Tardive dyskinesia (TD) is a persistent and often disabling hyperkinetic movement disorder associated with prolonged exposure to dopamine receptor blocking agents (e.g., antipsychotics, antiemetics). The use of anticholinergics for the treatment of movement disorders including TD is a common practice, despite a lack of supportive evidence and the potential to worsen TD. Moreover, there are now FDA-approved medications specifically indicated for TD. Two virtual meetings were held with movement disorder experts from neurology and psychiatry to better understand the real-world use of anticholinergics for TD.

In November 2020, a panel of eight experts was convened to gather insights on the challenges of differentiating TD from other drug-induced movement disorders (DIMDs) and to discuss appropriate treatments for TD and other DIMDs. A follow-up meeting was held in June 2021 to consolidate these insights. Key recommendations based on the panel discussions are presented.

The panel emphasized that while anticholinergics can help with managing some DIMDs, current evidence indicates that they are not effective in TD and may even worsen symptoms. Therefore, FDA-approved vesicular monoamine transporter 2 (VMAT2) inhibitors like valbenazine were recommended by the panel as first-line TD therapies. The panel noted that TD is often grouped under the term “extrapyramidal symptoms,” which leads to difficulty in differentiating TD from other DIMDs and the inappropriate treatment of TD with anticholinergics. The panel agreed that prophylaxis with anticholinergics is only appropriate in patients at high risk of acute dystonia. However, chronic anticholinergic use should be avoided whenever possible due to potentially serious adverse effects (e.g., cognitive difficulties) and anticholinergic burden, particularly in older patients. The potential for abuse, addiction, and diversion should also be considered when prescribing anticholinergics. Abrupt anticholinergic discontinuation can result in cholinergic rebound, which is characterized by sleep disturbances, gastrointestinal problems, urinary urgency, and manifestations of DIMDs. Thus, when used appropriately (e.g., for acute dystonia), anticholinergics should be prescribed at minimally effective doses and slowly tapered for successful discontinuation.

These findings align with the current TD treatment guidelines, including the lack of evidence for anticholinergic use and recommended first-line treatment with approved VMAT2 inhibitors. Conclusions from this panel highlight educational needs across HCPs on the phenomenology of DIMDs, the inappropriate use of anticholinergics for TD, TD risks and assessment, and treatment strategies for TD.

Neurocrine Biosciences, Inc.

We sought to examine real-world treatment patterns and healthcare resource utilization (HCRU) for patients receiving an antipsychotic (AP) and subsequently prescribed benztropine.

A retrospective analysis was conducted among patients with evidence of benztropine initiation using claims data from IQVIA’s New Data Warehouse from January 2017–March 2020. Patients were indexed on the date of first pharmacy claim for benztropine and had continuous enrollment in the 6 months prior (pre-index) and minimum 12 months post-index date, up to 24 months. Patients also had ≥1 pharmacy claim for an AP either pre-index or on the index date.

A total of 112,542 patients were included; 59% were female with mean age of 46 years. The most common comorbidities were bipolar disorder (BD; 28.3%), schizophrenia (SCZ; 28.3%), and depression (26.3%). Over half of the cohort (54.1%) had ≥2 comorbid conditions. Nearly 20% of patients had ≥20 medications (median 10–14) and medications with anticholinergic (AC) properties were used by 87.9%. Approximately 80% of patients had mild AC burden at baseline (using AC burden calculator). The median number of benztropine prescription fills was 5 with treatment duration <3 months in 44.3% of patients and <6 months in 61.7%. All-cause mean healthcare costs in the 12-month cohort (24-month cohort) were $11,755 ($23,128), mean costs for pharmacy were $9,229 ($18,148), and mean costs for inpatient stays were $34,669 ($41,280). Emergency room (ER) visits occurred in 47.3% and physician office visits in 78.9% of the cohort. In patients with available inpatient 12-month data (n=33,717), inpatient stays occurred in 4.0% (13.3% when extrapolated to total cohort). In patients with 24-month data (n=73,836), ER visits occurred in 61% of the cohort and inpatient stays in 6.6% (21.9% when extrapolated to the total cohort). Multivariate analyses showed baseline SCZ was associated with a significantly increased risk of ER visit of 30% and inpatient stay of 50%. Similarly, substance abuse was associated with an increased risk of ER visit of 85% and inpatient stay of about 40%. Other significant associations with ER visits included falls/accidents at baseline (148% increased risk), abnormal movement disorders (38% increased risk), and orthostatic hypotension (38% increased risk).

In this real-world analysis of patients initiating benztropine, polypharmacy and AC burden were frequently observed. BD, SCZ, and depression were the most common comorbidities. Healthcare costs and HCRU were high for the entire cohort; inpatient stays contributed to high costs. Baseline SCZ, falls/accidents (ER only), and substance abuse were significantly associated with ER and inpatient admissions. The comorbidity and medication profiles of this cohort may have influenced the high healthcare costs and HCRU observed in the study.

Neurocrine Biosciences, Inc.