Patients with tardive dyskinesia (TD) often have movements concentrated in the oromandibular region, with stereotyped oro-facial-lingual movements more commonly than in idiopathic cases. Experimental work points to altered Gamma-aminobutyric acid (GABAergic) and dopaminergic signaling in basal ganglia circuits—especially the striatum, globus pallidus, and substantia nigra pars reticulata (SNr). Dopamine depletion can strengthen certain GABAergic synapses and promote dopamine hypersensitivity, while both dopaminergic overactivity (eg, apomorphine) and chronic D2 blockade (eg, haloperidol) can induce orofacial dyskinesias in animal models. Tracing studies show that orofacial regions of the striatum project directly to SNr, which then connects to brainstem premotor centers for jaw, tongue, and facial muscles, aligning with the prominence of orolingual symptoms in TD.

Using graph-theoretic analysis of cortico-striato-thalamo-cortical (CSTC) connectivity, the authors modeled coarse and fine-grained networks to explain this vulnerability. At a coarse scale, raising the CSTC adjacency matrix to higher powers showed that SNr has the fewest cycles and walks, acting as a connectivity “bottleneck” that limits compensatory routing if this node is disrupted. At finer resolution, SNr displayed heterogeneous microconnectivity with subregions that have many alternative routes, particularly near orofacial representations, suggesting some local compensatory capacity but restricted options when damage is more extensive. Combined with somatotopic maps showing orofacial output shared between GPi and SNr, these findings support SNr’s central role in orolingual TD. The authors propose that targeted interventions at or via SNr (for example, through connected structures like the Subthalamic nucleus) might eventually help reshape these circuits to reduce repetitive orofacial movements.

Reference: Szalisznyó K, Silverstein DN. Why Does Tardive Dyskinesia Have Oro-facial Predominance? A Network Analysis. Brain Topogr. 2023 Jan;36(1):99-105. doi: 10.1007/s10548-022-00931-y.

Authors of this cross-sectional survey explored patient-reported barriers to tardive dyskinesia (TD) diagnosis and treatment among 327 adults with schizophrenia, bipolar disorder, or major depressive disorder who had TD-like symptoms and current or past antipsychotic use. Participants were grouped into three cohorts: undiagnosed (52%), diagnosed but untreated (30%), and diagnosed and treated (18%). Using descriptive statistics, machine-learning, and multivariable logistic regression, the study examined which factors were associated with receiving a TD diagnosis and, among those diagnosed, with receiving TD treatment.

Patients who talked to their healthcare providers about involuntary movements and were physically examined for TD were far more likely to be diagnosed than those who were not, highlighting communication and exam gaps as major barriers. Undiagnosed participants more often had lower income and lower employment, and those who frequently struggled with food or money were significantly less likely to be diagnosed, underscoring the role of socioeconomic disadvantage. Among those with a TD diagnosis, more frequent healthcare engagement (appointments within the last three months) was strongly associated with receiving TD treatment. Overall, the findings suggest that lack of symptom discussion, low socioeconomic status, and infrequent healthcare contact are key barriers to TD diagnosis and treatment. Researchers stress the need for better patient education and more proactive TD screening and conversation by clinicians.

Reference: Solis G, Chaijale N, Gonzalez A, et al. Patient perspectives on barriers to diagnosis and treatment of tardive dyskinesia from a cross-sectional survey (P4-5.018). Neurology. 2025 Apr 7. doi: 10.1212/WNL.0000000000212081.

This case report describes a 57-year-old woman with treatment-resistant major depression who developed severe tardive akathisia after combination therapy with escitalopram and the antipsychotic olanzapine. Despite stopping both medications and trying standard treatments for akathisia, her inner restlessness, inability to sit still, pacing, and severe distress persisted, leading to suicidal thoughts and hospitalization. A single-photon emission CT scan ruled out Parkinson’s disease, and her akathisia was rated as severe (5/5) on the Barnes Akathisia Rating Scale. The case underscores how akathisia is often missed or misattributed to anxiety or the primary illness, prompting medication increases that can worsen symptoms.

With standard options exhausted, the team and patient proceeded with electroconvulsive therapy (ECT). After 12 ECT sessions, both tardive akathisia and depressive symptoms went into complete remission, with no residual movement symptoms or ECT-related adverse effects. She remained well two years later on maintenance clomipramine. The authors note that selective serotonin reuptake inhibitors and antipsychotics, especially in combination, can induce extrapyramidal side effects such as akathisia, which is particularly difficult to treat and lacks clear guidelines. They present this as one of the first reports of full remission of tardive akathisia and depression with ECT, highlighting the need for greater clinical awareness, cautious polypharmacy, and further research on ECT and other potential treatments.

Reference: Emmanuel T. Remission of treatment-resistant depression with tardive akathisia with electroconvulsive therapy. BMJ Case Rep. 2019 Sep 18;12(9):e229714. doi: 10.1136/bcr-2019-229714.