Drug-induced movement disorders

Abstract

Movement disorders constitute a group of neurological diagnoses characterized by changes in muscle tone, the presence of inappropriate movements, the impairment in timing and sequencing of normal movements, and the absence of weakness. As a group, these disorders have their origin in disruption of brainstem and subcortical circuits, known as the basal ganglia system, that involves several neurotransmitters, primarily dopamine and acetylcholine, but also serotonin, norepinephrine, gamma amino butyric acid, and glutamate (Jankovic 2003). Some movement disorders relate to primary neurodegenerative diseases like Parkinson's disease or various parkinsonism-plus syndromes. In these cases, neurodegeneration occurs in selective, but often multiple brain regions within, and sometimes beyond the basal gangliar system. Other movement disorders are considered as non-degenerative conditions associated with central nervous system neurotransmitter imbalances, like primary dystonia and Gilles de la Tourette syndrome. Still others are clear genetic conditions, like Huntington's disease and familial tremor. In addition to these primary movement disorders, similar movement impairments can occur as a reflection of metabolic disturbances, infectious diseases, and cerebrovascular accidents. A final category of secondary movement disorders is composed of the syndromes directly related to medication side effects, collectively termed drug-induced movement disorders. In this latter category, psychiatric medications used to treat psychosis and mood disorders are particularly notable for their associations with movement disorders. Often collectively termed "extrapyramidal symptoms" or "EPS", these disorders are variable phenomenologically and include tremors, chorea, dystonia, tics, myoclonus, akathisia, chorea and parkinsonism (Gershanik 1993). This chapter focuses on clinical syndromes associated with dopamine-receptor blocking agents primarily used to treat psychosis, and agents used in the treatment of mood disorders, specifically antidepressants and lithium carbonate. Because anxiolytics are not associated with movement disorders except during drug withdrawal, they are not discussed. Likewise, drugs that are used in psychiatry but more typically prescribed in other medical arenas or in general medical care, like anticonvulsants or sleeping medications, are not discussed. Each section presents the clinical disorders associated with these psychiatric drugs in terms of phenomenology and temporal development relative to medication exposure. Then, a discussion of data related to biological mechanisms and treatment follows. The final focus concerns available information related to pharmacogenetic research and the search for genetic markers to identify subjects at particular risk for developing movement disorders related to psychotropic medications. Whereas no markers applicable to patient screening have yet been identified, the discussion highlights areas of current research and provides a context for future studies in this domain.