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Antipsychotic‐induced movement disorders – forgotten but not gone

2008; Wiley; Volume: 117; Issue: 6 Linguagem: Inglês

10.1111/j.1600-0447.2008.01206.x

1600-0447

Peter J. Weiden,

Parkinson's Disease Mechanisms and Treatments

Acta Psychiatrica ScandinavicaVolume 117, Issue 6 p. 401-402 Free Access Antipsychotic-induced movement disorders – forgotten but not gone Peter J. Weiden, Peter J. Weiden Invited Guest EditorSearch for more papers by this author Peter J. Weiden, Peter J. Weiden Invited Guest EditorSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1600-0447.2008.01206.xCitations: 13AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Parkinson's disease was first described by Dr James Parkinson in 1817 as paralysis agitans in an essay on shaking palsy (1). Parkinsonism is a neurologic syndrome caused by an imbalance of dopamine in the basal ganglia. The introduction of chlorpromazine in the 1950s was associated with a dramatic increase in the incidence of parkinsonian-like symptoms. There were many different types of motoric problems reported, and collectively these were referred to as extrapyramidal symptoms (the term 'EPS' is often a shorthand for the range of movement disorders induced by antipsychotics). Soon after the introduction of chlorpromazine in the 1950s, clinicians recognized that drugs, such as chlorpromazine, combined antipsychotic properties with a propensity to induce parkinsonism and other movement disorders. This connection formed the underpinning of two major hypotheses proposed in the 1960s. The first was the dopamine hypothesis of schizophrenia. This hypothesis was spectacularly successful and has, in various forms, remained one of the cornerstones of our understanding of the mechanism of action of antipsychotic drugs. The other major hypothesis was that the occurrence of parkinsonism was essential to achieve antipsychotic response. Not only was this theory wrong, it was also very damaging, because it made EPS a desired therapeutic target. Given how often antipsychotics are used, it is no surprise that by far the most common cause of secondary parkinsonism is iatrogenic and caused by this class of antipsychotics. The reintroduction of clozapine in the late 1980s was a turning point, as it conclusively disproved the fundamental linkage between EPS and therapeutic response. Around the same time, research on the consequences of EPS made it clear that EPS was not a benign side-effect, but just the contrary. The spectrum of EPS complications from the older antipsychotics was simply devastating. Taken together as a range of effects, EPS were (and continue to be) a major limitation of the 'conventional' pre-clozapine antipsychotics. The most striking and consistent benefit of the newer 'atypical' or second generation (post-clozapine) antipsychotics is that they are less likely to cause EPS. Even when EPS occurs, it is often less severe than what would have been seen in comparable situations with the pre-clozapine antipsychotics. These advances in reducing EPS morbidity may not always translate into 'real-world' practice. In this issue, the report by Sundram et al. found a disturbingly high prevalence of EPS in a community patient sample (2). In their cross-sectional study of 40 patients, 60% rated positive for akathisia, 65% for tardive dyskinesia and an astonishing 85% for antipsychotic-induced parkinsonism. Sundram et al. found intriguing associations between acculturation and generational immigration status on the likelihood of movement disorders that were significant even when antipsychotic dose and class (pre- vs. postclozapine) were taken into account (2). While one can argue that the current study is not designed as a true community prevalence study, larger effectiveness trials, such as Comparative Effectiveness of Antipsychotic Medications in Patients with Schizophrenia (CATIE), also tell us that EPS is forgotten but not gone (3). Almost all of the focus on the adverse events from the CATIE study has been on the weight and metabolic findings. While those findings are undoubtedly of great importance, so are the EPS results, especially when simply excluding the subgroup of patients where there were no data on reasons for discontinuation. In this reanalysis, 10.5% of patients stopped their assigned medication for EPS-related reasons. Among the patients treated with perphenazine, 21% discontinued for EPS, which represented over 50% of all the tolerability-related reasons for perphenazine (4). This editorial is most concerned about the urgent need to continue to study the neurologic sequelae of antipsychotic treatment. Both the authors and this journal are to be congratulated for not forgetting about EPS. If you look at back issues of major psychiatric journals from the 1970s and 1980s, you will see that publications related to side-effects of antipsychotics were almost exclusively focused on their neurologic side-effects. In retrospect, the exclusive focus on EPS was too narrow. For example, it left the field unprepared to promptly respond to the additional weight and metabolic burden that arrived full force on the post-clozapine antipsychotic era. However, a belated recognition of the problem of metabolic risks of antipsychotics should not be a reason for turning our backs to the continued problem of persistent EPS in the current era of atypical antipsychotics. This editorial is a plea to clinicians and researchers not to forget EPS. Our patients cannot afford to have us make the same mistake of overlooking EPS again (5, 6). We need to remember that 'mild' EPS is only 'mild' relative to the magnitude of the often crippling EPS that was so common during the pre-clozapine era. It is not 'mild' for patients who have to live with their restlessness, or continually feeling 'slowed down, like a zombie'. Antipsychotic-induced EPS remains a serious public health problem. While the situation is better than it was during the 'pre-clozapine' era, the EPS problem has not gone away for our patients. But it seems to have been forgotten. References 1 Weiden PJ. EPS profiles: the atypical antipsychotics are not all the same. J Psychiatr Pract 2007; 13: 13– 24. CrossrefPubMedGoogle Scholar 2 Sundram S, Lambert T, Pisculic D. Acculturation is associated with the prevalence of tardive dyskinesia and akathisia in community treated patients with schizophrenia. Acta Psychiatr Scand 2008; 117: 474– 478. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 3 Lieberman J, Stroup S, Mcevoy JP et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209– 1223. CrossrefCASPubMedWeb of Science®Google Scholar 4 Weiden PJ. Discontinuation and switching antipsychotic medication: lessons from the CATIE schizophrenia trial. J Clin Psychiatry 2007; 68(Suppl 1): 12– 19. CASPubMedWeb of Science®Google Scholar 5 Weiden PJ, Mann JJ, Haas GL, Mattson M, Frances A. Clinical nonrecognition of neuroleptic-induced movement disorders: a cautionary study. Am J Psychiatry 1987; 144: 1148– 1153. CrossrefCASPubMedWeb of Science®Google Scholar 6 Dixon L, Weiden PJ, Frances A, Rapkin B. Management of neuroleptic-induced movement disorders: effects of physician training. Am J Psychiatry 1989; 146: 104– 105. CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume117, Issue6June 2008Pages 401-402 ReferencesRelatedInformation