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Certain brain chemicals called neurotransmitters are associated with depression, including the neurotransmitters serotonin (ser-oh-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin). Research suggests that abnormalities in neurotransmitter activity can affect mood and behavior.

Combined reuptake inhibitors and receptor blockers are dual-action antidepressants. That is, they act on brain cells in two ways — both by inhibiting the reabsorption (reuptake) of neurotransmitters into nerve cells and by blocking nerve cell receptors. This leaves more of these neurotransmitters available in the brain, which boosts mood.

Antidepressants, in general, may also work by playing a neuroprotective role in how they relieve anxiety and depression. It's thought that antidepressants may increase the effects of brain receptors that help nerve cells keep sensitivity to glutamate — an organic compound of a nonessential amino acid — in check. This increased support of nerve cells lowers glutamate sensitivity, providing protection against the glutamate overwhelming and exciting key brain areas related to anxiety and depression.

Therapeutic effects of antidepressants may vary in people, due in part to each person's genetic makeup. It's thought that people's sensitivity to antidepressant effects, especially selective serotonin reuptake inhibitor effects, can vary depending on:

• How each person's serotonin reuptake receptor function works
• His or her alleles — the parts of chromosomes that determine inherited characteristics, such as height and hair color, which combine to make each person unique

Antidepressant medications are often the first treatment choice for adults with moderate or severe depression, sometimes along with psychotherapy. Although antidepressants may not cure depression, they can help you achieve remission — the disappearance or nearly complete reduction of depression symptoms.

Here are the combined inhibitors and blockers approved by the Food and Drug Administration specifically to treat depression:

• Trazodone
• Nefazodone
• Maprotiline

These antidepressants are available only in generic form. The brand-name versions are no longer manufactured for various reasons.

Although trazodone's mechanism of action leads to its classification as a combined reuptake inhibitor and receptor blocker, it is a triazolopyridine antidepressant. Trazodone often is prescribed along with other antidepressants because of its sleep-inducing effect. The chemical structure of triazolopyridines is unrelated to that of other antidepressant types.

Some of these medications may also be used to treat conditions other than depression.

Side effects of combined inhibitors and blockers include:

• Dry mouth
• Dizziness
• Drowsiness
• Lightheadedness
• Nervousness
• Nausea
• Constipation
• Weakness
• Vision problems
• Confusion
• Headache

Trazodone has been associated with priapism — persistent, usually painful erections not associated with sexual arousal. If this occurs, seek medical treatment immediately. Many of those cases have required surgical correction, resulting in permanent impairment of erectile function or impotence.

In rare cases, nefazodone (nuh-FAY-zoe-dohn) can cause life-threatening liver failure. Don't take it if you already have liver problems. Know the signs and symptoms of possible liver dysfunction, such as yellowing of your skin or the whites of your eyes, unusually dark urine, loss of appetite, nausea or abdominal pain. Contact your doctor immediately if you experience any of these problems. Also, be sure to talk to your doctor before using pimozide (Orap), carbamazepine (Carbatrol, Tegretol, others), triazolam (Halcion) or monoamine oxidase inhibitors (MAOIs) if you're taking nefazodone.

Maprotiline has been associated with seizures, so people with a history of seizures usually shouldn't take this medication. Also, maprotiline shouldn't be used in combination with MAOIs.

In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior in those ages 18 to 24. These symptoms are likely to occur in the first one to two months of treatment or when you change your dosage. Be sure to talk to your doctor about any changes in your symptoms. You may need more careful monitoring when beginning treatment or changing dosage, or you may need to stop the medication if your symptoms worsen. Adults age 65 and older taking antidepressants have a decreased risk of suicidal thoughts.

Work with your doctor or mental health provider to nix your irritability, sadness, guilt or anger and elevate your mood with this dual-action inhibitor and blocker that works for your good mental health.