Combination Therapy for ADHD Shows Promise

San Diego—Combination therapy has been used informally in mental health, but new evidence is emerging that combination therapy is safe and effective for difficult and treatment-resistant cases of attention-deficit hyperactivity disorder (ADHD). Oren Mason, MD, founder and director, Attention MD, presented research to demonstrate a variety of approaches to combination therapy in ADHD during a scientific session at the Psych Congress titled New Approach to ADHD Medication-Combination Therapy.

He began the presentation by highlighting the benefits and concerns of combination therapy (Table). There are 14 FDA-approved ADHD medications, and some of these medications include Boxed Warnings. Amphetamine, for example, has the potential for abuse and dependence, and misuse can cause sudden death and serious cardiovascular adverse reactions. Selective serotonin reuptake inhibitors may lead to suicidal ideation and behaviors. Atomoxetine may lead to suicidal ideation in children and adolescents, according to Dr. Mason.

The presentation continued with a history lesson in the use of combination therapy. Dr. Mason reviewed 4 early studies of combination therapy. One study by Connor DF et al compared the safety and efficacy of methylphenidate (MPH) combined with clonidine (n=8), clonidine monotherapy (n=8), or MPH monotherapy (n=8) in children age 6 to 16 with ADHD and comorbid aggressive oppositional defiant disorder. All 3 treatment groups showed significant improvements in attention deficits, impulsivity, oppositional, and conduct disordered symptoms as assessed by parent and teacher rating scales and laboratory measures.

A separate study by Quintana H et al showed improvement in ADHD symptom severity in children and adolescents (n=62) with partial response or intolerance to stimulants when switched to atomoxetine. After a 2-week crossover phase in which atomoxetine was titrated up and the stimulant was titrated down, patients remained on atomoxetine monotherapy for 5 weeks. Study results showed that ADHD Rating Scale IV (RS-IV) improved from 32 to 22 (P<.001) and 65% of patients favored atomoxetine.

Dr. Mason also reviewed recent published studies of combination therapy. A study conducted by Kollins SH et al of 198 children and adolescents with ADHD and incomplete response to an extended-release (XR) stimulant were randomized to receive clonidine XR (n=102) or placebo (n=96) in combination with their baseline stimulant medication. After 5 weeks, combination clonidine XR plus stimulant yielded improvements in ADHD-RS-IV (P=.014), ADHD-RS-IV inattention (P=.014), ADHD-RS-IV hyperactivity and impulsivity (P=.017), and Connors’ Parent Rating Scale (P<.062).

Clinical monitoring of combination therapy is an important component in treatment for ADHD. Monitoring safeguards patients and optimizes efficacy of therapy. Three tools are used in monitoring combination therapy: (1) vital signs, (2) structured symptom evaluation, and (3) clinical history, explained Dr. Mason. The structured symptom evaluation includes the clinician administered ADHD-RS-IV, patient self-report using the adult self-report scale, and Conners-Wells’ Adolescent Self-Report Scales. The evaluation also includes an observer report such as the National Initiative for Children’s Healthcare Quality Vanderbilt Assessment Scale—Parent Informant.

Whereas monotherapy for ADHD is historically preferred, its effects may be suboptimal or of limited duration. Also, monotherapy is not always sufficient to lead to functional improvements, according to Dr. Mason. Combination therapy for ADHD is typically a stimulant plus a nonstimulant. Early studies show promise for combination therapy with acceptable safety and tolerability and accessible safety monitoring. Improved symptom response with combination therapy leads to functional improvement, concluded Dr. Mason.