Nortriptyline is a tricyclic antidepressant (TCA) used to treat depression, and sometimes for off-label purposes like managing nerve or chronic pain. While effective, it can cause dangerous interactions with other medications, supplements, and substances. This guide provides an overview of the most critical combinations to avoid and why these precautions are vital for your health.
The Absolute Contradictions: MAOIs
One of the most severe interactions involves Monoamine Oxidase Inhibitors (MAOIs), a class of antidepressants that includes phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan). This combination can cause a potentially fatal condition known as serotonin syndrome, a result of excessive serotonin levels in the brain. Because of this risk, there is a strict washout period required when switching between these medications.
The Washout Period
- From MAOI to Nortriptyline: You must wait at least 14 days after discontinuing an MAOI before starting nortriptyline.
- From Nortriptyline to MAOI: Conversely, you should wait at least 14 days after stopping nortriptyline before beginning an MAOI.
- Other MAOIs: This warning also extends to other drugs with MAOI activity, such as the antibiotic linezolid and intravenous methylene blue.
The Dangers of Serotonergic Drugs
Nortriptyline's primary mechanism of action is affecting brain chemicals, including norepinephrine and serotonin. Combining it with other serotonergic drugs can dangerously elevate serotonin levels, leading to serotonin syndrome. This risk is heightened during initial treatment or when dosages are increased.
- Selective Serotonin Reuptake Inhibitors (SSRIs): Common SSRIs like fluoxetine (Prozac) and sertraline (Zoloft) can interact with nortriptyline. Your doctor must be aware of your complete medication history, especially if you have recently taken or stopped an SSRI. For instance, due to fluoxetine's long half-life, a five-week waiting period is recommended before starting an MAOI.
- Opioid-based Medicines: Opioids such as tramadol, fentanyl, and oxycodone are serotonergic and can increase the risk of serotonin syndrome. Taking these with nortriptyline also increases the risk of severe drowsiness and breathing problems.
- Migraine Medications (Triptans): Drugs for migraine headaches, such as sumatriptan and rizatriptan, are also serotonergic and carry a risk of serotonin syndrome when combined with nortriptyline.
- Herbal and OTC Products: The herbal supplement St. John's wort is well-known for its serotonergic effects and should never be taken with nortriptyline. Other supplements and vitamins should also be reviewed with a doctor.
Caution with Central Nervous System (CNS) Depressants
Nortriptyline itself can cause drowsiness and sedation. Combining it with other CNS depressants magnifies these effects, leading to excessive drowsiness, impaired motor function, and a higher risk of accidents.
- Alcohol: The effects of alcohol are significantly enhanced by nortriptyline, and consumption should be avoided entirely.
- Sedatives and Hypnotics: Sleeping pills, tranquilizers, and other sedatives, including benzodiazepines like alprazolam (Xanax) and lorazepam (Ativan), can cause severe drowsiness when mixed with nortriptyline.
- Antihistamines: Over-the-counter and prescription antihistamines for allergies or cold symptoms, such as diphenhydramine (Benadryl), can contribute to increased sedation.
- Muscle Relaxers: Medications like cyclobenzaprine (Flexeril) or tizanidine (Zanaflex) can increase the sedative effects of nortriptyline.
Critical Cardiac Concerns
Nortriptyline can affect heart rhythm and should be used with extreme caution, if at all, in individuals with certain heart conditions.
- Myocardial Infarction (Heart Attack): Nortriptyline is contraindicated during the acute recovery period after a heart attack.
- Cardiovascular Disease: People with existing cardiovascular disease should be closely monitored by a doctor due to the risk of arrhythmias, blood pressure fluctuations, and conduction defects.
- Brugada Syndrome: Nortriptyline can unmask a rare, potentially fatal genetic heart condition called Brugada syndrome. It should be avoided in patients with a confirmed or suspected diagnosis.
- Antiarrhythmic Medications: Concurrent use of nortriptyline with certain antiarrhythmic drugs like quinidine can be particularly dangerous and is often contraindicated.
Medications Affecting Nortriptyline Levels
Some drugs interfere with the enzymes that metabolize nortriptyline, leading to higher-than-normal plasma levels and an increased risk of side effects and toxicity.
- Cimetidine: Used for stomach ulcers, cimetidine can increase nortriptyline levels.
- Fluoxetine: In addition to its serotonergic effects, fluoxetine can also increase nortriptyline concentrations by inhibiting the enzyme CYP2D6.
- Terbinafine: This antifungal medication can increase nortriptyline levels, boosting the risk of toxicity.
Comparison of Major Nortriptyline Interaction Risks
| Drug Class | Examples | Type of Interaction | Potential Consequences |
|---|---|---|---|
| MAOIs | Phenelzine, Tranylcypromine, Linezolid | Increased Serotonin | Serotonin Syndrome (agitation, hyperthermia, seizures, death) |
| SSRIs & Serotonergic Drugs | Sertraline, Fluoxetine, Tramadol, St. John's wort | Increased Serotonin | Serotonin Syndrome |
| CNS Depressants | Alcohol, Opioids, Benzodiazepines, Antihistamines | Additive Sedation | Excessive drowsiness, impaired coordination, breathing problems |
| Cardiac Drugs | Quinidine, Antiarrhythmics | Cardiovascular effects | Arrhythmias, conduction defects, sudden cardiac death |
| Drugs Affecting Metabolism | Cimetidine, Fluoxetine | Increased Nortriptyline Levels | Higher risk of nortriptyline toxicity and side effects |
Conclusion: The Importance of a Complete Medication Review
This information underscores that taking nortriptyline requires careful consideration of all other substances being consumed. The list of potentially interacting medications is extensive and includes prescription drugs, over-the-counter products, and herbal supplements. The consequences of unchecked interactions range from uncomfortable side effects to life-threatening conditions like serotonin syndrome or sudden cardiac events.
Before starting nortriptyline, or any time a new medication is introduced, it is imperative to provide your healthcare provider with a complete and accurate list of everything you take. This includes all vitamins, herbal products, and any alcohol consumption. A thorough medication review is the single most important step you can take to ensure the safe and effective use of nortriptyline. For more detailed clinical information, consult trusted medical sources such as the National Institutes of Health (NIH) bookshelf.
