Diazepam Equivalents Research Articles

Characteristics of high-dose benzodiazepine use: nationwide cohort study on new benzodiazepine users with 5-year follow-up.

A nationwide register-based cohort study from Finland including 48 124 incident benzodiazepines and related drug (BZDR) users aged 18-65 years who initiated use in 2006 and were not dispensed BZDRs during 2004-2005. The follow-up was 5 years or until death, whichever occurred first. To investigate sociodemographic and clinical factors associated with high-dose use of BZDRs (i.e. Z-drugs) among new BZDR users. The temporal BZDR dose was calculated as a point estimate every 6 months after initiation as defined daily doses (DDDs) per day, based on the PRE2DUP method (an approach based on mathematical modelling of personal drug purchasing behaviours). Sociodemographic and clinical factors associated with dose categories were studied using multinomial logistic regression. During the 5-year follow-up, very high-dose BZDR use was observed in 7.4% (n = 3557) and medium high-dose use in 25.5% (n = 12 266) of the users (corresponding to ≥30 mg and 10-29 mg in diazepam equivalents, respectively). Very high-dose use was more common among men compared with women (10.9% versus 4.6%). Very high-dose use patterns were especially observed in younger age groups (18- to 25-year-olds). Compared with oxazepam, initiating BZDR use with clonazepam (adjusted odds ratio 3.86, 95% CI 3.24-4.60), diazepam (2.05, 1.78-2.36) or alprazolam (1.76, 1.52-2.03) was associated with increased odds for very high-dose use. Both medium high-dose and very high-dose BZDR use were associated with a lower level of education. In all, 58% of very high-dose use occurred in BZDR users who received their first prescription from general practitioners. Clinicians should be aware of the dose escalation risk especially when prescribing diazepam, alprazolam or clonazepam for psychiatric indications. If BZDRs are needed, our findings suggest favouring oxazepam.

The effect of lemborexant on insomnia in patients with psychiatric disorders: Detailed evaluation using the Athens Insomnia Scale.

Chronic insomnia disorder is common and associated with reduced quality of life. Benzodiazepine hypnotics are commonly prescribed for insomnia, but have potential side effects such as concentration impairment, somnolence, and dependence. Lemborexant (LEM) is an orexin receptor antagonist considered to have fewer side effects than benzodiazepine hypnotics. This study evaluated the effect of LEM on sleep in detail and examined whether benzodiazepine hypnotics can be gradually tapered by adding LEM. We retrospectively examined the effectiveness of LEM in 28 outpatients with insomnia. Insomnia symptoms were assessed using the Athens Insomnia Scale (AIS) before and after LEM administration. We also attempted to taper benzodiazepine hypnotics and assessed benzodiazepine dose using diazepam equivalents for some patients taking benzodiazepine hypnotics. Wilcoxon's signed-rank test was used for statistical analysis. The mean AIS score was significantly improved after LEM treatment (8.7 ± 5.2 vs. 3.8 ± 3.3; P < 0.01). Among the AIS subitems, significant improvement was observed for six items: sleep induction, awakenings during the night, sleep quality, well-being, functioning capacity, and sleepiness during the day. The mean benzodiazepine dose was significantly lower after LEM treatment (4.6 ± 5.0 mg vs. 2.1 ± 3.3 mg; P < 0.01). This study indicated the potential of LEM for improving insomnia and reducing benzodiazepine dose.

Changing prescribing practice for rapid tranquillization-a quality improvement project based on the Plan-Do-Study-Act method.

It is unclear how the evidence from clinical trials best translates into complex clinical settings. The aim of this quality improvement (QI) project was to change prescribing practice for rapid tranquillization in inpatient mental health care services examining the effectiveness of the Plan-Do-Study-Act (PDSA) method. A prospective QI project was conducted to ensure that intramuscular (IM) diazepam was substituted with IM lorazepam for benzodiazepine rapid tranquillization in inpatient mental health care. We monitored the prescription and administration of medication for rapid tranquillization before (N = 371), during (N = 1130) and after (N = 364) the QI intervention. Seven iterative PDSA cycles with a multiple-component intervention approach were conducted to gradually turn the prescribing practice in the desired direction. Simultaneously, a standard monitoring regimen was introduced to ensure patient safety. Lorazepam administrations gradually replaced diazepam during the intervention period which was sustained post-intervention where lorazepam comprised 96% of benzodiazepine administrations for rapid tranquillization. The mean dose of benzodiazepine administered remained stable from pre (14.40mg diazepam equivalents) to post (14.61mg) intervention phase. Close to full compliance (> 80%) with vital signs monitoring was achieved by the end of the observation period. It was possible to increase the quality of treatment of acute agitation in a large inpatient mental health care setting using a stepwise approach based on iterative PDSA cycles and continuous data feedback. This approach might be valuable in other prescribing practice scenarios with feedback from local stakeholders and opinion leaders.

A double-blind randomised crossover trial of low-dose flumazenil for benzodiazepine withdrawal: A proof of concept

IntroductionBenzodiazepines (BZD) are a class of anxiolytics with varying uses, which primarily act on the GABAA receptor resulting in hyperpolarisation. BZDs are often a difficult drug class to cease once neuroadaptation has occurred; recommendations usually involve gradual dose reductions at variable rates. A growing body of evidence has suggested that low-dose flumazenil, a GABAA receptor antagonist, may be a useful agent to allow for rapid detoxification. AimTo collect pilot data on the safety and efficacy of low-dose subcutaneous flumazenil to reduce BZD use, withdrawal symptoms, and craving in participants taking above and below the therapeutic maximum diazepam equivalent of 30 mg to inform on sample size for future trials. MethodIn a randomised double-blinded crossover study design, participants received low-dose flumazenil first (4 mg/24 h for approximately eight days) or placebo first. Groups were divided into those taking < 30 mg diazepam equivalent and ≥ 30 mg diazepam equivalent at baseline. Main outcome measures were percentage reduction in daily diazepam use, withdrawal symptoms, and craving scores from baseline, difference in diazepam use across the placebo first group, and flumazenil related adverse events. ResultsTwenty-eight participants were recruited and randomised to flumazenil first (n = 14) and placebo first (n = 14). In participants taking ≥ 30 mg diazepam equivalent at baseline (n = 15), flumazenil significantly reduced diazepam use by 30.5% (p = 0.024) compared to placebo. ConclusionLow-dose flumazenil may aid in BZD detoxification in participants taking daily diazepam equivalent doses greater than or equal to the therapeutic maximum (≥30 mg) by reducing the need for diazepam.

Benzodiazepine Treatment and Hospital Course of Medical Inpatients With Alcohol Withdrawal Syndrome in the Veterans Health Administration

ObjectiveTo describe initial benzodiazepine dosing strategies and factors associated with variation in benzodiazepine dosing in a national cohort of hospitalized patients with alcohol withdrawal syndrome (AWS). Patients and MethodsThis cross-sectional study included adult patients with AWS admitted to medical services and treated with benzodiazepines at 93 Veterans Health Administration hospitals in 2013. Treatment was categorized by initial benzodiazepine dosing strategy—fixed-dose, symptom-triggered, or front-loading. Associations with patient characteristics, facility, and cumulative benzodiazepine exposure, intensive care, and intubation were evaluated. ResultsAmong 6938 medical inpatients with AWS, 2909 (41.9%), 2829 (40.8%), and 1200 (17.3%) received treatment with symptom-triggered, fixed-dose, and front-loading benzodiazepines, respectively. The magnitude of differences in initial treatment associated with patient characteristics was small compared with differences associated with the predominant practice at a facility. Compared with fixed-dose therapy, symptom-triggered therapy was associated with higher cumulative benzodiazepine exposure (mean, 208-mg vs 182-mg diazepam equivalents) and higher probability of intensive care and intubation (28.2% vs 21.3% and 4.8% vs 3.5%, respectively). ConclusionThis study revealed that real-world AWS treatment of medical inpatients was often inconsistent with published guidelines recommending symptom-triggered long-acting benzodiazepines for AWS. The facility where a patient was hospitalized was associated with marked treatment variation. In contrast to prior randomized controlled trials conducted in specialized detoxification units, hospitalized patients who received symptom-triggered therapy in this study had greater cumulative benzodiazepine exposure and higher probability of intensive care and intubation than those receiving fixed-dose therapy.

Comparative effectiveness of long-acting injectable antipsychotics in a large naturalistic cohort across two European centers: Findings from the long-acting injectable antipsychotics collaborative (LAICO) study.

We aimed to evaluate and compare the use of the paliperidone palmitate-1 and 3-month (PP1M, PP3M), aripiprazole 1-month (A1M) and risperidone-LAI (RLAI) LAIs, using the following clinical outcomes: (1) the number of hospital admissions, (2) the number of hospital bed days, and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics, and biperiden. For that purpose, we designed a cross-sectional study, from 2015 to 2021, based on non-institutionalized population accessing care from mental health services in Spain and UK who were prescribed with LAIs during 1 year. A total of 993 patients using a LAI were included. PP1M and PP3M LAIs were associated with a decreased risk of being prescribed benzodiazepines (OR ​= ​0.35, 95%CI ​= ​0.16–0.80, p ​= ​0.012; OR ​= ​0.16, 95%CI ​= ​0.07–0.38, p ​= ​0.001, respectively) and oral antipsychotics (OR ​= ​0.23, 95%CI ​= ​0.09–0.54, p ​= ​0.001; OR ​= ​0.28, 95%CI ​= ​0.11–0.67, p ​= ​0.005, respectively) compared with RLAI. A1M was also associated with a decreased risk (OR ​= ​0.29, 95%CI ​= ​0.12–0.69, p ​= ​0.005) of antipsychotic prescription compared with RLAI. Moreover, PP1M and PP3M groups were treated with lower diazepam equivalents doses compared to the A1M (p ​= ​0.021, p ​= ​0.026) and RLAI groups (p ​= ​0.036, p ​= ​0.039). Finally, PP3M was associated with lower hospital admissions and bed days compared with A1M (p ​= ​0.001; p ​= ​0.001) and RLAI (p ​= ​0.018; p ​= ​0.001). In conclusion, paliperidone LAIs had a more favourable impact on overall bed usage compared to A1M and RLAI. Furthermore, paliperidone LAIs and A1M lowered the use of concomitant psychiatric medication versus the biweekly LAIs while differences in combination and augmentation practices between cohorts are also highlighted. Our findings could be useful for clinicians and their practice.

Medicine reviews: do they reduce benzodiazepine use in older Australians?

Medicine reviews are an opportunity to identify and address inappropriate prescribing. The aim of this study was to explore changes in benzodiazepine use among older Australians following a medicine review. Retrospective observational cohort study using linked administrative data. We used Medicare Benefits Schedule and Pharmaceutical Benefits Scheme claims from a random 10% sample of Medicare beneficiaries. We identified people aged 65 years or older who received a medicine review in 2013-14 and were using benzodiazepines at the time of review. We identified a propensity score matched comparison cohort of those using benzodiazepines who did not receive a review. Two outcome measures were used: any benzodiazepine use and changes to the quantity of benzodiazepines dispensed (diazepam equivalents) from baseline to 90 and 180 days following a medicine review. We identified 4002 people using benzodiazepines on the day of their medicine review, of whom approximately one-third discontinued benzodiazepines within 90 days (29.7%) and 180 days (36.4%;) after the review. We observed a similar discontinuation rate in the comparison group (32.6%, p = 0.006; and 38.0%, p = 0.12, respectively). In people who were dispensed lower quantities of benzodiazepines (less than 250 mg of diazepam equivalents in the 90 days before the medicine review), we found that 50.3% ceased using benzodiazepines or used lower quantities (measured as diazepam equivalents) following the medicine review (28.7% and 19.7% respectively). We also observed a reduction in the quantities used in people where initial exposure was high (3.4% ceased; 59.4% decreased). We observed a similar change in volume within the matched comparison group. Medicine reviews are not associated with any additional reduction in benzodiazepine use among older adults, up to 180 days after review, beyond what was observed in the general population.

744 Correlates to improvement in sleep in acute mania

Abstract Introduction Sleep disruption and reduced sleep duration are potential triggers and also core symptoms of a manic episode. Our understanding of how sleep duration changes during the course of a manic episode and its potential association with symptom improvement is limited. We examined the natural course of sleep duration and its association with time to discharge and other clinical and demographic factors in patients with mania. Methods This was a retrospective study conducted in patients admitted to an acute care psychiatric unit with a manic episode. Sleep duration was determined based on observer report as logged by nursing staff. Sleep duration at admission and discharge were determined by averaging the total sleep time on day 2/3 of hospitalization and day 3/2 preceding discharge date. We obtained data on possible confounders including antipsychotic (chlorpromazine equivalents), benzodiazepine (diazepam equivalents) and other hypnotic medication doses administered at admission and discharge. We examined the associations between the change in sleep duration from admission to discharge with length of hospitalization and other clinical and demographic characteristics. Results The sample consisted of 35 patients (54.3% male) aged 32 ± 9.96 years with an average length of hospitalization of 20.63 ± 18.62 days. The mean sleep duration on admission was 6.23 ± 1.77 hours and was 7.45 ± 1.49 hours on discharge, with a mean change of 1.23 ± 1.93 hours. The change in sleep duration was positively correlated with length of hospitalization (r=0.42; p=0.01). Other clinical factors including benzodiazepine or antipsychotic dose on admission, age, sex, and use of mood stabilizers were not correlated with the change in sleep duration. Conclusion There was a substantial improvement in the total sleep duration in patients with mania over the course of hospitalization. Overall, the change in sleep duration was only correlated to the length of stay and did not appear to be impacted by other clinical and demographic characteristics. Support (if any):

Evaluation of long-acting injectable antipsychotics with the corresponding oral formulation in a cohort of patients with schizophrenia: a real-world study in Spain.

To date, only a few studies compared some long-acting injectables (LAIs) antipsychotics showing similar symptom improvement, relapse rates and adherence to treatment. We evaluated the use of LAIs antipsychotics [aripiprazole-1-month (A1M); paliperidone-1-month and 3-month (PP1M and PP3M) and biweekly (2w)-LAIs] and their corresponding oral formulations through (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviour/attempts and (3) the use of concomitant benzodiazepines, oral antipsychotics and biperiden. A total of 277 patients, ≥18 years old, were included if were treated with the corresponding oral or LAI antipsychotic during at least 12 months and were previously diagnosed with schizophrenia. Our results showed that LAIs associated significantly lower suicidal behaviour, reduced the number of hospital admissions, lower diazepam and haloperidol equivalents and mean daily dose of biperiden intake versus oral antipsychotics. Furthermore, significant differences were found between LAIs. Specifically, PP3M was associated to lower hospital admissions versus A1M; PP1M and PP3M lower doses of diazepam equivalents versus 2w-LAIs and finally, PP1M lower antipsychotic intake versus 2w-LAIs. In conclusion, LAIs improved clinical outcomes by reducing the need for concomitant treatments and hospital admissions over oral antipsychotics. PP1M and PP3M showed better outcomes versus A1M and biweekly LAIs.

Potentially addictive drugs dispensing to patients receiving opioid agonist therapy: a register-based prospective cohort study in Norway and Sweden from 2015 to 2017

ObjectivesTo compare the use of benzodiazepines, z-hypnotics, gabapentinoids, opioids and centrally acting stimulants (CAS) among patients who had received opioid agonist therapy (OAT) in Norway and Sweden during the period...

Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017

BackgroundDispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017.MethodsInformation about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models.ResultsHalf of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20–23) diazepam equivalents in 2013 to 17 mg (95% CI: 16–17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309–421) in 2013 to 386 mg (95% CI: 349–423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1–3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6–3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs.ConclusionThe dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.

Intubation for Psychogenic Non-Epileptic Attacks: Frequency, Risk Factors, and Impact on Outcome

PurposePatients with psychogenic non-epileptic attacks (PNEA) sometimes receive aggressive treatment leading to endotracheal intubation. We sought to identify the frequency, risk factors, and impact on outcome of intubation for PNEA. MethodsWe retrospectively reviewed all PNEA patients admitted via the emergency department (ED) who had an episode of PNEA documented by continuous video electroencephalography (vEEG) at Henry Ford Hospital between January 2012 and October 2017. Patients with comorbid epilepsy were excluded. Clinical features, treatments, and vEEG reports were compared between intubated and non-intubated patients. ResultsOf 80 patients who were admitted via the ED and had PNEA documented by vEEG, 12 (15%) were intubated. Compared with non-intubated PNEA patients, intubated patients had longer duration of convulsive symptoms (25 [IQR 7-53] vs 2 [IQR 1-9] minutes, P = 0.01), were less likely to have a normal Glasgow Coma Scale score of 15 (33% vs 94%, P < 0.001), received higher doses of benzodiazepines (30 [IQR 16-45] vs 10 [IQR 5-20] mg of diazepam equivalents, P = 0.004), and were treated with more antiepileptic drugs (AEDs, 2 [IQR 1-3] vs 1 [IQR 1-2], P = 0.01). Hospital length of stay was longer (3 [IQR 3-5] vs 2 [IQR 2-3], P = 0.001), and the rate of complications (25% vs 4%, P = 0.04) and re-hospitalization from a recurrent episode of PNEA within 30 days was higher among intubated PNEA patients (17% vs 0%, P = 0.02). ConclusionFifteen percent of patients hospitalized for vEEG-documented PNEA were intubated. Intubated patients had longer length of stay, more in-hospital complications, and a high rate of re-hospitalization from recurrent PNEA symptoms. Prolonged duration of convulsive symptoms, depressed level of consciousness, and aggressive treatment with benzodiazepines were associated with intubation for PNEA.

Benzodiazepine resistant alcohol withdrawal: What is the clinician's preferred definition?

Although alcohol withdrawal is common, the recognition of benzodiazepine-resistant alcohol withdrawal is a relatively new concept. To provide a framework for both literature review and future research, we assessed clinicians' personal definition of resistant alcohol withdrawal. We developed a cross-sectional web-based survey. Administrators from collaborating toxicology and emergency medicine associations deployed the survey directly to their respective memberships. Only physicians, pharmacists, and other clinicians routinely treating alcohol withdrawal were eligible to participate. Respondents selected their preferred definition among the three most common author sources - JB Hack, NJ Benedict, D Hughes - or provided their own. Additional criteria to define resistant alcohol withdrawal were explored. 384 individuals answered the survey. Respondents were mostly attending physicians (79%), in full-time practice (90%), in emergency medicine (70%), and from North America (90%). The majority (64%) described resistant alcohol withdrawal as a high benzodiazepine dosage. Seizures (26%) and persistent tachycardia (16%) were also main characteristics. The median dose to describe high benzodiazepine dose (n = 146) was 40 mg per hour of diazepam equivalents (IQR 20-50). Available definitions were ranked equally as the preferred one: Hack (27%); Benedict (28%); Hughes (28%). Our results did not identify one single preferred definition for resistant alcohol withdrawal even though a high total dose of benzodiazepine is a major component. Hourly requirements of 40 mg of diazepam equivalents or more emerged as a possible threshold. These findings serve as a base to explore consensus guidelines or future research.

Medical Cannabis: Effects on Opioid and Benzodiazepine Requirements for Pain Control.

Background: There is currently little evidence regarding the use of medical cannabis for the treatment of intractable pain. Literature published on the subject to date has yielded mixed results concerning the efficacy of medical cannabis and has been limited by study design and regulatory issues. Objective: The objective of this study was to determine if the use of medical cannabis affects the amount of opioids and benzodiazepines used by patients on a daily basis. Methods: This single-center, retrospective cohort study evaluated opioid and benzodiazepine doses over a 6-month time period for patients certified to use medical cannabis for intractable pain. All available daily milligram morphine equivalents (MMEs) and daily diazepam equivalents (DEs) were calculated at baseline and at 3 and 6 months. Results: A total of 77 patients were included in the final analysis. There was a statistically significant decrease in median MME from baseline to 3 months (-32.5 mg; P = 0.013) and 6 months (-39.1 mg; P = 0.001). Additionally, there was a non-statistically significant decrease in median DE at 3 months (-3.75 mg; P = 0.285) and no change in median DE from baseline to 6 months (-0 mg; P = 0.833). Conclusion and Relevance: Over the course of this 6-month retrospective study, patients using medical cannabis for intractable pain experienced a significant reduction in the number of MMEs available to use for pain control. No significant difference was noted in DE from baseline. Further prospective studies are warranted to confirm or deny the opioid-sparing effects of medical cannabis when used to treat intractable pain.

Correlates of benzodiazepine dependence in patients with depression followed up in a psychiatric outpatient unit in Tunisia

Benzodiazepines may be prescribed to manage anxiety and insomnia in patients with depression. However, as noticed during our daily practice, a considerable proportion of patients treated for depression and receiving benzodiazepines developed a dependence to these medicines. Our aims were to estimate the proportion of patients with depression who develop a benzodiazepine dependence and to identify its correlates. We conducted a comparative study in Razi Hospital's outpatient psychiatry unit (Tunisia). We included patients aged 18 to 65 years who were diagnosed with depression during the first three quarters of 2014. Included patients were prescribed benzodiazepines. Follow-up period was of 2 years. A multivariate analysis was performed to identify dependence-associated factors. We included 54 patients, and 52% developed a benzodiazepine dependence during the follow-up period. Two associated factors were identified: a daily mean benzodiazepine dose of more than 9.5 milligrams of diazepam equivalents prior to taper off (p = .001) and a benzodiazepine taper-off initiated after the fifth week of benzodiazepine intake onset (p = .007). The proportion of patients who developed a benzodiazepine dependence was high. Low doses and time-limited benzodiazepine prescription should be taken into consideration when managing patients with depression in order to prevent dependence.

Deprescribing benzodiazepines.

Deprescribing benzodiazepines.

Outcome of neuropsychiatric symptoms and daily functioning of patients with dementia treated on an acute psychogeriatric ward

Background: Dementia is associated with progressive deterioration in multiple cognitive domains, functional impairment and neuropsychiatric symptoms (NPS).Aims: The aim of this study was to explore the factors associated with the outcome of NPS and daily functioning in patients with dementia during acute psychogeriatric hospitalization.Materials and method: The data (n = 175) were collected between 2009 and 2013 in naturalistic settings on one acute psychogeriatric ward at one university hospital in Finland. Behavioural symptoms were assessed using the Neuropsychiatric Inventory (NPI) and activities of daily living using the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL).Results: During the hospital stay (45 days ±30.4) NPI total score decreased from 33.9 to 18.2 (p < .001). Daily functioning score decreased from 31.7 to 20.9 (p < .001). The number of patients taking antipsychotics (96–130, p = .004) and anxiolytics (54–102, p < .001) increased from admission to discharge. Overall mean dosage (mg/day) of antipsychotics (from 40.2 to 72.0 in chlorpromazine equivalents, p < .00) and anxiolytics (from 3.43 to 7.47 in diazepam equivalents, p < .001) also increased. Higher antipsychotic dosage at discharge was a significant predictor for large NPI score change (p = .002) indicating better symptom reduction. Neither higher antipsychotic dosage or anxiolytic dosage at discharge were significant predictors for ADL score change.Conclusions: Neuropsychiatric symptoms improved while deterioration was found in daily functioning from admission to discharge. Higher antipsychotic dosage at discharge was a predictor for larger NPI score change indicating better symptom reduction. Preventing threatening ADL decline during hospital stay is especially important.

Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases

BackgroundIn toxicology, international classification systems focus on single intoxicants as the cause of death. It is, however, well known that very few drug related deaths are caused by a single substance and that information concerning the drug concentrations as well as the combinations of drugs are essential in order to ascertain the cause of death. The aim of the study was to assess whether those prone to fatal intoxications differ significantly from chronic drug users – in terms of demographics and drug exposure patterns. Material and methodsFatal psychoactive drug intoxications in Norway during 2012, where a forensic autopsy including toxicological analysis were performed, were included. Analytical findings in blood were compared with concentrations in blood from apprehended drivers under the influence of drugs and ethanol (DUID) during the same time period. The opioid and benzodiazepine concentrations were assessed as morphine and diazepam equivalents, respectively, in order to compare concentrations across the different groups. ResultsA total of 194 autopsy cases and 4811 DUID cases were included. Opioids were detected in around 90% of the drug intoxication cases, but in only 16% of the DUID cases. The number of substances detected in fatal intoxications was 4.9 compared to 2.6 in the DUID cases. The total opioid concentrations were significantly higher in the fatal intoxication cases compared to DUID cases (229ng/mL versus 56.9ng/mL morphine equivalents, respectively). Benzodiazepines were detected in 90% of the fatal cases. Only one fatal opioid mono-intoxication was found; a case with a very high methadone concentration (1238ng/mL). DiscussionMono-intoxication with heroin was not seen in any of the fatal intoxications in Norway, and single drug intoxications were rare (1.5%). Fatal intoxications were caused by a combination of drugs with significantly more substances as well as higher total drug concentrations among the fatal cases compared to the DUID cases. The combination of opioids and benzodiazepines seemed to represent an increased risk of death. ConclusionThe total load of drugs influence the degree of intoxication and the total concentration level must be considered, including the total number of substances. Our findings imply that international statistics regarding an opioid being the main intoxicant should have a shift in focus towards combinations of drugs (especially opioids and benzodiazepines) as a major risk factor for fatal drug overdoses.

Conversion factors for assessment of driving impairment after exposure to multiple benzodiazepines/z-hypnotics or opioids

AimsNorway has introduced legal concentration limits in blood for 28 non-alcohol drugs in driving under the influence cases. As of 2016 this legislation also regulates the assessment of combined effects of multiple benzodiazepines and opioids. We herein describe the employed methodology for the equivalence tables for concentrations of benzodiazepines/z-hypnotics and opioids implemented in the Norwegian Road Traffic Act. MethodsLegislative limits corresponding to impairment at blood alcohol concentrations (BAC) of 0.02%, 0.05% and 0.12% were established for 15 different benzodiazepines and opioids. This was based on a concept of a linear relationship between blood drug concentration and impairment in drug naïve users. Concentration ratios between these drugs were used to establish conversion factors and calculate net impairment using diazepam and morphine equivalents. ResultsConversion factors were established for 14 benzodiazepines/z-hypnotics (alprazolam, bromazepam, clobazam, clonazepam, etizolam, flunitrazepam, lorazepam, nitrazepam, nordiazepam, oxazepam, phenazepam, temazepam, zolpidem and zopiclone) and two opioids (methadone and oxycodone). ConclusionsConversion factors to calculate diazepam and morphine equivalents for benzodiazepines/z-hypnotics and selected opioids, respectively, have been operative in the Norwegian Road Traffic Act as of February 2016. Calculated equivalents can be applied by the courts to meter out sanctions.

Benzodiazepines May Be Worse Than Opioids

Opioid prescription for noncancer pain is increasing in Europe and the United States. Research and guidance have focused on the potential for dependency and medical side effects with high doses. In contrast, benzodiazepines have received little attention in the chronic pain literature, despite evidence for dependency and cognitive impairment in long-term use. We aimed to examine the relationship between these classes of medication use, mood, and functioning. This cross-sectional study included patients (N=229) with disabling chronic pain who were about to start intensive pain rehabilitation. They completed self-report measures of mood, functioning, and responses to pain. We examined each patient's medication use and calculated a single morphine equivalent (ME) dose per person, and a similar diazepam equivalent (DE) dose. We examined the relationship between drug dose, mood, and functioning. Higher DE doses were associated with worse outcomes in most domains. Higher ME doses were more narrowly associated with worse functioning. There was no evidence for any benefit of these drugs; higher doses were not associated with less pain, fear, or disability. Higher ME doses were not more problematic, contrary to our predictions. The combination of opioids and benzodiazepines was associated with particularly poor outcomes for mood. This study is the first to examine both opioid and benzodiazepine use together in chronic pain. We found the anticipated negative effects of opioid medication, and particularly consistent associations between benzodiazepine use and poor well-being. Future guidance on chronic pain prescription should focus on restricting benzodiazepine use.