BPH Medications May Increase Risk of Self-Harm, Depression

There have been growing concerns that the 5α-reductase inhibitors (5ARIs) finasteride and dutasteride—known to reduce the risk of urinary tract problems in men with benign prostatic hyperplasia—might increase the risk of suicide, self-harm, and depression. Despite regulatory warnings about these side effects, though, very little population research has assessed the potential mental health risks associated with 5ARI use.

A study published March 20 in JAMA Internal Medicine suggests older men who take 5ARIs may not be at an increased risk of suicide, but they may be more likely to experience depression or self-harm. The most pronounced risks occurred during the first 18 months of use.

“The recognition of depression and self-harm as potential adverse effects of 5ARIs is important given their significant impact. However, the relatively small magnitude of these risks should not dissuade physicians from prescribing these medications in appropriate patients,” Blayne Welk, M.D., an assistant professor of surgery at Western University in London, Ontario, and colleagues wrote. “This research may help physicians counsel patients on the risks of 5ARIs.”

Welk told Psychiatric News that it was important to quantify the risks of 5ARIs in older adults as many of the post-marketing reports of suicide and depression involved younger men who took finasteride for alopecia, or male pattern baldness.

“The daily dose of finasteride for hair loss is 1 mg [daily], but older men who take these agents for BPH require stronger doses of 5 mg daily, which potentially heightens the risks,” he said.

Welk and his colleagues examined administrative databases to gain clinical and prescription information on 93,197 men aged 66 and older in Ontario who started taking finasteride or dutasteride between 2003 and 2013, as well as a matched number of older men not prescribed these medications.

During the follow-up period, there were a total of 38 suicides among patients taking 5ARIs and 36 among the control group, which equated to no statistical difference. There were also 169 incidents of self-harm and 1,750 cases of depression in the 5ARI group, and 130 cases of self-harm and 1,231 cases of depression in the control group—differences that were found to be statistically significant.

When the investigators stratified these incidents of depression and self-harm over time, they found that the biggest differences in risk were in the first 18 months of therapy. During this time, there was a 1.94-fold increased risk of self-harm and a 1.88-fold increased risk of depression among 5ARI users. After 18 months, the risks of self-harm were no longer different between the 5ARI and control groups. However, depression risk remained slightly elevated (1.22-fold) in men taking 5ARI.

When the researchers compared mental health outcomes in men taking finasteride with those taking dutasteride, they found the men appeared to be at a similar risk of suicide, self-harm, and depression.

Welk pointed out that since his group used administrative data to identify depression diagnoses, they were unable to make any qualitative interpretations, such as the severity of depressive symptoms or if the patients had stopped taking their medication prior to the onset of symptoms.

Stephen Thielke, M.D., M.P.H., an associate professor of psychiatry at the University of Washington, commended Belk and his colleagues for undertaking this study. “These investigators are not psychiatrists but they conducted a thoughtful analysis of mental health symptoms and outcomes,” he said. “More efforts like this by other medical specialists would be welcome.”

Thielke added that the results lead to a classic conundrum: “Physicians always like it when everything points in the same direction in terms of risks and benefits. In this case, we have two disparate outcomes; a tangible benefit for prostate health but a very real risk of depression.”

In such cases, physicians must rely on their own personal and moral judgments, and no amount of scientific evidence will delineate the right choice, he said, echoing thoughts he wrote in an accompanying JAMA commentary.

For psychiatrists treating a depressed patient on 5ARIs, the decision poses the quandary of deciding whether or not to advise a patient to stop taking a medication that the psychiatrist did not prescribe in the first place. Therefore, it’s important to exclude all other possibilities that may explain the onset or worsening of depressive symptoms, Thielke said.

Fortunately, if finasteride or dutasteride are posing a serious mental health risk, Welk noted that there are other options for treating BPH-related urinary problems, including other medications or prostate surgery.

This study was supported by the Institute for Clinical Evaluative Sciences Western site. ■

An abstract of “Association of Suicidality and Depression With 5α-Reductase Inhibitors” can be accessed here. The accompanying commentary, “The Risk of Suicidality and Depression From 5α-Reductase Inhibitors” is available here.