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

Biol Psychiatry. 2019 Aug 1;86(3):221-229. doi: 10.1016/j.biopsych.2019.04.007. Epub 2019 Apr 15.

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.

Trial registration: ClinicalTrials.gov NCT02744391.

Keywords: Gait speed; Late-life depression; Levodopa; Positron emission tomography; Processing speed; Raclopride.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carbidopa / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Depressive Disorder, Major / drug therapy*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Drug Combinations
  • Female
  • Humans
  • Levodopa / pharmacology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • New York
  • Positron-Emission Tomography
  • Raclopride / pharmacology
  • Receptors, Dopamine D2 / metabolism
  • Walking Speed*

Substances

  • Dopamine Antagonists
  • Drug Combinations
  • Receptors, Dopamine D2
  • carbidopa, levodopa drug combination
  • Raclopride
  • Levodopa
  • Carbidopa
  • Dopamine

Associated data

  • ClinicalTrials.gov/NCT02744391