Monoamine+Oxidase+Inhibitors

 Monoamine Oxidase Inhibitors were the first oral antidepressant that was developed and introduced during the 1950’s, and which was originally used as a treatment for tuberculosis (Wimbiscus, 2010) . However, there was a decline in their prescription and use with the introduction of tricyclic antidepressants and then eventually SSRIs in the 1980’s ( Amsterdam, 2006) . As a result, they are now typically used as third or fourth-line options in the treatment of depression (Wimbiscus, 2010) . Reasons for this decline in use that are most commonly mentioned include the possible drug interactions and dietary restrictions that are associated with MAOI use, side effects, and preference for other treatments (Wimbiscus, 2010).

Another reason for this decline has been the increased number of pharmacologic tools that psychiatrists now have access to; further, physicians nowadays have less experience with these medications and are less inclined to prescribe its use (Fiedorowicz & Swartz, 2004). In a survey done by the Michigan Psychiatric Association in 1999, the findings indicated that 12% of psychiatrists admitted to never prescribing an MAOI to a patient, and 27% had not done so in the past 3 years (Fiedorowicz & Swartz, 2004). Only 2% of them reported regular use, compared to 24% only a decade earlier.

MAOI therapy has been shown to be an effective treatment of Major Depressive Disorder (MDD) with melancholic features, MDD with psychotic features, bipolar major depression, dysthimic disorder, and “double” depression. Effectiveness has also been shown as maintenance therapy in patients with recurrent MDD.

MAOIs work as monoamine agonists by increasing the levels of monoamines (serotonin, norepinephrine) by inhibiting monoamine oxidase, an enzyme that metabolizes the monoamine neurotransmitters (text2). MAOIs are categorized into two subtypes; isoenzyme A (MAOA) and isoenzyme-B (MAOB) (Wimbiscus, 2010). MAOA is primarily found within the intenstinal tract, sympathetic nerves and liver adrenal glands, while MAOB is mostly found in the brain and liver (Wimbiscus, 2010). MAOA is implicated in the antidepressant properties of MAOIs because of its specific metabolic actions to serotonin, norepinephrine, and tyramine (Fiedorowicz & Swartz, 2004). Being responsible for the degradation of tyramine, and its location in the intestinal tract, it is inhibition of MAOA that is largely associated with the dietary restrictions associated with MAOIs (Wimbiscus, 2010).


 * Dietary Restrictions **

Individuals who are taking MAOIs must be careful of the things they ingest due to the risk of hypertensive crises that are associated with the consumption of tyramine rich foods/drink (Wimbiscus, 2010).Tyramine is an amine that also acts as an elevator of blood pressure; typically it has no effect because it is rapidly metabolized in the liver by MAO, but when an individual is taking MAOIs this enzyme is inhibited and there is a risk of stroke as a result of the increase in blood pressure (Pinel, 2009, p.464) .

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Historically, these restrictions have <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">been very harsh; recent studies have determined that, through examination of tyramine content of foods, less than 6mg per serving will generally provide no symptoms or health risks. That being said, absolute dietary restrictions that an individual must adhere to include;
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;"> Aged cheeses and meats
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Banana peels
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Broad bean pods
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Spoiled meats
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Marmite
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Sauerkraut
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Soybean products
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%; line-height: 1.5;">Draft beers

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Typically, upon cessation of MAOI use, the individual is also advised to take 2 weeks before eating anything on the previous list (Wimbiscus, 2010).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">As of 2006, the development of a transdermal patch (selegiline patch) boasts that no tyramine restrictions are required, due to the lower dosage (Amsterdam, 2006)(Wimbiscus, 2010) <span style="background-color: #ffffff; font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">.


 * <span style="font-family: Arial,sans-serif; font-size: 14.5pt;">Side Effects **

<span style="font-family: Arial,sans-serif; font-size: 10.5pt;">Aside from the hypertensive reactions to tyramine, a potentially fatal syndrome known as Serotonin Syndrome can occur if an individual combines serotonergic antidepressants with MAOIs <span style="background-color: #ffffff; font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">(Fiedorowicz & Swartz, 2004).

<span style="font-family: Arial,sans-serif; font-size: 10.5pt;">The symptoms of this syndrome are typically divided into three categories:
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Mental status changes
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Motor symptoms
 * <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Autonomic instability

<span style="font-family: Arial,sans-serif; font-size: 10.5pt;">Overdoses can occur while on MAOIs, and involve severe Central Nervous System (CNS) excitation and an decrease in sympathetic nervous system function <span style="background-color: #ffffff; font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">(Fiedorowicz & Swartz, 2004) <span style="font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">. This manifests in a number of ways, including:
 * <span style="font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">Neuromuscular irritability
 * <span style="font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">Hyperthermia
 * <span style="font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">Hyper- or hypotension
 * <span style="font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">Arrhythmias

<span style="font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">These overdoses can be fatal if there is a lack of supportive care and any individual believed to be overdosing should be put under observation if they are experiencing these symptoms <span style="background-color: #ffffff; font-family: Arial,sans-serif; font-size: 10.5pt; line-height: 1.5;">(Fiedorowicz & Swartz, 2004).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Treatment Efficacy
<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Numerous studies have found that MAOIs are effective treatments in the management of major depressive disorder, specifically Atypical Depression, Treatment Resistant Major Depressive Disorder (MDD) and Bipolar Depression (Wimbiscus, 2010).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">In Bipolar Depression, there is evidence that MAOIs elicit a preferential response over Tricyclic Antidepressants (Fiedorowicz & Swartz, 2004). Additionally, the use of antidepressants for bipolar depression includes a risk of triggering a period of mania in some patients; however, MAOIs have been suggested to trigger milder manic states than has been found with other antidepressant (Pinel, 2009, p.465).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Treatment Resistant Depression (TRD) occurs along a continuum; early stage is characterized by a lack of response to initial antidepressant treatment, while advanced stage involves lack of response to at least three prior antidepressant treatments.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">New advances in MAOI therapy has included the introduction of a transdermal system of administration that increases the safety of MAOIs <span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">(Fiedorowicz & Swartz, 2004). The side effects of MAOIs are reduced as a result of transdermal administration because it bypasses the MAOA found in the intenstines and thus does not inhibit its metabolic ability in this location; consequently, orally ingested tyramines that are found in a wide variety of foods and drinks are able to be degraded and thus reduces the risk previously associated (Fiedorowicz & Swartz, 2004).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Despite compelling evidence-based data indicating that MAOI therapy is effective in TRD, physicians continue to avoid the use of these agents as a result of a scarcity of modern, controlled clinical trials with MAOIs in TRD. Without much clinical data, the reluctance and fears of MAOI use can be perpetuated (Amsterdam, 2006).