|The following article is part of conference coverage from US Psych Congress 2018 in Orlando, Florida. Psychiatry Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in psychiatry. Check back for the latest news from US Psych Congress 2018.|
ORLANDO, FL — The nonopioid medication lofexidine is safe and effective in managing opioid withdrawal syndrome (OWS), according to research presented at US Psych Congress 2018, October 25 to 28 in Orlando, Florida. Researchers noted it may expand the treatment options available for managing withdrawal when buprenorphine and methadone are unavailable or undesirable. It may also serve as a bridge to depot naltrexone.
Lofexidine, an alpha-2 adrenergic receptor agonist that reduces norepinephrine signaling in the brain, was approved by the US Food and Drug Administration in May 2018. Lofexidine mitigates opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.
Researchers conducted two phase 3, randomized, controlled trials to evaluate lofexidine’s safety and efficacy in treating OWS in men and women aged ≥18 years who were abruptly discontinuing short-acting opioids including heroin, oxycodone, and hydrocodone. This pooled database contained 865 opioid-dependent participants, 585 of whom were randomly assigned to lofexidine and 280 of whom were randomly assigned to placebo.
In study 1, participants were randomly assigned to either placebo or lofexidine 2.88 mg/d (0.72 mg 4 times per day) for 5 days. In study 2, participants were randomly assigned to placebo, lofexidine 2.88 mg/d (0.72 mg 4 times per day), or lofexidine 2.16 mg/d (0.54 mg 4 times per day) for 7 days.
The primary measure of efficacy was the Short Opiate Withdrawal Scale of Gossop (SOWS-G), a validated, subject-rated assessment of 10 common symptoms of OWS. A secondary outcome was the proportion of subjects completing the trail. To assess safety, researchers monitored adverse events (AEs), electrocardiograms (ECGs), and vital signs. In study 2, predefined changes in blood pressure and heart rate were reported as AEs and required study discontinuation if severe.
The researchers found that least squares (LS) averages for SOWS-G score (over days 1-7) and the peak SOWS-G average score (over days 1-5) were significantly lower for both doses of lofexidine compared with placebo, demonstrating reduction in OWS with lofexidine treatment. Participants treated with lofexidine were also significantly more likely to complete the 7-day withdrawal period compared with placebo-treated participants.
In addition, lofexidine was well tolerated. AEs related to reduction in blood pressure and heart rate were most common, and severe AEs were uncommon.
“In this large, pooled database of 865 opioid-dependent subjects, both doses of lofexidine were significantly superior to placebo for reducing OWS symptoms during the peak of OWS,” the researchers concluded.
Pirner M, Kasibhatla C, Clinch T, Alam D. Safety and efficacy analysis of lofexidine from pooled phase 3 studies. Presented at: US Psych Congress 2018; October 25-28, 2018; Orlando, FL. Poster 130.