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Depression is a very common mood disorder char-acterized by sadness and pessimism. Its cause is multifactorial, but pharmacological treatment is based on the presumption that its manifestations are due to a brain deficiency of dopamine, norepi-nephrine, and serotonin or altered receptor activi-ties. Up to 50% of patients with major depression hypersecrete cortisol and have abnormal circadian secretion. Current pharmacological therapy utilizes drugs that increase brain levels of these neurotrans-mitters: tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), MAO inhibitors, and atypical antidepressants. The mechanisms of action of these drugs result in some potentially serious anesthetic interactions. Electroconvulsive therapy (ECT) is increasingly used for refractory severe cases and may be continued prophylactically after the patient’s mood recovers. The use of general anes-thesia for ECT is largely responsible for its safety and widespread acceptance.
Tricyclic antidepressants may be used for the treat-ment of depression and chronic pain syndromes. All tricyclic antidepressants work at nerve synapses by blocking neuronal reuptake of catecholamines, serotonin, or both. Desipramine and nortriptyline are used because they are less sedating and tend to have fewer side effects. Other agents are gener-ally more sedating and include amitriptyline imip-ramine, protriptyline, amoxapine, doxepin, and trimipramine. Clomipramine is used in the treatment of obsessive–compulsive disorders. Most tricyclic antidepressants also have significant anticholinergic (antimuscarinic) actions: dry mouth, blurred vision, prolonged gastric emptying, and urinary retention. Quinidine-like cardiac effects include tachycardia, T-wave flattening or inversion, and prolongation of the PR, QRS, and QT intervals. Amitriptyline has the most marked anticholinergic effects, whereas doxepin has the fewest cardiac effects.
St. John’s wort is being used with increased fre-quency as an over-the-counter therapy for depres-sion. Because it induces hepatic enzymes, blood levels of other drugs may decrease, sometimes with serious complications. During the preoperative eval-uation, the use of all over-the-counter medications should be reviewed.
Antidepressant drugs are generally continued perioperatively. Increased anesthetic requirements, presumably from enhanced brain catecholamine activity, have been reported with these agents. Potentiation of centrally acting anticholinergic agents (atropine and scopolamine) may increase the likelihood of postoperative confusion and delirium.The most important interaction between anes-thetic agents and tricyclic antidepressants is anexaggerated response to both indirect-acting vaso-pressors and sympathetic stimulation. Pancuronium, ketamine, meperidine, and epinephrine-containing local anesthetic solutions should be avoided. Chronic therapy with tricyclic antidepressants is reported to deplete cardiac catecholamines, theo-retically potentiating the cardiac depressant effects of anesthetics. If hypotension occurs, small doses of a direct-acting vasopressor should be used instead of an indirect-acting agent. Amitriptyline’s anticholin-ergic action may occasionally contribute to postop-erative delirium.
MAO inhibitors block the oxidative deamination ofnaturally occurring amines. At least two MAO iso-enzymes (types A and B) with differential substrate selectivities have been identified. MAO-A is selec-tive for serotonin, dopamine, and norepinephrine, whereas MAO-B is selective for dopamine and phenylethylamine. Nonselective MAO inhibitors include phenelzine isocarboxazid, and tranylcy-promine. Selective MAO-B inhibitors are useful in the treatment of PD. Additionally, unlike older nonreversible MAO inhibitors, reversible, MAO-A inhibitors have been developed. Side effects include orthostatic hypotension, agitation, tremor, seizures, muscle spasms, urinary retention, paresthesias, and jaundice. The most serious sequela is a hypertensive crisis that occurs following ingestion of tyramine-containing foods (cheeses and red wines), because tyramine is used to generate norepinephrine.
The practice of discontinuing MAO inhibi-tors at least 2 weeks prior to elective surgery is not recommended. Phenelzine can decrease plasma cholinesterase activity and prolong the duration of succinylcholine. Opioids should generally be used with caution in patients receiving MAO inhibitors, as rare but serious reactions to opioids have been reported. Most serious reactions are associated with meperidine, resulting in hyperthermia, seizures, and coma. Meperidine should not be administered to patients receiving MAO inhibitors. As with tri-cyclic antidepressants, exaggerated responses to vasopressors and sympathetic stimulation should be expected. If a vasopressor is necessary, a direct-acting agent in small doses should be employed. Drugs that enhance sympathetic activity, such as ketamine, pancuronium, and epinephrine (in local anesthetic solutions), should be avoided.
SSRIs include fluoxetine, sertraline, and paroxetine, which some clinicians consider first-line agents of choice for depression. A surprisingly large fraction of patients undergoing elective surgery will be receiving one of these agents. These agents have little or no anti-cholinergic activity and do not generally affect cardiac conduction. Their principal side effects are head-ache, agitation, and insomnia. Other agents include the norepinephrine/dopamine reuptake inhibi-tors, the serotonin/norepinephrine reuptake inhib-itors, selective serotonin reuptake enhancers, and norepinephrine-dopamine disinhibitors. Patients taking St. John’s wort are at increased risk of sero-tonin syndrome, as are those taking drugs with similar effects (eg, MAO inhibitors, meperidine). Serotonin syndrome manifestations include agita-tion, hypertension, hyperthermia, tremor, acidosis, and autonomic instability. Treatment is supportive, along with the administration of a 5-HT antagonist (eg, cyprohepatadine).
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