Effect of apomorphine on motor and cognitive function in melancholic patients: a preliminary report

Given the many clinical parallels between melancholia and disorders associated with impaired dopaminergic function such as Parkinson's Disease (PD), it has been hypothesised that major depressive disorder, and in particular the psychomotor features of melancholic depression, may also be associated with a hypodopaminergic state. If this is the case, then the use of a dopamine agonist might lead to reversal of both the cognitive and motor impairments seen in these patients. A double-blind, placebo-controlled cross-over design was used to test the effect of apomorphine on motor and cognitive function in seven melancholic subjects (as defined by the CORE instrument) and five control subjects. The testing battery included the following items: finger tapping, rapid alternating movements, verbal fluency, Rey Auditory Verbal Learning Task, digit symbol substitution task and simple and complex reaction times. The independent t-test, after covarying for age, revealed significant impairment in melancholic subjects for the walking task and digit symbol substitution at baseline. Results of the ANCOVA revealed no impact of time or drug condition, either alone or in combination, upon task performance in either group whether assessed separately or jointly. Results of a MANCOVA revealed that apomorphine impaired performance on some cognitive tasks, and that this was seen to a lesser extent in melancholics than control subjects. There was no evidence that the dopamine agonist apomorphine improved cognitive or motor function in subjects with strictly defined melancholia, suggesting that psychomotor retardation is not associated with a hypodopaminergic state. Our conclusions, however, were limited by small sample size; minimal baseline task impairment in depressed compared to control subjects; mild sedation in many subjects during task performance; and lack of serum apomorphine levels.