Bret R Rutherford1, Mark Slifstein2, Chen Chen3, Anissa Abi-Dargham2, Patrick J Brown3, Melanie W Wall3, Nora Vanegas-Arroyave4, Yaakov Stern4, Veronika Bailey5, Emily Valente5, Steven P Roose3. 1. Columbia University Vagelos College of Physicians and Surgeons, New York, New York; New York State Psychiatric Institute, New York, New York. Electronic address: brr8@cumc.columbia.edu. 2. Stony Brook University Renaissance College of Medicine, Stony Brook, New York. 3. Columbia University Vagelos College of Physicians and Surgeons, New York, New York; New York State Psychiatric Institute, New York, New York. 4. Columbia University Vagelos College of Physicians and Surgeons, New York, New York. 5. New York State Psychiatric Institute, New York, New York.
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 [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.
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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