Evolution of neuroleptic-induced extrapyramidal syndromes under long-term neuroleptic treatment

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Abstract

Background

The long-term evolution of neuroleptic-induced extrapyramidal syndromes (EPS) of Parkinsonism, akathisia and tardive dyskinesia (TD) is still a controversial issue worth exploring.

Method

A total of 200 inpatients on regular typical neuroleptics (NL) and/or clozapine were assessed in 1995 with regard to the prevalence of EPS. Altogether, 83 patients could be reassessed in 2003/04 (63 had died) using the same methods. Strict definitions of EPS were used. The complete account of NL therapy the patients were prescribed between 1995 and 2003/04 (including atypical NL other than clozapine) was considered.

Results

The prevalences found in 1995 and 2003/04 were 17% and 29% for Parkinsonism, 14% and 14% for akathisia, and 24% and 13% for TD. There were considerable intra-individual fluctuations in EPS occurrence even when the overall prevalence rate remained the same. In intra-individual comparisons of EPS ratings on both assessments, there was a tendency for worsening of Parkinsonism to be associated with a current (2003/04) therapy with typical NL; worsening of akathisia was associated with a current therapy with atypical NL other than clozapine, amelioration of akathisia with a current therapy with clozapne; and, basically, there were no significant associations found between the changes in TD ratings and the long-term therapy with typical NL, clozapine, and other atypical NL, considering cumulative doses of all these drugs. In a multivariate analysis, there was a tendency for the long-term evolution of TD to depend on illness duration as the only variable.

Conclusions

There are intra-individual fluctuations in all EPS over longer time periods. The choice of current NL therapy has an impact on Parkinsonism and akathisia. The long-term evolution of TD appears independent of NL prescriptions.

Introduction

Neuroleptic drugs (NL) are indispensable in treating psychotic disorders, yet all of them are fraught with potentially serious side effects. The occurrence of extrapyramidal syndroms (EPS) in terms of Parkinsonism, akathisia, and tardive dyskinesia (TD) respresents one of the most serious complications of therapy with NL. In individual samples of patients treated wit typical NL and clozapine prevalences of these EPS were 36%, 9%, and 40% (Van Harten et al., 1996), 20%, 11%, and 22% (Modestin et al., 2000) and 23%, 31% and 32% (Janno et al., 2004) for Parkinsonism, akathisia, and TD, respectively. Regarding TD, considered to be the most frequent and significant complication encountered with NL treatment (Llorca et al., 2002), the overall mean prevalence among chronically treated patients was estimated to be about 24% (Jeste and Caligiuri, 1993).

Atypical NL are said to carry a substantially lower risk of EPS, including TD, than typical agents (Toffelson et al., 1997, Correll et al., 2004); atypical NL caused fewer EPS even when lower doses of typical NL were used in the individual trials (Geddes et al., 2000). On the other hand, the risk of EPS is not negligible even with atypical NL (Schatzberg et al., 2002), optimal doses of low-potency conventional NL might not induce more EPS than atypical NL (Leucht et al., 2003) and also, second-generation antipsychotics do not represent a homogneous group. Some atypical NL such as risperidone and amisulpride cause dose-related EPS (Davis et al., 2003). Furthermore, in some patients, weight gain and its complications caused by atypical NL may pose a greater long-term risk for the patient than EPS (Schatzberg et al., 2002), and recent effectiveness studies failed to demonstrate a significant difference between typical and atypical NL with regard to the ratings of Parkinsonism, akathisia, and dyskinesia (Lieberman et al., 2005, Jones et al., 2006).

In 1995 we studied the prevalence of neuroleptic-induced extrapyramidal syndromes in a sample of patients, treated with typical NL and/or clozapine (Modestin et al., 2000). Eight to nine years later, the same patients were re-assessed in order to study the longer-term evolution of these EPS and its relationship to the NL medication taken by the patients between both assessments. During this time period, other atypical NL were introduced on the broad-scale basis. Also, the influence of NL-induced EPS on quality of life and depressive symptoms was assessed.

Section snippets

Methods

In August 1995, in a cross-sectional study, 200 inpatients, all of them treated with typical neuroleptics and/or clozapine on a regular basis, were assessed with regard to the point prevalence of Parkinson syndrome, akathisia, and TD (Modestin et al., 2000). A re-assessment of the same sample in an identical way was carried out in 2003/2004. Additionally, quality of life and depression measures were applied at the second assessment to test their possible influence on the EPS ratings.

Results

In Table 1, 83 study participants are compared with 117 drop-outs with regard to the 1995 data. As can be seen, men were over-represented among the study participants. Incidentally, in the whole original sample, the majority (57%) were men. Also, the participants were significantly younger, this mainly due to the higher average age (64 years, SD = 20) of the deceased patients. There was a tendency for the organic disorders to be over-represented among the drop-outs in general and the deceased

Discussion

Out of a total of 200 patients in the original sample, only 83 could be included in this follow-up study. This was mainly due to the high mortality rate; the majority (54%) of the drop-outs had died. Among the study participants there was a higher proportion of men (66%) than in the original sample (57%). This may be explained by the fact that in the original sample the women were older than the men (53 years vs. 45 years, z = 2.61, p = 0.009), and age significantly predicted the drop-out due to

Role of funding source

There was no funding for this study.

Contributors

Jiri Modestin designed the study; Marianne Vogt Wehrli and Jiri Modestin wrote the study protocol; Marianne Vogt Wehrli and Patrik Lukas Stephan examined the patients; Marianne Vogt Wehrli collected the treatment data; Puspa Agarwalla undertook the statistical analyses; and Jiri Modestin wrote the manuscript draft. All authors have contributed to and have approved the final manuscript.

Conflict of interest

All authors declare that they have no conflicts of interest.

Acknowledgements

We gratefully acknowledge the patients who participated in the study.

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