Depression May Lurk in Stress-Response System

Article excerpt

NEW YORK -- Drugs that enhance serotonin or norepinephrine activity can effectively treat depression, but it cannot be deduced from this that the disorder is a result of deficiency or depletion of single neurotransmitters, Dr. Pedro L. Delgado said at a conference on psychopharmacology sponsored by New York University.

A more fundamental defect in depression is thought to involve the stress-response cascade, he said. Drugs that seem to have efficacy in depression generally enhance levels of monoamine neurotransmitters such as serotonin or norepinephrine. But it does not follow that the disease can be reduced to a deficiency of one or another of these substances. The complexity of the relationship between depression and neurotransmitter activity is suggested by 15 years of research into neurotransmitter depletion. Serotonin can be depleted within hours by blocking the passage of its precursor, tryptophan, across the blood brain barrier by administering a mixture of amino acids without tryptophan. A similar effect on norepinephrine can be achieved with an enzyme that blocks its synthesis from tyrosine.

According to repeated placebo-controlled studies, serotonin depletion leads to the return of symptoms in 60% of patients who have been successfully treated for depression with a selective serotonin reuptake inhibitor (SSRI). In these patients, norepinephrine depletion has no effect.

When depressed patients who have responded to the norepinephrine reuptake inhibitor desipramine are given a norepinephrine-blocking agent, symptoms return in 80%; serotonin depletion has no effect.

On the other hand, no study has induced depression in a healthy subject by serotonin or norepinephrine depletion, nor have symptoms been worsened in depressed subjects not under treatment with the respective drugs, said Dr. Delgado, professor and chair of psychiatry at Case Western Reserve University, Cleveland. …