Can You Take Diazepam with Pregabalin?

Severity assessment

Moderate. Concomitant use of diazepam and pregabalin can lead to increased central nervous system (CNS) depression, resulting in enhanced side effects such as dizziness, drowsiness, confusion, and difficulty concentrating [1].

Mechanism (plain English)

Both diazepam and pregabalin act on the central nervous system (CNS) to produce their effects. Diazepam is a benzodiazepine that enhances the effect of gamma-aminobutyric acid (GABA), a neurotransmitter that calms brain activity. Pregabalin is a gabapentinoid that also reduces nerve excitability by binding to a specific subunit of voltage-gated calcium channels in the brain and spinal cord, which decreases the release of several neurotransmitters, including glutamate, noradrenaline, and substance P. When taken together, their combined CNS depressant effects are additive, leading to a greater degree of sedation, drowsiness, and impaired cognitive and motor function than either drug alone [1].

Evidence level

Regulator-flagged. The MHRA has reviewed and strengthened warnings regarding the risks of addiction, dependence, withdrawal, and tolerance for gabapentinoids (including pregabalin) and benzodiazepines (including diazepam) [2].

Top regulator advisories

• TGA (Australia): The TGA advises caution when prescribing pregabalin concomitantly with other CNS depressants, including opioids, due to the risk of severe sedation, respiratory depression, coma, and death. Dosages and durations should be limited to the minimum required. [4]
• MHRA / NICE (UK): The MHRA has reviewed and strengthened warnings regarding addiction, dependence, withdrawal, and tolerance for gabapentinoids (including pregabalin) and benzodiazepines (including diazepam). They advise healthcare professionals to discuss these risks with patients prior to starting treatment and to implement a strategy for reducing or ending treatment safely. [2]
• FDA / CDC (US): The prescribing information for Lyrica CR (pregabalin) warns that respiratory depression may occur when used with concomitant CNS depressants. Patients should be monitored, and dosage adjusted as appropriate [3].
• EMA (Europe): While no specific advisory for diazepam and pregabalin interaction was found, EMA assessment reports for pregabalin highlight that it is unlikely to be involved in significant pharmacokinetic drug interactions. However, caution is generally advised when pregabalin is used with other CNS depressants due to potential additive effects [5].

Clinical risk factors that elevate the danger

Several factors can increase the danger of combining diazepam and pregabalin:

• Elderly patients: Older individuals may be more susceptible to the CNS depressant effects, leading to increased dizziness, drowsiness, and impaired coordination [1].
• Patients with respiratory impairment: Individuals with pre-existing respiratory conditions (e.g., COPD, sleep apnea) are at higher risk of respiratory depression when taking these medications concurrently [3].
• Concomitant use of other CNS depressants: Taking other medications that cause sedation, such as opioids, alcohol, antihistamines, or other anxiolytics, significantly increases the risk of severe CNS depression, respiratory depression, coma, and death [1, 3, 4].
• History of substance abuse: Patients with a history of alcohol or substance abuse may be at higher risk of developing dependence and addiction to both diazepam and pregabalin [2].
• Rapid dose escalation or abrupt discontinuation: Increasing doses too quickly or suddenly stopping either medication can exacerbate adverse effects or trigger withdrawal symptoms, including seizures [2, 3].
• Renal impairment: As pregabalin is primarily eliminated by the kidneys, impaired renal function can lead to increased drug levels and enhanced side effects [3].

What a patient should be told

• Understand the risks: Taking diazepam and pregabalin together can make you very drowsy, dizzy, confused, and can affect your breathing. This risk is higher if you are older, have breathing problems, or are taking other medicines that make you sleepy, including alcohol [1, 3, 4].
• Do not stop suddenly: Never stop taking these medications or change your dose without talking to your doctor or pharmacist first. Suddenly stopping can lead to withdrawal symptoms, including seizures [2, 3]. Your healthcare professional will help you gradually reduce the dose when it's time to stop.
• Watch for warning signs: Be aware of signs like extreme drowsiness, difficulty waking up, very slow or shallow breathing, or unusual confusion. If you experience these, seek medical attention immediately [1, 3].
• Discuss alternatives: If you are concerned about these risks or feel your medication is not working as well, talk to your doctor or pharmacist about safer alternative treatments or ways to manage your condition [2].
• Urgent care triggers: If you or someone you are with becomes unresponsive, has very slow breathing, or has difficulty breathing, call emergency services immediately.

Top 3 sources (with full citation)

1. Drugs.com. (n.d.). Diazepam + Pregabalin: Can You Take Them Together? Retrieved June 1, 2026, from https://www.drugs.com/drug-interactions/diazepam-with-pregabalin-862-0-1937-0.html
2. Medicines and Healthcare products Regulatory Agency (MHRA). (2026, January 8). Improving Information Supplied with Gabapentinoids (Pregabalin/Gabapentin), Benzodiazepines and Z-Drugs. GOV.UK. https://www.gov.uk/drug-safety-update/improving-information-supplied-with-gabapentinoids-pregabalin-slash-gabapentin-benzodiazepines-and-z-drugs
3. U.S. Food and Drug Administration (FDA). (2025, April). LYRICA CR (pregabalin) extended-release tablets, for oral use, CV - Full Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209501s010lbl.pdf
4. Therapeutic Goods Administration (TGA). (2021, February 1). Pregabalin and gabapentin. https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/pregabalin-and-gabapentin

Notes for the reviewing pharmacist

Pharmacists should be aware of the heightened risk of CNS and respiratory depression when diazepam and pregabalin are co-prescribed. Emphasize patient education on recognizing symptoms of over-sedation and the critical importance of not abruptly discontinuing either medication. Given the MHRA's strengthened warnings, proactive counseling on dependence, addiction, and withdrawal is essential, particularly for vulnerable populations such as the elderly or those with a history of substance abuse. Individualized tapering plans are crucial for safe discontinuation. While pharmacokinetic interactions are generally considered low for pregabalin, the pharmacodynamic additive effects with benzodiazepines are clinically significant and warrant careful monitoring and dose adjustment.

Source metadata JSON

{
  "pair": "diazepam + pregabalin",
  "severity": "Moderate",
  "evidence_level": "Regulator-flagged",
  "source_urls": "https://www.gov.uk/drug-safety-update/improving-information-supplied-with-gabapentinoids-pregabalin-slash-gabapentin-benzodiazepines-and-z-drugs;https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209501s010lbl.pdf;https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/pregabalin-and-gabapentin"
}