Aripiprazole induced tardive dyskinesia-accruing evidence

To the Editor

The low prevalence of extrapyramidal side effects with atypical antipsychotic medication has led to their widespread prescription for both approved and off label use. Aripiprazole is an ‘atypical’ atypical antipsychotic because it acts at the same receptor sites (D2 dopamine) as most typical antipsychotic agents, however, its actions as a partial dopamine agonist, a low serotonin 5-HT₂:D₂ affinity ratio and low 5-HT₁ receptor occupancy implied that aripiprazole had a low propensity for extrapyramidal side effects (EPSE) (Gupta and Masand, 2004). Aripiprazole has even been reported to be of benefit in the management of pre-existing tardive dyskinesia induced by other agents (Witschy and Winter, 2005). We discuss a case of tardive dyskinesia reinduced by aripiprazole and discuss implications for choice of antipsychotic medication in everyday clinical practice.

Mrs DS is a 46 year old, Caucasian woman with a history of borderline personality traits and bipolar affective disorder on treatment with sodium valproate (2g/day) and the antidepressant mirtazapine (45mg/day). Her early history is characterized by prolific substance abuse over a decade, although she has been abstinent from all illicit substances for the last several years. When under stress Mrs DS experiences micropsychotic episodes characterized by transient auditory hallucinations. She recently suffered a relapse of these symptoms on a background of shifting to a new town and following the death of her father- in-law. Her new GP prescribed her risperidone 4mg for hallucinatory phenomena and her symptoms appeared to respond favorably. Six weeks into the use of medications, she developed stereotypic movements of her head, neck and upper limbs, consistent with tardive dyskinesia. There were some rhythmic movements of her tongue, but no other noticeable bucco-oral movements. After a further 10 weeks of progressively worsening symptoms, the antipsychotic medication was changed to ziprasidone (60mg), with little relief. After a 3 month trial of ziprasidone the patient unilaterally discontinued her medication which resulted in a complete cessation of the abnormal movements over a 2 week period. Her GP then commenced her on aripiprazole 10mg/day, which resulted in a gradual reemergence of the tardive dyskinesia after the first fortnight of use. The consultation with these authors was sought 4 weeks after the commencement of aripiprazole, when her Abnormal Involuntary Scale (Guy, 1976) score was 21. A diagnosis of tardive dyskinesia was made, the aripiprazole was ceased, and clonazepam 0.5mg commenced with good effect.

The metabolic side effects of the atypical antipsychotic medications may have drawn attention away from the EPSE they can induce. Our case illustrates the typical risk factors that make an individual more susceptible to the induction of tardive dyskinesia on antipsychotic medication. These risks include older age group, female sex, pre-existing movement or neurodegenerative disorders, the presence of affective illness, and exposure to neuroleptics for greater than 6 months. The onset of symptoms in our case was swifter than usual with a good response to terminating the offending agent. While initial studies suggested an incidence of EPSE equivalent to that for subjects on placebo an increasing body of evidence suggests that these risks may be substantially higher (Hall et al., 2009). While aripiprazole appears to have reactivated tardive dyskinesia in this case, there is a growing body of other evidence that suggests aripiprazole itself can induce tardive dyskinesia (Peña, 2011).

This case contributes to the accruing evidence that supportsthe conclusion that atypical antipsychotic medications, including aripiprazole, can cause tardive dyskinesia. Clinicians can ill afford to relax their vigilance in monitoring clients for the emergence of movement disorders, even when they are being prescribed agents such as aripiprazole, that have been marketed as being relatively benign with regard to EPSE. This is especially important as most patients with tardive dyskinesia may be unaware of their abnormal movements, and are therefore unlikely to point these out themselves until they have become quite obvious. Although in our case the movement disorder remitted spontaneously, tardive dyskinesia can often be difficult to treat and contribute significantly to social stigma.