Profile of Solriamfetol in the Management of Excessive Daytime Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea: Focus on Patient Selection and Perspectives

Abstract

Excessive sleepiness (ES) is a symptom of obstructive sleep apnea (OSA) and narcolepsy that has severe consequences. Wake-promoting drugs and stimulants are utilized as accessory treatment in OSA to reduce propensity to sleep but they do not improve sleepdisordered breathing. Solriamfetol is a first-line therapeutic agent to combat sleepiness in OSA and narcolepsy patients that is approved both by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). For excessively sleepy adult patients with OSA despite primary treatment or narcolepsy patients without cataplexy, solriamfetol may be used as initial therapy or as replacement therapy in patients who fail treatment or experience unacceptable side effects with modafinil, armodafinil, pitolisant, or stimulants. It can also be used as add-on therapy in OSA or narcolepsy patients when ES is only partially controlled with modafinil, armodafinil, pitolisant, sodium oxybate, or stimulants. Solriamfetol is a phenylalanine derivative whose wake-promoting action may be mediated through its selective dopamine and norepinephrine reuptake inhibition. This paper reviews the profile of solriamfetol in treating ES associated with OSA or narcolepsy and discusses patient selection and clinical perspectives. Mechanism of action, pharmacology, pharmacokinetics, clinical efficacy, and tolerability of solriamfetol are described. The Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES) solriamfetol trials demonstrated the efficacy of solriamfetol in reducing propensity to sleep and maintaining wakefulness, with significant improvements in mean maintenance of wakefulness test (MWT) sleep latencies and significant reduction in Epworth Sleepiness Scale (ESS) scores compared to placebo. With solriamfetol, significantly higher percentages of patients showed improvement in patient's and clinician's global impression of change.

Current Management of Residual Excessive Daytime Sleepiness Due to Obstructive Sleep Apnea: Insights for Optimizing Patient Outcomes

“…Lower CV risk has been observed with solriamfetol and particularly with pitolisant (H 3 receptor antagonist/inverse agonist) than has been observed with modafinil (Table 4 ) [ 97 – 100 ]. Solriamfetol is approved for the treatment of EDS in OSA in the USA and in Europe [ 98 , 101 – 103 ]. In addition, pitolisant has been studied for EDS in OSA in the USA and in Europe [ 97 , 104 , 105 ]; it is approved in the USA for the treatment of EDS in narcolepsy [ 106 ] and in Europe for the treatment of EDS in OSA [ 107 , 108 ].…”

Pitolisant, a wake‐promoting agent devoid of psychostimulant properties: Preclinical comparison with amphetamine, modafinil, and solriamfetol

“…However, there are a limited number of clinical studies comparing safety and efficacy of these drugs. 8 , 47 Therefore, the current study was aimed at evaluating these compounds preclinically. The present in vitro and in vivo comparisons show that d ‐amphetamine, modafinil, and solriamfetol cause DA extracellular levels in the nucleus accumbens, hyperlocomotion, behavioral sensitization and hypophagia, which are common features of psychostimulants and drug‐abuse potential, whereas pitolisant was devoid of such effects.…”

“…[5][6][7] Stimulants such as methylphenidate and amphetamines are second-line drugs for EDS in narcolepsy, because of their sympathomimetic side effects, rebound hypersomnia, abuse potential and tolerance. 2,8 Most of these drugs, such as sodium oxybate, solriamfetol, and modafinil, have a psychostimulant component that is related, at least in part, to their ability to promote dopamine (DA) and norepinephrine (NE) neurotransmission, [9][10][11] either due to inhibition of the reuptake (and/or enhanced transporter internalization or transport reversal) of DA and NE and/or stimulation of their neuronal release. 12,13 Modafinil has been shown to enhance DA in various brain regions including the striatum.…”

Expert Opinion: Managing sleep disturbances in people with epilepsy

“…To date, there is no experimental or clinical data on use of solriamfetol in people with epilepsy. However, given its increasingly recognized beneficial effects on excessive daytime sleepiness in narcolepsy and OSA [112], future studies are warranted to gauge its potential role in managing sleepiness in people with epilepsy.…”