The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia.

Author(s): Smith D, Pernet A, Rosenthal JM, Bingham EM, Reid H, Macdonald IA, Amiel SA

Affiliation(s): Department of Diabetes, Guy's, King's and St Thomas', King's College School of Medicine, King's Denmark Hill Campus, London, UK.

Publication date & source: 2004-10, Diabetologia., 47(10):1704-11. Epub 2004 Oct 23.

Publication type: Clinical Trial; Randomized Controlled Trial

AIMS/HYPOTHESIS: Our hypothesis is that reducing release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with modafinil will enhance symptomatic and hormonal responses to hypoglycaemia. METHODS: Nine healthy men received, in random order, two 100-mg doses of modafinil or placebo, followed by an insulin clamp in which plasma glucose was either reduced stepwise to 2.4 mmol/l or was sustained at euglycaemia (four studies). Catecholamines, symptom scores and cognitive function were measured. RESULTS: Modafinil had no effect on the measured parameters during euglycaemia. During hypoglycaemia, autonomic symptom scores were significantly higher with modafinil (increase at lowest plasma glucose concentration 271.3+/-118.9 vs 211.2+/-80.4/40 min, p=0.019), and the heart rate response was increased (12,928+/-184 vs 6773+/-148 bpm/140 min, p=0.016). Deterioration in performance of two cognitive tasks was reduced: Stroop colour-word test (613+/-204 vs 2375+/-161/65 min, p=0.009) and accuracy of a simple reaction task (11.3+/-1.8 vs 9.4+/-3.7, p=0.039). CONCLUSIONS/INTERPRETATION: We conclude that modafinil improves adrenergic sensitivity and some aspects of cognitive function at hypoglycaemia, possibly by reducing neuronal central GABA concentrations.