Researchers at Rutgers and Columbia University have found an increased mortality risk for adults with depression who began augmentation — the use of two or more medications for better treatment — with newer antipsychotic drugs than those who initiated augmentation with a second antidepressant, according to a study.
Although antidepressants are the first-line pharmacological treatment option for depression, more than half of patients do not achieve remission from their first trial, according to the study. Subsequent treatment options include switching antidepressants followed by augmentation with a second antidepressant or newer antipsychotics, such as aripiprazole, quetiapine and olanzapine.
Randomized control trials have shown increased mortality risk for older adults with dementia treated with newer antipsychotics, but these trials were too small to detect mortality risk for other populations, said lead author Tobias Gerhard, an associate professor at the Ernest Mario School of Pharmacy.
“And this was really the motivation for this work,” Gerhard said. “To see whether, when we look at (a) very large number of patients that take these drugs for depression in clinical practice using, in this case, Medicaid billing data or administrative claims data, whether this mortality effect that was observed in older adults with dementia would apply to non-elderly adults that take the drugs for depression.”
The researchers analyzed data of 39,582 Medicaid insured patients ages 25-64 from 2001-10 that were linked to the National Death Index, according to the study. After a 90-day period of antidepressant treatment, patients either initiated augmentation with a newer antipsychotic or with another antidepressant.
There was a 45 percent relative increase in mortality risk for those who initiated augmentation with an antipsychotic, according to the study. This translated to one additional death for every 265 people taking antipsychotics for one year, according to a press release.
Antipsychotics are primarily used to treat schizophrenia and bipolar disorder, where the benefits clearly outweigh the risks of using the medication, Gerhard said. Meanwhile, clinical trials have shown that the effects of antipsychotics in reducing depression are limited, he said.
“When you have a small benefit and a small mortality risk, then it's really a harder decision,” Gerhard said. “So this work isn’t meant to make that decision, it's just meant to inform patients and physicians that there might be a mortality risk there, because currently, that's not something that is recognized.”
Most patients who initiate an antipsychotic for depression have not used multiple antidepressants for a sufficient amount of time to see the effects, Gerhard said. It takes approximately 4-6 weeks to see the effects of an antidepressant, and treatment guidelines recommend that antipsychotics be considered only after treatment with at least two antidepressants has failed, he said.
“My wish for this study is that it would motivate people to replicate it,” Gerhard said. “Ideally, (we would) have a funding agency that would fund the clinical trial to really show it with a stronger study design and that it would somewhat increase (caustion in the) use of antipsychotics so that, at least, you wouldn't use the drug without carefully making this trade-off between benefits and risks and without exhausting the recommended, less risky treatment alternatives.”