Patients taking antipsychotic medications for psychiatric disorders also have many risk factors for medical comorbidities and early death. While these risk factors were present before the arrival of the newer antipsychotic medications, the overall risk factor burden is exacerbated for those high-risk patients whose antipsychotic therapy causes or aggravates obesity or dyslipidemia. Therefore, there is an urgent need for effective interventions to address problems related to the additional iatrogenic burden from weight gain and dyslipidemias caused by antipsychotic medications. For patients with schizophrenia, complete discontinuation of antipsychotic therapy is not advisable and, therefore, pharmacologic options are narrowed to dose adjustments, adding adjunctive agents to induce weight loss, discontinuation of other adjunctive agents associated with weight gain, or changing the antipsychotic medication ("switching"). This article reviews the evidence showing that relative to other possible treatment options, switching to an antipsychotic with a lower propensity to induce weight gain or dyslipidemia can be effective for reversing the weight gain and dyslipidemia caused by previous antipsychotic treatment.
"The substitution of one antipsychotic
agent by another is informally known as “switching.” Based on the above, it is not
surprising that switching between antipsychotic medications commonly occurs in the routine
treatment of schizophrenia, in an effort to find the optimal regimen for an individual
Switching can be motivated by the desire to improve efficacy, tolerability, or
A number of switch techniques have been employed in evaluating optimal approaches to
the initiation of the new antipsychotic and/or the discontinuation of the pre-switch
Despite the appeal of switching antipsychotics, there are also potential concerns of
complications from attempting a switch, such as symptom exacerbation, insufficient efficacy,
and new tolerability problems emerging from the “post-switch” medication. "
[Show abstract][Hide abstract] ABSTRACT: To evaluate the long-term safety and tolerability of lurasidone in schizophrenia and schizoaffective disorder patients switched to lurasidone.
Patients in this multicenter, 6-month open-label, flexible-dose, extension study had completed a core 6-week randomized trial in which clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone. Patients started the extension study on treatment with the same dose of lurasidone taken at study endpoint of the 6-week core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if clinically indicated, starting on Day 7 of the extension study. The primary safety endpoints were the proportion of patients with treatment emergent adverse events (AEs), serious AEs, or who discontinued due to AEs. Secondary endpoints included metabolic variables and measures of extrapyramidal symptoms and akathisia, as well as the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), and the Calgary Depression Scale for Schizophrenia (CDSS). The study was conducted from August 2010 to November 2011.
Of the 198 patients who completed the 6-week core study, 149 (75.3%) entered the extension study and 148 received study medication. A total of 98 patients (65.8%) completed the 6-month extension study. Lurasidone 40, 80, and 120 mg were the modal daily doses for 19 (12.8%), 65 (43.9%), and 64 (43.2%) of patients, respectively. Overall mean (SD) daily lurasidone dose was 102.0 mg (77.1). The most commonly reported AEs were insomnia (13 patients [8.8%]), nausea (13 patients [8.8%]), akathisia (12 patients [8.1%]), and anxiety (9 patients [6.1%]). A total of 16 patients (10.8%) had at least one AE leading to discontinuation from the study. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, lipids, glucose, insulin, or prolactin. Movement disorder rating scales did not demonstrate meaningful changes. Treatment failure (defined as any occurrence of discontinuation due to insufficient clinical response, exacerbation of underlying disease, or AE) was observed for 19 patients (12.8% of patients entering) and median time to treatment failure was 58 days (95% CI 22-86). The discontinuation rate due to any cause was 50/148 (33.8%), and median time to discontinuation was 62 days (95% CI 30-75). The mean PANSS total score, mean CGI-S score, and mean CDSS score decreased consistently from core study baseline across extension visits, indicating an improvement in overall condition.
In this 6-month, open-label extension study, treatment with lurasidone was generally well-tolerated with sustained improvement in efficacy measures observed in outpatients with schizophrenia or schizoaffective disorder who had switched to lurasidone from a broad range of antipsychotic agents.
"The adverse effects of long term weight gain have not escaped regulatory bodies. A number of clinical practice guidelines , ,  and other studies – all recommend choosing psychotropics least likely to cause weight gain, or switching to those less likely to cause weight gain – if weight gain occurs. This is because the CATIE trial data does provide some evidence that patients who stayed on medications with high propensity to induce weight gain, showed greater weight gain than those who switched from these medications to other drugs that were less likely to cause weight gain . "
[Show abstract][Hide abstract] ABSTRACT: Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders.
To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics.
We developed a novel hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available we went on to evaluate randomly controlled trials, followed by cohort and other clinical trials, narrative reviews, and, where necessary, clinical opinion and anecdotal evidence. The data from the publication with the highest level of evidence based on our hierarchical classification was presented. Recommendations from an expert panel supplemented the evidence used to rank these drugs within their respective classes. Approximately 9500 articles were identified in our literature search of which 666 citations were retrieved. We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts. There were few discrepancies between published evidence and the expert panel in ranking these drugs.
Potential for weight gain is an important consideration in choice of any psychotropic. This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices.
PLoS ONE 06/2012; 7(6):e36889. DOI:10.1371/journal.pone.0036889 · 3.23 Impact Factor
"For patients suffering from schizophrenia, discontinuation of antipsychotic medication is not advisable, and thus switching to an antipsychotic with a lower propensity to induce weight gain needs be explored as a strategy. Our analysis suggests, in accord with previous findings , that aripiprazole could be useful for patients treated with other antipsychotics who show significant weight gain, a well-established side effect of many antipsychotics. "
[Show abstract][Hide abstract] ABSTRACT: Weight gain is one of the major drawbacks associated with the pharmacological treatment of schizophrenia. Existing strategies for the prevention and treatment of obesity amongst these patients are disappointing. Switching the current antipsychotic to another that may favorably affect weight is not yet fully established in the psychiatric literature. This meta-analysis focused on switching to aripiprazole as it has a pharmacological and clinical profile that may result in an improved weight control. Nine publications from seven countries worldwide were analyzed. These encompassed 784 schizophrenia and schizoaffective patients, 473 (60%) men and 311 (40%) women, mean age 39.4 ± 7.0 years. The major significant finding was a mean weight reduction by -2.55 ± 1.5 kgs following the switch to aripiprazole (P < .001). Switching to an antipsychotic with a lower propensity to induce weight gain needs be explored as a strategy. Our analysis suggests aripiprazole as a candidate for such a treatment strategy.
Journal of obesity 01/2011; 2011(1). DOI:10.1155/2011/898013
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