Wakefulness-promoting agents reduce excessive daytime sleepiness in OSA patients
Canada: Pitolisant, solriamfetol, and armodafinil-modafinil reduces daytime sleepiness for patients with obstructive sleep apnea (OSA) already taking conventional therapy, with solriamfetol likely superior, according to a systematic review and analysis of 14 trials.
Patients, however, may be more likely to discontinue these medications due to adverse events, including anxiety, headache, and insomnia. The review is published in the Annals of Internal Medicine.
Symptoms of EDS are often improved with standard treatment of OSA, but it may persist in up to 18 percent of OSA patients despite ongoing conventional therapy. EDS is associated with neuropsychological impairment and decreased quality of life, and treatment is a continued priority for clinicians. Pharmacological interventions for OSA include solriamfetol and armodafinil–modafinil approved for OSA treatment in the U.S., and pitolisant, which has been studied in previous trials but is not approved for the treatment of OSA.
Researchers from McMaster University, Dalhousie University, and the University of Toronto conducted a systematic review and meta-analysis of 14 trials enrolling 3,085 patients.
Key findings include:
- Fourteen trials comprising 3085 patients were eligible. At 4 weeks, compared with placebo, solriamfetol improves ESS scores (mean difference [MD], −3.85; high certainty), and armodafinil–modafinil (MD, −2.25; moderate certainty) and pitolisant–H3-autoreceptor blockers (MD, −2.78; moderate certainty) probably improve ESS scores.
- At 4 weeks, compared with placebo, solriamfetol (standardized mean difference [SMD], 0.9) and armodafinil–modafinil (SMD, 0.41) improved MWT (both high certainty), whereas pitolisant–H3-autoreceptor blockers probably do not (moderate certainty).
- At 4 weeks, armodafinil–modafinil probably increases the risk for discontinuation due to adverse events (relative risk [RR], 2.01; moderate certainty); solriamfetol may increase the risk for discontinuation due to adverse events (RR, 2.07; low certainty).
- Low certainty evidence suggests these interventions may not increase the risk for serious adverse events.
They included the use of armodafinil, modafinil, solriamfetol, and pitolisant–H3-autoreceptor antagonist. The authors found that solriamfetol, armodafinil–modafinil and pitolisant reduced daytime sleepiness for patients with OSA already on conventional therapy, and solriamfetol was likely superior in effectiveness. However, adverse events, including headache, insomnia, and anxiety, were associated with an increased risk for discontinuation in several trials.
According to the authors, future research should address potential long-term and rare harms that may be associated with these drugs and the potential differential effects of these drugs in patients who are not adherent to conventional OSA treatment.
Reference:
Tyler Pitre, Jasmine Mah, Sarah Roberts, Kairavi Desai, Yusing Gu, Clodagh Ryan, Jason W. Busse, and Dena Zeraatkar, https://doi.org/10.7326/M22-3473.
