Antidepressants: What to Know About Uses and Side Effects

Antidepressants are among the most prescribed medications in the United States. This is, in part, because the number of people diagnosed with depression and anxiety has been on the rise, and prescriptions jumped sharply among some age groups during the pandemic.

Despite the prevalence of these medications, some patients have “significant misconceptions” about how the drugs work, said Dr. Andrew J. Gerber, a psychiatrist and the president and medical director of Silver Hill Hospital in New Canaan, Conn.

About 80 percent of antidepressants are prescribed by primary care doctors who have not had extensive training in managing mental illness.

Dr. Paul Nestadt, an associate professor of psychiatry at the Johns Hopkins School of Medicine, said patients tell him, “‘You know, Doc, I’ve tried everything.’” But often, he said, “they never got to a good dose, or they were only on it for a week or two.”

Here are some answers to frequently asked questions about antidepressants.

How do antidepressants work?

There are many types of antidepressants, and they all work a bit differently.

In general, they initiate a change in the way brain cells — and different regions of the brain — communicate with one another, said Dr. Gerard Sanacora, a professor of psychiatry at the Yale School of Medicine.

Clinical trials have shown that antidepressants are generally more effective with moderate, severe and chronic depression than with mild depression. Even then, it’s a modest effect when compared with placebo.

The largest study of multiple antidepressants — nicknamed the STAR*D trial — found that half of the participants had improved after using either the first or second medication that they tried, and nearly 70 percent of people had become symptom-free by the fourth antidepressant.

Unfortunately there is no way of knowing ahead of time how an individual will respond to any given medication, so there might be a period of trial and error.

More research is needed to better understand how antidepressants work and their efficacy, especially when taken over the course of several years.

How do I know which one to take?

The most commonly prescribed antidepressants are selective serotonin reuptake inhibitors, or S.S.R.I.s, like Prozac or Zoloft, and serotonin-norepinephrine reuptake inhibitors, or S.N.R.I.s, like Cymbalta and Effexor. These two types tend to have fewer side effects than tricyclic antidepressants such as clomipramine or monoamine oxidase inhibitors like phenelzine.

Generally speaking, S.S.R.I.s and S.N.R.I.s are similarly effective.

But for some people, the differences between these medications — even ones in the same class — do not feel subtle at all. If one drug doesn’t feel right, there are other options. Experts advise working with your doctor to find the best fit.

How long do antidepressants take to work?

A common myth is that antidepressants are “quick fixes,” said Dr. Kao-Ping Chua, a pediatrician and health policy researcher at the University of Michigan Medical School. “They are most definitely not.”

In general, it can take one to two months to start seeing positive effects, experts say. And that’s assuming that you are taking the optimal amount.

In the beginning, clinicians tend to do more frequent check-ins so that they can monitor patients.

“It can take some time to identify the right dose,” Dr. Chua said. If the dosage is adjusted and it still isn’t working, “switching to a different antidepressant could be reasonable,” he said.

If you are experiencing acute or debilitating symptoms of depression, including thoughts of self-harm, seek immediate help by calling the Suicide and Crisis Lifeline by dialing 988.

Are side effects inevitable?

No.

Unlike older antidepressants, S.S.R.I. and S.N.R.I. medicines typically do not have many short-term side effects, and if they do, they are often mild.

Some of the most common ones, which can emerge within days of starting the medication, are a decrease in libido, headache, dry mouth and upset stomach. But many people experience no side effects at all, the experts said.

Short term side effects often fade as your body adjusts to the medication — you should know which ones are most likely to stick around within about two to three weeks of starting your medication, Dr. Nestadt said.

Decreased libido can be persistent, which may be a “dealbreaker,” he said. At that point, doctors might try to treat the problem with an additional medicine or switch to a different antidepressant.

Long-term use can bring other side effects, including weight gain or emotional dulling.

Finally, antidepressants may interact with other drugs. An S.S.R.I. paired with ibuprofen, for example, increases the risk of gastrointestinal bleeding. In addition, drinking alcohol while taking antidepressants is generally not advised.

Should I be doing anything else in addition to taking the medication?

Yes.

Therapy remains one of the first treatments recommended for depression. Antidepressants don’t make problems go away, but they can make it easier to cope with the problems, Dr. Chua said.

Lifestyle changes may also help, the experts said. Research has shown that exercising can reduce the symptoms of depression. And eating a heart-healthy diet may be beneficial, although more research is needed on how foods affect mood. Getting either too much or too little sleep also affects how we feel, so it’s important to get an adequate amount of rest.

Are antidepressants used for anything other than depression?

Yes.

They can also treat chronic pain conditions like shingles and migraines as well as anxiety, social phobia, post-traumatic stress disorder and obsessive-compulsive disorder.

What about the ‘black box’ warning?

In 2004, the Food and Drug Administration issued a “black box” warning saying that the use of certain antidepressants may be linked to suicidal ideation and behaviors in adolescents. Three years later, the warning was extended to include people ages 18 to 24.

The warning was based on an analysis of drug trials in which there were no suicides. The investigators did, however, find a significant risk of suicidal thoughts. Other studies have found that S.S.R.I.s decrease suicide rates and suicidal behavior among young people, which has led some experts to call for the warning to be re-evaluated.

How do I know when it’s time to get off antidepressants?

Psychiatrists usually recommend discussing whether to wean off the medication after you have been experiencing benefits for at least six months.

Studies show that “patients who are doing well on antidepressants are more likely to experience relapses of depression if they stop taking antidepressants,” Dr. Chua said.

But that’s not the case for everyone, he added, so check with your provider to decide whether to stop taking your medicine.

Psychotherapy may help people successfully discontinue antidepressants. But it’s always important to taper off the medication under a doctor’s supervision.

In some cases, if the tapering isn’t done slowly enough, patients may experience what are commonly called brain zaps, which feel like electric shocks, or other side effects such as nausea, said Dr. David J. Hellerstein, a professor of clinical psychiatry at Columbia University Irving Medical Center.

Slow tapering is especially important with an antidepressant that has a short half-life like Effexor or Paxil, he added. When patients discontinue drugs like those, the amount of medication in the body “tanks really quickly,” he added.

Some people with chronic and recurrent depression may need to take antidepressants indefinitely, Dr. Hellerstein said.

This is generally considered safe, he said, adding that it is significantly riskier for people to go without treatment.

If you are having thoughts of suicide, call or text 988 to reach the 988 Suicide and Crisis Lifeline or go to SpeakingOfSuicide.com/resources for a list of additional resources. Go here for resources outside the United States.