Recent advances in antidepressant drug treatment.

Psychiatric research has made remarkable advances in understanding the pathophysiology of depressive illnesses. Biologic depressions are now understood as neurotransmitter deficiency diseases. Certain forms of depression are treated with tricyclic antidepressant drugs, which increase the amount of available neurotransmitters. Complicating the clinical picture, however, is the problem of wide variability of levels of tricyclic drugs in the plasma of persons receiving the same dosage. Another problem is the apparent linear dose-response relationship of imipramine hydrochloride and its sister compound desipramine hydrochloride while amitriptyline and nortriptyline follow an inverted U-shaped dose-response curve. However, with newer, more sophisticated diagnostic methods, combined with monitoring of tricyclic drug levels in plasma, therapeutic efficacy can approach 90 percent. Available neurotransmitters also can be increased using monoamine oxidase (MAO) inhibitors. Although MAO inhibitors have been less popular than the tricyclic drugs, recent clinical research tends to support their efficacy. Distinct individual differences in the rate of metabolism of MAO inhibitors have been found. New methods are being devised to detect these differences and monitor directly the effects of these drugs. One of these methods, platelet MAO inhibition, shows some clinical promise. Tricyclic drugs and MAO inhibitors have recently been joined by lithium carbonate, which shows notable efficacy in removing acute manic-depressive symptoms as well as preventing their return during maintenance treatment. Its utility in treating cyclic depressions without mania is now being explored by researchers.