Solriamfetol in the USA is marketed under the brand name Sunosi, represents a significant advancement in treating excessive daytime sleepiness associated with sleep disorders. As a dopamine and norepinephrine reuptake inhibitor (DNRI), it promotes wakefulness without the amphetamine-like structure of many traditional stimulants. In the United States, its legal framework is shaped by dual oversight from the Food and Drug Administration (FDA) for approval and the Drug Enforcement Administration (DEA) for controlled substance classification. This article delves into solriamfetol’s regulatory journey, current status as a Schedule IV controlled substance, prescription requirements, and broader implications for patients and healthcare providers as of September 2025. While it offers therapeutic benefits, its controlled nature underscores efforts to prevent misuse amid rising awareness of sleep-related conditions.

FDA Approval and Indications of Solriamfetol in the USA

The FDA granted approval to solriamfetol on March 20, 2019, following rigorous clinical trials demonstrating its efficacy in improving wakefulness. Developed by Jazz Pharmaceuticals, Sunosi was authorized for adults experiencing excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea (OSA). The approval was based on data from the TONES (Treatment of OSA and Narcolepsy Excessive Sleepiness) program, which included four phase 3 studies showing significant reductions in sleepiness scores compared to placebo. Doses range from 75 mg to 150 mg once daily for narcolepsy and 37.5 mg to 150 mg for OSA, taken orally in the morning to align with natural wake cycles.

This milestone made solriamfetol the first DNRI approved for these indications, filling a gap for patients unresponsive to or intolerant of other treatments like modafinil or amphetamines. The FDA’s decision highlighted its acceptable safety profile, with common side effects including headache, nausea, decreased appetite, and anxiety. However, a boxed warning addresses potential cardiovascular risks, such as elevated blood pressure and heart rate, necessitating monitoring in patients with hypertension or heart conditions.

DEA Scheduling and Controlled Substance Designation

Following FDA approval, the DEA is responsible for scheduling drugs with abuse potential under the Controlled Substances Act (CSA). Solriamfetol was initially placed in Schedule IV via an interim final rule on June 17, 2019, and this was finalized on January 7, 2020. Schedule IV classification indicates a low potential for abuse relative to Schedule III substances, an accepted medical use, and limited risk of physical or psychological dependence.

The DEA’s decision was informed by FDA recommendations, preclinical data showing minimal euphoria or reinforcing effects in animal models, and human studies indicating low abuse liability compared to stimulants like phentermine (Schedule IV) or methylphenidate (Schedule II). Unlike higher-scheduled drugs, solriamfetol does not produce the intense “high” associated with dopamine surges in reward pathways, contributing to its milder classification. As of 2025, no rescheduling has occurred, though ongoing post-marketing surveillance monitors for emerging abuse patterns.

Implications of Schedule IV Status

Being a Schedule IV controlled substance imposes specific legal requirements to curb diversion and misuse. Prescriptions can be issued with up to five refills within six months, but electronic prescribing is encouraged under the DEA’s EPCS (Electronic Prescriptions for Controlled Substances) mandate to enhance tracking. Pharmacists must verify patient identity and maintain detailed records, and interstate prescribing follows state-specific rules, often requiring compliance with the Ryan Haight Online Pharmacy Consumer Protection Act for telehealth.

Possession without a valid prescription is a federal offense, potentially leading to misdemeanor charges, fines up to $1,000, or up to one year in prison for first-time offenders. Repeat violations or intent to distribute escalate to felonies with harsher penalties. Manufacturing or distribution without DEA registration is strictly prohibited, aligning with broader efforts to combat prescription drug abuse. For healthcare providers, prescribing solriamfetol requires a DEA registration number, and they must adhere to state prescription drug monitoring programs (PDMPs) to prevent doctor-shopping.

Compared to non-controlled alternatives like caffeine supplements, solriamfetol’s status ensures regulated access but can create barriers, such as prior authorizations from insurers or limited pharmacy stocking due to controlled substance quotas.

Prescription Requirements for Solriamfetol in the USA and it’s Availability

Solriamfetol in the USA is available only by prescription from licensed healthcare providers, such as neurologists, sleep specialists, or primary care physicians trained in sleep medicine. Diagnosis typically involves polysomnography for OSA or multiple sleep latency tests for narcolepsy to confirm eligibility. It’s not available over-the-counter, and any online sales claiming otherwise are likely illegitimate, risking counterfeit products or legal repercussions.

Commercial availability began shortly after DEA scheduling in 2019, with Jazz Pharmaceuticals launching Sunosi through specialty pharmacies. As of 2025, generic versions are not yet widespread due to patent protections extending into the 2030s, keeping costs higher—around $800-$1,000 for a 30-day supply without insurance. Patient assistance programs, like JazzCares, offer copay support for eligible individuals. Telemedicine has expanded access, but prescribers must conduct in-person evaluations for initial controlled substance prescriptions under federal law, with exceptions during public health emergencies.

Alternatives of Solriamfetol in the USA

• Modafinil (Provigil) and armodafinil (Nuvigil) are wake-promoting eugeroics, approved for narcolepsy, obstructive sleep apnea, and shift work disorder. Modafinil decreases dopamine reuptake; armodafinil is its longer-acting R-enantiomer.
• Pitolisant (Wakix), also FDA-approved in 2019, is a first-in-class histamine H₃ receptor inverse agonist that enhances histaminergic activity and improves wakefulness with minimal abuse potential.
• Sodium oxybate (Xyrem) is a CNS depressant approved since 2002 for EDS and cataplexy—improves nighttime sleep consolidation but requires a strict REMS and carries substantial safety warnings.

Safety & Tolerability

• Real-world pharmacovigilance data (FDA FAERS, 2019–2023) reports:
  • Modafinil: signals for cognitive disorders, fetal growth restriction, abuse, and inefficacy.
  • Solriamfetol: signals include suicidal ideation, restless legs, somnambulism, and drug inefficacy.
  • Pitolisant: fewer signals overall but includes psychiatric and nervous system adverse events.
  • Sodium oxybate: higher number of signals, particularly psychiatric, respiratory, and pregnancy-related risks.
• Sodium oxybate carries a black box warning for respiratory depression, abuse potential, and serious CNS depression under its REMS protocol.
• Solriamfetol and modafinil/armodafinil are Schedule IV controlled substances—lower abuse risk than traditional stimulants.
• Pitolisant is not a controlled substance and shows minimal abuse potential

Legal status of the Solriamfetol in the USA as an FDA-approved, DEA Schedule IV controlled substance reflects a balanced approach to innovation and safety. Since its 2019 approval and scheduling, it has provided a valuable option for managing debilitating sleepiness while minimizing abuse risks through stringent controls. For patients, this means reliable access via prescription, but with safeguards like PDMP checks and refill limits. As sleep medicine evolves, solriamfetol’s framework could influence future wakefulness agents, emphasizing evidence-based regulation. Individuals considering this medication should consult healthcare professionals to navigate its legal and clinical nuances effectively.