Methylphenidate in Adults With Attention Deficit/Hyperactivity Disorder

Methylphenidate (MPH) is the first-line pharmacological treatment for adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Nevertheless, there is considerable interindividual variability regarding the dose required, tolerability and response rates to MPH. The aim of this study is to address the clinical and genetic predictors of MPH treatment outcomes in ADHD.

Study Overview

• Status: Recruiting
• Conditions: Attention Deficit Disorder With Hyperactivity
• Intervention / Treatment: Drug: Immediate-release Methylphenidate

Detailed Description

Methylphenidate (MPH) is the most prescribed psychostimulant for children and adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Meta-analyses and systematic reviews have shown that MPH is safe and efficacious in attenuating the core symptoms of ADHD, promoting overall clinical improvement. However, many patients still do not show an appropriate clinical response to the MPH treatment and there is considerable interindividual variability regarding the dose required, tolerability and response rates to MPH. Therefore, it is essential to address the clinical and genetic predictors of MPH treatment outcomes in ADHD.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eugênio H Grevet, MD, PhD; Phone Number: +55 51 3359-8094; Email: ehgrevet@gmail.com
• Study Contact Backup: Name: Claiton HD Bau, MD, PhD; Phone Number: +55 51 33086718; Email: claiton.bau@gmail.com

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Recruiting
      • Program on Attention-Deficit/Hyperactivity Disorder (PRODAH); Hospital de Clínicas de Porto Alegre
      • Contact: Eugênio H Grevet, MD, PhD; Phone Number: +55 51 3359-8094; Email: ehgrevet@gmail.com
      • Contact: Claiton HD Bau, MD, PhD; Phone Number: +55 51 33086718; Email: claiton.bau@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• White Brazilian of European descent
• Fulfillment of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) diagnostic criteria for ADHD
• Eligibility to immediate-release MPH (IR-MPH) treatment

Exclusion Criteria:

• Contraindication for IR-MPH use
• Current stimulant treatment
• Evidence of a clinically significant neurological disease that might affect cognition (e.g., delirium, dementia, epilepsy, head trauma, and multiple sclerosis)
• Current or past history of psychosis
• Estimated intelligence quotient score lower than 70

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IR-MPH; Immediate-release methylphenidate (IR-MPH) 10 mg two or three times daily with doses increasing weekly until symptom control	Drug: Immediate-release Methylphenidate; Standard initial dose of 10 mg, twice or three times daily with doses increasing weekly until symptom control or occurrence of limiting adverse effects; Other Names: Ritaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported changes in severity of ADHD symptoms	Evaluated by Swanson, Nolan and Pelham Rating Scale - Version IV (SNAP-IV) adapted to adults. Assessment points at baseline, 6 weeks, 3 months, 6 months and 1 year of treatment	1yr

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported changes in severity of oppositional defiant disorder symptoms	Evaluated by Swanson, Nolan and Pelham Rating Scale - Version IV (SNAP-IV) adapted to adults. Assessment points at baseline, 6 weeks, 3 months, 6 months and 1 year of treatment	1yr
Psychiatrist's judgment of improvement of patient's symptoms	Evaluated by Clinical Global Impression - Improvement scale (CGI-I). Assessment points at baseline, 6 weeks, 3 months, 6 months and 1 year of treatment	1yr

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of ADHD diagnosis	Assessed by Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in side effects	Evaluated by Barkley's Stimulants Side Effects Rating Scale. Assessment points at baseline, 6 weeks, 3 months, 6 months and 1 year of treatment	1yr
Changes in measures of anxiety	Evaluated by Beck Anxiety Inventory (BAI). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in measures of depression	Evaluated by Beck Depression Inventory (BDI). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in scores of mood disorders	Evaluated by Mood Disorder Questionnaire (MDQ). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in insomnia problems	Evaluated by Insomnia Severity Index (ISI). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in scores of physical activity	Evaluated by International Physical Activity Questionnaires (IPAQ). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in measures of quality of life	Evaluated by Adult ADHD Quality of Life Questionnaire (AAQoL). Assessment points at baseline, 6 months and 1 year of treatment	1yr
Changes in measures of functional impairment in the main contexts of patient's life	Evaluated by Sheehan Disability Scale (SDS). Assessment points at baseline, 3 months, 6 months and 1 year of treatment	1yr

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: Federal University of Rio Grande do Sul; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordination for the Improvement of Higher Education Personnel
• Investigators: Principal Investigator: Eugênio H Grevet, MD, PhD, Hospital de Clinicas de Porto Alegre

Publications and helpful links

General Publications

• Morin CM, Belleville G, Belanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011 May 1;34(5):601-8. doi: 10.1093/sleep/34.5.601.
• Brod M, Johnston J, Able S, Swindle R. Validation of the adult attention-deficit/hyperactivity disorder quality-of-life Scale (AAQoL): a disease-specific quality-of-life measure. Qual Life Res. 2006 Feb;15(1):117-29. doi: 10.1007/s11136-005-8325-z.
• Gomes-Oliveira MH, Gorenstein C, Lotufo Neto F, Andrade LH, Wang YP. Validation of the Brazilian Portuguese version of the Beck Depression Inventory-II in a community sample. Braz J Psychiatry. 2012 Dec;34(4):389-94. doi: 10.1016/j.rbp.2012.03.005.
• Gorenstein C, Andrade L. Validation of a Portuguese version of the Beck Depression Inventory and the State-Trait Anxiety Inventory in Brazilian subjects. Braz J Med Biol Res. 1996 Apr;29(4):453-7.
• Faraone SV, Spencer T, Aleardi M, Pagano C, Biederman J. Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2004 Feb;24(1):24-9. doi: 10.1097/01.jcp.0000108984.11879.95.
• Epstein T, Patsopoulos NA, Weiser M. Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2014 Sep 18;(9):CD005041. doi: 10.1002/14651858.CD005041.pub2.
• Castells X, Cunill R, Capella D. Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials. Eur J Clin Pharmacol. 2013 Mar;69(3):347-56. doi: 10.1007/s00228-012-1390-7. Epub 2012 Sep 16.
• Retz W, Retz-Junginger P. Prediction of methylphenidate treatment outcome in adults with attention-deficit/hyperactivity disorder (ADHD). Eur Arch Psychiatry Clin Neurosci. 2014 Nov;264 Suppl 1:S35-43. doi: 10.1007/s00406-014-0542-4. Epub 2014 Sep 18.
• Steele M, Jensen PS, Quinn DM. Remission versus response as the goal of therapy in ADHD: a new standard for the field? Clin Ther. 2006 Nov;28(11):1892-908. doi: 10.1016/j.clinthera.2006.11.006.
• Swanson JM, Schuck S, Porter MM, Carlson C, Hartman CA, Sergeant JA, Clevenger W, Wasdell M, McCleary R, Lakes K, Wigal T. Categorical and Dimensional Definitions and Evaluations of Symptoms of ADHD: History of the SNAP and the SWAN Rating Scales. Int J Educ Psychol Assess. 2012 Apr;10(1):51-70.

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Anticipated): December 1, 2032
• Study Completion (Anticipated): December 1, 2032

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimate): November 1, 2016

Study Record Updates

• Last Update Posted (Estimate): November 1, 2016
• Last Update Submitted That Met QC Criteria: October 31, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: treatment; ADHD; Adults; Methylphenidate
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: 100358

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED