Recommendations for the responsible use of benzodiazepines in mental health care in Serbia

Authors: Nađa P. Marić, Milutin Kostić, Janko Samardžić, Slobodanka Pejović- Nikolić, Olivera Vuković
Publisher: Institute of Mental Health, Belgrade, 2020. ISBN 978-86-82277-69-9

Recommendations for the responsible use of benzodiazepines in mental health care in Serbia, written by Marić NP, Kostić M, Samardžić J, Pejović- Nikolić S and Vuković O, and published in 2020 by the Institute of Mental Health in Belgrade, is a contemporary and comprehensive book intended for psychiatrists, other health workers, associates and students, as well as all readers interested in the application of medicines which are amongst the most frequently used medications in the general population, both globally and in Serbia. These recommendations have been published in the year marking six decades since the first molecule from the benzodiazepine group was registered for therapeutic application.

Benzodiazepines are one of the pharmacological agents that are most frequently prescribed to patients and which are used more and more in many countries all over the world. In addition to application in clinical therapy, non-medical use and abuse of benzodiazepines is also registered, representing an increasingly present public health problem. It is estimated that 20% of the people in Serbia use one of the benzodiazepines, and that in more than 4% of the cases this use is at acritical level, as measured by the number of emergency admissions resulting from the overuse of CNS depressors.

The book Recommendations for the responsible use of benzodiazepines in mental health care in Serbia has appeared at a time when we are faced with the global pandemic caused by the SARS-COV-2 virus, but also with the uncertainty and all the unknowns that it brings with it, consequently leading to the deterioration of mental health in the population. Bearing in mind the legislation that is currently in effect in Serbia, general practitioners have a great responsibility, since they are authorized to prescribe benzodiazepines, without consulting a specialist, for significantly longer periods than the recommendations suggest. This necessitates the modification of such legislation, but also emphasizes the significance of the recommendations.

A group of psychiatry and pharmacology professors, teaching fellows and assistants from the Faculty of Medicine of the Belgrade University took upon itself a challenging task and systematically gathered and presented a review of Serbian and international literature as well as levels of proof on benzodiazepine use. As an example of good practice, recommendations from the Guidebook issued by the Singapore Ministry of Health in 2008¹, have been presented in the book, together with stated levels of proof and the category of recommendations applied.

The book Recommendations for the responsible use of benzodiazepines in mental health care in Serbia has three chapters and appendices. The first chapter describes the history of the development and application of benzodiazepines as well as their pharmacological characteristics (pharmacokinetics and the pharmacological profile). It also describes the risks that the use of benzodiazepines carries, which have been neglected until now; such as falls, fractures, traffic accidents and work-related injuries. An overview of benzodiazepines according to Anatomical Therapeutic and Chemical (ATC) Classification is also given. The most frequently used benzodiazepines and “Z drugs”: alprazolam, bromazepam, diazepam, lorazepam, midazolam, clonazepam and zolpidem are presented as well, with a detailed tabular overview of the pharmacokinetic characteristics of these drugs. The parallel between the pharmacokinetic characteristics of the most commonly prescribed benzodiazepines from the anxiolytic group of drugs and the most commonly prescribed “Z drug” has also been presented clearly, together with the equivalent dose as compared to 10 mg of diazepam, the time needed for the medication to reach peak plasma concentration following drug administration, as well as the average elimination time. The basic regulations regarding benzodiazepine prescription are presented, as are the epidemiological data on the application of these drugs and their non-medical use.

The second chapter contains the description of the indications, length of application, contraindications, and interactions of benzodiazepines with other drugs. A recommendation is given to doctors that, when prescribing any of the drugs from the benzodiazepine group, they should carefully consider the length of use for acute complaints in every individual patient. The indications for the application of benzodiazepines, which include panic disorder, generalized anxiety disorder, social phobia, insomnia, catatonia, as well as symptoms occurring during alcohol discontinuation, epileptic seizure, acute dystonia, putting a patient under anesthesia and acute hypertensive crisis, are precisely listed and described. In the description of the contraindications it is especially emphasized that these medications are contraindicated in children and adolescents, as well as that the dosage needs to be adjusted in elderly patients. It is also stressed that benzodiazepines are recommended with great caution in the treatment of post-traumatic stress disorder. The groups of drugs that benzodiazepines interact with are listed in detail, as well as the interactions with other substances, for instance alcohol. A recommendation is given regarding detailed assessment of interactions, their prevention or mitigation and the reader is referred to relevant data bases.

In the third chapter, the authors of these recommendations emphasize the danger of abuse, dependency and “recreational” use of this group of drugs, which is backed by current information. Special attention is given to the duration of the effects and the risks of use, as well as to the responsible approach to treatment with benzodiazepines. The importance of the development of drug tolerance coupled with loss of effectiveness is explained and it is stressed that there is no proof of long-term effectiveness or of effectiveness outside the prescribed indications. Vulnerable groups are outlined, and it is stated that benzodiazepine use can be decreased where psychotherapy is more easily accessible. The types of benzodiazepine users are defined, with special attention to the application of benzodiazepines in patients with psychotic disorders, and a warning against the practice of prescribing these drugs to this group of patients, stating the resulting side-effects, is noted, since their application in such cases is associated with an increase in cognitive difficulty, dysfunctionality and with a higher mortality rate. Pregnant and lactating women are marked as one of the important vulnerable categories, and adverse effects of benzodiazepine application, in pregnancy, on the newborn are described. Insight is provided into the application of benzodiazepines in combination with antidepressants, as well as into the advantages and disadvantages of their combined use, but also into the lack of consistent proof related to this problem.

The way that the book is written, and the presentation of the data is contemporary and accessible for application by health professionals. The recommendations are simple to implement, they are unambiguous and leave no room for different interpretation. The authors have substantiated their assertions with a variety of proof from literature, with an especially careful insight into cases of inconsistent proof. Bearing in mind the high frequency of benzodiazepine use and non-medical use in Serbia, a guidebook which unites recommendations in one place, but also draws attention to the adverse effects of both short-term and long-term use of these drugs, is of great importance.

This pioneer undertaking can be assessed very highly, and it leaves room for further work with the emergence of new scientific evidence. These recommendations can be significant for all doctors in the entire system of health care, at all of its levels, primary, secondary and tertiary, and for all those involved in population health care and health improvement, and who, in their everyday clinical practice, come into contact with patients who have been prescribed drugs belonging to the benzodiazepine group.