Summarize the Dorrego et al. randomized double‑blind crossover study comparing methylphenidate with lithium in adults with attention‑deficit/hyperactivity disorder without major medical or psychiatric comorbidities.

Summary of the Dorrego et al. Randomized Double-Blind Crossover Study

The Dorrego et al. study found that methylphenidate and lithium produced similar improvements in ADHD symptoms, irritability, aggression, and mood symptoms in adults with ADHD, though this single small crossover trial provides only preliminary evidence and should not change current practice favoring stimulants as first-line therapy. 1

Study Design and Population

• This was a randomized, double-blind, crossover trial examining methylphenidate versus lithium in adults with ADHD. 1
• Patients received 8 weeks of methylphenidate treatment (up to 40 mg/day) and 8 weeks of lithium treatment (up to 1,200 mg/day) in random order, with independent evaluators blind to group assignment assessing response every 2 weeks. 1
• The study population consisted of adults with ADHD without major medical or psychiatric comorbidities, though the exact sample size was not reported in the abstract. 1

Primary and Secondary Outcomes

• The primary outcome measure was the Conners' Adult ADHD Rating Scale sum score for the clusters of hyperactivity, impulsivity, and learning problems. 1
• Secondary outcome measures included scores of irritability, overt aggression, antisocial behavior, anxiety, and depression, as well as scores on tests of verbal learning and sustained attention. 1

Key Findings

• Both lithium and methylphenidate produced similar improvements on the primary outcome measure of ADHD symptoms (hyperactivity, impulsivity, and learning problems). 1
• Both medications also showed comparable improvements on secondary measures including irritability, aggressive outbursts, antisocial behavior, anxiety, and depression. 1
• The authors characterized these as "preliminary findings," indicating the need for larger confirmatory studies. 1

Clinical Context and Limitations

• Despite these findings, current guidelines strongly recommend stimulants (methylphenidate or amphetamines) as first-line treatment for adult ADHD, with 70-80% response rates and the largest effect sizes from over 161 randomized controlled trials. 2
• Lithium is FDA-approved for bipolar disorder (acute mania and maintenance therapy down to age 12 years) but is not a standard ADHD treatment. 3
• The study's crossover design and small preliminary nature limit generalizability, and lithium carries significant monitoring requirements (blood levels, thyroid function, renal function) and side effects that make it impractical as routine ADHD therapy. 3

Implications for Practice

• This study does not support using lithium as a standard ADHD treatment, as methylphenidate remains the evidence-based first-line option with superior safety profile and ease of use. 3, 2
• The finding that lithium improved irritability and aggression may be relevant for the subset of ADHD patients with comorbid mood instability or bipolar disorder, where mood stabilizers should be optimized before adding stimulants. 3, 2
• For adults with ADHD and prominent irritability or aggression, the standard approach remains optimizing stimulant therapy first, then adding mood-stabilizing agents if needed for persistent mood symptoms. 2