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The lifetime prevalence of suicide is around 5% in patients with schizophrenia. Non-adherence to antipsychotic medication is an important risk factor, but prospective studies investigating joint effects of antipsychotic drugs, antidepressants, and benzodiazepines on suicidality are scarce. We aimed to investigate how use and non-use of psychotropic medications are associated with suicidality in schizophrenia.
Methods
An open cohort study followed all patients consecutively admitted to a psychiatric acute unit during a 10-year period with a diagnosis of schizophrenia (n = 696). Cox multiple regression analyses were conducted with use of antipsychotics, antidepressants, and benzodiazepines as time-dependent variables. Adjustments were made for age, gender, depressive mood, agitated behavior, and use of alcohol and illicit substances.
Results
A total of 32 (4.6%) suicide events were registered during follow-up. Of these, 9 (28%) were completed suicides and 23 (72%) were attempted suicides. A total of 59 (8.5%) patients were readmitted with suicidal plans during the follow-up. Compared to non-use, use of antipsychotics was associated with 70% lower risk of attempted or completed suicide (adjusted hazard ratio [AHR] = 0.30, p < 0.01, CI 0.14–0.65) and 69% reduced risk of readmission with suicidal plans (AHR = 0.31, p < 0.01, CI 0.18–0.55). Use of prescribed benzodiazepines was associated with 126% increased risk of readmission with suicidal plans (AHR = 2.26, p = 0.01, CI 1.24–4.13).
Conclusions
Adherence to antipsychotic medication is strongly associated with reduced suicidal risk in schizophrenia. The use of prescribed benzodiazepines was identified as a significant risk factor for being readmitted with suicidal plans.
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.
Methods
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.
Results
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.
Conclusion
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.
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.
Aims
To investigate sociodemographic and clinical factors associated with high-dose use of BZDRs (i.e. Z-drugs) among new BZDR users.
Method
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.
Results
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.
Conclusions
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.
Edited by
David Kingdon, University of Southampton,Paul Rowlands, Derbyshire Healthcare NHS foundation Trust,George Stein, Emeritus of the Princess Royal University Hospital
Anxiety symptoms and anxiety disorders are common in community settings and primary and secondary medical care. Anxiety symptoms are often mild and only transient, but many people are troubled by severe symptoms that cause both considerable personal distress and a marked impairment in social and occupational function. The principal anxiety disorders are currently considered to comprise panic disorder, generalised anxiety disorder, social anxiety disorder, agoraphobia, specific phobias, separation anxiety disorder and selective mutism. Additional conditions (not considered further here) include substance/medication-induced anxiety disorder, anxiety disorder due to another medical condition, other specified anxiety disorder and unspecified anxiety disorder. Together, anxiety disorders constitute the most frequent mental disorders, with an estimated 12-month prevalence of approximately 10–14 per cent.
Although the societal impact of anxiety disorders is substantial, many of those who could benefit from psychological or pharmacological treatment are neither recognised nor treated. Recognition relies on maintaining a keen awareness of the psychological and physical symptoms of anxiety disorders, and accurate diagnosis rests on identifying the pathognomonic features of specific conditions.
Evidence suggests that cannabis may be a causal factor for development of schizophrenia. We aimed to investigate whether use of antipsychotic medication, benzodiazepines, and psychiatric service use differs among patients with schizophrenia depending on whether psychosis was precipitated by a diagnosis of cannabis use disorder (CUD).
Methods
We utilized the nationwide Danish registries to identify all individuals with an incident diagnosis of schizophrenia from 1995 to 2016. We also collected information on whether first CUD diagnosis preceded schizophrenia and thus defined a group of potentially cannabis-related schizophrenia. We compared the cannabis-related schizophrenia group both with all non-cannabis-related patients with schizophrenia and with non-cannabis-related patients with schizophrenia that were propensity-score matched to cases using a range of potentially confounding variables.
Results
We included 35 714 people with incident schizophrenia, including 4116 (11.5%) that were cannabis-related. In the unmatched-comparison analyses, there were no clear differences over time in use of antipsychotics and benzodiazepines related to whether the diagnosis of schizophrenia was cannabis-related. After propensity-score matching, use of antipsychotics and benzodiazepines was significantly lower among cannabis-related cases of schizophrenia. In the unmatched comparison, the cannabis-related group had significantly more days admitted than the non-cannabis-related group. This was markedly attenuated after propensity-score matching.
Conclusions
Our findings indicate the importance of considering cannabis-related cases of schizophrenia as a potentially distinct disorder in terms of prognosis. It is unclear, however, if these differences are due to different biological types of schizophrenia being compared or if they rather indicate behavioral differences such as reduced adherence and treatment-seeking.
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.
Methods
This register-based nationwide cohort study from Finland included 37,703 incident BZDR users aged 18–60 years who initiated BZDR use in 2006. During the first year of use, BZDR users were categorized as long-term users (≥180 days) versus short-term users based on PRE2DUP method. The main outcome was LMM, defined as receipt of disability pension, long-term sickness absence (>90 days), or long-term unemployment (>180 days). 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.
Results
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.
Conclusions
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.
Dental fear and phobia are common with a prevalence of around 1 in 6 Australian adults (1). Fear of dental care can lead to significant stress and avoidance resulting in neglect and deterioration of oral health (2). The aim of anxiolysis is to improve patient comfort in order to complete dental examination, investigations and procedures (3). This chapter will focus on the pharmacological measures used for anxiolysis in community dentistry.
Behavioural treatments are recommended first-line for insomnia, but long-term benzodiazepine receptor agonist (BZRA) use remains common and engaging patients in a deprescribing consultation is challenging. Few deprescribing interventions directly target patients. Prescribers’ support of patient-targeted interventions may facilitate their uptake. Recently assessed in the Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study, Sleepwell (mysleepwell.ca) was developed as a direct-to-patient behaviour change intervention promoting BZRA deprescribing and non-pharmacological insomnia management. BZRA prescribers of YAWNS NB participants were invited to complete an online survey assessing the acceptability of Sleepwell as a direct-to-patient intervention. The survey was developed using the seven construct components of the theoretical framework of acceptability (TFA) framework. Respondents (40/250, 17.2%) indicated high acceptability, with positive responses per TFA construct averaging 32.3/40 (80.7%). Perceived as an ethical, credible, and useful tool, Sleepwell also promoted prescriber–patient BZRA deprescribing engagements (11/19, 58%). Prescribers were accepting of Sleepwell and supported its application as a direct-to-patient intervention.
In generalized convulsive status epilepticus (GCSE), a seizure lasts longer than 5 minutes or two seizures occur without an interval return to baseline.
The most common error in managing status epilepticus is not administering enough benzodiazepine. If the patient is refractory to benzodiazepines, there are multiple appropriate agents for second-line treatment (e.g., levetiracetam, valproate, fosphenytoin). A timely and early intubation may be the safest option and provide the best outcome for the patient.
Nonconvulsive status epilepticus (NCSE) presents without muscle involvement, and may be suspected clinically, but needs electroencephalography (EEG) to make the diagnosis.
Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.
Methods
Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome.
Results
Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7–39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38–4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0–79%). Quality was good in four studies.
Conclusions
Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.
Since 2018, the International Task Force on Benzodiazepines (ITFB), a group of academic psychiatrists and academic psychologists, has advocated that clinical guidelines should change to promote benzodiazepines from second- to first-line treatment for anxiety disorders, accept their use as maintenance treatment for anxiety conditions (in particular, panic disorder) and increase their use in gastrointestinal disorders. There is merit in much of what the ITFB argues, but in this article I analyse four major claims it has made in opinion editorials that I believe are not fully supported by the available evidence.
Benzodiazepines have attracted controversy from shortly after their introduction. They have been subject to periodic calls for their use to be re-evaluated on the basis that their risks have been overstated and their benefits underappreciated. Claims made in recent editorials from the International Task Force on Benzodiazepines in support of their wider use are critiqued in this issue. I examine here whether there is a case to change the conclusions of previous reconsiderations of the question.
Catatonia is a neuropsychiatric condition that causes disruption of movement, emotion, and behaviors. Children and adults with underlying psychiatric conditions are particularly susceptible to developing catatonia, which may result in medical and psychiatric complications. Although catatonia research has been growing at a rapid rate in the last 20 years, it continues to be met with inefficiencies in its diagnosis and incertitude in its treatment. In the pediatric population, catatonia is plagued by diagnostic overshadowing, where the catatonia is erroneously attributed to existing pathologies that lead to a prolonged disease state. This paper describes three pediatric patients with catatonia that fell victim to diagnostic overshadowing. More rigorous training and education are imperative to improve the efficient recognition and treatment of children with catatonia.
Only three population-based observational human studies provided evidence that benzodiazepines (BZD) are associated with clinically adverse respiratory outcome. Striking was the finding that BZD drug exposure was associated with a 32% significantly increased adjusted risk of all-cause mortality, including, of note, the subgroup of individuals with no comorbidities. Causation, however, cannot be inferred in observational study design and, highly likely, recipients received BZD’s in these studies to help treating anxiety related to inter alia pre-existing respiratory symptoms.
Objectives
Based on one fatal particular case, authors of current rapport explain what can go wrong when BZD’s are given in patient with respiratory impairment.
Methods
Authors provide a model on how an increase in carbon dioxide can lead to impaired cerebral autoregulation in a person with pre-existing respiratory decompensation. Discussion of integrative metabolic and vascular physiology.
Results
Case rapport of a 18 y.o. otherwise healthy man, who was hospitalized with a novel episode of diabetic ketoacidosis accompanied by profound hypocapnia and anxiety, and who deteriorated and died shortly after airway management because of a clinically important acid-base balance disturbance caused by increased carbon dioxide. All the blood tests and results of respiratory monitoring were collected and carefully assessed.
Conclusions
Current case suggests that the P(CO(2))--HCO(3) hypothesis is consistent with known data on impaired cerebral autoregulation in diabetic ketoacidosis, driven mainly by increased levels of pCO2. In our opinion, it indicates the recommendation not to administrate BZD’s in patients with pre-existing compensatory hyperventilation as it may counter to the logic of adaptive physiology.
The treatment of sleep disorders in older people requires knowledge of the changes in sleep in old age. In the case of multimorbid older people, pharmacological aspects such as interactions must also be taken into account. Sleep in old age is characterised by a lower depth of sleep and more frequent awakenings. The duration of sleep corresponds to that in middle adulthood. In multimorbid older people, sleep is often chronically impaired by pain and/or obstructive breathing disorders. Many medications can have a negative effect on sleep. This applies to cortisone, for example. Antipsychotics can also worsen sleep by worsening nocturnal myoclonia. Ideally, sleep disorders should first be addressed non-pharmacologically. For benzodiazepines, preparations with a short half-life should be chosen. An algorithm is presented. References:
Gulia KK, Kumar VM. Sleep disorders in the elderly: a growing challenge. Psychogeriatrics 2018;18(3):155-165. Samara MT, Huhn M, Chiocchia V, Schneider-Thoma J, Wiegand M, Salanti G, Leucht S. Efficacy, acceptability, and tolerability of all available treatments for insomnia in the elderly: a systematic review and network meta-analysis. ActaPsychiatr Scand. 2020;142(1):6-17.
The social media platform Reddit is a contemporary context where we have an opportunity to identify problems experienced by people regarding different aspects of life. The platform is virtually anonymous which might make users discuss their problems more freely. Reddit is divided in subreddits where different subjects are discussed and the discussions are controlled by creators and moderators. I have identified a quite active subreddit targeted towards recovering addicts of benzodiazepines; r/benzorecovery.
Objectives
* To analyze strategies of recovery in user narrative * To identify techniques commonly used and the how they are described * To construct metadata in order to assess how frequent the discussion of a different techniques are
Methods
Technically, what is done in this study, is adding mark-up metadata to different discussion. A rudimentary form of analysis suitable with a larger digital corpus where content metadata is added (Gilliland Swetland 2000). The metadata is constructed through a hermeneutical method in which the researcher analyses the subreddit.
Results
Answering question like: Example: DIY-tapering; different ways to limit drug use by using less. 1) how common are discussion of taperings in relation to other subjects? 2) Is tapering commonly discussed together with other subjects and techniques?
Conclusions
Using a method of categorization and metadata mark-up we could gain a good understanding of the problems among recovering benzodiazepine addicts. We will also have the possibility to identify concepts that addicts themselves discuss and relate these to professional concepts thus creating better possibilities of communication between professionals and clients.
Psychopharmacological interventions for the management of the neuro-behavioral manifestations of PWS that have been described throughout the book are the main focus of this particular chapter. A majority of patients with PWS are on one or more psychiatric medications by the time they reach adulthood. Patients with PWS are uniquely vulnerable to psychiatric illness and require a thorough assessment and diagnosis in order to receive appropriate treatment. This chapter outlines the main classes of medication that have been or, in our opinion, ought to be utilized in patients with PWS. We specifically address their common indications, side effects, and dosage recommendations, among other characteristics. Additionally, the complex phenomenon of drug–drug interactions is discussed in some detail, due to the high incidence of “polypharmacy” in PWS. We recognize that a significant portion of caregiver burden is attributable to neuro-behavioral symptoms and endeavor to provide the information necessary to guide providers in addressing that.
Benzodiazepines (BZD) are psychotropic drugs prescribed in psychiatry for their anxiolytic, hypnotic and sedative properties. Several guidelines aimed to limit the chronic use of BZDs. However, BZDs prescribing that does not comply with international recommendations remains widespread, estimated in France at 20% for hypnotic BZDs.
Objectives
The aims of our study were to evaluate BZDs prescribing practices in the treatment of insomnia and to assess their compliance with international recommendations.
Methods
This is a cross-sectional study conducted through a Google-forms self-administered questionnaire,intended for psychiatrists and psychiatric residents, over a period of two months, from April 1 to May 31, 2019.
Results
One hundred physicians practicing in psychiatry answered our questionnaire. The response rate was 28%. Four BZDs are recommended for the treatment of insomnia, none of which is available in Tunisia. Almost the third of the participants did not systematically look for signs of sleep apnea syndrome before treating an insomnia (30.5%). For treating insomnia, the majority of the participants began by indicating hygieno-dietetic rules (64%), 4% prescribed directly a BZD. Cognitive behavioral therapy was not indicated at all by the particiants. The maximum duration of prescribing BZDs in insomnia was 4 weeks in 20% of cases, and more than 4 weeks in 38% of cases. Among the participants, 41% prescribed BZDs for the treatment of chronic insomnia.
Conclusions
Insomnia appear to be badly managed and early drug prescribing is frequent. These practices do not comply with the recommendations of good practice and increase the risk of dependance and other side effects.
Benzodiazepines (BZD) are psychotropic drugs prescribed in psychiatry for their anxiolytic, hypnotic and sedative properties. Since anxiety, agitation and insomnia are common in psychoses and mood disorders, BZDs are frequently prescribed in the treatment of these pathologies. Guidelines remain rare with regard to the use of BZDs in the treatment of psychosis and bipolar disorder.
Objectives
Our study aimed to evaluate BZDs prescribing practices in psychoses and bipolar disorder and to assess the specific risks related to the use of these molecules in the population suffering from severe mental disorder.
Methods
This is a descriptive cross-sectional study conducted through a Google-forms self-administered questionnaire, intended for psychiatrists and psychiatric residents, over a period of two months, from April 1 to May 31, 2019.
Results
One hundred physicians practicing in psychiatry answered our questionnaire. The response rate was 28%. BZDs were prescribed during thymic or psychotic relapses by 88.6% of the participants. During relapses, the main indication for BZDs was anxiety (81.3%), insomnia (80.2%), and catatonia (59.4%). Among the participants, 24.8% indicated that they maintained a long-term treatment with BZDs in patients with psychosis, and 11.4%in patients with bipolar disorder. The participants estimated that the long-term use of BZDs in patients with severe mental disorder represented an increased risk of : dependence (94.3%), behavioral disinhibition (30.5%), suicide (22.9%), anger, hostility and violence (31.4%).
Conclusions
Few guidelines concern the use of BZDs in psychosis and bipolar disorder. However, this prescription remains very frequent in current practice, with clinical and therapeutic features specific to this population.