Many noncyclic antidepressants are available. These can be classified as selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), and fluvoxamine (Luvox); serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine (Effexor), desvenlafaxine (Pristiq) duloxetine (Cymbalta), milnacipran (Savella) and levomilnacipran (Fetzima); norepinephrine-dopamine reuptake inhibitors (NDRIs), including bupropion (Wellbutrin); and others, including trazodone (Desyrel) and mirtazapine (Remeron), the latter a tetracyclic antidepressant. Bupropion is also marketed under the brand name Zyban for smoking cessation. In overdose these drugs are generally less toxic than the tricyclic antidepressants and the monoamine oxidase (MAO) inhibitors, although serious effects, such as seizures, hypotension, cardiac arrhythmias, and serotonin syndrome, occasionally occur. Noncyclic and tricyclic antidepressants are described in Table II–8.
Table Graphic Jump Location TABLE II–8.ANTIDEPRESSANTS ||Download (.pdf) TABLE II–8. ANTIDEPRESSANTS
| ||Usual Adult Daily Dose (mg) ||Neurotransmitter Effectsa ||Toxicityb |
|Tricyclic antidepressants |
| Amitriptyline ||75–200 ||NE, 5-HT ||A, H, QRS, Sz |
| Amoxapine ||150–300 ||NE, DA ||A, H, Sz |
| Clomipramine ||100–250 ||NE, 5-HT ||A, H, QRS, Sz |
| Desipramine ||75–200 ||NE ||A, H, Sz |
| Doxepin ||75–300 ||NE, 5-HT ||A, H, QRS, Sz |
| Imipramine ||75–200 ||NE, 5-HT ||A, H, QRS, Sz |
| Maprotiline ||75–300 ||NE ||A, H, QRS, Sz |
| Nortriptyline ||75–150 ||NE ||A, H, QRS, Sz |
| Protriptyline ||20–40 ||NE ||A, H, QRS, Sz |
| Trimipramine ||75–200 ||NE, 5-HT ||A, H, QRS, Sz |
|Newer, noncyclic drugs |
| Bupropion ||200–450 ||DA, NE ||Sz |
| Citalopram ||20–40 ||5-HT ||Sz, SS |
| Desvenlafaxine ||50 ||5-HT, NE ||Sz, SS |
| Duloxetine ||30–180 ||5-HT, NE ||Sz, SS |
| Escitalopram ||10–30 ||5-HT ||Sz, SS |
| Fluoxetine ||20–80 ||5-HT ||Sz, SS |
| Fluvoxamine ||50–300 ||5-HT ||Sz, SS |
| Levomilnacipran ||40–120 ||5-HT, NE ||Sz, SS |
| Milnacipran ||100–200 ||5-HT, NE ||Sz, SS |
| Mirtazapine ||15–45 ||Alpha2 ||Sz |
| Nefazodone ||100–600 ||5-HT, Alpha2 ||H |
| Paroxetine ||20–50 ||5-HT ||Sz, SS |
| Sertraline ||50–200 ||5-HT ||Sz, SS |
| Trazodone ||50–400 ||5-HT, Alpha2 ||H, Sz, SS |
| Venlafaxine ||30–600 ||5-HT, NE ||Sz, SS |
|Monoamine oxidase inhibitors ||See Monoamine oxidase inhibitors |
MECHANISM OF TOXICITY
SSRIs inhibit serotonin reuptake transporters resulting in increased stimulation of serotonin receptors in the brain. SNRIs inhibit both serotonin and norepinephrine reuptake transporters and also increase stimulation of CNS norepinephrine receptors. Most agents cause CNS depression. Bupropion is a stimulant that can also cause seizures, presumably related to inhibition of reuptake of dopamine and norepinephrine.
Trazodone and mirtazapine produce peripheral alpha-adrenergic blockade, which can result in hypotension and priapism.
Serotonin reuptake inhibitors, such as fluoxetine, citalopram, sertraline, paroxetine, fluvoxamine, venlafaxine, and trazodone, may interact with each other, with chronic use of an MAO inhibitor, or with dextromethorphan to produce the "serotonin syndrome" (see below and Hyperthermia).
None of the drugs in this group has significant anticholinergic effects.
Pharmacokinetics. These drugs have ...