Treatment Response to VMAT2 Inhibitors in Older Adults with Tardive Dyskinesia
The correct answer is D: All of the above - treatment response is significantly improved compared with placebo, response assessed by AIMS appears approximately similar to that in younger adults, and response is attenuated after VMAT2 washout.
Evidence Supporting Treatment Efficacy in Older Adults
Significant Improvement Over Placebo
VMAT2 inhibitors demonstrate robust efficacy in treating tardive dyskinesia across all age groups, including older adults:
Deutetrabenazine shows significant reduction in total AIMS scores compared to placebo (standardized mean difference = -0.40, weighted mean difference = -1.44, p<0.001), with responder rates (≥50% AIMS reduction) more than doubling versus placebo (risk ratio = 2.13, number-needed-to-treat = 7) 1
Valbenazine demonstrates even stronger efficacy with AIMS score reduction (standardized mean difference = -0.58, weighted mean difference = -2.07, p<0.001) and tripled responder rates versus placebo (risk ratio = 3.05, number-needed-to-treat = 4) 1
The American Psychiatric Association recommends VMAT2 inhibitors (valbenazine or deutetrabenazine) as first-line pharmacotherapy for moderate to severe or disabling tardive dyskinesia 2
Similar Response Across Age Groups
The published data specifically indicate that older adults respond comparably to younger patients:
Stratified analyses from VMAT2 inhibitor trials demonstrate that older adults have similar or greater benefits than younger people when treated with this drug class 3
Both deutetrabenazine and valbenazine maintain efficacy in older populations without evidence of attenuated response based on age 1
The AIMS-based assessment shows consistent treatment effects regardless of patient age, with a clinically meaningful improvement threshold of 2 points established across all age groups 4
Response Attenuation After Washout
Discontinuation studies clearly demonstrate symptom recurrence following VMAT2 inhibitor withdrawal:
In dose-blinded valbenazine studies, TD symptom recurrence towards baseline severity levels occurred within 4 weeks after valbenazine withdrawal 1
This washout effect confirms that the therapeutic benefit is medication-dependent and symptoms return when treatment is discontinued, supporting the need for continued therapy 1
Safety Profile in Older Adults
VMAT2 inhibitors demonstrate favorable tolerability in the elderly population:
No increased cumulative or specific adverse events versus placebo were observed in acute trials, and extension study data showed no increased risk over time 1
No concerns about increased risk of depression or suicide emerged in the TD population treated with VMAT2 inhibitors 1
Both valbenazine and deutetrabenazine are FDA-approved specifically for treating TD in adults, with efficacy demonstrated in class 1 studies 2
Clinical Monitoring Recommendations
For older adults receiving VMAT2 inhibitors:
Perform baseline AIMS assessment before initiating treatment to document severity 5, 6
Continue regular monitoring at least every 3-6 months using standardized AIMS measures to track progression and treatment response 5, 2
Personalize follow-up visits with questions about functioning and distress related to specific TD symptoms 7
A 2-point decrease in AIMS total score represents the minimal clinically important difference and should be the target for meaningful improvement 4