Can a patient with a history of depression or anxiety take nortriptyline (tricyclic antidepressant) with magnesium supplements before bed?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 10, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Can Nortriptyline Be Taken with Magnesium Supplements Before Bed?

Yes, nortriptyline can be taken with magnesium supplements before bed—there are no documented contraindications or significant drug interactions between these two agents, and this combination may actually be beneficial for patients with depression. 1

Rationale for Combined Use

Nortriptyline Timing and Properties

  • Nortriptyline is specifically recommended for bedtime dosing due to its sedating properties, making it particularly useful in patients with agitated depression and insomnia 1
  • The typical dosing is 10 mg at bedtime, with a maximum of 40 mg per day (given twice daily if needed), and it has a therapeutic blood level "window" of 50-150 ng/mL 1
  • As a secondary amine tricyclic antidepressant, nortriptyline has a more favorable tolerance profile with lower risk for cardiotoxic, hypotensive, and anticholinergic effects compared to other TCAs 1

Magnesium's Role in Depression

  • Magnesium supplementation has demonstrated clinically significant improvement in depression symptoms, with one randomized clinical trial showing a net improvement of -6.0 points on PHQ-9 scores (P<0.001) with 248 mg elemental magnesium daily 2
  • Effects were observed within two weeks and were independent of concurrent antidepressant use, suggesting magnesium can be safely combined with antidepressants like nortriptyline 2
  • Magnesium deficiency is associated with major depression, and antidepressants including tricyclics (amitriptyline, a close relative of nortriptyline) actually increase intracellular magnesium concentrations as part of their mechanism of action 3

Practical Considerations

  • The typical effective magnesium dose for depression is 125-300 mg with each meal and at bedtime, with rapid recovery often seen in less than 7 days 4
  • Magnesium chloride at 248 mg elemental magnesium per day showed 83% adherence and was well tolerated without need for close monitoring 2
  • Taking both medications at bedtime is logical: nortriptyline's sedating effects align with sleep promotion, and magnesium can be dosed at bedtime as part of a divided daily regimen 1, 4

Important Caveats

Monitor for Additive Sedation

  • While not contraindicated, be aware that both nortriptyline and magnesium can promote sleep and sedation 1, 5
  • Start with lower doses if combining initially (nortriptyline 10 mg, magnesium 125-248 mg) and titrate based on response and tolerability 1, 4

Anticholinergic Effects

  • Nortriptyline's anticholinergic side effects (dry mouth, constipation, urinary retention) can be minimized by starting with low bedtime dosing and slow titration 1
  • Magnesium may actually help with constipation, a common TCA side effect 2

No Direct Drug Interaction Evidence

  • The reviewed guidelines and research do not identify any pharmacokinetic or pharmacodynamic interactions between nortriptyline and magnesium 1, 4, 3, 2
  • Magnesium's effects on depression appear complementary rather than antagonistic to antidepressant mechanisms 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Magnesium in major depression.

Magnesium research, 2009

Guideline

Mirtazapine Treatment Guidelines for Major Depressive Disorder

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.