Opportunity cost of antidepressant prescribing in England: analysis of routine data.
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Antidepressive Agents↗
Biomedical subjects
David Gunnell
Publications and source records attributed to David Gunnell.
Missing deaths from pesticide self-poisoning at the IFCS Forum IV.
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Health Policy↗
Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review.
OBJECTIVE: To investigate whether selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of suicide related outcomes in adults. DESIGN: Meta-analysis of randomised controlled trials of SSRIs compared with placebo in adults submitted by pharmaceutical companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA). PARTICIPANTS: Over 40,000 individuals participating in 477 randomised controlled trials. MAIN OUTCOME MEASURES: Suicide, non-fatal self harm, and suicidal thoughts. RESULTS: An estimated 16 suicides, 172 episodes of non-fatal self harm, and 177 episodes of suicidal thoughts were reported. We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded (odds ratio 0.85, 95% credible interval 0.20 to 3.40). We found weak evidence of an increased risk of self harm (1.57, 0.99 to 2.55). Risk estimates for suicidal thoughts were compatible with a modest protective or adverse effect (0.77, 0.37 to 1.55). The relative frequency of reported self harm and suicidal thoughts in the trials compared with suicide indicates non-fatal end points were under-recorded. CONCLUSION: Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, but larger trials with longer follow up are required to assess the balance of risks and benefits fully. Any such risks should be balanced against the effectiveness of SSRIs in treating depression. When prescribing SSRIs, clinicians should warn patients of the possible risk of suicidal behaviour and monitor patients closely in the early stages of treatment.
Adult↗
Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study.
OBJECTIVE: To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants. DESIGN: Nested case-control study. SETTING: Primary care in the United Kingdom. PARTICIPANTS: 146,095 individuals with a first prescription of an antidepressant for depression. MAIN OUTCOME MEASURES: Suicide and non-fatal self harm. RESULTS: 1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs. CONCLUSION: We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.
Adolescent↗
The epidemiology and prevention of suicide by hanging: a systematic review.
BACKGROUND: Hanging is one of the most commonly used methods for suicide worldwide. In England and a number of other countries, its incidence has increased over the last 30 years. This review summarizes the published literature on suicide by hanging. The focus is on its epidemiology in England and on identifying potential means of prevention. METHODS: We searched Medline (1966-2003), Embase (1980-2003), CINAHL (1982-2003) and PsycINFO (1967-2003). As considerable research on suicides occurring in prisons and psychiatric hospitals in England and Wales has been carried out by the National Confidential Inquiry into Suicide and Homicide (Manchester) and the Prison Service's Safer Custody Group, we obtained additional information from these sources. RESULTS: Only a small proportion (around 10%) of hanging suicides occur in the controlled environments of hospitals, prisons, and police custody; the remainder occur in the community. The most commonly used ligatures (rope, belts, flex) and ligature points (beams, banisters, hooks, door knobs, and trees) are widely available; thus prevention strategies focused around restriction of access to means of hanging are of limited value. Around 50% of hanging suicides are not fully suspended--ligature points below head level are commonly used. Case fatality following attempted suicide by hanging is around 70%; the majority (80-90%) of those who reach hospital alive survive. CONCLUSION: Strategies to reduce suicide by hanging should focus on the prevention of suicide in controlled environments, the emergency management of 'near-hanging' and on the primary prevention of suicide in general. More research is required to better understand the recent rise in popularity of this method.
Adolescent↗
Breastfeeding in infancy and blood pressure in later life: systematic review and meta-analysis.
The influence of breastfeeding on blood pressure in later life is uncertain. The authors conducted a systematic review of published studies from which estimates of a mean difference (standard error) in blood pressure between breastfed and bottle-fed subjects could be derived. They searched MEDLINE and Excerpta Medica (EMBASE) bibliographic databases, which was supplemented by manual searches of reference lists. Fifteen studies (17 observations) including 17,503 subjects were summarized. Systolic blood pressure was lower in breastfed compared with bottle-fed infants (pooled difference: -1.4 mmHg, 95% confidence interval (CI): -2.2, -0.6), but evidence of heterogeneity between study estimates was evident (chi(2)(16) = 42.0, p < 0.001). A lesser effect of breastfeeding on systolic blood pressure was observed in larger (n > or = 1,000) studies (-0.6 mmHg, 95% CI: -1.2, 0.02) compared with smaller (n < 1,000) studies (-2.3 mmHg, 95% CI: -3.7, -0.9) (p for difference in pooled estimates = 0.02). A small reduction in diastolic blood pressure was associated with breastfeeding (pooled difference: -0.5 mmHg, 95% CI: -0.9, -0.04), which was independent of study size. If causal, the small reduction in blood pressure associated with breastfeeding could confer important benefits on cardiovascular health at a population level. Understanding the mechanism underlying this association may provide insights into pathways linking early life exposures with health in adulthood.
Adolescent↗
Gunshot suicides in England--a multicentre study based on coroners' records.
BACKGROUND: Gunshot suicides account for 2.5% of suicides in England and Wales. This amounts to more than 100 deaths per year. Information about such deaths may assist in the development of suicide prevention strategies. METHOD: We have examined coroners' inquest records for all gunshot suicides between 1st January 2000 and 31st December 2001 in 24 coroners' jurisdictions in England. RESULTS: Fifty-eight gunshot suicides were identified, including one homicide-suicide. Ninety-three per cent of cases were male. Sport or occupational usage was the main reason for owning the gun. Ten per cent were farmers or farm-workers. In 20% of cases the gun did not belong to the individual who used it for suicide. This was more likely in younger suicides. Seven (12.1%) individuals used illegally owned handguns. Large amounts of alcohol had been consumed before the act in nine cases. Nearly three-quarters (72.9%) of individuals with diagnostic information had a probable diagnosis of depression. However, only 22.4% had ever had contact with psychiatric services. Two shotgun certificate holders were under the care of psychiatric services at the time of their death and two others had a history of previous self-harm. CONCLUSIONS: Strategies to reduce the number of gunshot suicides need to focus on limiting access to guns. These include restricting access to guns by non-certificate holders and those who may be at increased risk of suicide, and holding regular gun amnesties.
Adolescent↗
Could associations between breastfeeding and insulin-like growth factors underlie associations of breastfeeding with adult chronic disease? The Avon Longitudinal Study of Parents and Children.
OBJECTIVE: The influence of infant feeding method (breast/formula) on growth factor levels could underlie associations of breastfeeding with childhood growth and risk factors for cardiovascular disease. We investigated associations of having been breastfed with serum IGF-I and IGFBP-3 in childhood. METHODS: Prospective birth cohort study (subsample of the Avon Longitudinal Study of Parents and Children, UK) based on 871 children born in 1991/1992 who underwent clinical follow-up and blood tests at age 7-8 years. A total of 488 (56%) children had complete data. RESULTS: In children with complete data, the age- and sex-standardized IGF-I levels of those who were partially or exclusively breastfed were 6.1 and 13.8 ng/ml higher, respectively, than those who were never breastfed (increase in IGF-I levels per category of breastfeeding exclusivity: 7.1 ng/ml; 95% CI: 0.3-13.9; P = 0.04). In models also controlling for birthweight, gestational age, mother's age, and socioeconomic and dietary factors, the breastfeeding-IGF-I association was attenuated (regression coefficient: 3.3 ng/ml; -4.2-10.7; P = 0.4); further adjustment for IGFBP-3 made little difference (regression coefficient: 4.1 ng/ml; -2.8-10.9; P = 0.2). There was little evidence for an association between breastfeeding and IGFBP-3 or the molar ratio IGF-I/IGFBP-3. CONCLUSIONS: The positive association between breastfeeding and IGF-I could be due to residual confounding or to chance. Nevertheless, the magnitude of the fully adjusted effect estimate and the novelty of the association suggest that larger studies should now be conducted to confirm or refute the hypothesis that variations in IGF-I by infant feeding mode explain associations of breastfeeding with health in later life.
Breast Feeding↗
Breast feeding and cardiovascular disease risk factors, incidence, and mortality: the Caerphilly study.
STUDY OBJECTIVE: To investigate the association of having been breast fed with cardiovascular disease risk factors, incidence, and mortality. DESIGN: Prospective cohort study. SETTING: Caerphilly, South Wales. PARTICIPANTS: All men aged 45-59 years living in and around the study area. Of 2818 eligible men, 2512 (89%) were seen. Altogether 1580 men (63%) obtained details of how they had been fed in infancy (ever breast fed or only bottle fed) from their mother or a close female relative. A subset of 1062 subjects reported on whether bottle fed or the duration of breast feeding if breast fed. MAIN RESULTS: Breast feeding was not associated with stature, blood pressure, insulin resistance, total cholesterol, or fibrinogen. In fully adjusted models (controlling for age, birth order, and social position in childhood and adulthood), breast feeding was associated with greater body mass index than bottle feeding (difference: 0.41 kg/m(2) (95% CI: 0.01 to 0.81). There was a positive association between breast feeding and coronary heart disease mortality (hazard ratio: 1.73; 1.17 to 2.55) and incidence (1.54; 1.17 to 2.04) (fully adjusted models). There was no evidence of a duration-response effect, which might be expected if an adverse effect of breast feeding was causal. CONCLUSION: These data provide little evidence of a protective influence of breast feeding on cardiovascular disease risk factors, incidence, or mortality. A possible adverse effect of breast feeding on coronary heart disease incidence was observed but may have a number of explanations, including selection and information bias. In view of these limitations, further long term studies with improved measures of infant feeding are required to confirm or refute these findings.
Body Height↗
Strong inverse association between height and suicide in a large cohort of Swedish men: evidence of early life origins of suicidal behavior?
OBJECTIVE: Previous studies have found associations between poor fetal and infant growth and the risk of suicide. The authors' goal was to investigate the association between height--a measure of childhood growth--and suicide risk. METHOD: The authors conducted a record linkage study of the birth, conscription, mortality, family, and census register data of 1,299,177 Swedish men followed from age 18 to a maximum of age 49. RESULTS: There were 3,075 suicides over an average follow-up period of 15 years. There was a strong inverse association between height and suicide risk. In fully adjusted models, a 5-cm increase in height was associated with a 9% decrease in suicide risk. CONCLUSIONS: The strong inverse association between height and suicide may signify the importance of childhood exposure in the etiology of adult mental disorder or reflect stigmatization or discrimination encountered by short men in their adult lives.
Adolescent↗
Social adversity in childhood and the risk of developing psychosis: a national cohort study.
OBJECTIVE: There is conflicting evidence concerning the association of social childhood factors and subsequent psychosis. Previous studies have had inadequate designs. The aim of the present study was to describe a broad range of social factors during childhood and the risk of developing psychosis later in life in a national cohort. METHOD: The study population consisted of all children born in Sweden in 1963-1983-2.1 million persons-in family households participating in the national census of 1970, 1980, 1985, or 1990. Hazard ratios were estimated for five different indicators of socioeconomic position (living in rented apartments, low socioeconomic status, single-parent households, unemployment, and households receiving social welfare benefits) from hospital admissions for schizophrenia and other psychoses during 1987-2002. RESULTS: Increased age- and sex-adjusted hazard ratios for schizophrenia and other psychoses were found for all childhood socioeconomic indicators, ranking from lowest to highest hazard ratio: rented apartments, low socioeconomic status, single-parent households, unemployment, and households receiving social welfare benefits. Hazard ratios increased with an increasing number of adverse social factors present. Those with four measures of adversity had a 2.7-fold higher risk of schizophrenia than those with none. CONCLUSIONS: The results indicate that social adversity in childhood and fetal life is independently associated with the risk of developing schizophrenia and other psychoses later in life. The risks increased with an increasing number of exposures, suggesting a dose-response relationship.
Adult↗
Suicide by hanging: multicentre study based on coroners' records in England.
We studied 162 cases of hanging by suicide occurring in 24 coroners' jurisdictions in England within a 6-month period in 2001. Prison and psychiatric ward suicides accounted for only 6% of these. The most frequently used ligatures (ropes, belts and cable) and ligature points (beams, girders, lofts and trees) are commonly available in community settings, limiting opportunities for prevention. In only half the cases (52%) were victims fully suspended with both feet off the ground. Four per cent had also taken an overdose.
Adult↗
Help-seeking behaviour in men and women with common mental health problems: cross-sectional study.
BACKGROUND: Many people with mental health problems do not seek professional help but their use of other sources of help is unclear. AIMS: To investigate patterns of lay and professional help-seeking in men and women aged 16-64 years in relation to severity of symptoms and socio-demographic variables. METHOD: Postal questionnaire survey, including the 12-item General Health Questionnaire (GHQ-12), sent to a stratified random sample (n=15,222) of the population of Somerset. RESULTS: The response rate was 76%. Only 28% of people with extremely high GHQ-12 scores (> or = 8) had sought help from their general practitioner but most (78%) had sought some form of help. Males, young people and people living in affluent areas were the least likely to seek help. CONCLUSIONS: Health promotion interventions to encourage appropriate help-seeking behaviour in young people, particularly in men, may lead to improvements in the mental health of this group of the population.
Adolescent↗
Crisis card following self-harm: 12-month follow-up of a randomised controlled trial.
No intervention has been shown to be effective in preventing repetition of self-harm. In the 6-month follow-up of a large randomised controlled trial, we previously reported no effectiveness of the provision of a card offering 24-h crisis telephone consultation on repetition of self-harm. However, there was a possible benefit among those presenting following a first episode (OR=0.64, 95% CI 0.34-1.22). Here we report the 12-month follow-up of the trial. The results confirm no overall benefit of the intervention (OR=1.19, 95% CI 0.85-1.67). Among those with a first episode of self-harm, the possible benefit of the intervention had diminished (OR=0.89, 95% CI 0.52-1.52), although a modest effect cannot be excluded.
Crisis Intervention↗
Epidemiology of intentional self-poisoning in rural Sri Lanka.
We investigated the epidemiology of intentional self-poisoning in rural Sri Lanka by prospectively recording 2189 admissions to two secondary hospitals. Many patients were young (median age 25 years), male (57%) and used pesticides (49%). Of the 198 who died,156 were men (case fatality 12.4%) and 42 were women (4.5%). Over half of female deaths were in those under 25 years old; male deaths were spread more evenly across age groups. Oleander and paraquat caused 74% of deaths in people under 25 years old; thereafter organophosphorous pesticides caused many deaths. Although the age pattern of self-poisoning was similar to that of industrialised countries, case fatality was more than 15 times higher and the pattern of fatal self-poisoning different.
Adolescent↗
The usefulness of coroners' data on suicides for providing information relevant to prevention.
Coroners' records are an accessible source of information on suicides. To assess their usefulness in relation to the investigation of specific methods of suicide, we examined coroners' records for 492 suicides across 24 jurisdictions in England. Generally data on demographic variables were well recorded. Information on contact with general practitioner and psychiatric services was less commonly available. Where those who had self-poisoned died in hospital, information on treatment and blood levels of drugs taken were not routinely available. For suicides by hanging, information on the source of ligature was frequently missing. Where firearms were used, information about licensing and storage were not routinely recorded. Generally there was wide variation across coroners in information relevant to specific methods. The use of standardized forms by coroners would assist studies of factors associated with suicide and potentially provide a representative source of information relevant to suicide prevention.
Coroners and Medical Examiners↗
Association of insulin-like growth factor I and insulin-like growth factor-binding protein-3 with intelligence quotient among 8- to 9-year-old children in the Avon Longitudinal Study of Parents and Children.
BACKGROUND: Insulin-like growth factor I (IGF-I) is a hormone that mediates the effects of growth hormone and plays a critical role in somatic growth regulation and organ development. It is hypothesized that it also plays a key role in human brain development. Previous studies have investigated the association of low IGF-I levels attributable to growth hormone receptor deficiency with intelligence but produced mixed results. We are aware of no studies that investigated the association of IGF-I levels with IQ in population samples of normal children. OBJECTIVES: To investigate the association of circulating levels of IGF-I and its principle binding protein, IGF-binding protein-3 (IGFBP-3), in childhood with subsequent measures of IQ. METHODS: The cohort study was based on data for 547 white singleton boys and girls, members of the Avon Longitudinal Study of Parents and Children, with IGF-I and IGFBP-3 measurements (obtained at a mean age of 8.0 years) and IQ measured with the Wechsler Intelligence Scale for Children (at a mean age of 8.7 years). We also investigated associations with measures of speech and language based on the Wechsler Objective Reading Dimensions test (measured at an age of 7.5 years) and the Wechsler Objective Language Dimensions test (listening comprehension subtest only, measured at an age of 8.7 years). For some children (n = 407), IGF-I (but not IGFBP-3) levels had been measured at approximately 5 years of age in a previous study. Linear regression models were used to investigate associations of the IGF-I system with the measures of cognitive function. RESULTS: Three hundred one boys and 246 girls were included in the sample. IGF-I levels (mean +/- SD) were 142.6 +/- 53.9 ng/mL for boys and 154.4 +/- 51.6 ng/mL for girls. IQ scores (mean +/- SD) were 106.05 +/- 16.6 and 105.27 +/- 15.6 for boys and girls, respectively. IGF-I levels were associated positively with intelligence. For every 100 ng/mL increase in IGF-I, IQ increased by 3.18 points (95% confidence interval [CI]: 0.52 to 5.84 points). These positive associations were seen in relation to the verbal component (coefficient: 4.27; 95% CI: 1.62 to 6.92), rather than the performance component (coefficient: 1.06; 95% CI: -1.67 to 3.78), of IQ. There was no evidence that associations with overall IQ differed between boys and girls. In a data set with complete information on confounders (n = 484), controlling for birth weight (adjusted for gestation), breastfeeding, and BMI slightly strengthened the associations of IGF-I levels with IQ. Additionally controlling for maternal education and IGFBP-3 levels attenuated the associations (change in IQ for every 100 ng/mL increase in IGF-I levels: 2.51 points; 95% CI: -0.42 to 5.44 points). The weakening of associations in models controlling for markers of parental socioeconomic position and education could reflect shared influences of parental IGF levels on parents' own educational attainment and their offspring's IGF-I levels. In unadjusted models examining associations of Wechsler Objective Reading Dimensions and Wechsler Objective Language Dimensions test scores with IGF-I levels, there was no strong evidence that performance on either of these tests was associated with circulating IGF-I levels, although positive associations were seen with both measures. Associations between IGF-I levels measured at age 5 and Wechsler Intelligence Scale for Children scores (n = 407) were similar to those for IGF-I levels measured at age 7 to 8. For every 100 ng/mL increase in IGF-I levels at 5 years of age, IQ increased by 2.3 points (95% CI: -0.21 to 4.89 points). CONCLUSIONS: This study provides some preliminary evidence that IGF-I is associated with brain development in childhood. Additional longitudinal research is required to clarify the role of IGF-I in neurodevelopment. Because IGF-I levels are modifiable through diet and other environmental exposures, this may be one pathway through which the childhood environment may influence neurodevelopment.
Birth Weight↗
Cross-sectional associations of diet and insulin-like growth factor levels in 7- to 8-year-old children.
BACKGROUND: The insulin-like growth factors (IGF) are polypeptide hormones which are associated with several adult diseases including cancer and coronary heart disease. The dietary determinants of circulating levels of components of the IGF system are of interest, as these may mediate some of the effects of diet on later health. However, few studies have examined the relationship between diet and IGF levels in children. OBJECTIVE: To investigate associations between diet and IGF-I and IGFBP-3 levels in 7- to 8-year-old children. METHODS: This study used subjects participating in the Avon Longitudinal Study of Parents and Children. Diet was assessed using a 3-day unweighed food diary. Confounding variables considered were maternal education, housing tenure, birthweight, and body mass index. RESULTS: Complete information on dietary intakes, IGF levels, and all confounding variables were available for 521 children (287 boys). IGF-I was positively associated with intakes of protein, magnesium, zinc, calcium, potassium, and phosphorus, and IGFBP-3 was positively associated with energy. The IGF-I/IGFBP-3 ratio was positively associated with intakes of protein, zinc, and phosphorus. There was some evidence that the dietary determinants of the IGF system differed between the sexes. None of the foods examined were strongly associated with IGF levels, in particular, there was no association with red meat or vegetable intake. CONCLUSION: These data suggest that the IGF axis in children is affected by diet. This may provide a mechanism whereby childhood diet could have a long-term effect on risk of chronic disease.
Child↗