What vitamins should you not take with amitriptyline?

October 10, 2025 •

4 min read

While no standard vitamins are contraindicated with amitriptyline, the herbal supplement St. John's Wort poses a significant risk of causing a severe drug interaction known as serotonin syndrome. This critical distinction highlights the importance of understanding which supplements are safe and which must be avoided when taking this medication.

Quick Summary

Taking the herbal supplement St. John's Wort with amitriptyline is extremely dangerous and can cause serotonin syndrome. Most standard vitamins are generally safe, but you should still consult a doctor before combining supplements with this medication.

Key Points

Avoid St. John's Wort: Never combine amitriptyline with the herbal supplement St. John's Wort, as it can cause a life-threatening condition called serotonin syndrome.
Standard Vitamins Are Generally Safe: Most essential vitamins and minerals, including standard B vitamins and vitamin D, do not have a known dangerous interaction with amitriptyline.
Grapefruit Can Increase Amitriptyline Levels: Grapefruit juice can inhibit an enzyme that metabolizes amitriptyline, potentially raising its levels in your blood and increasing side effects.
Watch Out for Other Supplements: Supplements like tryptophan, 5-HTP, DHEA, and SAMe can also interact with amitriptyline and should be avoided.
Inform Your Doctor or Pharmacist: Always inform your healthcare provider about all prescription drugs, over-the-counter medicines, vitamins, and herbal products you are taking to ensure safety.
Complementary Use Requires Guidance: While a combination of amitriptyline and vitamin B12 (methylcobalamin) is sometimes used for neuropathic pain, this should only be done under a doctor's supervision.

St. John's Wort: A Severe Interaction Risk

Among all over-the-counter supplements, the most dangerous one to combine with amitriptyline is the herbal remedy St. John's Wort (Hypericum perforatum). This is not a vitamin, but it's a commonly used supplement for mood support, and mixing it with a tricyclic antidepressant like amitriptyline can lead to a life-threatening condition called serotonin syndrome.

What is Serotonin Syndrome?

Both amitriptyline and St. John's Wort increase serotonin levels in the brain. When these two substances are combined, the resulting overabundance of serotonin can trigger a rapid and dangerous cascade of symptoms, including:

Confusion or disorientation
Agitation and restlessness
Rapid heart rate and high blood pressure
Excessive sweating and fever
Dilated pupils
Muscle rigidity or spasms
In severe cases, seizures, coma, and even death can occur.

Why the Interaction Occurs

The interaction is two-fold:

Additive Serotonergic Effects: Both substances affect serotonin pathways. While amitriptyline blocks serotonin reuptake, St. John's Wort also inhibits the reuptake of serotonin, norepinephrine, and dopamine, leading to an additive effect that can dangerously raise serotonin levels.
Enzyme Induction: St. John's Wort is a potent inducer of certain liver enzymes (particularly CYP3A4 and CYP1A2) that are responsible for metabolizing amitriptyline. This can lead to unpredictable fluctuations in amitriptyline levels, either reducing its effectiveness or increasing toxicity, especially when St. John's Wort use is stopped.

Standard Vitamins: Generally Safe, But Use Caution

For most essential vitamins and minerals, there are no specific contraindications for use with amitriptyline. A standard multivitamin or a single-vitamin supplement is unlikely to cause a dangerous interaction. However, this does not mean that all combinations are without consideration. You should always inform your doctor and pharmacist about any supplements you are taking, even vitamins.

Vitamin B and Amitriptyline

Studies have shown that certain B vitamins may offer complementary effects when taken with tricyclic antidepressants, although evidence is often preliminary or weak. For instance, a combination of amitriptyline and methylcobalamin (a form of vitamin B12) is sometimes used to manage neuropathic pain. This is because B12 aids in nerve regeneration, complementing amitriptyline's role in pain perception. Nonetheless, high-dose B vitamin supplements should still be cleared by your doctor.

Vitamin D and Amitriptyline

No significant drug interactions have been found between vitamin D3 (cholecalciferol) and amitriptyline. In fact, some research suggests vitamin D may have neuroprotective effects and could be a complementary treatment for conditions like migraine, for which amitriptyline is often prescribed off-label. However, as with any supplement, a doctor should monitor calcium and phosphorus levels if high-dose vitamin D is used.

Other Supplements and Food Interactions

Beyond St. John's Wort, several other supplements and even certain foods can interact with amitriptyline. Some of these can also increase the risk of serotonin syndrome or alter the drug's effectiveness.

Supplements to Avoid or Use with Caution

Tryptophan: This supplement is a precursor to serotonin and can increase the risk of serotonin syndrome when combined with amitriptyline.
DHEA and SAMe: These supplements are also known to interact with amitriptyline and should be avoided unless specifically approved by a physician.
5-HTP: Similar to tryptophan, 5-Hydroxytryptophan can increase serotonin levels and should be avoided.
Yohimbe: This supplement can increase blood pressure and should not be used with amitriptyline.

Key Food Interactions

Grapefruit: Grapefruit and grapefruit juice can inhibit liver enzymes (CYP3A4) that metabolize amitriptyline, potentially leading to higher drug levels and an increased risk of side effects.
Alcohol: Combining alcohol with amitriptyline can intensify sedative effects, causing increased drowsiness, confusion, and other dangerous side effects.

Comparison of Key Interactions with Amitriptyline


Supplement/Vitamin	Type of Interaction	Risk Level	Rationale	Management	Advice
St. John's Wort	Serotonin Syndrome, altered metabolism	Major	Both increase serotonin; also alters liver enzymes that process amitriptyline.	Avoid combination entirely.	Never take St. John's Wort with amitriptyline.
Tryptophan/5-HTP	Serotonin Syndrome	Major	Increases brain serotonin levels, leading to an unsafe additive effect.	Avoid combination.	Do not take serotonin precursors alongside amitriptyline.
Standard Multivitamin	None specified	Minor/None	No known direct adverse interaction with core ingredients.	Usually fine, but inform your doctor.	Safe for most, but always confirm with a doctor.
B Vitamins	Potential metabolic effect (varies), complementary benefits	Minor	Some studies suggest benefits, but evidence is weak or contradictory.	Discuss with a healthcare provider.	May be used therapeutically (like B12), but requires medical oversight.
Vitamin D	None specified	Minor/None	No known drug interaction with amitriptyline.	Generally safe, but monitor with high doses.	Safe for most, especially at recommended doses.
Grapefruit Juice	Inhibits metabolism	Moderate	Can increase amitriptyline levels, potentially increasing side effects.	Avoid consumption.	Limit or eliminate grapefruit from your diet.

Conclusion

When taking amitriptyline, the most critical takeaway is to avoid the herbal supplement St. John's Wort due to the significant risk of serotonin syndrome. Unlike this potent herbal remedy, most standard vitamins and minerals, such as Vitamin B and Vitamin D, do not pose a direct threat and are generally safe to take with amitriptyline, though high doses should always be managed under a doctor's care. Always remember to provide a complete list of all medications, including any over-the-counter supplements or herbal remedies, to your healthcare provider. This diligence ensures your safety by preventing dangerous interactions and allowing for a better-managed treatment plan.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult with your healthcare provider or pharmacist for personalized guidance regarding medications and supplements.

Frequently Asked Questions

Yes, standard vitamin C supplements are generally safe to take with amitriptyline and are not known to cause any significant interactions. However, you should still inform your doctor about all supplements you take.

Yes, there is no known interaction between standard doses of vitamin D3 and amitriptyline. Some research even suggests vitamin D may have some complementary neuroprotective benefits, but high doses should be monitored by a doctor.

Yes, vitamin B12 is often considered safe and is sometimes even used in combination with amitriptyline for neuropathic pain management, under medical supervision. There is no known direct negative interaction with B12.

Combining St. John's Wort with amitriptyline can cause a dangerous and potentially life-threatening condition called serotonin syndrome, due to excessive serotonin levels in the brain.

Yes, besides St. John's Wort, other supplements like tryptophan, 5-HTP, DHEA, and SAMe are known to interact with amitriptyline and should be avoided.

Yes, you should avoid or limit consuming grapefruit and grapefruit juice, as they can increase the levels of amitriptyline in your blood and increase the risk of side effects.

A standard multivitamin typically does not cause a dangerous interaction with amitriptyline, but it is always best to discuss all supplements with your doctor or pharmacist to be safe.

While some preliminary research has explored complementary effects of B1, B2, and B6 with similar antidepressants, evidence is not strong, and high doses should be discussed with a doctor. No major safety concerns are typically associated with standard doses.