Long-term Benzodiazepine Use Research Articles

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline.

It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife. The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949-1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995-2022. Associations were analysed using Cox proportional hazards and linear regression. In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68-0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = -1.66 [-2.09 to -1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = -2.42[-3.18 to -1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance. Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

Short-Term Efficacy and Safety of Suvorexant and Lemborexant: A Retrospective Study.

Given the risks of long-term benzodiazepine use, safer alternatives like orexin receptor antagonists (ORAs) are needed for insomnia treatment. This study aims to compare suvorexant and lemborexant, focusing on early-stage sleep duration as an efficacy measure and fall incidence as a safety measure. We included patients admitted to our hospital between April 1, 2022and December 31, 2022, who were newly prescribed suvorexant or lemborexant, excluding patients taking other concomitant sleep medications or antipsychotics. Primary and secondary endpoints were sleep duration during the first three days after taking the medications and the incidence of falls, respectively. We analyzed data from 48 and 57 patients taking suvorexant and lemborexant, respectively. When compared with that in the pre-treatment period, sleep duration was significantly longer on days 2 and 3 in the suvorexant group, and on all three days in the lemborexant group. On day 1 of drug administration, the lemborexant group had a significantly longer sleep duration than the suvorexant group (5.10 ± 1.84 vs. 5.93 ± 1.90 h, respectively; P = 0.017). Zero (0.0%) and three (5.3%) falls occurred in the suvorexant and lemborexant groups, respectively (P = 0.248). Lemborexant exerted a potent inhibitory effect on orexin 2 receptors, which could explain the longer sleep duration experienced by patients taking this drug on the first day of treatment.

Long-term benzodiazepine prescriptions in community psychiatry clinics.

Anecdotal evidence indicates that the prevalence of long-term benzodiazepine prescription is high and not in accordance with accepted prescribing guidelines. To determine the prevalence of long-term prescriptions of benzodiazepines and associations thereof in community psychiatry clinics. Of the 27 community psychiatry clinics, 5 were randomly selected. A descriptive, retrospective, and cross-sectional record review of files of 126 adult patients was conducted, to obtain sociodemographic and clinical characteristics. Descriptive statistics were presented as proportions and percentages. Fisher's exact test was used to determine any associations between long-term benzodiazepines use and demographic and clinical variables. Regression analyses were performed to determine the significance of any such associations. Approximately one out of every four patients were prescribed benzodiazepines. Most of the patients were males aged between 18 and 50 years, single and unemployed. The most common psychiatric diagnoses were bipolar disorders and psychotic disorders, and the majority had no comorbid medical illnesses or substance use. Ninety-three per cent of the patients were prescribed long-term (more than 180 days) benzodiazepines. There were no statistically significant associations between prescribing patterns and any sociodemographic and clinical characteristics (p > 0.05). This study found that nearly all the benzodiazepine prescriptions were long-term (over 180 days) and no statistically significant associations between this practice and any sociodemographic and clinical characteristics could be established. There is high prevalence rate of long-term benzodiazepine prescription in community psychiatry clinics, and as such clinical monitoring systems need to be established and enforced.

RE-TRABECULECTOMY + 5-FLUOROURACIL IN PRIMARY ANGLE CLOSURE GLAUCOMA PATIENTS AGGRAVATED BY CONSUMPTION OF SCHIZOAFFECTIVE DRUG

Introduction : PACG occurs when the anterior chamber angle is occluded by the iris thus reducing aqueous humor outflow. Most schizoaffective patients use anticholinergic drugs which may result in iridocorneal angle closure through deposition. This article reported a Re-Trabeculectomy + 5 FU surgery in PACG which was aggravated by the use of schizoaffective drugs
 Case Illustration : A 43 year old woman, underwent Re-Trabeculectomy + 5 FU on LE after increasing IOP and regularly took schizoaffective drugs. Tapering of schizoaffective therapy was done 1 month preoperatively. Patient presented with LE UCVA of 3/60 and LE IOP is 30.9 mmHg with three anti- glaucoma medications. LE examinations revealed VH1 AC, bayonet sign and cupping on funduscope, closed angle on gonioscope, nasal step defect on humphrey and diffuse RNFL thinning on OCT. On the first postoperative day LE IOP is 18.5 mmHg. The schizoaffective therapy was re-initiated from psychiatric and evaluation was done weekly
 Discussion : Re-trabeculectomy surgery have been done considering the failure of the first trabeculectomy and administration of 5-Fluorouracil as an anti-fibrosis. The benefits of reducing preoperative dose of schizoaffective drugs for a month due to having an anticholinergic effect and reduces IOP by 5 mmHg. Psychiatrists and ophthalmologists work together to try to administer basic schizoaffective drug doses and evaluate IOP to keep it under control.
 Conclusion : The re-operative action was carried out by adding anti-fibrosis and cooperating with psychiatry for postoperative tapering of schizoaffective drugs. Long-term use of antidepressant drugs and benzodiazepines increases PACG.

Mortality and health-related quality of life in older adults with long-term use of opioids, z-hypnotics or benzodiazepines: a prospective observational study at 5 years follow-up

ObjectivesDisease and medication use in older age is a consequence of age-related declining health. Multimorbidity followed by polypharmacy is common. Central nervous system depressing (CNSD) drugs such as opioids, benzodiazepines...

Long-term benzodiazepine use and risk of labor market marginalization in Finland: A cohort study with 5-year follow-up.

Benzodiazepines and related drugs (BZDRs) are widely used in the treatment of anxiety and sleep disorders, but cognitive adverse effects have been reported in long-term use, and these may increase the risk of labor market marginalization (LMM). The aim of this study was to investigate whether the risk of LMM is associated with new long-term BZDR use compared to short-term use. This register-based nationwide cohort study from Finland included 37,703 incident BZDR users aged 18-60years who initiated BZDR use in 2006. During the first year of use, BZDR users were categorized as long-term users (≥180days) versus short-term users based on PRE2DUP method. The main outcome was LMM, defined as receipt of disability pension, long-term sickness absence (>90days), or long-term unemployment (>180days). The risk of outcomes was analyzed with Cox regression models, adjusted with sociodemographic background, somatic and psychiatric morbidity, other types of medication and previous sickness absence. During 5 years of follow-up, long-term use (34.4%, N=12,962) was associated with 27% (adjusted Hazard Ratio, aHR 1.27, 95% CI 1.23-1.31) increased risk of LMM compared with short-term use. Long-term use was associated with 42% (aHR 1.42, 95% CI 1.34-1.50) increased risk of disability pension and 26% increased risk of both long-term unemployment and long-term sickness absence. These results indicate that long-term use of BZDRs is associated with increased risk of dropping out from labor market. This may be partly explained by cognitive adverse effects of prolonged BZDR use, which should be taken into account when prescribing BZDRs.

Patient-GP-Pharmacist cooperation towards individualized tapering schemes for long term benzodiazepine users

Long-term use of benzodiazepines and Z-drugs is associated with multiple side effects, such as increased sedation, fall risk, and an elevated risk of dependency and abuse. Avoiding initiation of treatment, or stopping treatment after a few weeks, is definitely the best-case scenario. But for patients that are already using benzodiazepines for more than 3 months (up to 20 years or more), a deprescribing methodology should be deployed. Abrupt withdrawal, particularly if the individual has been taking the drug in high doses, can result in severe symptoms, including psychotic reactions. The recommendation is for slow withdrawal, tapering the dosage gradually over a period of several months.
 Pharmacy compounding of capsules has been a possibility for many years, and allows to prepare and dispense individualized dosages to patients. Medical practitioners such as GP’s have always had the possibility to prescribe dose reduction schemes for patients motivated to taper off. Unfortunately, as benzodiazepines are not reimbursed in Belgium, this came at a high cost for patients.
 In 2022, pharmacy associations together with health insurance funds and the National Institute for Health and Disability Insurance (NIHDI) worked on a reimbursement scheme that allowed tapering off benzodiazepines. The patient-GP-pharmacist triangle is at the core of the scheme:
 -Pharmacists raise awareness when dispensing prescribed benzodiazepines, and prepare and dispense individualized doses
 -GP’s motivate patients to consider tapering and prescribe the programme
 -Patients engage in a tapering path and are intensively followed by the GP and the pharmacist
 Apart from the roles and responsibilities of the 3 parties, there are some rules set out to increase the change of successful tapering whilst keeping expenditure under control. For instance, a maximum daily consumption of 3 DDD set out, there is choice between 3 tapering schemes (5, 7 or 10 steps), and the total duration of the programme should not exceed 360 days.
 Critical success factors of these programs are: intrinsic motivation of the patient, therapeutic contract with 3 parties concerned, absence of financial penalty for patients, and smooth communication between prescriber and preparer/dispenser.

Benzodiazepine Discontinuation and Mortality Among Patients Receiving Long-Term Benzodiazepine Therapy

There is interest in reducing long-term benzodiazepine prescribing given harms associated with use, but the cumulative risks or benefits of discontinuation are unknown. To identify the association of benzodiazepine discontinuation with mortality and other adverse events among patients prescribed stable long-term benzodiazepine therapy, stratified by baseline opioid exposure. This comparative effectiveness study with a trial emulation approach included data from a US commercial insurance database between January 1, 2013, and December 31, 2017. Eligible participants were adults with stable long-term benzodiazepine prescription treatment. Data were analyzed between December 2022 and November 2023. Benzodiazepine discontinuation, defined as no benzodiazepine prescription coverage for 31 consecutive days identified during a 6-month grace period after baseline. Mortality during 12 months of follow-up; secondary outcomes included nonfatal overdose, suicide attempt or self-inflicted injury, suicidal ideation, and emergency department use, identified in medical claims. Inverse probability weighting was used to adjust for baseline confounders that potentially affected treatment assignment and censoring due to death or disenrollment. Primary analysis used an intention-to-treat approach; a secondary per-protocol analysis estimated associations after accounting for nonadherence. Analyses were stratified by opioid use. The study included 213 011 (136 609 female [64.1%]; mean [SD] age, 62.2 [14.9] years; 2953 Asian [1.4%], 18 926 Black [8.9%], 22 734 Hispanic [10.7%], and 168 398 White [60.2%]) and 140 565 (91 811 female [65.3%]; mean [SD] age, 61.1 [13.2] years; 1319 Asian [0.9%], 15 945 Black [11.3%], 11 989 Hispanic [8.5%], and 111 312 White [79.2%]) patients with stable long-term benzodiazepine use without and with opioid exposure, respectively. Among the nonopioid exposed, the adjusted cumulative incidence of death after 1 year was 5.5% (95% CI, 5.4%-5.8%) for discontinuers, an absolute risk difference of 2.1 percentage points (95% CI, 1.9-2.3 percentage points) higher than for nondiscontinuers. The mortality risk was 1.6 (95% CI, 1.6-1.7) times that of nondiscontinuers. Among those with opioid exposure, the adjusted cumulative incidence of death was 6.3% (95% CI, 6.0%-6.6%) for discontinuers, an absolute risk difference of 2.4 percentage points (95% CI, 2.2-2.7 percentage points) higher than for nondiscontinuers and a mortality risk 1.6 (95% CI, 1.5-1.7) times that of nondiscontinuers. Cumulative incidence of secondary outcomes was also higher among discontinuers. This study identifies small absolute increases in risk of harms among patients with stable long-term prescription benzodiazepine treatment who appear to discontinue relative to continuing treatment, including those with and without recent prescription opioid exposure. Policy broadly promoting benzodiazepine discontinuation may have unintended risks.

Benzodiazepine Dependence After Cardiothoracic Intensive Care: A Nationwide Cohort Study

BackgroundThis study aimed to describe benzodiazepine use after cardiothoracic intensive care unit (ICU) care, including factors associated with new long-term high-potency benzodiazepine use after critical care, and to determine whether benzodiazepine use is associated with an increased risk of death. MethodsA nationwide retrospective cohort study was conducted of all cardiothoracic ICU patients in Sweden between 2010 and 2018. All patients older than 18 years who survived the first 3 months after admission to a cardiothoracic ICU were eligible for inclusion. A total of 36,135 patients were screened, and 4163 were ineligible. ResultsIn the final study cohort of 31,972 benzodiazepine-naive patients admitted to critical care, 578 patients had persistent high-potency benzodiazepine use. The proportion of new persistent benzodiazepine users was 5% in the first 3 months after ICU care, followed by a decline to a consistent level of 2% at 2 years of follow-up. Factors associated with persistent benzodiazepine use included higher age, female sex, psychiatric and somatic comorbidities, substance abuse, and preadmission opioid and low-potency benzodiazepine use. Adjusted hazard ratio for death 6 to 18 months after admission for new persistent benzodiazepine users was 2.2 (95% CI, 1.5-3.1; P < .001). ConclusionsHigh-potency benzodiazepine consumption is increased 2 years after admission to cardiothoracic ICU care despite lack of support for long-term use of benzodiazepines. Being older and female, prior opioid use, and comorbid conditions were among risk factors for persistent benzodiazepine use. Persistent benzodiazepine users had an increased risk of death.

Long-Term Use of Benzodiazepines and Benzodiazepine-Related Drugs: A Register-Based Danish Cohort Study on Determinants and Risk of Dose Escalation.

The authors investigated the frequency and determinants of long-term use and risk of dose escalation of benzodiazepines and benzodiazepine-related drugs (benzodiazepine receptor agonists, or BZRAs). All adults ages 20-80 years living in Denmark on January 1, 2000 (N=4,297,045) were followed for redeemed prescriptions of BZRAs in the Danish National Prescription Registry from January 1, 2000, to December 31, 2020. For each drug class, we calculated long-term use for more than 1 or 7 years, and dose escalation measured as increase in dose to a level above the recommended level. Associations were examined using logistic regression. The authors identified 950,767 incident BZRA users, of whom 15% and 3% became long-term users for more than 1 or 7 years, respectively. These percentages were highest for individuals who initiated Z-drugs (17.8% and 4%). Among the 5% of BZRA users who had at least 3 years of continuous use, there was no indication of dose escalation, as the median dose remained relatively stable. However, 7% (N=3,545) of BZRA users escalated to doses above the recommended level. Psychiatric comorbidity, especially substance use disorder, was associated with higher risk of long-term use and dose escalation. A limited portion of the population that received BZRA prescriptions were classified as continuous users, and only a small proportion of this group escalated to doses higher than those recommended in clinical guidelines. Thus, this study does not, under the current regulations, support the belief that BZRA use frequently results in long-term use or dose escalation.

Examining Adult Patients' Success with Discontinuing Long-term Benzodiazepine Use: a Qualitative Study.

Little is known about patients' experiences with benzodiazepine (BZD) discontinuation, which is thought to be challenging given the physiological and psychological dependence and accompanying potential for significant withdrawal symptoms. The marked decline in BZD prescribing over the past decade in the US Department of Veterans Affairs healthcare system presents an important opportunity to examine the experience of BZD discontinuation among long-term users. Examine the experience of BZD discontinuation among individuals prescribed long-term BZD treatment to identify factors that contributed to successful discontinuation. Descriptive qualitative analysis of semi-structured interviews conducted between April and December of 2020. A total of 21 Veterans who had been prescribed long-term BZD pharmacotherapy (i.e., > 120days of exposure in a 12-month period) and had their BZD discontinued. We conducted semi-structured interviews with Veteran participants to learn about their BZD use and the process of discontinuation, with interviews recorded and transcribed verbatim. Data were deductively and inductively coded and coded text entered into a matrix to identify factors that contributed to successful BZD discontinuation. The mean age of interview participants was 63.0years (standard deviation 3.9); 94.2% were male and 76.2% were white. Of 21 participants, only 1 had resumed BZD treatment (prescribed by a non-VA clinician). Three main factors influenced success with discontinuation: (1) participants' attitudes toward BZDs (e.g., risks of long-term use, perceived lack of efficacy, potential for dependence); (2) limited withdrawal symptoms; and (3) effective alternatives, either from their clinician (e.g., medication, psychotherapy) or identified by participants. BZD discontinuation after long-term use is relatively well tolerated, and participants appreciated reducing their medication exposure, particularly to one associated with physical dependence. These findings may help reduce both patient and clinician anxiety related to BZD discontinuation.

Benzodiazepines and z-drugs - between treatment effectiveness and the risk of addiction

Benzodiazepines (BZDs) and Z-drugs are commonly prescribed medications for anxiety and sleep disorders. This review examines their efficacy, associated risks, and alternative treatment options. BZDs enhance the activity of gamma-aminobutyric acid (GABA), reducing anxiety, while Z-drugs selectively target GABA-A receptors' alpha-1 subunits for sedative effects. Despite their effectiveness, both drug classes carry the risk of addiction, physical and psychological dependence, and withdrawal symptoms. Side effects, such as drowsiness, dizziness, and cognitive impairment, are also associated with their use. Recent studies indicate that chronic use of BZDs and Z-drugs may lead to cognitive impairment and an increased risk of dementia in older adults. Furthermore, individual factors, dosage, duration of use, and drug interactions can affect their efficacy. Prescribing trends show a decline in benzodiazepine prescriptions and an increase in Z-drug use due to perceived safety advantages. However, evidence suggests that Z-drugs carry similar risks of adverse effects and addiction potential as benzodiazepines. Healthcare professionals should carefully assess patients before prescribing these drugs and monitor their use to prevent dependence and addiction. Brief interventions, patient education, drug withdrawal support, and cognitive behavioral therapy have shown effectiveness in reducing long-term benzodiazepine and Z-drug use. Alternative treatments, including cognitive behavioral therapy and relaxation techniques, should be considered, particularly for patients with a history of addiction or those at high risk of addiction. In conclusion, the risk of addiction, withdrawal symptoms, and adverse effects associated with benzodiazepines and Z-drugs necessitates cautious prescribing and the exploration of alternative treatment options.

Long-term use of benzodiazepines in chronic insomnia: a European perspective.

Chronic insomnia occurs in ~10% of the general population and has numerous negative health effects. The recommended first line treatment of cognitive behavior therapy for insomnia is not widely available for patients in Europe, so pharmacotherapies such as benzodiazepine receptor agonist agents (benzodiazepines and Z-drugs) are commonly used. However, their use is only recommended for ≤4 weeks due to unproven long-term efficacy in treatment of chronic insomnia, and the risk of tolerance, and the potential for dependence and misuse. In Europe, recommendations limiting the use of benzodiazepines (lowest dose and shortest duration) in chronic insomnia are not always followed, likely due to the lack of approved effective alternative therapies. Here we present a recent pilot survey of the pharmacological treatment landscape in chronic insomnia in five European countries (France, Germany, Italy, Spain, and the United Kingdom) and physicians' attitude toward treatment. The results suggest that benzodiazepines and Z-drugs are the most widely used treatments in chronic insomnia and are being used for longer than their recommended duration. Country variations in prescription rates were observed. Due to the known association between long-term benzodiazepine use and potential for developing dependence, further analysis of the literature was performed on the use and misuse of benzodiazepines. The results show that long-term use of benzodiazepines is associated with multiple consequences of treatment, including dependence, but also that previous use of benzodiazepines may increase the risk of opioid use disorder.

Long Term Use of Benzodiazepines and Delayed Awakeness from General Anesthesia: A Case Report

We present two delayed awaken cases that underwent general anesthesia and showed altered mentality with unresponsiveness in the postanesthesia care unit (PACU) after successful extubation in the operating room. Both patients had been taking benzodiazepines chronically before surgery. In case 1, extubation was carried out without any problems and arrived at the PACU. After 15 minutes, she suddenly developed hyperventilation, shivering, and a state of consciousness that does not respond to verbal command. Eyes were kept closed and she showed decreased pain withdrawal response in all extremities. After 90 minutes at PACU, she was able to obey simple verbal instructions. All symptoms showed gradual improvement within 5-6 hours. In case 2, 20 minutes after transferal to PACU, the patient showed drowsy mentality with no response to verbal or pain stimuli. Altered mental state lasted 3 days and motor weakness of extremities lasted 5 days. Brain MRI and other examinations showed no abnormalities. They were discharged without any neurological complications.

Factors associated with long-term benzodiazepine and Z-drug use across the lifespan and 5-year temporal trajectories among incident users: a Swedish nationwide register-based study

PurposeDespite being discouraged by guidelines, long-term use of benzodiazepines and related Z-drugs (BZDR) remains frequent in the real-world. An improved understanding of factors associated with the transition from new to long-term BZDR use and of temporal BZDR use trajectories is needed. We aimed to assess the proportion of long-term BZDR use (> 6 months) in incident BZDR-recipients across the lifespan; identify 5-year BZDR use trajectories; and explore individual characteristics (demographic, socioeconomic and clinical) and prescribing-related factors (pharmacological properties of the initial BZDR, prescriber’s healthcare level, and concurrent dispensing of other medications) associated with long-term BZDR use and distinct trajectories.MethodsOur nationwide register-based cohort included all BZDR-recipients in Sweden with first dispensation in 2007–2013. Trajectories of BZDR use days per year were built using group-based trajectory modelling. Cox regression and multinomial logistic regression were fitted to assess the predictors of long-term BZDR use and trajectories’ membership.ResultsIn 930,465 incident BZDR-recipients, long-term use increased with age (20.7%, 41.0%, and 57.4% in 0–17, 18–64, and ≥ 65-year-olds, respectively). Four BZDR use trajectories emerged, labelled ‘discontinued’, ‘decreasing’, ‘slow decreasing’ and ‘maintained’. The proportion of the ‘discontinued’ trajectory members was the largest in all ages, but reduced from 75.0% in the youths to 39.3% in the elderly, whereas the ‘maintained’ increased with age from 4.6% to 36.7%. Prescribing-related factors, in particular multiple BZDRs at initiation and concurrent dispensing of other medications, were associated with increased risks of long-term (vs short-term) BZDR use and developing other trajectories (vs ‘discontinued’) in all age groups.ConclusionsThe findings highlight the importance of raising awareness and providing support to prescribers to make evidence-based decisions on initiating and monitoring BZDR treatment across the lifespan.

Alprazolam

Although alprazolam is approved only for use in panic disorder and generalized anxiety disorder, it is used for numerous other conditions, not only by psychiatrists but also by medical professionals in general. This commentary critically analyzes the use of alprazolam. A narrative review approach was adopted, using relevant articles and textbooks, to compile pertinent literature for the aforementioned topic. Among all its adverse reactions, the most bothersome concern about the use of alprazolam is its potential for abuse and dependence. This can be attributed to certain unique pharmacokinetic and pharmacodynamic properties of this benzodiazepine. Also, the withdrawal triggered by use of alprazolam is challenging to treat. Alternate pharmacological and non-pharmacological strategies for use in anxiety and insomnia are available, which might be safer than alprazolam. Also, policy changes can serve as an answer to curb alprazolam abuse to some extent. Alprazolam might still be a good choice for individuals who do not have a history of abuse of other substances, with adequate psychoeducation and close monitoring of their usage pattern. There is a need to reconsider the need for long-term use of benzodiazepines in general, and alprazolam in particular. However, they still might be an appropriate choice in individuals where abuse and dependence are less likely.

A Comparison between Perceptions of Psychiatric Outpatients and Psychiatrists Regarding Benzodiazepine Use and Decision Making for Its Discontinuation: A Cross-Sectional Survey in Japan

Although long-term use of benzodiazepines and z-drugs (BZDs) is not recommended, little is known about the stakeholders' perceptions. This study aimed to assess and compare the perceptions of BZD use and decision making regarding its discontinuation between psychiatric outpatients and psychiatrists. A cross-sectional survey was conducted. Of 104 outpatients, 92% were taking hypnotics and 96% were taking anxiolytics for ≥a year, while 49% were willing to taper hypnotic/anxiolytics within a year of starting. Most psychiatrists felt that "patient and psychiatrist make the decision together on an equal basis" compared to patients (p < 0.001), while more patients felt that "the decision is (was) made considering the psychiatrists' opinion" compared to psychiatrists (p < 0.001). Of 543 psychiatrists, 79% reported "patients were not willing to discontinue hypnotic/anxiolytic" whereas a certain number of patients conveyed "psychiatrists did not explain in enough detail about hypnotic/anxiolytic discontinuation such as procedure (18.3%), timing (19.2%), and appropriate condition (14.4%)". The results suggest that the majority of psychiatric outpatients were taking hypnotic/anxiolytics for a long time against their will. There might be a difference in perceptions toward hypnotic/anxiolytic use and decision making for its discontinuation between psychiatric outpatients and psychiatrists. Further research is necessary to fill this gap.

To treat or not to treat? High-potency benzodiazepine use in a case of comorbid hallucinogen persisting perception disorder and alcohol use disorder.

Hallucinogen persisting perception disorder (HPPD) is characterized by visual disturbances that resemble psychedelic intoxication and linger after use has ceased. The most common substances precipitating HPPD, lysergic acid diethylamide (LSD) and psilocybin, are posited to do so via damage to serotonergic neurons involved in vision. Mr. N is a 37-year-old with a history of alcohol, cannabis, LSD, cocaine, and nicotine use disorders who described visual distortions that resolved when he drank heavily or received benzodiazepines for withdrawal. He did not appear psychotic. Over 20 years after his last LSD use, he continued to experience illusions of halos around objects, moving walls, and figures appearing cartoonish. He understood that his perceptual disturbances were not reality based. During hospitalization for suicidal ideation, laboratory tests, head computed tomography (CT), and electroencephalogram (EEG) studies offered no explanation for his visual disturbances other than HPPD. The visual distortions remitted with scheduled clonazepam treatment, although chemical dependency treatment programs were hesitant to accept him while on a benzodiazepine. This case emphasizes the importance of diagnostic clarification when patients present with perceptual disturbances that do not fit typical psychotic presentations. Our discussion will distinguish misperceptions from hallucinations and review the pathophysiology of HPPD. Last, we will discuss management strategies for patients with co-occurring HPPD and substance use disorders. It is necessary to discern the correct cause of visual disturbances in order to provide proper treatment. The risks and benefits of long-term benzodiazepine use must be weighed when deciding whether to prescribe them for patients with comorbid HPPD and alcohol use disorder. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use

Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term (mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms. Prolonged BDZ exposure may induce adaptive changes in the function of several receptors, including the primary target, gammaaminobutyric acid receptor type A (GABAAR), but also other neurotransmitter receptors such as glutamatergic. The present study investigated the potential effects of prolonged ALP treatment on components of glutamatergic neurotransmission, with special emphasis on N-Methyl-D-aspartate receptor (NMDAR) in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with potential onset of tolerance and involvement of the glutamatergic system in its development. Specifically, an increase in NMDAR subunits (NR1, NR2A, NR2B), a decrease in vesicular glutamate transporter 1 (vGlut1), and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed, alongside a decrease in α1-containing GABAAR following the treatment. By describing the development of compensatory actions in the glutamatergic system, the present study provides valuable information on neuroadaptive mechanisms following prolonged ALP intake.

Benzodiazepines and Mood Stabilizers in Schizophrenia Patients Treated with Oral versus Long-Acting Injectable Antipsychotics—An Observational Study

Schizophrenia is a chronic, invalidating, and polymorphic disease, characterized by relapses and remission periods. The main treatment option in schizophrenia are antipsychotics, administered as an oral or as a long-acting injectable (LAI) formulation. Although international guidelines rarely recommend it, mood stabilizers (MS) and/or benzodiazepines (BZD) are frequently prescribed as adjunctive therapy in schizophrenia patients for various reasons. This is an observational, cross-sectional study including stabilized schizophrenia patients. A total of 315 patients were enrolled. Of these, 77 patients (24.44%) were stabilized on LAIs and 238 (75.56%) patients on oral antipsychotics (OAP). Eighty-four patients (26.66%) had concomitant treatment with MS and 119 patients (37.77%) had concomitant benzodiazepine treatment. No statistical significance was observed in MS or BZD use between LAIs and OAPs. In total, 136 patients (43.17%) were stabilized on antipsychotic monotherapy. Our study shows that the long-term use of benzodiazepines and mood stabilizers remains elevated among stabilized schizophrenia patients, regardless of the antipsychotic formulation (oral or LAI). Patients receiving second-generation LAI antipsychotics (SGA-LAI) seem to be more likely to be stabilized on monotherapy compared to those receiving oral antipsychotics. Further randomized controlled trials are necessary in order to clarify the benefits of the current drug polypharmacy trends.