Psychogenic Hyperphagia: Excessive Eating as Stereotypy in a Patient with Catatonia.

Catatonia is a complex syndrome with unique cognitive, psychomotor, and mood features. Mannerisms and stereotypies are catatonic signs that have been extensively observed and described in the literature, mostly in the context of movements or motor acts. Stereotypies are commonly described as repetitive psychomotor or verbal acts with the abnormality not inherent in the act but in its frequency. Mannerisms, like stereotypies, are repetitive psychomotor or verbal acts, but they are fundamentally odd in nature. Recently, several reports have described these phenomena in the context of complex behaviors, such as eating and drinking. Identification and appreciation of personal and cultural norms, in addition to a careful analysis of behavioral processes and actions, are important tools for clinicians to identify these potentially elusive and often missed patterns of behavior in patients with catatonia. We present the case of a 30-year-old male with a psychiatric history of treatment-resistant, recurrent major depressive disorder with psychotic features who presented to the inpatient psychiatric unit with signs of catatonia, including repeated, purposeless eating. The patient's chart was reviewed, and a literature review was conducted using PubMed with the keywords catatonia, stereotypies, mannerisms, and hyperphagia. The patient, who was diagnosed with catatonia and expressed hyperphagia as a stereotypy, responded to lorazepam. This case shows that hyperphagia may present as a stereotypy in patients with catatonia.

Influence of GABAA and GABAB receptor activation on auditory sensory gating and its association with anxiety in healthy volunteers.

BACKGROUND: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). AIMS/METHODS: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety. RESULTS: Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety. CONCLUSIONS: These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABAB receptor signaling in anxiety-associated gating dysregulation.

Catatonia in patients with dementia: A descriptive study of clinical profiles and treatment response.

BACKGROUND: Catatonia is a highly prevalent syndrome in patients presenting with major neurocognitive disorders (dementia). In this study, we aim to provide a comprehensive description of the clinical and therapeutic aspects of catatonia in patients with dementia. METHOD: This descriptive study, conducted between September 2015 and June 2022, collected data from 25 patients diagnosed with dementia, out of 143 patients treated for catatonia in our specialized psychiatry department. We collected sociodemographic, clinical and treatment data for each patient. RESULTS: Dementia patients constituted 17% of the catatonic cases. Predominantly female, the cohort had a mean age of 65. Diagnoses included Alzheimer's (4 patients, 17%) and Parkinson's (1 patient, 4%) diseases, Lewy body dementia (5 patients, 21%), vascular dementia (4 patients, 17%) and frontotemporal lobar degeneration (10 patients, 41%). The mean Bush-Francis Catatonia Rating Scale score upon admission was 20/69. Overall, complete remission of catatonia was achieved in 75% of patients (n=18), with only 13% (n=3) responding to lorazepam alone, while others required additional interventions such as electroconvulsive therapy (ECT) and/or amantadine. Vascular dementia was predominantly observed in cases resistant to treatment. CONCLUSION: The findings indicate a frequent co-occurrence of catatonia and dementia, highlighting treatability yet suggesting a potential for resistance to lorazepam, which varies by dementia diagnosis. Investigating the mechanisms underlying this resistance and the variability in treatment response is crucial for developing more precise therapeutic strategies.

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety.

BACKGROUND: Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed because many patients do not respond to current agents or experience unwanted side effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalized anxiety in healthy volunteers. METHODS: Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic "lorazepam" or "saline." Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. RESULTS: Participants administered sham "lorazepam" reported significant positive expectations of reduced anxiety (P = .001), but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (Ps > .350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. CONCLUSIONS: Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function or behavior in line with a Bayesian predictive coding framework attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.

Predictors for and use of rescue medication in adults with epilepsy: A multicentre cross-sectional study from Germany.

BACKGROUND: Seizure clusters, prolonged seizures, and status epilepticus are life-threatening neurological emergencies leading to irreversible neuronal damage. Benzodiazepines are current evidence-based rescue therapy options; however, recent investigations indicated the prescription of mainly unsuitable benzodiazepines and inappropriate use of rescue medication. OBJECTIVE: To examine current use, satisfaction, and adverse events concerning rescue medication in patients with epilepsy in Germany. PATIENTS AND METHODS: The study was conducted at epilepsy centres in Frankfurt am Main, Greifswald, Marburg, and Münster between 10/2020 and 12/2020. Patients with an epilepsy diagnosis were assessed based on a questionnaire examining a 12-month period. RESULTS: In total, 486 patients (mean age: 40.5, range 18-83, 58.2 % female) participated in this study, of which 125 (25.7 %) reported the use of rescue medication. The most frequently prescribed rescue medications were lorazepam tablets (56.8 %, n = 71 out of 125), buccal midazolam (19.2 %, n = 24), and rectal diazepam (10.4 %, n = 13). Seizures continuing for over several minutes (43.2 %, n = 54), seizure clusters (28.0 %, n = 35), and epileptic auras (28.0 %, n = 35) were named as indications, while 28.0 % (n = 35) stated they administered the rescue medication for every seizure. Of those continuing to have seizures, 46.0 % did not receive rescue medication. On average, rescue medication prescription occurred 7.1 years (SD 12.7, range 0-66) after an epilepsy diagnosis. CONCLUSIONS: Unsuitable oral benzodiazepines remain widely prescribed for epilepsy patients as rescue medication. Patients also reported inappropriate use of medication. A substantial proportion of patients who were not seizure-free did not receive rescue medication prescriptions. Offering each patient at risk for prolonged seizures or clusters of seizures an individual rescue treatment with instructions on using it may decrease mortality and morbidity and increase quality of life. .

EEG and video documentation of benzodiazepine challenge in catatonic stupor: A case report.

INTRODUCTION: Catatonia, a psychomotor disorder characterized by diverse clinical signs, including stupor and mutism, remains elusive in its causes and a challenge to diagnose. Moreover, it is often underrecognized due to its resemblance to disorders of consciousness. However, when diagnosing catatonia, an antipsychotic medication may exacerbate the condition. The first-line treatment typically includes benzodiazepines and/or electroconvulsive therapy (ECT). CASE REPORT: A 60-year-old woman with systemic lupus erythematosus (SLE) and epilepsy presented with catatonic stupor. Despite stable treatment, she experienced an acute deterioration in consciousness, requiring hospitalization. Her condition improved markedly following a benzodiazepine challenge, as documented on EEG. This improvement was short-lived, but a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes, as documented by a video recording. The patient was treated with lorazepam 1.5 mg/day orally and did not experience further relapses. DISCUSSION: The diagnosis of catatonia had been based on her scores on the Bush-Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), despite meeting only two DSM-5 criteria for catatonia (stupor and mutism). The diagnosis was supported by EEG and video documentation, excluding other potential differential diagnoses such as nonconvulsive status epilepticus and encephalopathy. Additional quantitative EEG analyses indicated that benzodiazepine administration increased brainwide alpha and beta band power significantly, suggesting that the benzodiazepine normalized attention, consciousness, and long-range synchronization. This report additionally emphasizes the significance of video recordings in managing catatonia, and it helps in accurately tracking symptoms, documenting comprehensively, and improving patient understanding, which is crucial for treatment adherence.

A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department.

BACKGROUND: Phenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. OBJECTIVES: We compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. METHODS: This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. RESULTS: Among the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. CONCLUSIONS: Patients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

Risk of suicide attempts and intentional self-harm on alprazolam.

BACKGROUND: From 2000-2021, U.S. suicide deaths have risen 36 %. Identification of pharmacological agents associated with increased suicide risk and safer alternatives may help reduce this trend. METHODS: An exposure-only within-subject time-to-event pharmacoepidemiologic study of the dynamic association between alprazolam treatment and suicide attempts over 2-years. Parallel analyses were conducted for diazepam, lorazepam and buspirone. Data for 2,495,520 patients were obtained from U.S. private insurance medical claims MarketScan from 2010 to 2019. FINDINGS: Alprazolam was associated with over a doubling of risk of suicide attempts (HR=2.21, 95 % CI=2.06,2.38). A duration-response analysis for the modal dose (0.5 mg) revealed a 5 % increase in suicidal events per additional month of treatment (HR=1.05, 95 % CI=1.04,1.07). Parallel analyses with long-acting (diazepam) and short-acting (lorazepam), found similar associations (diazepam HR=2.87, 95 % CI=2.56,3.21; lorazepam HR=1.83, 95 % CI=1.69,2.00), whereas the non-benzodiazepine anxiolytic, buspirone, showed significantly less risk (HR=1.25, 95 % CI=1.13,1.38), and no increased risk in patients with an attempt history (HR=1.05, 95 % CI=0.70,1.59). INTERPRETATION: This study confirmed an earlier signal linking alprazolam to increased suicide attempt risk. The increased risk extends to benzodiazepines in general, regardless of half-life and risk of withdrawal seizure. Buspirone appears to be a safer treatment than benzodiazepines, particularly in patients at increased risk for suicide.

Thought Blocking as a Manifestation of Catatonia: A Case Report.

ABSTRACT: Catatonia is an underrecognized disorder that has been widely described as a psychomotor syndrome, with little emphasis on its thought and cognitive dimensions. The current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision describes only motor and behavioral presentations, whereas a few catatonia scales describe only one form of thought disorders, which is thought perseveration. Thought blocking, a disorder of the thought process, is characterized by regular interruptions in the thought stream. It was described by several scholars as a sign of schizophrenia, with few reports describing thought blocking in association with catatonia. In this article, we describe the course of a patient with bipolar I disorder who presented with catatonia and demonstrated thought blocking. Her catatonic symptoms and thought blocking improved with the addition of lorazepam, recurred upon lorazepam discontinuation, and improved with resumption of lorazepam, demonstrating a clear on/off phenomenon. This report highlights the importance of recognizing thought and cognitive manifestations of catatonia, as it can enhance recognition and improve treatment.

Negative emotionality downregulation affects moral choice but not moral judgement of harm: a pharmacological study.

Previous neuroscientific research has expounded on the fundamental role played by emotion during moral decision-making. Negative emotionality has been observed to exert a general inhibitory effect towards harmful behaviors against others. Nevertheless, the downregulation of negative affects at different levels of moral processing (e.g. impersonal versus personal moral dilemmas) alongside its possible interactions with other factors (e.g. perspective taking) hasn't been directly assessed; both of which can assist in predicting future moral decision-making. In the present research, we empirically test (Study 1, N = 41) whether downregulating negative emotionality through pharmacological interventions using lorazepam (a GABA receptor agonist), modulate the permissibility of harm to others -i.e. if participants find it more morally permissible to harm others when harm is unavoidable (inevitable harm moral dilemmas), than when it may be avoided (evitable harm moral dilemmas). Furthermore, using another sample (Study 2, N = 31), we assess whether lorazepam's effect is modulated by different perspective-taking conditions during a moral dilemma task -e.g. "is it morally permissible for you to […]?" (1st person perspective), relative to "is it morally permissible for [x individual] to […]?" (3rd person perspective)-, where the outcome of the different scenarios is controlled. The results of both studies converge, revealing an emotion-dependent, rather than an outcome-dependent, pharmacological modulation. Lorazepam only influenced interpersonal moral judgments when not modulated by the evitable/inevitable condition. Furthermore, there was a significant interaction between perspective-taking and drug administration, as lorazepam exerted a larger effect in modulating moral choices rather than moral judgements.

Trace analysis of 47 psychotropic medications in environmental samples by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Psychotropic medications are one of the most prescribed pharmaceuticals in the world. Given their frequent detection and ecotoxicity to the no-target organism, the emission of these medications into environments has gradually draw attention. The study developed a sensitive and reliable analytic method to simultaneously investigate 47 psychotropic medications in four matrices: wastewater, surface water, activated sludge, and sediment by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). These 47 target analytes include 24 antidepressants, 17 antianxiety drugs, 5 anticonvulsants, and 1 relevant hormone. Solid phase extraction (SPE) was employed to extract analytes from water-phase samples. Ultrasonic Solvent Extraction method with Enhanced Matrix Removal clean-up (USE-EMR) was utilized to extract target compounds from solid-phase samples, which requires more straightforward and convenient procedures than previous methods. The extraction recoveries of all analytes ranged from 80 % to 120 % in these four sample matrices. In this study, The limit of quantitation for 47 psychotropic medications were 0.15 ng/L (estazolam) to 2.27 ng/L (lorazepam), 0.08 ng/L (desvenlafaxine) to 2 ng/L (mianserin), 0.22 ng/g (dry weight, dw) (nordiazepam) to 3.65 ng/g (dw) (lorazepam), and 0.07 ng/g (dw) (carbamazepine) to 2.85 ng/g (lorazepam), in wastewater, surface water, sludge, and sediment, respectively. In addition, the developed method was employed to analyse actual samples in two wastewater treatment plants and their receiving rivers. Carbamazepine, escitalopram, clozapine, desvenlafaxine, diazepam, lamotrigine, sertraline, temazepam, and venlafaxine were nearly ubiquitous in all matrices. Moreover, this study indicated that the inadequate removal efficiencies of psychotropic medications in wastewater treatment plants (WWTPs) had resulted in a persistent discharge of these contaminants from human sources into environments.

The role of benzodiazepines in common conditions: a narrative review focusing on lormetazepam.

This review aimed to examine the place of benzodiazepines, specifically lormetazepam, in the treatment of insomnia, including during pregnancy or in patients with psychodermatoses. PubMed was searched for the term "lormetazepam" in association with MeSH terms encompassing anxiety, insomnia/sleep disorders, pregnancy/gestation, and psychodermatoses/skin disorders. English-language articles up to 31 July 2022 were identified. Ad hoc searches for relevant literature were performed at later stages of review development. Multiple randomized, placebo-controlled studies have demonstrated that lormetazepam dose-dependently increases total sleep time, decreases wakefulness over a dosing range of 0.5-2.0 mg, and improves subjective assessments of sleep quality. Lormetazepam is as effective as other benzodiazepines in improving sleep duration and quality, but is better tolerated than the long-acting agents with minimal next-day effects. Benzodiazepines can be used as short-term monotherapy at the lowest effective dose during the second or third trimesters of pregnancy; lormetazepam is also a reasonable choice due to its limited transplacental passage. Insomnia associated with skin disorders or pregnancy can be managed by effective symptom control (especially itching), sleep hygiene, treatment of anxiety/depression, and a short course of hypnotics.

Lorazepam in catatonia - Past, present and future of a clinical success story.

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1-2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population. METHODS: In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days. RESULTS: A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups. CONCLUSION: Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.