Does zopiclone increase alcohol tolerance in adults with insomnia or sleep disorders?

Zopiclone Does Not Increase Alcohol Tolerance

Zopiclone does not increase alcohol tolerance; rather, it produces dangerous additive sedative effects when combined with alcohol, and patients must be explicitly warned to avoid this combination. 1

Critical Safety Warning

The combination of zopiclone with alcohol creates additive CNS depression that significantly impairs psychomotor performance and increases risk of serious adverse events. 1 This is a pharmacodynamic interaction where both substances enhance each other's sedative effects without altering the body's tolerance to either substance. 2

Mechanism of Interaction

• Zopiclone acts as a GABA-A receptor agonist, producing sedation through enhancement of GABAergic neurotransmission 3
• Alcohol also enhances GABA activity and depresses CNS function through multiple mechanisms 2
• When combined, these agents produce additive sedative effects without pharmacokinetic interaction - meaning the blood levels of each drug remain unchanged, but their combined effects on the brain are amplified 2
• Clinical trials specifically demonstrate that adding ethanol to zopiclone treatment results in additive sedative effects without altering the pharmacokinetic parameters of the drug 2

FDA and Guideline Warnings

All benzodiazepine receptor agonists, including zopiclone, carry explicit warnings about avoiding concomitant alcohol use. 1

The American Academy of Sleep Medicine guidelines specifically state:

• Additive effect on psychomotor performance occurs with concomitant CNS depressants and/or alcohol use 1
• The FDA has recommended warnings regarding adverse effects associated with benzodiazepine receptor agonist hypnotics, emphasizing the importance of avoiding the combination of these hypnotics with alcohol 1
• Patients should be cautioned about using only prescribed doses and avoiding combination with alcohol, other sedatives, and sleep restriction 1

Clinical Implications

There is no evidence that zopiclone increases tolerance to alcohol or vice versa. The concern is entirely about the acute combined effects:

• Enhanced sedation and drowsiness 2
• Increased risk of complex sleep-related behaviors (sleep-driving, sleep-eating) 1
• Greater cognitive and psychomotor impairment 1
• Increased risk of respiratory depression, particularly in patients with compromised respiratory function 1
• Higher risk of falls, accidents, and injuries 1

Special Populations at Higher Risk

• Elderly patients are at increased risk for adverse effects from the combination and should receive lower doses of zopiclone (and avoid alcohol entirely) 1
• Patients with compromised respiratory function (asthma, COPD, sleep apnea) face particular danger from combined CNS depression 1
• Those with hepatic impairment may have prolonged effects of zopiclone and should use reduced doses while strictly avoiding alcohol 1

Common Clinical Pitfall

The most important pitfall is patients self-medicating insomnia with alcohol while taking prescribed zopiclone. 1 Clinicians must:

• Explicitly counsel patients that alcohol will not improve sleep quality and creates dangerous interactions with zopiclone 1
• Screen for alcohol use disorders before prescribing zopiclone, as patients with substance use history may be better candidates for non-scheduled alternatives like ramelteon 1
• Emphasize that the combination does not build tolerance but rather compounds risk with each use 2

Patients who use alcohol to treat insomnia should not be prescribed zopiclone until alcohol use is addressed. 1