Tardive dyskinesia from atypical antipsychotic agents in patients with mood disorders in a clinical setting

Abstract

Background

There is a paucity of information on the risks and clinical characteristics of tardive dyskinesia with atypical antipsychotic agents in patients with mood and anxiety disorders in clinical practice.

Methods: The authors retrospectively screened the charts of 268 patients with a mood or anxiety disorder treated with atypical antipsychotic agents from a psychiatric practice. Fifteen patients who developed tardive dyskinesia were identified and further data was collected on these patients.

Results

Tardive dyskinesia occurred in 5.9% of patients after exposure to an atypical antipsychotic agent for a mean of 28.7 months (range: 1–83). The average dosage of the offending agent in chlorpromazine equivalents was 350 mg/day (range: 67–969). All patients experienced oral-buccal-lingual stereotypy, which was frequently severe in nature, but completely resolved in all but one patient. Most patients (90.9%) who consented to a second trial of an atypical antipsychotic did not experience a relapse of TD.

Limitations: All patients were treated in a clinical practice setting by a single psychiatrist, which may limit the generalizability of the findings.

Conclusions

The observed rate of TD represents a real world estimate of the risk of TD with atypical antipsychotic agents in patients with mood disorders. Fortunately, with early recognition symptoms appear to be reversible and further treatment with another atypical antipsychotic does not necessarily lead to relapse.

Introduction

Second-generation or atypical antipsychotic agents have emerged as an important part of the psychopharmacologic repertoire for the treatment of mood disorders. Although once limited mainly to the treatment of psychotic illness, nearly all atypical antipsychotics are currently FDA-approved for the treatment of bipolar disorder and three are approved for treatment-resistant unipolar depression (olanzapine, quetiapine and aripiprazole). With the prescription of these agents to an expanding segment of the population comes the obligation for clinicians and researchers to be fully aware of their safety profile.

Metabolic syndrome is perhaps the most significant safety concern with several atypical antipsychotics, but this risk is thought to be offset by the relative freedom from extrapyramidal side effects. Many randomized, controlled trials concluded that these drugs, with their atypical receptor-binding profile, carry minimal or even placebo rate of extrapyramidal side effects (Nasrallah et al., 2006), but it is important to remember that the primary outcome of these studies was efficacy and most studies of this kind lack power to detect meaningful differences in side effects. With respect to tardive dyskinesia (TD), the delayed onset of symptoms results in great underestimation of risk in short-term, randomized, controlled trials (Gentile, 2007). A systematic review of long-term studies conducted between 2004–2008 found an annualized incidence of TD of 3.9% for atypical antipsychotics and 5.5% for typical antipsychotics in patients with schizophrenia, which represents an increase in incidence of TD for atypical antipsychotics since the authors' last review in 2004 (Correll and Schenk (2008)). Furthermore, a recent epidemiologic study found that the risk of TD with atypical antipsychotics in a general population of psychiatric outpatients is about two-thirds that of typical antipsychotics. This is in stark contrast to previous studies where the risk of TD with atypical antipsychotics was deemed one-quarter that of typical antipsychotics (Woods et al., 2010). We are not aware of any long-term studies that assess the risk of TD with atypical antipsychotics in patients with mood disorders; however, based on older studies with typical antipsychotic agents, patients with mood disorders appear to have a greater risk than patients with schizophrenia (Keck et al., 2000). Clearly, more research is critically needed to further delineate the risk of this disfiguring and potentially irreversible extrapyramidal syndrome in patients with mood disorders. The aim of this study is to retrospectively describe the clinical characteristics of TD from atypical antipsychotic agents in patients with mood and anxiety disorders in the clinical setting.