methylphenidate (Ritalin) and long-acting (Matoride) on symptoms of attention deficit hyperactivity disorder in children aged 6–18 years: A single-blind, randomized clinical trial


1 Department of Psychiatry, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Psychiatry, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Epidemiology and Biostatistics, School of Health, Behavioral Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Background: This study aimed to evaluate the efficacy and safety of long-acting versus short-acting methylphenidate on the symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents aged 6–18 years. Materials and Methods: This single-blind, randomized clinical trial was conducted on 150 children and adolescents aged 6–18 years with ADHD based on the Diagnostic and Statistical Manual of Mental Disorder-5 criteria. The patients were randomly assigned to two groups (Matoride or Ritalin). In the first group, Ritalin was prescribed 2/3 times a day, and in the second group, Matoride was prescribed once a day for 3 weeks. The Conner's questionnaire was completed by the parents of the participants for evaluation of the performance and symptoms of ADHD in both groups at the beginning and 3 weeks after treatment. In addition, the incidence of any drug complications at the end of 3-week treatment period was evaluated. Results: There were no statistically significant differences between the two groups before the intervention (P > 0.05) in the dimensions of attention deficit, emotional reaction, behavioral disorder, learning disorder, and impulsivity. At the postinterventional periods, behavioral disorder of the Ritalin group was statistically significantly lower than that of the Matoride group (P = 0.001). This treatment did not have a statistically significant effect on the total score of Conners (P = 0.255). Complications were seen in 58 cases (77.3%) of Matoride group and 49 ones (67.1%) of the Ritalin group. Weight loss in the Ritalin group was higher than that of the Matoride group (P = 0.019). Compared to the Ritalin group, anxiety was higher in the Matoride group (P = 0.022). Conclusion: Given the similar effect of Matoride and Ritalin and no significant difference in drug complications, it seems that Matoride (slow release) can be used as an alternative to Ritalin (short acting).


Spaniardi AM. Attention-deficit/hyperactivity disorder. In: KAPLAN and SADOCK'S Comprehensive Textbook of Psychiatry. 10th ed., Vol. II. Philadelphia: Wolters Kluwer; 2016. 9141.  Back to cited text no. 1
Sadock BJ. Synopsis of Psychiatry. 11th ed., Vol. II. Philadelphia: Wolters Kluwer; 2015. 4177.  Back to cited text no. 2
Pelham WE, Gnagy EM, Burrows-Maclean L, Williams A, Fabiano GA, Morrisey SM, et al. Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics 2001;107:E105.  Back to cited text no. 3
Wolraich ML, Greenhill LL, Pelham W, Swanson J, Wilens T, Palumbo D, et al. Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Pediatrics 2001;108:883-92.  Back to cited text no. 4
Gau SS, Shen HY, Soong WT, Gau CS. An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Child Adolesc Psychopharmacol 2006;16:441-55.  Back to cited text no. 5
Schachar R, Ickowicz A, Crosbie J, Donnelly GA, Reiz JL, Miceli PC, et al. Cognitive and behavioral effects of multilayer-release methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2008;18:11-24.  Back to cited text no. 6
Döpfner M, Gerber WD, Banaschewski T, Breuer D, Freisleder FJ, Gerber-von Müller G, et al. Comparative efficacy of once-a-day extended-release methylphenidate, two-times-daily immediate-release methylphenidate, and placebo in a laboratory school setting. Eur Child Adolesc Psychiatry 2004;13 Suppl 1:I93-101.  Back to cited text no. 7
Steele M, Weiss M, Swanson J, Wang J, Prinzo RS, Binder CE. A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. Can J Clin Pharmacol 2006;13:e50-62.  Back to cited text no. 8
Weiss M, Hechtman L, Turgay A, Jain U, Quinn D, Ahmed TS, et al. Once-daily multilayer-release methylphenidate in a double-blind, crossover comparison to immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2007;17:675-88.  Back to cited text no. 9
Punja S, Zorzela L, Hartling L, Urichuk L, Vohra S. Long-acting versus short-acting methylphenidate for paediatric ADHD: A systematic review and meta-analysis of comparative efficacy. BMJ Open 2013; 3 (3):e002312.  Back to cited text no. 10
López FA, Leroux JR. Long-acting stimulants for treatment of attention-deficit/hyperactivity disorder: A focus on extended-release formulations and the prodrug lisdexamfetamine dimesylate to address continuing clinical challenges. Atten Defic Hyperact Disord 2013;5:249-65.  Back to cited text no. 11
Alizadeh H. Theoretical explanation of attention deficit disorder/hyperactivity disorder: Behavioral inhibition pattern and self-control nature. Res Except Child Fall 2005;17:323-48. Available from: 03. September. 2017 last access  Back to cited text no. 12
Conners CK. Conners' rating scales: Revised technical manual. North Tonawand (NY): Multi-Health System; 1997.  Back to cited text no. 13
Haertling F, Mueller B, Bilke-Hentsch O. Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin® LA) in school children under daily practice conditions. Atten Defic Hyperact Disord 2015;7:157-64.  Back to cited text no. 14
Cascade E, Kalali AH, Weisler RH. Short-acting versus Long-acting Medications for the Treatment of ADHD. Psychiatry (Edgmont) 2008;5:24-7.  Back to cited text no. 15
Spencer TJ, Biederman J, E. Ciccone P, Madras BK, Dougherty DD, Bonab AA, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and longacting oral methylphenidate. Am J Psychiatry 2006;163:387-95.  Back to cited text no. 16
Kollins SH, Rush CR, Pazzaglia PJ, Ali JA. Comparison of acute behavioral effects of sustained-release and immediate-release methylphenidate. Exp Clin Psychopharmacol 1998;6:367-74.  Back to cited text no. 17
Hechtman L. Considerations in selecting pharmacological treatments for attention deficit hyperactivity disorder. Lung Cancer 2019;10: 1-9.  Back to cited text no. 18
Wilens TE, Gignac M, Swezey A, Monuteaux MC, Biederman J. Characteristics of adolescents and young adults with ADHD who divert or misuse their prescribed medications. J Am Acad Child Adolesc Psychiatry 2006;45:408-14.  Back to cited text no. 19
Williams RJ, Goodale LA, Shay-Fiddler MA, Gloster SP, Chang SY. Methylphenidate and dextroamphetamine abuse in substance-abusing adolescents. Am J Addict 2004;13:381-9.  Back to cited text no. 20
Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, et al. Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: Proof-of-concept and proof-of-product studies. Arch Gen Psychiatry 2003;60:204-11.  Back to cited text no. 21