LETTER TO THE EDITOR Levodopa has mood‐enhancing effects in healthy elderly adults Dopaminergic medications, such as L‐3,4‐dihydroxyphenylalanine (levodopa), are a mainstay of treatment in Parkinson's disease (PD), a neurodegenerative movement disorder with prominent cognitive and psychiatric symptoms. Recently, dopaminergic medications have been proposed as a possible treatment for mood disorders, depression in particular. PD patients are characterized by marked degeneration of dopaminergic neurons. The possibility that dopaminergic deficits contribute to high rates of depression, anxiety, and apathy in PD has been considered. Previous findings for potential mood‐enhancing effects of levodopa in PD were largely inconsistent. 1-5 Whether levodopa is effective in mood, anxiety, or apathy remains unclear. The aim of the present study was to test the potential for levodopa to affect mood, anxiety, and apathy independent of patho- physiological processes related to PD. We administered a single dose of levodopa/carbidopa 100/25 mg to 24 healthy older adults (M age ± SEM = 66.13 ± 1.30 years; 11 males, 13 females). Participants had no history of neurological or psychiatric illnesses, including alcohol or substance abuse problems, and had no contraindications to levocarb. Written informed consent was obtained prior to beginning the experiment in accordance with the Declaration of Helsinki. This study was approved by the Health Sciences Research Ethics Board of the University of Western Ontario. Across two testing sessions separated by a week, participants were assessed once after receiving levodopa/carbidopa 100/25 mg and once after receiving the equivalent volume of placebo, in counterbalanced order across individuals. Both drug and placebo were administered orally in identical capsules to maintain double‐ blindedness. After 45 minutes, to allow for enhanced plasma dopamine levels, standardized and validated self‐report psychiatric rating measures were administered. These included the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Starkstein Apathy Scale (SAS). For each psychiatric measure, we performed 2 × 2 mixed ANOVAs with Order (L/P vs P/L) as the between‐subject factor and Session (levo- dopa vs placebo) as the within‐subject variable. Higher scores on our measures indicated greater self‐reported ratings of depression, anxiety, and apathy, respectively. Our analyses revealed a significant main effect of Session for BDI scores [F(1,22) = 6.699, MSE = 1.008, P = .017, η 2 p = 0.223] but not for BAI or SAS (both F values < 1). Participants reported lower BDI scores when treated with levodopa compared to placebo (Table 1). There was no main effect of Order for any measure (all F values < 1). There was a marginally significant Order × Session interaction effect for BDI [F(1,22) = 4.053, MSE = 1.008, P = .056] but not for BAI or SAS (both F values < 1). Bonferroni‐corrected pairwise comparisons demonstrated greater reduction in the BDI ratings in the levodopa session when it was performed second (ie, P/L). Our finding of mood‐enhancing effects of levodopa in healthy elderly adults is in line with previous investigations in PD 1-4 —but are preliminary at best. The magnitude of difference between placebo and levodopa was small (Table 1), however, the effect size was moder- ate (η 2 p = 0.223). BDI scores in our sample of healthy older adults were low in both sessions. The current study assessed mood in a random sample rather than in a group selected on the basis of prior diagnosis of depression or even subjective endorsement of low mood. In line with this, our participants scored in the minimal depression range on levodopa (0‐10) and the minimal to mild depression range in the pla- cebo session (0‐15). It is unclear whether levodopa's effect would extrapolate to more severe depression based on our findings at this time. Our results, however, are clear in providing motivation for a larger scale, veritable clinical trial. Despite caution regarding interpretation and extrapolation of our findings to other populations, the current study has a number of unique strengths. Unlike previous studies, we investigated the effect of levodopa (a) in a randomized, placebo‐controlled, crossover design, (b) using standardized and validated psychiatric measures, and (c) across sessions separated by a mere week, reducing confounds of symptom progression or regression to the mean. That a small improve- ment followed only a single dose of levodopa could in fact signal its potential efficacy and speed of action, which would be a highly desirable property in significant, high‐risk cases of depression. In summary, our results hint at the potential of levodopa as a mood enhancer or potentially as a therapy to augment antidepressant medications. We offer preliminary evidence that these effects occur quickly, after a single dose. Further exploration in patient populations are suggested. TABLE 1 Psychiatric rating scale measures for participants on levodopa versus placebo Levodopa Placebo P value BDI 3.17 (0.70) 3.92 (0.87) 0.017* BAI 2.96 (0.70) 2.83 (0.65) 0.809 SAS 10.04 (0.76) 9.57 (0.77) 0.536 Values are reported as means (±SEM). BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory II; SAS, Starkstein Apathy Scale. *P < .05. Received: 9 August 2017 Accepted: 25 September 2017 DOI: 10.1002/gps.4824 Int J Geriatr Psychiatry. 2017;1–2. 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