Tranylcypromine

Tranylcypromine, sold under the brand name Parnate among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI). It is used primarily as an antidepressant in the treatment of major depressive disorder, including treatment-resistant depression. Along with phenelzine and isocarboxazid, tranylcypromine is one of the classic irreversible, non-selective MAOIs used in modern psychiatric practice. Tranylcypromine is also known as trans-2-phenylcyclopropyl-1-amine and is formed pro forma from the cyclization of amphetamine's isopropylamine side chain. As a result, it is classified structurally as a substituted phenethylamine and amphetamine, or more specifically as a phenylcyclopropylamine.

Medical uses Tranylcypromine is used to treat major depressive disorder, especially when depression has not responded sufficiently to other antidepressant treatments. Modern guidance on classic MAOIs recommends considering tranylcypromine, phenelzine, or isocarboxazid after insufficient response to other antidepressant treatments and before electroconvulsive therapy when a rapid treatment response is not required. Tranylcypromine may be particularly considered when psychomotor retardation is prominent or when depression has predominantly melancholic or endogenous features, although modern expert guidance cautions that a strict division between tranylcypromine for melancholic depression and phenelzine for anxious depression is not always clinically reliable. The typical effective dose range is 30–60 mg/day, and expert clinicians may use doses up to 80–100 mg/day when clinically indicated, with greater side-effect burden at higher doses. Some improvement may occur within days or weeks, but the full antidepressant effect of a given dose may take 4–6 weeks. In addition to major depressive disorder, tranylcypromine has been studied or used in other psychiatric conditions, including obsessive–compulsive disorder, panic disorder, and ADHD. Systematic reviews and meta-analyses have reported that tranylcypromine is significantly more effective in the treatment of depression than placebo and has efficacy over placebo similar to that of other antidepressants such as tricyclic antidepressants.

Contraindications and precautions Contraindications and precautions include:

Inability or unwillingness to follow the required dietary tyramine restrictions and medication precautions. Pheochromocytoma, because of the risk of severe hypertensive reactions. Porphyria. Serious or unstable cardiovascular or cerebrovascular disease, depending on individual risk assessment. Stable hypertension is not itself a contraindication to classic MAOI treatment, because MAOIs commonly lower blood pressure and may cause orthostatic hypotension. Hypertensive reactions during MAOI treatment are mainly associated with tyramine ingestion or interacting sympathomimetic drugs rather than ordinary baseline hypertension itself. Foods containing substantial amounts of tyramine, especially spoiled, aged, cured, fermented, or matured foods. This is a dietary restriction rather than a contraindication to treatment itself. Drugs with significant serotonin reuptake inhibition or serotonin-releasing activity, because of the risk of serotonin toxicity. Examples include selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, clomipramine, imipramine, tramadol, tapentadol, methadone, meperidine, dextromethorphan, dextropropoxyphene, pentazocine, levorphanol, and MDMA. Use with another classic irreversible MAOI is generally avoided outside a planned specialist-supervised switch, because full MAO-A and MAO-B inhibition is already expected and evidence for routine long-term dual-MAOI treatment is limited. This is distinct from medically supervised switching between phenelzine, tranylcypromine, and isocarboxazid, where modified washouts or cautious transitions have been used by some expert clinicians under close monitoring. Stimulant and sympathomimetic drugs vary in risk depending on mechanism, dose, and route. Medium- or high-dose amphetamines and MDMA are generally avoided because of monoamine-releasing activity, including serotonergic activity. Cocaine is also avoided because of potent monoamine reuptake inhibition and sympathomimetic cardiovascular effects. Low-dose amphetamines, ephedrine, and pseudoephedrine are relative rather than absolute contraindications; if used, reduced dosing, slow titration, and blood pressure monitoring are advised. Other stimulants or wakefulness-promoting agents, such as methylphenidate, modafinil, and bupropion, are not automatically contraindicated but require low starting doses, slow titration, and monitoring when combined with MAOIs. L-DOPA given without carbidopa may cause hypertensive reactions. Some specific antihypertensive drugs, such as methyldopa and reserpine, are generally avoided with MAOIs. Antihypertensive drugs as a class are not contraindicated. Certain anesthetic-related drugs require avoidance or special caution, especially serotonergic opioid analgesics such as meperidine (pethidine) and tramadol, as well as pancuronium, a muscle relaxant sometimes used with general anesthetics. Other opioids listed as serotonergic or uncertain-risk include methadone, tapentadol, dextromethorphan, dextropropoxyphene, pentazocine, and levorphanol. Up-to-date MAOI literature does not support routine discontinuation of MAOI treatment before surgery or general anesthesia. In most cases, potentially serious interactions can be avoided through careful selection or dose adjustment of anesthetic, analgesic, and vasopressor agents before, during, and after surgery; the MAOI should not be discontinued without consultation with the prescribing clinician.

Dietary restrictions

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