Selective serotonin reuptake inhibitors (SSRIs)

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Selective serotonin reuptake inhibitors (SSRIs)

SSRIs (selective serotonin reuptake inhibitors) are the most commonly prescribed antidepressants. They can ease symptoms of moderate to severe depression, are relatively safe and generally cause fewer side effects than other types of antidepressants.

How selective serotonin reuptake inhibitors work

SSRIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Most antidepressants work by changing the levels of one or more of these naturally occurring brain chemicals.

SSRIs block the reabsorption (reuptake) of the neurotransmitter serotonin (ser-oh-TOE-nin) in the brain. Changing the balance of serotonin seems to help brain cells send and receive chemical messages, which in turn boosts mood. SSRIs are called selective because they seem to primarily affect serotonin, not other neurotransmitters.

Selective serotonin reuptake inhibitors approved to treat depression

SSRIs approved by the Food and Drug Administration to treat depression, with their generic names followed by brand names in parentheses, include:

  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac, Prozac Weekly, Sarafem)
  • Paroxetine (Paxil, Paxil CR, Pexeva)
  • Sertraline (Zoloft)
  • Fluoxetine combined with the atypical antipsychotic olanzapine (Symbyax)

Some SSRIs are available in extended-release form or controlled-release form, often designated with the letters XR or CR. These SSRIs provide controlled release of the medication throughout the day or for a week at a time with a single dose.

These medications may also be used to treat conditions other than depression.

Side effects of selective serotonin reuptake inhibitors

All SSRIs work in a similar way and generally cause similar side effects. However, each SSRI has a different chemical makeup, so one may affect you a little differently from another.

Side effects of SSRIs can include:

  • Nausea
  • Dry mouth
  • Headache
  • Diarrhea
  • Nervousness, agitation or restlessness
  • Reduced sexual desire or difficulty reaching orgasm
  • Inability to maintain an erection (erectile dysfunction)
  • Rash
  • Increased sweating
  • Weight gain
  • Drowsiness
  • Insomnia

You may experience less nausea with extended- and controlled-release forms of SSRIs. As with most antidepressants, sexual side effects are common with SSRIs. They occur in over half the people who take them.

Safety concerns with selective serotonin reuptake inhibitors

SSRIs are relatively safe. However, there are some things you should think about before you take one of these antidepressants:

  • Antidepressants and pregnancy. Some antidepressants may harm your unborn child if you take them during pregnancy or while you're breast-feeding. Paxil in particular appears to increase the risk of birth defects, including heart and lung problems. If you're taking an antidepressant and you're considering getting pregnant, talk to your doctor or mental health provider about the possible dangers. Don't stop taking your medication without contacting your doctor first.
  • Drug interactions. When taking an antidepressant, be sure to tell your doctor about any other medications or supplements you're taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal remedies.
  • Blood-thinning medications and SSRIs. Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or anticoagulants, such as warfarin (Coumadin), may increase the risk of bleeding when combined with a SSRIs.
  • Serotonin syndrome. Rarely, an SSRI can cause dangerously high levels of serotonin. This is known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include other antidepressants, medications for certain health conditions and the herbal supplement St. John's wort. Signs and symptoms of serotonin syndrome include confusion, rapid or irregular heart rate, dilated pupils, fever, and unconsciousness. Seek immediate medical attention if you have any of these signs or symptoms.

Suicide risk and antidepressants

The Food and Drug Administration (FDA) requires that all antidepressants carry a warning that some children, adolescents and young adults may be at increased risk of suicide when taking antidepressants. Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior — especially in the first few weeks after starting an antidepressant. Keep in mind, antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with selective serotonin reuptake inhibitors

SSRIs aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including:

  • Nausea
  • Headache
  • Dizziness
  • Lethargy
  • Flu-like symptoms

This is sometimes called discontinuation syndrome. Talk to your doctor before stopping so that you can gradually taper off the medication.

Finding the right antidepressant

Each person may react differently to a particular antidepressant and may be more susceptible to particular side effects. Because of this, one antidepressant may work better for you than another.

Properties of one particular SSRI may make it a better choice than another for you. For example, if you have low energy, a more energizing SSRI — such as fluoxetine (Prozac) — may be beneficial. If you're anxious, an SSRI that may help ease anxiety — such as paroxetine (Paxil) — may be a good option. When choosing an antidepressant, your doctor will take into account your particular symptoms, what other health problems you have, what other medications you take and what has worked for you in the past. Sometimes a combination of antidepressants may be the best treatment choice.

Inherited traits play a role in how antidepressants affect you. In some cases, DNA tests such as cytochrome P450 (CYP450) tests may give clues as to whether an antidepressant is likely to ease symptoms or cause side effects. DNA testing isn't widely used yet, but is becoming more common.

It can take a long time to find the best treatment for depression. It takes several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. You may need to try several antidepressants before you find the right one, but hang in there. With patience, you and your doctor can find a medication that works well for you.

Last Updated: 2010-12-09
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