Noradrenergic and serotonergic receptor system function in panic disorder and depression.

Recent studies which have utilized the administration of neurotransmitter agonists and antagonists to study presynaptic and postsynaptic receptor system function in panic disorder and major depression are reviewed. In panic disorder, patients have been found to be overly sensitive to the alpha-2 adrenergic agonist clonidine, and the alpha-2-adrenergic antagonist yohimbine, but they have relatively normal responses to tryptophan, the precursor of serotonin, and MCPP, a directly acting serotonin agonist. In depression, patients appear to have relatively normal responses to clonidine and yohimbine except for some supersensitivity to yohimbine effects on blood pressure and subjective symptoms. In contrast to the panic disorder patients, depressed patients demonstrate a neuroendocrine subsensitivity to tryptophan. Taken together, these studies suggest a relative abnormality in the alpha-2-adrenergic regulation of the noradrenergic system in panic disorder and a subsensitivity of the serotonergic system in depression. The pharmacologic treatment response in panic disorder and depression is similar in that both conditions respond to tricyclic antidepressants and monoamine oxidase inhibitors, but different in that panic disorder does not respond to atypical antidepressants such as trazodone and bupropion, but does respond to benzodiazepines, in contrast to depression. The possible mechanisms involved in producing these findings and the methods to more fully study possible receptor system abnormalities in these illnesses are discussed.