Studies Provide Comparative Data on Antidepressant Safety and Efficacy

Sertraline may be more effective than cognitive behavioral therapy (CBT) for treating depression in patients on dialysis, according to a study at Kidney Week 2018. Another study found elevated heart risks with selective serotonin reuptake inhibitors (SSRIs) with greater QT-prolonging effects.

Almost one-quarter of patients on dialysis have depression, but many don’t receive treatment, said Rajnish Mehrotra, MD, professor of medicine at the University of Washington in Seattle. One obstacle has been the dearth of data on depression treatment in patients on dialysis, who are typically excluded from clinical trials of antidepressants in the general population, noted Magdalene Assimon, PharmD, PhD, a postdoctoral fellow at the University of North Carolina Kidney Center in Chapel Hill. There have been few studies specifically exploring the comparative efficacy or safety of antidepressant therapies in patients on dialysis.

“We extrapolate both efficacy and safety evidence [from trials in other populations], which may or may not apply to patients on dialysis because of their unique situation with drug pharmacokinetics and their cardiovascular burden,” Assimon said.

But the two studies presented at Kidney Week 2018 may help begin to close the knowledge gap.

CBT versus sertraline

During the High Impact Trials session, Mehrotra presented results of a multicenter randomized trial that began with depression screening for 2569 patients in 41 dialysis facilities across 3 metropolitan areas. The 636 patients with Beck Depression Inventory (BDI) scores greater than or equal to 15 were randomized to receive either a motivational interview about depression treatment or a brief encounter with a research staff member who alerted patients to their depression and asked if they would like to participate in a treatment study. The study found no significant difference in treatment initiation between those two groups (66% vs. 64%, respectively).

“It is possible that we pre-selected individuals [who] were interested in getting treatment anyway, and that is why we were not able to show a difference between people randomized to engagement versus control,” Mehrotra said.

The 120 patients who decided to initiate therapy were then randomized to CBT or the SSRI sertraline. Patients receiving CBT were given the option of having a therapy session during dialysis or a separate private session. Both groups saw a decline in depression symptoms, but sertraline resulted in a greater decrease in depression symptoms as measured by the Quick Inventory of Depressive Symptoms (QIDS-C)—1.84 compared with CBT. Patients on sertraline also had more improvement on measures of disability, energy/vitality, life satisfaction, and sleep.

“In patients undergoing hemodialysis with major depressive disorder, depressive symptoms improved both with individual CBT and sertraline, but improvement was greater with sertraline,” Mehrotra said.

However, sertraline was associated with a higher frequency of adverse events, he noted. Patients who received sertraline were more likely to be hospitalized and had threefold more mild and moderate adverse events than those receiving CBT. Mehrotra said he hopes the results help guide clinicians and patients on dialysis to choose the depression therapies that are the best fit for themselves.

“This comparative-effectiveness, randomized controlled trial could allow for informed decision-making by patients and physicians based on preference, cost, and availability,” he said.

Assimon agreed that patient preferences are key in depression treatment. She noted that some patients may find it more convenient to take medication than undergo CBT.

“[The trial] is a step in the right direction, because it shows, again, that the drug is efficacious,” said Assimon. However, she cautioned the study is likely not large enough to assess safety.

SSRI heart risks

Use of SSRIs in patients on dialysis who have depression will likely increase because of a new quality metric in Medicare’s ESRD Quality Incentive Program that promotes depression screening and treatment, noted Assimon. But some drugs in the class have been associated with prolonged QT intervals in electrocardiograms of patients taking the medications, according to a drug safety communication from the US Food and Drug Administration (FDA). Prolonged QT intervals can lead to potentially deadly heart rhythm abnormalities, according to the FDA. Such adverse effects may be particularly concerning for patients on dialysis who are at increased risk of heart problems.

“The general consensus is that end stage renal disease creates a proarrhythmic environment,” Assimon said.

To assess the heart risks of SSRIs, Assimon and her colleagues looked at 2007–2014 data from the United States Renal Data System on patients on dialysis enrolled in Medicare. They compared the risk of sudden cardiac arrest in the first year of taking citalopram and escitalopram, which have greater QT-prolonging effects, with the risk while taking fluoxetine, fluvoxamine, paroxetine, and sertraline, which have more modest effects on QT intervals. The study included 65,654 patients. Taking citalopram or escitalopram was associated with an increased 1-year risk of sudden cardiac death (adjusted hazard ratio 1.14; 95% CI: 1.05–1.25) compared to the SSRIs with lower QT-prolonging potential. Women, patients age 75 or older, and those with structural heart disease or taking additional QT-prolonging medications were particularly at risk.

“Our results suggest that SSRI therapy selection should be individualized, and clinicians should consider the differential QT-prolonging properties,” Assimon said. For example, they should consider factors like age, gender, existing heart conditions, and concurrent medications when prescribing SSRIs. They may want to consider monitoring patients with ECGs.

Mehrotra also urged caution about potential QT-prolonging drugs, including SSRIs.

“It is important to be careful when using drugs that prolong QTc (whether SSRIs or others) in patients with end-stage renal disease,” he said. “A significant proportion of patients undergoing dialysis have baseline QTc, and a longer QTc does increase risk for sudden cardiac death, the most common cause of death in patients undergoing dialysis.”

He noted that he and his colleagues considered cardiac risk during the design phase of the trail. They chose sertraline because it has been used in large clinical trials of patients with congestive heart failure and coronary artery disease and was not associated with a higher risk of cardiac events.

“This reassured us when selecting the drug,” he said.

“Comparative Efficacy of Therapies for Depression for Patients Undergoing Hemodialysis
” Oral abstract 148

“The Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors (SSRIs) in the Hemodialysis (HD) Population” Oral Abstract 093

December 2018 (Vol. 10, Number 12)