Phenelzine, which also goes by the brand name Nardil, is a first-generation MAO inhibitor. Nardil is both an antidepressant and anxiolytic (anxiety-reducer). Today, first-generation MAO inhibitors like phenelzine are rarely prescribed for depression except as a second or third line of treatment after other medications have failed. Nardil is one of the first effective antidepressants to be created; however, it comes with a high risk of complications and potentially harmful interactions with other drugs and certain foods. For this reason, patients must exercise caution when taking an MAO inhibitor like Nardil.
Phenelzine is an irreversible MAO inhibitor, meaning that the changes that that phenelzine affects in brain chemistry do not return to normal after the treatment is stopped. Though the changes remain in place, the levels of phenelzine are usually depleted in the body after about two to three weeks following the final dose. At this point, it’s safe to eat foods that conflict with Nardil and to begin taking other antidepressants like selective serotonin reuptake inhibitors (SSRIs) and tricyclics.
Phenelzine was invented in the 1950’s during the pharmaceutical industry’s first big push to mass produce mental health medications. Today, MAO inhibitors are prescribed for medication-resistant or atypical depression. It’s standard protocol for doctors to start the patients with safer alternatives like SSRIs and tricyclic antidepressants due to the lower risk of harmful side effects and drug interactions. SSRIs like Prozac also have a higher success rate than MAO inhibitors.
The mental health side effects of Nardil can include somnolence, lethargy, sedation, anorexia, insomnia, and, in rare cases, mania, hypomania, and psychosis. Severe symptoms of mania and psychosis are more likely to occur when patients have a history of high alcohol consumption, viral infection, liver damage, or are of old age. Phenelzine can also trigger nausea, vomiting, dizziness, dry mouth, blurry vision, weight fluctuation, high or low blood pressure, and sexual dysfunction, among others.
Nardil is not considered to be psychologically addictive in the same sense as other drugs. Stopping phenelzine treatment doesn’t typically result in drug cravings in the same way that stopping anti-anxiety medications like benzodiazepines (Xanax) or opioids do.
The federal government allows doctors and psychiatrists to prescribe Nardil for depression and anxiety as well as for a variety of other mental health disorders such as panic disorder (PD), dysthymia, bulimia, bipolar disorder, social anxiety disorder, and post-traumatic stress disorder (PTSD).
Nardil and other MAO inhibitors don’t mix well with other substances due to the risk of liver toxicity, high blood pressure, and other potential complications. Phenelzine is not an attractive drug to use when cutting and distributing illicit recreational substances like fake Xanax and MDMA (ecstasy).
MAO inhibitors like Nardil can lead to a hypertensive crisis when mixed with food or alcohol that contains the nutrient tyramine. Tyramine is a natural byproduct of fermentation and is present in large quantities in many types of alcohol and foods. Foods to be avoided when taking phenelzine include fermented products like cheese and many processed types of meat. Chocolate is also high in tyramine.
Nardil achieves its antidepressant and anti-anxiety effects by increasing the expression of several key neurotransmitters in the brain. MAO inhibitors like phenelzine prevent the breakdown of the monoamine neurotransmitters serotonin, melatonin, epinephrine, and norepinephrine. In a more round-about way, phenelzine increases the expression of GABA as well. GABA is a neurotransmitter that’s critical for reducing anxiety in patients with social anxiety disorder. The well-known anxiolytic medication Xanax operates by significantly boosting GABA levels in the brain.
Nardil is taken orally in pill form. It’s metabolized by the liver and reaches peak plasma concentrations within 43 minutes. The half-life of phenelzine is 11.6 hours.
Phenelzine remains active in the system of most patients for two to three weeks following their final dose. This is the amount of time it takes for the body to replenish its enzyme stores. However, because the effects of Nardil on brain chemistry are irreversible, the brain will continue to inhibit the breakdown of monoamine neurotransmitters indefinitely to some degree.
Phenelzine metabolites are excreted in the urine. After oral administration of a 30-mg dose of Nardil, 73% of the dose can be recovered in the urine after a period of 96 hours. Phenelzine does not need to be present in the blood to remain active. Frequently, a single 30 mg dose is plenty to maintain the effects of the drug.
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