Can You Take Quetiapine with Pregabalin?

Severity assessment

Major. The combination significantly increases the risk of central nervous system (CNS) depression, leading to severe drowsiness, dizziness, and potentially respiratory depression or coma.

Mechanism (plain English)

Both pregabalin and quetiapine act on the brain in ways that can cause sedation and impair mental and physical functions. Pregabalin works by binding to a specific protein in the brain and spinal cord (the alpha-2-delta subunit of voltage-gated calcium channels), which reduces the release of certain neurotransmitters, leading to a calming effect. Quetiapine is an antipsychotic medication that affects several chemical messengers in the brain, including dopamine and serotonin, and also has strong sedative properties due to its action on histamine receptors. When taken together, their individual sedative effects are added, leading to a greater overall depression of the central nervous system. This additive effect can result in increased drowsiness, dizziness, confusion, and problems with coordination and breathing.

Evidence level

Regulator-flagged. The U.S. Food and Drug Administration (FDA) labels for both pregabalin and quetiapine contain warnings regarding additive central nervous system depression when co-administered with other CNS depressants.

Top regulator advisories (cite verbatim or close paraphrase)

• TGA (Australia): No pair-specific public advisory found. The Australian Product Information for pregabalin (e.g., APO-PREGABALIN ARTG 308104) and quetiapine (e.g., SEROQUEL XR ARTG 138920) generally warn about CNS depressant effects and caution against concomitant use with other CNS depressants. For pregabalin, the TGA-approved Consumer Medicine Information (CMI) states: "Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop. Some medicines and pregabalin may interfere with each other. These include: medicines for anxiety, depression or other mental illnesses; medicines for pain; medicines for epilepsy; medicines for sleep." [1]
• MHRA / NICE (UK): No specific pair-specific guidance found. The MHRA advises on pregabalin's potential for dependence and withdrawal, and its CNS depressant effects. The Summary of Product Characteristics (SmPC) for quetiapine (e.g., from medicines.org.uk) states: "Caution should be exercised when SEROQUEL is used in combination with other centrally acting medicinal products and alcohol." [2]
• FDA / CDC (US): The FDA label for pregabalin (Lyrica) states: "There are also postmarketing reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medications." and "Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when LYRICA was co-administered with these drugs [oxycodone, lorazepam, or ethanol]." [3] The FDA label for quetiapine (Seroquel) states: "Most common adverse reactions (incidence ≥5% and twice placebo): Adults: somnolence, dry mouth, dizziness, constipation, asthenia, abdominal pain, postural hypotension, pharyngitis, weight gain, lethargy, ALT increased, dyspepsia." and "Atypical antipsychotic drugs, including SEROQUEL, may cause somnolence, postural hypotension, motor, and sensory impairment." [4]
• EMA (Europe): No specific pair-specific advisory found. EMA product information for both drugs generally highlights CNS depressant effects and the need for caution with other CNS depressants.

Clinical risk factors that elevate the danger

• Elderly patients: Increased sensitivity to CNS depressant effects and higher risk of falls.
• Patients with pre-existing respiratory conditions: Increased risk of respiratory depression.
• Concomitant use of other CNS depressants: Including opioids, benzodiazepines, alcohol, or other sedatives, which further amplify CNS depression.
• Rapid dose escalation: Especially during the initial titration phase of either medication.
• Renal impairment: As pregabalin is primarily excreted by the kidneys, impaired renal function can lead to higher drug levels and increased side effects.

What a patient should be told

• Risk of severe drowsiness and dizziness: You may feel very sleepy, dizzy, or lightheaded, especially when starting these medications or increasing the dose. This can affect your ability to drive or operate machinery safely.
• Do not stop suddenly: Do not stop taking pregabalin or quetiapine suddenly without talking to your doctor, as this can lead to withdrawal symptoms or worsening of your condition.
• Warning signs: Be aware of signs of excessive sedation, confusion, difficulty breathing, or extreme dizziness. If you experience these, seek medical attention immediately.
• Discuss alternatives: Always inform your doctor or pharmacist about all other medications you are taking, including over-the-counter drugs, herbal supplements, and alcohol. They can help assess the risks and discuss safer alternatives if needed.
• Urgent care triggers: If you or someone else notices severe drowsiness, unresponsiveness, very slow or shallow breathing, or difficulty waking up, seek urgent medical help immediately.

Top 3 sources (with full citation)

1. Therapeutic Goods Administration (TGA). APO-PREGABALIN pregabalin 75 mg capsule blister (ARTG 308104). Australian Register of Therapeutic Goods. July 23, 2019. Available at: https://www.tga.gov.au/resources/artg/308104
2. Medicines and Healthcare products Regulatory Agency (MHRA). Quetiapine 25 mg film-coated tablets. Summary of Product Characteristics. Undated. Available at: https://www.medicines.org.uk/emc/product/3079/smpc
3. U.S. Food and Drug Administration (FDA). LYRICA (pregabalin) Capsules, CV, Oral Solution, CV Full Prescribing Information. Revised: May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021446s035,022488s013lbl.pdf
4. U.S. Food and Drug Administration (FDA). SEROQUEL (quetiapine) tablets, for oral use Full Prescribing Information. Revised: January 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020639s072lbl.pdf

Notes for the reviewing pharmacist

This interaction is primarily pharmacodynamic, leading to additive CNS depression. While no direct pharmacokinetic interaction between pregabalin and quetiapine is typically reported, the combined sedative effects are clinically significant. Postmarketing data for pregabalin highlight severe outcomes like respiratory failure and coma when combined with other CNS depressants, underscoring the importance of careful patient selection, education, and monitoring. Misconceptions may arise if patients or prescribers focus solely on pharmacokinetic interactions, overlooking the critical additive pharmacodynamic effects. Particular attention should be paid to elderly patients, those with respiratory compromise, or those concurrently using other sedating medications. Patient counseling should emphasize the signs of excessive sedation and the critical importance of not self-adjusting doses or discontinuing abruptly. The risk of falls due to dizziness and orthostatic hypotension (especially with quetiapine) should also be highlighted.

Source metadata JSON

{
  "pair": "pregabalin + quetiapine",
  "severity": "Major",
  "evidence_level": "Regulator-flagged",
  "source_urls": "https://www.tga.gov.au/resources/artg/308104;https://www.medicines.org.uk/emc/product/3079/smpc;https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021446s035,022488s013lbl.pdf;https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020639s072lbl.pdf"
}