Observational evidence linking psychotropic medicines to the dispensing of opioid agents in later life.

BACKGROUND: The use of opioid medicines is common in developed countries, particularly among older adults and those with mental health disorders. It is unclear if the association between mental disorders and opioid medicines is causal, or is due to reverse causality or confounding. METHODS: We used a 10% random sample of the Australian Pharmaceutical Benefits Scheme (years 2012-2022) to examine the cross-sectional, case-control and longitudinal association between the dispensing of antidepressants, anxiolytics, hypnotics, antipsychotics and lithium, and opioid medicines. We used logistic regression, structural equation models (SEM), and Cox regression to analyze the data. Analyses were adjusted for age (years), sex, and number of non-psychotropic medicines dispensed during the year. RESULTS: The 2022 file contained 804 334 individuals aged 50 years or over (53.1% women), of whom 181 690 (22.6%) received an opioid medicine. The adjusted odds ratio of being dispensed opioid medicines was 1.44 (99% CI = 1.42-1.46) for antidepressants, 1.97 (99% CI = 1.92-2.03) for anxiolytics, 1.55 (99% CI = 1.51-1.60) for hypnotics, 1.32 (99% CI = 1.27-1.38) for antipsychotics, and 0.60 (99% CI = 0.53-0.69) for lithium. Similar associations were noticed when we compared participants who were or not dispensed opioid medicines in 2022 for exposure to psychotropic agents between 2012 and 2021. SEM confirmed that this association was not due to reverse causality. The dispensing of antidepressants was associated with increased adjusted hazard (HR) of subsequent dispensing of opioid medicines (HR = 1.29, 99% CI = 1.27-1.30). Similar associations were observed for anxiolytics, hypnotics and antipsychotics, but not lithium. CONCLUSIONS: The dispensing of opioid medicines is higher among older individuals exposed to antidepressants, anxiolytics, hypnotics and antipsychotics than those who are not. These associations are not due to reverse causality or study design. Preventive strategies seeking to minimise the risk of inappropriate use of opioid medicines in later life should consider targeting this high-risk population.

Management of Phenibut Use Disorder and Withdrawal in a Geriatric Patient.

Phenibut is a misused substance which has shown an increase in use over the past decade. Marketed as a "dietary supplement," it is not approved in the United States for use and is not regulated by the Food and Drug Administration. The substance, however, is readily available for purchase through online markets. It has a similar drug profile as alcohol, gabapentin and benzodiazepines. Clinical effects of this drug include physiologic dependence, euphoria, anxiolysis, antispasticity, sedation, and possible nootropic properties. While there are emerging new cases of managing phenibut withdrawal, no cases currently feature phenibut addiction and withdrawal management in the geriatric population. Here we discuss such a case of phenibut addiction and withdrawal in a 68-year-old male who initially began misusing phenibut to alleviate anxiety and insomnia precipitated by worsening affective disorder, sedative, hypnotic, or anxiolytic use disorder, and alcohol use disorder.

Use of benzodiazepine and related drugs in migrants and Finnish-born persons: a nationwide register-based study.

AIMS: Benzodiazepines and related drugs (BZDR) are often used longer than generally recommended. The aim is to study patterns of use among migrant and Finnish-born users of BZDR, and to identify factors that are associated with long-term use and BZDR polytherapy. METHODS: This register-based study includes a nationwide sample of migrants (n=8729) and their Finnish-born controls (n=11 388) who had purchased BZDR in 2011-2014, but not in 2009-2010. Information on drug purchases was obtained from the National Prescription Register and the duration of drug use was estimated using PRE2DUP method. The main outcomes were long-term use of BZDR, polytherapy and time until discontinuation of BZDR use. Sociodemographic variables and information on preceding psychiatric diagnoses were included as covariates. Logistic and Cox regression analyses were the statistical methods used. RESULTS: Only migrants from Sub-Saharan Africa were more likely to discontinue the medication once initiated than Finnish-born users. Migrants were significantly less likely to be long-term users (adjusted odds ratio 0.79, 95% CI 0.70-0.89) or polytherapy users (aOR 0.90, 95% CI 0.84-0.97) of BZDR compared with Finnish-born participants. CONCLUSIONS: Migrants had less long-term and concomitant use of several BZDR than Finnish-born participants. The pattern of use is more optimal among migrants, but it may also reflect poorer access to mental health treatment.

Effects of electroconvulsive therapy on the use of anxiolytics and sleep medications: a propensity score-matched analysis.

AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.

Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability.

This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus® was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus®, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.

Impact of preoperative treatment with antidepressants and/or anxiolytics on outcomes after colorectal surgery with an enhanced recovery programme: a monocentric retrospective study.

BACKGROUND: Preoperative use of antidepressants and anxiolytics was reported to increase length of hospital stay (LOS) and worsen surgical outcomes. However, the surgical procedures studied were seldom performed with an enhanced recovery programme (ERP). This study investigated whether these medications impaired postoperative recovery after colorectal surgery with an ERP. METHODS: The data of all patients scheduled for colorectal surgery between November 2015 and December 2019 prospectively included in our database were analysed. All the patients were managed with the same ERP. Demographic data, risk factors, incidence of postoperative complications, LOS, and adherence to the ERP were compared between patients with and without preoperative antidepressant and/or anxiolytic treatment. RESULTS: Of the 502 patients, 157 (31.3%) were treated with antidepressants and/or anxiolytics. They were older (65.7 vs. 59.5 years, p < 0.001), sicker (higher ASA physical status score, p = 0.001), and underwent surgery more frequently for cancer (73.9 vs. 56.8%, p < 0.001). Overall adherence to ERP (p = 0.99) and adherence to the postoperative items of ERP (p = 0.29), incidence of postoperative complications (35.7 vs. 33.2%, p = 0.61), and LOS (4 [2-7] vs. 4 [2-7], p = 0.99) were similar in the two groups. CONCLUSIONS: Our findings suggest that preoperative treatment with antidepressants and/or anxiolytics does not worsen outcome after elective colorectal surgery with an ERP, does not impact adherence to ERP, and does not prolong LOS. ERP seems efficacious in patients treated with these medications, who should therefore not be excluded from this programme.

Relationship between falls and the use of hypnotics, antidepressants, antipsychotics, and anxiolytics in patients with rheumatoid arthritis: A cross-sectional study.

Objectives This cross-sectional study aimed to determine the relationship between falls and use of psychotropic medications in patients with rheumatoid arthritis. Methods The psychotropic medication group included patients with rheumatoid arthritis prescribed psychotropic medications (hypnotics/sedatives, antidepressants, antipsychotics, and anxiolytic [benzodiazepines] drugs). Poisson regression with robust variance was performed to investigate the relationship between falls and the use of psychotropic medications, with adjustment for age, sex, rheumatoid arthritis disease activity, stroke, dementia, diabetes mellitus, and osteoarthritis. Results Of the 307 patients enrolled, 49 (16.0%) used psychotropic medications, and 70 (22.8%) experienced at least one fall per year. Nineteen of the 49 patients (38.8%) taking psychotropic medications and 51 of 258 (19.8%) not taking psychotropic medications experienced at least one fall per year. Falls were significantly more frequent in the group with psychotropic medications than in the group without psychotropic medications (adjusted incidence rate ratio, 1.63; 95% confidence interval; 1.08-2.48, p = 0.02). No relationship was found between the number of falls and the use of psychotropic medications (adjusted incidence rate ratio, 1.16; 95% confidence interval; 0.39-3.44, p = 0.78). Conclusions There may be a relationship between psychotropic medication use and falls in patients with rheumatoid arthritis.

National prescription patterns of antidepressants among patients with amyotrophic lateral sclerosis: An analysis of the Korean National Health Insurance database.

INTRODUCTION/AIMS: The current status of antidepressant use in patients with amyotrophic lateral sclerosis (ALS), such as the prevalence and factors associated with it, has not been systematically investigated. We aimed to analyze the prevalence and patterns of antidepressant prescriptions in patients with ALS and depression, and to identify factors associated with antidepressant prescriptions after the diagnosis of ALS. METHODS: The data of patients with ALS and the prescription of antidepressants were retrieved from the Korean National Health Insurance claims data. A multivariate logistic regression model was used to identify factors associated with antidepressant prescriptions. RESULTS: In total, 533 of 2955 patients had depressive disorders, and 426 were prescribed antidepressants. Selective serotonin reuptake inhibitors and tricyclic antidepressants were the most frequently prescribed drugs. Adjusted odds ratios (ORs) were 1.379 for the prescription of antidepressants in females. For various age groups, compared with those aged 80 years and older, adjusted ORs were 1.889 for those in their 70s, 2.319 for those in their 60s, 2.872 for those in their 50s, 2.854 for those in their 40s, and 3.363 for those under 40 years of age. Adjusted ORs were 1.662 for patients with a history of a psychiatric disorder and 1.861 for those with a history of psychiatric pharmacotherapy (all P < .05). DISCUSSION: Most patients with ALS who had depression received antidepressant prescriptions. In young females with a previous psychiatric disorder or pharmacotherapy, an in-depth evaluation for a depressive disorder should be performed.

Psychiatric considerations in the oncology setting.

An aging population and advances in diagnostics and treatment have resulted in a rapidly growing population of people impacted by cancer. People live longer after a cancer diagnosis and tolerate more aggressive treatments than in the past. Younger patients struggle with diversions from the normal developmental milestones in career and relationships, while older patients deal with the dual challenges of aging and cancer. Cancer's transition from likely death to survival has increased interest in its impact on psychosocial issues and quality of life, rather than just longevity. In this article, the authors review the psychiatric diagnosis and management of the mental health issues most often encountered in oncology. Oncology treatment teams, including oncologists, nurses, social workers, and other ancillary staff, are often on the front lines of addressing psychiatric distress and clinical syndromes when psychiatrists are not easily available. The purpose of this review article is to highlight opportunities for nonpsychiatrists to improve identification and treatment of psychosocial distress and psychiatric syndromes and to request formal psychiatric consultation in appropriate situations. Psychotherapeutic, psychopharmacologic, cognitive, and behavioral-oriented interventions, as well as supportive interventions, are discussed for treating patients who are facing challenges during active cancer treatment, survivorship, and at the end of life. This review is not exhaustive but highlights the more common psychosomatic medicine and palliative care scenarios that impact cancer patient care. The importance of recognizing and addressing burnout and compassion fatigue in multidisciplinary professionals who care for those treated for cancer is also discussed given the secondary impact this can have on patient care.

The role of prenatal exposure to antidepressants, anxiolytic, and hypnotics and its underlying illness on the risk of miscarriage using BIFAP database.

PURPOSE: Despite the notable increase on the prescription of antidepressants and anxiolytics during pregnancy, recommendation on maintaining the treatment during prenatal period is still controversial. We aimed to separately assess the role of effects of the antidepressants and anxiolytic and the underlying illness, controlled by potential confounding associated with miscarriage onset. METHODS: We used data from a validated pregnant cohort aged 15-49 years from 2002 to 2016 using BIFAP database. All confirmed miscarriages were used to perform a nested control analysis using conditional logistic regression. Women were classified according to use of each drug of interest into four mutually exclusive groups: nonusers, users only during prepregnancy, continuers, and initiators during first trimester. Adjusted odds ratios (aORs) for major confounders during pregnancy such as number of visits to primary care practitioners visits, obesity, smoking, HTA, diabetes with 95% confidence intervals were calculated. RESULTS: Compared with nonusers, antidepressants continuers had the highest increased risk of miscarriage aOR (95%) of 1.29 (1.13-1.46), being continuers of paroxetine and fluoxetine the antidepressants with the strongest association. Likewise, continuers of anxiolytics and initiators showed an increased risk of 1.19 (1.04-1.37) and 1.30 (1.13-1.50). When separating the effect between the condition itself or the treatment, women exposed during first trimester, regardless treatment duration and/or the underlying illness, had the highest risk 1.27 (1.08-1.51) for antidepressants and 1.25 (1.13-1.39) for anxiolytics. CONCLUSIONS: Our analysis showed an association between prenatal exposure to antidepressants and anxiolytics and miscarriage onset after controlling by potential confounding adjusting for confounders and the underlying illness. This association was not supported for hypnotic medications. Further studies are warranted to evaluate the risk of miscarriage among subpopulation of pregnant women requiring these medications.

Analysis of regional differences in the amount of hypnotic and anxiolytic prescriptions in Japan using nationwide claims data.

BACKGROUND: In Japan, there has been no investigation of regional differences in the number or amount of prescriptions of anxiolytics or hypnotics. Attributes related to the high amount of prescriptions for these drugs are unknown. We investigated recent trends and regional differences in the amount of prescriptions of hypnotics and anxiolytics in Japan and identified factors associated with these regional differences. METHODS: The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open data from 2015 to 2018 were used. We calculated diazepam-equivalent doses (mg) for each drug and the total amount of prescriptions per capita for hypnotics and anxiolytics by sex and age. In addition, we calculated the standardized claim ratio (SCR) of the amount of prescriptions by prefecture. We investigated factors associated with regional differences in the SCRs of hypnotics and anxiolytics using the prefectures' medical, socioeconomic, and physical characteristics by an ecological study using a linear mixed-effects model. RESULTS: The amount of prescriptions of hypnotics and anxiolytics, specifically, the amount of prescriptions of benzodiazepine receptor agonists (BZRAs), decreased in many of the adult age groups from 2015 to 2018. The regression analysis revealed that the number of medical clinics per capita, the number of public assistance recipients per capita, the proportion of persons whose HbA1c ≥ 6.5%, and the proportion of persons whose BMI ≥25 kg/m2 were positively and significantly associated with the SCR of hypnosis. In contrast, the number of public assistance recipients per capita and the proportion of persons whose BMI ≥25 kg/m2 were positively and significantly associated with the SCR of anxiolytics. CONCLUSIONS: Factors associated with prescription amount of hypnotics and anxiolytics were revealed in this study, and a further study is needed for investigating causal relationships between the prescriptions amount and the associated factors using individual data.

Effects of medical service fee revision on reducing irrational psychotropic polypharmacy in Japan: an interrupted time-series analysis.

PURPOSE: According to the revised Japanese medical service fees aimed at reducing irrational psychotropic polypharmacy, medical service fees are reduced if the number of simultaneously prescribed psychotropic drugs exceeds the standard. This study primarily aims to examine the effect of the 2018 revision. METHODS: Using a large Japanese administrative claims database, we retrospectively identified five groups (April 2013-September 2018) prescribed at least one drug from the following drug groups: anxiolytics, hypnotics, sum of anxiolytics and hypnotics, antipsychotics, and antidepressants (study population in each group: 547,511, 406,524, 759,137, 112,929, and 201,046, respectively). We used an interrupted time-series design to evaluate changes in the proportion of patients prescribed more than the standard number of drugs. RESULTS: After the 2018 revision, the proportion of patients prescribed more than the standard number of drugs significantly decreased only for the sum of anxiolytics and hypnotics; estimated changes in level and trend were - 0.60% [- 0.69%, - 0.52%] and - 0.04% [- 0.06%, - 0.02%] per month, respectively. The proportion of patients exhibiting a decrease in the number of prescribed drugs from more than the standard to within the standard increased when the revision was enforced (April 2018); this proportion in April 2018 was 36.3%, while all other proportions were in the range of 12.1-22.3%. CONCLUSION: The 2018 revision promoted a reduction in the number of prescribed drugs, which served as an important factor in the decrease in the proportion of patients prescribed more than the standard number of drugs for the sum of anxiolytics and hypnotics.

New 1,2,4-oxadiazole derivatives with positive mGlu4 receptor modulation activity and antipsychotic-like properties.

Considering the allosteric regulation of mGlu receptors for potential therapeutic applications, we developed a group of 1,2,4-oxadiazole derivatives that displayed mGlu4 receptor positive allosteric modulatory activity (EC50 = 282-656 nM). Selectivity screening revealed that they were devoid of activity at mGlu1, mGlu2 and mGlu5 receptors, but modulated mGlu7 and mGlu8 receptors, thus were classified as group III-preferring mGlu receptor agents. None of the compounds was active towards hERG channels or in the mini-AMES test. The most potent in vitro mGlu4 PAM derivative 52 (N-(3-chloro-4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)phenyl)picolinamide) was readily absorbed after i.p. administration (male Albino Swiss mice) and reached a maximum brain concentration of 949.76 ng/mL. Five modulators (34, 37, 52, 60 and 62) demonstrated significant anxiolytic- and antipsychotic-like properties in the SIH and DOI-induced head twitch test, respectively. Promising data were obtained, especially for N-(4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)picolinamide (62), whose effects in the DOI-induced head twitch test were comparable to those of clozapine and better than those reported for the selective mGlu4 PAM ADX88178.

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events.

Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs. Besides pharmacological intervention, "positive environmental stimuli", which have the advantage of exerting no side-effects, have been shown to modulate inflammation-related markers in human beings. Therefore, we now investigated whether environmental enrichment (EE) would be sufficient to modulate upregulated neuroinflammation in high-anxiety HABs. We show for the first time that EE can indeed attenuate enhanced trait anxiety, even when presented as late as adulthood. We further found that EE-induced anxiolysis was associated with the attenuation of enhanced microglial density (using Iba-1 as the marker) in the DG and medial prefrontal cortex. Additionally, EE reduced Iba1 + CD68+ microglia density within the anterior DG. Hence, the successful attenuation of trait anxiety by EE was associated in part with the normalization of neuro-inflammatory imbalances. These results suggest that pharmacological and/or positive behavioral therapies triggering microglia-targeted anti-inflammatory effects could be promising as novel alternatives or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals predisposed to trait anxiety.

Stress-mediated hyperactivity and anhedonia resistant to diazepam and fluoxetine in drosophila.

Distresses may induce behavioral phenotypes constituting heuristic models for psychopharmacology studies. In several species, including Drosophila, antidepressants counteract stress-induced phenotypes allowing the use of these models to test new psychoactive drugs. Here, we developed a novel and time-efficient protocol to provoke stress-induced phenotypes in Drosophila for the study of psychopharmacological agents. In the first experiment, flies (n = 12/groups) were exposed to a random-sequence of different types of stresses during nearly 24 h (including social isolation, fasting, heat, and electric shock), a protocol named short-term variable stress (SVS). Second, flies were exposed to a single stressful stimulus (social isolation, fasting, heat shock or electric shock, n = 12/groups). Next, flies submitted to SVS protocol were treated with vehicle, diazepam or fluoxetine (n = 12/groups). At the end of the stress protocols, behavioral phenotypes were evaluated in the open field (OF) and sucrose preference tests. In comparison to the unstressed group, flies exposed to SVS exhibited hyperactivity, as well as shorter times exploring the boundaries of the OF. In contrast to fasting stress, SVS reduced sucrose preference in flies. By analyzing the effects of individual stimuli on fly behavior, fasting and electric shock appear to be the predominant influences on the SVS-induced behaviors. Although fluoxetine or diazepam reduced the initial locomotor activity of flies, no treatment prevented the sequelae of SVS. Altogether, this study provides a time-efficient model system for the study of stress-mediated hyperactivity and anhedonia-like state resistant to fluoxetine and diazepam. The applications of SVS in Drosophila to preclinical psychopharmacology require further studies. LAY SUMMARY Exposition to unpredictable stress plays a significant role in psychiatric disorder's onset. Behavioral traits of these disorders can be partially modeled in rodents aimed at developing psychopharmacological therapies. However, studies in rodents were questioned by ethical issues. Focused on 3Rs principles, we developed a preclinical model for stress and psychopharmacology research in Drosophila. Variable stress induced behavioral alterations, including hyperlocomotion and reduced preference for sucrose in flies. However, behavioral alterations were resistant to fluoxetine and diazepam.

Relationship between administrative characteristics of long-term care institutions and use of antipsychotics and anxiolytics in residents with cognitive impairment.

OBJECTIVES: To identify the facility characteristics that are associated with prescribing practices of typical and atypical antipsychotics, and anxiolytics in residents with cognitive impairment in long-term care (LTC) institutions. METHODS: A cross-sectional analysis of a country-representative sample of 23 LTC institutions in Poland was conducted in 2015-2016. Trained staff from each facility used the InterRAI-LTCF tool and drug dispensary cards on the day of resident's assessment to collect data on medication use from 455 residents with cognitive impairment. We used the anatomical therapeutic chemical classification and a multiple correspondence analysis. RESULTS: We identified facility characteristics associated with higher rate of prescribing of: typical antipsychotics (nursing home, private ownership status, higher staff/bed ratio of physicians and nurses, and lower as refers to care assistants); atypical antipsychotics (residential home, public ownership status, higher staff/bed ratio of care assistants, and lower as refers to physicians); and anxiolytics (residential home, facilities of small size, public ownership status, higher staff/bed ratio of care assistants, lower of nurses and physicians). In the facilities where less residents received typical antipsychotics, anxiolytics were prescribed more often, and vice versa (rho = -0.442; p = 0.035). CONCLUSION: This study showed a considerable variation in the use of typical and atypical antipsychotics, and anxiolytics between nursing and residential homes, which was associated with their organization (type, size, ownership status, and employment rate). We found a negative correlation between prescribing typical antipsychotics and anxiolytics, which made us aware that these medications may be used interchangeably in LTC facilities, despite the fact that both should be avoided.

Does cognitive behavioral therapy for anxiety disorders assist the discontinuation of benzodiazepines among patients with anxiety disorders? A systematic review and meta-analysis.

Long-term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta-analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta-analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.

Tualang Honey: A Decade of Neurological Research.

Tualang honey has been shown to protect against neurodegeneration, leading to improved memory/learning as well as mood. In addition, studies have also demonstrated its anti-inflammatory and antioxidant properties. However, a substantial part of this research lacks systematization, and there seems to be a tendency to start anew with every study. This review presents a decade of research on Tualang honey with a particular interest in the underlying mechanisms related to its effects on the central nervous system. A total of 28 original articles published between 2011 and 2020 addressing the central nervous system (CNS) effects of Tualang honey were analysed. We identified five main categories, namely nootropic, antinociceptive, stress-relieving, antidepressant, and anxiolytic effects of Tualang honey, and proposed the underlying mechanisms. The findings from this review may potentially be beneficial towards developing new therapeutic roles for Tualang honey and help in determining how best to benefit from this brain supplement.

Hypnotic prescription by GPs is associated with their personal drug consumption but not by their insomnia status.

French general practitioners (GPs) are known to widely prescribe medications to treat insomnia despite their negative effects. GPs' easy access to self-medication may affect their mental representation of sleep and hypnotics, and subsequently their professional behaviour. Our aim was to examine the association between GPs' personal hypnotic drug consumption habits and their management of patients with sleep disturbances. A randomized sample of Alsatian GPs participated in a survey based on questionnaires including the Pittsburgh Sleep Quality Index, the Dysfunctional Beliefs About Sleep in 10 questions to characterize sleep, and an evaluation of their management strategies regarding sleep for both patients and themselves. Two-hundred and forty-nine GPs were included (response rate of 51%). Demographics of the GPs' samples were representative of those of the Alsatian GP population. Fifteen percent of the survey respondents met insomnia criteria. For the management of their own sleep disturbances, 14.3% of GPs were taking hypnotic drugs and 8.7% were taking anxiolytics, with greater drug consumption in the insomnia group. In a multivariate analysis, GPs who personally consumed these medications prescribed significantly more of them to patients, whereas their insomnia status had less impact. Other factors such as gender and type of practice were not associated with a higher prescription rate. Our results indicate that GPs' personal drug consumption can have a significant impact on the management of their patients, therefore suggesting that actions towards GPs' health improvement may also benefit their patients and the public.

The ethanolic extract obtained from Campomanesia pubescens (D.C.) O.BERG fruits exerts anxiolytic and antidepressant effects on chronic mild stress model and on anxiety models in Wistar rats: Behavioral evidences.

Objectives: Campomanesia pubescens (DC) O.BERG (Myrtaceae) fruits contain high levels of flavonoids and are widely consumed by the South American population. In the central nervous system (CNS), some flavonoids act as modulators of GABA-A receptors and monoamine oxidase inhibitors, resulting in anxiolytic antidepressants effects, respectively. The objective of the present study was to evaluate the anxiolytic and antidepressant effects of ethanolic extract of C. pubescens fruits (EEFCP) in rats.Methods: In order to prove the antidepressant effect of the EEFCP, rats were submitted to the chronic mild stress model, to the sucrose preference test (SPT), and the forced swimming test. To test the anxiolytic effects, the Elevated plus-maze (EPM), open field (OF), and Marble-Burying models were used.Results: After 2 weeks of treatment, imipramine 25 mg/kg, EEFCP 250 mg/kg, and EEFCP 500 mg/kg reversed the anhedonic behavior measured by SPT and significantly reduced the immobility time of animals under stress. In addition, treatment with diazepam 2 mg/kg, EEFCP 250 mg/kg, and EEFCP 500 mg/kg increased the percentage of entries and time spent on the open arms of the EPM, increased locomotion, rearing, and reduced the grooming time in OF.Discussion: The chemical analysis of the EEFCP indicated high content of flavonoids and the behavioral analysis revealed an antidepressant and anxiolytic effect, suggesting that these phytochemicals may be involved with these actions in the CNS.