Low amounts of the neurotransmitter serotonin have been linked to depression. SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft) increase levels of serotonin in the brain. All of the SSRI antidepressants are equally effective and have similar rates and types of side effects, although it is possible that an individual might respond better or experience fewer side effects with a particular SSRI drug. Side effects are not always a reason to change selective serotonin reuptake inhibitors. For example, Paxil can produce a sedative effect in some people, but this may be beneficial to people who suffer from both anxiety and depression.

Because side effects of SSRIs are more mild than most other antidepressants, most doctors now consider them the first-line drug treatment for depression. Studies have demonstrated that SSRI medications are as effective as tricyclics; about half of those who take an SSRI see their symptoms of depression lift completely. Advantages of SSRIs over other antidepressants such as tricyclics include a lower risk of fatal overdoses and serious heart rhythm disturbances in people with heart disease. SSRIs are also effective against dysthymia (chronic low-grade depression).

SSRI Side Effects

SSRI antidepressants can produce side effects such as anxiety, nervousness, insomnia, drowsiness, and nausea. Another troublesome side effect is sexual dysfunction —diminished sexual desire, changes in the sensations of arousal, or disturbances in the ability to achieve orgasm —which may occur in about 37% of both men and women taking these drugs. Sexual side effects usually develop within the first week of starting an SSRI, though they may arise more slowly as blood levels of the medication build up.

Strategies to alleviate sexual dysfunction include switching to a medication with a low rate of sexual side effects (such as the dopamine reuptake inhibitor bupropion [Wellbutrin]), waiting to see if sexual side effects abate, changing the time when you take the medication (possibly to nighttime), reducing the dosage, taking drug holidays (for example, not taking the medication on the weekend), or adding an erectile dysfunction drug like sildenafil (Viagra). If you experience worrisome symptoms, do not make any changes in your drug regimen on your own —be sure to consult your doctor first.

Recently, it was recognized that SSRI medications may produce neurological side effects —symptoms like those of Parkinson’s disease, such as impaired muscle tone, tremors, spasms, or feelings of restlessness. These symptoms can become so severe that sitting still becomes impossible. Fortunately, they are rare: In one study, they occurred in only 0.3% of people. By comparison, the most common side effects of Prozac —agitation and anxiety —occurred in twice as many people, although they were still relatively uncommon. If you experience any of these symptoms, contact your doctor before you stop taking your medication.

In addition, people taking a combination of drugs that raise the level of serotonin in the body can develop a disorder called serotonin syndrome. The most common causes are taking an SSRI at the same time as a monoamine oxidase (MAO) inhibitor or a triptan migraine drug (for example, frovatriptan [Frova], rizatriptan [Maxalt], sumatriptan [Imitrex], and others). The syndrome is characterized by altered mental status, neuromuscular abnormalities, and dysfunction of the autonomic nervous system, which controls involuntary reflexes that affect breathing, heart rate, blood pressure, and the digestive tract. Tricyclic antidepressants may also contribute to serotonin syndrome.

SSRIs can increase the risk of gastrointestinal bleeding, particularly when taken with nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, according to a recent Danish study. This increased risk of bleeding means blood is less likely to clot, an effect that may be beneficial to certain people at risk for heart attacks and ischemic strokes —conditions caused by blood clotting. Another study found that depressed heart patients treated with the SSRI Zoloft showed significant reductions in the level of clotting factors in their blood, compared with those receiving a placebo. However, in people already taking an anticoagulant to prevent or treat blood clots, an SSRI may increase the risk of gastrointestinal bleeding, according to a recent study.

A recent Canadian study found that SSRIs may increase the risk of fractures in older adults, possibly by compromising bone quality and strength as well as by increasing the chance of falling.

Although the side effects tend to be similar among the SSRIs, Luvox and Paxil may be more likely to cause nausea, and diarrhea is more common with Zoloft. Because Prozac may take several days to clear from the body, interactions with other drugs are more likely to occur. One advantage of Prozac is that it is now available in a once-a-week capsule.

SSRI Withdrawal

SSRIs are not addictive in the conventional medical use of the word, but suddenly discontinuing their use after taking them for more than six weeks is known to produce both physical and psychological withdrawal symptoms.

About one quarter of people who abruptly stop taking an SSRI experience such as dizziness, nausea, lethargy, and headache. Other SSRI withdrawal symptoms include irritability, nervousness, crying spells, flu-like symptoms (body aches, chills, and fatigue), and shooting pains in and around the head.

SSRI withdrawal —also called SSRI discontinuation syndrome — is not dangerous, but it can be distressing. Fortunately, it is usually mild, commences within one week of stopping treatment, and resolves within three weeks.

To minimize SSRI discontinuation syndrome, doses of SSRIs (like other antidepressants) should be reduced gradually.

Publication Review By: Karen L. Swartz, M.D.

Published: 04 Mar 2011

Last Modified: 22 Jun 2011