Effects of L-DOPA Monotherapy on Psychomotor Speed and [11C]Raclopride Binding in High Risk Depressed Older Adults

Abstract Background A high-risk subgroup of older patients with depression has slowed processing and gait speeds. This study examined whether carbidopa/levodopa (L-DOPA) monotherapy increased dopamine availability, increased processing/gait speed, and relieved depressive symptoms. Methods Adult outpatients with depression >59 years old underwent baseline [ 11 C]raclopride positron emission tomography followed by open L-DOPA for 3 weeks (1 week each of 150 mg, 300 mg, and 450 mg). Generalized estimating equations tested the pre- and post-L-DOPA differences in processing and gait speed measures, depressive symptoms, and reported side effects. The decrease in binding potential between the pre- and posttreatment scans indexed enhanced synaptic dopamine availability induced by L-DOPA treatment. Results Thirty-six subjects participated (age, 75.3 ± 7.5 years; 44.4% male). Significant, dose-dependent increases in processing and gait speed were observed with L-DOPA (450-mg dose: processing speed factor score effect size = 0.41, p  = .001; dual-task gait speed effect size = 0.43, p  = .002). [ 11 C]raclopride decrease in binding potential was significantly different from 0 in sensorimotor ( t 24 = −4.85, p t 24  = −2.52, p  = .019) but not in limbic striatum ( t 24  = 0.265, p  = .793). Depressive symptoms decreased significantly on the Hamilton Rating Scale for Depression (effect size = −0.37, p  = .002). Dropout rate was 8.3%, and nausea was the most frequently reported side effect. Conclusions By enhancing availability of dopamine, L-DOPA improved processing and gait speed in older adults with depression and significantly decreased [ 11 C]raclopride binding in selected striatal subregions.