Concomitant use of monoamine oxidase inhibitor and tyrosine in parenteral nutrition.

Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of tyramine in the body, and can cause a sudden increase in blood pressure with significant tyramine build up. This phenomenon, when it occurs, is known as tyramine pressor response. It is unknown if tyrosine administered in parenteral nutrition (PN) leads to tyramine build-up with concomitant use of MAOIs. It is also unknown if PN patients who are taking MAOI are at risk for the tyramine pressor response. This is a theoretical possibility as tyrosine endogenously undergoes decarboxylation to produce tyramine. We describe our experience with a 67-year-old woman with severe depression who was on the MAOI, transdermal selegiline. Her clinical course was complicated by an inability to take adequate per oral (PO) intake and she met criteria for unspecified severe protein-calorie-malnutrition in the context of social or environmental circumstances. Therefore, she required PN initiation. PlenamineTM (B. Braun, Bethlehem, PA, USA) was used as the amino acid source in the PN, which contains 39 mg of tyrosine per 100 ml of solution. The patient was monitored closely for any signs of hypertensive crisis while on PN and selegiline. She safely tolerated the combined therapy without any side effects. This is the first documented report of co-administration of PN containing tyrosine along with a MAOI. Our findings suggest that the dose of selegiline used in this patient can be co-administered safely in the setting of PN. However, further study is needed to verify our findings beyond this one patient. In conclusion, we recommend initiating PN and increasing it to goal in patients taking MAOIs, gradually, while monitoring for hypertensive crisis given the theoretical possibility of the tyramine pressor response.

Safety comparisons among monoamine oxidase inhibitors against Parkinson's disease using FDA adverse event reporting system.

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations.

Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.

Comparative efficacy and safety of monoamine oxidase type B inhibitors plus channel blockers and monoamine oxidase type B inhibitors as adjuvant therapy to levodopa in the treatment of Parkinson's disease: a network meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: The monoamine oxidase type B inhibitors plus channel blockers (MAO-BIs plus) are a new class of antiparkinsonian drug with additional mechanisms of action for their property as ion channel blockers. The present study aimed to compare the efficacy and safety of MAO-BIs plus and conventional MAO-BIs, as well as their corresponding doses, as adjuvant therapy to levodopa in the treatment of Parkinson's disease (PD). METHOD: Randomized controlled trials enrolling PD patients treated with selegiline, rasagiline, safinamide or zonisamide as adjuvant therapy to levodopa were identified. Bayesian network meta-analysis was conducted. RESULTS: Thirty-one randomized controlled trials comprising 7142 PD patients were included. Compared with levodopa monotherapy, the combination therapy of MAO-BIs and levodopa was significantly more effective, with a mean difference of 2.74 (1.26-4.18) on the Unified Parkinson's Disease Rating Scale (UPDRS) III score change for selegiline, 2.67 (1.45-3.87) for safinamide, 2.2 (0.98-3.64) for zonisamide and 2.04 (1.24-2.87) for rasagiline. No significant difference was detected amongst MAO-BIs. The surface under the cumulative ranking results showed that safinamide 100 mg and rasagiline 1 mg ranked first in improving UPDRS III and UPDRS II, respectively. Zonisamide 100 mg ranked first in reducing OFF time. For safety outcomes, rasagiline was associated with a higher incidence of adverse events than placebo and safinamide. MAO-BIs plus had a higher probability of being safer agents compared to conventional MAO-BIs. CONCLUSIONS: Monoamine oxidase type B inhibitors plus, conventional MAO-BIs and the corresponding doses are similar in efficacy in PD treatment. MAO-BIs plus might be safer than conventional MAO-BIs. Head-to-head comparisons are needed for further investigation.

Efficacy and safety of MAO-B inhibitor versus donepezil in Chinese elderly stroke patients with Alzheimer disease: A potential therapeutic option.

This pilot study designed to evaluate the efficacy and safety of MAO-B inhibitor in comparison with Donepezil (DNP) in elderly Chinese patients with Alzheimer disease (AD). In the present clinical trial, Chinese elderly patients aged ≥65 years with a confirmed diagnosis of AD were enrolled. The patients received MAO-B inhibitor (Selegiline 5 mg) or DNP 10 mg daily (reference) for 6 months. The efficacy and safety data were collected from 120 patients (60 patients in each group) every 3 weeks until 6 months. The primary endpoints were to assess the change in cognitive score from baseline in both the treatment group. The result of the present study showed that the patients treated with MAO-B inhibitor and DNP have similar efficacy and safety profile Considering the clinical benefit, mean (SD) improvement in sign and symptoms was numerically greater in DNP-treated patients as compared to MAO-B inhibitor at endpoint visit (SIB: 12.3 (3.7) vs 11.3 (4.2); AD severity: 14.2 (3.5); CIBIS+/CIBIC: 10.2 (2.7) vs 9.4 (3.2); ADCS-ADL: 14.3 (4.2) vs 13.2 (3.4); MMSE: 14.3 (3.7) vs 12.2 (3.2), P>0.05 respectively for each comparison). However, a statistical difference in terms of clinical benefit was similar between both the treatment groups (p>0.05). Overall, both the study drugs were found comparable in relieving the symptoms of AD (severity score after end of treatment: 14.2 vs 13.4 respectively; p >0.05). This indicates that MAO-B inhibitor is a potential target for the treatment of AD in China. The results of the present study may help to design a large clinical trial to evaluate the efficacy and safety of MAO-B inhibitor in comparison with DNP in AD patients.

Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer's disease.

Monoamine oxidase-B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer's disease (AD) because of its association with aberrant γ-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.

A Randomized Double-Blind Placebo-Controlled Phase III Trial of Selegiline Monotherapy for Early Parkinson Disease.

BACKGROUND: In Japan, selegiline has been approved for combination therapy with levodopa for Parkinson disease (PD). We conducted a trial of selegiline monotherapy for early PD. METHODS: In this 12-week controlled phase III trial, a total of 292 subjects were randomized to receive placebo (n = 146) (full analysis set 140) or selegiline (n = 146) (full analysis set 139). The primary outcome measure was the change in the Unified Parkinson Disease Rating Scale part I + II + III total score from baseline to the final visit. Other secondary measures and a safety profile were evaluated. RESULTS: Selegiline monotherapy reduced the primary outcome measure by -6.26 ± 7.86 compared with the placebo -3.14 ± 6.98 (mean ± SD, P = 0.0005 by analysis of covariance). There was no significant difference in the number of adverse events between the 2 groups (P > 0.05). CONCLUSIONS: Selegiline monotherapy reduced the total Unified Parkinson Disease Rating Scale part I + II + III score and was well tolerated in Japanese patients with early PD.

Rotigotine in Combination with the MAO-B Inhibitor Selegiline in Early Parkinson's Disease: A Post Hoc Analysis.

BACKGROUND: Monoamine oxidase B (MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson's disease (PD). OBJECTIVE: To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. METHODS: In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose ≤8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks. Post hoc analyses were performed on pooled data for patients receiving an MAO-B inhibitor (selegiline) at a stable dose at randomization and throughout the studies, with groups defined as "Selegiline+Rotigotine" and "Selegiline+Placebo". Outcome measures included change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living), III (motor), UPDRS II+III and responders (patients achieving ≥20%, ≥25% or ≥30% decrease in UPDRS II+III). As post hoc analyses, p-values are exploratory. RESULTS: 130 patients were evaluable for efficacy analyses ("Selegiline+Rotigotine": 84, "Selegiline+Placebo": 46). Combined treatment with rotigotine and selegiline improved UPDRS III and UPDRS II+III scores versus selegiline alone (LS-mean [95% CI] treatment difference for UPDRS III: -4.89 [-7.87 to -1.91], p = 0.0015; for UPDRS II+III: -5.76 [-9.71 to -1.82], p = 0.0045). Higher proportion of patients in the "Selegiline+Rotigotine" group were classified as ≥20%, ≥25% or ≥30% responders (all p < 0.001). Combined treatment appeared more effective in patients aged ≤65 years versus > 65 years (although patient numbers in the subgroups were low). Adverse event profile was consistent with the known safety profile of rotigotine. CONCLUSIONS: In these post hoc analyses, adjunctive treatment with rotigotine in patients already receiving an MAO-B inhibitor improved UPDRS II+III score; this appeared to be largely driven by improvements in the motor aspects of PD.

Prescribing pattern and resource utilization of monoamine oxidase-B inhibitors in Parkinson treatment: comparison between rasagiline and selegiline.

Difference between selegiline and rasagiline for effectiveness in Parkinson's disease (PD) is uncertain, nevertheless their costs highly differ: rasagiline is more expensive than selegiline. This study was aimed to compare prescribing pattern and resource utilization in PD patients treated with rasagiline or selegiline. Historic cohort study, based on databases of three Italian Local Health Authorities was performed. Patients with PD and receiving rasagiline or selegiline between 01-07-2009 and 31-12-2011 were selected and followed-up for 12 months. As outcomes, and relevant costs, were evaluated: (a) anti-parkinson prescriptions; (b) hospitalization for PD and for fracture; (c) antiinflammatory and antirheumatic prescriptions; (d) antipsychotic prescriptions; (e) hospitalization for cardiovascular diseases; (f) cardiovascular prescriptions; (g) ambulatory visits or diagnostic tests. Average annual cost per patient was considered for both PD-related expenditure (a + b + c) and overall cost (a + b + c + d + e + f + g). Differences between rasagiline and selegiline were analysed by generalized linear model. Overall 1607 patients were selected: 63.7 % under selegiline and 36.2 % under rasagiline. Hospitalizations for PD occurred more in rasagiline group than in selegiline one (13.6 vs. 8.0 %, p < 0.001), whereas hospitalizations for fractures less in rasagiline group than in selegiline one (1.4 vs. 3.8 %, p = 0.005). Dopamine agonists (66.0 vs. 31.0 %, p < 0.001) and levodopa (73.9 vs. 49.0 %, p < 0.001) were prescribed more frequently in rasagiline group than in selegiline one. The choice to prescribe rasagiline produced a statistically significant increase in both overall cost (+2404 €, p < 0.001) and PD-related cost (+2363 €, p < 0.001). In conclusion, prescribing patterns and health resource utilization highly differ between rasagiline and selegiline. There is no homogeneous prescription behaviour among clinicians in preferring one or the other MOAB-I, on the basis of demographic, clinical and therapeutic characteristics of patients with PD.

A critical appraisal of the selegiline transdermal system for major depressive disorder.

The selegiline transdermal system (STS) is the first antidepressant transdermal medication approved by the US FDA for the treatment of major depressive disorder. Its unique antidepressant delivery system allows for steady release of selegiline over 24 h with minimal fluctuation in drug serum levels. It is able to deliver high enough central nervous system concentrations required for an antidepressant effect without substantially inhibiting Monoamine oxidase-A in the gastrointestinal and hepatic system, thereby reducing the risk of tyramine hypertensive crises especially at the lowest doses. Patient adherence theoretically could be improved due to ease of use and once-daily dosing when compared to oral counterparts' need for multiple daily doses. Clinical trials have established that doses between 6 and 12 mg over 24 h have been effective for major depressive disorder and tolerated among patients. Episodes of hypertensive crisis with STS have been minimally reported thus far. Overall, STS appears to be an effective agent for major depressive disorder when held to regulatory standards and post marketing analyses. This paper reviews the pharmacologic characteristics of STS and results of studies investigating its clinical efficacy and safety.

The effect of R-(-)-deprenyl administration on reproductive parameters of rat males.

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same strain. Subsequently, animals were killed by thiopental, and their blood and sperm were collected. We found that epididymis of males exposed to R-(-)-deprenyl had higher sperm count (P<0.05), and females who mated with these males gave birth to a greater number of offspring (P<0.05) compared to control. The blood of experimental animals contained higher levels of testosterone (P<0.05), FSH (P<0.01), and total antioxidants (P<0.01). We did not detect sperm DNA fragmentation in control or in experimental males. Interestingly, round spermatids were often observed inside seminiferous tubules of experimental animals, but obviously without any negative consequences on male fertility. Our findings could be verified on a sample of human male volunteers treated for infertility, because human organism tolerate higher doses of R-(-)-deprenyl, which is a selective inhibitor of monoamine oxidase B employed in our experiment and used in the therapy of Parkinson׳s disease, rather well.

A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents.

OBJECTIVE: A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features. METHODS: Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I). RESULTS: Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial. CONCLUSIONS: These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group.

Three cases of impulse control disorder in Parkinson's disease patients receiving dopamine replacement therapy.

Impulse control disorders (ICDs) are a known side effect of dopamine replacement therapy in patients with Parkinson's disease (PD). They can have devastating consequences for patients and their families.

Safety of selegiline transdermal system in clinical practice: analysis of adverse events from postmarketing exposures.

OBJECTIVE: The objective of this analysis is to present the safety profile of selegiline transdermal system (STS) in clinical practice after US Food and Drug Administration approval by analyzing reported postmarketing adverse events (AEs). METHOD: Deidentified data were obtained on AEs, regardless of causality, as collected and compiled in the pharmaceutical company's adverse event collection systems/databases after the launch of STS in the United States. All reports of hypertensive crisis, suicide attempts, and STS overdoses were carefully examined to independently determine relation of the AE to STS. RESULTS: From April 2006 to October 2010, a total of 3,155 AEs in 1,516 patients were reported (5.2% of the total exposures; N = 29,141), regardless of causality. The most frequently reported categories of AEs were general disorders (no. of AEs = 1,037, 3.6%) and central nervous system (CNS) disorders (no. of AEs = 574, 2.0%). A total of 266 reports (0.9%) were classified as serious AEs; CNS disorders (no. of AEs = 71, 26.7%) and cardiac and vascular disorders (no. of AEs = 44, 16.5%) were most common. There were 13 self-reports of possible hypertensive events or hypertension, although objective clinical data were not submitted in any of these cases. Thirteen drug-drug interactions (0.04%) were reported, and 5 were classified as serious. CONCLUSIONS: The most commonly reported AEs were application site reactions and insomnia. Very few patients reported a hypertensive event, and there were no objectively confirmed reports of hypertensive crisis with food at any STS dose. Therapeutic doses of STS appear to have a safety profile in clinical practice that is consistent with that observed in clinical trials. However, given the relatively modest exposure numbers, continued safety monitoring is recommended.

Cardiovascular baroreceptor activity and selective inhibition of monoamine oxidase.

Cardiovascular baroreceptor responsiveness of conscious rats treated with selective inhibitors of monoamine oxidase (MAO) types A and B was determined by measurement of blood pressure (BP) and heart rate (HR) responses to intravenous injection of phenylephrine and sodium nitroprusside. Treatment with selegiline (1 or 5 mg/kg p.o. daily for 7 days) did not significantly modify resting levels of BP and HR, lower or upper HR plateau levels, or HR/BP gain. Treatment with clorgyline (2 mg/kg p.o. daily for 7 days) increased HR/BP gain but also did not modify resting BP or HR, or lower and upper plateau levels of HR. The results are compatible with an effect of MAO-A inhibition to modify monoamine levels in medullary areas participating in CNS control of blood pressure.

Selegiline and rasagiline: twins or distant cousins?

Parkinson's disease is a complicated disease state that affects patients' quality of life. The first monoamine oxidase (MAO-B) inhibitor for PD, selegiline (Eldepryl), was approved by the Food and Drug Administration (FDA) in 1996, and rasagiline (Azilect) received FDA approval in 2006. At first, pharmacists may assume that rasagiline is just another me-too drug. There are three areas in which the two medications differ from each other: MAO type A inhibitors are found in high concentrations in the intestines, and MAO type B inhibitors are found mostly in the brain. If MAO-A inhibition occurs, the body cannot protect itself from exogenous amines such as tyramine. The absorbed tyramine can cause hypertensive crisis, also known as the cheese reaction. Selegiline's capsule product labeling includes a bolded warning that it "should not be used at daily doses exceeding 10 mg per day because of the risks associated with non-selective inhibition of MAO." It also says, "the selectivity of selegiline for MAO B may not be absolute, even at the recommended daily dose." The fact that rasagiline has the same effect has been challenged by two main-stream studies. Selegiline is a propargyl amphetamine derivative that undergoes extensive first-pass metabolism to L-methamphetamine and L-amphetamine. Rasagiline's major metabolite is amioindan, which has no amphetaminelike properties. Selegiline has been reviewed looking for neuroprotection, but studies have been unable to come to a definite positive neuroprotection conclusion. Proponents of rasagiline's neuroprotective effects also point to clinical studies in humans that demonstrate delayed and reduced need for future use of levodopa. In summary, selegiline and rasagiline look more and more like distant cousins instead of twins.

Tolerability and efficacy of switching from oral selegiline to Zydis selegiline in patients with Parkinson's disease.

Selegiline is a monoamine-B specific inhibitor used to treat Parkinson's disease. A Zydis sublingual preparation has more efficient absorption and less first pass amphetamine metabolites. We conducted an open label oral to Zydis switch study to evaluate tolerability of rapid switch, and relative efficacy, in 48 subjects from 5 sites. Overall patients preferred the Zydis preparation. Per clinician global impressions, fluctuations improved and the "on" UPDRS part II scores improved. Total UPDRS and measures of fatigue and sleep were unchanged. Adverse events were mild. Patients generally preferred the Zydis selegiline preparation but the modest difference is of unclear clinical significance given the open label nature of the trial.

MAO inhibitors: risks, benefits, and lore.

Monoamine oxidase (MAO) inhibitors were the first antidepressants introduced, but their use has dwindled because of their reported side effects, their food and drug interactions, and the introduction of other classes of agents. However, interest in MAO inhibitors is reviving. Here, we discuss their use, risks, and benefits in clinical medicine.