Adjunctive Intranasal Esketamine Rapidly Decreases Depression Symptoms

Intranasal esketamine taken twice weekly can rapidly reduce symptoms of people with treatment-resistant depression, according to a study in JAMA Psychiatry.

Esketamine is the mirror image molecule of ketamine. The two molecules are very similar biologically, but esketamine is reported to produce fewer psychomimetic side effects like delirium or hallucinations.

Ella Daly, M.D., of Janssen Research and Development and colleagues recruited 67 adults with treatment-resistant depression; treatment resistance was defined as having a history of inadequate response to two or more antidepressants. The patients were randomly divided so that half received placebo while the other half received 28 mg, 56 mg, or 84 mg of esketamine twice weekly for two weeks. All participants continued the antidepressants they were receiving at study entry during the trial.

The researchers found that all three esketamine doses produced significantly greater reductions in the participants’ Montgomery-Asberg Depression Rating Scale scores from baseline after one week. The improvements escalated with dose, with 4.2, 6.3, and 9.0-point improvements for the 28 mg, 56 mg, and 84 mg doses, respectively.

After 15 days, all participants were invited to enroll in a 60-day open-label period, during which they received esketamine twice weekly for two weeks, weekly for three weeks, and then every two weeks thereafter. The improvements in depressive symptoms were maintained during the open-label period despite the reduced dosing frequency, and for up to two months after the discontinuation of esketamine.

“In general, the esketamine doses used in this study appeared to be safe, with no new or unexpected safety concerns observed,” the authors wrote. “Overall, transient increases in blood pressure after the dose, particularly increases in systolic blood pressure, support an increase in cardiac output as the underlying mechanism, consistent with previous reports of ketamine.”

To read more about this topic, see the Psychiatric News article “Ketamine Is a Potent Antidepressant, but How Does It Work?”

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Lurasidone Found to Be Safe, Effective in Patients With Mixed Forms of Major Depression

Once daily treatment with lurasidone for six weeks decreased depressive and manic symptoms in patients with mixed forms of major depression with limited adverse effects, according to a study published Tuesday in AJP in Advance.

A growing body of evidence suggests that manic symptoms below the threshold for hypomania (mixed features) are common in individuals with major depressive disorder. Little is known of the best treatment options for this form of depression, but some clinical trials have suggested that standard antidepressants may be ineffective for this condition and associated with potential treatment-related complications, including suicidal ideation and behavior, manic switch, agitation, and impulsivity.

For the current study, researchers from Stanford University and Sunovion Pharmaceuticals randomly assigned patients aged 18-75 with a major depressive disorder (based on DSM-IV-TR criteria) who also reported two to three manic symptoms for at least two weeks prior to screening to take lurasidone (20-60 mg) or placebo daily for six weeks.

Lurasidone significantly improved depressive symptoms compared with placebo, as indicated by changes from baseline in Montgomery-Åsberg Depression Rating Scale score and the Clinical Global Impressions severity subscale score. Manic symptoms were also significantly improved in the lurasidone group, and treatment with lurasidone was associated with significant improvement both in anxiety symptoms and in patient-reported functional impairment. Nausea (6.4% and 2.0% in the lurasidone and placebo groups, respectively) and somnolence (5.5% and 1.0%) were the most common adverse events reported by the study participants.

“There is a pressing need for evidence-based treatments of major depressive disorder presenting with subthreshold hypomanic symptoms (mixed features), especially given its complex course and associated morbidity,” the study authors wrote. “Treatment with lurasidone was well tolerated, with a favorable benefit-risk profile in this difficult-to-treat clinical population. Further investigation is needed to determine whether these findings are applicable to other agents in the atypical antipsychotic class.”

For related information on lurasidone’s effectiveness in treating bipolar I depression, see the Psychiatric News article “Data Released Backing Lurasidone’s New Indication.”

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