Miscellaneous antidepressants

Miscellaneous antidepressants

Other antidepressants in use today include:

·                 maprotiline and mirtazapine, tetracyclic antidepressants

·                 bupropion, a dopamine reuptake blocking agent

·                 venlafaxine, a serotonin-norepinephrine reuptake inhibitor

·                 trazodone, a triazolopyridine agent

·                 nefazodone, a phenylpiperazine agent.

Pharmacokinetics

The paths these antidepressants take through the body may vary:

§    Maprotiline and mirtazapine are absorbed from the GI tract, dis-tributed widely in the body, metabolized by the liver, and excreted by the kidneys.

§    Bupropion is well absorbed from the GI tract and metabolized by the liver. Its metabolites are excreted by the kidneys. It appears to be highly bound to plasma proteins.

§    Venlafaxine is rapidly absorbed after oral administration, par-tially bound to plasma proteins, metabolized in the liver, and ex-creted in urine.

§    Trazodone is well absorbed from the GI tract, distributed widely in the body, and metabolized by the liver. About 75% is excreted in urine; the remainder is excreted in stool.

§    Nefazodone is rapidly and completely absorbed but, because of extensive metabolism, only about 20% of the drug is available. The drug is almost completely bound to plasma proteins and is excret-ed in urine.

Pharmacodynamics

Much about how these drugs work has yet to be fully understood:

·                 Maprotiline and mirtazapine probably increase the amount of norepinephrine, serotonin, or both in the CNS by blocking their reuptake by presynaptic neurons (nerve terminals).

·                 Bupropion was once thought to inhibit the reuptake of the neu-rotransmitter dopamine; however, it more likely acts on nonadren-ergic receptors.

·                 Venlafaxine is thought to potentiate neurotransmitter activity in the CNS by inhibiting the neural reuptake of serotonin and norepi-nephrine.

·                 Trazodone, although its action is unknown, is thought to exert antidepressant effects by inhibiting the reuptake of norepineph-rine and serotonin in the presynaptic neurons.

·                 Nefazodone’s action isn’t precisely defined. It inhibits neuronal uptake of serotonin and norepinephrine. It’s also a serotonin an-tagonist, which explains its effectiveness in treating anxiety.

Pharmacotherapeutics

These miscellaneous drugs are all used to treat depression. Tra-zodone may also be effective in treating aggressive behavior and panic disorder.

Drug interactions

All of these antidepressants may have serious, potentially fatal, ef-fects when combined with MAOIs. Each of these drugs also car-ries its own specific risks when used with other drugs:

·                 Maprotiline and mirtazapine interact with CNS depressants to cause an additive effect.

·                 Bupropion combined with levodopa, phenothiazines, or TCAs increases the risk of adverse reactions, including seizures.

·                 Trazodone may increase serum levels of digoxin and phenytoin. Its use with antihypertensive agents may increase hypotensive ef-fects. CNS depression may be enhanced if trazodone is adminis-tered with other CNS depressants.

·                 Nefazodone may increase the digoxin level if administered with digoxin. It increases CNS depression when combined with CNS depressants. (See Adverse reactions to miscellaneous antidepres-sants.)