Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design.
OBJECTIVE
To evaluate lisdexamfetamine dimesylate maintenance of efficacy in adults with attention-deficit/hyperactivity disorder (ADHD).


METHODS
Adults (aged 18-55 years) who had ADHD meeting DSM-IV-TR criteria, baseline ADHD Rating Scale-IV (ADHD-RS-IV) with adult prompts total scores of < 22, and Clinical Global Impressions-Severity of Illness (CGI-S) ratings of 1, 2, or 3 were enrolled. After previously receiving commercially available lisdexamfetamine dimesylate (30, 50, or 70 mg/d) for ≥ 6 months with acceptable tolerability and maintaining response during a 3-week open-label phase at a stable lisdexamfetamine dimesylate dose, the participants entered a 6-week double-blind randomized withdrawal phase on treatment with lisdexamfetamine dimesylate (same dose) or placebo. Data were collected from April 2009 to July 2010. The primary outcome was the proportion of participants having symptom relapse (≥ 50% increase in ADHD-RS-IV score and ≥ 2 rating-point increase in CGI-S score).


RESULTS
A total of 116 participants were randomized (lisdexamfetamine dimesylate n = 56; placebo n = 60). At the randomized withdrawal phase baseline, mean (SD) ADHD-RS-IV scores for lisdexamfetamine dimesylate and placebo were 10.6 (4.96) and 10.6 (4.82), respectively. At endpoint, 8.9% (5/56) of adults taking lisdexamfetamine dimesylate and 75.0% (45/60) taking placebo (P < .0001) showed symptom relapse; most showed relapse after 1 and 2 weeks of the randomized withdrawal phase (4 and 0 adults taking lisdexamfetamine dimesylate, 26 and 10 taking placebo, respectively). During the randomized withdrawal phase, treatment-emergent adverse events were reported in 48.2% and 30.0% of participants in the lisdexamfetamine dimesylate and placebo groups, respectively. Treatment-emergent adverse events with incidence ≥ 5% in the lisdexamfetamine dimesylate and placebo groups were headache (14.3% and 5.0%), insomnia (5.4% and 5.0%), and upper respiratory tract infection (8.9% and 0%).


CONCLUSIONS
In adults with ADHD on medium- to long-term treatment, lisdexamfetamine dimesylate demonstrated maintenance of efficacy vs placebo upon randomized withdrawal. A majority of patients given placebo showed symptom relapse by 2 weeks. The safety profile of lisdexamfetamine dimesylate was generally consistent with previous lisdexamfetamine dimesylate studies.


BACKGROUND
ClinicalTrials.gov identifier: NCT00877487.
Bayou City Research, Houston, TX 77007, USA. drmattbrams@aol.com
Matthew
M
Brams
Richard
R
Weisler
Robert L
RL
Findling
Maria
M
Gasior
Mohamed
M
Hamdani
M Celeste
MC
Ferreira-Cornwell
Liza
L
Squires
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects*; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008134:Long-Term Care; D008297:Male; D055502:Secondary Prevention; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D016896:Treatment Outcome; D055815:Young Adult
D000697:Central Nervous System Stimulants; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine