Who’s Afraid of Benzodiazepines?

The questions are (a) where this specific discrepancy about the use of benzodiazepines between some experts and many clinicians in the field is coming from and (b) why do some psychiatrists and other physicians so vigorously oppose or are afraid of prescribing benzodiazepines. Is the disagreement reflecting the difference between evidence-based medicine and the practice of real-life clinical medicine? Are the differences in the eyes of the beholders? It is also important to note that most prescribers of benzodiazepines are in primary care specialties – during 2014–2016, approximately 48% of visits at which benzodiazepines were prescribed in a primary care setting [5]. Among nonprimary care prescribers, visits to psychiatrists accounted for 28% (14.6% of all visits) of those where benzodiazepines were prescribed [5]. That seems low, considering that psychiatrists should be most comfortable and competent in prescribing psychotropic medications.

We can speculate about the answers to these questions. As far as the hesitancy or opposition of some experts is concerned, this may depend on the area of their clinical expertise or on the body of clinical research they have conducted. Physicians involved in the treatment of substance use disorders tend to view prescribing benzodiazepines unfavorably. Use of benzodiazepines in this population of patients is controversial and routine benzodiazepine use should be avoided when patients are actively abusing certain substances (namely alcohol and opioids), although not necessarily all (e.g., cocaine and stimulants). Many experts have also been heavily involved in clinical trials of alternatives of benzodiazepines, e.g., selective serotonin reuptake inhibitors (SSRIs), and thus may be consciously or unconsciously avoiding benzodiazepines. Similarly, experts in geriatric psychiatry mostly avoid prescribing benzodiazepines due to some of their side effects that are specific to geriatric patients (which may actually be a question of dosage). It is also presumable that experts, either those in academia or those in busy clinical trial centers, do not see as many complex patients with anxiety or anxiety disorders as compared to clinicians in busy clinical practices.

As far as a fear of prescribing benzodiazepines among psychiatrists and other physicians, there are, in my opinion, four main reasons: (1) psychiatrists may be afraid of prescribing medications that they perceive to be complicated to prescribe or “dangerous”; (2) the “scarecrow” of substance abuse and dependence; (3) marketing of other medications for anxiety, e.g., SSRIs; and (4) various not fully substantiated claims such as the association between benzodiazepines and dementia, depression, and rebound anxiety following benzodiazepine discontinuation.

Concern among psychiatrists about prescribing certain medications has been illustrated in several surveys. A survey of prescribing practices for MAOIs in Michigan in the late 1990s [6] documented that psychiatrists believed that MAOIs were efficacious but used them infrequently primarily due to concerns about side effects and drug interactions. In another survey of prescribing practices [7], clinicians, despite the lack of evidence, perceived newer agents to be more efficacious than the older agents such as tricyclic antidepressants and MAOIs (both classes were perceived as also having more side effects). Finally, in a survey of prescribing phosphodiesterase-5 inhibitors [8] among psychiatrists, many believed that these medications were efficacious but did not prescribe them because of possible side effects or considered these medications out of the scope of their practice. Unfortunately, this survey was limited by a low response rate. Nevertheless, there seems to be a general trend of psychiatrists’ dislike of prescribing medications they consider “dangerous,” complicated or out of scope.

The abuse of and dependence on benzodiazepines is a complex issue that has been addressed in various publications (e.g., [9-11]). As noted, substance abuse specialists view benzodiazepines harshly, but this maybe out of clinical context. The report of the Task Force on Benzodiazepine Dependency [9] noted that although benzodiazepines may be abused, they do not strongly reinforce their own use and are not widely abused drugs. Silberman et al. [11] emphasized that patients with no history of abuse are not prone to abusing benzodiazepines. They [11] also note that while misuse of benzodiazepines is common, this may not reflect abuse, and there is no evidence that misuse leads to abuse. It is important to note that according to the text revision of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) [12], tolerance and withdrawal, which are frequently mentioned when discussing anxiolytic abuse disorder, are not considered to be met for individuals taking these medications under medical supervision. The DSM-5-TR also notes that patients may take benzodiazepines according to a physician’s direction for a legitimate medical indication over extended periods of time. Finally, the DSM-5-TR (p. 626) states that, “Even if physiological signs of tolerance or withdrawal are manifested, many of these individuals do not develop symptoms that meet the criteria for sedative, hypnotic, or anxiolytic use disorder because they are not preoccupied with obtaining the substance and its use does not interfere with the performance of usual social or occupational roles.” These statements illustrate that the issue of benzodiazepine abuse needs to be viewed within a clinical context and may be an unnecessary “scarecrow” for many.

The issue of pharmaceutical industry marketing of alternatives for benzodiazepines is well known. Some companies were heavily fined for illegally marketing some alternatives, e.g., Pfizer for marketing pregabalin. SSRIs have been approved by the Food and Drug Administration (FDA) for various anxiety disorders. Benzodiazepines were not approved by the FDA in many of the same indications as their patents expired prior to some diagnostic entities for which SSRIs received approval that were defined in our diagnostic systems. Some of the alternatives have not been properly compared with benzodiazepines in the treatment of anxiety. They are probably not as efficacious and may face similar issues as benzodiazepines (e.g., withdrawal or even possible substance abuse). We should also not forget that the pharmaceutical industry does influence prescribers via financing “experts” – psychiatrists dominate a list of physicians who receive the most payments from the pharmaceutical industry.

Finally, there are some issues perpetuated in the literature and beyond that may discourage psychiatrists from prescribing benzodiazepines. It has been proposed that benzodiazepines cause or are associated with dementia, as suggested by some methodologically questionable studies. Yet, as demonstrated by recent more rigorous studies (e.g., [13, 14]), it is not the case. Similarly, while there have been some reports of the association of benzodiazepines with depression, Smith and Salzman [15] concluded that while it seems to be prudent to assume that benzodiazepine treatment occasionally leads to significant depression or even suicide (as many other medications), there are “no data to support the view that depression is a regular or even frequent concomitant of therapeutic benzodiazepine use”. On the other hand, benzodiazepines could be a very effective and preferable treatment for anxious depression [16]. As far as rebound anxiety goes, it seems to be a phenomenon difficult to distinguish from a recurrence of the underlying anxiety disorder or a discontinuation syndrome and is easy to manage. As Greenblatt et al. [4] (p. 357) emphasized, “since benzodiazepines cure neither anxiety nor insomnia, symptom recurrence can be anticipated after discontinuation of the drug.”

The issues raised here about fears of prescribing benzodiazepines are mostly real; however, they all could be addressed through appropriate, informed, and compassionate prescribing by educated, competent psychiatrists and physicians. We should all remember the patient’s benefit and the saying primum non nocere, and that patients come first. In describing a clinical situation in which a patient’s benzodiazepine was discontinued by a new prescriber after the patient had done well for several years, which led to the patient being suddenly back homebound and anxious, Rosenbaum [17] stated, “The doctor might feel a bit better, but the patient would be devastated.” We need to ask ourselves whether it is ethical to withdraw benzodiazepines from patients when they are clearly indicated and pose a low risk to benefit ratio because of the prescriber’s fear or bias.

We are clearly facing a serious situation. Psychiatrists are gradually deleting useful classes of medications from their armamentarium. Benzodiazepines are just the latest example. Patients are paradoxically lucky that other disciplines are still willing to prescribe them. Other disciplines actually find them to be a valuable addition to their armamentarium, as they help in areas such as cardiovascular and gastrointestinal disorders and conditions [18, 19]. Psychiatrists should join the rest of medicine in appreciating the value of some of psychiatry’s medicines, namely benzodiazepines, and use them appropriately for the benefit of our patients. We need to think and strategize on how to make psychiatrists and other physicians comfortable with prescribing benzodiazepines despite their fears, the onslaught of negative publicity, and overregulations.

The crisis of prescribing certain psychopharmacological agents is actually more serious than just a lack of will and fear. Markowitz and Friedman [20], in their viewpoint about the lack of National Institute of Mental Health (NIMH) funding for psychotherapy and clinical research, mention the demise of clinical researchers as a consequence. The skills to conduct clinical research disappear with their demise and will be difficult and costly to reinstitute. We are facing an analogous situation in clinical psychopharmacology – we are losing psychiatrists who are willing and able to prescribe all psychotropic medication, and thus we are also losing those who could teach and make comfortable future generations in prescribing beyond SSRIs and second-generation antipsychotics.

Hopefully, the answer could be found in solid articles such as Dubovsky and Marshall [1] and many others; in improving the education of our trainees in helping them and allowing them to prescribe all available medications in spite of their and our discomfort and fears; in improving the continuing psychopharmacology education of all physicians, which should include education in appropriate prescribing of all available medications including benzodiazepines; in answering unsubstantiated claims and regulations; and in fighting negative marketing, nonsensical bans, and unsubstantiated fears. In all this, we should remind ourselves that, as Pogo (a cartoon character by Walt Kelly, 1970) said, “We have met the enemy and he is us,” and that patients’ fears and anxieties trump ours.

The author has no conflict of interest to declare.

None.

Richard Balon is the sole author of this editorial.