FDA approves Depression drug after rejecting it multiple times in 20 years

Gepirone hydrochloride extended-release (ER), marketed as Exxua, has finally received FDA approval for the treatment of major depressive disorder (MDD) in adults. This antidepressant is unique as it selectively targets the serotonin 1A receptor, which plays a crucial role in regulating mood and emotions. Gepirone ER had faced multiple rejections from the FDA over nearly two decades, but this recent approval marks a significant milestone.

The approval is based on data from two 8-week clinical trials involving outpatients aged 18 to 69 who met the criteria for MDD. Both trials demonstrated that gepirone ER was superior to a placebo in improving depression scores measured by the 17-item Hamilton Depression Rating Scale (HAMD-17). In a maintenance study, patients who responded to gepirone ER during open-label treatment experienced a significantly lower rate of relapse compared to those who switched to a placebo.

Notably, the labeling for this drug does not list sexual dysfunction or weight gain as adverse reactions, attributed to its unique mechanism of action. However, like other antidepressants, gepirone ER carries a black box warning for an increased risk of suicidal thinking and behavior in young adults. Common adverse events associated with this drug include dizziness, nausea, insomnia, abdominal pain, and dyspepsia. Less common risks include serotonin syndrome and manic episodes in individuals with bipolar disorder.

Certain contraindications for gepirone ER use include a prolonged QTc interval, severe liver problems, concomitant use of monoamine oxidase inhibitors (MAOIs), strong CYP3A4 inhibitors, and moderate CYP3A4 inhibitors. Electrolyte abnormalities should be corrected before starting treatment, and patients should be closely monitored, particularly those with specific cardiac conditions. ECGs should also be performed at various stages of treatment to ensure safety.