How long should a patient be off a MAOI before a different antidepressant is introduced?

Introduction

Monoamine oxidase inhibitors (MAOI) are antidepressant drugs with efficacy similar to other classes of antidepressant drugs. Originally developed for treatment of tuberculosis, MAOI were the first clinically effective modern antidepressant drugs Healy (1998). Although MAOI are no longer first line drugs for treatment of unipolar depression due to complex, unpredictable and often severe interactions with many food-derived amines and drug interactions, this class of drugs is still in clinical use.

MAOI increase monoamine levels in CNS and the peripheral tissues by inhibition of monoamine oxidase, a flavin-containing mitochondrial enzyme. Two forms of MAO, type A and type B, are non-selectively inhibited by classical MAO I. MAO-A is found in norepinephrine and serotonin neurons and regulates metabolic degradation of serotonin and catecholamines. This is thought to be the site of therapeutic action in depression. Classical MAOI irreversibly inhibit MAO and therefore side effects, drug interactions, and food interactions persist as long as two to three weeks following discontinuation of drug. The biochemical effect of MAOI to elevate serotonin and norepinephrine levels occurs rapidly. However, the therapeutic relief of depression requires several weeks of daily treatment. Selective and reversible MAO-A inhibitors are effective in treating major depression without many of the drug and food interactions associated with classical MAOI Baldessarini (2001), Yamada and Yasuhara (2004).

MAO-B is found in brain and regulates degradation of dopamine. Selective MAO-B inhibitors are used in the treatment of Parkinson's Disease and Alzheimer's Disease.

Parkinsonism

The monoamine oxidase inhibitors can be used in patients who have Parkinson’s disease, for two reasons. First, this is a disorder in which depression is common. Secondly, the selective type B inhibitor selegiline was originally thought to benefit patients with parkinsonism, possibly by increasing brain dopamine concentrations [26].

However, a long-term study showed higher death rates in patients with early mild Parkinson’s disease taking combined selegiline and levodopa compared with those taking levodopa alone. The authors concluded that the combination of selegiline with levodopa offers no advantage to patients with early mild Parkinson’s disease, and that although selegiline may help symptoms in advanced Parkinson’s disease it is best avoided in patients with postural hypotension, frequent falls, confusion, and dementia [27].

Dental consequences of MAOI

MAOIs can cause serious drug and food interactions. Interactions most relevant for the practicing dentist include the prolongation and enhancement of the CNS effects of the opioid analgesics, barbiturates, and other CNS depressants. MAOIs given in conjunction with meperidine cause potentially fatal reactions, including hyperthermia, excitement, and seizures, in addition to reactions that resemble an opioid overdose. Meperidine should not be used concurrently or for several weeks after therapy with MAOIs. Other opioids, which are not similar chemically to meperidine, may be used with caution.

Hypotension can develop with the concomitant use of general anesthetics and MAOIs. It is prudent to discontinue the use of MAOIs for 2 weeks before surgery. Neither epinephrine nor levonordefrin is potentiated by inhibition of MAO activity.

Monoamine oxidase (MAO) inhibitors

MAO inhibitors are medications that inhibit enzymes that break down monoamine neurotransmitters such as dopamine, serotonin, and norepinephrine. The levels of these neurotransmitters in the brain and peripheral nervous system therefore increase. MAOIs have been shown in double-blind, placebo-controlled studies to be helpful in treating re-experiencing symptoms in PTSD. The use of MAO inhibitors is contraindicated in patients with comorbid substance use because of potential life-threatening interactions with illicit drugs and alcohol. Patients on MAOIs also must adhere to a special diet devoid of foods and beverages with tyramine (an amino acid that interacts with neurotransmitters increased by MAOIs) in order to avoid potentially dangerous side effects. Many patients are not willing or reliably able to restrict their diet in this manner.

False Transmitters and Monoamine Oxidase Inhibition

MAOIs are powerful drugs used to treat depression and Parkinson disease. They include phenelzine, iproclozide, isocarboxazid, tranylcypromine, selegiline, rasagiline, and moclobemide. MAO catalyzes the oxidation of monoamines such as norepinephrine, serotonin (MAO-A), phenylethylamine (MAO-B), and dopamine (MAO-A,B). Dietary amines (e.g., tyramine derived from fermentation processes in cheese, wine, and beer) can cause a hypertensive reaction in patients taking MAOIs. In the presence of MAOIs, tyramine displaces norepinephrine from synaptic vesicles, leading to profound hypertension. When an indirect-acting sympathomimetic drug such as ephedrine is administered, an exaggerated BP increase can occur, especially in the first weeks of therapy with an MAOI. With long-term use, there is downregulation of adrenergic receptors, and TCAs and selective serotonin reuptake inhibitors are usually continued through the perioperative period given their rapid excretion and long latency period for effectiveness.51 MAOIs require discontinuation before surgery to allow restoration of enzyme activity. Irreversible MAOIs should be discontinued 2 weeks before surgery or switched to a reversible MAOI (moclobemide), which needs to be stopped only 24 hours before surgery.52 Because dopamine is a substrate for MAO, it should be administered at much lower doses in patients taking an MAOI or TCA. Use of meperidine with an MAOI can lead to hypertension, convulsions, and coma. Because of their risk for lethal dietary and drug interactions, MAOIs are generally used only when patients are unresponsive to first-line antidepressants.

PROBLEM ANALYSIS

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are a class of medications that block the degradation of dopamine, norepinephrine, and serotonin (5-hydroxytryptamine, or 5-HT). The MAOI phenelzine has been reported to be effective in decreasing intrusive thoughts and avoidant behaviors and in treatment of atypical depressive symptoms characterized by hypersomnia, hyperphagia, and comorbid symptoms of anxiety. The maximum daily dose is 60 mg, but some patients may tolerate a daily dose of up to 90 mg.

MAOIs are associated with anticholinergic side effects including dry mouth, urinary retention, constipation, and blurred vision. They can also cause orthostatic hypotension and sexual dysfunction. Because of their irreversible inhibitory effects, they can cause a fatal hypertensive crisis if ingested with food

Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOIs) are a group of antidepressant drugs that inhibit the action of monoamine oxidase (Brooker 2008). Monoamine oxidase is an enzyme that breaks down neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin.

Oral doses of essential oils increase the potential for an essential oil to have an effect on MAOIs (Tisserand & Young 2013). Eugenol inhibits monoamine oxidase A (MAOA) and there is a potential link between the antidepressant activity of eugenol and its MAOA inhibitory activity (Tao et al 2005). Large amounts (>50%) of eugenol are found in the essential oils from bud, leaf, and stem of clove (Syzygium aromaticum) and from cinnamon leaf (Cinnamomum verum). Therefore, these essential oils could affect MAOIs if taken orally.

Monoamine Oxidase Inhibitors

Traditional monoamine oxidase (MAO) inhibitors, which are both nonselective and irreversible, were the first effective drugs used for the treatment of depression. Only two drugs now on the market are included in the group of MAO inhibitors: phenelzine (Nardil) and tranylcypromine (Parnate). These drugs act by inhibiting the two forms of MAO—type A and type B. Inhibition of type A MAO results in the antidepressant effects seen with MAO inhibitors. More than 80% of type A MAO must be bound to serum proteins before adverse effects can be seen clinically. Resynthesis of new enzymes takes 10 to 14 days. If a patient is changing from an MAO inhibitor drug to a tricyclic drug, 2 weeks or more must elapse after the MAO inhibitor is stopped and the tricyclic agent is begun. Significant drug interactions may occur between MAO inhibitors and opioids and sympathomimetic amines. MAO inhibitors potentiate the depressant activity of opioids. They can produce a hypertensive crisis if combined with specific sympathomimetic amines (see Table 29-7).4,10,24

Phenylethylamine and phenylephrine must not be given to patients who are taking MAO inhibitors. MAO metabolizes these agents, and their use with an MAO inhibitor could lead to significant potentiation of their pressor effects (see Chapter 4). These adverse effects are not seen with epinephrine and levonordefrin. Many OTC cold remedies contain phenylephrine and should not be prescribed for patients who are taking MAO inhibitors (see Table 29-7).

Tyramine is a naturally occurring amine that releases norepinephrine from sympathetic nerve endings. Dietary tyramine is deaminated by gastrointestinal MAO-A. In the presence of MAO inhibitors, dietary tyramine is rapidly absorbed into the circulation, and a hypertensive crisis may result. Patients taking these agents must therefore avoid foods that contain high concentrations of tyramine. Such foods include aged foods such as cheeses, red wines, and pickled fish, as well as bananas and chocolate.4,10,24