Minor tranquillizers for short-term treatment of newly onset symptoms of anxiety and distress: a systematic review with network meta-analysis of randomized trials.

Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1-4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress. We searched the PsycInfo, MEDLINE, EMBASE and Cochrane Library databases and extracted data following a predefined hierarchy of outcomes. We assessed risk of bias using the Cochrane Risk of Bias tool and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). We included 34 randomized trials comprising a total of 7044 patients with adjustment disorders or anxiety spectrum disorders. The network meta-analysis showed that regarding the critical outcome symptoms of anxiety within 1-4 weeks benzodiazepines (SMD - 0.58, 95% CI - 0.77 to - 0.40), quetiapine (SMD - 0.51, 95% CI - 0.90 to - 0.13) and pregabalin (SMD - 0.58, 95% CI - 0.87 to - 0.28) all performed better than placebo with no statistically significant difference between the drugs. Data on other important outcomes were inconsistently reported. Adverse effects varied, but overall, it was uncertain whether adverse effects differed between interventions. The evidence regarding the risk of dependence was uncertain, but dependence may be a concern in susceptible individuals even with short-term treatment. Overall, the certainty of the evidence according to GRADE was rated as low to very low across outcomes. Despite the limitations in the evidence, the results of this review can inform treatment guidelines, supporting clinicians in the choice of minor tranquillizer in this prevalent and help-seeking, clinically heterogeneous population.

Mortality and suicide in schizophrenia: 21-year follow-up in rural China.

BACKGROUND: Little is known about the trend and predictors of 21-year mortality and suicide patterns in persons with schizophrenia. AIMS: To explore the trend and predictors of 21-year mortality and suicide in persons with schizophrenia in rural China. METHOD: This longitudinal follow-up study included 510 persons with schizophrenia who were identified in a mental health survey of individuals (≥15 years old) in 1994 in six townships of Xinjin County, Chengdu, China, and followed up in three waves until 2015. Kaplan-Meier survival analysis and Cox hazard regressions were conducted. RESULTS: Of the 510 participants, 196 died (38.4% mortality) between 1994 and 2015; 13.8% of the deaths (n = 27) were due to suicide. Life expectancy was lower for men than for women (50.6 v. 58.5 years). Males consistently showed higher rates of mortality and suicide than females. Older participants had higher mortality (hazard ratio HR = 1.03, 95% CI 1.01-1.05) but lower suicide rates (HR = 0.95, 95% CI 0.93-0.98) than their younger counterparts. Poor family attitudes were associated with all-cause mortality and death due to other causes; no previous hospital admission and a history of suicide attempts independently predicted death by suicide. CONCLUSIONS: Our findings suggest there is a high mortality and suicide rate in persons with schizophrenia in rural China, with different predictive factors for mortality and suicide. It is important to develop culture-specific, demographically tailored and community-based mental healthcare and to strengthen family intervention to improve the long-term outcome of persons with schizophrenia.

Subjective health-related quality of life in community-dwelling middle-aged and older adults with early-onset schizophrenia.

Background: Long-term outcome in schizophrenia remains unsatisfactory due to continued premature deaths and insufficient health treatment. Subjective quality of life (SQoL) measurements hold important information and have meaningful implications regarding ways of improving general health status. This study investigated the physical and mental SQoL and associated clinical and sociodemographic outcomes among community-dwelling middle-aged and older people with early-onset schizophrenia.Materials and methods: A cross-sectional interview study where participants residing in the Region of Southern Denmark were identified through The Danish Psychiatric Central Register. Of a total of 278 eligible individuals, 59 people aged 55-82 years old participated. The SQoL measure Medical Outcomes Short Form 36 version 2 (SF36) was used. Scores were compared by age groups with normative data for the Danish population. Associated outcomes were measured using Positive And Negative Symptom Scale Remission and others.Results: Increased mental SQoL was associated with schizophrenia in remission (adjusted B 9.43, p = .001), increased Mental Health Recovery Measure score (adjusted B 0.55, p < .001) and increased GAF score (adjusted B 0.32, p < .001). Comparing with Danish Normative data, mental SQoL was reduced (p = .001) among 55-64-year olds, but presented levels similar to the general population at ages over 65 years. Physical quality of life was similar to the general population.Conclusion: Over 65-year olds with schizophrenia seemed to have SQoL similar to their age peers in the general population. Aiming treatment at achieving state of remission or recovery would be an amenable measure toward increasing mental SQoL among middle-aged people with schizophrenia.

Excess medical comorbidity and mortality across the lifespan in schizophrenia.: A nationwide Danish register study.

INTRODUCTION: People with severe mental illness have greater risk of un-detected and inadequately treated medical disorders, adding up to the risk of premature death. This study investigated how chronic medical comorbidity evolved across the lifespan in schizophrenia and the associated impact on mortality. METHOD: A register-based retrospective nested case-control study was conducted, identifying incident cases of cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), cancer and diabetes, as well as mortality due to these diseases, across the lifespan in schizophrenia. SAMPLE: A schizophrenia cohort consisting of 4924 individuals aged 18-40 years registered with a diagnosis of schizophrenia (ICD-8: 295.0-3 + 295.9) during admission to a psychiatric hospital unit in 1970-79. Schizophrenia cases were age and gender matched with 22,597 controls in the general population. RESULTS: Rate ratio (RR) of CVD and cancer were similar to controls. The RR of COPD and diabetes were increased across the lifespan. The probability of having been diagnosed prior to dying from CVD, cancer, pulmonary diseases or diabetes was markedly reduced in schizophrenia cases compared to controls. The RR of all-cause mortality and mortality from CVD, COPD and diabetes remained elevated in all age groups in schizophrenia. Registration of medical comorbidity was associated with increased survival. CONCLUSION: Excess medical comorbidity persists across the lifespan and into older age. No age-related decrease in incidence of major chronic medical comorbidities in schizophrenia was found except for diabetes.

Physical Health, Medication, and Healthcare Utilization among 70-Year-Old People with Schizophrenia: A Nationwide Danish Register Study.

OBJECTIVES: In light of the excess early mortality in schizophrenia, mainly due to physical illnesses, we investigated medical comorbidity, use of medication, and healthcare utilization among individuals with schizophrenia who survived into older ages to uncover potential factors contributing to their longevity. DESIGN: A nationwide register-based case-control study comparing 70-year-olds with and without schizophrenia. SETTING: Cases were drawn from the Danish Psychiatric Central Register. Age- and sex-matched controls were drawn from the general population via the Civil Registration System. PARTICIPANTS: All Danish inhabitants who were diagnosed and registered with early onset schizophrenia in 1970-1979 and still alive at age 70 years. Controls alive at age 70 years. MEASUREMENTS: Chronic medical comorbidity, medications, and inpatient and outpatient healthcare utilization extracted from Danish healthcare registers. RESULTS: Older adults with schizophrenia did not differ from controls with regard to registered chronic medical illnesses, but were significantly less likely to receive medication for cardiovascular diseases (OR: 0.65; 99.29% CI: 0.50, 0.83) and more likely to be treated with analgesics (OR: 1.46; 99.29% CI: 1.04, 2.05). Overall, hospital admissions and number of days hospitalized were equal to controls, but with significantly fewer general medical outpatient contacts (RR: 0.37; 98.75% CI: 0.24, 0.55). CONCLUSIONS: Because the literature suggests that excess mortality continues into old age, it is possible that medical diseases were under-registered and/or under-treated. Focus on adequate medical treatment, in particular for cardiovascular disease, is needed. Future integration of psychiatric and general medical healthcare, especially outpatient care, might further optimize health outcomes for older adults with schizophrenia.

The risk of offspring developing substance use disorders when exposed to one versus two parent(s) with alcohol use disorder: A nationwide, register-based cohort study.

AIM: Few population-based, family studies have examined associations between exposure to one vs. two parent(s) with alcohol use disorder (AUD) and the risk of offspring developing substance use disorder (SUD). Moreover, these studies have focused solely on the development of AUD, and not SUD, in offspring. The purpose of this study was to investigate whether exposure to one vs. two parent(s) with AUD increases the risk of offspring developing SUD. METHODS: A population-based, cohort study was conducted in which offspring born in Denmark between 1983 and 1989 were followed through national registries until 2011. Register-based data were obtained from the: Psychiatric Central Research Register, National Patient Registry, Civil Registration System, Fertility Database, and Cause of Death Register. Adjusted hazard ratios were calculated using multivariate Cox-regression models. FINDINGS: A total of 398,881 offspring were included in this study. Of these, 3.9% had at least one parent with AUD. Parental AUD was significantly associated with the development of SUD in offspring. Having one parent with AUD was linked to a 1.44-fold increased risk (95% CL, 1.29-1.61), while having two parents with AUD was linked to a 2.29-fold increased risk (95% CI, 1.64-3.20). No significant differences were found in relation to either parental or offspring gender. CONCLUSIONS: Exposure to parental AUD is linked to an increased risk of offspring developing SUD. This risk is additive for offspring exposed to double parental AUD. The findings have important implications for clinical assessment and intervention strategies, as well as the management of offspring exposed to parental AUD.

Aromaticity effects on the profiles of the lowest triplet-state potential-energy surfaces for rotation about the C=C bonds of olefins with five-membered ring substituents: an example of the impact of Baird's rule.

A density functional theory study on olefins with five-membered monocyclic 4n and 4n+2 π-electron substituents (C4H3X; X=CH(+), SiH(+), BH, AlH, CH2, SiH2, O, S, NH, and CH(-)) was performed to assess the connection between the degree of substituent (anti)aromaticity and the profile of the lowest triplet-state (T1) potential-energy surface (PES) for twisting about olefinic C=C bonds. It exploited both Hückel's rule on aromaticity in the closed-shell singlet ground state (S0) and Baird's rule on aromaticity in the lowest ππ* excited triplet state. The compounds CH2=CH(C4H3X) were categorized as set A and set B olefins depending on which carbon atom (C2 or C3) of the C4H3X ring is bonded to the olefin. The degree of substituent (anti)aromaticity goes from strongly S0 -antiaromatic/T1 -aromatic (C5H4 (+)) to strongly S0 -aromatic/T1- antiaromatic (C5H4(-)). Our hypothesis is that the shapes of the T1 PESs, as given by the energy differences between planar and perpendicularly twisted olefin structures in T1 [ΔE(T1)], smoothly follow the changes in substituent (anti)aromaticity. Indeed, correlations between ΔE(T1) and the (anti)aromaticity changes of the C4 H3 X groups, as measured by the zz-tensor component of the nucleus-independent chemical shift ΔNICS(T1;1)zz , are found both for sets A and B separately (linear fits; r(2) =0.949 and 0.851, respectively) and for the two sets combined (linear fit; r(2) =0.851). For sets A and B combined, strong correlations are also found between ΔE(T1) and the degree of S0 (anti)aromaticity as determined by NICS(S0,1)zz (sigmoidal fit; r(2) =0.963), as well as between the T1 energies of the planar olefins and NICS(S0,1)zz (linear fit; r(2) =0.939). Thus, careful tuning of substituent (anti)aromaticity allows for design of small olefins with T1 PESs suitable for adiabatic Z/E photoisomerization.

Z/E-photoisomerizations of olefins with 4npi- or (4n + 2)pi-electron substituents: zigzag variations in olefin properties along the T(1) state energy surfaces.

[Figure: see text]. A quantum chemical study has been performed to assess changes in aromaticity along the T1 state Z/E-isomerization pathways of annulenyl-substituted olefins. It is argued that the point on the T1 energy surface with highest substituent aromaticity corresponds to the minimum. According to Baird (J. Am. Chem. Soc. 1972, 94, 4941), aromaticity and antiaromaticity are interchanged when going from S0 to T1. Thus, olefins with S0 aromatic substituents (set A olefins) will be partially antiaromatic in T1 and vice versa for olefins with S0 antiaromatic substituents (set B olefins). Twist of the C=C bond to a structure with a perpendicular orientation of the 2p(C) orbitals (3p*) in T1 should lead to regaining substituent aromaticity in set A and loss of aromaticity in set B olefins. This hypothesis is verified through quantum chemical calculations of T1 energies, geometries (bond lengths and harmonic oscillator measure of aromaticity), spin densities, and nucleus independent chemical shifts whose differences along the T1 PES display zigzag dependencies on the number of -electrons in the annulenyl substituent of the olefin. Aromaticity changes are reflected in the profiles of the T1 potential energy surfaces (T1 PESs) for Z/E-isomerizations because olefins in set A have minima at 3p* whereas those in set B have maxima at such structures. The proper combination (fusion) of the substituents of set A and B olefins could allow for design of novel optical switch compounds that isomerize adiabatically with high isomerization quantum yields.