Management of attention-deficit hyperactivity disorder in adults: focus on methylphenidate hydrochloride

Figures & data

Table 1 Treatment of adult ADHD

Medication	Duration of action	Dose	Side effects	Comments
Methylphenidate (MPH)
Short-acting: (Focalin, Ritalin, Methylin)	3 to 8 h	10 to 80 mg/day	Insomnia; loss of appetite; weight loss; headache; nervousness; increase in pulse rate and blood pressure	Titrate dose weekly by 5 to 10 mg; monitor pulse rate and blood pressure; apregnancy risk: category C; contraindicated in lactation
Intermediate-acting: (Ritalin SR, Methylin ER, Metadate ER, Metadate CD, Ritalin LA)	8 to 12 h	10 to 80 mg/day
Long-acting: Concerta, Daytrana (patch)	10 to 12 h	18 to 72 mg/day 10 to 60 mg/day patch		Patch on for 9 h and off for 15 h
Dextroamphetamine (DEX)
Short-acting (Dexedrine)	4–6 h	5 to 45 mg/day	Insomnia; loss of appetite; weight loss; headache; nervousness;	Titrate by 5 mg per week; pregnancy category C; monitor blood pressure and pulse
Long-acting (Dexedrine spansules)	6 to 8 h	5 to 45 mg/day	increase in pulse rate and blood pressure
Mixed amphetamine salts (AMP)
Adderall	4 to 6 h	5 to 40 mg/day	Insomnia; loss of appetite; weight loss; headache; nervousness; palpitation; tachycardia; elevation of blood pressure	Pregnancy category C; monitor blood pressure and pulse; dosing in the morning to reduce sleep disturbances; titrate by 2.5 to 5 mg/week
Adderrall XR	8 to 10 h	5 to 60 mg/day
Lisdexamfetamine (Vyvanse)		30 to 70 mg/day
Bupropion
(Wellbutrin)	12 h	37.5 to 450 mg/day	Insomnia; increase risk of seizures; headache	Pregnancy category B; effect on lactation unknown; contraindicated in patients with seizures and bulimia; response after 4 to 5 weeks
Atomoxetine
(Strattera)	24 h	40 to 80 mg/day	Sleep disturbance; nausea; vomiting; dyspepsia; abdominal pain; headache; changes in blood pressure and pulse rate; jaundice and hepatotoxicity	Pregnancy category C; effect on lactation unknown; should be discontinued in patients who develop jaundice or elevated liver function tests
Tricyclic antidepressants (TCA)
Desipramine or imipramine Nortriptyline (Pamelor)	24 h	10–150 mg/day 10 to 150 mg/day	Dry mouth; constipation; changes in pulse rate, blood pressure; conduction abnormalities	Monitor therapeutic levels; response after 4 weeks; monitor ECG before and after stabilization on treatment
Clonidine		0.2 to 0.4 mg/day	Effects on blood pressure and heart rate, dry mouth, dizziness	Effective for impulsivity and hyperactivity, tics and sleep disturbances

Notes:

^a FDA Use in Pregnancy Ratings: Category A: No risk indicated in controlled studies, B: No evidence of risk in humans, C: Inability to rule out risk, D: Positive evidence of risk, X: Contraindicated in pregnancy.

Adapted with permission from Moss SB, Nair R, Vallarino A, Wang S. Attention deficit/hyperactivity disorder in adults. Prim Care. 2007;34(3):445–473.² Copyright © Elsevier; Kolar D, Keller A, Golfinopoulos M, Cumyn L, Syer C, Hechtman L. Treatment of adults with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2008;4(2):389–403.¹⁷ Copyright © 2008 Dove Medical Press; Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894–921.³² Copyright © 2007 Wolters Kluwer Health.

Table 2 Efficacy of methylphenidate (MPH) in the treatment of ADHD^{38,53,55–58,60,61}

Study	N	Method	Duration	Conclusion
Faraone^Citation53	253	Meta-analysis of 6 randomized placebo controlled trials		Mean effect size for MPH was 0.9 (P < 0.001) and larger effect size of 1.3 was noticed with higher doses of MPH (>0.9 mg/kg/day)
Spencer^Citation38	146	Randomized, placebo-controlled, parallel study	6 weeks	Therapeutic response (76% vs 19%)
Medori^Citation55	401	Randomized, double blind, placebo controlled study of 18, 36 and 72 mg of OROS MPH	5 weeks	Change in total score on Connor’s Adult ADHD Rating Scale: mean change −10.6 (P = 0.01) for 18 mg, −11.5 (P = 0.01) for 36 mg, and −13.7 (P < 0.001) for 72 mg vs −7.6 for placebo
Rosler^Citation61	359	Randomized, placebo controlled, parallel study of methylphenidate ER	24 weeks	Response of more than 30% reduction of the WRAADDS score, 61% compared to 42% in the placebo group. 55% of subjects on MPH and 37% placebo showed improvement in CGIS
Biederman^Citation58	141	Randomized placebo controlled, parallel study of OROS MPH	6 week	66% of subjects (n = 44) on OROS MPH and 39% of subjects (n = 23) on placebo showed improvement in CGIS and >30% reduction in Adult ADHD Investigator System Report Scale Score
Jain U^Citation56	50	Double blind, placebo controlled, cross over study using once daily novel biphasic multilayer release (MLR) methylphenidate	6 weeks	Improvement in CGIS (Global Improvement: 2.6 vs 3.7; P = 0.0015), CAARS-S (12.2 vs 5.4; P = 0.0083), and CAARS-O (10.9 vs 6.6; P = 0.1404)
Reimherr^Citation57	47	Double blind, placebo controlled, crossover trial of OROS MPH		40% (N = 19) had ADHD with both significant emotional and oppositional symptoms. OROS methylphenidate superior to placebo for all clinical measures: total WRAADDS score decrease of 42% vs 13%, P < 0.001 and total ADHD-RS score decrease of 41% vs 14%, P = 0.003
Fallu^Citation60	30	Pilot, uncontrolled, open label	38 days	Statistically significant improvements observed in executive function

Abbreviations: ADHD-RS, Adult ADHD-Rating Scale; CAARS-S, Conners’ Adult ADHD Rating Scales Self-rated; CAARS-O, Conners’ Adult ADHD Rating Scales Observer Rated; CGI-I, Clinical Global Impressions-Improvement scale; WRAADDS, Wender-Reimherr Adult Attention Deficit Disorder Scale.

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