Melatonin - Lyrica (Pregabalin) Interaction
Herbal: Melatonin
Also Known As: N-Acetyl-5-Methoxytryptamine
Drug: Pregabalin
Brand names:
Lyrica, Lyrica CR
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 25, 2025
Interaction Details
Pregabalin is classified as belonging to the following category: Cns Depressants
Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.
Interaction Rating
Likelihood of Occurrence
PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
Pharmacist Analysis
Melatonin can interact with drugs that cause sedation or CNS depression, such as benzodiazepines, opioids, and alcohol, leading to additive effects (i.e., additive sedation and drowsiness effects).
This interaction can increase drowsiness and impair cognitive and motor functions, which may be unsafe for activities that require alertness and concentration, such as driving or operating heavy machinery.
However, if you are using melatonin solely for sleep at night, the interaction is generally not of significant concern.
Nevertheless, it is advisable to consult with a healthcare provider before taking melatonin with other medications, especially those that affect the central nervous system.
References
- Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31.
Melatonin Overview
Melatonin is a hormone that is produced naturally in the pineal gland. It is involved in several different bodily processes, such as the regulation of the body's sleep-wake cycle.
Melatonin is available as a dietary supplement and is often used to help people with sleep disorders, such as insomnia, fall asleep more easily.
There is some evidence to suggest that melatonin supplements may be helpful in reducing the time it takes to fall asleep and improving sleep quality, although the results of studies on this topic have been mixed. Studies show better support for some specific conditions, such as Delayed sleep phase syndrome (DSPS) and Non-24-hour sleep-wake disorder.
Melatonin is generally considered to be safe when used in the short term, although it can cause side effects in some people, such as dizziness, headache, and nausea.
While melatonin is a natural hormone, it is often synthesized for its use in dietary supplements.
Pregabalin Overview
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Pregabalin capsules, oral solution (liquid), and extended-release (long-acting) tablets are used to relieve neuropathic pain (pain from damaged nerves) that can occur in your arms, hands, fingers, legs, feet, or toes if you have diabetes and postherpetic neuralgia (PHN; the burning, stabbing pain or aches that may last for months or years after an attack of shingles). Pregabalin capsules and oral solution are also used to relieve neuropathic pain that can occur after a spinal cord injury and to treat fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep). Pregabalin capsules and oral solution are used along with other medications to treat certain types of seizures in adults and children 1 month of age and older. Pregabalin is in a class of medications called anticonvulsants. It works by decreasing the number of pain signals that are sent out by damaged nerves in the body.
Melatonin - More Interactions
Melatonin interacts with 1425 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
| Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
| Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
| Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
| Unknown | No interactions have been reported or no interaction data is currently available. |
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Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Drug descriptions are provided by MedlinePlus.
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Dr. Brian Staiger, PharmD
In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!
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