Is Zaleplon a Controlled Substance?

Yes, zaleplon is classified as a Schedule IV controlled substance by federal regulation. 1

Regulatory Classification

Zaleplon is federally regulated as a Schedule IV controlled substance under the Drug Enforcement Administration (DEA) scheduling system 1
This classification places zaleplon in the same category as other benzodiazepine receptor agonists (BzRAs) used for insomnia treatment 2
Patients who prefer not to use a DEA-scheduled drug may be appropriate candidates for alternative agents like ramelteon, particularly for sleep initiation difficulty 2

Abuse liability studies demonstrate that zaleplon has an abuse potential similar to benzodiazepine and benzodiazepine-like hypnotics: 1

Two controlled studies assessed abuse liability at supratherapeutic doses (25 mg, 50 mg, and 75 mg) in subjects with known histories of sedative drug abuse 1
The results confirmed zaleplon possesses abuse potential comparable to other hypnotics in this class 1
Individuals with a history of addiction to or abuse of drugs or alcohol are at risk of habituation and dependence and should be under careful surveillance when receiving zaleplon 1

The potential for physical dependence with zaleplon appears relatively low compared to other hypnotics: 1

Controlled studies of 14-, 28-, and 35-night durations assessed physical dependence potential 1
Some patients (mostly those treated with 20 mg) experienced mild rebound insomnia on the first night following withdrawal that resolved by the second night 1
The Benzodiazepine Withdrawal Symptom Questionnaire did not detect evidence for a withdrawal syndrome following abrupt discontinuation in pre-marketing studies 1
However, seizures have been observed in two patients in clinical trials with zaleplon, and seizures and death have been seen following withdrawal in animal studies at doses many times higher than human therapeutic doses 1

No development of tolerance to zaleplon was observed for time to sleep onset over 4 weeks of treatment 1
Tolerance to hypnotic effects generally did not occur during 5 weeks' treatment or during long-term treatment (6 or 12 months) according to available studies 3

Because zaleplon is a Schedule IV controlled substance, prescribers must: 1

Maintain careful surveillance when prescribing to patients with histories of substance use disorders 2
Consider alternative non-scheduled agents (such as ramelteon) for patients with substance abuse history, particularly when the primary complaint is sleep initiation difficulty 2
Be aware that both medications carry potential for misuse, though zaleplon shows relatively low potential for withdrawal syndrome 4
Avoid combining zaleplon with other CNS depressants or alcohol due to additive effects on psychomotor performance 4