Stigmatization of Benzodiazepines: Pharmacologic and Nonpharmacologic Contributions

Prescribing benzodiazepines to treat anxiety is widely viewed as problematic in current psychiatry. Residents are warned to avoid them; published guidelines advise using them only as a second-line treatment, rarely as monotherapy, and never chronically; some clinics prohibit them entirely; and practitioners who use them may risk censure from institutions or regulatory agencies [1]. Remarkably, the published literature on benzodiazepine efficacy, toxicity, and abuse potential provides no support for this sweepingly negative view of these medications, and, in fact, largely contradicts it. The comprehensive review by Dubovsky and Marshall [2] is the most recent confirmation of the disconnect between the common wisdom and the evidence base.

Benzodiazepines have an uncommon pharmacologic profile that makes it likely that they will be misunderstood. They have the potential to be abused, and they may be difficult to discontinue due to withdrawal phenomena, but they reinforce their own administration only weakly, if at all [3-5]. That they share the first two characteristics with primary drugs of abuse has often blinded psychiatry to the fact that the third quality – self re-enforcement – is the essential criterion for an addictive drug [6]. In addition, they belong to the class of “minor tranquilizers” that were the first mass-market prescription psychotropics, starting with meprobamate in 1955. Following the introduction of chlordiazepoxide in 1960, they inherited the meprobamate tradition of being prescribed for a broad range of anxiety-related complaints, including the stresses of daily living, often without clear indications and contraindications or criteria for discontinuation [7]. As the liabilities of benzodiazepines came to light, their association with this prescribing practice added to casting a pall over their legitimacy [8].

Stigmatization of benzodiazepines can be understood as the failure of psychiatry to make crucial distinctions: between benzodiazepine abuse as a cause of addiction versus their abuse as a result of previously established addiction, between abuse of benzodiazepines and their misuse, between physiologic dependence and addiction, and between prescriptions of benzodiazepines for difficulties in living and their prescription for well-diagnosed anxiety disorders [9, 10]. A fear-based reaction to benzodiazepine abuse, these failures in conceptual rigor were cemented in the minds of psychiatrists when benzodiazepines were abandoned by the pharmaceutical industry in the 1970s, leaving little financial support for anyone to study or stand up for them [11]. As a result, many psychiatrists and primary care physicians either were convinced to avoid them entirely or were left to prescribe them in suboptimal ways, with results that reinforced their misconceptions.

Clinicians who view anxiety patients with no history of substance abuse as likely to become addicted to benzodiazepines often prescribe them reluctantly, in inadequate doses, with warnings to “take this only when you really need it.” Practice of this kind heightens anxiety by conveying distrust, focuses patients unhelpfully on their anxiety symptoms, and constrains them to taking their PRN medication only when it is too late to really help them. In such a situation, patients taking extra doses in panicky attempts to control their anxiety may be misunderstood as engaging in abuse (using medication to get high), rather than misusing their medications (taking medication for symptom relief, but other than as prescribed). Patients who find themselves in this dilemma are often described as having become “drug-seeking” as a result of taking benzodiazepines, a step on the road to addiction.

Prescribing practices can also produce pseudo-tolerance. While tolerance develops to the sedating effects of benzodiazepines, and perhaps to motor impairment, the research literature tells us that anxiety disorder patients on long-term benzodiazepines do not escalate their doses or lose their anxiolytic effects [12-14]. However, clinicians often see benzodiazepine tolerance as a unitary phenomenon, leading to the common belief that patients taking them for anxiety tend to escalate their doses. This misconception is reinforced when benzodiazepines are prescribed for insomnia that is not due to anxiety, with only short-term benefits and likely requests for dose escalation. A similar situation can occur when clinicians prescribe benzodiazepines for anxious personality disorder patients, without first discussing the limits of what medication can be expected to do. Many such patients seek global elimination of negative effect – essentially emotional anesthesia – rather than just relief from anxiety symptoms; when it becomes clear that the anxiolytic effect provided by a benzodiazepine does not meet this expectation, they may seek higher doses, creating the impression that they have become tolerant to a prior good effect.

In the eyes of many psychiatrists, the most damning aspect of benzodiazepines is their capacity to produce a withdrawal syndrome when taken chronically. Psychiatry recognized this capacity only reluctantly – first accepting manufacturers’ claims that it did not exist, then postulating that it existed only for people taking higher than therapeutic doses [15]. However, once the reality of low-dose withdrawal phenomena became inescapable, the field overestimated its prevalence and severity and equated it with substance abuse, linguistically anchored by the word “dependence.” While, in itself, a withdrawal syndrome reflects only a property of a drug – that is, physiologic dependence – the word inevitably carries a pejorative connotation about the behavior of people who take it – that is, that they are addicted. In DSM III, physiologic dependence alone was enough to define substance abuse; while this form of dependence has been disentangled from substance-use disorders in subsequent DSM versions, ICD 10 still uses “drug dependence” as the name of the syndrome of persistent appetitive use of a substance in the face of adverse consequences – that is, addiction. This linguistic and clinical confusion leads to the not-uncommon directive by clinicians that patients who are doing well on stable doses of long-term benzodiazepines are “dependent” and must taper off them, despite not manifesting any behavioral features of a substance use disorder.

The risk of a withdrawal syndrome – the strongest factor perpetuating the view that benzodiazepines should be used only as short-term treatment – is arguably the least researched and most poorly understood aspect of these medications. Early studies suggested that somewhat less than half the patients taking long-term benzodiazepines experience withdrawal phenomena, even when withdrawn abruptly [16]. Later studies of withdrawal suggested that 18%–84% of patients are unable to remain abstinent post-withdrawal, and advocacy groups describe patients who believe that withdrawing from benzodiazepines, or even remaining on them long term, left them chronically symptomatic or dysfunctional [17, 18]. To whatever extent this occurs, it is a troubling risk of benzodiazepine use, but it is hard to reconcile with the experience of clinicians who routinely treat patients without encountering such a syndrome.

It has been suggested that widespread, perhaps irreversible neurophysiologic adaptation to benzodiazepines is the mechanism of such phenomena [19]. However, lack of systematic study of benzodiazepine withdrawal leaves us in the dark about the true prevalence of severe, sustained withdrawal phenomena, what the risk factors are, and how much of the reported phenomenology is due to misattribution, return of untreated anxiety, tendency toward somatization, or suboptimal taper methods. Unfortunately, lack of research funding is likely to keep us ill-informed for the foreseeable future.

The anti-anxiety efficacy of benzodiazepines has not been seriously challenged. Ideally, they would be prescribed like other psychotropics, based on their benefits and liabilities. However, they have come to be stigmatized by a fear narrative that has precluded evidence-based reasoning. The opioid epidemic, which conflates opioids and benzodiazepines in the minds of the public and many physicians, has only solidified this narrative. The consequences of these failures fall most heavily on anxiety disorder patients, especially those whose lives have been limited by panic disorder, social anxiety disorder, and mixed anxiety disorders. Those who have not been helped by other treatments are at risk for being unable to find a doctor who will prescribe benzodiazepines, and those who have done well on them long term are at risk for having them withdrawn by clinicians who view successful long-term treatment with benzodiazepines as a form of addiction. One can only hope that publication of scholarly reviews, such as that of Dubovsky and Marshall [2], will begin to move psychiatry toward a more informed and open-minded approach to using benzodiazepines in treating potentially incapacitating anxiety disorders.