Clinical risk factors for the development of tardive dyskinesia

Tardive dyskinesia (TD) is a severe condition that can affect almost 1 out of 4 patients on current or previous antipsychotic treatment, including both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). While two novel vesicular monoamine transporter inhibitors, deutetrabenazine and valbenazine, have shown acute efficacy for TD, the majority of patients do not remit, and TD appears to recur once treatment is withdrawn. Hence, prevention of TD remains a crucial goal.

We provide a clinically oriented overview of risk factors for TD, dividing them into patient-, illness- and treatment-related variables, as well as nonmodifiable and modifiable factors.

Unmodifiable patient-related and illness-related risk factors for TD include older age, female sex, white and African descent, longer illness duration, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related and treatment-related factors include diabetes, smoking, and alcohol and substance abuse, FGA vs SGA treatment, higher cumulative and current antipsychotic dose or antipsychotic plasma levels, early parkinsonian side effects, anticholinergic co-treatment, akathisia, and emergent dyskinesia.

Clinicians using dopamine antagonists need to consider risk factors for TD to minimize TD and its consequences.