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If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
If you have depression, you may be familiar with medications like selective serotonin reuptake inhibitors (SSRIs) such as Prozac (generic name fluoxetine; see Important Safety Information) or serotonin-norepinephrine reuptake inhibitors (SNRIs) like Cymbalta (generic name duloxetine; see Important Safety Information).
But when these medications aren’t effective enough at relieving your symptoms, healthcare providers may turn to other treatments, such as MAOIs.
What are MAOIs?
MAOIs, which stands for monoamine oxidase inhibitors, are drugs used to treat mental health conditions like depression. A healthcare provider may prescribe an MAOI for depression if other medications haven’t worked well enough to improve your symptoms.
Some commonly used MAOIs include selegiline (brand name Emsam), isocarboxazid (brand name Marplan), phenelzine (brand name Nardil), and tranylcypromine (brand name Parnate).
What are MAOIs used for?
The U.S. Food and Drug Administration (FDA) approves MAOIs for treating:
- Depression (major depressive episode): MAOIs are not always the first choice if you have depression. But if the first-line medications (such as SSRIs) don’t work or your symptoms are too severe, studies suggest that MAOIs may be a good choice (Thase, 2012; Fekadu, 2012)
- Parkinson’s disease: Some MAOIs are FDA-approved to treat Parkinson’s disease, a condition that affects how your brain and nervous system allow your body to move, causing symptoms like tremors or stiffness. One review found that MAOIs combined with typical Parkinson’s disease treatments helped decrease participants’ symptoms more than standard treatments alone (Binde, 2018).
Sometimes, healthcare providers will prescribe MAOIs off-label to treat other conditions if they feel it’s an appropriate treatment for their patient. MAOIs are sometimes used off-label for:
- Bulimia (bulimia nervosa): A review of clinical studies found that people with bulimia nervosa who took MAOIs experienced less binge eating and had a higher chance of going into recovery than those who took a placebo (Flament, 2012).
- Panic attacks (panic disorder): A clinical trial of people with panic disorder found that almost 75% of people who took an MAOI experienced significant improvement in their symptoms (Nardi, 2010).
- Social anxiety disorder: In clinical trials, people who took MAOIs for social anxiety disorder had significantly fewer symptoms than those who took a placebo (Blanco, 2010; Stein, 2004).
Healthy coping skills for anxiety, depression, and anger
How do MAOIs work?
MAOIs work by blocking a protein (enzyme) called monoamine oxidase (MAO). This enzyme usually helps your body get rid of excess chemicals called neurotransmitters, including serotonin, epinephrine, and dopamine.
But when these chemicals get too low, they may contribute to depression and anxiety. MAOIs stop MAO from clearing these chemicals away, helping to regulate your mood and stress levels.
MAOI side effects
Side effects of MAOIs are common and include (SubLahan, 2021; FDA, 2014):
- Feeling dizzy or lightheaded
- Being nauseous or throwing up
- Insomnia or excessive sleepiness
- Dry mouth
- Increased or decreased libido
MAOIs are not always the first-choice treatment because they have the potential to cause several severe side effects, including (FDA, 2014):
- High blood pressure: MAOIs may cause a hypertensive crisis, which is dangerously high blood pressure. This side effect is more likely to happen if you combine an MAOI with specific medications or foods containing a chemical called tyramine. Foods that contain tyramine include cured meats like dry sausage, aged cheeses like parmesan or bleu cheese, fava beans, hot dogs and other processed meats, soybeans, pickled foods like sauerkraut, and alcoholic beverages.
- Low blood pressure: MAOIs may significantly lower your blood pressure, especially if you’re over the age of 65.
- Serotonin syndrome: MAOIs raise your level of a chemical called serotonin. Serotonin syndrome is a dangerous and possibly deadly reaction that may occur when serotonin levels get too high. It’s especially risky if you’re taking a second drug that increases your serotonin, such as antidepressants, herbs like St. John’s Wort, and even recreational substances like ecstasy (MDMA). Symptoms of this condition include high fever, hallucinations, abnormal heart rhythms, high or low blood pressure, and coma.
- Abnormal movements (dyskinesia): MAOIs may increase your level of a chemical called dopamine, which affects your movement, so you may experience muscle twitching or jerking.
- Falling asleep spontaneously: Some people who take MAOIs fall asleep unexpectedly, even when driving, so it’s best not to drive while taking this medication before seeing how it affects you.
- Mental health changes: While MAOIs can be effective at treating depression, they may negatively affect other aspects of your mental health. For instance, hallucinations are possible, and in some cases, they can cause people to feel paranoid or act aggressively. Some people become impulsive and start bingeing things like food, sex, shopping, or recreational substances.
Because of these potential risks, your healthcare provider will likely monitor you closely to catch any issues early. Be sure to let your provider know if you experience any of these (or other) disruptive side effects.
What does anxiety feel like?
MAOIs are available only by prescription and can’t be purchased over-the-counter. The available forms and typical starting dosages depend on the specific drug used. For example:
- Selegiline is available either as a tablet that dissolves in your mouth or a patch that you stick to your skin. The typical starting dose is 1.25 mg once a day for six weeks (FDA, 2014).
- Phenelzine comes in 15 mg tablets. The typical starting dose is 15 mg three times a day (FDA-b, 2007).
- Tranylcypromine is available as a 10 mg tablet. The typical starting dose is 15 mg a day (FDA-a, 2007).
Your healthcare provider may increase your dose of any of these medications, depending on how you respond and tolerate side effects.
You may have a higher risk of side effects or severe toxicity if you have specific risk factors or underlying medical conditions. It’s a good idea to speak to a healthcare provider before you take an MAOI if you have any of the following risk factors (FDA, 2014):
- You’re taking another MAOI inhibitor at the same time.
- You’re taking a medication that raises serotonin levels.
- You have heart disease or high blood pressure.
- You have any condition that affects the blood vessels in the brain.
- You’re pregnant or breastfeeding.
- You have a history of liver or kidney disease.
- You have a history of headaches.
- You have a tumor called a pheochromocytoma, which raises your blood pressure.
- You’re over 65.
MAOIs also carry a black box warning—the FDA’s strongest warning for serious risks—about its potential to increase the risk of having suicidal thoughts or suicidal behaviors, especially in younger people.
Because of this, MAOIs are not approved for children (FDA-a, 2007; FDA-b, 2007). In addition to this, some MAOIs also contain a black box warning about the risk of hypertensive crisis when combined with tyramine (FDA, 2018).
MAOI drug interactions
MAOIs may have severe interactions with other types of drugs, including (FDA, 2014; FDA-b, 2007):
- Opioids: Opioids like meperidine (Demerol) may cause serotonin syndrome if you take them with MAOIs.
- Antidepressants: Antidepressant medications like SSRIs (for example, fluoxetine), SNRIs, and tricyclic antidepressants (TCAs, such as amitriptyline) may increase your risk of serotonin syndrome if you take them with your MAOI.
- Stimulants: Medications that stimulate your nervous system (amphetamines like Adderall) can increase your risk of a hypertensive crisis if you take them along with an MAOI.
- Herbs: Some herbs or supplements, such as St. John’s Wort, may increase your risk of serotonin syndrome when mixed with MAOIs.
- Recreational substances: Drugs that increase your serotonin levels, like ecstasy (MDMA), can increase your risk of serotonin syndrome if you use them while taking an MAOI.
- Anti-anxiety medications: Buspirone (brand name Buspar; see Important Safety Information) is a medication you may take for anxiety. If you take it with an MAOI, it may cause dangerously high blood pressure.
- Other MAOIs: Taking more than one MAOI simultaneously may increase your risk of a dangerously high blood pressure.
- Tyramine: Tyramine isn’t a drug by itself, but it’s found in many foods, including fermented cheeses, dried and cured meats like salami, pickled fish like herring, snow peas, fava beans, hot dogs, soy sauce, chocolate, and caffeinated beverages. MAOIs may raise your levels of tyramine and may cause a severe or fatal hypertensive crisis. It’s important to go over all dietary restrictions with a healthcare provider before starting an MAOI.
- Cough and cold medicine: Dextromethorphan is a cough and cold medicine that may cause symptoms like hallucinations, paranoia, and psychotic behavior if you take it with an MAOI.
High functioning depression: symptoms and treatment options
MAOIs may help treat depression that doesn’t respond to standard medications. However, it carries a risk of many severe side effects, so it’s used less frequently. A healthcare provider can help you determine whether an MAOI is a good treatment for you.
- American Psychiatric Association (APA). (2010). Practice guideline for the treatment of patients with major depressive disorder. Retrieved Feb. 10, 2022 from https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf
- Bauer, M., Pfennig, A., Severus, E., et al. (2013). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. The World Journal of Biological Psychiatry, 14(5), 334–385. doi:10.3109/15622975.2013.804195. Retrieved from https://pubmed.ncbi.nlm.nih.gov/23879318/
- Binde, C. D., Tvete, I. F., Gåsemyr, J., et al. (2018). A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson’s disease. British Journal of Clinical Pharmacology, 84(9), 1917–1927. doi:10.1111/bcp.13651. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089809/
- Blanco, C., Heimberg, R. G., Schneier, F. R., et al. (2010). A placebo-controlled trial of phenelzine, cognitive behavioral group therapy, and their combination for social anxiety disorder. Archives of General Psychiatry, 67(3), 286–295. doi:10.1001/archgenpsychiatry.2010.11. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856667/
- Fekadu, A., Rane, L. J., Wooderson, S. C., et al. (2012). Prediction of longer-term outcome of treatment-resistant depression in tertiary care. The British Journal of Psychiatry, 201(5), 369–375. doi:10.1192/bjp.bp.111.102665. Retrieved from https://pubmed.ncbi.nlm.nih.gov/22955008/
- Flament, M. F., Bissada, H., & Spettigue, W. (2012). Evidence-based pharmacotherapy of eating disorders. The International Journal of Neuropsychopharmacology, 15(2), 189–207. doi:10.1017/S1461145711000381. Retrieved from https://pubmed.ncbi.nlm.nih.gov/21414249/
- McGrath, P. J., Stewart, J. W., Nunes, E. V., et al. (1993). A double-blind crossover trial of imipramine and phenelzine for outpatients with treatment-refractory depression. The American Journal of Psychiatry, 150(1), 118–123. doi:10.1176/ajp.150.1.118. Retrieved from https://pubmed.ncbi.nlm.nih.gov/8417553/
- Nardi, A. E., Lopes, F. L., Valença, A. M., et al. (2010). Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with panic disorder comorbid with social anxiety disorder. Psychiatry Research, 175(3), 260–265. doi:10.1016/j.psychres.2008.06.025. Retrieved from https://pubmed.ncbi.nlm.nih.gov/20036427/
- Sidhu, G. & Marwaha, R. (2022). Phenelzine. StatPearls. Retrieved on Feb. 10, 2022 from https://www.ncbi.nlm.nih.gov/books/NBK554508/
- Stein, D. J., Ipser, J. C., & Balkom, A. J. (2004). Pharmacotherapy for social phobia. The Cochrane Database of Systematic Reviews, 4, CD001206. doi:10.1002/14651858.CD001206.pub2. Retrieved from https://pubmed.ncbi.nlm.nih.gov/15495010/
- Sub Laban, T. & Saadabadi, A. (2021). Monoamine oxidase inhibitors (MAOI). StatPearls. Retrieved on Feb. 10, 2022 from https://www.ncbi.nlm.nih.gov/books/NBK539848/
- Suchting, R., Tirumalajaru, V., Gareeb, R., et al. (2021). Revisiting monoamine oxidase inhibitors for the treatment of depressive disorders: A systematic review and network meta-analysis. Journal of Affective Disorders, 282, 1153–1160. doi:10.1016/j.jad.2021.01.021. Retrieved from https://pubmed.ncbi.nlm.nih.gov/33601690/
- U.S. Food and Drug Administration (FDA-a). (2007). Marplan (Isocarboxazid). Retrieved Feb. 10, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011961s039lbl.pdf
- U.S. Food and Drug Administration (FDA-b). (2007). Nardil: Phenelzine Sulfate Tablets. Retrieved Feb. 10, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf
- U.S. Food and Drug Administration (FDA). (2018). Parnate (Tranylcypromine sulfate). Retrieved Feb. 10, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012342s064lbl.pdf
- U.S. Food and Drug Administration (FDA). (2014). Highlights of Prescribing Information: Selegiline. Retrieved Feb. 10, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021479s005lbl.pdf
- Wimbiscus, M., Kostenko, O., & Malone, D. (2010). MAO inhibitors: risks, benefits, and lore. Cleveland Clinic Journal of Medicine, 77(12), 859–882. doi:10.3949/ccjm.77a.09103. Retrieved from https://pubmed.ncbi.nlm.nih.gov/21147941/
Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.