General practitioners' perceptions of the tolerability of antidepressant drugs: a comparison of selective serotonin reuptake inhibitors and tricyclic antidepressants.

OBJECTIVE: To examine inceptions and discontinuations of antidepressants in general practice. DESIGN: An observational study analysing data from an ongoing cross sectional postal survey. Every three months a representative sample of 250 doctors recorded prescribing activity for four weeks. This provided 4000 general practitioner weeks of recording per year. SETTING: A representative panel of general practitioners in England, Wales, and Scotland. SUBJECTS: Patients who began a new course of an antidepressant or had their treatment stopped or changed by the general practitioner between 1 July 1990 and 30 June 1995. MAIN OUTCOME MEASURES: Numbers of patients prescribed a new course of antidepressant; numbers discontinuing treatment; the ratio of antidepressant discontinuations to antidepressant inceptions; reasons for discontinuation; proportion of switches to another antidepressant. RESULTS: There were 13,619 inceptions and 3934 discontinuations of selective serotonin reuptake inhibitors and tricyclic antidepressants during the study. The number of newly prescribed courses of antidepressants increased by 116%, mostly due to an increase in prescribing of serotonin reuptake inhibitors. The ratio of total discontinuations to inceptions was significantly lower for serotonin reuptake inhibitors (22%) than for tricyclic antidepressants (33%). Differences persisted when controlled for age and sex of patients and severity of depression. However, there was more switching away from selective serotonin reuptake inhibitors when they failed (72%) than from tricyclic antidepressants (58%). CONCLUSIONS: Selective serotonin reuptake inhibitors are less likely than tricyclic antidepressants to be discontinued. A prospective study is needed in general practice to assess the implications of differences in discontinuation rates and switches on clinical and economic outcomes.     

Antidepressant drugs in the elderly: Are the indications as long term as the treatment?

In a community study of 761 people aged 70 years and over 45 (5·9%) were found to be taking long term tricyclic antidepressants. Forty four were compared with matched controls. There was no evidence that tricyclic antidepressants were being used to compensate for poor physical health or function. Twenty subjects had a clear history of depression; three of these required additional treatment and five might have coped without continued drug treatment. Twelve of the remainder had started treatment with tricyclic antidepressants as hypnotics and 11 as a trial because of suspected depression. They had continued taking the drugs over a long period.Regular review of both the adequacy of and the necessity for continued treatment with tricyclic antidepressants in the elderly is recommended.     

Lay people's attitudes to treatment of depression: results of opinion poll for Defeat Depression Campaign just before its launch.

OBJECTIVE: To investigate the attitudes of the general public towards depression before the Defeat Depression Campaign of the Royal Colleges of Psychiatrists and General Practitioners; these results form the baseline to assess the change in attitudes brought about by the campaign. DESIGN: Group discussions generated data for initial qualitative research. The quantitative survey comprised a doorstep survey of 2003 people in 143 places around the United Kingdom. RESULTS: The lay public in general seemed to be sympathetic to those with depression but reluctant to consult. Most (1704 (85%)) believed counselling to be effective but were against antidepressants. Many subjects (1563 (78%)) regarded antidepressants as addictive. CONCLUSIONS: Although people are sympathetic towards those with depression, they may project their prejudices about depression on to the medical profession. Doctors have an important role in educating the public about depression and the rationale for antidepressant treatment. In particular, patients should know that dependence is not a problem with antidepressants.     

Misunderstandings in prescribing decisions in general practice: qualitative study

ObjectivesTo identify and describe misunderstandings between patients and doctors associated with prescribing decisions in general practice.DesignQualitative study.Setting20 general practices in the West Midlands and south east England.Participants20 general practitioners and 35 consulting patients.Results14 categories of misunderstanding were identified relating to patient information unknown to the doctor, doctor information unknown to the patient, conflicting information, disagreement about attribution of side effects, failure of communication about doctor''s decision, and relationship factors. All the misunderstandings were associated with lack of patients'' participation in the consultation in terms of the voicing of expectations and preferences or the voicing of responses to doctors'' decisions and actions. They were all associated with potential or actual adverse outcomes such as non-adherence to treatment. Many were based on inaccurate guesses and assumptions. In particular doctors seemed unaware of the relevance of patients'' ideas about medicines for successful prescribing.ConclusionsPatients'' participation in the consultation and the adverse consequences of lack of participation are important. The authors are developing an educational intervention that builds on these findings.     

Effects of corticosterone and amyloid-beta on proteins essential for synaptic function: Implications for depression and Alzheimer's disease

The relationship between Alzheimer's disease (AD) and depression has been well established in terms of epidemiological and clinical observations. Depression has been considered to be both a symptom and risk factor of AD. Several genetic and neurobiological mechanisms have been described to underlie these two disorders. Despite the accumulating knowledge on this topic, the precise neuropathological mechanisms remain to be elucidated. In this study, we propose that synaptic degeneration plays an important role in the disease progression of depression and AD. Using primary culture of hippocampal neurons treated with oligomeric Aβ and corticosterone as model agents for AD and depression, respectively, we found significant changes in the pre-synaptic vesicle proteins synaptophysin and synaptotagmin. We further investigated whether the observed protein changes affected synaptic functions. By using FM^®4-64 fluorescent probe, we showed that synaptic functions were compromised in treated neurons. Our findings led us to investigate the involvement of protein degradation mechanisms in mediating the observed synaptic protein abnormalities, namely, the ubiquitin–proteasome system and autophagy. We found up-regulation of ubiquitin-mediated protein degradation, and the preferential signaling for the autophagic–lysosomal degradation pathway. Lastly, we investigated the neuroprotective role of different classes of antidepressants. Our findings demonstrated that the antidepressants Imipramine and Escitalopram were able to rescue the observed synaptic protein damage. In conclusion, our study shows that synaptic degeneration is an important common denominator underlying depression and AD, and alleviation of this pathology by antidepressants may be therapeutically beneficial.     

A geographically-restricted but prevalent Mycobacterium tuberculosis strain identified in the West Midlands Region of the UK between 1995 and 2008

Background

We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.

Methodology/Principal Findings

Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the “Mercian” strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95%CI = 4.56–17.87, p<0.01), Black Caribbean (OR = 5.68, 95%CI = 2.96–10.91, p<0.01) resident in Wolverhampton (OR = 9.29, 95%CI = 5.69–15.19, p<0.01) and negatively associated with age >65 years old (OR = 0.25, 95%CI = 0.09–0.67, p<0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95%CI = 2.00–46.78, p<0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95%CI = 1.45–27.02, p = .01) were observed as social risk factors for infection.

Conclusions/Significance

The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain.     

Prescribing selective serotonin reuptake inhibitors as strategy for prevention of suicide.

OBJECTIVE--To evaluate a policy to reduce the incidence of suicide by means of changing the prescribing of antidepressants from the older tricyclic antidepressants to the routine first line use of selective serotonin reuptake inhibitors or newer tricyclic and related antidepressants. DESIGN--Cost effectiveness analysis with sensitivity analyses using observational data on costs, volume of prescribing, deaths, and toxicity. SETTING--United Kingdom primary care. INTERVENTIONS--Selective serotonin reuptake inhibitors or newer tricyclic and related antidepressants compared with the use of older tricyclics. MAIN OUTCOME MEASURES--Cost per life saved and cost per life year saved. RESULTS--The potential number of lives which may be saved from a switch to the routine first line use of selective serotonin reuptake inhibitors is between 300 and 450 each year. The cost per life year gained ranges from 19,000 pounds to 173,000 pounds, depending on the assumptions used. The cost per life year gained through the use of the newer tricyclic and related antidepressants is considerably lower. CONCLUSIONS--The cost per life year gained through avoiding suicides by the routine first line use of serotonin reuptake inhibitors is likely to be high. The new tricyclics and related drugs are of similar toxicity to the serotonin reuptake inhibitors but are considerably cheaper and so are most cost effective for this purpose. Further research is required on such prescribing. Because of the great uncertainties the shift to considerably more expensive options must be further investigated.     

No magic bullets: a systematic review of 102 trials of interventions to improve professional practice.

OBJECTIVE: To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes. DATA SOURCES: MEDLINE, SCISEARCH, CINAHL and the Research and Development Resource Base in CME were searched for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive. STUDY SELECTION: Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed random or quasi-random allocation methods in their study designs to assign individual subjects or groups. Interventions included such activities as conferences, outreach visits, the use of local opinion leaders, audit and feedback, and reminder systems. DATA EXTRACTION: Details extracted from the studies included the study design; the unit of allocation (e.g., patient, provider, practice, hospital); the characteristics of the targeted health care professionals, educational interventions and patients (when appropriate); and the main outcome measure. DATA SYNTHESIS: The inclusion criteria were met by 102 trials. Areas of behaviour change included general patient management, preventive services, prescribing practices, treatment of specific conditions such as hypertension or diabetes, and diagnostic service or hospital utilization. Dissemination-only strategies, such as conferences or the mailing of unsolicited materials, demonstrated little or no changes in health professional behaviour or health outcome when used alone. More complex interventions, such as the use of outreach visits or local opinion leaders, ranged from ineffective to highly effective but were most often moderately effective (resulting in reductions of 20% to 50% in the incidence of inappropriate performance). CONCLUSION: There are no "magic bullets" for improving the quality of health care, but there are a wide range of interventions available that, if used appropriately, could lead to important improvements in professional practice and patient outcomes.     

Prescribing of psychoactive drugs for chronically ill elderly patients.

The prescribing of psychoactive drugs for 1431 chronically ill elderly patients being assessed for long-term institutional or community care was surveyed. Psychoactive drugs had been prescribed for about one quarter of the patients; benzodiazepines were the most frequently prescribed group. Judging from the extensive prescribing of flurazepam and chloral hydrate, commonly used hypnotics, the main reason psychoactive drugs were prescribed was to provide night-time sedation. Antidepressants and drugs promoted as useful in improving cognitive function were infrequently prescribed. Commendable prescribing practices included the infrequent use of "cerebral vasodilators" and barbiturates. Questionable prescribing practices included the infrequent use of tricyclic antidepressants in severely depressed patients and the use of tranquilizers in patients described by their attending physician as markedly or extremely withdrawn.     

Connecting human–nature relationships to environmental behaviors that minimize the spread of aquatic invasive species

Management of aquatic invasive species (AIS) is widely recognized as a global conservation concern driven by myriad factors, particularly individual behaviors. A burgeoning literature focused on the human dimensions of AIS has begun to provide insight into the complexities of behavior change; however, most studies are bound to specific geographic locales and have prevented resource management agencies from making regionally valid statements about the anthropogenic factors contributing to biological invasions. We examined stakeholders’ awareness and knowledge of AIS transmission in an evaluation of educational outreach campaign logos and illustrated how human–nature relationships were related to behaviors relevant to AIS reduction at two case study sites. Drawing from a thematic analysis of data from semi-structured interviews with organisms-in-trade hobbyists and recreational water users in the state of Illinois, we observed high awareness of environmental impacts and modes of transmission by the two groups. Both awareness advanced through AIS outreach and a diversity of human–nature relationships were helpful for understanding reported environmental behaviors. Specifically, stakeholders’ views of their relationships with nature affected decisions to engage in activities that contributed to social-ecological change. Results also revealed preferences for national rather than state-level outreach campaign logos, which carry implications for designing communication strategies that will minimize the likelihood of biological invasions in freshwater ecosystems.     

A Cluster Randomised Controlled Trial of a Pharmacist-Led Collaborative Intervention to Improve Statin Prescribing and Attainment of Cholesterol Targets in Primary Care

Background

Small trials with short term follow up suggest pharmacists’ interventions targeted at healthcare professionals can improve prescribing. In comparison with clinical guidance, contemporary statin prescribing is sub-optimal and achievement of cholesterol targets falls short of accepted standards, for patients with atherosclerotic vascular disease who are at highest absolute risk and who stand to obtain greatest benefit. We hypothesised that a pharmacist-led complex intervention delivered to doctors and nurses in primary care, would improve statin prescribing and achievement of cholesterol targets for incident and prevalent patients with vascular disease, beyond one year.

Methods

We allocated general practices to a 12-month Statin Outreach Support (SOS) intervention or usual care. SOS was delivered by one of 11 pharmacists who had received additional training. SOS comprised academic detailing and practical support to identify patients with vascular disease who were not prescribed a statin at optimal dose or did not have cholesterol at target, followed by individualised recommendations for changes to management. The primary outcome was the proportion of patients achieving cholesterol targets. Secondary outcomes were: the proportion of patients prescribed simvastatin 40 mg with target cholesterol achieved; cholesterol levels; prescribing of simvastatin 40 mg; prescribing of any statin and the proportion of patients with cholesterol tested. Outcomes were assessed after an average of 1.7 years (range 1.4–2.2 years), and practice level simvastatin 40 mg prescribing was assessed after 10 years.

Findings

We randomised 31 practices (72 General Practitioners (GPs), 40 nurses). Prior to randomisation a subset of eligible patients were identified to characterise practices; 40% had cholesterol levels below the target threshold. Improvements in data collection procedures allowed identification of all eligible patients (n = 7586) at follow up. Patients in practices allocated to SOS were significantly more likely to have cholesterol at target (69.5% vs 63.5%; OR 1.11, CI 1.00–1.23; p = 0.043) as a result of improved simvastatin prescribing. Subgroup analysis showed the primary outcome was achieved by prevalent but not incident patients. Statistically significant improvements occurred in all secondary outcomes for prevalent patients and all but one secondary outcome (the proportion of patients with cholesterol tested) for incident patients. SOS practices prescribed more simvastatin 40 mg than usual care practices, up to 10 years later.

Interpretation

Through a combination of educational and organisational support, a general practice based pharmacist led collaborative intervention can improve statin prescribing and achievement of cholesterol targets in a high-risk primary care based population.

Trial Registration

International Standard Randomised Controlled Trials Register ISRCTN61233866     

Comparison of escitalopram alone and combined with zolpidem in treating major depression and related sleep impairments

Escitalopram has been shown to be effective for treating major depression (MDD); however, research is lacking regarding its effect on treating MDD-related sleep impairments. The purpose of this study was to assess the efficacy of escitalopram monotherapy and investigate changes in insomnia, depressive symptoms, and quality of life (QOL). Participants were 14 patients with MDD who enrolled in a clinical trial at Jikei University Katsushika Medical Center. Escitalopram monotherapy was used, and hypnotics were administered three times per week for individuals suffering from sleep impairments. The following variables were assessed: (1) sleep quality [Pittsburgh sleep quality index (PSQI)], (2) depression [Zung self-rating depression scale (ZSRDS)], and (3) quality of life (QOL) as determined by the Sheehan disability scale (SDISS) and short form (36) health survey (SF-36). These assessments were conducted prior to any treatment (pre-test) and again 8–12 weeks after treatment (post-test). Monotherapy (E = escitalopram alone; n = 6) and combination therapy (E+ = escitalopram + zolpidem; n = 8) groups were compared. All participants completed the full protocol (average 9.4 ± 1.8 weeks). Regardless of treatment group, participants improved on all assessments (including sleep impairment). However, groups did not differ in their level of improvement. A two-factor ANOVA revealed that the E+ group showed particular improvements in QOL. In treating MDD and associated sleep impairments, zolpidem did not confer additional benefits. Thus, clinicians should consider E monotherapy for patients with MDD-related sleep impairments before prescribing combination therapies.

     

Audit of public education campaign to encourage earlier detection of malignant melanoma.

OBJECTIVES--To evaluate a public campaign to encourage earlier referral and treatment of primary cutaneous malignant melanoma and thus reduce mortality related to melanoma. DESIGN--Production and distribution of educational material aimed at adults. Update information sent to general practitioners before campaign. Analysis of data on melanoma before and after campaign in June 1985. SETTING--West of Scotland, population 2.7 million. MAIN OUTCOME MEASURES--Total numbers of referrals per month to melanoma clinic, numbers of melanomas diagnosed, change in distribution of thickness, and mortality before and after introducing the campaign. RESULTS--Referrals to the pigmented lesion clinic increased by 278%, from five a week in June-July 1984 to 19 a week in June-July 1985. Twice as many women as men were referred to the clinic (49% of referrals were of women aged under 65). The numbers of newly diagnosed primary cutaneous melanoma were 63 (12/month) in January-May 1985 and 146 (21/month) in June-December 1985, an increase of 131%. The percentage of tumours detected that were less than 1.5 mm thick rose significantly by 16% (95% confidence interval 11% to 19%), from 38% (328) in 1979-84 to 54% (592) in 1985-9. Mortality began to fall in women from 1988. CONCLUSIONS--The public education campaign succeeded in reducing the absolute number of thick tumours and melanoma related mortality in women.     

Explaining clinical behaviors using multiple theoretical models

Background

High-risk prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents accounts for a significant proportion of hospital admissions due to preventable adverse drug events. The recently completed PINCER trial has demonstrated that a one-off pharmacist-led information technology (IT)-based intervention can significantly reduce high-risk prescribing in primary care, but there is evidence that effects decrease over time and employing additional pharmacists to facilitate change may not be sustainable.

Methods/design

We will conduct a cluster randomised controlled with a stepped wedge design in 40 volunteer general practices in two Scottish health boards. Eligible practices are those that are using the INPS Vision clinical IT system, and have agreed to have relevant medication-related data to be automatically extracted from their electronic medical records. All practices (clusters) that agree to take part will receive the data-driven quality improvement in primary care (DQIP) intervention, but will be randomised to one of 10 start dates. The DQIP intervention has three components: a web-based informatics tool that provides weekly updated feedback of targeted prescribing at practice level, prompts the review of individual patients affected, and summarises each patient's relevant risk factors and prescribing; an outreach visit providing education on targeted prescribing and training in the use of the informatics tool; and a fixed payment of 350 GBP (560 USD; 403 EUR) up front and a small payment of 15 GBP (24 USD; 17 EUR) for each patient reviewed in the 12 months of the intervention. We hypothesise that the DQIP intervention will reduce a composite of nine previously validated measures of high-risk prescribing. Due to the nature of the intervention, it is not possible to blind practices, the core research team, or the data analyst. However, outcome assessment is entirely objective and automated. There will additionally be a process and economic evaluation alongside the main trial.

Discussion

The DQIP intervention is an example of a potentially sustainable safety improvement intervention that builds on the existing National Health Service IT-infrastructure to facilitate systematic management of high-risk prescribing by existing practice staff. Although the focus in this trial is on Non-steroidal anti-inflammatory drugs and antiplatelets, we anticipate that the tested intervention would be generalisable to other types of prescribing if shown to be effective.

Trial registration

ClinicalTrials.gov, dossier number: NCT01425502