If you were at risk for developing depression, would you take a pill to prevent it?
For years, physicians have prescribed antidepressants to treat people grappling with depression. Some people can benefit from taking these medications during an acute episode. Others with a history of recurrent depression may take antidepressants to help prevent relapses.
But researchers are studying a new use for these medications: to prevent depression in people who may have never had it before.
It has long been known that people with head and neck cancer are vulnerable to becoming depressed. These types of cancers can impair functionality at the most basic levels, like speaking or swallowing. Treatments, such as surgery and radiation, for these diseases can be debilitating. Some studies have estimated that up to half of patients with head and neck cancers may experience depression.
A group of researchers in Nebraska examined what would happen if non-depressed patients were given antidepressants before receiving treatment for head and neck cancer. Published in 2013, the results of the randomized, placebo-controlled trial were startling: Patients taking an antidepressant were 60 percent less likely to experience depression compared with peers who were given a placebo.
In medicine, this approach is often referred to as prophylaxis, or a treatment used to prevent disease.
Prophylactic antidepressants have shown promise in other high-risk patient populations as well. A meta-analysis published in 2014 found that prophylactic antidepressants cut down the incidence of depressive episodes among people receiving therapy for hepatitis C by more than 40 percent. Randomized trials suggest that patients who take antidepressants early after a stroke experience significantly lower rates of depression. Small studies have also found that people receiving treatment for melanoma may be less likely to develop depressive symptoms if they are pre-treated with antidepressants.
These findings provide compelling reasons for physicians and patients to consider using these medicines to preempt mental-health issues. But this experimental frontier — which relies on prediction and prevention — is controversial.
After all, there aren't guidelines for how to treat a depressive episode that hasn't happened yet. It's not clear how long patients should stay on these medications or at what level of risk someone warrants prophylactic antidepressants.
And although antidepressants are usually well tolerated, these medications can come with side effects ranging from headaches to diarrhea to life-threatening reactions. These side effects can be immediate and obvious, whereas the benefits of prophylactic medications may be harder to appreciate over the long term.
Some critics have raised concerns about the financial incentives behind those who are promoting prophylactic antidepressants. For instance, one of the trials examining depression in stroke patients used the antidepressant escitalopram in the study; readers later discovered a lead author had undisclosed financial ties to Forest Laboratories, a company that manufactures this medication.
Indeed, antidepressants are already among the most widely prescribed medications in the United States; as many as 1 in 8 American adults take these medications each year. Expanding the use of antidepressants to people who have never had depression could substantially increase national consumption of psychiatric medications.
Others have taken issue with the idea of medicating patients against distressing situations. In a 2001 letter to the Lancet, Druin Burch mocked the idea of prophylactic antidepressants: "Antidepressants could be given prophylactically for weaning and for puberty, and to medical students before their final exams," the British physician wrote. "Worried relatives in hospital could be greeted — before any news was given — by a prescription for 2 months' worth of selective serotonin reuptake inhibitors to be started immediately in case the worst should happen. One could save money on hospital art and the niceties of interior decoration by simply prophylactically dosing all who worked and stayed there with a decent antidepressant."
This satire raises key questions about using pharmaceuticals to prevent depression: Can taking a pill really protect us from the emotional ravages of stroke or cancer? Are there other ways of helping patients cope with circumstances that place them at risk for depression?
Therapy may have an important role to play. The controversial escitalopram trial found that problem-solving therapy may also be effective in preventing post-stroke depression. Studies suggest that interventions such as cognitive behavioral therapy — a type of talk therapy that helps people change negative thinking patterns — may be useful in preventing postpartum depression. Meanwhile, mental-health experts are looking at whether stepped-care programs, which take a graduated approach to therapy and medication referrals, can help avert depression among vulnerable populations, such as elderly patients.
In the age of personalized medicine, it's not yet clear what role prophylactic antidepressants will play. So far, just a handful of studies have shown promising results among particularly high-risk patients. It remains to be seen whether these results can be replicated in larger trials and whether the medical community adopts these treatments. During my time in medical school and now in my residency in psychiatry, I have yet to see these kinds of prophylactic treatments — medication or otherwise — for people who have never had depression.
We may never be able to take away the stress of a disfiguring surgery, the despair from losing the ability to speak or the sadness that comes with a cancer diagnosis. But these studies suggest that doctors may be able to prepare patients for challenging situations in ways that protect them from sliding into clinical depression. Some patients may benefit from early use of antidepressants, others with therapy or a combination of the two.
If health-care providers are paying more attention to the mental health of patients at risk for depression, that seems like a step in the right direction.
Morris is a resident physician in psychiatry at the Stanford University School of Medicine.