Tardive Dyskinesia Research Review

Using item 8 of the Abnormal Involuntary Movement Scale (AIMS) to assess improvement in patients with tardive dyskinesia

Citrome, et al. CNS Spectr. 2021;26:152.

Background
The Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) is usually the primary efficacy measure in tardive dyskinesia (TD) clinical trials. However, item 8 of the AIMS (healthcare professional’s global impression of severity) might also be an appropriate assessment in real-life healthcare settings. To explore the potential of item 8 as a clinical measure, post hoc analyses were conducted using data from a long-term study of valbenazine, an approved TD medication.

Methods
In KINECT 4, adults with TD received once-daily valbenazine (40 or 80 mg) for 48 weeks. Analyses included 2 sets of AIMS item 8 scores: based on investigators’ ratings of item 8 using protocol-defined descriptors and based on investigators' highest scores from items 1-7 (analyzed post hoc). Shift analyses included an improvement from score 3 at baseline (moderate or severe) to score 2 at Week 48 (none to mild).

Results
At baseline in all 163 participants, the AIMS item 8 mean scores were 3.2 (protocol) and 3.3 (post hoc). In participants with a score of 3 at baseline per investigator ratings using protocol-defined descriptors, 95.9% [94/98] shifted to a score 2 by Week 48. A similar result (93.9% [93/99]) was found when item 8 was based on investigators’ highest scores from items 1-7.

Conclusion
Shift analyses using AIMS item 8 scores indicated that most participants in KINECT 4 had a clinically meaningful improvement after 48 weeks of once-daily treatment with valbenazine. AIMS item 8 may be an appropriate clinical measure for assessing changes in TD severity.

Clinical Commentary (Joseph P. McEvoy, MD)
Clinical care has changed. Regulatory agencies demand documented attention to an ever-increasing list of priorities. Business models expect healthcare professionals to “see” patients in 20-minute visits, during which they are to bring the patient to their actual or virtual office, assess the patient’s psychopathology (eg, depression or psychosis or irritability or insomnia), ask about and examine for adverse events of somatic treatments, decide about new treatments and obtain informed consent for these, write prescriptions or e-prescribe, and summarize instructions for the patient until the next visit. The healthcare professional may not be able to methodically complete the entire AIMS examination by having the patient remove her/his shoes, looking at each body area in detail in frontal and profile views, having the patient walk back and forth and complete several activation maneuvers as in clinical research settings.

Clinical Insights

• If the patient receives dopamine receptor–blocking agents, the healthcare professional should ask about and examine them for TD.
• Since 20 minutes is not adequate time to conduct an entire AIMS evaluation, healthcare professionals must use judgment in prioritizing what is important for each individual patient.
• Experienced healthcare professionals look for shortcuts to achieve what is most important for the well-being of the patient.
• This article suggests that healthcare professionals who train themselves to briefly (a few seconds at each body area: head/face/neck, upper extremities, trunk, lower extremities) and then record a global rating of TD absence/presence at minimal/mild/moderate/severe are capturing most of the variance that would be captured if all items were scored individually and 1-7 summed.
• In my clinical practice, I conduct 2 activation maneuvers that take <1 minute: hold arms out straight in front, wrists loose, hands hanging limp, and say 5 words beginning with the letter “t”; hold your mouth open while touching the fingers of your nondominant hand sequentially to your thumb.

Summary
It is unarguably important to examine patients who are receiving dopamine receptor–blocking agents for TD regularly. Although the AIMS is well-designed research and clinical tool, much of what is important can be gained with a summary global judgment (item 8) of the abnormal movement status.

Clinical Commentary (Sanjay Gupta, MD)
There is a dichotomy between the clinical practice world of psychiatry and academic psychiatry. Most patients with severe and persistent mental illness are seen in clinics such as community mental health centers. As someone who is involved in both settings, I see both sides of this issue.

The AIMS scale is the gold standard for assessing TD in patients receiving antipsychotics. However, the advent of atypical antipsychotics may have caused healthcare professionals to become lax in TD monitoring. The changes in medicine and psychiatry practice have also played a role. The FDA approval of 2 new TD treatments highlighted delays in diagnosis and treatment of TD, making it impossible to ignore this condition in clinical practice. TD causes cosmetic problems as well as functional impairments and can contribute to associated depression and anxiety in those afflicted. Just as hepatitis C treatment approvals led to routine assessment and diagnosis, the effective and timely treatment of TD requires periodic screening of all patients.

In current clinical practice, using electronic medical records, sending a new prescription, note-taking, and proofing consume time at the expense of thorough patient assessment and AIMS. This study suggests that focusing on item 8 (overall severity of the movements) of the AIMS test provides a rapid, yet effective, TD screening tool for clinical settings with significant time constraints.

Shift analyses described in this study measured clinically meaningful improvements (severe to moderate, moderate to mild, or mild to normal), indicating that AIMS item 8 scores may be an appropriate clinical measure for assessing changes in TD severity

Clinical Insights

• In clinical practice, item 8 would be a rapid clinical assessment (easier to do and interpret than the sums of items 1-7) and would get done. Modifications are needed for the current times.
• The above study revealed decent reliability between the protocol-based method of the study investigators and the post hoc method based on the highest score of investigators of items 1-7.

Summary
In my opinion, rather than not rating, an overall assessment is a welcome approach that we healthcare professionals can adopt. Many of us may be using this approach informally, and this study validates this approach. The key is to screen and address the issue of TD treatment. Not addressing TD in today’s practice may be considered negligent.