Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.

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Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

Suicidal behavior is a leading cause of injury and death worldwide. Information about the epidemiology of such behavior is important for policy-making and prevention. The authors reviewed government data on suicide and suicidal behavior and conducted a systematic review of studies on the epidemiology of suicide published from 1997 to 2007. The authors' aims were to examine the prevalence of, trends in, and risk and protective factors for suicidal behavior in the United States and cross-nationally. The data revealed significant cross-national variability in the prevalence of suicidal behavior but consistency in age of onset, transition probabilities, and key risk factors. Suicide is more prevalent among men, whereas nonfatal suicidal behaviors are more prevalent among women and persons who are young, are unmarried, or have a psychiatric disorder. Despite an increase in the treatment of suicidal persons over the past decade, incidence rates of suicidal behavior have remained largely unchanged. Most epidemiologic research on suicidal behavior has focused on patterns and correlates of prevalence. The next generation of studies must examine synergistic effects among modifiable risk and protective factors. New studies must incorporate recent advances in survey methods and clinical assessment. Results should be used in ongoing efforts to decrease the significant loss of life caused by suicidal behavior.

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Suicide and Suicidal Behavior

Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multifactorial and its heritability is estimated to be approximately 35%. In addition, environmental factors, such as sexual, physical or emotional abuse during childhood, are strongly associated with the risk of developing MDD. No established mechanism can explain all aspects of the disease. However, MDD is associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. In this Primer, we provide an overview of the current evidence of MDD, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment.

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Major depressive disorder

Most patients with neuropathic pain symptoms present and are managed in primary care, with only a minority being referred for specialist clinical assessment and diagnoses. Previous reviews have focused mainly on specific neuropathic pain conditions based in specialist settings. This is the first systematic review of epidemiological studies of neuropathic pain in the general population. Electronic databases were searched from January 1966 to December 2012, and studies were included where the main focus was on neuropathic pain prevalence and/or incidence, either as part of a specific neuropathic pain-related condition or as a global entity in the general population. We excluded studies in which data were extracted from pain or other specialist clinics or focusing on specific population subgroups. Twenty-one articles were identified and underwent quality assessment and data extraction. Included studies differed in 3 main ways: method of data retrieval, case ascertainment tool used, and presentation of prevalence/incidence rates. This heterogeneity precluded any meta-analysis. We categorised comparable incidence and prevalence rates into 2 main subgroups: (1) chronic pain with neuropathic characteristics (range 3–17%), and (2) neuropathic pain associated with a specific condition, including postherpetic neuralgia (3.9–42.0/100,000 person–years [PY]), trigeminal neuralgia (12.6–28.9/100,000 PY), painful diabetic peripheral neuropathy (15.3–72.3/100,000 PY), glossopharyngeal neuralgia (0.2–0.4/100,000 PY). These differences highlight the importance of a standardised approach for identifying neuropathic pain in future epidemiological studies. A best estimate of population prevalence of pain with neuropathic characteristics is likely to lie between 6.9% and 10%.

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Neuropathic pain in the general population: A systematic review of epidemiological studies

Poverty and common mental disorders in low and middle income countries: A systematic review

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61446-9.pdf

Epidemiology of major depressive disorder in elderly Nigerians in the Ibadan Study of Ageing: a community-based survey

Best current estimates of neuropathic pain prevalence come from studies using screening tools detecting pain with probable neuropathic features; the proportion experiencing significant, long-term neuropathic pain, and the proportion not responding to standard treatment are unknown. These “refractory” cases are the most clinically important to detect, being the most severe, requiring specialist treatment. The aim of this study was to estimate the proportion of neuropathic pain in the population that is “refractory,” and to quantify associated clinical and demographic features. We posted self-administered questionnaires to 10,000 adult patients randomly selected from 10 general practitioner practices in 5 UK locations. The questionnaire contained chronic pain identification and severity questions, cause of pain, SF-12, EQ-5D, S-LANSS (Self-administered Leeds Assessment of Neuropathic Signs and Symptoms), PSEQ (Pain Self-Efficacy Questionnaire), use of neuropathic pain medications, and health care utilisation. These data were combined to determine the presence and characteristics of “refractory” neuropathic pain according to the defining features identified by a Delphi survey of international experts. Graded categories of chronic pain with and without neuropathic characteristics were generated, incorporating the refractory criteria. Completed questionnaires were returned by 4451 individuals (response rate 47%); 399 had “chronic pain with neuropathic characteristics” (S-LANSS positive, 8.9% of the study sample); 215 (53.9%) also reported a positive relevant history (“Possible neuropathic pain”); and 98 (4.5% of all Chronic Pain) also reported an “adequate” trial of at least one neuropathic pain drug (“Treated possible neuropathic pain”). The most refractory cases were associated with dramatically poorer physical and mental health, lower pain self-efficacy, higher pain intensity and pain-related disability, and greater health care service use.

Neuropathic pain in the community: more under-treated than refractory?

Little is known about factors that determine the QoL of elderly persons living in developing societies undergoing rapid social changes. A representative sample of elderly Nigerians, aged 65 years and over (n = 2152), was assessed for QoL using the World Health Organization Quality of Life instrument (WHOQoL-Bref). Other than sociodemographic factors, respondents were also evaluated for major depressive disorder, physical conditions as well as for social network, support and engagement. Using linear regression modeling, these factors were explored for their ability to predict the physical, psychological, social and environmental domains of QoL. Economic status was the most consistent predictor of the four domains of QoL, with the coefficients ranging between 1.0 and 1.68 (p < 0.001 in every instance). Among health variables, functional disability (range: 7.07-19.86) and self-rated overall health (range: 7.89-18. 42) were the most salient. Participation in community activities (range 7.74-17.48) was the most consistent social predictor. Even though health factors are important, social factors, in particular those relating to the quality of social support and participation, are the most important predictors of QoL.

Determinants of quality of life of elderly Nigerians: results from the Ibadan Study of Ageing

Background. Suicide is a leading cause of death worldwide but information about it is sparse in Sub-Saharan Africa. Suicide-related behaviours can provide an insight into the extent of this compelling consequence of mental illness.Method. Face-to-face interviews were conducted with a representative sample of persons aged 18 years and over (n=6752) in 21 of Nigeria's 36 states (representing about 57% of the national population). Suicide-related outcomes, mental disorders, as well as history of childhood adversities were assessed using the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI).Results. Lifetime prevalence estimates of suicide ideation, plan and attempts were 3·2% [95% confidence interval (CI) 1·4–6·5], 1·0% (95% CI 0·4–7·5) and 0·7% (95% CI 0·5–1·0) respectively. Almost two of every three ideators who made a plan went on to make an attempt. The highest risks for transition from ideation to plan and from plan to attempt were in the first year of having ideation or plan respectively. Mental disorders, especially mood disorders, were significant correlates of suicide-related outcomes. Childhood adversities of long separation from biological parents, being raised in a household with much conflict, being physically abused, or being brought up by a woman who had suffered from depression, anxiety disorder, or who had attempted suicide were risk factors for lifetime suicide attempt.Conclusions. History of childhood adversities and of lifetime mental disorders identify persons at high-risk for suicide-related outcomes. Preventive measures are best delivered within the first year of suicide ideation being expressed.

The profile and risks of suicidal behaviours in the Nigerian Survey of Mental Health and Well-Being.

Objectives To determine weight change patterns in Scottish patients 2 years after diagnosis of type 2 diabetes and to examine these in association with medium-term glycaemic, mortality and cardiovascular outcomes. Setting Using a retrospective cohort design, ethical approval was obtained to link the Scottish diabetes care database to hospital admission and mortality records. Participants 29 316 overweight/obese patients with incident diabetes diagnosed between 2002 and 2006 were identified with relevant information for ≥2 years. Primary and secondary outcome measures Weight records over time provided intrapatient weight change and variation and glycated haemoglobin (HbA1c) gave measures of glycaemic control. These characteristics and demographic variables at diagnosis were linked with notifications of death (2–5 years after diagnosis) and cardiovascular events (0–5 year after diagnosis). Results By 2 years, 36% of patients had lost ≥2.5% of their weight. Increasing age, being female and a higher body mass index at diagnosis were associated with larger proportions of weight lost (p Conclusions Our results suggest that weight loss or being weight stable with little weight variability early after diabetes diagnosis, are associated with better glycaemic control and we identified groups less able to lose weight. With respect to mortality and cardiovascular outcomes, although weight change at 2 years was a weak predictor, major weight variability appeared to be the more relevant factor.

https://bmjopen.bmj.com/content/bmjopen/6/7/e010836.full.pdf

Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes: a retrospective cohort study

Ebenezer Afolabi

Papers

Epidemiology of major depressive disorder in elderly Nigerians in the Ibadan Study of Ageing: a community-based survey

Neuropathic pain in the community: more under-treated than refractory?

Determinants of quality of life of elderly Nigerians: results from the Ibadan Study of Ageing

The profile and risks of suicidal behaviours in the Nigerian Survey of Mental Health and Well-Being.

Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes: a retrospective cohort study