Evolution of neuroleptic-induced extrapyramidal syndromes under long-term neuroleptic treatment
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.
References (47)
- et al.
Incidence of tardive dyskinesia with typical versus atypical antipsychotics in very high risk patients
Biol. Psychiatry
(2003) - et al.
New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis
Lancet
(2003) - et al.
Tardive dyskinesias and antipsychotics: a review
Eur. Psychiatry
(2002) - et al.
Prevalence of extrapyramidal syndromes in psychiatric inpatients and the relationship of clozapine treatment to tardive dyskinesia
Schizophr. Res.
(2000) - et al.
Does akathisia influence psychopathology in psychotic patients treated with clozapine?
Biol. Psychiatry
(1999) - et al.
The prevalence of tardive dystonia, tardive dyskinesa, parkinsonism and akathisia. The Curaçao extrapyramidal syndromes study I
Schizophr. Res.
(1996) - et al.
WHOQOL-100 AND WHAOQOL-BREF
(2000) A rating scale for drug-induced akathisia
Br. J. Psychiatry
(1989)- et al.
Movement disorders associated with atypical antipsychotic drugs
J. Clin. Psychiatry
(2002) - et al.
Neuroleptic-induced tardive dyskinesia and parkinsonism: changes during several years of continuing treatment
Psychopharmacol. Bull.
(1986)
Principles of Psychopharmacology
Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies
Am. J. Psychiatry
A meta-analysis of the efficacy of second-generation antipsychotics
Arch. Gen. Psychiatry
Übersichtstabellen
Übersichtstabellen
Neuroleptic-induced vs. genuine motor disorders
Tardive dyskinesia and antipsychotics: a 5-year longitudinal study of frequency, correlates and course
Internat. Clin. Psychopharmacol.
Unified Parkinson's disease rating scale
Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects
Arch. Gen. Psychiatry
Modern antipsychotic drugs: a critical overview
Can. Med. Assoc. J.
Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis
BMJ
Nithsdale schizophrenia surveys 23: movement disorders
Br. J. Psychiatry
Cited by (26)
The psychopharmacology of catatonia, neuroleptic malignant syndrome, akathisia, tardive dyskinesia, and dystonia
2019, Handbook of Clinical NeurologyReliability and validity of an instrument for the assessment of bradykinesia
2016, Psychiatry ResearchAkathisia: Prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset
2015, Schizophrenia ResearchCitation Excerpt :Our results suggest that patients with akathisia should benefit from a switch to another antipsychotic medication rather than from an add-on therapy. Modestin et al. (2008) suggested that among SGA, clozapine alone may reduce chronic akathisia in patients with schizophrenia in the long course, whereas switching to another SGA may not influence or even worsen akathisia. These results, however, were no longer significant after correction for multiple tests.
Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder
2014, NeurotherapeuticsClozapine and tardive movement disorders: A review
2013, Asian Journal of PsychiatryCitation Excerpt :Studies (Leppig et al., 1989; Naber et al., 1989; Wilson, 1992; Nair et al., 1996; Dalack et al., 1998) which have evaluated the changes in prevalence and severity of TS after starting clozapine (see Table 2) for management of primary psychiatric disorder suggest that many patients who receive clozapine have improvement in TS with clozapine (Leppig et al., 1989; Naber et al., 1989; Wilson, 1992; Nair et al., 1996; Dalack et al., 1998). Further some of the comparative studies suggest that the improvement in severity and prevalence of TS with clozapine is more than that seen with haloperidol (Tamminga et al., 1994; Rosenheck et al., 1997), whereas, others suggest no difference between clozapine, typical antipsychotics and other atypical antipsychotics (Modestin et al., 2000, 2008; Novick et al., 2009, 2010). With respect to use of clozapine for management of TS, the data is limited to 28 publications in the form of case reports and case series, describing 34 cases (see Table 3).