Effects of S-ketamine on brain activation in healthy women, healthy
women prone to depression and fibromyalgia patients.

The NMDA receptor antagonist ketamine is used as an anesthetic, painkiller and, more recently, also as an antidepressant, even though the neural mechanism of its antidepressant action is still unknown. Ketamine causes rapid improvements in mood and suicidality in treatment-resistant patients (Berman et al., 2000; Caddy, Giaroli, White, Shergill, & Tracy, 2014; Krystal, Sanacora, & Duman, 2013; Murrough et al., 2013; Singh et al., 2016; Zarate et al., 2006). However, the effects of ketamine in groups of depressed patients other than treatment-resistant / severely depressed, are still unknown. Previously, we investigated the effects of S(+)-ketamine on brain activation in healthy male participants but the results are difficult to extrapolate to depressed patients as well as to women. To further elucidate the (neural) mechanisms of ketamine, which may underlie its (rapid) antidepressant response, we will investigate the effects of ketamine on brain activation in healthy women, women prone to depression and fibromyalgia patients.

The primary aim of this project is to further elucidate the (neural) mechanisms of ketamine, which may underlie its (rapid) antidepressant response.

-30 (baseline), 20, 30, 60, 90, 120 and 150 minutes after the start of the administration MRI scans will be acquired.

Questionnaires will be administered at baseline, 40, 80, 110, 150 and 180 minutes after the start of the administration.

Arterial blood samples will be obtained at intervals used for pharmacokinetic studies.

Esketamine 0.4 mg/kg or placebo will be administered intravenously in 40 minutes.