COMMENTARY
Benzodiazepines: A Perspective
Jerrold F. Rosenbaum, M.D.
A week after the mandate for all to shelter at home in
Massachusetts, I received this message from a severely ill
disease-phobic patient (who was working remotely with her
behavioral medicine psychologist to reduce her disabling
fears): “I am very thankful I have lorazepam at home with me
these days! I am trying hard not to take it and am putting forth
great effort on what I am thankful for each day.”
I confess that some of the most gratifying memories in my
career had to do with benzodiazepines. In the early 1980s,
there was a woman with agoraphobia in Beacon Hill who,
after being given alprazolam and the support of a visiting
research assistant, declared she had walked on grass for the
first time in many years (having missed her son’s wedding,
among other events over that time.) There was the physician
with a history of panic attacks, ongoing social anxiety, and
irritable bowel syndrome who achieved remission for de-
cades on clonazepam and as-needed alprazolam for emer-
gencies, eventually tapering to a low dose of clonazepam
at bedtime. At his 60th college reunion, he encountered a
classmate he had once admired and, knowing she had also
held affection for him, he later mused to me that “if I had met
you back then, I wonder how my life might have unfolded
differently.” There was the college freshman who had onset of
panic attacks in the first days of school, with family then
preparing to fly him back home, who returned to class, rather
than home, protected by a benzodiazepine. Admittedly, these
anecdotes derive from a time before much of what we have
come to know about the efficacy of cognitive and behav-
ioral therapies and before we talked of concepts like anxiety
sensitivity and exposure to bodily symptoms.
The anxiety about benzodiazepine prescribing is an old
story (1). The efficacy of benzodiazepines in anxiety is well
established, but based on the current practice of many more
recently trained physicians, these medications reduce anxi-
ety for the physicians themselves by their refusing to pre-
scribe them. My own son, a first-year resident in psychiatry,
looks at me as if I served on the wrong side in the Spanish Civil
War when I speak of benzodiazepines.
During the early years of my career, I studied mainly
higher-potency benzodiazepines in a variety of conditions,
but principally in panic disorder, and I helped lead pivotal
studies for U.S. Food and Drug Administration approval of
clonazepam for panic disorder (2). I perceived that popular
opinion and research funding agencies trivialized anxiety
distress, even as we have come to appreciate the critical role
of anxiety and insomnia in risk for suicidal behavior (3).
488 ajp.psychiatryonline.org
My work turned to focus on the antecedents of anxiety and
the potential for early recognition and interventions to limit
lifelong disability (4). As others have also reported, roughly
one in six individuals appear to be born predisposed to de-
velop uncomfortable physiological and behavioral responses
that predispose to fearful behaviors, and in some cases this
predisposition evolves into recurrent or lifelong social anx-
iety and other mood and anxiety disorders (5). Behavioral
interventions help many young individuals (6). For others,
as adults, when given an adequate prescription of a benzo-
diazepine in a regimen avoiding interdose rebound, their
symptoms will respond well, and they will ask if this is how
normal people feel. Indeed, patients with panic disorder may
be subsensitive to benzodiazepines and require higher doses
than those without severe anxiety (7).
This commentary is not meant to be a call for a ben-
zodiazepine renaissance but rather an attempt to offer
a perspective. Beyond
their established efficacy The efficacy of
in anxiety distress and benzodiazepines in anxiety
insomnia and fueling the is well established, but based
debate between “pharma- on the current practice
cological Calvinism and
of many more recently
psychotropic hedonism”
trained physicians, these
(8), these medications
can also offer transient medications reduce
relief and comfort from anxiety for the physicians
stress; in a world replete themselves by their refusing
with distress, it may be to prescribe them.
difficult for people to re-
frain from seeking a comforting remedy. Thus, these medi-
cations’ potential for nonmedical use, and their associated
risks and side effects, is a concern but is not of itself a reason
always to deny comfort and relief. As the aphorism guides us:
“To cure sometimes, to relieve often, and to comfort always.”
There may be times when the best or only way to comfort will
be to use or add a benzodiazepine.
That said, if one can do as well or better with agents or
methods less fraught with concerns, it would be a most
reasonable decision. Now, 40 years from my first perspective
publication on benzodiazepines (1), I work at a center for
the treatment of anxiety disorders, the majority of which is
staffed by brilliant and highly skilled psychologists trained in
cognitive-behavioral therapy (CBT). In 1976, our department
hired its first behaviorist, and now there are hundreds on our
staff. I have seen that light and am passionate that this is the
Am J Psychiatry 177:6, June 2020

approach of first choice. But still, there are far too few of these
skilled experts to meet the need in this country, and, even at
our center, the wait for treatment can be long. There is ev-
idence that other approaches (9), perhaps any caring and
thoughtful psychotherapy, can be helpful whatever the un-
derlying theoretical model. But even with the most established
evidence-based psychotherapy, some patients’ symptoms do
not respond to treatment, or they suffer residual symptoms.
Some benzodiazepine prescribing is straightforward, for
example, as a brief intervention for acute distress or as-needed
use for a phobic anxiety (e.g., airplanes) or transient insomnia.
Some prescribing situations are, however, to be avoided
if possible, like prescribing to manage persisting distress
resulting from a personality disorder or for patients with
known current or past substance use disorders. But pre-
scribing is never carefree. An important guideline is to avoid
chronic administration for acute problems and to set a goal
for those on maintenance therapy of gradually working to
find the lowest effective dose, which over time might be-
come less or none, especially in older patients, in whom
increasing sensitivity to the medication, the likely presence
of more drugs interacting, memory concerns, and fall risk
are important clinical issues to be assessed. This approach
respects both patients’ symptoms and the physiological
dependence that results from sustained use. Past phar-
macoepidemiological studies (10) have also indicated that
individuals chronically using benzodiazepines, compared
with others, were more ill, had higher levels of psychic
distress, and generally met criteria for disorder. The ma-
jority of this population had discussed their treatment with
a physician in the previous 4 months. Although many pa-
tients on chronic treatment can taper off, assessment at
follow-up of these patients indicates that ongoing treat-
ment was for chronic or recurrent anxiety and not just for
physiological dependence (11). Rates of successful taper can
be enhanced by CBT approaches (12).
The question of the risk of prescribing a benzodiazepine
and inadvertently inducing a substance use disorder is a
complicated issue. The older literature on the addiction pro-
pensity of benzodiazepines seemed reassuring (13) in sug-
gesting that these drugs were not strong reinforcers and were
less likely than others to be the preferred drug of misuse. The
voice of the substance use disorder community strongly
counters this notion, citing the high rates of benzodiazepine
misuse, especially in the substance-using population, and,
recently and most alarmingly, given the adverse synergistic
risk with overdose, compounding the opioid use epidemic.
Although benzodiazepine overdoses are of a lower lethal-
ity compared with other drugs ingested in overdose (14),
given their availability, they are frequently used in overdose
and increase risk when combined with agents with a nar-
rower therapeutic margin and greater lethality in overdose.
Thus, responsible prescribing, beyond considering alter-
natives, requires knowing the patient and monitoring drug
consumption. Concern about one population, however, need
not proscribe the use of benzodiazepines in other populations
Am J Psychiatry 177:6, June 2020
COMMENTARY
who might benefit with a chance to live their lives with
greater freedom from anxiety.
In 1984, Carl Salzman (then the chair of the APA Task
Force on Benzodiazepine Prescribing) and I debated, at an
American College of Psychiatrists conference, the issue of
whether benzodiazepines were overprescribed. Then, as
now, one of the key issues was alternatives. A remark I made
about azapirones as alternatives (e.g., buspirone) went viral:
“Everything you want in an anxiolytic except efficacy.”
Maybe that was not fair, but it was a debate, and inasmuch as
for the next four decades I continually encountered that
quote (even from those who did not know its origins), the
concern must have resonated with colleagues.
These days, we have more than tricyclic antidepressants,
monoamine oxidase inhibitors, and buspirone as treatment
alternatives. Other GABA-ergic drugs, including gabapentin
and tiagabine, are viewed by some as safer to prescribe, al-
though they are not side-effect free and are of uncertain
efficacy relative to the much better studied benzodiaze-
pines in treating anxiety. New GABA-ergic drugs are being
developed for mood disorders, and it is not yet clear how they
compare with benzodiazepines, which also reduce many
symptoms that occur with mood disorders. In an effort to
avoid prescribing benzodiazepines, many clinicians default
to low doses of second-generation antipsychotics such as
quetiapine. Antipsychotics had long been used acutely for
their ataractic effects, but ongoing use was less endorsed
because of concerns about tardive dyskinesia, metabolic ef-
fects, and even increased risk of sudden death from different
mechanisms.
I do favor antidepressants, particularly selective serotonin
reuptake inhibitors (SSRIs) and serotonin-norepinephrine
reuptake inhibitors (SNRIs), over benzodiazepines for
treatment of persisting anxiety disorders. The “standard
advice” for these classes is interestingly opposite to that
for benzodiazepines. In the case of antidepressants, we ad-
vocate ensuring adequate dose and duration and maintaining
treatment for the long term or indefinitely for persisting or
recurrent disorders, while for benzodiazepines, we insist
on keeping doses low and discontinuing early. With both
classes, we encounter distressing symptoms with abrupt
withdrawal that can obscure the difference between dis-
continuation effects and relapse (15). Early nonadherence,
however, often follows prescribing of SSRIs or SNRIs in
part because of induction of anxiety or agitation, although
benzodiazepines rarely worsen or induce those symptoms.
Indeed, benzodiazepines are efficacious in helping some pa-
tients with anxiety tolerate SSRI initiation (16). With both
classes of medication, some patients’ symptoms respond very
well and some less well, and response may fade for some over
time. Although there are no known irreversible effects from
long-term administration, for both SSRIs and benzodiazepines
there is a small percentage of those treated who attribute
persisting postdiscontinuation symptoms to treatment. The
main controversy around prescribing of these medications
centers on the issues of abuse liability, cognitive impairment,
ajp.psychiatryonline.org 489
COMMENTARY
and physical dependence. As with most of our therapeutics,
we lack long-term studies comparing outcomes of patients on
benzodiazepines with those on alternative pharmacologic,
behavioral, or even no treatment. The use of “big data” and
new tools, such as artificial intelligence and machine learn-
ing for studying longitudinal electronic health record data,
should give us insight into the true risks and benefits of
benzodiazepine use.
As with the article in this issue of the Journal by Osler and
Jørgensen (17), what we learn with well-designed studies
may run counter to long-held beliefs. In this case, the notion
that benzodiazepines contributed to cognitive decline was
not proven when outcomes were accounted for use by in-
dication. In fact, the results of the study suggest that cu-
mulative use might even be neuroprotective. This finding
is plausible especially in light of recent findings that de-
pression, often associated with anxiety and managed in part
with benzodiazepines, is a risk for or precursor of dementia
(18), that insomnia risks preventing the brain’s glymphatic
system from clearing b-amyloid (19), and that stress over time
increases risk for neurodegenerative diseases (20).
To close with a banality, benzodiazepines are medica-
tions. As such, they are intended to be prescribed by those
trained in how and when to use them and in how to weigh
risks and benefits. They are also intended to be prescribed
to address suffering, distress, and functional loss from
psychiatric symptoms and disorders. As with many tools
available to clinicians, they are imperfect but are poten-
tially beneficial.
AUTHOR AND ARTICLE INFORMATION
Department of Psychiatry, Center for Anxiety and Traumatic Stress Dis-
orders, Massachusetts General Hospital, Harvard Medical School, Boston.
Send correspondence to Dr. Rosenbaum (jrosenbaum@mgh.harvard.edu).
The author thanks Daniella Levine for assistance with preparation of this
commentary.
Dr. Rosenbaum is cofounder of and holds equity in Psy Therapeutics and is
a scientific adviser to Odin (formerly Luminopia) and Terran Biosciences.
Accepted April 3, 2020.
Am J Psychiatry 2020; 177:488–490; doi: 10.1176/appi.ajp.2020.20040376
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