Are all ADHD medications created equal? Exploring the differences that enable evening dosing

Figures & data

Figure 1. Considerations for attention-deficit/hyperactivity disorder medication selection.

Figure 2. Evolution of drug delivery technologies. Characteristics of example short-, intermediate-, and long-acting stimulants used in the treatment of ADHD [7,18,19]. Approximate timing of new technology introduction follows from left to right across the diagram. ^aTiming of dosing depends on whether the medication is being used as a single dose or in multiple doses and alone or in conjunction with a long-acting medication (either to provide rapid onset in the morning or to extend duration in the later part of the day). ADHD, attention-deficit/hyperactivity disorder; CR, controlled release; DR/ER-MPH, delayed-release and extended-release methylphenidate; ER, extended release; IR, immediate release; MEROS, methylphenidate extended-release oral suspension; OROS, osmotic-release oral system; SODAS, spheroidal oral drug absorption system.

Figure 3. Comparison of pharmacokinetic curves for long-acting stimulants given in the morning versus evening-dosed DR/ER-MPH. Simulated plasma concentration versus time curves for single doses of (a) OROS MPH 54 mg, (b) d-MPH ER 20 mg, (c) MEROS 60 mg, and (d) DR/ER-MPH 100 mg. Dashed vertical lines indicate when the medication dose was taken. Adapted from Gomeni et al.: Model-based approach for establishing the predicted clinical response of a delayed-release and extended-release methylphenidate for the treatment of attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2020;40:350–358. Published by Wolters Kluwer Health, Inc. © Robert Gomeni, et al., 2020 licensed under Creative Commons Attribution 4.0 (CC BY). Proportions of immediate-release and extended-release methylphenidate data are from Childress et al. 2019 [18]. conc, concentration; d-MPH ER, extended-release dexmethylphenidate; DR, delayed release; DR/ER-MPH, delayed-release and extended-release methylphenidate; ER, extended release; IR, immediate release; MEROS, methylphenidate extended-release oral suspension; MPH, methylphenidate; OROS, osmotic-release oral system.

Figure 4. Achievement of norm-referenced thresholds for impairment before and after DR/ER‑MPH dose optimization. Proportion of patients who met thresholds for impairment on the BSFQ and PREMB-R PM at baseline and after 6 weeks of DR/ER-MPH treatment in the phase 3, dose-optimization clinical trial (Study 1) [33]. BSFQ, Before School Functioning Questionnaire; DR/ER-MPH, delayed-release and extended-release methylphenidate; PREMB-R PM, Parent Rating of Evening and Morning Behavior-Revised, Evening subscale.

Table 1. Criteria for considering DR/ER-MPH.

Clinical Rationale for Considering DR/ER-MPH

Indicated for the treatment of ADHD in patients aged 6 years and older [43] Demonstrated ability to provide functional improvement into the late afternoon/evening [14,15] Titratable duration – increasing the dose extends the time window of therapeutic blood concentration Potential for curtailing tolerability issues by minimizing peak-to-trough fluctuations May reduce challenges with adherence, either due to forgetting morning medication or missing afternoon ‘booster’ doses intended to extend duration of effect Improving morning symptom control may translate to benefits for the patient and their family [41] Long-acting stimulants are less likely to be misused, abused, or diverted than short-acting stimulants [4–6]

Considerations/Cautions for Methylphenidate Formulations (including DR/ER-MPH)

Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmias, or coronary artery disease [43] Consider the benefits and risks in patients for whom an increase in blood pressure or heart rate would be problematic [43] Avoid use in a patient who is actively manic or suicidal; use with caution in patients with controlled bipolar disorder

Contraindications for Methylphenidate Formulations (including DR/ER-MPH)

Known hypersensitivity to methylphenidate or product components [43] Concurrent treatment with an MAOI or use of an MAOI within the preceding 14 days [43]

ADHD, attention-deficit/hyperactivity disorder; DR/ER-MPH, delayed-release and extended-release methylphenidate; MAOI, monoamine oxidase inhibitor.

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