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Why are MAO inhibitors so rarely prescribed?

This article discusses trends in prescribing practice of MAO inhibitors, perceptions of MAO inhibitors among providers, and gaps in knowledge of MAO inhibitors among providers.

MAO inhibitors were the first prescription antidepressants in the U.S. and introduced to the market in the 1950s. [1] In the late 1950s, tricyclic antidepressants were introduced into the market. [2] Given the relative scarcity of antidepressants in the 1950s and 1960s, MAO were frequently used as a first-line treatments for major depression disorder. However, early reports of potentially fatal interactions with MAO inhibitors resulted in them quickly losing favor among prescribers. [3] Over the next few decades, with the introduction of novel treatments such as fluoxetine in 1988, MAO inhibitor use progressively declined. [2, 4-6]

 

 

In Canada, a study found that the yearly incidence rate or rate of new prescriptions for MAO inhibitors had dropped from 3.1 per 100,000 in 1997 to 1.4 per 100,000 in 2006. [7] The study also found that the prevalence or current rate of MAO inhibitor use has dropped from 400 in 1997 to 216 in 2006. The study’s authors concluded: “The low prescription rate of MAOIs is not consistent with the continued recommendation of MAOIs by expert opinion leaders and consensus guidelines for use in atypical depression and treatment-refractory depression. While their use appeared safe, heightened awareness of the potential risk of concomitant use of serotonergic agents is necessary. Relative underuse of the MAOIs for a significant subgroup of depressed patients with atypical and treatment-refractory depression remains a concern.”

 

 

In the U.S., a 1997 survey to psychiatrists with a response rate of 64% found that 12% of respondents never prescribed a MAO inhibitor, 27% had not prescribed a MAO inhibitor in at least 3 years, and 14% had last prescribed a MAO inhibitor between 1 to 3 years ago. [8] The study reported that the most frequent reasons respondents provided for not prescribing MAO inhibitors were concerns for side effects and drug interactions, preference for other treatments, and concerns for dietary restrictions with MAO inhibitor use. The study’s authors concluded: “The results document the commonly held view that practicing psychiatrists believe MAOIs are efficacious but use them infrequently, primarily due to concerns about side effects and drug interactions.” Similar reasons have been reported in other studies. [9-11]

 

 

Concerns for MAO inhibitor, while valid, use have found to be largely exaggerated. [9, 12-14] Dr. Gillman writes: “In an era when the tyramine content of foods was much higher (1960 to 1964) and MAOI users received no dietary guidance, only 14 deaths were reported among an estimated 1.5 million patients who took MAOIs.” [15] He goes on to write: “Very few foods now contain problematically high tyramine levels, that is a result of great changes in international food production methods and hygiene regulations.”

 

 

Nevertheless, MAO inhibitors have been effective in atypical and treatment-resistant depression [16-20] and anxiety disorders such as generalized anxiety disorder, panic disorder, and social phobia [21-26] with support from current FDA and professional society guidelines [27-34] and studies showing a 70% response rate with MAO inhibitors in these cases. [35, 36] Thus, many providers advocate for increased use of MAO inhibitors. [9, 37-41]

 

In many cases when MAO inhibitors do fail, it is often because inadequate doses are used. [3, 42-44]

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