Last month, the research round-up provided you with an overview of three varied articles on the topic of opioid stewardship. This month, we will review three articles concerned with prescribing benzodiazepines.
The first article looks at the co-prescribing of opioids and benzodiazepines in oncology care. The second article reviews the use of benzodiazepines in status epilepticus. Finally, our third article deals with benzodiazepine use versus clonidine in alcohol withdrawal management.
Opioids and benzodiazepines in oncology: perspectives on co-prescribing and mitigating risks
This article, published in the Journal of Geriatric Oncology, sought to understand the practices of cancer care providers around the prescription of opioids and benzodiazepines when co-prescribed in cancer care, and to elucidate and mitigate potential harms.
The research aimed to understand the extent of this common co-prescribing pairing using outpatient settings in two large academic medical centres located on the eastern border of the United States. These centres provided oncological and palliative care management of pain and other symptoms. This qualitative study, using semi-structured interviews, sought attitudes on current prescribing practices for opioids and benzodiazepines and included factors affecting clinical decision-making and risk mitigation between March and September 2023. Interviewees included medical doctors and advanced practice providers. In total, 20 providers were recruited with an even split between oncology and palliative care settings.
‘The authors suggest that the treatment of patients with all types of status epilepticus treated with benzodiazepines was suboptimal regarding both overall usage and dosing’
Findings showed that the majority of cancer patients received opioids for pain, so the focus of the discussion centred around the decisions to co-prescribe benzodiazepines. Thematic data analysis elucidated three themes worthy of discussion. These were, reluctance to prescribe benzodiazepines, medication safety precautions, and risk assessment and monitoring.
The findings showed that providers were reluctant to co-prescribe benzodiazepines except in certain circumstances due to risk of falls, delirium and addiction potential. The cited needing to be cautious and unfamiliarity as primary issues. Results showed that providers used an array of precautionary measures to mitigate risks form a medication safety perspective.
These included a one provider approach, education around use of naloxone, safety checks, advice on driving while on the medication, and family and carer involvement. From a risk assessment and monitoring perspective it was found that most providers checked state prescription monitoring databases as well as rigorous review of notes and charts before co-prescribing was initiated or continued.
Another finding was that many providers felt uncomfortable discussing substance misuse history due to concerns about stigma and acknowledging value-based judgment in this area with risk of bias.
The authors conclude that there are still opportunities to improve provision including consistent review of medications, increased awareness of use of naloxone, and better attention to addressing potential substance misuse issues.
Use of benzodiazepines in patients with status epilepticus requiring second-line antiseizure medication treatment
This article, published in the journal Epilepsy Research, aimed to investigate whether management of status epilepticus with benzodiazepines was adequate in a population of patients where second-line anti-seizure medication was required. A secondary aim was to ascertain if suboptimal benzodiazepine treatment was identified, along with factors that could explain this phenomenon.
The study was conducted in a single centre university hospital in Finland and comprised a retrospective analysis of data from the patient register of any patient over 16 requiring second-line intravenous anti-seizure medication for status epilepticus after the administration of benzodiazepines. This was carried out looking at records from a one-year period in 2015. Treatment was considered to be suboptimal if it was not in line with the latest European, Finnish or American guidelines.
After application of inclusion and exclusion criteria, 109 episodes covering 94 patients were included for study. Inclusion and exclusion criteria were around types of statis epilepticus (convulsive, post-ictal, non-convulsive and focal) and the common second-line medications used to treat (including fosphenytoin, lacosamide, levetiracetam and valproate).
Results showed that, in the majority of the episodes (77%), benzodiazepines were administered and 43% of these were in line with accepted guidelines. In the non-convulsive group studied, benzodiazepines were used less frequently, and when used did not always conform to guidelines than in other groups. For focal seizures, adherence to guideline prescription was very low with issues around dose and administration noted.
The authors suggest that the treatment of patients with all types of status epilepticus treated with benzodiazepines was suboptimal regarding both overall usage and dosing, especially for patients with non-convulsant type. In fact, less than half of the episodes studied conformed to guideline use. It was also noted that when benzodiazepines were given intravenously, the dose was lower than that when administered via other routes such as buccal or rectal.
Finally, the clinical characteristics of the patients did not influence the dosage of drug administered. They conclude that there is frequent suboptimal use and non-adherence to guidelines and suggest that changes are required to ensure timely and adequate usage of benzodiazepines as first-line management and that this is essential for improving the care of this patient group.
A detox dilemma beyond benzodiazepines: clonidine's quandary in alcohol withdrawal management
Our final article, published in the American Journal on Addictions, aimed to assess how frequently clonidine is used as an adjunct for the known increase in blood pressure and pulse seen in alcohol withdrawal management as opposed to benzodiazepines.
They acknowledge that benzodiazepines are the mainstay of treatment in the Unites States and conducted this pilot observational study in a single site Department of Veterans' Affairs centre using retrospective data collection from patient records.
The retrieval of data was between July 2022 to June 2023 and included patients with alcohol withdrawal which was managed using a standard Clinical Institute Withdrawal Assessment for Alcohol score.
After application of inclusion and exclusion criteria, 167 patient records were identified for analysis. The mean age of this group was 54 (years) with a range of 24–78 years. There were 90 (93.8%) males and six (6.2%) females. Of these 167 patients, 99 (59.3%) carried a diagnosis of hypertension.
Of the 241 medication doses given for the management of elevated blood pressure/pulse, 235 (97.5%) were for benzodiazepines (broken down to 223 prescribed lorazepam and 12 were prescribed diazepam) whereas only six (2.5%) were prescribed clonidine.
The authors observed, as suspected, that benzodiazepines seemed to sometimes be used more than strictly necessary, and that there may be underuse of adjunctive medications, including clonidine. They state it is important to understand that adjunctive treatment should be not aimed at replacing benzodiazepines as the primary drug choice, rather they should be considered in that there could be a potential reduction of benzodiazepine usage. This may subsequently reduce risk of side and adverse effects by diminishing overuse and that this intervention could improve outcomes for patients experiencing withdrawal who need management of their elevated blood pressure/pulse.
They conclude that this pilot observational study, which only looked at clonidine as an adjunct, was not generalisable and that further study should include other adjuvant medications included within withdrawal management guidelines with a view to minimising benzodiazepine overuse.
Conclusion
For many prescribers, benzodiazepines can be a drug that appears in their ‘worry list’, often due to the chance of developing addiction and poor safety profile. However, we can see from these three articles that there are areas of clinical practice that can benefit from benzodiazepine prescribing, as long as safety concerns are paramount and guidelines followed.