Optimizing the glutamatergic challenge model for psychosis, using S(+)-ketamine to induce psychomimetic symptoms in healthy volunteers

In this study, 36 healthy volunteers (21 males and 15 females) received infusions of S(+)-ketamine or placebo to achieve pseudo-steady state concentrations of 180 and 360 ng/mL during two hours. The target of 360 ng/mL induced increasingly more intensive effects than expected, and the targets were subsequently reduced to 120 and 240 ng/mL, which were considered tolerable. There was a clear, concentration-dependent psychomimetic effect as shown on all subscales of the positive and negative syndrome scale (e.g. positive subscale +43.7%, 95%CI 34.4–53.7%, p < 0.0001 for 120 ng/mL and +70.5%, 95%CI 59.0–82.8%, p < 0.0001 for 240 ng/mL) and different visual analogue scales. The startle reflex was inhibited (prepulse inhibition) by both main target concentrations to a similar extent, suggesting a maximum effect. Ketamine was found to constitute a robust model for induction of psychomimetic symptoms and the optimal concentration range for a drug interaction study would be between 100 and 200 ng/mL.

Source: Journal of Psychopharmacology - March 17, 2015 Category: Psychiatry Authors: Kleinloog, D., Uit den Boogaard, A., Dahan, A., Mooren, R., Klaassen, E., Stevens, J., Freijer, J., van Gerven, J. Tags: Original Papers Source Type: research