Effect of the dopamine stabilizer OSU 6162 on mental fatigue in neurological patients

Objective: The (‐)‐enantiomer of OSU6162 is a phenylpiperidine derivative characterized as a dopamine stabilizer, given its affinity for dopamine D2 receptors leading to mixed activating and inhibitory effects on behavior. More recently this compound has also been found to be a partial agonist on a number of serotonergic receptors, which further contributes to its behaviorally stabilizing properties. Early clinical studies have shown beneficial actions in patients with Parkinson's disease, Huntington's disease, schizophrenia, and metal fantigue. The present report deals with the actions of this agent in patients with mental fatigue of long duration following upon stroke or traumatic brain injury (TBI). Methods: OSU6162 was given orally for four weeks in doses increasing from 15 to 45 mg b.i.d. to twelve patients suffering from mental fatigue, following upon stroke (N=6) or TBI (N=6). OSU6162 was compared with placebo using a double‐blind, randomized crossover design. Patients included were well rehabilitated physically with no gross impairment in cognitive functions other than those related to the mental fatigue. Results: OSU6162 caused a remarkable improvement in mental stamina, as evaluated by a self assessment scale on mental fatigue. Statistical significance was reached on the primary end‐point (Mental Fatigue Scale). Principal component analysis demonstrated an overall positive treatment effect in seven of 12 patients. Beneficial responses were seen already during the first few days of active drug treatment. Increasing dosage caused no further improvement. Side effects consisted of short‐lasting mild nausea and attenuated appetite. These side effects disappeared upon dose reduction. Conclusion: OSU6162 offers promise as a candidate for treatment of mental fatigue after a stroke or TBI and deserves to be tested in other brain disorders accompanied by fatigue.