Melatonin is a hormone your brain naturally produces to regulate your sleep-wake cycle [1.10.3]. Its availability as an over-the-counter supplement has made it a go-to for people struggling with sleep issues like jet lag or insomnia. However, just because it's readily available does not mean it is free from risks, especially when taken with other medications and substances [1.4.3]. Understanding potential drug interactions is essential for using melatonin safely and effectively.
Combining melatonin with certain drugs can alter their effectiveness, increase the risk of side effects, or cause unwanted reactions [1.2.1, 1.3.1]. Some interactions may lead to excessive drowsiness, while others can affect blood pressure, blood sugar levels, or the body's ability to clot blood [1.2.3]. This article provides a comprehensive guide on what should not be taken with melatonin, based on current medical knowledge. Always consult with a healthcare provider before starting any new supplement, including melatonin, to review your current medications and health conditions [1.3.3].
Medications That Increase Sedation (CNS Depressants)
One of the most common interactions involves substances that depress the central nervous system (CNS). Melatonin itself causes drowsiness, and when combined with other CNS depressants, this effect can become dangerously amplified [1.7.1, 1.7.3]. This additive sedative effect can lead to excessive sleepiness, impaired coordination, slowed breathing, and difficulty waking up [1.12.1]. It can make activities like driving or operating machinery hazardous [1.10.2].
Examples of CNS depressants to use with caution or avoid include:
- Benzodiazepines: (e.g., alprazolam, diazepam) [1.2.3]
- Opioid pain medications: (e.g., codeine, morphine) [1.2.4, 1.2.3]
- Certain Antidepressants: (e.g., trazodone, amitriptyline) [1.2.3]
- Barbiturates: (e.g., phenobarbital)
- Sleep Medications (Z-drugs): (e.g., zolpidem, zaleplon) [1.2.4, 1.2.3]
- Muscle Relaxants: (e.g., cyclobenzaprine) [1.2.3]
- Antihistamines (first-generation): (e.g., diphenhydramine) [1.2.3]
- Alcohol: Experts recommend against mixing melatonin and alcohol due to the risk of cumulative effects and unwanted reactions [1.12.1, 1.12.3].
Blood Thinners (Anticoagulants and Antiplatelets)
Melatonin may slow blood clotting [1.10.2]. When taken with anticoagulant or antiplatelet medications, it can increase the risk of bruising and bleeding [1.5.1, 1.10.2]. While there have been no reports of life-threatening bleeding from this interaction with warfarin, it is crucial to be cautious [1.4.3]. If you are on blood thinners, your doctor may need to monitor your blood more frequently or adjust your medication dose if you start or stop taking melatonin [1.2.3].
Examples of these medications include:
- Warfarin (Coumadin) [1.5.4]
- Clopidogrel (Plavix) [1.2.2]
- Aspirin
- Herbal supplements like garlic and ginkgo biloba can also affect blood clotting and should be used with care [1.5.3].
Blood Pressure Medications
The interaction between melatonin and blood pressure drugs is complex. Some research suggests melatonin can lower blood pressure, which could cause it to drop too low (hypotension) when combined with antihypertensive drugs [1.2.3, 1.4.4]. Conversely, other sources state that melatonin might worsen blood pressure control in people taking these medications [1.2.1, 1.4.2]. Specifically, melatonin may reduce the effectiveness of nifedipine, a common calcium channel blocker, potentially leading to a rise in blood pressure [1.4.3, 1.10.2]. Due to these conflicting effects, it is vital to consult a healthcare provider and monitor blood pressure closely if you take these medications [1.2.3].
Diabetes Medications
Melatonin may affect blood sugar levels [1.6.3]. Combining melatonin with diabetes medications could potentially cause blood sugar to drop too low (hypoglycemia) [1.6.2]. The evidence on this interaction is conflicting, and the effect may depend on the timing of medication and meals [1.2.3, 1.6.1]. People with diabetes should talk to their doctor before using melatonin and may need to monitor their blood glucose more frequently [1.6.1].
Immunosuppressants
Immunosuppressant medications are used to dampen the immune system's activity, often after an organ transplant or to treat autoimmune diseases [1.2.3]. Melatonin, in contrast, can stimulate immune function [1.9.1, 1.9.4]. This opposing action means that melatonin could interfere with and reduce the effectiveness of immunosuppressive therapy [1.9.2, 1.10.2]. Individuals taking these medications should avoid melatonin [1.9.3].
Examples of immunosuppressants include:
- Cyclosporine [1.2.3]
- Corticosteroids [1.2.3]
- Medications used after an organ transplant [1.10.2]
Seizure Medications (Anticonvulsants)
Using melatonin might increase the risk of having a seizure [1.10.2]. Melatonin may inhibit the effects of anticonvulsants, potentially increasing seizure frequency, especially in children with neurological disabilities [1.10.1]. While some studies have investigated melatonin's potential anti-seizure properties, the results are mixed, and its use in people with seizure disorders remains controversial [1.10.3, 1.10.4]. Therefore, individuals with epilepsy or other seizure disorders should avoid melatonin or use it only under strict medical supervision [1.10.2].
Other Notable Interactions
- Fluvoxamine (Luvox): This medication, used for obsessive-compulsive disorder, is a potent inhibitor of the enzyme that breaks down melatonin [1.8.4]. Taking them together can significantly increase melatonin levels in the body—by as much as 17-fold—leading to excessive drowsiness and other side effects. This combination is generally not recommended [1.8.1, 1.8.2].
- Contraceptive Drugs: Birth control pills can cause the body to produce more melatonin naturally. Adding a melatonin supplement might further raise these levels, increasing the risk of side effects like drowsiness [1.2.1, 1.10.2].
- Caffeine: Caffeine can interfere with melatonin in two ways. It can block the liver enzyme that breaks down melatonin, increasing its levels in the body [1.2.3, 1.11.1]. As a stimulant, it can also counteract melatonin's sleep-promoting effects, making it harder to fall asleep [1.3.3]. It is best to avoid caffeine for at least six hours before taking melatonin [1.2.3].
Comparison of Common Melatonin Interactions
| Medication/Substance Class | Potential Interaction | Level of Concern | Examples |
|---|---|---|---|
| CNS Depressants | Increased drowsiness, sedation, slowed breathing [1.7.1, 1.7.3] | High | Alcohol, Benzodiazepines, Opioids [1.2.3] |
| Blood Thinners | Increased risk of bleeding and bruising [1.5.1] | Moderate to High | Warfarin, Clopidogrel [1.2.2, 1.5.4] |
| Blood Pressure Meds | May lower blood pressure too much or interfere with effectiveness [1.2.1, 1.2.3] | Moderate | Nifedipine, Beta-blockers [1.4.3] |
| Diabetes Meds | May cause blood sugar to drop too low (hypoglycemia) [1.6.2] | Moderate | Insulin, Metformin [1.3.3] |
| Immunosuppressants | May interfere with medication effectiveness by stimulating the immune system [1.9.1] | High | Cyclosporine, Corticosteroids [1.2.3] |
| Seizure Meds | May increase seizure frequency or inhibit medication effects [1.10.1, 1.10.2] | High | Carbamazepine, Phenytoin [1.2.4, 1.3.3] |
| Fluvoxamine | Significantly increases melatonin levels, causing excessive drowsiness [1.8.1] | High | Fluvoxamine (Luvox) [1.8.1] |
| Caffeine | Can increase melatonin levels but also counteract its sedative effects [1.3.3, 1.11.3] | Low to Moderate | Coffee, Tea, Energy Drinks [1.2.3] |
Conclusion
While melatonin is a useful supplement for many, it is not without risks. Its interactions with a wide range of common medications and substances can lead to outcomes from increased drowsiness to more serious health concerns like bleeding or seizures. The most critical step before taking melatonin is to have an open conversation with your doctor or pharmacist. They can review your complete medication list, including other supplements and herbal remedies, to identify any potential interactions and ensure melatonin is a safe choice for you.
