BACKGROUND: Benzodiazepines are frequently prescribed to treat anxiety and insomnia, but long-term use has been associated with the development of dependence, tolerance, and cognitive decline, especially among older adults. This study aimed to investigate the pattern of consumption and factors associated with inappropriate prescribing of benzodiazepines in primary health care.
METHODS: This is a cross-sectional analytical study, using dispensing records of diazepam, clonazepam, and nitrazepam from public pharmacies in a Brazilian municipality between 2018 and 2022. Metrics for benzodiazepine consumption were DDD (Defined Daily Dose) and DDD/1000PD (per 1000 population per day). Long-term/prolonged benzodiazepine use was defined as consuming at least 90 DDD and at least 2 dispensations per year. To ascertain associations between long-term use and predictor variables, a multivariate logistic regression model was utilized.
RESULTS: A total of 40402 participants were included, with an average age of 55 years (SD = 0.30), 38.5% were older aged. Diazepam and nitrazepam exceeded the daily dose recommended. There was a reduction in diazepam consumption during the study period, as calculated by DDD/1.000PD, while the consumption of other benzodiazepines remained stable. However, a significant increase in diazepam consumption is noted when considering the last decade. Prolonged use was observed in 29.1% of participants, with a significant prevalence among the older people (34.8% of them were long-term users) and advancing age was identified as a risk factor for long-term use. Higher PDDs were also associated with long-term use and aging. Participants who used different benzodiazepines during the period had a higher risk of prolonged use.
CONCLUSIONS: These results provide insights into the prevalence of problematic utilization of benzodiazepines in primary health care. Authorities and health care providers must take steps to encourage gradual cessation of prolonged benzodiazepine prescriptions and the embrace of suitable strategies for addressing anxiety and insomnia within primary health care settings.

Familial paroxysmal non-kinesigenic dyskinesia, which is a major form of paroxysmal dyskinesias, is characterized by intermittent attacks that include one side, subsequently spreading to the other side, involving the limbs and face, and is triggered by caffeine, alcohol, emotional stress, fatigue, and sleep deprivation, but not by sudden movement. A 26-year-old man had experienced dystonic movements and a choreiform right arm spreading to his arms, legs, and face since the age of one year. Oral dyskinesias and, rarely, dysarthria were also observed. Attacks lasting approximately five minutes occurred several times per day. Over three generations, his family members inherited a c.26C > T (p. Ala9Val) missense mutation in exon 1 of PNKD/MR-1 in an autosomal dominant manner and reported similar symptoms with clinical manifestations ranging from mild to severe. His scores on the Self-Rating Depression Scale, State-Trait Anxiety Inventory, and Profile of Mood States were high. This suggests that the patient also had comorbidities of anxiety and depression. The patient\'s attacks decreased from two times per week to once every two months, and his State-Trait Anxiety Inventory score decreased by 5-10 points on treatment with clonazepam and sertraline, allowing his condition to become stable enough that he was able to participate in society. Drug therapy with clonazepam and sertraline is the preferred treatment for reducing attacks in PNKD patients with strong anxiety and depression.

The global concern over water pollution caused by contaminants of emerging concern has been the subject of several studies due to the complexity of treatment. Here, the synthesis of a graphene oxide-based magnetic material (GO@Fe3O4) produced according to a modified Hummers\' method followed by a hydrothermal reaction was proposed; then, its application as a photocatalyst in clonazepam photo-Fenton degradation was investigated. Several characterization analyses were performed to analyze the structure, functionalization and magnetic properties of the composite. A 23 factorial design was used for the optimization procedure to investigate the effect of [H2O2], GO@Fe3O4 dose and pH on clonazepam degradation. Adsorption experiments demonstrated that GO@Fe3O4 could not adsorb clonazepam. Photo-Fenton kinetics showed that total degradation of clonazepam was achieved within 5 min, and the experimental data were better fitted to the PFO model. A comparative study of clonazepam degradation by different processes highlighted that the heterogeneous photo-Fenton process was more efficient than homogeneous processes. The radical scavenging test showed that O 2 · - was the main active free radical in the degradation reaction, followed by hydroxyl radicals (•OH) and holes (h+) in the valence layer; accordingly, a mechanism of degradation was proposed to describe the process.

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970s. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) is not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.

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OBJECTIVE: Lance-Adams syndrome is a rare and debilitating disorder characterized by successful cardiopulmonary resuscitation resulting in myoclonus activity. Alcohol withdrawal seizures from alcohol use disorder may further exacerbate Lance-Adams syndrome. We aim to present a case of Lance-Adams syndrome complicated by alcohol withdrawal seizures and successfully treated with a combination of valproate, clonazepam, and gabapentin.
METHODS: The patient\'s electronic medical record, direct patient care experiences, and a comprehensive literature search were used for this case report. We report a 41-year-old male patient with Lance-Adams syndrome with concurrent alcohol use disorder. Treatment was improved when adding gabapentin for alcohol use disorder treatment, alongside combination antiepileptic therapy. A PubMed search was conducted to examine Lance-Adams syndrome case reports of successful combination antiepileptic therapy, with a secondary evaluation of patients with concurrent alcohol use disorder.
RESULTS: The literature search yielded 18 articles, which resulted in 21 individual cases in which combination antiepileptic drug therapy was successful in treating myoclonus secondary to Lance-Adams syndrome; however, none of the case reports utilized gabapentin synergistically. One case described Lance-Adams syndrome complicated by alcohol consumption and similar to our patient, the patient used alcohol to abolish myoclonic activity.
CONCLUSIONS: To the best of our knowledge, this is the first case report documenting a patient with Lance-Adams syndrome and concurrent alcohol use disorder, with a positive effect of gabapentin use. Gabapentin, when used for alcohol use disorder treatment, may be an appropriate adjunct agent in the management of patients receiving combination antiepileptic therapy for the treatment of Lance-Adams syndrome.

Hyperekplexia (HPX) is a rare hereditary disorder characterized by an exaggerated startle reflex and neonatal hypertonia. It exhibits both autosomal dominant and autosomal recessive inheritance patterns, depending on the gene involved. It could be a fatal neurogenetic disorder, but it is treatable. We reported a nine-month-old female child with mild gross motor delay, an exaggerated startle reflex, and multiple episodes of transient hypertonia. Neurological and electrophysiological investigations and clinical presentation suggested the diagnosis of hereditary HPX. The child showed a good response to oral clonazepam, with a reduced frequency of such episodes and attainment of age-specific milestones.

Benzodiazepines are commonly used drugs to treat anxiety in crime witnesses. These increase GABA inhibitory effects, which impairs aversive memory encoding and consolidation. Eyewitness memory is essential in justice. However, memory is malleable leading to false memories that could cause a selection of an innocent in a lineup. Here, we studied whether a low dose of Clonazepam impairs memory encoding as well as consolidation of faces and narrative of the event. We performed two experiments using a double-blind and between subject design (N = 216). Day 1: subjects watched a crime video and received Clonazepam 0.25 mg (CLZ group) or placebo (PLC group) before (Exp. 1) or after the video (Exp. 2) to assess the effect on encoding and consolidation. One week later, the memory was assessed using a present and absent target lineup and asking for a free recall. Regarding encoding, we found that in the CLZ group memory was impaired in the free recall task, while no differences were found for recognition memory. Regarding consolidation, we did not observe memory measures that were affected by this dose of benzodiazepines. The results suggest that while some aspects of eyewitness memory could be modulated even with low doses of benzodiazepine, others could not be affected. More studies should be performed with higher doses of CLZ similar to those administered in real life. These results are relevant in the judicial field to assess the reliability of the eyewitness elections under the effects of this drug.

BACKGROUND: Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia.
METHODS: This open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years.
RESULTS: Each group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (-4.5 ± 2.9 vs -3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events.
CONCLUSIONS: A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.