Continuing Education Activity

Monoamine oxidase inhibitors (MAOIs) are pharmacologic agents used in the management of depressive disorders and, in some cases, Parkinson disease. Although effective, MAOIs carry a risk of toxicity, particularly in the event of overdose. This activity provides a comprehensive review of MAOI pharmacology, clinical presentation of overdose, symptom severity, and risk factors associated with specific agents. Nonselective, irreversible MAOIs such as phenelzine and tranylcypromine are associated with an increased risk of hypertensive crisis when ingested with tyramine-rich foods. In contrast, selective monoamine oxidase B inhibitors, such as selegiline, have a lower risk of hypertension. Recognition of symptoms, including agitation, flushing, tachycardia, hypo- or hypertension, palpitations, muscle twitching, hyperreflexia, seizures, and high fever, is critical, as prompt medical intervention is essential to prevent life-threatening complications.

The activity further explores strategies for safe clinical use of MAOIs, including patient assessment, monitoring requirements, and the role of interprofessional healthcare teams in managing therapy. Evidence-based approaches for individualized dosing, symptom recognition, and risk mitigation are presented to support optimal patient outcomes. By emphasizing interprofessional collaboration, standardized monitoring, and patient education, this activity reinforces best practices for minimizing overdose risk, adverse effects, and complications associated with MAOI therapy.

Objectives:

• Identify safe and appropriate use of monoamine oxidase inhibitors in clinical practice.
• Assess adverse effects and interaction risks associated with MAOI therapy.
• Implement evidence-based monitoring and patient education strategies for the use of MAOIs.
• Communicate clinical findings and treatment plans within interprofessional teams to enhance patient safety and treatment efficacy in MAOI management.

Indications

Monoamine oxidase (MAO) inhibitors (also known as MAOIs), introduced in the 1950s,[1][2] represent a distinct class of antidepressants used to treat various forms of depression and certain nervous system disorders, including panic disorder, social phobia, and depression with atypical features.[3] Atypical features may include symptoms such as oversleeping and overeating. Although MAOIs were the first antidepressants developed, they are no longer considered first-line therapy because of dietary restrictions, adverse effects, and safety concerns. MAOIs are typically reserved for patients who have not responded to other treatment options.

FDA-Approved Indications With Classification

Nonselective monoamine oxidase inhibitors: These inhibitors are differentiated into type A (MAO-A) and type B (MAO-B). The US Food and Drug Administration (FDA) has approved the drugs mentioned below.

• Phenelzine: According to prescribing information, phenelzine is indicated for the treatment of atypical, nonendogenous, or neurotic depression, which may present with mixed anxiety and depressive symptoms, phobia, or hypochondria. The drug is also used for the treatment of resistant depression and is considered suitable for patients who have not responded to the first-line antidepressant drugs.[4]

• Tranylcypromine: Tranylcypromine is prescribed for adults with treatment-resistant major depressive disorder (MDD) who have not achieved an adequate response to other antidepressant therapies. Tranylcypromine is not recommended as a first-line treatment for MDD due to the potential for severe adverse reactions, drug interactions, and dietary restrictions.

• Isocarboxazid: Isocarboxazid is indicated for the treatment of MDD in patients who have not responded to first-line therapy.[5] The efficacy of isocarboxazid beyond 6 weeks has not been systematically assessed in randomized controlled trials.

Selective monoamine oxidase inhibitor type B: Selective MAO-B inhibitors are approved by the FDA for the management of certain neurologic and psychiatric conditions.

• Selegiline: Selegiline is approved as adjunctive therapy for patients with Parkinson disease who, despite receiving levodopa/carbidopa therapy, demonstrate a decline in the quality of their response.[6][7]

• Selegiline transdermal system: Selegiline transdermal patch is approved for the treatment of MDD.[8][9]

• Rasagiline: Rasagiline is approved by the FDA for the treatment of Parkinson disease.[10]

• Safinamide: Safinamide is approved as adjunctive therapy to levodopa/carbidopa in patients with Parkinson disease who experience "off" episodes.[11][12][13][14]

MAO-B inhibitors are a possible option for initial dopaminergic therapy in patients with early Parkinson disease and mild motor symptoms, supported by Level C evidence from the American Academy of Neurology.[15]

Off-Label Uses

Neurological disorders that may benefit from MAOIs include Parkinson disease and multiple system atrophy.[16][17] Multiple system atrophy is a neurodegenerative disease characterized by symptoms affecting movement and blood pressure regulation. In addition, patients with panic disorder who do not respond to standard treatments may also benefit from MAOIs.[18][19]

Mechanism of Action

MAOIs block the monoamine oxidase enzyme, which is responsible for breaking down neurotransmitters such as norepinephrine, serotonin, dopamine, and tyramine in the brain. By inhibiting this breakdown, MAOIs increase the levels of these neurotransmitters, allowing them to continue exerting their effects on the cells affected by depression.[20]

There are 2 types of MAOs: MAO-A and MAO-B. MAO-A is mainly distributed in the placenta, gut, and liver, whereas MAO-B is found primarily in the brain, liver, and platelets. Serotonin and noradrenaline are substrates of MAO-A, while phenylethylamine, methylhistamine, and tryptamine are substrates of MAO-B. Dopamine and tyramine are metabolized by both MAO-A and MAO-B. Selegiline and rasagiline are irreversible, selective inhibitors of MAO-B, whereas safinamide is a reversible, selective inhibitor of MAO-B.[21]

MAOIs may act as either reversible or irreversible inhibitors. Moclobemide is an example of a reversible inhibitor of MAO-A, whereas tranylcypromine, phenelzine, isocarboxazid, and selegiline irreversibly inhibit MAO. At low doses, selegiline acts as a selective, irreversible MAO-B inhibitor, but it loses selectivity at higher doses.[22]

It is important to note that the selegiline transdermal system is indicated for treating MDD, whereas the oral formulation of selegiline is indicated as adjunctive therapy to levodopa/carbidopa in patients with Parkinson disease. The transdermal route bypasses first-pass metabolism, resulting in higher systemic bioavailability and inhibition of both MAO-A and MAO-B, which contributes to its antidepressant efficacy. In contrast, oral selegiline at standard doses for Parkinson primarily targets MAO-B.[23] However, at higher doses, it becomes nonselective and inhibits both MAO-A and MAO-B.[24]

Pharmacokinetics 

Absorption: Absorption characteristics vary by agent and formulation, influenced by bioavailability and first-pass metabolism. Selegiline's systemic exposure varies with formulation—oral tablets produce higher amphetamine-like metabolite levels than buccal or transdermal routes, which bypass significant first-pass metabolism. Phenelzine is rapidly absorbed, reaching peak plasma concentration (Cmax) within approximately 0.5 to 1 hour. Tranylcypromine typically peaks within 1 to 3 hours (occasionally showing a biphasic profile), while isocarboxazid reaches peak levels in approximately 1 to 2 hours with relatively low bioavailability. Rasagiline achieves its maximum concentration (Tmax, the time taken to reach the highest drug concentration in the blood) at approximately 1 hour, while safinamide reaches peak levels within 2 to 4 hours and has about 95% bioavailability.

Distribution: Older nonselective MAOIs exhibit extensive penetration into the central nervous system (CNS). Rasagiline and safinamide also distribute widely within CNS tissues. Protein binding is generally moderate for most agents.

Metabolism: Phenelzine, tranylcypromine, and isocarboxazid undergo extensive hepatic metabolism to polar urinary metabolites, with clinical washout determined more by MAO enzyme resynthesis (≈2 weeks for irreversible inhibitors) than by plasma clearance. Phenelzine is oxidized and acetylated to phenylacetic and p-hydroxyphenylacetic acids. Tranylcypromine forms hydroxylated and N-acetyl derivatives, while isocarboxazid is converted to hippuric acid. Selegiline produces desmethyl and amphetamine-like metabolites, which are reduced with buccal or transdermal dosing. Rasagiline is primarily metabolized by CYP1A2, while safinamide is mainly processed through non-CYP amidase metabolism. Metabolic characteristics influence dosing and interaction risk: use formulation-specific precautions with selegiline, monitor for CYP1A2 interactions with rasagiline, and adjust dosing for hepatic impairment with safinamide. For older nonselective agents, PubChem-derived pharmacokinetic data (Tmax, half-life, Vd, urinary recovery) support rational washout and interaction planning, with the understanding that irreversible MAO inhibition may outlast plasma detectability.

Excretion: MAOIs are primarily eliminated in the urine as metabolites. The elimination half-life of phenelzine is approximately 11.6 hours, that of tranylcypromine ranges from 1.5 to 3.2 hours, and that of isocarboxazid ranges from 1.5 to 4 hours, with urinary recovery of roughly 42% to 45% (mainly as hippuric acid) within 24 hours. The terminal half-life of safinamide is approximately 20 to 26 hours. For irreversible MAOIs, washout duration is governed by enzyme resynthesis rather than plasma elimination alone.[PubChem and DailyMed, accessed Aug 9, 2025]

Administration

Available Dosage Forms and Strengths

• Phenelzine is available as a 15-mg oral tablet.
• Isocarboxazid is available as a 10-mg oral tablet.
• Tranylcypromine is available as a 10-mg oral tablet.
• Selegiline is available as 5-mg oral tablets and capsules, and as a 1.25-mg orally disintegrating tablet.
• The selegiline transdermal system is available in strengths of 6 mg/24 h, 9 mg/24 h, and 12 mg/24 h; each offered as a single patch.
• Rasagiline is available as 0.5-mg and 1-mg oral tablets.
• Safinamide is available as 50-mg and 100-mg oral tablets.

MAOIs are primarily administered orally but are also available as transdermal patches.[1] The skin patch formulations have been FDA-approved and may offer greater benefits to patients compared with oral dosage forms. For example, selegiline can be administered as a transdermal patch, which is associated with fewer adverse effects than oral administration.[1] Patients receiving lower doses of MAOIs may not require as stringent dietary restrictions as those receiving higher doses; however, dietary precautions vary depending on the specific drug and formulation. Clinicians should follow product-specific recommendations.

MAOIs approved by the FDA include isocarboxazid, phenelzine, selegiline, and tranylcypromine.[25] When initiating MAOI therapy, patients should be informed that the antidepressant effects generally appear within 2 to 3 weeks. However, patients should take the antidepressant for at least 6 months for the maximal therapeutic benefit. Discontinuation before 6 months is associated with a higher risk of symptomatic relapse.

Adult Dosage

Phenelzine: Phenelzine is generally initiated at 15 mg orally 3 times daily, with titration to 60 to 90 mg per day based on tolerance and clinical response. Following symptom control, the dose is gradually tapered to a maintenance level, which may be as low as 15 mg daily or every other day.

Tranylcypromine: Tranylcypromine is recommended at a starting dose of 30 mg per day in divided doses. If the response is inadequate, the dose may be increased by 10 mg per day every 1 to 3 weeks, up to a maximum of 60 mg per day, with slower titration advised for patients at risk of hypotension, such as older adults.

Isocarboxazid: Isocarboxazid is started at 10 mg orally twice daily and may be increased by 10 mg every 2 to 4 days to reach 40 mg per day by the end of the first week if tolerated. Further increases of up to 20 mg per week may be made as needed, to a maximum of 60 mg per day, divided into 2 to 4 doses. Caution is advised when exceeding 40 mg per day due to limited data at higher doses.

Selegiline: Selegiline is prescribed at 10 mg per day in 2 divided doses (5 mg at breakfast and 5 mg at lunch) for Parkinson disease patients experiencing a waning response to levodopa/carbidopa. Higher doses offer no additional benefit and increase the risk of adverse effects. After 2 to 3 days, an individualized neurological assessment may guide cautious reduction of the levodopa/carbidopa dose. 

Selegiline transdermal system: The selegiline transdermal system is applied once daily to dry, intact skin on the upper torso below the neck and above the waist, the upper thigh, or the outer upper arm. The recommended starting and target dose is 6 mg/24 h. If needed, the dose may be increased by 3 mg/24 h at intervals of no less than 2 weeks, up to a maximum of 12 mg/24 h. Tyramine-rich foods and beverages must be avoided at doses of 9 mg/24 h or higher and for 2 weeks after dose reduction or discontinuation, as hypertensive crises may occur if dietary restrictions are not followed. Long-term treatment may be required, and periodic reassessment of benefit is advised. All patients should be screened for personal or family history of bipolar disorder before initiating therapy.

Rasagiline: Rasagiline is initiated at 0.5 mg orally once daily in patients receiving levodopa. If 0.5 mg is well tolerated but the clinical response is inadequate, the dose may be increased to 1 mg once daily. When rasagiline is added to levodopa, the levodopa dose may be reduced based on individual response. The recommended dose should not be exceeded due to the risk of hypertension. In patients receiving CYP1A2 inhibitors, such as ciprofloxacin, or in those with mild hepatic impairment, rasagiline should be limited to 0.5 mg once daily.

Safinamide: Safinamide is initiated at 50 mg orally once daily, at a consistent time and without regard to meals, as adjunctive therapy to levodopa/carbidopa for “off” episodes in Parkinson disease.[12][26] After 2 weeks, the dose may be increased to 100 mg once daily based on individual response; doses above 100 mg confer no additional benefit and increase the risk of adverse events. If a dose is missed, patients should resume the usual regimen with the next scheduled dose. To discontinue safinamide 100 mg, taper by reducing to 50 mg once daily for 1 week. In patients with moderate hepatic impairment (Child-Pugh class B), the dose should not exceed 50 mg daily. Safinamide is contraindicated in individuals with severe hepatic impairment (Child-Pugh class C).

Specific Patient Populations

Hepatic impairment: Phenelzine sulfate and isocarboxazid are contraindicated in patients with active liver disease or abnormal hepatic function due to an increased risk of hepatotoxicity. Tranylcypromine has been associated with rare cases of hepatitis and elevated transaminases; liver function should be monitored, and treatment discontinued if hepatotoxicity develops. Oral selegiline requires no specific dosage adjustment but should be used with clinical judgment in severe hepatic dysfunction. The transdermal selegiline does not require dose adjustment in mild or moderate hepatic impairment, but it has not been examined in severe hepatic impairment; therefore, transdermal selegiline should be used with caution in such cases. Rasagiline should be limited to 0.5 mg once daily in moderate impairment (Child-Pugh class B) and is contraindicated in severe impairment (Child-Pugh class C). Safinamide should be reduced to 50 mg daily in moderate impairment (Child-Pugh class B) and is contraindicated in severe impairment (Child-Pugh class C), as mentioned above.[27]

Renal impairment: Routine dose adjustment is not necessary for patients with mild to moderate renal impairment when using these agents; however, clinical monitoring is recommended. Phenelzine and tranylcypromine may be used cautiously in renal impairment, particularly in older adults who may accumulate active metabolites. Isocarboxazid should not be used in severe renal impairment. Oral selegiline lacks formal renal dosing recommendations but should be used with caution in severe impairment. Dosage adjustment of transdermal selegiline is not required in patients with mild, moderate, or severe renal impairment; however, its use is not recommended in those with an estimated glomerular filtration rate below 15 mL/min/1.73 m² or in those on dialysis due to insufficient clinical data. Rasagiline does not require dose adjustment in patients with mild or moderate renal impairment; however, its use has not been studied in those with severe renal impairment. Safinamide may be administered at standard doses regardless of renal function.[28]

Pregnancy considerations: The use of MAOIs during pregnancy requires careful assessment of maternal benefits and potential fetal risks. Phenelzine and tranylcypromine have demonstrated fetal harm in animal studies and should be reserved for treatment-resistant depression when safer alternatives are unavailable. Human pregnancy data are limited for isocarboxazid, selegiline (oral or transdermal), rasagiline, and safinamide; initiation should involve consultation with a maternal–fetal medicine specialist, appropriate fetal monitoring, and shared decision-making to determine whether the potential maternal benefit outweighs fetal risk. There are limited human pregnancy data for isocarboxazid, selegiline (oral or transdermal), rasagiline, and safinamide. Initiation of these agents should involve consultation with a fetal medicine specialist, appropriate fetal monitoring, and shared decision-making to assess whether the potential maternal benefits outweigh the possible risks to the fetus.

Breastfeeding considerations: Decisions regarding nursing while on MAOIs must balance infant exposure and maternal need for psychiatric stability. Tranylcypromine and isocarboxazid are known to be excreted in human milk and generally warrant discontinuation of either the drug or breastfeeding.[29][30] For phenelzine, selegiline (oral and transdermal), rasagiline, and safinamide, where lactation data are limited, select an alternative treatment.[31] The manufacturer of the selegiline transdermal patch suggests that breastfeeding is not advised during treatment and for 7 days after the final dose.[32][33][34]

Pediatric patients: None of the MAOIs, including phenelzine, tranylcypromine, isocarboxazid, selegiline (oral or transdermal), rasagiline, or safinamide, is approved for individuals younger than 18 due to a lack of safety and efficacy data in pediatric populations. The selegiline transdermal system is contraindicated for patients younger than 12.

Older patients: Older adults may be more susceptible to orthostatic hypotension, drug accumulation, and CNS effects. Although phenelzine has not shown age-specific adverse findings, tranylcypromine carries an elevated risk of postural hypotension and should be initiated at the lower end of the dosing range. No formal geriatric dose adjustments exist for isocarboxazid, selegiline (oral or transdermal), rasagiline, or safinamide, but cautious initiation and monitoring for hypotension, cognitive changes, or falls are recommended.

Adverse Effects

The most frequently reported adverse effects are dry mouth, nausea, diarrhea, constipation, drowsiness, insomnia, dizziness, and/or lightheadedness. Furthermore, if applied via a patch, a skin reaction may occur at the patch site.[25] It is recommended that patients scheduled for elective surgery requiring general anesthesia discontinue MAOI therapy at least ten days prior to the procedure to prevent potential drug interactions.[35][36]

Drug-Drug and Drug-Food Interactions

• Naltrexone-bupropion extended release should be avoided in patients who are treated with or have taken MAOIs within the past 14 days.[37]

• Tramadol, meperidine, dextromethorphan, and methadone are contraindicated in patients receiving MAOIs as they are at high risk for causing serotonin syndrome.[22]

• In general, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), bupropion, mirtazapine, St. John's wort, and sympathomimetic amines, including stimulants, are contraindicated with MAOIs.[22]

• MAOIs prevent the breakdown of tyramine found in the body and certain foods, drinks, and other medications. Patients taking MAOIs who consume tyramine-containing foods or drinks will exhibit elevated serum tyramine levels.[38][39] A high level of tyramine can cause a sudden increase in blood pressure, called the tyramine pressor response.[39] Although it is rare, a high tyramine level can trigger a cerebral hemorrhage, which can even result in death.

• Eating foods high in tyramine can trigger a reaction with serious consequences.[39] Patients should be aware that tyramine levels can increase with the aging of food; therefore, they should be encouraged to choose fresh foods rather than leftovers or food prepared hours earlier. Examples of foods with high levels of tyramine include fish and certain meats, such as sausage, turkey, liver, and salami.[40][41] Additionally, certain fruits can contain tyramine, such as overripe fruits, avocados, bananas, raisins, or figs. Further examples include cheeses, alcohol, and fava beans; all of these should be avoided even after 2 weeks of stopping MAOIs, per product-specific guidelines.[41] Anyone taking MAOIs is at risk for an adverse hypertensive reaction, with accompanying morbidity.

Contraindications

MAOIs can cause drug-drug interactions, drug-food interactions, and overdoses, and patients should be made aware of these risks.[25] For example, combining MAOIs with other antidepressants, such as SSRIs, should be avoided.[42] The combination of these medications can result in serotonin syndrome, a potentially life-threatening condition.

The first cases of serotonin syndrome were reported in the 1960s among patients receiving MAOIs in combination with tryptophan. Affected individuals exhibited symptoms such as fever, confusion, increased perspiration, muscle rigidity, seizures, liver or kidney dysfunction, and variations in heart rate and blood pressure. A washout period of at least 14 days is recommended when transitioning from an MAOI to another antidepressant to reduce the risk of drug interactions. Additionally, MAOIs should be avoided in patients with uncontrolled hypertension, confirmed or suspected cerebrovascular disease, or cardiovascular disease.

Box Warnings: Monoamine Oxidase Inhibitors

Antidepressant-labeled monoamine oxidase inhibitors: Antidepressant-labeled MAOIs, such as phenelzine, tranylcypromine, and isocarboxazid, have the class box warning mandated for all antidepressants regarding an increased risk of suicidal thinking and behavior in children, adolescents, and young adults. This warning emphasizes the importance of closely monitoring pediatric patients for clinical worsening, suicidality, or unusual behavioral changes, particularly during the initial treatment or dose adjustments. In addition, tranylcypromine's box warning explicitly includes the risk of hypertensive crisis associated with ingestion of significant amounts of dietary tyramine. The transdermal selegiline system, approved for MDD, carries the same antidepressant box warning for suicidality in pediatric and young adult patients. Box warnings for MAOIs are summarized here. Verify the exact box warning on the FDA product label for each drug.

Monoamine oxidase type B–selective agents for Parkinson disease: MAO-B–selective agents approved solely for Parkinson disease, such as selegiline oral formulation, rasagiline, and safinamide, currently lack box warnings in their FDA labeling.

Warning and Precautions

Hypertensive crisis: MAOIs can trigger a hypertensive crisis if patients consume foods or beverages high in tyramine or are exposed to specific pharmacologic agents. The risk is increased in individuals with hyperthyroidism or preexisting cardiovascular or cerebrovascular disease. Patients should receive thorough dietary counseling and education on recognizing early symptoms such as sudden severe headache, palpitations, chest pain, nausea, vomiting, sweating, visual changes, or confusion. Blood pressure should be monitored regularly, and if hypertensive crisis is suspected, the drug should be discontinued immediately and appropriate emergency treatment, including rapid blood pressure reduction and supportive care, should be initiated.

Serotonin syndrome: Concomitant use of MAOIs with serotonergic agents—including SSRIs, SNRIs, TCAs, certain opioids, triptans, and herbal preparations such as St. John's wort—is contraindicated because of the risk of serotonin syndrome, a potentially life-threatening condition. Clinicians should monitor for symptoms such as agitation, hyperreflexia, clonus, hyperthermia, and autonomic instability. If serotonin syndrome develops, both the MAOI and any serotonergic agents should be discontinued immediately, and supportive and symptomatic care should be initiated.

Risk of mania in bipolar disorder: MAOIs may trigger manic or mixed episodes in patients with bipolar disorder. A thorough psychiatric history, including screening for prior episodes of mania or hypomania and family history of bipolar disorder, is recommended before initiating therapy.

Urgent requirement for contraindicated drugs: If urgent treatment with a contraindicated drug, such as linezolid, intravenous methylene blue, or a direct-acting sympathomimetic, is necessary, the MAOI should be discontinued as soon as clinically feasible before the introduction of the other agent, and the patient should be closely monitored for adverse events throughout the overlap.

Withdrawal reactions: Abrupt discontinuation of MAOIs can result in withdrawal symptoms, including dizziness, nausea, irritability, insomnia, anxiety, paresthesia, or, in rare cases, seizures. Whenever possible, discontinuation should be achieved through gradual dose tapering.[43]

Seizure risk: Seizures have been reported both during overdose and following withdrawal from MAOIs, particularly in the context of misuse. Patients with a history of seizure disorders should be monitored closely.

Hypoglycemia in patients with diabetes: MAOIs may potentiate the hypoglycemic effects of insulin or oral antidiabetic drugs, thereby increasing the risk of clinically significant hypoglycemia in patients with diabetes mellitus. Regular monitoring of blood glucose levels and appropriate adjustment of antidiabetic therapy are recommended.

Cognitive and motor impairment: MAOIs may cause hypotension, sedation, or confusion, which can potentially impair the ability to operate motor vehicles or heavy machinery. Patients should be cautioned against engaging in such activities until they have adequate experience with the drug to determine its effects on their cognitive and motor performance.

Dyskinesia: MAO-B inhibitors, including safinamide and rasagiline, may cause new-onset dyskinesia or exacerbate existing dyskinesia when used in combination with levodopa. Clinicians should monitor for involuntary movements and consider reducing the dose of levodopa or another dopaminergic drug if dyskinesia occurs.

Hallucinations and psychotic-like behavior: MAO-B inhibitors may cause hallucinations or other psychotic-like behaviors due to increased central dopaminergic tone. Their use should generally be avoided in patients with psychotic disorders. If hallucinations or psychotic symptoms develop, the clinician should consider dose reduction or discontinuation.

Excessive daytime somnolence: MAO-B inhibitors may cause excessive daytime sleepiness and sudden episodes of falling asleep during activities such as driving, eating, or talking. These events can occur months or even more than a year after treatment initiation and often follow unrecognized drowsiness. Clinicians should assess for risk factors, including sedating drugs, sleep disorders, or drug interactions. Patients should be advised to avoid driving or other potentially dangerous activities if somnolence develops. The drug should ordinarily be discontinued if a patient falls asleep during daily activities.

Impulse control disorders: Patients receiving MAO-B inhibitors may develop strong and uncontrollable urges such as gambling, hypersexuality, or binge eating.[44] Because patients may not recognize these behaviors as abnormal, clinicians should ask patients and caregivers about new or increased urges. Dose reduction or discontinuation should be considered if these behaviors arise.

Monitoring

Although MAOIs are no longer considered first-line treatment, they remain in clinical use, and careful attention to safety precautions is essential when initiating therapy.[42] Patients should be encouraged by health providers to carry identification cards or wear a wristband.[25] Patients should always notify every doctor they encounter, whether dental or medical, to avoid any health consequences, especially due to the influence of medications on the vasculature, as well as read the box warnings. Baseline and periodic blood pressure should be obtained. Additionally, baseline liver function tests should be obtained due to the risk of hepatotoxicity associated with isocarboxazid, phenelzine, and tranylcypromine.[45][46][47]

Toxicity

Signs and Symptoms of Overdose

Patients receiving MAOIs may experience overdose, presenting with adverse effects similar to those previously described but often of greater severity.[48] Symptoms generally develop gradually within 24 to 48 hours and may be nonspecific, ranging from mild to severe or even life-threatening. Depending on the MAOI prescribed, some may cause coma, while others (eg, tranylcypromine overdose) can result in death(eg, overdosing on tranylcypromine) can result in death.[25]

The severity of toxicity depends on both the dose ingested and the specific MAOI involved. For example, phenelzine and tranylcypromine, being nonselective and irreversible inhibitors, increase the risk of hypertensive crisis when ingested with tyramine-rich foods.

In contrast, selegiline, a selective MAO-B inhibitor, carries a lower risk of hypertensive reactions.[16] Patients who experience agitation, flushing, tachycardia, hypotension or hypertension, palpitations, muscle twitching, increased deep tendon reflexes, seizures, or high fever should seek immediate medical attention.[25]

Management of Overdose

There is no specific antidote for MAOI overdose. For patients presenting with a hypertensive emergency due to MAOI overdose, phentolamine should be administered.[39] Supportive care is critical and includes airway protection, seizure management with benzodiazepines, and symptomatic treatment as needed. Cyproheptadine may be considered for serotonin syndrome after consultation with a medical toxicologist and critical care physicians.[49] Consultation with the US National Poison Control Center at 1-800-222-1222 is recommended for complicated cases.

Enhancing Healthcare Team Outcomes

The safety and optimal treatment of psychiatric or neurologic disorders are vital to patient health. MAOIs should be avoided in patients with a history of seizures or epilepsy, as these agents can increase seizure frequency. Also, individuals with a history of alcoholism, angina, severe headaches, peripheral arterial disease, diabetes, kidney or liver disease, a history of a recent myocardial infarction or stroke, an overactive thyroid, and pheochromocytoma should not receive MAOI therapy, since this may cause a hypertensive crisis.[2]

Caution is also advised in patients with a family history of depression, neurologic disorders, or suicide attempts. Given the potential for serious adverse outcomes, obtaining a thorough family and medical history is essential before initiating therapy. Educating patients about the possible risks and adverse effects of MAOIs is critical to their well-being, as it provides them with the opportunity for better outcomes.

As with other illnesses, depression and other psychiatric treatment plans pose multiple dilemmas for physicians.[48] These patients may need to try various medication regimens before achieving effective treatment. Someone experiencing depression or panic attacks may have significant life changes, and usually, the family physician is aware of these changes. 

While psychiatrists are almost always involved in the care of patients with various mental health conditions, it is essential to consult with an interprofessional team of specialists. This team includes a family physician who manages overall health and coordinates care, an internal medicine specialist who addresses medical comorbidities, a mental health nurse with specialized training who provides psychosocial support and monitoring, and neurologists who evaluate eligibility for Parkinson disease and other neurologic conditions. Pharmacists ensure safe medication management, including monitoring for potential drug-drug interactions.[50]

Other healthcare providers, such as additional nurses and social workers, contribute significantly by assisting with patient care and addressing psychosocial needs. Each member provides an essential component of the patient’s treatment plan. Evidence suggests that promoting interprofessional communication and consulting specialists can enhance patient outcomes and adherence to treatment plans.[51]

An interprofessional team approach and effective communication among primary care physicians, advanced practice providers, psychiatrists, neurologists, pharmacists, and nurses are crucial to minimizing potential adverse effects and enhancing patient outcomes related to MAOIs.

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Disclosure: Preeti Patel declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.