Although sadness is something we all experience from time to time, depression interferes with daily life and normal functioning, causing pain not only for us but also for those who care about us.

Current research suggests depression is caused by a combination of genetic, biological, environmental and psychological factors. Major depressive disorder (MDD) affects approximately 16 million people in the United States and 121 million people worldwide.

But hope may be on the horizon.

Typically, antidepressants are the first-line treatment for moderate and severe depression in primary care, and there has been a steady rise in antidepressant prescribing in recent years. While many patients with MDD respond to antidepressant treatment, 10 to 30 percent do not improve or only partially respond.

In these cases known as treatment-resistant depression (TRD) — which is associated with chronicity, morbidity and functional disability — patients do not respond adequately to appropriate courses of at least two antidepressants.

A new study published in Biological Psychiatry has demonstrated that esketamine, which has a novel mechanism of action, produced rapid effects in patients who did not respond to currently available therapies. Jaskaran Singh from Janssen Research & Development, LLC in San Diego and colleagues examined the safety and efficacy of esketamine in 30 patients with TRD.

Patients were randomly assigned 1:1:1 to receive an intravenous (IV) infusion of 20 mg/kg or .40 mg/kg esketamine or placebo over 40 minutes on Day 1. The primary endpoint was change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from Day 1 (baseline) to Day 2. Nonresponders who received placebo on Day 1 were randomly assigned to 1:1 to IV eskatamine .20 mg/kg or .40 mg/kg on Day 4.

The earliest antidepressant effect was noted two hours after the first infusion. Within three days, over 60 percent of patients who received either dose of eskatamine improved in depressive symptoms, compared to only 37 to 56 percent of patients after six to 12 weeks with conventional antidepressants.

The results were statistically significant and clinically meaningful for both esketamine dose groups with a robust onset of efficacy evident two hours after infusion as assessed by MADRS total score, results that stand in sharp contrast to the time course (4-12 weeks post dose) of response typically seen with conventional oral treatments for MDD. The outcome measures reflecting improvement in depressive symptoms did not different significantly between the two doses of IV esketamine, suggesting equal efficacy and safety.

The researchers suggest additional studies are needed to assess alternative formulations of esketamine to avoid the inconvenience of IV infusion and to develop treatment paradigms that would enable sustained long-term response.