Changes in antipsychotic drug prescribing by general practitioners in the United Kingdom from 1991 to 2000: A population-based observational study

Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 12/2003; 56(5):569-75. DOI: 10.1046/j.1365-2125.2003.01905.x
Source: PubMed


To estimate changes in the frequency of use of various antipsychotic drugs in the UK from 1991 to 2000 and to relate these changes to patients' characteristics.
We conducted a population-based observational study using data from general practices that contribute information to the General Practice Research Database (GPRD). The study population comprised men and women 10-99 years old. We estimated annual use, first-time use, duration of use and, in a sample of 200 patients, indications for use of various antipsychotic drugs, and we observed how these measures had changed over the past decade.
The annual use of antipsychotic drugs increased from 10.5 per thousand in 1991 to 12.2 per thousand in 2000, an overall increase of 16%. The increase was greater in men (25.2%) than women (2.7%). At the same time, the rate of new use of antipsychotic drugs was stable in men and decreased by 21% in women. The difference between patterns of annual use and rates of new use is attributable to the increasing average annual duration of treatment in both men and women during the past decade. Thioridazine, which the UK Committee on the Safety of Medicines (CSM) recently recommended should be used only for second-line treatment of schizophrenia in adults, was the most commonly prescribed antipsychotic throughout the study period. Its use increased as a proportion of all antipsychotic drug use from 1991 to 2000 in men and women aged 10-69 years, but decreased in older users. More than half of all first-time use of antipsychotic drugs in the sample of patients we evaluated was for treatment of depression, anxiety states, and panic disorders, while less than 10% was for treatment of schizophrenia and other psychoses.
The use of antipsychotic drugs has increased in the UK during the past decade, primarily due to increased average annual duration of use rather than higher rates of new use. Most antipsychotic drug use appears to have been prescribed to treat nonpsychotic disorders. It will be of interest to see whether the use of thioridazine, which was the most widely prescribed antipsychotic during 1991-2000, decreases during the next decade in response to the recent CSM recommendation.

  • Source
    • "Whilst the MHRA considers a small number of allegations of illegal promotion each year, the majority of complaints are, therefore, administered by the PMCPA[10]. Whereas both the law and the ABPI Code prohibit off-label promotion, off-label prescribing is lawful (albeit controversial) and widespread—for example, in oncology121314, psychiatry[15,16], paediatrics171819, and palliative care[20,21]. Although some off-label prescribing is evidence based and/or unavoidable222324, studies also show that a significant amount of offlabel use takes place without sufficient scientific evidence supporting this practice[2,25,26], and there is also evidence that off-label prescribing has caused serious harm to patients[27,28]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: European Union law prohibits companies from marketing drugs off-label. In the United Kingdom-as in some other European countries, but unlike the United States-industry self-regulatory bodies are tasked with supervising compliance with marketing rules. The objectives of this study were to (1) characterize off-label promotion rulings in the UK compared to the whistleblower-initiated cases in the US and (2) shed light on the UK self-regulatory mechanism for detecting, deterring, and sanctioning off-label promotion. Methods and findings: We conducted structured reviews of rulings by the UK self-regulatory authority, the Prescription Medicines Code of Practice Authority (PMCPA), between 2003 and 2012. There were 74 off-label promotion rulings involving 43 companies and 65 drugs. Nineteen companies were ruled in breach more than once, and ten companies were ruled in breach three or more times over the 10-y period. Drawing on a typology previously developed to analyse US whistleblower complaints, we coded and analysed the apparent strategic goals of each off-label marketing scheme and the practices consistent with those alleged goals. 50% of rulings cited efforts to expand drug use to unapproved indications, and 39% and 38% cited efforts to expand beyond approved disease entities and dosing strategies, respectively. The most frequently described promotional tactic was attempts to influence prescribers (n = 72, 97%), using print material (70/72, 97%), for example, advertisements (21/70, 30%). Although rulings cited prescribers as the prime target of off-label promotion, competing companies lodged the majority of complaints (prescriber: n = 16, 22%, versus companies: n = 42, 57%). Unlike US whistleblower complaints, few UK rulings described practices targeting consumers (n = 3, 4%), payers (n = 2, 3%), or company staff (n = 2, 3%). Eight UK rulings (11%) pertaining to six drugs described promotion of the same drug for the same off-label use as was alleged by whistleblowers in the US. However, while the UK cases typically related to only one or a few claims made in printed material, several complaints in the US alleged multifaceted and covert marketing activities. Because this study is limited to PMCPA rulings and whistleblower-initiated federal cases, it may offer a partial view of exposed off-label marketing. Conclusion: The UK self-regulatory system for exposing marketing violations relies largely on complaints from company outsiders, which may explain why most off-label promotion rulings relate to plainly visible promotional activities such as advertising. This contrasts with the US, where Department of Justice investigations and whistleblower testimony have alleged complex off-label marketing campaigns that remain concealed to company outsiders. UK authorities should consider introducing increased incentives and protections for whistleblowers combined with US-style governmental investigations and meaningful sanctions. UK prescribers should be attentive to, and increasingly report, off-label promotion.
    Full-text · Article · Jan 2016 · PLoS Medicine
  • Source
    • "The atypical antipsychotic drug olanzapine (OLZ, Fig. 1a) is amongst the most commonly prescribed antipsychotic drugs, not only for adults [1] [2] [3] [4] [5] but also for youths [6] [7]. Treatment with OLZ is associated with several health risks, including cardiovascular complications, an increased risk of sudden cardiac death (SCD) [8], diabetic complications ranging from ''mild glucose intolerance to diabetic ketoacidosis'' [9], a lowered seizure threshold level in epilepsy [10] [11] and fatal status epilepticus [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Olanzapine (OLZ) is amongst the most commonly prescribed antipsychotic drugs and is associated with substantial instability. The aim of this study was to investigate the instability of OLZ and to identify the degradants formed from its breakdown. Three experiments were conducted to monitor the degradation of OLZ and the formation of degradants in blood (1), water (2), and post-extraction at 4 °C (3). All three sample sets were analysed in duplicate and repeated in the absence (A) and presence (B) of 0.25% ascorbic acid. One degradant was identified in sample sets 2A and 3A with m/z 329 and confirmed as 2-hydroxymethyl-OLZ (2-OH-OLZ) using LC-MS techniques. The addition of 0.25% ascorbic acid slowed the degradation of OLZ down in all three experiments and inhibited the formation of 2-OH-OLZ in sample sets 2A and 3A. To investigate the influence of oxygen on the degradation of OLZ and the formation of 2-OH-OLZ in water, an additional experiment (4) was conducted. Sample sets were prepared containing different vortexing or sonication steps in order to alter the oxygen content in the samples. Statistical analysis confirmed that degradation increased significantly following vortexing for 1 min while sonication did not affect the rate of degradation of OLZ further suggesting the involvement of oxygen in the degradative processes. 2-OH-OLZ was only identified as a degradant of OLZ in aqueous solutions. It also degrades over time but its product is currently unknown and is under investigation.
    Full-text · Article · Feb 2012 · Forensic science international
  • Source
    • "The increase in time spent on medication is likely to represent both increased prescribing and increased adherence to medication [20], [29]. Previous studies of antipsychotic prescribing trends have found that, over time, patients have been prescribed medications (for all indications) for longer periods [30], and this has been shown specifically in the bipolar disorder patient group [31]. Our results differ from some studies from the United States, which found that lithium prescription for bipolar declined, over the period 1990–2005 [31], [32], [33]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine changes in prescribing patterns in primary care of antipsychotic and mood stabiliser medication in a representative sample of patients with bipolar disorder in the United Kingdom over a fifteen year period and association with socio-demographic factors. We identified 4700 patients in the Health Improvement Network (THIN) primary care database, who had received treatment for bipolar disorder between 1995 and 2009. The proportion of time for which each individual was prescribed a particular medication was studied, along with variation by sex, age and social depravation status (quintiles of Townsend scores). The number of drugs an individual was taking within a particular year was also examined. In 1995, 40.6% of patients with bipolar disorder were prescribed a psychotropic medication at least twice. By 2009 this had increased to 78.5% of patients. Valproate registered with the greatest increase in use (22.7%) followed by olanzapine (15.7%) and quetiapine (9.9%). There were differences by age and sex; with young (18-30 year old) women having the biggest increase in proportion of time on medication. There were no differences by social deprivation status. By 2009, 34.2% of women of childbearing age were treated with valproate. Lithium use overall remained relatively constant, whilst second generation antipsychotic and valproate use increased dramatically. Changes in prescribing practice preceded published trial evidence, especially with the use of second generation antipsychotics, perhaps with inferences being made from treatment of schizophrenia and use of first generation antipsychotics. Women of childbearing age were prescribed valproate frequently, against best advice.
    Full-text · Article · Dec 2011 · PLoS ONE
Show more