COMPARATIVE TOLERABILITY PROFILES OF THE NEWER VERSUS OLDER ANTIDEPRESSANTS

Although the standard tricyclic antidepressants (TCAs) are generally e ffective in the treatment of depression, they can cause several troubl esome adverse effects. Chief among these are their anticholinergic act ions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium i n the ill and elderly. Cardiovascular effects of TCAs include orthosta tic hypotension, tachycardia and cardiac conduction slowing. Many TCAs are sedating and promote weight gain. Also problematic is the potenti al lethality of TCAs in overdose. The continual introduction of a host of new antidepressants over the past 15 years has provided an opportu nity to improve the benefit-risk ratio for many patients by reducing m edication-related toxicity. Selective serotonin reuptake inhibitors (S SRIs) and amfebutamone (bupropion), among others, are examples of effe ctive antidepressants free of tricyclic-like anticholinergic, cardiova scular, sedating and appetite/weight-increasing effects. However, the new-generation drugs also present adverse effects of their own, includ ing gastrointestinal distress, agitation and drug-drug interactions in the case of the SSRIs, and the risk of seizures or psychosis in amfeb utamone recipients. Monoamine oxidase (MAO) inhibitors have also been refined; reversible inhibitors of MAO-type A afford protection against the usually feared hypertensive reaction to indirect sympathomimetic substances. The availability of new-generation antidepressants thus in creases the likelihood of clinical response with a reduction in unwant ed toxicity.