In a new study, adults with depression who added newer antipsychotic medications to their treatment had an increased mortality risk compared to a control group that added a second antidepressant.
Physicians managing adults with depression should be aware of this potential for increased mortality, the study finds.
Although antidepressants are the first-line pharmacological treatment for depression, many people don’t respond to the first course of treatment.
Subsequent treatment options include switching to another antidepressant followed by various augmentation strategies, including prescribing a second antidepressant and newer antipsychotics, such as aripiprazole, quetiapine, and olanzapine.
“Antipsychotics have well-recognized and often serious adverse effects, including a more than 50% increased mortality risk in older adults with dementia,” says lead author Tobias Gerhard, an associate professor at Rutgers University’s Ernest Mario School of Pharmacy.
“It had been previously unknown whether this mortality risk applies to nonelderly adults using newer antipsychotics as augmentation treatment for depression.
The clinical trials that led to the approval of various newer antipsychotics for depression were just too small and too short to be informative for this question.”
For the new study in PLOS ONE researchers looked at data of 39,582 Medicaid beneficiaries ages 25 to 64 from 2001 to 2010, linked to the National Death Index.
After a period of treatment with a single antidepressant, study patients received prescriptions for a newer antipsychotic or a second antidepressant.
The researchers found a 45% relative increase in mortality risk for those initiating a newer antipsychotic, which for the study cohort translated to one additional death for every 265 people taking the antipsychotic for one year.
“Our results require replication, ideally with a publicly financed pragmatic randomized controlled trial.
However, in the meantime, our study suggests that physicians should consider prescribing antipsychotics to adults with depression carefully, as the potential health risks are substantial and the benefits are quite modest and controversially debated,” says Gerhard.
“Of particular relevance for our results is a finding from our previous work. It is well-known that most antidepressants take about four to six weeks to be fully effective.
However, contrary to the drug label and treatment guidelines many patients in the United States initiate antipsychotic treatment for depression without having completed an adequate prior trial with a single antidepressant,” Gerhard says.
“Our results emphasize the importance of considering newer antipsychotics only after non-response to less risky, evidence-based treatment options has been established.”
