Antidepressant Medications Anti-depressant Drugs Antidepressant: tranylcypromine, Parnate
A white or almost white crystalline powder, odourless or with
a faint odour of cinnamaldehyde. Tranylcypromine sulphate
13.7 mg is approximately equivalent to 10 mg of tranycy
promine. Soluble in water; very slightly soluble in alcohol
and in ether: practically insoluble in chloroform.
Tranylcypromine, a non-hydrazine reversible MAO inhibitor, is
indicated for the symptomatic treatment of moderate to severe
depression. The drug may be used to treat psychotic depressive
states such as: Depressive phases of manic-depressive psychosis,
involutional melancholia, reactive depressions and psychoneurotic
depressions of moderate to severe intensity.
Pharmacokinetics
Tranylcypromine is readily absorbed from the gastro-intestinal
tract. peak plasma concentrations occurring about 1 to 3
hours after ingestion. It is excreted in the urine mainly in the
form of metabolites. Tranylcypromine has a reported plasma
elimination half-life of about 2.5 hours.
in 9 depressed patients. tranylcypromine absorption was rap-
id after oral dosing.' Absorption was biphasic in 7. Elimina-
tion was also rapid, with an elimination half-life of 1.54 to
3.15 hours. From 2 to 7 hours after dosing, standing systolic
and diastolic blood pressures were lowered, and standing
pulse was raised. The onset of the effect on standing systolic
blood pressure correlated with the time of peak plasma tran-
ylcypromine concentration. Maximum orthostatic drop of
blood pressure and rise in pulse rate occurred 2 hours after
dosing. Mean plasma tranylcypromine concentrations corre
lated with mean orthostatic drop of systolic blood pressure
and rise of pulse rate. Patients experiencing clinically signifi
cant hypotensive reactions to tranylcypromine may benefit
from changes in their dose regimen aimed at minimizing peak
concentrations.
Contraindications
In patients with cerebrovascular or cardiovascular disorders or a
history of recurrent or frequent headaches. As tranylcypromine may
cause blood pressure changes, administer with great care to patients
with confirmed or suspected cerebrovascular defect, hypertension or
cardiac disease. Regulate physical activity in the latter, as
tranylcypromine may suppress anginal pain. The drug should be used
with caution in individuals beyond the age of 60 because of the
possibility of existing cerebral sclerosis with damaged vessels.
In combination with certain drugs. Because the effect of many
antidepressant drugs may persist for 10 to 20 days, do not commence
tranylcypromine therapy within a week of discontinuing treatment
with such drugs; then use half the normal dosage for the first week.
Similarly, allow 1 week to elapse between the discontinuation of
tranylcypromine and the administration of any other drug that is
contraindicated with tranylcypromine.
Alcoholic beverages have been known to precipitate a severe
reaction. Therefore, the patient should avoid alcoholic drinks,
especially red wines (such as chianti), sherry and beer (including
non-alcoholic beer).
Patients on tranylcypromine therapy should also be advised not to
consume excessive amounts of caffeine in any form (coffee, tea, cola
drinks, etc.) because of possible enhanced effects of caffeine on
the CNS.
Adverse Side Effects
The most common adverse effect is insomnia, which can usually be
overcome by giving the last dose of the day not later than 3 pm, by
reducing the dose or by prescribing a mild hypnotic. Other possible
adverse effects include weakness, drowsiness, dizziness, dry mouth,
nausea, diarrhea, abdominal pain, or constipation. Tachycardia,
anorexia, edema, palpitation, blurred vision, chills, urinary
retention, sweating, impotence, tinnitus, muscle spasm and tremors,
paresthesia, skin rash and mild jaundice have been reported in rare
instances.
Serious hypertensive crises may occur in patients receiving
tranylcypromine. These responses are not usually dose related and
are associated with a distinctive reaction characterized by some or
all of the following symptoms: occipital headache which may radiate
frontally, palpitation, neck stiffness or soreness, nausea or
vomiting, sweating (sometimes with fever and sometimes with cold,
clammy skin) and photophobia. Either tachycardia or bradycardia may
be present, and associated constricting chest pain and dilated
pupils may occur. Intracranial bleeding, sometimes fatal in outcome,
has been reported in association with this paradoxical increase in
blood pressure. If a hypertensive reaction occurs, discontinue the
drug and institute hypotensive therapy. Headache tends to abate as
blood pressure lowers. Phentolamine mesylate (5 mg i.v.) is
recommended for use in acute cases. Do not use reserpine or
rauwolfia alkaloids parenterally as they may, paradoxically,
increase hypertension. For milder reactions injectable
chlorpromazine may be indicated. These drugs should be administered
with caution in order to avoid producing an excessive hypotensive
effect. Fever should be managed by means of external cooling. Other
symptomatic and supportive measures may be instituted if required.
Acute distress generally subsides in 24 hours or less.
Overdose
Characteristic symptoms are similar to those described under Adverse
Effects; however, these effects may be intensified and severe
additional manifestations may be seen, depending on the degree of
overdosage. Some patients exhibit insomnia, restlessness and
anxiety, progressing in severe cases to agitation, mental confusion
and incoherence. Hypotension, dizziness, weakness and drowsiness may
occur, progressing in severe cases to extreme dizziness and shock. A
few patients have displayed hypertension with severe headache and
other symptoms. Rare instances have been reported in which
hypertension was accompanied by twitching or myoclonic fibrillation
of skeletal muscles with hyperpyrexia, sometimes progressing to
generalized rigidity and coma.
Although tranylcypromine is rapidly excreted, its MAO inhibiting
action may continue for approximately 1 week. Treatment normally
consists of general supportive measures, close observation of vital
signs, and steps to counteract specific symptoms as they occur.
Adverse Effects :
As for MAOls in general (see Phenelzine).
Tranylcypromine has a stimulant action and insomnia
common side-effect if it is taken in the evening,
Hypertensive reactions are more likely to occur with trany
promine than with other MAOls, but severe liver damage
curs less frequently. Tranylcypromine should not be use
patients with hyperthyroidism.
Dependence. Dependence on tranylcypromine with toler
ance has been reported in patients receiving high doses '
or without a history of previous substance abuse.
Effects on the cardiovascular system. Although orthos-
tatic hypotension is the more common effect of MAOI on
blood pressure, hypertension can occur. A hypertensive crises
has been described in two patients after only one dose of
tranylcypromine· In the first case it was thought possible
that an autointeraction may have occurred between tranylcypromine and amphetamine to which it is partly metabolised.
In the second case the provocation of hypertension led to the
finding of a previously-undiagnosed phaeochromocytoma
and it was suggested this may have been a possibility in pre-
vious reports of hypertension induced by MAOls.
Porphyria. Tranylcypromine was considered to be unsafe in
patients with acute porphyria because it has been shown to be
porphyrinogenic in animals.
Drug Interactions: Alcohol / Possibility of excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, death Anesthetics, general / Hypotensive effect; use together with caution Antidepressants, tricyclic / Concomitant use excitation, sweating, tachycardia, tachypnea, hyperpyrexia, disseminated intravascular coagulation, delirium, tremors, convulsions, death. Antihypertensive drugs / Exaggerated hypotensive effects Beta-adrenergic blocking drugs / Exaggerated hypotensive effects Buspirone / Elevated BP Dextromethorphan / Brief episodes of psychosis or bizarre behavior Ephedra / See Sympathomimetic drugs below Fluoxetine / Possibility of hyperthermia, rigidity, myoclonic movements, death Ginseng / Risk of headache, mania, or tremors MAO Inhibitors / Concomitant use of tranylcypromine with other MAO inhibitors may cause a hypertensive crisis or severe seizures. Discontinue the MAO inhibitor at least 7-10 days before initiating a new drug. However, such combinations have been used together successfully Meperidine / See Narcotics Narcotics / Possibility of excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, death St. John's wort / Do not use with tranylcypromine Scotch broom herb / Risk of hypertensive crisis Selective serotonin reuptake inhibitors /See Fluoxetine Sympathomimetic drugs--amphetamine, cocaine, dopa, ephedrine, epinephrine, metaraminol, methyldopa, methylphenidate, norepinephrine, phenylephrine, phenylpropanolamine. Many OTC cold products, hay fever medications, and nasal decongestants contain one or more of these drugs / All peripheral, metabolic, cardiac, and central effects are potentiated for up to 2 weeks after termination of MAO inhibitor therapy. Symptoms include acute hypertensive crisis with possible intracranial hemorrhage, hyperthermia, coma, and possibly death Thiazide diuretics / Exaggerated hypotensive effects Tryptophan / Possibility of behavioral and neurologic effects, including disorientation, confusion, amnesia, delirium, agitation, hypomania, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillation,and Babinski signs Tyramine-rich foods--beer, broad beans, certain cheeses (Brie, cheddar, Camembert, Stilton), Chianti wine, chicken livers, caffeine, cola beverages, figs, licorice, liver, pickled or kippered herring dry sausage (Genoa salami, hard salami, pepperoni, Lebanon bologna), tea, cream, yogurt, yeast extract, and chocolate / Possible precipitation of hypertensive crisis, including severe headache, hypertension, intracranial hemorrhage, death Yeast, Brewer's / BP
Uses and Administration
Tranylcypromine. A cyclopropylamine derivative, is an MAOI
with actions and uses similar to those of Phenelzine .
It produces a less prolonged inhibition of the enzymes than
phenelzine.
Tranylcypromine is used in the treatment of depression,
the risks associated with traditional non-
selective MAOl.s such as tranylcypromine usually mean that
other antidepressants are preferred. It is given by mouth as the
sulphate in doses equivalent to tranylcypromine 10 mg in the
morning and 10 mg in the afternoon: If the response is inade-
quate after a week. 10 me may be given additionally at mid
day: a dosage of 30 mg daily should only be exceeded with
caution, although some authorities have allowed a maximum
dose of 60 mg daily. Once a satisfactory response has been
obtained the dosage may he gradually reduced for mainte-
nance, some patients may continue to respond to 10 mg daily.
Tranylcypromine should be withdrawn gradually to reduce
the risk of withdrawal symptoms.
Dosage
•Tablets Major depressive syndrome without melancholia.
Individualize the dose. Usual effective dose: 30 mg/day given in divided doses. If there are no signs of improvement in 2 weeks, the dose can be increased by 10 mg/day at intervals of 1 to 3 weeks, up to a maximum of 60 mg/day.