Magazine article Clinical Psychiatry News

New MAO Inhibitors Offer Reversibility, Selectivity. (MAO Inhibitors Revisited)

Magazine article Clinical Psychiatry News

New MAO Inhibitors Offer Reversibility, Selectivity. (MAO Inhibitors Revisited)

Article excerpt

In contrast to classic monoamine oxidase (MAO) inhibitors, a new generation of compounds exists with respect to reversibility and selectivity for the two isoforms of MAO, said Andrew A. Nierenberg, MD, associate professor of psychiatry at Harvard Medical School in Boston.

The new compounds have just begun maing their way to the United States market. Use of the agents outside the U.S. to date suggests that they represent a potentially important new option for treatment of major depression.

Dr Nierenberg pointed out that MAO inhibitors were the first effective antidepressants. They remain viable options for treatment of typical depression, treatment-resistant illness, and the depressive phase of bipolar disorder. However, use of MAO inhibitors has been limited because of the potential for a tyramine effect and associated hypertensive crisis, necessitating a special diet and vigilance in monitoring for potential interactions with other drugs.

"We eat or drink something containing tyramine and we get a release of norepinephrine," said Dr Nierenberg. "If we inhibit intestinal monoamine oxidase A, we get in trouble. That's when the potential for a hypertensive crisis occurs. Fear of the hypertensive crisis has limited the use of MAO inhibitors and has really made most psychiatrists put the compounds much lower down on the list of medications we could be giving to our patients."

Problem Free?

The new generation of MAO inhibitors may be largely free of the problem areas that have limited use of classic inhibitors, which have been supplanted over the years by tricyclic antidepressants and, more recently, the selective serotonin reuptake inhibitors.

"In particular, the reversible inhibitors of monoamine oxidase A are free of the tyramine effect, so that no dietary restrictions are needed, and fewer adverse drug interactions occur," said Dr Nierenberg.

In comparing classic versus newer MAO inhibitors, Dr Nierenberg used the comparative analogy of "extra-strength glue versus stic-on notes." The classic compounds bind irreversibly to MAO, forming an essentially unbreaable bond. In contrast, the newer agents are characterized by reversible binding.

"Just lie self-stic notes, you can peel off the new compounds without leaving a mar," he commented.

The prototype for reversible MAO-A (RIMA) inhibitors is moclobemide, already on the maret in Europe. …

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