Phenelzine

Brand Names: Nardil

Clinical Names: Phenelzine

Summary

generic name: Phenelzine

trade name: Nardil®

type of drug: Antidepressant, specifically monoamine oxidase (MAO) inhibitor.

used to treat: Depression, particularly in the treatment of depressed patients with mixed anxiety and depression and phobic or hypochondriacal features and are clinically characterized as “atypical”, “nonendogenous” or “neurotic”.

adverse drug effects: The most important reaction associated with phenelzine administration is the occurrence of hypertensive crises, which have sometimes been fatal.

overview of interactions:
• nutrients affecting drug performance and toxicity: Sympathomimetic substances, including Tryptophan, Tyrosine

• diet affecting drug performance and toxicity: Tyramine-containing Foods

• food affecting drug performance and toxicity: Aspartame (NutraSweet®)

• food affecting drug performance and toxicity: Caffeine or Chocolate

• nutrient affected by drug: Vitamin B6 (Pyridoxine)

• herb affecting drug performance and toxicity: Cytisus scoparius (Scotch Broom)

• herb affecting drug performance and toxicity: Eleutherococcus senticosus (Siberian Ginseng)

• herb affecting drug performance and toxicity: Ephedra sinica, Ephedra vulgaris (Ma Huang)

• herb affecting drug performance and toxicity: Panax ginseng (Chinese Ginseng)

• herb affecting drug performance and toxicity: Passiflora incarnata (Passion Flower)

• herb affecting drug performance and toxicity: Rauwolfia serpentina (Rauwolfia)

• herb affecting drug performance and toxicity: Selenicereus grandiflorus (Night Blooming Cereus)



Interactions

nutrients affecting drug performance and toxicity: Sympathomimetic substances, including Tryptophan, Tyrosine

• mechanism: The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises. Individuals taking phenelzine should avoid sympathomimetic drugs (including amphetamines, cocaine, methylphenidate, dopamine, epinephrine and norepinephrine), or related compounds (including methyldopa, L-dopa, L-tryptophan, L-tyrosine and phenylalanine).
(Alvine G, et al. J Clin Psychiatry 1990 Jul;51(7):311; Goff DC. Am J Psychiatry 1985 Dec;142(12):1487-1488; Levy AB, et al. Can J Psychiatry 1985 Oct;30(6):434-436; Threlkeld DS. Facts and Comparisons Drug Information, Apr 1997.)

diet affecting drug performance and toxicity: Tyramine-containing Foods

• nutritional concerns: Hypertensive crises during phenelzine therapy may also be induced by consumption of foods with a high concentration of tyramine or dopamine. Consequently patients being treated with phenelzine should avoid high protein food that has undergone protein breakdown by aging, fermentation, pickling, smoking or bacterial contamination; patients should also avoid cheeses (especially aged varieties), pickled herring, beer, wine, liver, yeast extract (including brewer's yeast in large quantities), dry sausage (including Genoa salami, hard salami, pepperoni and Lebanon bologna), pods of broad beans (fava beans) and yogurt. Individuals with concerns about phenelzine and tyramine-containing foods should discuss the issue with their prescribing physician, pharmacist, or a nutritionally-trained healthcare professional. .
(Bieck PR. Psychiatr Prax 1989 Aug;16 Suppl 1:25-31.)

food affecting drug performance and toxicity: Aspartame (NutraSweet®)

• report: Reports have been published of two cases were reported involving men who were being treated with phenelzine and experienced restlessness, agitation, tremor, and insomnia after drinking large quantities of cola drinks containing aspartame.
(Shader RI, Greenblatt DJ. J Clin Psychopharmacol 1985 Apr;5(2):65.)

food affecting drug performance and toxicity: Caffeine or Chocolate

• nutritional concerns: Excessive amounts of caffeine or chocolate can also potentiate hypertensive reactions. Also, reports have been published of two cases were reported involving men who were being treated with phenelzine and experienced restlessness, agitation, tremor, and insomnia after drinking large quantities of cola drinks containing aspartame.
(Shader RI, Greenblatt DJ. J Clin Psychopharmacol 1985 Apr;5(2):65.)

nutrient affected by drug: Vitamin B6 (Pyridoxine)

• research: There have been several reports of Vitamin B6 (Pyridoxine) deficiency and peripheral neuropathy associated with long-term phenelzine therapy. Likewise, isoniazid and hydralazine, drugs with chemical structures similar to phenelzine, are known to cause vitamin B6 deficiency.
(Demers RG, et al. South Med J 1984 May;77(5):641-642; Heller CA, Friedman PA. Am J Med 1983 Nov;75(5):887-888; Goodheart RS, et al. Aust N Z J Med 1991 Jun;21(3):339-340.)

• nutritional support: Individuals using phenelzine should discuss the issue of potential depletion of Vitamin B6 with their prescribing physician or a nutritionally-trained healthcare professional, especially if they have experienced any symptoms of peripheral neuropathy. Vitamin B6 levels can be monitored and any course of supplementation should be supervised.
(Demers RG, et al. South Med J 1984 May;77(5):641-642; Heller CA, Friedman PA. Am J Med 1983 Nov;75(5):887-888; Goodheart RS, et al. Aust N Z J Med 1991 Jun;21(3):339-340.)

herb affecting drug performance and toxicity: Cytisus scoparius (Scotch Broom)

• mechanism: Scotch Broom contains high levels of tyramine.

• herbal concerns: Consumption of Scotch Broom by an individual taking phenelzine carries a significant risk of MAOI-type reactions which could include symptoms such as diarrhea, sweating, flushing, high or irregular blood pressure, and pounding chest. However, it is likely that an individual would have to consume a large amount of the plant to trigger such a response.

herb affecting drug performance and toxicity: Eleutherococcus senticosus (Siberian Ginseng)

• mechanism: Eleutherosides could theoretically potentiate the drug's action. However, no substantive research has confirmed this speculation.

herb affecting drug performance and toxicity: Ephedra sinica, Ephedra vulgaris (Ma Huang)

• mechanism: Ephedrine, as well as other alkaloidal constituents of Ephedra, may produce adverse interactions with phenelzine.

• herbal concerns: Ephedra and ephedrine-containing substances should be avoided during phenelzine therapy. Individuals with concerns about phenelzine and ephedra/ephedrine should consult with their prescribing physician, pharmacist, or an herbally-trained healthcare professional.
(Threlkeld DS. Apr 1997)

herb affecting drug performance and toxicity: Panax ginseng (Chinese Ginseng)

• mechanism: The triterpene glycosides in Panax ginseng could theoretically potentiate the drug's action. However, despite a lengthy discussion on the potential for such an adverse interaction and a handful of sometimes questionable case reports, as of yet, no substantive research has confirmed this speculation.
(Jones BD, Runikis AM. J Clin Psychopharmacol 1987 Jun;7(3):201-202; Shader RI, Greenblatt DJ. J Clin Psychopharmacol 1988 Aug;8(4):235; Staba EJ. Lancet 1985 Dec 7;2(8467):1309-310; Barna P. Lancet 1985 Sep 7;2(8454):548; Shader RI, Greenblatt DJ. J Clin Psychopharmacol 1988 Aug;8(4):235.)

herb affecting drug performance and toxicity: Passiflora incarnata (Passion Flower)

• mechanism: Indole alkaloids could theoretically potentiate the drug's action. However, no substantive research has confirmed this speculation.

herb affecting drug performance and toxicity: Rauwolfia serpentina (Rauwolfia)

• mechanism: Indole alkaloids. MAO inhibitors inhibit the destruction of serotonin and norepinephrine, which are believed to be released from tissue stores by rauwolfia alkaloids.

• herbal concerns: Caution should be exercised when rauwolfia is used concomitantly with an MAO inhibitor, including phenelzine.

herb affecting drug performance and toxicity: Selenicereus grandiflorus (Night Blooming Cereus)

• mechanism: Isoquinoline could theoretically potentiate the drug's action. However, no substantive research has confirmed this speculation.

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

References

Alvine G, Black DW, Tsuang D. Case of delirium secondary to phenelzine/L-tryptophan combination. J Clin Psychiatry 1990 Jul;51(7):311. (Letter)

Barna P. The case of ginseng. Lancet 1985 Sep 7;2(8454):548.

Bieck PR. [Hypertensive crises with reversible inhibitors of monoamine oxidases? Results of tyramine interaction studies]. Psychiatr Prax 1989 Aug;16 Suppl 1:25-31. [Article in German]
Abstract: Healthy ambulatory subjects took 6 different MAO inhibitors (MAOIs) orally for 2 to 4 weeks. The new reversible MAO-A inhibitors brofaromine and moclobemide were compared with the irreversible MAOIs clorgyline, selegiline, phenelzine and tranylcypromine. Pressor responsiveness to oral tyramine was assessed before, during and after treatment. In unmedicated subjects, doses of tyramine to raise systolic blood pressure by at least 30 mmHg (PD30) ranged between 200 and 800 mg. During treatment with MAOIs, the PD30 decreased. The ratio of median effective doses (ED50) of tyramine (pre- vs post-treatment) was: selegiline 5, moclobemide 7, brofaromine 10, clorgyline 10, phenelzine 13 and tranylcypromine 55. Pressor responsiveness normalized within 8 days after stopping the reversible MAOIs and 30 days after tranylcypromine. The increased sensitivity after phenelzine persisted for longer than 8 weeks and after clorgyline for longer than 15 weeks. The results suggest that the two reversible MAO-A inhibitors moclobemide and brofaromine carry a much reduced liability to tyramine-related hypertensive reactions.

Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14-20.

Demers RG, McDonagh PH, Moore RJ. Pyridoxine deficiency with phenelzine. South Med J 1984 May;77(5):641-642.
Abstract: Pyridoxine (vitamin B6) deficiency developed in two young men treated with phenelzine. Alleviation of symptoms possibly associated with this deficiency and correction of subnormal serum B6 levels occurred with the administration of pyridoxine. With the increased use of phenelzine, all physicians should be alert to this potential problem and instruct patients to eat an adequate amount of foods containing B6. If untoward reactions occur during phenelzine treatment, B6 deficiency should be considered.

Diamond S, Pepper BJ, Diamond ML, Freitag FG, Urban GJ, Erdemoglu AK. Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports. Neurology 1998 Jul;51(1):274-276.
Abstract: With the use of the newer antidepressants beyond the traditional tricyclics and monoamine oxidase inhibitors, newer options in headache prophylaxis are provided as well as the potential for undesirable and even potentially life-threatening interactions between medications. In this article, four patient reports of a specific interaction--the serotonin syndrome--are presented. These events resulted from transitioning headache patients from an older antidepressant (phenelzine) to a newer antidepressant (venlafaxine).

Dyck LE, Dewar KM. Inhibition of aromatic L-amino acid decarboxylase and tyrosine aminotransferase by the monoamine oxidase inhibitor phenelzine. J Neurochem 1986 Jun;46(6):1899-1903.
Abstract: The concentration of p-tyramine in the rat striatum was increased significantly by intraperitoneal injection of phenelzine (5 or 100 mg/kg). Unlike other monoamine oxidase (MAO) inhibitors, phenelzine had no effect on p-tyramine levels in the first 1-2 h following injection. The high dose of phenelzine increased the p-tyramine levels much more than the low dose. In addition, the high dose of phenelzine increased striatal p-tyrosine levels significantly 12 h after injection. Further studies showed that phenelzine inhibited the tyrosine aminotransferase activity of rat liver homogenates; the IC50 was 50 microM. Phenelzine also inhibited the aromatic L-amino acid decarboxylase activity of rat brain homogenate with an IC50 of 25 microM. Following intraperitoneal injection of 100 mg/kg phenelzine, the initial concentration of phenelzine in the striatum appears to be high enough to inhibit aromatic L-amino acid decarboxylase. It is suggested that the multiple enzyme inhibition caused by administration of high doses of phenelzine accounts for its unusual effects on striatal p-tyramine levels compared with other MAO inhibitors, i.e., its initial lack of effect on p-tyramine levels followed later by very large increases in p-tyramine levels.

Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998 Oct;54(8):589-594.
Abstract: This paper provides a systematic review of adverse drug reactions (ADRs) associated with the use of extracts of the herb St. John's wort (Hypericum perfbratum L.) for the treatment of mild to moderate depression. METHODS: Searches of four computerized literature databases were performed for records of (ADRs). Manufacturers of hypericum products, the international drug monitoring centre of the World Health Organization (WHO) and the national drug safety monitoring bodies of Germany and the United Kingdom were also contacted for information. RESULTS: Information on (ADRs) originates from case reports, clinical trials, post-marketing surveillance and drug monitoring studies. Collectively, the data suggest that hypericum is well tolerated, with an incidence of adverse reactions similar to that of placebo. The most common adverse effects are gastrointestinal symptoms, dizziness/confusion and tiredness/sedation. A potential serious adverse effect is photosensitivity, but this appears to occur extremely rarely. CONCLUSIONS: Hypericum has an encouraging safety profile. However, as most of the current data originate from short-term investigations, more long-term studies are desirable.

Evans DL, Davidson J, Raft D. Early and late side effects of phenelzine. J Clin Psychopharmacol 1982 Jun;2(3):208-210.

Fankhauser C, Charieras T, Caille D, Rovei V. Interaction of MAO inhibitors and dietary tyramine: a new experimental model in the conscious rat. J Pharmacol Toxicol Methods 1994 Dec;32(4):219-224.
Abstract: The aim of this study was to assess a new model for tyramine-induced pressor effects in the rat. The predictivity of the test is improved by simulating the real clinical situations where tyramine is ingested with food and beverages containing the amine. The pressor effect was investigated after oral administration of tyramine in a feed preparation or in a water solution by continuously recording blood pressure just above the aorta junction via a left-carotid catheter. The response was quantified by measurement of peak systolic blood pressure and as the percentage of tyramine-sensitive rats (TSR) in which the maximal pressor response to the amine was higher than 30 mm Hg (clinical risk threshold). Tyramine elicited, after oral administration (by gavage), a statistically significant dose-dependent increase in blood pressure from the dose of 10 mg/kg in solution (i.e. 23 +/- 3 mm Hg, N = 36) and 40 mg/kg in feed preparation (i.e., 20 +/- 2 mm Hg, N = 26). Almost all rats showed a systolic blood pressor increase higher than 30 mm Hg after oral administration of tyramine at a dose of 80 mg/kg p.o. in solution (TSR = 96%). Administration of tyramine in food (80 mg/kg) significantly delayed the time of the peak blood pressure (13 +/- 2 min instead of 7 +/- 0.5 min in solution, p < .001). Under these conditions, the tyramine threshold dose of TYR 30 (dose inducing an average response equivalent to the clinical risk threshold) was 14 mg/kg p.o. in solution and 67 mg/kg p.o. in feed preparation, respectively.

Goff DC. Two cases of hypomania following the addition of L-tryptophan to a monoamine oxidase inhibitor. Am J Psychiatry 1985 Dec;142(12):1487-1488.
Abstract: The combination of L-tryptophan and a monoamine oxidase inhibitor (MAOI) has been reported to be an effective antidepressant regimen. Neurotoxicity has previously been associated with this combination. The author presents two cases of hypomania following the addition of L-tryptophan to an MAOI.

Goodheart RS, Dunne JW, Edis RH. Phenelzine associated peripheral neuropathy -- clinical and electrophysiologic findings. Aust N Z J Med 1991 Jun;21(3):339-340.
Abstract: Phenelzine associated sensorimotor peripheral neuropathy is reported in two patients. Symptoms were predominantly sensory, and improvement occurred after withdrawal of phenelzine. Electrophysiologic findings were consistent with an axonal process.

Heller CA, Friedman PA. Pyridoxine deficiency and peripheral neuropathy associated with long-term phenelzine therapy. Am J Med 1983 Nov;75(5):887-888.
Abstract: A 51-year-old, nonalcoholic, nondiabetic woman with sensorimotor peripheral neuropathy and pyridoxine deficiency associated with long-term phenelzine therapy is described. Since phenelzine, like hydralazine and isoniazid, is a hydrazine capable of reducing pyridoxine levels in the rat, it is suggested that phenelzine, like hydralazine and isoniazid, may cause a pyridoxine-responsive peripheral neuropathy in humans.

Hölzl J, Demisch L, Gollnik B. Investigations about antidepressive and mood changing effects of Hypericum perforatum. Planta Med 1989;55:643.

Hunter KR, Boakes AJ, Laurence DR, Stern GM. Monoamine oxidase inhibitors and L-dopa. Br Med J 1970 Aug 15;3(719):388.

Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol 1987 Jun;7(3):201-202. (Letter)

Levy AB, Bucher P, Votolato N. Myoclonus, hyperreflexia and diaphoresis in patients on phenelzine-tryptophan combination treatment. Can J Psychiatry 1985 Oct;30(6):434-436.
Abstract: Three cases are presented on patients on an MAOI who developed a transient syndrome of myoclonus, hyperreflexia, jaw quivering, teeth chattering and diaphoresis after L-Tryptophan was added. Caution is advised when considering the addition of a serotonergic agent to MAOI's.

Marley E, Wozniak KM. Interactions of non-selective monoamine oxidase inhibitors, tranylcypromine and nialamide, with inhibitors of 5-hydroxytryptamine, dopamine or noradrenaline re-uptake. J Psychiatr Res 1984;18(2):191-203.
Abstract: Rats pretreated with tranylcypromine and given clomipramine, developed head and body twitches, forelimb flexor-extensor movements and wet dog shakes, phenomena which failed to develop when pretreatment incorporated p-chlorophenylalanine (PCPA) but were unabated when this included alpha-methyl-p-tyrosine (AMPT). Locomotor activity, itself enhanced by tranylcypromine, was further and significantly elevated compared to saline, by clomipramine or imipramine in grouped rats (n = 3) but not in single or paired rats; desipramine lacked such action. This effect of clomipramine was prevented when PCPA was incorporated into the pretreatment and that of imipramine by including PCPA or AMPT. Brain monoamine oxidase (MAO) A inhibition was 92% and that of MAO B, 80%. Cortical hydroxytryptamine (5-HT) and noradrenaline concentrations as well as hypothalamic 5-HT, were significantly elevated by tranylcypromine, as was dopamine in the striatum, nucleus accumbens and tuberculum olfactorium. Hyperthermia developed in tranylcypromine pretreated rats given paroxetine or fluoxetine. Myoclonic phenomena were elicited by paroxetine, fluoxetine, clomipramine or imipramine in nialamide pretreated rats but these were less intense than in rats pretreated with phenelzine or tranylcypromine. Fatalities were fewer than in rats pretreated with tranylcypromine or phenelzine. Brain MAO A inhibition was 92% and that of MAO B, 69%.

Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998 Nov 9;158(20):2200-2211. (Review)

Shader RI, Greenblatt DJ. Bees, ginseng and MAOIs revisited. J Clin Psychopharmacol 1988 Aug;8(4):235. (Editorial)

Shader RI, Greenblatt DJ. Phenelzine and the dream machine-ramblings and reflections. J Clin Psychopharmacol 1985 Apr;5(2):65. (Editorial)

Staba EJ. Ginseng. Lancet 1985 Dec 7;2(8467):1309-1310.

Threlkeld DS, ed. Central nervous system drugs, antidepressants, monoamine oxidase inhibitors. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1997.

Tordoff SG, Stubbing JF, Linter SP. Delayed excitatory reaction following interaction of cocaine and monoamine oxidase inhibitor (phenelzine). Br J Anaesth 1991 Apr;66(4):516-518.
Abstract: A case report is presented in which a patient receiving the monoamine oxidase inhibitor, phenelzine, developed a delayed excitatory reaction following administration of topical cocaine spray during anaesthesia for vocal cord surgery. The pharmacological basis of the drug interaction is discussed.

Upton, R. Ed. St. John’s wort, Hypericum perforatum. In: American Herbal Pharmacopoeia and Therapeutic Compendium, Santa Cruz, CA: AHP, 1997.