Academic journal article Perspectives in Psychiatric Care

Mechanisms of Antidepressant Action: In Brief

Academic journal article Perspectives in Psychiatric Care

Mechanisms of Antidepressant Action: In Brief

Article excerpt

After a 4-year hiatus, this column returns as a regular fixture of Perspectives. As before, the emphasis will be on biological aspects of understanding and/or treating mental disorders. It is an interesting time to reintroduce this column, because now we can look back on the "decade of the brain" in its entirety and begin assessing its impact on psychiatric care.

While the congressional pronouncement heartened many of us concerned with psychiatric nursing's pre-1990s reluctance to embrace biological constructs, it will be up to those with a greater breadth of vision to distill the decade's overall impact. It seems fair to say, even this early in the decade's review, that psychiatric nursing took the clarion call seriously and made substantial inroads into addressing the specialty's brain-related knowledge deficits. For example, in 1990 some psychiatric nursing textbooks still were alienating families with the suggestion that bad mothering (e.g., the schizophrenogenic mother) caused schizophrenia. You will not see such concepts in textbooks today. Further, all textbooks and journals now pay closer attention to psychotropic drugs and psychobiology than before the decade of the brain. Whether the overall field of psychiatric care evolved as hoped will be debated, but it is clear that important changes occurred in psychiatric nursing during those 10 years. This relaunching of Biological Perspectives aims at continuing a contribution to this momentum. In that vein, we address an area of psychiatric care undergoing significant change during the decade of the brain--antidepressant therapy.

During the 1990s and just before, a number of new antidepressant drugs were introduced: sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), bupropion (Wellbutrin), venlafaxine (Effexor), nefazodone (Serzone), mirtazapine (Remeron), and citalopram (Celexa). As new antidepressants, they empowered clinicians because they were, in Preskorn's (1994) words, "rationally developed." This rational development, or molecular targeting, starkly contrasted the serendipitous "discovery" of monoamine oxidase inhibitors (MAOIs) in 1952 (a better antituberculosis drug was sought) and tricyclic antidepressants (TCAs) in 1956 (a better antipsychotic was the goal). Prior to the selective serotonin reuptake inhibitors (SSRIs) and other "new" drugs mentioned above, clinicians had limited choices--for instance, when a TCA failed, the clinician was forced to stay "within class" or switch to the multiproblemed MAOIs. Since the numerous antidepressants available today provide improvement over the limited options of just a few years ago, it seems prudent to review just what makes them different from each other.

As it turns out, the array of antidepressant medications available today can be distinguished by at least seven distinct mechanisms of action; see Bezchlibnyk-Butler & Jeffries (1997) and Stahl (1998).

1. Blocking enzymatic breakdown. The MAOIs were the first antidepressants "discovered," and the only antidepressants inhibiting neurotransmitter breakdown as a primary mechanism of action. Monoamine oxidase can be found in the liver, intestines, and terminals of monoamine-producing neurons. This enzyme can be further differentiated into type A (metabolizes nor-epinephrine and serotonin) and type B (metabolizes dopamine). MAOIs inactivate monoamine oxidase, resulting in increased levels of monoamines (dopamine, norepinephrine, serotonin). The older, nonselective drugs (e.g., phenelzine, tranylcypromine) inhibit both types A and B, while newer agents such as moclobemide (inhibits type A) and selegiline (inhibits type B) are more selective. MAOIs are known to cause serious interactions with tyramine-containing foods and with a number of drugs, particularly indirect-acting sympathomimetics and serotonin-enhancing agents. MAOIs have a narrow therapeutic index.

2. Nonselective inhibition of norepinephrine and serotonin uptake. …

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