Antidepressants Side Effects, Effectiveness Questioned In New ISMP Report

A drug safety group is taking issue with a recent study on the overall effectiveness of antidepressants, indicating that it painted too rosy of a picture for a class of drugs that often do not work, and may carry serious and potentially life-threatening side effects. 

On May 16, the Institute for Safe Medication Practices (ISMP) issued its latest QuarterWatch Report (PDF), highlighting concerns about the safety and effectiveness of antidepressants.

The report took aim at a recent study published in the medical journal in The Lancet, which found that most antidepressants are more effective than a placebo.

While the study indicated that not all depressants were equal, and determined that some appeared to be far less effective than others, the ISMP report suggests the study got a lot wrong, and resulted in too positive of an outlook.

As an example, the ISMP took a look at Trintellix (vortioxetine), a medication which fell about at the midpoint of effectiveness in The Lancet study.

Trintellix was put on the market in 2014, originally under the name Brintellix. However, Takeda had to change the drug’s name due to its similarity to Brilinta; a blood thinner.

The antidepressant drug is used to treat adult patients with major depressive disorders (MDD). It is part of a class of antidepressants called serotonin reuptake inhibitors (SSRIs), which are designed to re-balance chemical levels in the brain to decrease depression. The medication is manufactured by Takeda Pharmaceuticals

The ISMP noted that the drug has been linked to hundreds of adverse event reports of aggression and hostility, as well as suicidal thoughts, sexual desire disorders, and eating disorders; particularly excessive hunger and abnormally large food intake. Takeda told the ISMP that many of those reports may be linked to the patients’ depression and not the drug itself.

However, the ISMP also looked at data from clinical trials before the drug was approved, indicating that the results of those trials also show that the drug has limited effectiveness on top of potential safety issues.

“While the FDA judged it an effective treatment, vortioxetine failed to demonstrate a benefit in 4/10 clinical trials and the trials did not document more benefit than a placebo in U.S. patient subgroups taking the recommended 10 mg daily starting dose in any trial,” the ISMP noted. “Treatment failure occurred in 19%-20% taking vortioxetine, who declined to complete the trial primarily because of adverse effects or lack of efficacy.”

The ISMP report also indicates that those results were the best the clinical trial could do, even though it was limited to patients with the most severe forms of depression, where the odds of the drug showing a strong benefit were highest.

Trintellix was cited as one example of problems throughout the antidepressant drug class, which ISMP indicates The Lancet study failed to encapsulate.

“This review of vortioxetine illustrates that the new meta-analysis in The Lancet fails to communicate the marginal efficacy and substantial side effect profile of typical antidepressant drugs,” the ISMP report states. “The placebo effects were large (32% improved substantially), and the difference from the drug effect might be too small to detect without a sensitive scoring instrument such as used in the trials. Only more severe depression was studied, likely because previous studies in mild and more moderate depression have failed.”