Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are a newer class of antidepressant medications. The first drug in this class was fluoxetine (Prozac), which hit the U.S. market in 1987.

It's still not clear precisely how SSRIs affect depression. Certain brain chemicals called neurotransmitters are associated with depression, including the neurotransmitter serotonin (ser-oh-TOE-nin). Research suggests that abnormalities in neurotransmitter activity can affect mood and behavior. SSRIs seem to relieve symptoms of depression by blocking the reabsorption (reuptake) of serotonin by certain nerve cells in the brain. This leaves more serotonin available, which enhances neurotransmission — the sending of nerve impulses — and improves mood. SSRIs are called selective because they seem to affect only serotonin, not other neurotransmitters.

Some SSRIs are available in extended-release forms or controlled-release forms, often designated with the letters XR or CR. These forms, which aren't suitable for everyone, are intended to provide controlled release of the medication throughout the day or for a week at a time with a single dose.

Here are the SSRIs that have been approved by the Food and Drug Administration specifically to treat depression, with their generic names followed by available brand names in parentheses:

• Citalopram (Celexa)
• Escitalopram oxalate (Lexapro)
• Fluoxetine (Prozac, Prozac Weekly)
• Paroxetine (Paxil, Paxil CR)
• Sertraline (Zoloft)

Side effects and safety concerns

SSRIs are generally safer than other classes of antidepressants. They're less likely to have adverse interactions with other medications and they're less dangerous if taken as an overdose. Although all SSRIs have the same general mechanism of action and side effects, they do have some different pharmacological characteristics. That means you may respond differently to certain SSRIs or experience different side effects with different SSRIs.

Side effects of SSRIs include:

• Nausea
• Sexual dysfunction, including reduced desire or orgasm difficulties
• Headache
• Diarrhea
• Nervousness
• Rash
• Agitation
• Restlessness
• Increased sweating
• Weight gain
• Drowsiness
• Insomnia

You may experience less nausea with controlled release forms of SSRIs.

A rare but potentially life-threatening side effect of SSRIs is serotonin syndrome. This condition, characterized by dangerously high levels of serotonin in the brain, can occur when an SSRI interacts with antidepressants called monoamine oxidase inhibitors (MAOIs). Serotonin syndrome can also occur when SSRIs are taken with other medications or supplements that affect serotonin levels, such as St. John's wort.

Signs and symptoms of serotonin syndrome include confusion, hallucinations, extreme agitation, fluctuations in blood pressure and heart rhythm, fever, seizures and even coma. Serotonin syndrome requires immediate medical treatment.

SSRIs aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including nausea, headache, dizziness, lethargy and flu-like symptoms. This is sometimes called discontinuation syndrome. Talk to your doctor before stopping any medication so you can gradually taper off.

In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior, particularly early in 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 at the beginning of treatment or upon a change in treatment, or you may need to stop the medication if your symptoms worsen.