Presenter of 2 Presentations
THE CURRENT STATUS OF TARDIVE DYSKINESIA
Tardive dyskinesia (TD) is a delayed onset movement disorder associated with the long-term use of dopamine antagonists. The typical manifestation is of choreo-athetoid movements affecting the oral, lingual, buccal, and facial musculature, although any striated muscle group may be affected, and the movements may be dystonic, stereotypic, or tic-like in some cases. This has led to the subcategorisation of TD into sub-syndromes, and a debate between lumpers and splitters. The epidemiology of TD is best documented in relation to first-generation antipsychotics, and several risk and protective factors have been described. The risk is much lower with second-generation antipsychotics, but no drug is free of the risk, with the possible exception of clozapine. The pathophysiology of TD is incompletely understood, with dopamine supersensitivity and neuronal degeneration, and a combination of the two, being the prevalent hypotheses. There is no consistently effective treatment, and prevention remains the best strategy that should be incorporated into any treatment plan involving the longer-term use of dopamine antagonists. Drug treatment of TD is symptomatic, and any benefit needs to be balanced against adverse effects. There has been much recent interest in vesicular monoamine transporter 2 (VMAT2) inhibitors, with three such drugs – tetrabenazine, deutetrabenazine, and valbenazine – having been shown to have beneficial effects in controlled studies. Other strategies include the use of GABAergic drugs, switching to clozapine, use of botulinum toxin, medical cannabis, and the rare use of ECT and deep brain stimulation.
While we have seen several new psychotropic drugs being introduced in the last three decades, none can be considered to be a major breakthrough. The majority have been me-too drugs, considered only marginal advances over previous drugs. Drug development in psychiatry has been referred to as a stalled revolution. Several advances are in the offing, which involve the translation of advances in novel molecular mechanisms and insights from genetics, but their promise is uncertain.
The more significant advances have been through neuropsychiatric approaches, in which mental illness has been understood in relation to medical and neurological diseases. Earlier examples of this included the success with antiepileptic drugs which are now in common psychiatric use. Knowledge from surgical interventions and the increasing understanding of neural networks have facilitated the development of brain stimulation, both non-invasive (repetitive transcranial magnetic stimulation and direct current stimulation) and invasive (deep brain stimulation). Rapid advances in the understanding of brain-immune mechanisms have introduced immunotherapy for psychotic and mood disorders. Work with hallucinogens has led to the introduction of ketamine and esketamine, and an increased interest in psilocybin and other similar drugs. Developments in neural networks, the brain-machine interface, and artificial intelligence promise to transform mental health in the future.
These developments lead to the conclusion that the future of psychiatry is best served by the neuropsychiatric approach in which mental health sits securely within medicine, and neuroscience guides all interventions.