Antipsychotic prescribing trends: A review of pharmacoepidemiological studies

INSERM U657, Université Victor Segalen Bordeaux2, Bordeaux Cedex, France.
Acta Psychiatrica Scandinavica (Impact Factor: 5.61). 01/2010; 121(1):4-10. DOI: 10.1111/j.1600-0447.2009.01425.x
Source: PubMed


To review findings from pharmaco-epidemiological studies exploring antipsychotic (AP) drugs prescribing trends.
We retrieved original studies that explored AP prescribing trends in general population samples since 2000. For each study, we extracted information on sampling method, period, assessment of AP use and corresponding estimates (incidence rates, prevalence rates, pharmacy sales, prescription data) and diagnostic assessment.
Nearly all studies meeting the inclusion criteria (n = 17) showed an increase in AP prescriptions, mainly because of a dramatic rise in second-generation antipsychotics (SGAP) prescriptions. APs are often prescribed for non-psychotic disorders in adults as well as in children and adolescents.
Considering the growing number of persons from the general population exposed to APs, population studies assessing the risk/benefit ratio of SGAP use in disorders other than psychosis are necessary, particularly in children and adolescents.

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    • "Second-generation antipsychotics (SGAs), clozapine, olanzapine and risperidone, have improved quality of life of billions psychiatric patients worldwide and became essential in the clinical guidelines for treatment of schizophrenia (SZ) [3] [44]. Although the primary target of this drugs are SZ patients, estimated in 1% of world population [40] [39], leading experts have warned on the exponential increase of the " off-label " applications of SGAs, which include non- SZ adults [75], adolescents and children [86] suffering from a wide range of psychiatric conditions [127]. Intriguingly, several of the increasing off-label indications in non-SZ patients still lack sufficient safety – and efficacy – evidence. "
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    ABSTRACT: Second generation antipsychotics (SGAs), such as clozapine, olanzapine, risperidone and quetiapine, are among the most effective therapies to stabilize symptoms schizophrenia (SZ) spectrum disorders. In fact, clozapine, olanzapine and risperidone have improved the quality of life of billions SZ patients worldwide. Based on the broad spectrum of efficacy and low risk of extrapyramidal symptoms displayed by SGAs, some regulatory agencies approved the use of SGAs in non-schizophrenic adults, children and adolescents suffering from a range of neuropsychiatric disorders. However, increasing number of reports have shown that SGAs are strongly associated with accelerated weight gain, insulin resistance, diabetes, dyslipidemia, and increased the cardiovascular risk. These metabolic alterations can develop in as short as six months after the initiation of pharmacotherapy, which is now a controversial fact in public disclosure. Although the percentage of schizophrenic patients, the main target group of SGAs, is estimated in only 1% of the population, during the past ten years there was an exponential increase in the number of SGAs users, including millions of non-SZ patients. The scientific bases of SGAs metabolic side effects are not yet elucidated, but the evidence shows that the activation of transcriptional factor SRBP1c, the D1/D2 dopamine, GABA2 and 5HT neurotransmitions are implicated in the SGAs cardiovascular toxicity. Polypharmacological interventions are either non- or modestly effective in maintaining low cardiovascular risk in SGAs users. In this review we critically discuss the clinical and molecular evidence on metabolic alterations induced by SGAs, the evidence on the efficacy of classical antidiabetic drugs and the emerging concept of antidiabetic polyphenols as potential coadjutants in SGA-induced metabolic disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Pharmacological Research 07/2015; DOI:10.1016/j.phrs.2015.07.022 · 4.41 Impact Factor
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    • "Over the last two decades, the risk of diabetes associated to antipsychotics attracted considerable clinical interest in psychiatry. The main reason for this emerging issue was a marked rise in second-generation antipsychotics' (SGAP) use, a class with less extrapyramidal Adverse Drug Reactions (ADRs) than first-generation antipsychotics (FGAP) (Geddes et al., 2000; Verdoux et al., 2010), but more likely to cause or exacerbate diabetes (Expert Group, 2004; Saddichha et al., 2008). Among SGAP, glycemic dysregulations and diabetes are more frequent with olanzapine or clozapine than with risperidone , quetiapine or aripiprazole (Starrenburg and Bogers, 2009; Reynolds and Kirk, 2010; Meyer et al., 2008). "
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    ABSTRACT: Pharmacodynamic mechanisms of diabetes induced by antipsychotic drugs remain unclear, while numerous receptors have been suspected to be involved in the genesis of this Adverse Drug Reaction (ADR). We investigated potential relationships between antipsychotics׳ receptor occupancy (serotonin 5-HT1A, 5-HT2A, 5-HT2C, histamine H1, muscarinic M3, adrenergic α1, α2 or dopaminergic D2 D3 occupancies) and reports of diabetes using VigiBase(®), the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. All ADR reports from 15 first and second generation antipsychotic drugs recorded in VigiBase(®) were extracted. Logistic regression models, completed by disproportionality analysis, were used to determine the associations between antipsychotics׳ receptor occupancy and ICSRs of diabetes on VigiBase(®). During the study period, 94,460 ICSRs involved at least one of the 15 antipsychotics of interest. Diabetes was reported in 1799 (1.9%) patients. Clozapine was the most frequently suspected drug (n=953; 53.0%). A significant and positive association was found between histamine H1, muscarinic M3 and serotonin 5-HT2C, 5-HT2A receptor occupancies and reports of diabetes. A multivariable stepwise regression model showed that only serotonin 5-HT2c (AOR=2.13, CI 95% 1.72-2.64) and histamine H1 (AOR=1.91, CI 95% 1.38-2.64) predicted the risk for diabetes mellitus (p<0.001). Using an original pharmacoepidemiology-pharmacodynamic (PE-PD) approach, our study supports that antipsychotic drugs blocking simultaneously histamine H1 and serotonin 5-HT2C receptors are more frequently associated with diabetes reports in VigiBase(®) than other antipsychotics. These findings should encourage investigation of histamine H1 and serotonin 5-HT2C properties for predicting the risk of glycemic effects in candidate antipsychotics. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2015; DOI:10.1016/j.euroneuro.2015.07.010 · 4.37 Impact Factor
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    • "The arrival of the second-generation antipsychotics (SGAPs) in the 1990s has undoubtedly favored this increase [5]. SGAPs were believed to induce less neurological adverse drug reactions than first-generation antipsychotics (FGAPs) [5], even if extrapyramidal side effects may also occur with SGAPs [6]. Moreover, some SGAPs have exhibited new pharmacological profiles, which may have contributed to the emergence of new off-label indications and OLP practices. "
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    ABSTRACT: New antipsychotics continuously arrive on the market, which thereby influences the approved and off-label prescribing (OLP) schemes. We aimed to identify the recent trends in the OLP of antipsychotics. We conducted a literature review based on three different populations: adult, pediatric, and elderly patients. A literature search was performed in the PubMed and ScienceDirect databases using the following keyword algorithm: "off-label" AND ("antipsychotic*" OR "neuroleptic*"). The period investigated ranged from January 2000 to January 2015. Only English-written pharmacoepidemiological studies were included. Seventy-seven relevant results were identified. Among adults, OLP consisted of 40 to 75% of all antipsychotic prescriptions. The main indications were mood disorders, anxiety disorders, insomnia and agitation. Quetiapine was the most frequently prescribed off-label antipsychotic, especially for anxiety and insomnia. Among children, OLP was estimated between 36 and 93.2% of all antipsychotic prescriptions. Risperidone and aripiprazole were primarily used and were most often prescribed for attention deficit hyperactivity disorder, anxiety, or mood disorders. Among elderly individuals, OLP consisted of 22 to 86% of all antipsychotic prescriptions. Antipsychotic OLP was particularly frequent for agitation; however, a recent decrease in this OLP was identified. Antipsychotics have largely been prescribed off-label in recent years. The types of antipsychotic OLP practices differ according to the age category of patients. OLP is often used in cases of therapeutic dead-ends or for specific disorders with few or no currently approved medications. However, other OLP practices only reflect temporary prescription trends for mild symptoms, which may induce safety concerns.
    Current pharmaceutical design 06/2015; 21(23). DOI:10.2174/1381612821666150619092903 · 3.45 Impact Factor
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