Specific Antipsychotic Drugs Prescribed for Dementia Could Increase Mortality

Clin. Invest. (2012) 2(4), 355–358

NEWS

Specific antipsychotic drugs prescribed for dementia could increase mortality

The largest US nursing home resident study reveals that different types of antipsychotic drugs have varying effects on the risk of mortality in elderly patients

Elderly patients treated with specific 180 days. The other drugs investigated did antipsychotic drugs for dementia are at not demonstrate clinically meaningful dif- “…future research should be increased risk of death, according to a ferences. The effects of the antipsychot- pragmatic. It should focus on population-based cohort study involving ics were strongest soon after the initiation identifying the key components 75,445 nursing home residents aged 65 or of treatment and remained after dose of non-drug-based interventions older. The results emphasize the compel- adjustment. There was a dose–response and on establishing the service ling need to develop alternative treatment relationship for all drugs except quetiapine. structures that can deliver them methods for older patients with dementia. The authors of the study concluded as simply and efficiently as Currently, up to a third of all elderly that the “clinicians may want to consider possible.” patients in nursing homes are treated with this evidence when evaluating … the best antipsychotic drugs. However, recently, approach to treatment of behavioral prob- Written by Francesca Edelmann, Production concerns over the safety of antipsychotic lems.” However, they indicated that the Editor. drugs in the elderly have accumulated current non-pharmacological interven- and, accordingly, the US FDA has issued tions for dementia are often insuf- Sources: Huybrechts KF, Gerhard T, Crystal S et al. Differential risk of death in older residents advisory warnings for the use of both ficient in patients with severe and in nursing homes prescribed specific conventional and atypical antipsychotics persistent or recurrent symptoms antipsychotic drugs: population based in older patients. Researchers in the USA and, in the absence of proven effec- cohort study. BMJ 344, e977 (2012); McCleery J. Antipsychotic prescribing in undertook the largest study involving US tive and safe alternative pharmaco nursing homes. BMJ 344, e1093 nursing home residents, to investigate the logical treatments, it is likely that (2012). increased risk of mortality due to specific antipsychotic drugs will continue to antipsychotic drugs: haloperidol, aripipra- be used widely, despite the fact that zole, olanzapine, quetiapine, risperidone there is not evidence of their efficacy and and ziprasidone. data confirming their risk. Jenny McCleery from the Oxford NHS “The use of any antipsychotic in Foundation Trust (Oxford, UK) agreed dementia is undesirable given with this conclusion. “The use of any antipsychotic in dementia is unde- the increased risk of death and sirable given the increased risk the many other adverse effects of death and the many other of these drugs, in addition to adverse effects of these drugs, their limited efficacy against in addition to their limited target behavioral and efficacy against target behav- psychological symptoms.” ioral and psychological symptoms.” She added that It was found that that there is variation “future research should be pragmatic. It in the risk of death according to the type should focus on identifying the key com- of drug used. In comparison with risp- ponents of non-drug-based interventions eridone, the reference group, haloperidol and on establishing the service struc- caused an increased risk and quetiapine tures that can deliver them as simply and caused a decreased risk of mortality within efficiently as possible.”

Improving clinical trials much more about their condition through Therapeutic in molecular oncology online educational resources. Speaking misconception still exclusively to Clinical Investigation, West Oncologists have recently described explains a novel side to this increased prevalent in Phase I trials a new outlook on patient patient knowledge base: “The dynamic of how physicians, at least oncologists, inter- The frequency of misconception participation in lung cancer trials amongst patients enrolled in Phase I with molecular preselection act with motivated patients is shifting to a more bidirectional, collaborative mutual clinical trials has been elucidated by a group of medical oncologists In a recent paper in the Journal of Thoracic sharing of information, as opposed to a Oncology, Howard West from the Swedish historically unidirectional approach of the In a research article, which is to be published Cancer Institute (WA, USA) and Ross physician having access to all of the medi- in Cancer, Rebecca Pentz from the Emory Camdige of the University of Colorado cal management options and the patient University School of Medicine (GA, USA) School of Medicine (CO, USA) describe relying on a single doctor to provide all and colleagues report their investigation into new suggestions for tackling the growing insight and treatment recommendations.” misconceptions held by patients enrolled in problem of patient recruitment in lung The authors also discuss how the struc- Phase I clinical trials. The research team’s cancer trials for patients with specific ture of clinical trials needs to be updated findings suggest more education is necessary mutations. They hope this research will to suit the new molecular basis of oncology to avoid the misconceptions still present in influence new molecular oncology trial research. As West explains, “geographic Phase I trial participants. design and implementation. diversity of patients with these narrow In their research two particular forms of Molecular preselection is becoming clinical and molecular parameters will misconception were studied. First, thera- more prevalent in oncology clinical trials greatly limit the ability of trials to enroll peutic misconception, which is when a due to increased scientific knowledge on patients from single centers.” He hopes patient believes the aim of the trial is to the basis of cancer progression. This means that their work will encourage sponsors of improve the health of the enrolled patients patients should be able to receive more clinical trials to invest in new strategies to (i.e., a therapeutic aim), rather than to personalized treatment. However, new fight this emerging problem. A key method forward research. Second, therapeutic issues have arisen in the implementation described in their paper is telemedicine- misestimation, which is when a patient of these trials, since patients with specific based platforms, to enable remote selec- wrongly understands the risks or chances mutations (required for a specific oncology tion and follow-up of patients enrolling of health benefits. trial) are more geographically dispersed. in these trials. Telemedicine is defined as Although therapeutic misconception is a the use of electronic communication to well-known issue to arise in clinical trials, “…geographic diversity of exchange medical information between the team felt there was a lack of recent “sys- patients with these narrow two sites. Additionally, the authors suggest tematic, empirical evaluation” of the fre- that trial providers could reimburse either quency of this, and other misunderstand clinical and molecular parameters the patient or clinician for travel costs to ings in clinical trial participants. The team will greatly limit the ability of remote trial sites, or host the trial at various interviewed 95 patients enrolled in Phase I trials to enroll patients from disperse sites. trials. Of these patients, 68.4% of the inter- single centers.” West details his plans for future work: “I viewees were found to have therapeutic mis- am working on developing a telemedicine- conception. On further analysis this was In the paper by West and Camdige vari- based platform for consultations and gen- found to be associated with lower educa- ous methods for tackling this problem are eral clinical oversight of patients who are a tion and family income, but not associated discussed, focusing particularly on lung prohibitive distance away from an expert on with a patient’s lack of treatment options. A cancer trials. First, the pair describe how their particular cancer. This approach could higher proportion of patients were found to online patient communities can assist in easily be applied to clinical research efforts have therapeutic misestimation, with 95% the advertisement of trials. West leads the as well, provided that forward-thinking of patients falling into this category. Global Resource for Advancing Cancer research sponsors are inclined to overcome Additionally, the team investigated the Education (GRACE), which is an online the bottleneck of low geographic density of patient’s thoughts on the perceived risks social media community. In the paper he their target research population.” and benefits of participating in the trial. describes one particular success of this site They found that 39% patients mentioned – in February 2010, after publishing a pod- Written by Alice O’Hare, Assistant the risks of investigational agents and 41% Commissioning Editor. cast detailing one particular clinical trial, mentioned uncertain outcomes (due to this patients traveled from 15 different US states Source: West HJ, Camidge DR. Have mutation, being research rather than tested therapeu- and one from South Africa to participate. will travel: utilizing online patient communities tics). Only 3% of patients mentioned the and new trial strategies to optimize clinical Leading on from this point, the authors research in the era of molecularly diverse risks that could arise solely due to this identify that patients can additionally learn oncology. J. Thorac. Oncol. 7(3), 482–484 (2012). being research, such as biopsies.

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Looking to the perceived outcomes of Conversely only 37.6% were pessimists, Written by Alice O’Hare, Assistant Commissioning Editor. the trial, the researchers found that slightly believing the opposite. over half (54.6%) of the sample group were The researchers conclude that therapeu- Source: Pentz RD, White M, Harvey RD et al. optimistic – defined by believing that “their tic misconception is still high, and suggest Therapeutic misconception, misestimation, and optimism in participants enrolled in Phase 1 chance of benefit was greater, and that their that more education is necessary to avoid trials. Cancer. doi: 10.1002/cncr.27397 (2012) risk was lower than the population chance.” this lack of understanding. (Epub ahead of print).

US nationwide trial has implications for emergency seizure treatment A national trial conducted across the USA comparing delivery of anticonvulsant medication may have implications for paramedics

Researchers from the University of researchers hypothesized that the intra- Looking at the scene of the emergency, Cincinnati (OH, USA) have collaborated muscular route would be found to be intramuscular therapy was found to be with local paramedics to compare the noninferior. administrated within a median time of efficacy and safety of two differing meth- The research comprised part of 1.2 min, compared with 4.8 min for ods for delivering medication to seizing RAMPART, and was carried out over a intravenous administration. Conversely, patients. Their research, to be published in national scale – involving 79 hospitals the time it took for the medication to the New England Journal of Medicine, has and 33 emergency medical services agen- take effect (i.e., for the convulsions to implications for prehospital care of seizing cies in the USA. The double-blinded, stop) was a median of 3.3 min for intra- patients by paramedics. randomized trial was unusual in that muscular compared with 1.6 min for Status epilepticus is defined as a pro- the patients receiving the medication intravenous. longed seizure lasting more that 5 min. could not consent (due to their condi- Overall, the research indicates that Traditionally, in this situation paramed- tion). Therefore, the trial was regulated for status epilepticus, intramuscular ics administer intravenous anticonvulsant under a special US FDA ruling “exception midazolam is as safe and effective as the medication. However, since this is rela- from informed consent,” and awareness traditional intramuscular medication. tively slow to administer, intramuscular of the trial was raised within the com- Co-investigator Jason McMullan from administration (with an autoinjector, munities before the trial launch. Author the University of Cincinnati explains the which is similar to an epipen) would be Arthur Pancioli from the University of implications of these results and future preferential to many in the medical pro- Cincinnati expressed gratitude to the prospects: “The use of the auto-injectors fession. The aim of this clinical trial was public: “We would like to thank … our could further improve the excellent care to compare the efficacy of intramuscular community for their trust in allowing us our paramedics provide to their patients midazolam with intravenous lorazepam to perform this study. Without this type every day. While the auto-injectors are for status epilepticus. The of research, critical opportunities to help not yet commercially available, this trial patients with neurological emergencies provides an opportunity to change the would be lost.” way that paramedics everywhere deliver The research teams elucidated that time-critical treatment for status epilep- when intramuscular midazolam was ticus and improve the potential outcomes administrated on arrival at the emergency for our patients.” department, 73.4% (329 of 448) patients

were without seizure and required no res- Written by Alice O’Hare, Assistant cue therapy. When intravenous lorazepam Commissioning Editor. was administrated, only 63.4% of patients Sources: Silbergleit R, Durkalski V, Lowenstein D had this outcome. et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N. Engl. J. Med. 366, 591–600 (2012); National trial shows auto-injectors faster, more effective than iv lines in stopping prolonged seizures: www. healthnews.uc.edu/news/?/15315

future science group Clin. Invest. (2012) 2(4) 357 NEWS

Zioptan™ is approved by the US FDA

ZioptanTM, an eye drop that aims to reduce heightened eye pressure, has recently been approved by the US FDA for use in patients with open-angle glaucoma or ocular hypertension

Ocular hypertension is a heightened pres- showed reduced eye pressure at 3- and USA), Edward Cox, explained the signifi- sure in the eye, which is a leading risk 6-month intervals. The patients’ eye pres- cance of this approval: “Zioptan’s approval factor of glaucoma (the most common sures decreased from a baseline of 23–26 provides an alternative treatment option for of which is open-angle glaucoma). This mmHg by an average of 6–8 mmHg at patients living with this potentially blind- condition can in turn lead to blindness. 3 months and 5–8 mmHg at 6 months. ing disease.” Merck expects their newly Zioptan™, which is marketed by Merck approved product to be commercially (NJ, USA), is a prostaglandin analog. This “…Zioptan’s approval provides an available in the near future. type of medication works by increasing the alternative treatment option for removal of fluid from the eye. patients living with this Written by Alice O’Hare, Assistant Zioptan has been shown to be safe and Commissioning Editor. effective in various long-term clinical tri- potentially blinding disease.” als. A total of 905 patients were enrolled Sources: FDA press release: www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ over five clinical studies, the longest of The director of the Office of Anti ucm291966.htm; Merck press release: www. which was 24 months. Patients treated microbial Products at the US FDA’s Centre merck.com/newsroom/news-release-archive/ with eye drop once daily in the evening for Drug Evaluation and Research (MD, prescription-medicine-news/2012_0213.html

Korlym™ approved by the US FDA for hyperglycemic control in patients with endogenous Cushing’s syndrome

Korlym™, a therapeutic for the treatment of hyperglycemia in endogenous Cushing’s syndrome, is the first of its kind to be approved by the US FDA

The US FDA has recently approved the use of carried out specialized fast-track proce- Korlym™, a cortisol receptor blocker, for the dures to ensure the therapeutic reached “…the FDA carried out specialized control of blood sugar levels in certain adults the patients without undue delay. Among fast-track procedures to ensure with endogenous Cushing’s syndrome. This various studies, the safety and efficacy of the therapeutic reached the subset of patients are characterized by Type Korlym has been proven in a clinical trial patients without undue delay.” 2 diabetes or glucose intolerance and fail to with 50 patients. respond to, or are not candidates for, surgery. Korlym, which is marketed by Corcept Written by Alice O’Hare, Assistant Endogenous Cushing’s syndrome is defined Therapeutics (CA, USA), has been Commissioning Editor. by an overproduction of cortisol and thus approved in a dosage strength of 300mg this new therapeutic prevents the unwanted tablets. The company has approved the Sources: US FDA press release: www.fda.gov/ effects of this steroid hormone. distribution of the drug through a central NewsEvents/Newsroom/PressAnnouncements/ ucm292462.htm; Corcept Therapeutics press This is the first approved medicine for pharmacy, allowing better access for suf- release: www.corcept.com/news_events/ this condition, and accordingly the FDA ferers of this rare disease. pr_1329524335

The editorial team welcomes suggestions for timely, relevant items for inclusion in the news. If you have newsworthy information, please contact: Cara Sutton, Managing Commissioning Editor, Clinical Investigation Tel.: +44 (0)20 8371 6090; E-mail: [email protected]

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