Side Effects of Atypical Antipsychotics: Extrapyramidal Symptoms and the Metabolic Syndrome

Harvard South Shore Psychiatry Program, Brockton, MA, USA.
Harvard Review of Psychiatry (Impact Factor: 1.73). 07/2006; 14(3):152-64. DOI: 10.1080/10673220600748486
Source: PubMed


In this article we examine the two major classes of side effects with atypical antipsychotics: extrapyramidal symptoms (EPS) and the metabolic syndrome (the triad of diabetes, dyslipidemia, and hypertension, with associated obesity). We conclude that atypical antipsychotics continue to have notable risks of EPS, particularly akathisia, and that these agents also appear to increase the risk of the metabolic syndrome, though this effect seems most marked with clozapine and olanzapine. Novel conclusions based on this review are as follows: we provide a classification scheme based on low versus high D2 binding affinity (which is, to our knowledge, a new means of classifying atypical antipsychotics); we emphasize that the akathisia risk is likely equal among agents and that tardive dyskinesia is an early, and not late, risk in treatment (a common misconception); we make the methodological point that in randomized clinical trials, there is a high risk of false-negatives regarding side effects; we raise the issue of confounding bias in epidemiological studies of metabolic syndrome; and we stress the need to compare side effects in the same studies and not different studies. Future prospective observational cohort studies must target side effects and be designed to collect and analyze data on confounding factors.

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    • "Since patients in the FGA (perphenazine) group were free from previous TD, CATIE study does not enable true comparison between FGAs and SGAs regarding TD, but it offers some valuable insight into predisposing factors for TD registered as baseline. These factors are older age, previous exposure to FGA and anticholinergic medication, previous longer antipsychotic treatment, and acute EPS [13] [24]. The CUtLASS-1 study showed unexpectedly the increase of TD incidence in the SGA group of patients during the 12th week of treatment, but this was probably due to switch of treatment (withdrawal of D2 blocking drug and the initiation of an SGA with more anticholinergic effects). "
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    ABSTRACT: Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.
    Full-text · Article · Jun 2014 · BioMed Research International
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    • "Since the introduction of psychotropic medications, evidence has suggested that these drugs (a) may be effective in treating positive psychiatric symptoms (Leucht, Hierl, Kissling, Dold, & Davis, 2012); (b) have limited effects on the negative and cognitive symptoms that often predict long-term disability (Bowie et al., 2010; Milev, Ho, Arndt, & Andreasen, 2005); and (c) induce significant side effects in almost every organ system (Shirzadi & Ghaemi, 2006). Because of side effects and other concerns, some people opt not to take medications, though decisions like these may lead to relapse and increased functional disability (Kreyenbuhl , Nossel, & Dixon, 2009; Velligan et al., 2009). "
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    ABSTRACT: Objective: To address gaps in the literature concerning the relationships among participation in peer-led mental health programs, the development of self-determination in service use, and medication use and engagement with medication prescribers and other traditional providers, we conducted focus groups with individuals involved in Wellness Recovery Action Plan (WRAP) programs. Method: We carried out five focus groups with 54 WRAP participants and/or facilitators, and analyzed transcripts using a grounded theory approach. Results: Emergent themes revealed differences of opinion regarding the role and value of medication adherence, broad agreement on the benefits of WRAP in increasing self-determination and self-awareness, and positive effects of participation on patient self-advocacy, medication-related decision-making and meaningful engagement with traditional providers. Conclusions and implications for practice: Findings emphasize the importance of examining the influence of stand-alone peer-led program involvement on relationships with traditional providers and decisions regarding medication use, as well as the heterogeneity of consumer treatment values, choices, and associated outcomes.
    Full-text · Article · Jul 2013 · Psychiatric Rehabilitation Journal
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    • "In the last twenty years, the introduction of second-generation antipsychotic drugs has caused substantial somatic consequences, such as weight gain (Tandon and Halbreich, 2003), hyperlipidemia (Meyer and Koro, 2004) and insulin resistance (Nasrallah and Newcomer, 2004; Wu et al., 2006). Furthermore, the use of these drugs is associated with the development of metabolic syndrome (Meyer et al., 2005; Shirzadi and Ghaemi, 2006) and type 2 diabetes (Henderson, 2002; Cohen, 2004; Melkersson and Dahl, 2004; Newcomer, 2005). Older patients using second-generation antipsychotics show a 1.6-to 1.7-fold increase in the risk of death (Schneider et al., 2005), which is at least partly due to sudden cardiac death and cerebrovascular accidents. "
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    ABSTRACT: This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality in patients with schizophrenia. This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 80,569 patients with schizophrenia and 241,707 age- and sex-matched control participants without schizophrenia. The participants were randomly selected from the 23,981,020-participant NHIRD, which consists of 96% Taiwanese participants. Participants who had experienced a stroke between 1999 and 2003 were excluded. Using data from the NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and patient survival after stroke were calculated for both groups. After adjusting for confounding risk factors, a Cox proportional-hazards model was used to compare the five-year stroke-free survival rate to the all-cause mortality rate across the two cohorts. Over five years, 1380 (1.71%) patients with schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting for demographic characteristics and comorbid medical conditions, patients with schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05-1.22; P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the follow-up period. After adjusting for patient, physician and hospital variables, the all-cause mortality hazard ratio for patients with schizophrenia was 1.23 (95% CI=1.06-1.41; P=0.0052). During a five-year follow-up, the likelihood of developing a stroke and the all-cause mortality rate were greater among patients with schizophrenia as compared with the control group.
    Full-text · Article · Mar 2012 · Schizophrenia Research
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