Term usually applied to chemical treatments for DEPRESSION, though also applies to other physical treatments, such as ELECTROCONVULSIVE THERAPY (ECT). Chemical antidepressants were first recognized by clinical observation in the late 1950s and early 1960s amongst substances being developed for other purposes: the MONOAMINE OXIDASE INHIBITORS (MAOIs), for example, emerged from a group of drugs targeted at tuberculosis. The earliest of the modern antidepressant agents used in clinical practice today were thus discovered, rather than designed.
Antidepressants are broadly classified in terms of their chemical structure or mode of action. Most act in some way to increase the availability of monoamines at the SYNAPTIC CLEFT (see MONOAMINE HYPOTHESIS OF DEPRESSION). The MAOIs (for example phenelzine, tranylcypromine) act in the main by inhibiting irreversibly the enzyme MONOAMINE OXIDASE (MAO), which catalyses the breakdown of monoamines intracellularly. Consequently, the amount of monoamine available for synaptic transmission is increased. Because the drugs act systemically, MAO in the gut is also disabled and the dietary substance TYRAMINE is permitted to enter the circulation in abnormally high amount. Intake of foodstuffs containing tyramine (such as mature cheeses) must be restricted in patients taking MAOIs. A newer, reversible inhibitor of MAO, moclobemide, has lessened the danger of such interactions.
The TRICYCLICS (such as AMITRIPTYLINE and IMIPRAMINE), named after their structure, block the reuptake of monoamines from the synaptic cleft with varying degrees of selectivity. Many have other pharmacological actions, such as ANTICHOLINERGIC effects, which contribute to their side-effect profile. Tricyclics are potentially cardiotoxic, and may be lethal in overdose. The newer selective serotonin reuptake inhibitors SSRIs (for instance PROZAC) and serotonin and noradrenaline reuptake inhibitors SNRIs have a more specific reuptake blocking activity (for SEROTONIN, and serotonin and NORADRENALINE respectively), and though not free from side-effects themselves, may be better tolerated than the older tricyclics. They are safer if taken in overdose. At present, they are considerably more expensive. There are also effective ‘atypical’ antidepressants which neither block monoamine reuptake, nor inhibit MAO, such as the alpha 2 ADRENOCEPTOR antagonist, mianserin.
Chemical antidepressants are very effective in depressive disorder. DOUBLE BLIND STUDIES indicate that most of the wide variety of antidepressants are equally effective, with 70% of depressed patients responding. Tricyclics may, however, be more effective than MAOIs and SSRIs in particularly severe de-pressive illnesses. For reasons that remain poorly understood, all antidepressants take between 14 and 21 days to exert their therapeutic action.
IAN C.REID
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