Nontricyclic antidepressants

After discovery of TCAs and monoamine oxidase inhibitors, collectively called first-generation antidepressants, many other classes of antidepressants were discovered. These include amoxapine and maprotiline that affect reuptake of monoamines similar to secondary amine TCAs. Trazodone is a weak inhibitor of serotonin reuptake but has little effect on norepinephrine uptake. Bupropion inhibits reuptake of norepinephrine and dopamine. In addition to its use as an antidepressant, bupropion is used as an aid to stop smoking. Venlafaxine and mirtazapine are other non-TCAs with novel properties of inhibiting both norepinephrine and serotonin. Their side effects profile is lower than that of TCAs (43).

The other class of antidepressants called SSRIs has become the most widely prescribed group of antidepressants in the USA. In addition to inhibiting serotonin uptake, these drugs interact with serotonin receptors to cause pharmacological response. Advantages of SSRIs over TCAs include their lack of adrenergic, antihis-taminic and anticholinergic effects, better tolerability, and superior safety profile. SSRIs are also used in the treatment of obsessive-compulsive disorder, panic disorder, bulimia, and many other conditions. Drug interactions include any drug that increases serotonin concentrations including monoamine oxidase inhibitors, tramadol, sibutramine, meperidine, sumatriptan, lithium, St. John's wort, ginkgo biloba, and atypical antipsychotic agents. Overdose situations or drug-drug interactions leading to an increase in serotonin may cause serotonin syndrome. The syndrome is associated with changes in mental status, agitation, myoclonus, diaphoresis, shivering, tremor, diarrhea, incoordination, and fever (2). SSRIs that are commonly used and measured in the laboratory include citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Some pharmacological properties of these antidepressants are summarized in Table 2.

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