What Are the Long-Term Effects of Taking Antidepressants?

Michael O. Schroeder

Starkly contrasting views took center stage last month in a raging international debate over the long-term use of antidepressants and other psychiatric drugs.

In the debate, published in prominent medical journal The BMJ, Denmark-based researcher Peter C. Gøtzsche contended that taking antidepressants could increase a person's risk of dying prematurely, that the drugs do little for patients over a placebo and that the medicines should be scrapped altogether. Countering that view, London-based researcher Allan H. Young held that psychiatric drugs, which include antidepressants, are rigorously investigated for safety and effectiveness, and are needed to treat debilitating mental illness that could shorten a person's life expectancy.

The stark differences of opinion reflect widespread disagreement among mental health professionals over proper treatment. That leaves patients in the U.S., and abroad, dealing not only head-on with mental health challenges, but struggling to make sense of all the conflicting advice.

Arguing his case, Gøtzsche estimated there were likely 15 times more suicides among people taking antidepressants than reported by the Food and Drug Administration, which issued a black-box warning on antidepressants more than a decade ago. The agency did so after conducting meta-analyses of hundreds of studies involving nearly 100,000 patients that showed the rate of suicidal thinking or suicidal behavior doubled among those taking antidepressants to 4 percent of patients, up from 2 percent of patients given a placebo.

Gøtzsche argued that the modest effect of antidepressants and other psychiatric drugs doesn't justify the cost.

"Psychiatric drugs are responsible for the deaths of more than half a million people aged 65 and older each year in the Western world," he wrote. That's 539,000 in the U.S. and the European Union combined by his estimates, which he based on studies showing higher mortality rates in older patients taking antipsychotic drugs, such as those used to treat schizophrenia; benzodiazepines, which are prescribed to treat panic and anxiety disorders; and antidepressants. The figure wasn't broken down by type of medication.

Gøtzsche went so far as to suggest discontinuing the use of almost all psychiatric drugs, including all antidepressants, ADHD drugs and dementia drugs. "This would lead to healthier more long lived populations," he says.

On the contrary, researcher Allan H. Young argued in the published debate that psychiatric drugs are as beneficial as other treatments used for common, complex medical conditions -- and are sorely needed. "More than a fifth of all health related disability is caused by mental ill health, studies suggest, and people with poor mental health often have poor physical health and poorer (long term) outcomes," he wrote.

Young, who disclosed to The BMJ having done paid lectures and been on advisory boards for major companies that produce psychiatric drugs, says studies show that overall, taking psychiatric drugs lower mortality rates, including from suicide. He adds that it's crucial to consider the experience of the individual patient being treated with psychiatric drugs.

Young didn't discuss antidepressants specifically. But clinicians stateside, who did not participate in The BMJ debate, piggybacked on his point that, for certain patients, like those struggling with major depression, the drugs could make a critical difference.

"In general, there is controversy regarding the use of medications, and I think there is some concern about the overuse of medications and, at times, inappropriate prescribing," says Dr. Ben Weinstein, assessment division director at Menninger Clinic, a psychiatric center in Houston, and an associate professor of psychiatry at Baylor College of Medicine. "Taking medication of any sort is not something that should be done lightly, and it should be done in an informed way."

But just as risks related to non-mental health medications shouldn't prevent doctors from ever prescribing those drugs, Weinstein contends that stopping all antidepressants would be more harmful than helpful. "The risk of severe depression is higher than the risk of using medications appropriately," he says.

Those with depression are more likely to suffer a heart attack or stroke than those without the mental health condition, and some research now suggests treating depression, including with antidepressants, might lower cardiovascular risk.

"I think that would be a tremendous mistake," he says of Gøtzsche's suggestion that clinicians cease prescribing antidepressants altogether. "Appropriate prescribing of medications, I believe, saves lives."

Dr. Dost Ongur, chief of the psychotic disorders division at McLean Hospital in Boston, and an associate professor of psychiatry at Harvard Medical School, agrees.

Ongur and a colleague of Weinstein's, Dr. Blake Haren, medical director of the adult division at Menninger, say research related to suicide doesn't prove antidepressants themselves cause individuals to commit suicide at a higher rate.

They note that the mental health issues patients face, like depression, raise suicide risk and make it difficult to discern the role of antidepressants alone. In other words, an observed link between psychiatric medications and suicidal thinking and behavior doesn't prove the drugs lead more patients to take their lives.

Still, the FDA black-box warning remains in effect for the drugs, and additional risks related to antidepressants -- some common and mild, others rare and potentially life-threatening -- highlight the need for a precise risk-benefit analysis in determining which patients are appropriate candidates for antidepressants, and how long those patients should take the drugs.

"The risks of adverse events related to antidepressants come in all varieties. Some ... you could live with them, like dry mouth or an occasional headache," Ongur says. "Others are quite severe and even life-threatening at times, although those are extremely rare."

Ongur -- who served in 2013 on a scientific advisory board for Eli Lilly & Co. that met once to consider strategies for development of new antidepressants -- points to Wellbutrin, a widely used antidepressant, among other examples.

"At high doses in some people [it] can be associated with seizures," he says of the drug, also called bupropion. In addition: "Tricyclic antidepressants, which are an older class of medications that have been available since the 60s, are associated with abnormalities in heart rhythm. There is more recent evidence that even SSRIs" -- or serotonin reuptake inhibitors, the most widely prescribed class of antidepressants -- "at higher doses, can cause heart rhythm abnormalities."

Patients who take antidepressants usually do so for at least months if not years, since the medications take four to six weeks to start working. "Ultimately, we don't know very well how these medications interact with the brain in the long-term," Ongur says.

That means standard rules of medication still apply: You want to take the drug as long as necessary, but no longer. In the case of taking antidepressants to treat depression, that includes being careful not to stop too early either, which could cause a relapse -- though relapses can occur in patients who take antidepressants daily, as prescribed.

Many patients struggle with this phenomenon, called tachyphylaxis, also known as "Prozac poop-out." "So somebody who stays on an antidepressant for several years, who initially responded well, may start to see a return of symptoms even though they're on the full dose of the medication," Ongur says.

Some research indicates taking antidepressants could worsen depression in patients down the road.

Long-term antidepressant use may also be associated with an increased risk of Type 2 diabetes, according to a study published last year in Journal of Clinical Psychiatry. Though others have disputed the link, researchers recommended long-term use of antidepressants be evaluated more cautiously for this potential risk.

In general, Ongur says patients should weigh risks of relapse from depression against potential treatment harms when talking with a provider about starting on -- or continuing -- antidepressants, and in discussing how long to take the drugs.

For patients with milder symptoms, if medication is prescribed at all, it may be taken shorter term, while clinicians say those with major depression are most likely to benefit from taking the medication -- and long-term.

Those prescribed antidepressants to treat other issues, including off-label uses for which a given drug wasn't originally approved, should pay close attention to whether the doctor follows the "community standard," Ongur adds, and prescribes it as medical peers do.

According to the Centers for Disease Control and Prevention, about 1 in 10 Americans ages 12 and older report taking antidepressants, one of the most commonly prescribed classes of medications behind only analgesics, or drugs to treat pain, and cholesterol-lowering medicines.

Whether an antidepressant is prescribed to treat an anxiety disorder, migraines, irritable bowel syndrome or for anything else, Ongur says, "You have to really weigh, how bad [is this issue] for me? Do I really need this medicine? After all, with any medicine you're putting a chemical in your body." For example, if you only have an occasional migraine, you might forgo taking it; while frequent migraines that interfere with work or family life might make it worth it, he says.

Whether for off-label uses or for the treatment of depression ask, too, about alternative treatment approaches and lifestyle changes to determine if you'd be better off without medication or if there are things you can do to enhance a drug's effects. Studies show the combination of antidepressants and talk therapy is typically more effective at treating depression than medication alone.

Experts say the severity of depression and the length of time a patient has experienced symptoms often determine how well one might fare without medication. Exercise -- cardio in particular -- is recognized as a natural antidepressant.

While some couldn't imagine going off medication, Ongur says, others try various antidepressants to no avail, though clinician's caution against stopping antidepressants abruptly as that can cause withdrawal, which can worsen symptoms of depression.

Whatever you do, if you're facing depression, experts agree you shouldn't avoid seeking professional help -- even though professionals disagree on whether antidepressants are the answer.