While most medications do not impact the circadian rhythm or melatonin production directly, there are several classifications of pharmacological compounds that can impact typical results, depending on the dosage and the individual’s physiology.
Circadian Rhythm/Melatonin Drug Interactions
General Guidance
A general guideline is to stop any medication that your patient can safely and comfortably discontinue under your care for 3-5 days before beginning the assessment. For any medications that cannot be discontinued comfortably or are medically necessary, it is best not to take them within 8 hours prior to beginning the assessment or during the assessment collection period. Most providers recommend that daily medications be administered immediately after the last sample is collected.
Melatonin Supplementation
While measurable levels of exogenous melatonin supplementation or melatonin-containing supplements typically persist in saliva for up to 24 hours, we frequently observe prolonged disruption post-supplementation. This can manifest as elevated melatonin levels, phase shifts, and oscillating profiles. This phenomenon is inter-individual dependent and also influenced by the duration and dosage of routine supplementation. It is recommended to follow a washout period for melatonin supplementation as outlined below:
- 3 days (minimum) for < 3 mg dosing as needed
- 5 days (better) for < 3 mg routine dosing, or up to 5 mg dosing as needed
- 10 days (best) for 3-5 mg routine dosing, or up to 10 mg dosing as needed
- 15 days (ultimate) for up to 10 mg routine dosing
Circadian Rhythm Drug Interaction Index
While assessing every pharmacological compound, dosage, and combination effect would be astronomical, we are working to create an index of medications that likely impact either circadian timing or melatonin production. Please note that the evidence below is anecdotal and has not been part of a formal clinical trial – however, it is still important to note in the event that atypical results are present. Although the clinical significance is typically moderate, emerging evidence suggests that certain medications elevate the probability of impact to a clinically significant level, as delineated in the table provided below:
Medication Name/Class | Effect on Melatonin | Impact Probability |
Stimulants | May Dysregulate Levels | High |
Sedatives | May Dysregulate Levels | High |
Beta-blockers | May Dysregulate Levels | High |
Selective Serotonin Reuptake Inhibitors (SSRIs) | May Dysregulate Levels | High |
Selective Serotonin Reuptake Inhibitors (SSRIs) | May Dysregulate Levels | High |
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) | May Dysregulate Levels | Moderate |
Anxiolytics | May Dysregulate Levels | Moderate |
Benzodiazepines | May Decrease Levels | Moderate |
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) | May Decrease Levels | Moderate |
Proton Pump Inhibitors (PPIs) | May Decrease Levels | Moderate |
Antipsychotics | May Decrease Levels | High |
H2 Blockers | May Decrease Levels | Moderate |
Corticosteroids | May Decrease Levels | High |
H2 Blockers | May Decrease Levels | Moderate |
Beta-agonists | May Decrease Levels | Moderate |
Medications by Name | Effect on Melatonin | Impact Probability |
Buspirone | May Dysregulate Levels (commonly increases) | High |
Fluvoxamine | May Decrease Levels | Moderate |
Mirtazapine | May Increase Levels | High |
Fluoxetine | May Increase Levels | High |
Clonidine | May Increase Levels | High |
Lithium | May Increase Levels | High |
Topiramate | May Increase Levels | High |
Carbamazepine | May Increase Levels | Moderate |