SSRIs – Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs, a popular antidepressant type, can help you overcome depression symptoms and feel good again. Discover how Prozac and other SSRIs boost your mood and what side effects they may cause.
By Mayo Clinic staff

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

How SSRIs work
Precisely how SSRIs affect depression isn’t clear. Certain brain chemicals called neurotransmitters are associated with depression, including the neurotransmitter serotonin (ser-oh-TOE-nin). Some research suggests that abnormalities in neurotransmitter activity 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 in the brain. Increased serotonin enhances neurotransmission — the sending of nerve impulses — and improves mood. SSRIs are called selective because they seem to affect only serotonin, not other neurotransmitters.

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.

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

Here are the SSRIs approved by the Food and Drug Administration (FDA) specifically to treat depression, with their generic, or chemical, names followed by available brand names in parentheses:

* Citalopram (Celexa)
* Escitalopram (Lexapro)
* Fluoxetine (Prozac, Prozac Weekly)
* Paroxetine (Paxil, Paxil CR, Pexeva)
* Sertraline (Zoloft)

Also, an olanzapine and fluoxetine combination (Symbyax) recently received FDA approval for treating bipolar depression. Symbyax is classed as both an SSRI antidepressant and an atypical antipsychotic.
These medications may also be used to treat conditions other than depression.

Side effects of SSRIs
All SSRIs have the same general mechanism of action and side effects. However, individual SSRIs have some different pharmacological characteristics. That means you may respond differently to certain SSRIs or have different side effects with different SSRIs. For instance, you may have unpleasant side effects with one SSRI but not another. Also, they’re less likely to have adverse interactions with other medications and are less dangerous if taken as an overdose.

Side effects of SSRIs include:
* Nausea
* Sexual dysfunction, including reduced desire or orgasm difficulties
* Dry mouth
* Headache
* Diarrhea
* Nervousness
* Rash
* Agitation
* Restlessness
* Increased sweating
* Weight gain
* Drowsiness
* Insomnia

You may experience less nausea with extended- and 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). Because of this, don’t take any SSRIs while you’re taking any MAOIs or within two weeks of each other. Serotonin syndrome can also occur when SSRIs are taken with other medications, including:

* Pain relief medication such as tramadol (Ultram)
* Migraine medications such as sumatriptan (Imitrex) and rizatriptan (Maxalt)
* Supplements that affect serotonin levels, such as St. John’s wort

Serotonin syndrome requires immediate medical treatment. Signs and symptoms include:

* Confusion
* Restlessness
* Hallucinations
* Extreme agitation
* Fluctuations in blood pressure
* Increased heart rate
* Nausea and vomiting
* Fever
* Seizures
* Coma

Safety concerns with SSRIs
Studies show that Paxil increases the risk of birth defects in women taking the drug during their first trimester of pregnancy. Women who take Paxil during their first three months of pregnancy are nearly two times as likely to give birth to a child with a birth defect — in particular a heart defect — as are women taking other antidepressants.

The American College of Obstetricians and Gynecologists recommends avoiding Paxil during pregnancy, if possible. If you’re taking Paxil and you’re considering getting pregnant, talk to your doctor or mental health provider about switching to another antidepressant or stopping treatment. Don’t stop taking Paxil without contacting your doctor first, though.

Also, the FDA warns that infants whose mothers took SSRIs while pregnant may be at an increased risk of persistent pulmonary hypertension. This risk is increased in women who take SSRIs at 20 weeks or later in pregnancy. This rare but serious lung problem occurs when a newborn’s circulatory system doesn’t adapt to breathing outside the womb.

Use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) or anticoagulants, such as warfarin (Coumadin), while taking SSRIs may increase the risk of gastrointestinal bleeding and should be monitored by your doctor.

Recent studies have shown that Symbyax and other antipsychotics should not be prescribed to older people for treatment of dementia-related psychosis. Symbyax and other antipsychotic drugs raise the risks of heart failure, sudden death and pneumonia in older people with dementia-related psychosis.

Stopping treatment with SSRIs
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.

Suicidal feelings and SSRIs
Antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior in those ages 18 to 24. These symptoms or thoughts are most likely to occur during the first one to two months of treatment or when you change your dosage, but they can occur at any time during treatment. Be sure to talk to your doctor about any changes in your symptoms. You may need more careful monitoring when starting 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.

Talk with your doctor or mental health provider to nix your irritability, sadness or anger and boost your mood with SSRIs. Feel good again.

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