Alterations in plasma endocannabinoid concentrations among individuals with major depression treated with electroconvulsive therapy.

The role of the endocannabinoid system (ECS) in depression and suicidality has recently emerged. The purpose of the study was to identify changes in plasma endocannabinoid concentrations of several endocannabinoids and correlate them with depressive symptoms and suicidality in patients with severe major depression undergoing electroconvulsive therapy (ECT). The study included 17 patients that were evaluated in four visits at different stages of therapy. At each visit depression, anxiety and suicidality symptoms were assessed and blood samples collected. Several endocannabinoid concentrations increased following six sessions of ECT, as 2-AG (p < 0.05) and LEA (p < 0.01), and following twelve sessions of ECT, as 2-AG (p < 0.05), AEA (p < 0.05), LEA (p < 0.05) and DH-Gly (p < 0.05). Endocannabinoids also correlated with symptoms of depression, anxiety and suicidality at baseline and at the sixth ECT session. Finally, we found one endocannabinoid, l-Gly, that differentiated between remitted and not-remitted patients at the seventh and thirteenth ECT sessions (p < 0.05). Our findings suggest that depression is markedly related to imbalance of the endocannabinoid system, and further regulated by ECT. Plasma endocannabinoids could be promising biomarkers for detection of depression response and remission.

Short-term chloral hydrate as an add-on treatment may improve sleep and alleviate agitation in inpatients with treatment resistant schizophrenia: a retrospective case series study.

Introduction: Chloral hydrate (CH), a medication dating back to 1832, is tranquilizer and sleep promoter still used today. It remains an option for short-term insomnia therapy and sedation before medical procedures, despite its controversial safety profile. Methods: This study investigated the potential benefits of chloral hydrate addition for increasing sleep duration and reducing agitation and violence in inpatients with treatment-resistant schizophrenia (TRS). A retrospective, observational case series design was utilized, analyzing data from fourteen patients diagnosed with TRS disorders. Results: CH addition increased the rate of full night sleep and decreased the rates of agitation and verbal and physical violence events. Notably, no adverse events including falls were reported during CH addition. Discussion: CH shows some short-term benefits in improving sleep disorders and reducing violent and agitated behavior in patients with TRS. Our study has limitations due to its small sample size, retrospective design and lack of a control group. A large-scale, double-blind, randomized trial is needed to further explore the efficacy and safety of CH in psychiatric populations with TRS accompanied by agitation, violence and disturbed sleep.

Inflammation Markers Among Schizophrenia Patients Who Use Cannabis.

OBJECTIVES: The mechanism of inflammation of the immune system, for example, such circulatory markers as the neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV), has been shown in many studies to be associated with schizophrenia. In addition, it has been shown that the cannabidiol component reduces the activation of the acquired immune system. This study examined the differences in the levels of NLR and MPV among schizophrenia patients with cannabis use versus those without. METHODS: In 2019 to 2020, a retrospective cross-sectional study was conducted based on digital medical records. Demographic, clinical, and complete blood cell count data were collected from records of rehospitalization of active psychotic schizophrenia inpatients. Data on NLR, MPV values, and demographic and clinical characteristics were compared between the groups and according to the degree of prevalence of cannabis use. RESULTS: No differences were found in the NLR and MPV values between the groups. CONCLUSION: The results were contrary to our expectations. These results may be explained by the presentation of a "pseudo-balanced" picture created when multiple processes affect inflammatory indices.

Comparison of medical treatment of patients with schizophrenia in general practitioners' clinics versus mental health clinics: A cohort study.

OBJECTIVES: Individuals with schizophrenia have more cardiometabolic comorbidities than the general population, live about twenty years less and consume more medical services. They are treated at general practitioners' clinics (GPCs) or at mental health clinics (MHCs). In this cohort study we investigated the association between patients' main treatment setting, cardiometabolic comorbidities and medical services utilization. METHODS: Demographics, healthcare services utilization, cardiometabolic comorbidities and medication prescriptions of patients with schizophrenia were retrieved from an electronic database for the period 1.1.2011 to 31.12.2012 and compared between patients treated mostly in MHCs (N = 260) and those treated mostly in GPCs (N = 115). RESULTS: GPC patients tended to be older (mean age 39.8 ± 13.7 vs. 34.6 ± 12.3 yrs., p < 0.0001), of lower socioeconomic status (42.6% vs 24.6%, p = 0.001) and have more cardiometabolic diagnoses (hypertension: 19.1% vs 10.8%, diabetes mellitus: 25.2% vs 17.0%, p < 0.05) than MHC patients. The former received more cardiometabolic disorder medications and utilized more secondary and tertiary medical services. Charlson Comorbidity Index (CCI) was higher in the GPC group than in the MHC group (1.8 ± 1.9 vs.1.2 ± 1. 6, p < 0.0001). A multivariate binary logistic regression analysis, adjusted for age, sex, SES and CCI found lower adjusted odds ratio for the MHC group versus the GPC group, of visiting an EMD, a specialist or to be hospitalized. CONCLUSIONS: The current study highlights the critical importance of integrating GPCs and MHCs, thus offering patients combined physical and mental care at a single location. More studies on the potential benefits of such integration to patients' health are warranted.

Adherence of patients with schizophrenia to hypothyroidism treatment.

Adherence to prescription medications is critical for both remission from schizophrenia and control of physical comorbidities. While schizophrenia with comorbid hypothyroidism is common, there is little research on adherence to hypothyroidism treatment in this population. The current study used a retrospective, matched case-control design. The cohort included 1,252 patients diagnosed with schizophrenia according to ICD-10 and 3,756 controls matched for gender, age, socioeconomic status and ethnicity without diagnosis of schizophrenia. All data were retrieved from the electronic medical database of a large health maintenance organization. Retrieved data included demographics, thyroid functionality test results and prescribed medications. Measures of adherence to therapy were used for analyses as were data from follow-ups of patients with hypothyroidism. A diagnosis of hypothyroidism was found in 299 patients, 115 of whom were also diagnosed with schizophrenia. The 184 without schizophrenia constituted the control group. No statistically significant differences were found between the two groups regarding prescriptions for L-thyroxin and TSH levels and number of TSH tests. Adherence of patients with schizophrenia to hypothyroidism treatment was found to be as good as that of individuals without a schizophrenia diagnosis.

Factors affecting the willingness of mental health staff to get vaccinated against COVID-19.

RATIONALE AND OBJECTIVE: At the beginning of vaccination against coronavirus disease 2019 (COVID-19), information about the effects of the vaccine was not known and hesitancy was observed among the population. The mental health staff members in our center in Israel had to decide whether to get vaccinated or not. The objective of this study was to evaluate the differences in demographic characteristics of vaccinated and nonvaccinated mental health care workers (HCWs), and to identify their reasons for or against vaccination. METHOD: Data on characteristics of 357 staff members at a mental health center (MHCS) in Israel and their attitudes regarding COVID-19 vaccination, those who were nonvaccinated, were collected via anonymous questionnaires, from 1 January to 10 January 2021. The groups were then compared using χ2 , Fisher's exact tests, t test or Mann-Whitney nonparametric test as appropriate. A logistic regression was then performed using the significant variables and odd ratios presented. RESULTS: Eighty-one per cent of the sample received at least the first dose of the vaccine. Results indicated differences in seniority (p < 0.001), profession (p < 0.001), department (p < 0.001), risk groups (p < 0.05), religion (p < 0.001), religiosity (p < 0.001), previous care for COVID-19 patients (p < 0.05) and level of interaction with patients (p < 0.01), between the vaccinated and nonvaccinated staff. The factor that was found to be most influential regarding vaccination and which convinced those originally against the vaccine to become vaccinated was the level of scientific knowledge about the vaccine. CONCLUSION: Efforts and resources should focus on the dissemination of reliable scientific data about the vaccine, to increase vaccination rates among mental HCWs.

Vitamin D as a Protective Factor in COVID-19 Infection in Elderly Schizophrenia and Dementia Inpatients: A Case Series.

BACKGROUND: Risk factors for severe coronavirus disease-2019 (COVID-19) infection include old age, chronic illness, and neurological conditions. In contrast, high vitamin D levels are known to augment immune activity and to reduce the severity of viral infections. Recently, a possible association between the likelihood of COVID-19 infection, COVID-19 severity, and vitamin D blood levels was reported. OBJECTIVES: To assess the possible association between vitamin D long-term supplementation and COVID-19 symptomatic severity and complications of COVID-19 infection in elderly psychiatric inpatients, a high at-risk group. METHODS: We conducted a retrospective case series study. Data of 14 elderly COVID-19 positive inpatients, presenting with dementia or schizophrenia and other medical conditions were extracted from medical records. All patients maintained a 800 IU daily dose of vitamin D prior to the infection. RESULTS: Most of the inpatients were asymptomatic or presented very few symptoms. No need for intensive care unit intervention or deaths were reported. Cognitive functioning of the patients remained unchanged. CONCLUSIONS: Pre-existing vitamin D supplementation may reinforce immunity and reduce COVID-19 severity in elderly psychiatric inpatients.

Olanzapine intramuscular shows better efficacy than zuclopenthixol acetate intramuscular in reducing the need for restraint, but not in comparison to haloperidol intramuscular.

Many psychotic patients are treated with antipsychotic medications during acute agitation and aggressive behavior episodes in an attempt to achieve a rapid calming effect. Those medications include olanzapine, zuclopenthixol acetate, and haloperidol intramuscular administration. This study compared the effectiveness of these injections in reducing the need for restraint during agitated-psychotic episodes that include aggression. Sociodemographical and clinical data were retrieved from the electronic medical records of 179 patients who needed rapid calming while hospitalized in a mental health center with acute psychosis. The treatments administered were olanzapine intramuscular, zuclopenthixol acetate intramuscular, and haloperidol intramuscular. The assessed outcomes were rate of restraint and violent behavior. Olanzapine was found significantly more effective in reducing the need for restraint compared to zuclopenthixol acetate. No significant differences were found between haloperidol and the other two with regard to restraint. Neither were other significant differences found between the groups with regard to violent or self-harming behaviors. No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge. In conclusion, in inpatients with acute agitated psychosis, olanzapine intramuscular shows better efficacy in reducing the need for restraint, at least as compared to zuclopenthixol acetate intramuscular.

A Double-Blind, Placebo-Controlled Trial of Bupropion Add-on to Olanzapine or Risperidone in Overweight Individuals With Schizophrenia.

BACKGROUND: Weight gain due to antipsychotics is a challenging clinical problem because, to date, no effective pharmacological strategies have been found. Bupropion is often used in people with schizophrenia for smoking cessation and is well tolerated. However, studies on its use as weight loss treatment are scarce. The aim of the study was to examine the effectiveness of bupropion as a single weight loss treatment in overweight individuals maintained on long-term olanzapine or risperidone. METHODS: This randomized, double-blind, placebo-controlled, 8-week study included 26 overweight (body mass index ≥27 kg/m2) individuals with schizophrenia maintained on olanzapine (10-20 mg/d) or risperidone (2-4 mg/d). Participants were randomly allocated to a study group that received bupropion (150-300 mg/d) or to a placebo group. The positive and Negative Syndrome Scale and the Clinical Global Impression-Severity Scale were used to assess severity of psychosis at baseline and end of study (8 weeks). RESULTS: Bupropion addition, but not placebo, was associated with a significant reduction in body weight. Severity of psychotic symptoms was not altered in either group. CONCLUSIONS: The results demonstrate the efficacy of bupropion, compared with placebo, in patients maintained on chronic treatment with olanzapine or risperidone, both known to be major contributors to significant weight gain.

Creatine kinase levels in psychotic patients who use cannabinoids.

Elevated serum levels of creatine kinase enzymes have been found in brain injuries and psychosis. Cannabinoid use is associated with increased frequency and duration of hospitalizations. We examined whether creatine kinase levels differ in psychotic cannabinoid users and the association between creatine kinase levels and clinical measures (duration of hospitalization and need for mechanical restraint). Computerized medical records of 124 men hospitalized due to acute psychotic episodes were reviewed. Creatine kinase levels and various clinical measures at admission were documented. Cannabis users were significantly younger than nonusers. Duration of illness was longer among nonusers. Log creatine kinase among cannabinoid users (N = 32) was numerically higher compared to nonusers (N = 92) (5.6 ± 1 vs. 5.2 ± 0.9, respectively). Significantly higher rate of elevated creatine kinase levels (creatine kinase > 195 U/l) was detected in the cannabinoid users compared to nonusers (59.4% vs. 38%, respectively; P < 0.04). No association was found between creatine kinase levels and use of mechanical restraints and hospitalization days. Higher rate of elevated creatine kinase levels was observed in hospitalized psychotic cannabinoid users, possibly due to a cannabis activity at peripheral or brain tissues. Studies in larger, more diverse clinical populations are needed to confirm this finding and to clarify the biological mediators of elevated creatine kinase levels in psychotic cannabinoid users.

Thyroid function assessment before and after diagnosis of schizophrenia: A community-based study.

Alterations in thyroid hormone levels may affect brain and mental disorders. Conversely, schizophrenia and its antipsychotic treatments can affect thyroid hormone levels. However, data on thyroid hormone levels during the course of schizophrenia disorder are scant. The aim of the study was to assess the rate of thyroid hormone disorders in outpatients before and after diagnosis of schizophrenia. A retrospective matched-control design was used. The cohort included 1252 patients suffering from ICD-10 schizophrenia, and 3756 control subjects matched for gender, age, socioeconomic status, and origin. All were identified from the database of a large health management organization. The pertinent clinical data were collected from the electronic medical records. There was no significant between-group difference in the distribution of thyroid-stimulating hormone levels. Before diagnosis, both groups had a similar rate of hypothyroidism. After diagnosis of schizophrenia and initiation of antipsychotic treatment, the rate of hypothyroidism was significantly higher in the patient group. It remained significantly higher after exclusion of patients receiving lithium. The increased rate of hypothyroidism in patients with schizophrenia after, but not before, the diagnosis of schizophrenia suggests that antipsychotic medications may affect thyroid hormone levels. Screening for thyroid disorders is warranted in patients with schizophrenia under antipsychotic treatment.

Mortality, morbidity and medical resources utilization of patients with schizophrenia: A case-control community-based study.

Patients with schizophrenia have higher level of mortality and physical comorbidity compared to control population. However the association to primary-, secondary- and tertiary-medical resources utilization is not clear. We used a retrospective community-based cohort of patients with schizophrenia (n=1389; age 37.53 years, 64.3% males) and, age-, gender-, and socioeconomic status-matched controls (n=4095; age 37.34 years; 64.3% males) who were followed-up for nine years. Mortality rate of patients was almost twice as high as that of matched controls (7% versus 3.8%). Diagnoses of ischemic heart disease and hypertension were more prevalent among controls than patients (8.2% versus 5%, and 21.6% versus 15.8%, respectively). Tertiary medical resources utilization was higher among patients with schizophrenia than control population (mean hospital admissions per year: 0.2 versus 0.12, emergency department visits: 0.48 versus 0.36). Patients that died were more likely to have cardiovascular disease, to be admitted to general hospital and to spend more days in hospital than patients that did not die. There is a discrepancy between lower rates of cardiovascular disease diagnoses but higher rates of mortality and tertiary medical resources utilization among patients with schizophrenia when compared to control population. This may stem from an under-diagnosis and, eventually, under-treatment of these patients.

Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

BACKGROUND: While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. METHODS: This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. RESULTS: Twenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs -0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size=0.17, significance lost following Bonferroni correction). CONCLUSIONS: Vitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation.

Low adherence to antidepressants is associated with increased mortality following stroke: A large nationally representative cohort study.

Post stroke depression is common and pervasive. In the general population, there has been some controversy that antidepressant (AD) medication is associated with premature mortality. Data is still lacking regarding the association between adherence to antidepressants (AD) and all-cause mortality. In this retrospective analysis of a population-based cohort of patients, 32,361 post-stroke patients who purchased at least one AD were followed for all-cause mortality over 4-years. Adherence to AD was measured as a ratio between dispensed and prescribed durations and was modeled as: non-adherence (<20%, n=8619), poor (20-50%, n=5108), moderate (50-80%, n=5656), and good (>80%, n=12,978) adherence. Multivariable survival analyses, adjusted for demographic and clinical variables including physical comorbidities known to influence mortality, were conducted. Unadjusted mortality rates were 16.5%, 20.2%, 22.2% and 23.7% in those classified as non-adherent, poor, moderate and good adherence respectively (χ2=174.6, p<0.0001). In the adjusted model, the non-adherent and poor adherence groups had significantly increased mortality Hazard Ratios (HR) of 1.25 (95% CI: 1.17-1.33) and 1.17 (95% CI: 1.09-1.26) respectively compared to the good adherence group. This nationally representative data suggests that poor adherence to AD is associated with increased all-cause mortality among people who had a stroke. Given our findings and the high prevalence of anxiety and depression along with AD effectiveness, efforts to promote AD adherence in this population may be warranted in clinical practice.

Amantadine augmentation therapy for obsessive compulsive patients resistant to SSRIs-an open-label study.

BACKGROUND: It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)- a weak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone. METHODS: Eight patients (5 males and 3 females, aged 42.6 ± 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed. RESULTS: Significant reductions in total Y-BOCS (28 ± 4.5 vs. 18.8 ± 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 ± 3.2 vs. 10.6 ± 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 ± 3.3 vs. 8.1 ± 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered. CONCLUSIONS: AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.

Pharmacogenetics of antidepressive drugs: a way towards personalized treatment of major depressive disorder.

Major depressive disorder is one of the most prevalent psychiatric disorders, and in spite of extensive ongoing research, we neither fully understand its etiopathological background, nor do we possess sufficient pharmacotherapeutic tools to provide remission for all patients. Depression is a heterogenous phenomenon both in its manifestation and its biochemical and genetic background with multiple systems involved. Similarly, the employed pharmaceutical agents in the treatment of depression also effect multiple neurotransmitter systems in the brain. However, we do not yet possess sufficient tools to be able to choose the medication that treats the symptoms most effectively while contributing to minimal side effects in parallel and thus provide personalized pharmacotherapy for depression. In the present paper we review genetic polymorphisms that may be involved in the therapeutic effects and side effects of antidepressive medications and which, in the future, may guide customized selection of the pharmacotherapeutic regimen in case of each patient.