Biochemistry and treatment strategies for depression

Major depressive disorder is a relatively common illness. Many depressed patients are seen by a primary care physician and not a psychiatrist. Several lines of evidence suggest a biochemical etiology for depression. Some research suggests at least two distinct biochemical depressions, one involving an abnormality of the norepinephrine neurotransmitter system and the other involving an abnormality of the serotonin system. Individual tricyclic antidepressants appear to have differential effects on these two neurotransmitters. This may explain why some depressed patients respond better to one tricyclic than to another. This factor also provides a treatment rationale for switching a nonresponsive depressed patient from one tricyclic, after an adequate trial, to the "opposite" tricyclic. Pretreatment levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) separate depressed patients quite accurately into two groups: imipramine responders and amitriptyline responders. Future research in this area may lead to clinically useful laboratory tests for the treatment of depression.