MAO inhibitors

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as powerful anti-depressants, as well as effective therapeutic agents for panic disorder and social phobia. They are particularly effective in treatment-resistant depression and atypical depression. They are also used in the treatment of Parkinson's disease and several other disorders. Reversible inhibitors of monoamine oxidase A (RIMAs) are a subclass of MAOIs that selectively and reversibly inhibit the MAO-A enzyme. RIMAs are used clinically in the treatment of depression and dysthymia. Due to their reversibility, they are safer in single-drug overdose than the older, irreversible MAOIs, and weaker in increasing the monoamines important in depressive disorder. RIMAs have not gained widespread market share in the United States. New research into MAOIs indicates that much of the concern over their supposed dangerous dietary side effects stems from misconceptions and misinformation, and that it is still underutilized despite demonstrated efficacy. New research also questions the validity of the perceived severity of dietary reactions, which has been based on outdated research. Despite this, many psychiatrists still reserve monoamine oxidase inhibitors as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed. MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety disorder and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOIs appear to be particularly effective in the management of bipolar depression according to a recent retrospective-analysis. There are reports of MAOI efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports. MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety. MAOIs appear to be particularly indicated for outpatients with dysthymia complicated by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feeling rejected. Newer MAOIs such as selegiline (typically used in the treatment of Parkinson's disease) and the reversible MAOI moclobemide provide a safer alternative and are now sometimes used as first-line therapy. People taking MAOIs generally need to change their diets to limit or avoid foods and beverages containing tyramine. If large amounts of tyramine are consumed, they may suffer hypertensive crisis, which can be fatal. Examples of foods and beverages with potentially high levels of tyramine include animal liver and fermented substances, such as alcoholic beverages and aged cheeses. Excessive concentrations of tyramine in blood plasma can lead to hypertensive crisis by increasing the release of norepinephrine (NE), which causes blood vessels to constrict by activating alpha-1 adrenergic receptors. Ordinarily, MAO-A would destroy the excess NE; when MAO-A is inhibited, however, NE levels get too high, leading to dangerous increases in blood pressure.