Evaluation of repeated dosing of a dexmedetomidine oromucosal gel for treatment of noise aversion in dogs over a series of noise events.

BACKGROUND: Noise aversion is a common behavioural disorder in dogs; affected dogs show fear behaviours in response to noise stimuli. Pharmacological treatment is effective for many dogs; clinical reports suggest anxiolytic treatment lowers the need for treatment over time. We aimed to evaluate the effect of dexmedetomidine oromucosal gel for dogs with noise aversion over a series of noise events. Furthermore, we evaluated burden of care for owners of dogs with noise aversion via questionnaire. METHODS: Owners of enrolled dogs completed records for 10 noise events indicating whether their dog received dexmedetomidine gel and pretreatment and post-treatment anxiety scores; adverse events were noted. Owners were queried about burden of care. RESULTS: Twenty-two client-owned dogs completed recordings for 10 events. Logistic regression results showed a significant effect for time of event with decreased probability of receiving treatment for subsequent events (OR=0.75, P=0.0017). Within an event, significant improvement in anxiety was seen (median improvement 11 points; paired Wilcoxon; P<0.0001). We found overall burden of care was manageable, yet many owners agreed with statements regarding frustration (42 per cent), stress (46 per cent), guilt (42 per cent) and sadness (75 per cent) about their dog's condition. CONCLUSIONS: Repeated use of dexmedetomidine gel for noise events resulted in decreased need for administration. Burden of care is important to discuss with clients.

A Novel Study Design Using Continuous Intravenous and Intraduodenal Infusions of Midazolam and Voriconazole for Mechanistic Quantitative Assessment of Hepatic and Intestinal CYP3A Inhibition.

The extent of a drug-drug interaction (DDI) mediated by cytochrome P450 (CYP) 3A inhibitors is highly variable during a dosing interval, as it depends on the temporal course of victim and perpetrator drug concentrations at intestinal and hepatic CYP3A expression sites. Capturing the time course of inhibition is therefore difficult using standard DDI studies assessing changes in area under the curve; thus, a novel design was developed. In a 4-period changeover pilot study, 6 healthy men received intraduodenal or intravenous infusions of the CYP3A substrate midazolam (MDZ) at a rate of 0.26 mg/h for 24 hours. This was combined with intraduodenal or intravenous infusion of the CYP3A inhibitor voriconazole (VRZ), administered at rates of 7.5 mg/h from 8 to 16 hours and of 15 mg/h from 16 to 24 hours, after starting midazolam administration. Plasma and urine concentrations of VRZ, MDZ, and its major metabolites were quantified by liquid chromatography-tandem mass spectrometry and analyzed by semiphysiological population pharmacokinetic nonlinear mixed-effects modeling. A model including mechanism-based inactivation of the metabolizing enzymes (maximum inactivation rate constant kinact , 2.83 h-1 ; dissociation rate constant KI , 9.33 µM) described the pharmacokinetics of VRZ well. By introducing competitive inhibition by VRZ on primary and secondary MDZ metabolism, concentration-time profiles, MDZ and its metabolites were captured appropriately. The model provides estimates of local concentrations of substrate and inhibitor at the major CYP3A expression sites and thus of the respective dynamic extent of inhibition. A combination of intravenous and intraduodenal infusions of inhibitors and substrates has the potential to provide a more accurate assessment of DDIs occurring in both gut wall and liver.

Sedative and Anxiolytic Activities of Opuntia ficus indica (L.) Mill.: An Experimental Assessment in Mice.

Ethnobotanical field surveys revealed the use of fruits of Opuntia ficus indica (L.) Mill. for treating diabetes, burns, bronchial asthma, constipation, kidney stones, and rheumatic pains and as a sedative in Turkish folk medicine. This study aimed to verify the efficacy of the fruits of O. ficus indica experimentally and to define components responsible for the activity using bioassay-guided procedures. The crude methanolic extract of the fruits was sequentially fractionated into five subextracts: n-hexane, dichloromethane, ethyl acetate, n-butanol, and water. Further experiments were carried out on the most active subextract, that is, the ethyl acetate (EtOAc) subextract, which was further subjected to fractionation through successive column chromatographic applications on Sephadex LH-20. For activity assessment, each extract or fraction was submitted to bioassay systems; traction test, fireplace test, hole-board test, elevated plus-maze test, and open-field test were used for sedative and anxiolytic effects, and a thiopental-induced sleeping test was used for the hypnotic effect. Among the subextracts obtained from the methanolic extract, the EtOAc subextract showed significant sedative and anxiolytic effects in the bioassay systems. From the EtOAc subextract, major components were isolated, and their structures were determined as isorhamnetin, isorhamnetin 3-O-glucoside, isorhamnetin 3-O-rutinoside, and kaempferol 3-O-rutinoside using spectral techniques. In conclusion, this study confirmed the claimed use of the plant against anxiety in Turkish folk medicine.

Association between immigration status and anxiety, depression, and use of anxiolytic and antidepressant medications in the Hispanic Community Health Study/Study of Latinos.

PURPOSE: The purpose of this study was to investigate the association between undocumented immigration status and anxiety, depression, and use of anxiolytic or antidepressant medications in the Hispanic Community Health Study/Study of Latinos. METHODS: Cross-sectional analysis of data collected between 2014 and 2017. Participants were categorized as U.S.-born citizens, naturalized citizens, documented noncitizens, or undocumented noncitizens. We calculated prevalence and prevalence ratios for anxiety, depression, and use of anxiolytic or antidepressant medication, by immigration status. RESULTS: Of 9257 participants, 1403 (15%) were undocumented noncitizens, 2872 (31%) were documented noncitizens, 3766 (41%) were naturalized citizens, and 1216 (13%) were U.S.-born citizens. Prevalence of anxiety was lower among undocumented than documented noncitizens (9 vs. 15%, P < .0001) but not significantly different in adjusted analyses. Prevalence of depression was similar among undocumented and documented noncitizens (20 vs. 24%, P = .07) and not significantly different in adjusted analyses. Among participants with depression, 7% of undocumented and 27% of documented noncitizens reported use of antidepressants (adjusted prevalence ratio 0.49, 95% CI 0.27-0.87). CONCLUSIONS: Undocumented noncitizens had similar likelihood of anxiety and depression, but lower likelihood of antidepressant use, compared with documented noncitizens. These results may reflect the resilience of an undocumented population facing multiple stressors but suggest that this group may be undertreated for depression.

Adultification of Black Children in Pediatric Anesthesia.

BACKGROUND: Unconscious racial bias in anesthesia care has been shown to exist. We hypothesized that black children may undergo inhalation induction less often, receive less support from child life, have fewer opportunities to have a family member present for induction, and receive premedication with oral midazolam less often. METHODS: We retrospectively collected data on those <18 years of age from January 1, 2012 to January 1, 2018 including age, sex, race, height, weight, American Society of Anesthesiologists (ASA) physical status, surgical service, and deidentified anesthesiology attending physician. Outcome data included mask versus intravenous induction, midazolam premedication, child life consultation, and family member presence. Racial differences between all outcomes were assessed in the cohort using a multivariable logistic regression model. RESULTS: A total of 33,717 Caucasian and 3901 black children were eligible for the study. For the primary outcome, black children 10-14 years were 1.3 times more likely than Caucasian children to receive mask induction (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.1-1.6; P = .001). Child life consultation was poorly documented (<0.5%) and not analyzed. Black children <15 years of age were at least 31% less likely than Caucasians to have a family member present for induction (AOR range, 0.4-0.6; 95% CI range, 0.31-0.84; P < .010). Black children <5 years of age were 13% less likely than Caucasians to have midazolam given preoperatively (AOR, 0.9; 95% CI, 0.8-0.9; P = .012). CONCLUSIONS: This study suggests that disparities in strategies for mitigating anxiety in the peri-induction period exist and adultification may be 1 cause for this bias. Black children 10 to 14 years of age are 1.3 times as likely as their Caucasian peers to be offered inhalation induction to reduce anxiety. However, black children are less likely to receive premedication with midazolam in the perioperative period or to have family members present at induction. The cause of this difference is unclear, and further prospective studies are needed to fully understand this difference.

Efficacy and cost savings with the use of a minimal sedation / anxiolysis protocol for intra-articular corticosteroid injections in children with juvenile idiopathic arthritis: a retrospective review of prospectively collected data.

BACKGROUND: Intra-articular corticosteroid injections (IACI) are frequently used in the treatment of juvenile idiopathic arthritis. There is a paucity of evidence-based research describing methods of pain and anxiety control for this procedure. IACI were mostly performed under general anesthesia for children younger than 13 years old in our institution as of 2014. We started to integrate sedation services more commonly in our institution with the minimal sedation/anxiolysis (MSA) protocol outlined as an alternative to general anesthesia for IACI in 2015. The purpose of this study was to evaluate the effectiveness and cost savings of a minimal sedation protocol for intra-articular corticosteroid injections in juvenile idiopathic arthritis patients after instituting this protocol at our institution. METHODS: The MSA protocol included nitrous oxide, intranasal fentanyl, a topical numbing agent, acetaminophen, ibuprofen, ondansetron and child life intervention. A retrospective review of prospectively collected data was performed on a total of 80 consecutive patients with juvenile idiopathic arthritis who underwent joint injections using the protocol. RESULTS: The procedure was successfully completed in greater than 95% of the patients. The median pain score (measured on a verbal numeric scale of 0-10) reported by the patient was 1 (IQR 0-2.5), by the parent 1 (IQR 0-2), by the rheumatologist 1 (IQR 0-1), and by the sedationist 1 (IQR 0-1). Degree of motion during the procedure was reported by the rheumatologist and the sedationist as none in 68% of the patients, mild in 36% and moderate in 6%. Patient, parent, rheumatologist and sedationist rated satisfaction as very high in the vast majority (94%). Emesis was reported in only 2 (2.5%) patients, no significant adverse events were reported, and no patients progressed to a deeper level of sedation than intended. Financial analysis revealed a 33% cost reduction compared with the use of general anesthesia in the operating room. CONCLUSIONS: A minimal sedation/anxiolysis protocol (including nitrous oxide, intranasal fentanyl, a topical numbing agent, acetaminophen, ibuprofen, ondansetron and child life intervention), provides safe and effective analgesia for intra-articular corticosteroid injection in a subset of patients with juvenile idiopathic arthritis and offers a lower cost alternative to general anesthesia.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. Method: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. Results: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. Conclusion: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

Using anxiolytics in a pediatric otolaryngology clinic to avoid the operating room.

INTRODUCTION: There is increasing concern regarding the risks associated with the use of general anesthesia in pediatric patients. Many otolaryngologic procedures performed under general anesthesia can also be performed in clinic. We hypothesize that anxiolytics can aid in performing common procedures in clinic thus avoiding the need to undergo general anesthesia in the OR. METHODS: We performed a retrospective review of patients undergoing inoffice procedures with anxiolytics in our pediatric otolaryngology outpatient clinic between February 2013 and January 2017. Charts were reviewed for age, past medical history, procedure type/duration, and outcome. These results were then compared to a cohort undergoing similar procedures in the OR. RESULTS: A total of 34 patients underwent an in-office procedure with an anxiolytic. The success rate was 97% (33/34). The average age was 6.2 years. Six children (17%) had a known history of chromosomal abnormalities and 2 children (6%) had autism. The four most common procedures performed were cerumen impaction removal (8), flexible laryngoscopy (6), ear canal foreign body removal (5), and septal cautery (4). Performing similar procedures in the OR resulted in an average additional cost of $822. CONCLUSIONS: Performing procedures with anxiolytics in a pediatric otolaryngology clinic is safe, expeditious, and cost-effective. Anxiolytics can provide an effective alternative to general anesthesia.

Activation of Anxiogenic Circuits Instigates Resistance to Diet-Induced Obesity via Increased Energy Expenditure.

Anxiety disorders are associated with body weight changes in humans. However, the mechanisms underlying anxiety-induced weight changes remain poorly understood. Using Emx1Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some amygdalar subregions. The resulting mutant mice displayed impaired GABAergic transmission and elevated anxiety. They were leaner when fed either a chow diet or a high-fat diet, owing to higher sympathetic activity, basal metabolic rate, brown adipocyte thermogenesis, and beige adipocyte formation, compared to control mice. BDNF re-expression in the amygdala rescued the anxiety and metabolic phenotypes in mutant mice. Conversely, anxiety induced by amygdala-specific Bdnf deletion or administration of an inverse GABAA receptor agonist increased energy expenditure. These results reveal that increased activities in anxiogenic circuits can reduce body weight by promoting adaptive thermogenesis and basal metabolism via the sympathetic nervous system and suggest that amygdalar GABAergic neurons are a link between anxiety and metabolic dysfunction.

A study of the reasons for prescribing and misuse of gabapentinoids in prison including their co-prescription with opioids and antidepressants.

PURPOSE: Electronic medical case files of male prisoners in a category B prison in London were studied to establish a prevalence during an eight-month period of the use of and the reasons for prescribing gabapentinoids in prison and also to establish prescribing standards in prison and compliance with these. In addition, the prevalence of co-prescription of gabapentinoids with opioids and antidepressants, particularly tricyclic antidepressants such as amitriptyline, was also assessed in light of the increased risk of respiratory depression resulting in death when these drugs are used in combination. The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: A retrospective, SystmOne case-file based survey was undertaken searching by SNOMED CT supplemented by examination of free text, in a category B prison for males (Capacity 1,500 prisoners; Average turnover of prisoners up to 6,000 per year), to establish practice standards related to the prescription of Gabapentinoids in the prison and determine compliance with these. FINDINGS: In total, 109 cases were identified of prisoners having been prescribed gabapentinoids, pregabalin in 66 cases (61 per cent) and gabapentin in 43 cases (39 per cent). In 36 cases (33 per cent) prescriptions were for unlicensed indications. This in fact represented 50 per cent of the cases where the indications were documented. In 51 cases (47 per cent) gabapentinoids were prescribed with an opioid substitute. In 14 cases (13 per cent), prescribed gabapentinoids were diverted to other prisoners. PRACTICAL IMPLICATIONS: The initiation of gabapentinoids in prison should be avoided. For prisoners who are also receiving opioid substitutes or are abusing opiates, it may be unsafe to continue on gabapentinoids. Issues raised by this study are likely to apply to other prisons, secure forensic psychiatric facilities and indeed community mental health and primary care as well. SOCIAL IMPLICATIONS: Risk of dependance on gabapentinoids including risk of mortality when taken with opioids and opioid substitutes. ORIGINALITY/VALUE: This is an original study conducted at a category B prison in London.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.

OBJECTIVE: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. METHOD: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. RESULTS: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. CONCLUSION: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

Consequences on economic outcomes of generic versus brand-name drugs used in routine clinical practice: the case of treating peripheral neuropathic pain or generalized anxiety disorder with pregabalin.

BACKGROUND: Discrepancies are seen between arguments in favor of and against prescribing generic versus brand-name drugs. OBJECTIVE: To provide real-world evidence on treatment persistence, economic and clinical outcomes of pregabalin, generic versus brand-name (Lyrica®, Pfizer), routinely used to treat neuropathic pain (NP) or generalized anxiety disorder (GAD). METHODS: Electronic medical records from subjects' first starting treatment with pregabalin between January-2015 and June-2016 were analyzed. Persistence, resources utilization, and costs were assessed, along with remitter and responder rates. RESULTS: A total of 4860 records were analyzed. Discontinuation was lower with brand-name than with generic in NP (adjusted hazard ratio [HR]: 0.70 [95% CI: 0.58-0.85], p < 0.001) and GAD patients (HR: 0.63 [0.45-0.84], p < 0.001). Adjusted mean total costs were lower with brand-name: €1500 [1428-1573] vs. €2003 [1864-2143] in NP and €1528 [1322-1734] vs. €2150 [1845-2454] in GAD (both p < 0.001). More patients were remitters/ responders with brand-name in NP (55.0% vs. 46.7% and 59.2% vs. 48.4%, respectively; p < 0.001) and GAD (58.6% vs. 48.7% and 64.6% vs. 47.2%, respectively; p < 0.001). CONCLUSIONS: As a consequence of higher persistence in routine practice, patients who first started therapy with pregabalin brand-name versus generic showed better pain or anxiety outcomes at a lower cost to payers in Spain.

Continuity of treatment with benzodiazepines in dementia patients: an analysis of German health insurance claims data.

Long-term treatment with benzodiazepines (BZD) should be avoided in dementia patients because of an increased risk of adverse events. We evaluated how continuously dementia patients were prescribed BZD over 12 months. For this observational study, we used claims data from a large German public sickness fund for 2014 and 2015, including patients with an incident diagnosis of dementia in 2014. The aim was to evaluate the continuity of treatment, the frequency of BZD prescriptions and defined daily doses were evaluated. In total, 1298 (5.6%) patients received 4.7±5.2 BZD prescriptions in 2015 on average. Thereof, lorazepam (47.5%), oxazepam (18.6%), diazepam (14.5%), and bromazepam (12.2%) were most often prescribed. 30.7% of the patients received at least one BZD prescription in each quarter of 2015. Although the total number of patients receiving BZD decreased in 2015, defined daily doses for single substances remained mainly unchanged. The incident diagnosis of dementia was not associated with modifications of prescription behavior. The treatment with BZD was not discontinued in a large proportion of dementia patients, increasing the risk of adverse events. Physicians' awareness of avoiding BZD should be improved and further evidence for the appropriate treatment of psychiatric symptoms in dementia (e.g. sleep disturbances, anxiety) is required.

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study.

BACKGROUND: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. METHODS: Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003-2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ2 tests examined associations between individual pain severity and opioid prescriptions. RESULTS: The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25-40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. CONCLUSIONS: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common.

The Effect of False-positive Mammograms on Antidepressant and Anxiolytic Initiation.

BACKGROUND: Despite reported increases in anxiety following a false-positive mammogram, there is little evidence the effect rises to the clinical level of initiating medication. OBJECTIVE: To analyze the effect of a false-positive mammogram on antidepressant or anxiolytic initiation and identify subpopulations most at risk. SUBJECTS: MarketScan commercial and Medicaid claims databases used to identify women ages 40-64 undergoing screening mammography with no prior antidepressant or anxiolytic claims. RESEARCH DESIGN: Using a retrospective cohort design, we estimated the effects of a false-positive relative to a negative mammogram on the likelihood of initiating antidepressants or anxiolytics using multivariate logistic models estimated separately by insurance type. RESULTS: At 3 months after a false-positive mammogram, the relative risk (RR) for antidepressant or anxiolytic initiation was 1.19 [95% confidence interval (CI), 1.06-1.31] for the commercially insured and 1.13 (95% CI, 0.96-1.29) in the Medicaid population. In addition, 4 subgroups were at particularly elevated risk: commercially insured women ages 40-49 (RR=1.33; 95% CI, 1.13-1.54) or whose false-positive required multiple tests to resolve (RR=1.37; 95% CI, 1.17-1.57), included a biopsy (RR=1.68; 95% CI, 1.18-2.17), or whose resolution took >1 week (RR=1.21; 95% CI, 1.07-1.34). CONCLUSIONS: False-positive mammograms were associated with significant increases in antidepressant or anxiolytic imitation among the commercially insured. Follow-up resources may be particularly beneficial for cases taking longer to resolve and involving biopsies or multiple tests. The results highlight the need to resolve false-positives quickly and effectively and to monitor depressive symptoms following a positive result.

Prevalence and correlates of coprescribing anxiolytic medications with extensive prescription opioid use in Veterans Health Administration patients with metastatic cancer.

OBJECTIVE: To examine the prevalence and correlates of concomitant anxiolytic prescription fills in Veterans Health Administration (VHA) patients with metastatic cancer who have extensive prescription opioid use. DESIGN, SETTING, AND PARTICIPANTS: National VHA data for fiscal year 2012 were used to identify veterans diagnosed with metastatic cancer (ICD-9 codes 196-199) who also had extensive prescription opioid use (at least 10 opioid prescriptions during the year, comprising the highest 29 percent of opioid users). Bivariate and multivariate analyses were used to examine correlates of receiving anxiolytic medication among veterans with metastatic cancer and extensive prescription opioid use. RESULTS: Of the 5,950 veterans with metastatic cancer and extensive prescription opioid use, 51 percent also received anxiolytic medication, of whom 64 percent had a medical indication and 85 percent had a psychiatric or medical indication for psychotropics. Of those with extensive prescription opioid use who filled an anxiolytic, 64 percent also received antidepressants and 38 percent received three or more classes of psychotropic medication (ie, polypharmacy). In multivariate analyses, factors associated with receipt of an anxiolytic included any anxiety disorder, insomnia, the prescription of antidepressants or antipsychotics, bipolar disorder, younger age, more emergency department visits, and greater number of opioid prescriptions. CONCLUSIONS: VHA patients with metastatic cancer and extensive prescription opioid use who are prescribed anxiolytics are likely to have a Food and Drug Administration-approved indication for psychotropics, and anxiolytics in particular, but represent a clinically vulnerable group which merits careful monitoring.

Predicting chronic benzodiazepine use in adults with depressive disorder: Retrospective cohort study using administrative data in Quebec.

OBJECTIVE: To identify predictive variables of incident chronic benzodiazepine (BZD) use that could be assessed by prescribing physicians. DESIGN: Retrospective cohort study using public health and drug insurance administrative data. SETTING: Quebec. PARTICIPANTS: New adult BZD users from January 1, 1999, to March 31, 2006, with a diagnosis of depressive disorder in the previous year were included. Chronic BZD use was defined as BZD availability at least 50% of the days between day 181 and day 365 following initiation. MAIN OUTCOME MEASURES: Potential associations between chronic BZD use and age; sex; drug insurance status; recent hospitalization; comorbidity; presence of chronic pain; use of psychotropic medication; mental health diagnoses; number, type, and duration of BZDs prescribed; and the prescribing physician's specialty. RESULTS: Selection led to an exhaustive cohort of 13 688 patients aged 18 to 64 years, and 3683 aged 65 and older. For the 18 to 64 age group, the combination of disability insurance and more than 1 BZD increased the proportion of chronic users from 14.4% to 53.4%. For patients 65 and older, the main correlates of chronic BZD use included claiming more than 1 BZD (adjusted odds ratio 2.24, 99% CI 1.65 to 3.06) and recent hospitalization (adjusted odds ratio 1.70, 99% CI 1.38 to 2.10). Recently hospitalized older patients with a prescription duration of less than 8 days were the highest-risk group identified (57.8%). CONCLUSION: Physicians should be aware that patients are more likely to become chronic BZD users if they receive disability insurance or following a hospitalization. Combination of BZDs is a potentially problematic practice that could be increasing the risk of chronic use.

[Effect of the economic crisis on consumption of psychotropic drugs in Asturias (Spain)]. / Efecto de la crisis económica sobre el consumo de psicofármacos en Asturias.

OBJECTIVE: To assess whether the economic crisis of 2008 has changed the consumption of anxiolytics, hypnotics-sedatives and antidepressants in Asturias (Spain). METHOD: We conducted a descriptive study of drug use from 2003 -2013. The defined daily doses of 1000 inhabitants per day (DHD) were calculated for anxiolytics, hypnotics-sedatives and antidepressants. Linear regression coefficients (b) of the DHD were obtained for the pre-crisis period (2003-2008) and the crisis period (2009-2013). RESULTS: The consumption of anxiolytics increased by 40.25%, that of hypnotics by 88.11% and that of antidepressants by 80.93%. For anxiolytics: b-(2003-2008)=4.38 DDI/year and b-(2009-2013)=1.08 DDI/year. For hypnotics-sedatives: b-(2003-2008)=2.30 DDI/year and b-(2009-2013)=0.40 DDI/year. For antidepressants: b-(2003-2008)=5.79 DDI/year and b-(2009-2013)=2.83 DDI/year. CONCLUSIONS: The rise in consumption of the three subgroups during the crisis period was lower than that of the pre-crisis period. This study does not confirm the influence of the economic crisis on the rise in consumption of these drugs.

Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior.

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine (2.5 and 5 mg/kg), and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg). Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg) and morphine (5 mg/kg), but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg) but not pregabalin (30 mg/kg) increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents.