Effects of L-DOPA monotherapy on psychomotor speed and [11C] raclopride binding in high-risk older adults with depression

Rutherford, Bret R.; Slifstein, Mark; Chen, Chen; Abi-Dargham, Anissa; Brown, Patrick; Wall, Melanie M.; Vanegas-Arroyave, Nora; Stern, Yaakov; Bailey, Veronika; Valente, Emily; Roose, Steven P.

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 [11C]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). [11C]raclopride decrease in binding potential was significantly different from 0 in sensorimotor (t24 = −4.85, p < .001) and associative striatum (t24 = −2.52, p = .019) but not in limbic striatum (t24 = 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 [11C]raclopride binding in selected striatal subregions.


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Biological Psychiatry

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May 4, 2021