Updates from the Annual Society of Biological Psychiatry Meeting

Rapid antidepressant effects possible with the cholinergic antagonist scopolamine Rapid onset of antidepressant effects was achieved with three intravenous infusions (4 μg/kg) of the acetylcholine receptor blocker scopolamine (also used to treat sea sickness), reported Furey & Drevets. This study used a double-blind crossover design, in which unipolar depressed patients were initially divided into two groups—one received scopolamine while the other received placebo. Then the groups switched and began using the other drug. The rapid onset effects of the three scopolamine infusions persisted into the follow-up period, while those who received placebo first improved when switched to the active infusions. EDITOR’S NOTE: Since scopolamine is an antagonist of cholinergic muscarinic receptors, these observations are consistent with data indicating that patients with mood disorders have an increased number of these receptors or a hypersensitivity to acetylcholine. The rapid onset of antidepressant effects with intravenous scopolamine is one of several new experimental approaches that all suggest antidepressant responses can be achieved much faster than the two weeks or more it takes conventional antidepressants to have an effect. Scopolamine joins a group of rapid-acting interventions that includes intravenous ketamine, the hypothalamic peptide thyrotropin-releasing hormone (TRH), and even one night of sleep deprivation, which all produce antidepressant effects very quickly. These procedures provoke a critical clinical treatment question: what manipulations best sustain these antidepressant effects for the longer term? When the acute-onset antidepressant response of a single infusion of ketamine could not be maintained with the anti-glutamatergic drug riluzol, as had been hoped, investigators from Mt. Sinai in New York began exploring the utility of repeated ketamine infusions. They were able to extend the acute onset of antidepressant effects of ketamine with three successive intravenous infusions. The infusions were well-tolerated, and there was no increase in dissociative or psychotic symptoms. Nancy Diazgarnados, working with Carlos Zarate at the NIMH, reported that a single i.v. (0.5 mg/ kg) infusion of ketamine in patients with treatment-resistant depression led to rapid onset of improvement in suicidal ideation, in addition to the previously reported improvement in depression and anxiety. Repeated infusions of ketamine can extend its acuteonset antidepressant effects