Selective Serotonin Reuptake Inhibitors (SSRIs)
Although these drugs may have fewer and more tolerable side effects than some earlier-generation antidepressants, side effects—which can vary somewhat based on the specific medication—may still occur.
SSRIs can also produce withdrawal symptoms, and they may have some adverse interactions with certain types of drugs, including other antidepressants, non-steroidal inflammatory drugs, and lithium.
Studies have shown that SSRIs are more effective than a placebo in alleviating depression, and their effectiveness may be enhanced if they are combined with therapy.
What Are SSRIs?
Selective serotonin reuptake inhibitors (SSRIs) are medications that are commonly used to treat depression, anxiety, and several other mental health issues. They are the most commonly prescribed antidepressant and are likely to cause fewer side effects than other antidepressant medications.1
People usually take SSRIs for at least 4 to 9 months. But some people take them for several years.
SSRIs are used in the treatment of other mental health problems as well, including:2
- Anxiety disorders (e.g., generalized anxiety, social anxiety disorder).
- Obsessive-compulsive disorder (OCD).
- Panic disorder.
- Post-traumatic stress disorder (PTSD).
- Bulimia nervosa.
Other conditions that can be treated with SSRIs include fibromyalgia, hot flashes, premenstrual dysphoric disorder (PMDD), premature ejaculation, and irritable bowel syndrome.2
Common SSRIs include:1
- Escitalopram (Lexapro).
- Citalopram (Celexa).
- Sertraline (Zoloft).
- Fluoxetine (Prozac).
- Paroxetine (Paxil).
People usually take SSRIs for at least 4 to 9 months. But some people take them for several years. It depends on how the person responds to the medication and whether there is a risk of depression relapse.3
Studies show that in the absence of antidepressants, 50 out of 100 people with depression are likely to experience symptom relapse within a period of two years. When antidepressants are introduced, only 23 out of 100 people are likely to experience relapse of symptoms.3
How Do They Work?
Serotonin is a neurotransmitter important in sending signals between the nerve cells in the brain. It plays a key role in the regulation of a person’s mood, emotion, and sleep.2
SSRIs inhibit the reabsorption of serotonin back into the nerve cells (called reuptake). This mechanism results in higher levels of active serotonin in the brain.2
While low serotonin activity is not necessarily the direct cause of depression, an increase in serotonin may be associated with improvements in a person’s mood.2 This is why SSRIs are commonly prescribed to people who are battling mental health issues. They are often combined with psychotherapy and various other behavioral interventions.
SSRIs may have a wide range of side effects, including:1
- Decreased sex drive.
- Sexual dysfunction (e.g., erectile dysfunction, delayed orgasm).
- Blurred vision.
Less common side effects include:1
- Thoughts of suicide.
- Bruising or bleeding easily.
- Movement issues (e.g., muscle rigidity, trembling).
- Difficulty urinating.
The effects may differ from one drug to another. Paroxetine, for instance, is more likely to cause nausea, weight gain, drowsiness, constipation, and dry mouth compared to other SSRIs. Similarly, fluoxetine is more likely to cause weight loss, insomnia, anxiety, and agitation. Sertraline is more likely to cause diarrhea and headache.4
Sexual dysfunction—exhibited by symptoms like loss of libido, delayed orgasm, and impotence—is a common side effect of SSRIs. Still, sertraline and paroxetine may cause sexual dysfunction at a higher rate compared to other drugs.4
Physicians can’t predict exactly how a person might react to a drug. But they take a number of factors into consideration—the person’s physical condition, age, severity of symptoms, and any other ailments—to make sure the drug they prescribe is likely to be tolerated by the person.
If the person does not respond well to the drug or if the drug does not have any effect on their symptoms, the physician might ask them to discontinue the drug and prescribe a different one.
The withdrawal or discontinuation symptoms associated with selective serotonin reuptake inhibitors are generally mild and not life-threatening. Common symptoms include:2,5,6
- Sleep problems.
- Upset stomach.
- Blurred vision.
- “Electric shock” sensations.
- Seizures (rare).
The number and severity of symptoms experienced usually differ from one person to another, depending on their health, dose, and length of use. The symptoms usually peak in the first week and fade after that.6
Symptoms usually peak in the first week and fade after that.
The half-life of a drug is a key factor that can determine the severity and extent of discontinuation symptoms associated with it. Paroxetine has the shortest half-life among the drugs discussed above and the most likely to produce severe withdrawal symptoms. Fluoxetine has the longest half-life among the drugs and is the least likely to produce severe withdrawal.5
To minimize the risk of withdrawal symptoms, SSRIs should be discontinued slowly over a period of 1 or 2 weeks, with a gradual reduction in the dose.5
The Risk of Drug Interaction
The risk of drug interaction can be accurately determined on a case-by-case basis, depending on the other medications a person is already taking and the specific antidepressant they are prescribed. However, certain types of medications may be more likely to negatively interact with SSRIs to dangerously increase the risk of bleeding or serotonin syndrome (anxiety, high blood pressure, tremors, muscle rigidness, and confusion).2,7 They include:2
- Non-steroidal inflammatory drugs (NSAIDs), a class of analgesics that includes ibuprofen or naproxen.
- Antiplatelet or “blood thinner” therapies (e.g., aspirin, Plavix), which are used to prevent blood clots.
- Lithium, a drug used to treat depression and bipolar disorder.
- Theophylline, which is used to treat asthma.
- Triptans, which help relieve migraines.
- Other antidepressants, particularly tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-norepinephrine reuptake inhibitors.
People who take antidepressants are generally advised not to drink, as alcohol could worsen their symptoms. It can also increase drowsiness.2
In some cases, people who drink while on SSRIs might notice a change in their alcohol tolerance. They might lose their inhibition with respect to sexual and violent behavior and have only vague memories of what they did while intoxicated.8
How Effective Are SSRIs?
Selective serotonin reuptake inhibitors are generally effective in treating the symptoms of depression. As is the case with other medications, their effectiveness might differ from one person to another, depending on a number of factors.
Studies conducted on people with severe depression show that those who take SSRIs or other antidepressants are more likely to be relieved of their symptoms than those who take a placebo.
Several studies showed that symptom improvement attributed to the placebo effect was limited to 20 to 40 per 100 people, while antidepressants relieved the symptoms of 40 to 60 per 100 people.3
Another study that reviewed 522 antidepressant trials found that 5 specific antidepressant treatment regimens were relatively more effective and discontinued less frequently than others. Three of the medications used in these treatment trials were SSRIs:9
- Escitalopram (Lexapro).
- Sertraline (Zoloft).
- Paroxetine (Paxil).
In addition, a study published in the Journal of the American Medical Association found that a combination of antidepressants and cognitive behavioral therapy could be very beneficial for people suffering from severe depression.10
The study showed that those who underwent cognitive behavioral therapy in addition to taking SSRIs had a recovery rate of 75.2%, whereas those who only took antidepressants had a recovery rate of 65.6%.10
Data from the National Center for Health Statistics shows that antidepressant use has been on the rise in the United States. From 1999 to 2002, 7.7% of the population aged 12 and above was on antidepressants. From 2011 to 2014, that rate increased to 12.7%—a 65% increase over a period of 15 years.11
Women were twice as likely to take antidepressants as men, and non-Hispanic whites, both men and women, were more likely to take antidepressants than people from other races.11
A New York Times analysis in 2018 found that 15.5 million Americans had been taking antidepressants for at least 5 years. Almost 25 million had been on antidepressants for at least 2 years, which was a 60% increase since 2010.12
Taking SSRIs to Treat Depression
Selective serotonin reuptake inhibitors can be effective in treating the symptoms of depression and other mental health problems. However, it is important to follow the prescribing physician’s instructions carefully to minimize the risk of side effects and drug interactions.
The drug should not be discontinued or continued beyond the prescribed period unless approved by the physician. Although SSRIs are not considered addictive, stopping the treatment suddenly or missing several doses could lead to a withdrawal-like discontinuation syndrome in some cases. The dose should be reduced safely and gradually under professional guidance and supervision.
Again, different people may react in different ways to the same antidepressant. For instance, one drug may work better for one person than for another, or one person may experience more side effects than another after taking a particular antidepressant. The supervising physician will take all these factors into account when monitoring a patient’s prescription.
. Mental Health America. Antidepressants: Selective Serotonin Reuptake Inhibitors (SSRIs).
. National Health Service. (2018). Selective Serotonin Reuptake Inhibitors (SSRIs): Overview and Dosage.
. Institute for Quality and Efficiency in Health Care. (2006). Depression: How effective are antidepressants?
. Ferguson, J. (2001). SSRI Antidepressant Medications: Adverse Effects and Tolerability. The Primary Care Companion, 3(1), 22-27.
. Marken, P., and Munro, J. (2000). Selecting a Selective Serotonin Reuptake Inhibitor: Clinically Important Distinguishing Features. The Primary Care Companion, 2(6), 205-210.
. Harvard Health. (2014). What are the real risks of antidepressants?
. Volpi-Abadie, J., Kaye, A., and Kaye, A. (2013). Serotonin Syndrome. The Ochsner Journal, 13(4), 533-540.
. Herxheimer, A., and Menkes, D. (2011). Drinking alcohol during antidepressant treatment—a cause for concern? The Pharmaceutical Journal, 287, 732.
. National Institute for Health Research. (2018). The most effective antidepressants for adults revealed in major review.
. Hollon, S., DeRubeis, R., and Fawcett, J. (2014). Effect of Cognitive Therapy With Antidepressant Medications vs Antidepressants Alone on the Rate of Recovery in Major Depressive Disorder. JAMA Psychiatry, 71(10), 1157-1164.
. Centers for Disease Control and Prevention, National Center for Health Statistics. (2017). Antidepressant Use Among Persons Aged 12 and Older: United States, 2011-2014.
. Carey, B. and Gebeloff, R. (2018). Many People Taking Antidepressants Discover They Cannot Quit. The New York Times.