Antipsychotics Prescribed to Adults With Depression Linked to Higher Mortality Rate

Researchers have found that adults suffering from depression who started to take a dose of newer antipsychotic drugs have a higher mortality risk in comparison to a control group that initiated augmentation with a second antidepressant.

The research was carried out by scientists from Rutgers and Columbia University and was published in the journal PLOS ONE.

Even though antidepressants are the primary pharmacological treatment for depression, many people do not react to the first course of medication. Further treatment options include trying another antidepressant as well as various augmentation methods, such as augmentation with a second antidepressant and augmentation with newer antipsychotics like aripiprazole, quetiapine, and olanzapine.

“Antipsychotics have well-recognized and often serious adverse effects, including a more than 50 percent increased mortality risk in older adults with dementia,” said lead author Tobias Gerhard, an associate professor at Rutgers Ernest Mario School of Pharmacy. “It had been previously unknown whether this mortality risk applies to non-elderly adults using newer antipsychotics as an 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.”

Newer Antipsychotic Augmentation Poses Higher Risk of Mortality

The study analyzed data of 39,582 Medicaid beneficiaries aged 25 to 64 from 2011 to 2010, linked to the National Death Index. After a period of medication with a single antidepressant, patients either started augmentation with a newer antipsychotic or with a second antidepressant.

The experts found a 45 percent relative increase in mortality risk for those that initiated a newer antipsychotic treatment, which means there’s one additional death for every 265 people taking the antipsychotic for one year.

“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,” said Gerhard.

“Of particular relevance for our results is a finding from our previous work,” the researcher explained. “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. Our results emphasize the importance of considering newer antipsychotics only after non-response to less risky, evidence-based treatment options has been established.”

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