Association between antidepressant prescribing and suicide rates in OECD countries: an ecological study.

INTRODUCTION: We have conducted an ecological study to assess the association between antidepressant prescribing and suicide rates using the Organisation for Economic Co-operation and Development (OECD) health data, making this the largest ecological study in recent times. METHOD: Data were derived for the years 1995-2008 from the OECD health data set. The residuals for all variables were adjusted for country and year within each country. These were then analysed to identify predictors of suicide rate. Pearson's rank correlation coefficient and linear regression model were employed to assess associations and identify significant predictors of suicide rate. RESULTS: Suicide rate has significant positive correlations with antidepressant rates (p=0.031) and unemployment (p=0.028). It also has a significant negative correlation with inpatient psychiatric beds (p=0.039). The actual coefficients are less than ±0.16, indicating weak relationships. After adjusting for other variables, the only variable that is a statistically significant predictor of suicide rate is antidepressant prescribing (p=0.005, r²=0.09). DISCUSSION: Our analysis using this large data set suggests a statistically significant, albeit weak positive, association between antidepressant prescribing and suicide rates.

Advancements in Surfactant Carriers for Enhanced Oil Recovery: Mechanisms, Challenges, and Opportunities.

Enhanced oil recovery (EOR) techniques are crucial for maximizing the extraction of residual oil from mature reservoirs. This review explores the latest advancements in surfactant carriers for EOR, focusing on their mechanisms, challenges, and opportunities. We delve into the role of inorganic nanoparticles, carbon materials, polymers and polymeric surfactants, and supramolecular systems, highlighting their interactions with reservoir rocks and their potential to improve oil recovery rates. The discussion includes the formulation and behavior of nanofluids, the impact of surfactant adsorption on different rock types, and innovative approaches using environmentally friendly materials. Notably, the use of metal oxide nanoparticles, carbon nanotubes, graphene derivatives, and polymeric surfacants and the development of supramolecular complexes for managing surfacant delivery are examined. We address the need for further research to optimize these technologies and overcome current limitations, emphasizing the importance of sustainable and economically viable EOR methods. This review aims to provide a comprehensive understanding of the emerging trends and future directions in surfactant carriers for EOR.

In autoimmune diabetes the transition from benign to pernicious insulitis requires an islet cell response to tumor necrosis factor alpha.

The islet-infiltrating and disease-causing leukocytes that are a hallmark of insulin-dependent diabetes mellitus produce and respond to a set of cytokine molecules. Of these, interleukin 1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma are perhaps the most important. However, as pleiotropic molecules, they can impact the path leading to beta cell apoptosis and diabetes at multiple points. To understand how these cytokines influence both the formative and effector phases of insulitis, it is critical to determine their effects on the assorted cell types comprising the lesion: the effector T cells, antigen-presenting cells, vascular endothelium, and target islet tissue. Here, we report using nonobese diabetic chimeric mice harboring islets deficient in specific cytokine receptors or cytokine-induced effector molecules to assess how these compartmentalized loss-of-function mutations alter the events leading to diabetes. We found that islets deficient in Fas, IFN-gamma receptor, or inducible nitric oxide synthase had normal diabetes development; however, the specific lack of TNF- alpha receptor 1 (p55) afforded islets a profound protection from disease by altering the ability of islet-reactive, CD4(+) T cells to establish insulitis and subsequently destroy islet beta cells. These results argue that islet cells play a TNF-alpha-dependent role in their own demise.

Plasma norepinephrine and prediction of outcome in major depressive disorder.

BACKGROUND: Several epidemiologic and clinical factors have been shown to predict long term outcome in major depressive disorder (MDD). The value of biological predictors has not been extensively studied. This study examined whether plasma norepinephrine may be useful in predicting outcome in MDD. METHODS: Forty patients were followed up 8 years after an index major depressive episode. Three outcome variables were assessed: time to first recurrence (the primary outcome measure), the Lee and Murray criteria and the Depression Outcome Scale (DOS). The results were examined against plasma norepinephrine value, at the index episode, using survival analysis and linear regression. RESULTS: High plasma norepinephrine at the index episode was positively and significantly associated with time to first recurrence for patients with nonpsychotic MDD (n = 31, chi 2 = 8.38, on 1 df, p < .01). Similarly, plasma norepinephrine was significantly associated with good global outcome, both using Lee and Murray criteria (n = 34, adjusted R2 = .24, p < .01) and DOS criteria (n = 31, adjusted R2 = .17, p < .01) for this group of patients. In contrast, plasma norepinephrine was not significantly related to outcome for MDD with psychotic features. CONCLUSIONS: Plasma norepinephrine at index episode seems to be a predictor of outcome in MDD.

Beta 2-adrenoceptor antagonism in anxiety.

The relative role of beta 1- and beta 2-adrenoceptor antagonism in the management of anxiety symptoms is not clear. We studied the effect of ICI 118,551, a selective beta 2-antagonist, in 51 patients presenting with acute anxiety symptoms and fulfilling DSM-III criteria for anxiety disorder. All patients received placebo during the first week of treatment followed by thrice daily diazepam (2 mg) or ICI 118,551 (50 mg) or placebo for 4 weeks with double-blind, random allocation. Hamilton anxiety scale scores improved on all treatments but there was no significant difference between treatments. Beta 2-adrenoceptor antagonism does not appear to be effective in acute anxiety neurosis. Some earlier literature suggests that beta 1-antagonism may be more important.

Differences and variability in plasma noradrenaline between depressive and anxiety disorders.

Plasma noradrenaline (NA) levels were compared between two groups of patients with major depressive disorder (melancholic/psychotic and non-melancholic), patients with general anxiety disorders and healthy controls. The melancholic/psychotic depressed group had the highest plasma NA levels. This only reached statistical significance with respect to the control group. Within the depressed group, there was no association between plasma NA levels and age, weight loss, ratings of depression, anxiety or plasma cortisol levels. Variance of plasma NA was greatest in the melancholic/psychotic depressed group. A review of previous studies shows an association between raised plasma NA, depressive illness and alterations in NA variance. This association may be limited to melancholic/psychotic depressed patients. The above findings support a dysregulated noradrenergic system in depressive illness.

The effects of reboxetine, a noradrenaline reuptake inhibitor, on the plasma noradrenaline response to a cold pressor test in healthy volunteers.

Previous studies have shown peripheral abnormalities in noradrenergic activity in depressed melancholic patients. These abnormalities have a relationship with short-term and long-term outcome. Little is known about the effects of antidepressant treatment on these peripheral measures such as plasma noradrenaline (NA) and the plasma NA response to a laboratory stressor, the cold pressor test (CPT). The present study examines the effects of the antidepressant reboxetine, a noradrenaline reuptake inhibitor, on baseline plasma NA and the plasma NA response to a CPT, in nine healthy volunteers compared to placebo. A double-blind crossover design was used, with each agent given for 4 weeks with a 4-week washout period. There was no effect of reboxetine on baseline plasma NA. The plasma NA response to reboxetine, with a CPT, was blunted 3 days after commencing treatment. Reboxetine alters the plasma NA response to a CPT independent of baseline plasma NA.

Plasma norepinephrine response to a cold pressor test in subtypes of depressive illness.

Noradrenergic systems have been shown to be disordered in depressive illness. The plasma norepinephrine response to a cold pressor test was used to investigate norepinephrine activity in subtypes of depressive illness. Patients with melancholic or psychotic depression, non-melancholic depression, general anxiety disorder and normal control subjects had a cold pressor test carried out under standard conditions. Blood samples were taken to measure plasma norepinephrine during the test. The plasma norepinephrine response to a cold pressor test was reduced in the melancholic/psychotic depressed patients compared to control subjects. No other intergroup comparisons were statistically significant. These results suggest noradrenergic systems are disturbed and subresponsive to stress in melancholic/psychotic depressed patients. This does not appear related to other clinical or biochemical factors.

Deliberate self-poisoning presenting at a rural hospital in Northern Ireland 1976-1996: relationship to prescribing.

PURPOSE: This study reports on a project to monitor deliberate self-poisoning in a rural area of Northern Ireland over a 20-year period. Comparison is made with reports from large urban centres. In addition, a local prescribing database allows assessment of any association between psychotropic drug prescription and use for deliberate self-poisoning. MATERIALS AND METHODS: Frequency of self-poisoning, demographic details and drugs used were recorded for all episodes of deliberate self-poisoning occurring at Craigavon Area Hospital for the years 1976, 1986, 1991 and 1996. It was possible to compare prescriptions of psychotropic drugs with their use for deliberate self-poisoning between the years 1991 and 1996 in the region served by the hospital, using the Defined Daily Dose (DDD) system. RESULTS: In this rural area the pattern of deliberate self-poisoning has changed, as in urban centres, with a rise in frequency and the male/female ratio approaching unity. The pattern of drug use has altered, with paracetamol overtaking benzodiazepines as the most commonly used agent. More recently, antidepressants have become the second most frequently used drug class for this purpose. Psychotropic medications used for self-poisoning altered in proportion to their prescription between the years 1991 and 1996. CONCLUSIONS: In the face of a continuing rise in deliberate self-poisoning, which is effecting both urban and rural areas, care should be taken to prescribe the least toxic agent available as this is associated with likely frequency of self-poisoning for most classes of psychotropic drug.

Accuracy of weightbearing at three target levels during bilateral upright stance in patients with neuropathic feet and control subjects.

The purposes of this study were to (1) describe errors in weightbearing at three target levels for patients with neuropathic feet and control subjects, (2) compare the absolute errors at the three target levels between groups, and (3) identify predictor variables of errors in weightbearing by the neuropathic group. The groups of 26 subjects were matched for age and height. Weightbearing was measured with digital scales while subjects attempted to adjust their weight through a designated lower extremity to each target level (25, 50, and 75% of body weight). Analysis of variance indicated no significant difference in the percentage weightbearing between groups at the three target levels. There was a significant difference in errors made in weightbearing by the groups at the three target levels. Mean errors ranged from 8.5 to 9.7% for the neuropathic group and from 2.4 to 6.6% for the control group. The findings cast doubt on the utility (in the absence of feedback) of requesting individuals, particularly those with neuropathic feet, to weightbear at specific target levels.

An audit of acute psychiatric admission bed occupancy in Northern Ireland.

The Northern Ireland Section (Irish Division) of the Royal College of Psychiatrists were requested to investigate apparent increasing pressures on acute psychiatric beds. Information on bed occupancy and associated service activity was collected by clinicians on site in every psychiatric unit in Northern Ireland over the past eight years. Three separate years (1987, 1991 and 1995) were studied. Bed occupancy rose across these three years. There was an associated reduction in the number of acute psychiatric beds, reduction in adult continuing care beds, increased recorded referrals to psychiatric units and evidence of considerable numbers of new long-stay patients and difficulties with community placements. Acute bed occupancy in Northern Ireland is high, frequently over 100% and rising. Occupancy rose between each of the years studied. The problem is not confined to urban areas and several associated service factors may be contributing. Without change, acute bed provision will inevitably fail to match mental health needs.

Plasma noradrenaline response to electroconvulsive therapy in depressive illness.

BACKGROUND: Abnormalities of catecholaminergic function have been hypothesised to cause depressive illness. Plasma noradrenaline can be used as a marker of central noradrenergic activity. It is of interest to examine the change in resting plasma noradrenaline in patients with depressive illness over a course of electroconvulsive therapy (ECT) and relate this to their clinical state. METHOD: Patients referred for ECT who suffered from DSM-III-R major depressive disorder or dysthymia were recruited. Blood samples were taken before and after each treatment, during a course of ECT, to measure plasma noradrenaline and cortisol. Clinical ratings were carried out weekly during the course of ECT. RESULTS: Plasma noradrenaline fell significantly in those patients with melancholic/psychotic depressions but increased in those with non-melancholic depressive illness. There was a strong trend indicating that a fall in plasma noradrenaline was associated with improvement in depression ratings in the melancholic/psychotic patients only. CONCLUSIONS: Electroconvlusive therapy decreases plasma noradrenaline in melancholic/psychotic depressive illness and this shows a trend associated with clinical improvement.

5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia.

Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) are associated with suicidal behaviour in patients with depressive illness, but studies of the relation between CSF 5-HIAA and suicide in schizophrenia have been inconclusive and have not included long-term follow-up. In a prospective study, we measured 5-HIAA in CSF taken from 30 schizophrenic patients in a drug-free state, and followed these patients for 11 years. 10 patients made suicide attempts during follow-up. Suicide attempters had significantly lower concentrations of CSF 5-HIAA at initial evaluation than non-attempters (mean [SE] 6.7 [2.2] vs 23.6 [5.6] ng/ml, p < 0.05). Our findings provide further evidence of the relation between serotoninergic dysfunction and suicide, and suggest a role for drugs with serotoninergic effects in schizophrenia.

Potential role of resident islet macrophage activation in the initiation of autoimmune diabetes.

The purpose of this study was to evaluate the effects of resident islet macrophage activation on beta cell function. Treatment of freshly isolated rat islets with TNF-alpha and LPS results in a potent inhibition of glucose-stimulated insulin secretion. The inhibitory actions of TNF + LPS are mediated by the intraislet production and release of IL-1 followed by IL-1-induced inducible nitric oxide synthase (iNOS) expression by beta cells. The IL-1R antagonist protein completely prevents TNF + LPS-induced nitrite production, iNOS expression and the inhibitory effects on glucose-stimulated insulin secretion by rat islets. Resident macrophages appear to be the source of IL-1, as a 7-day culture of rat islets at 24 degrees C (conditions known to deplete islets of lymphoid cells) prevents TNF + LPS-induced iNOS expression, nitrite production, and the inhibitory effects on insulin secretion. In addition, macrophage depletion also inhibits TNF + LPS-induced IL-1alpha and IL-1beta mRNA expression in rat islets. Immunocytochemical colocalization of IL-1beta with the macrophage-specific marker ED1 was used to provide direct support for resident macrophages as the islet cellular source of IL-1. IL-1beta appears to mediate the inhibitory actions of TNF + LPS on beta cell function as TNF + LPS-induced expression of IL-1beta is fourfold higher than IL-1alpha, and Ab neutralization of IL-1beta prevents TNF + LPS-induced nitrite production by rat islets. These findings support a mechanism by which the activation of resident islet macrophages and the intraislet release of IL-1 may mediate the initial dysfunction and destruction of beta cells during the development of autoimmune diabetes.