Looking Ahead: Tardive Dyskinesia Care

Antipsychotic-induced TD update.Recent data indicate that prevalence rates of antipsychotic-induced TD in patients with schizophrenia are lower in those treated with newer generation antipsychotics (21%) vs those treated with first-generation antipsychotics (30%). Studies have found that the new VMAT2 inhibitors-valbenazine and deutetrabenazine-are effective and may be considered first-line pharmacotherapy.

Care barriers. The VMAT2 inhibitors offer, for the first time, an evidence-based therapeutic approach to TD for patients who may not need continued antipsychotic treatment and could be withdrawn from antipsychotics and in patients with psychotic disorders who require maintenance antipsychotic treatment. However, several barriers to providing effective care and promoting safety may arise from areas of limited or inconclusive data, bias and misunderstanding, and neglect of training about TD.

Stepping over the barriers. To overcome the management barriers, a stepwise treatment algorithm was newly proposed: (1) recognition and diagnosis; (2) documentation of severity, distribution, and phenomenology; (3) differential diagnosis and lab investigation; (4) neurological consultation; (5) discussion of treatment options with patient and caregiver; (6) review of antipsychotic treatment; (7) review of anticholinergic treatment; and (8) specific antidyskinetic treatment on an individualized basis.

On updating guidelines, it’s unanimous. With FDA approval of the VMAT2 inhibitors, a recently modified Delphi process addressed the need for updated clinical guidelines. Psychiatrists and neurologists who responded to an online survey agreed unanimously that all patients taking dopamine receptor blocking agents be screened, the Abnormal Involuntary Movement Scale (AIMS) is the standard structured assessment for monitoring severity, and treatment with first generation antipsychotics, older age, and longer cumulative exposure to antipsychotics are risk factors.

Consensus rules. Participants of the same online survey reached a consensus that a semi-structured assessment could be used for more frequent routine screening (76%), a patient with an AIMS score >2 that affects 1 body area should be considered as having possible TD (89%), and TD is most often evident in orofacial musculature (93%). Unanimity or consensus was reached on possible treatment approaches: Discussion of treatment options with patients/caregivers, modification of antipsychotic regimen, treatment with VMAT2 inhibitor, and modification of anticholinergic regimen.

Global improvement, patients satisfied. Previously, in the KINECT 3 and KINECT 4 long-term studies, valbenazine improved TD in patients who received doses of 40 or 80 mg for up to 48 weeks. Now, in a long-term rollover study, adults who received once-daily valbenazine showed ongoing, meaningful TD improvements-the percentage with Clinical Global Impression of Severity-TD score ≤2 increased from baseline to week 48-and continued patient satisfaction rates were high in those treated for >1 year.

Treatment effects vary with body region. In a post hoc analysis of KINECT 3 data, patients treated with valbenazine had statistically significant, clinically relevant improvements in TD severity in specific body regions. For response per AIMS item, significant differences between valbenazine and placebo were found in the lips, jaw, tongue, and upper extremities. In those with an AIMS item score ≥1 at baseline, the percentage with a ≥1-point improvement at week 6 was significantly higher in all 7 body regions.

Safe, effective with mood disorder. In patients who had a primary mood disorder-bipolar or depressive-once-daily treatment with valbenazine resulted in 6-week and sustained TD improvements. Significant differences were found between valbenazine and placebo for week 6 AIMS response and Change-Tardive Dyskinesia response. The agent was generally well tolerated-no unexpected treatment-emergent adverse events, worsening in psychiatric symptoms, or emergence of suicidality.