In Debate

Are There Guidelines for the Responsible Prescription

of Benzodiazepines?
Nady el-Guebaly, MD, DPH, DPsych, FRCPC'; Jitender Sareen, MD, FRCPC^;
Murray B Stein, MD, MPH, FRCPC^

Can J Psychiatry. 2010;55(11):709-714.

The Prevalence of Prescriptions and

Their Indications

enzodiazepines are reportedly the most frequently prescribed psychotropic medication. Among adults in the
United States and Canada, 3% to 4% are using BDZs at any
one time' About 100 million prescriptions are written per
year. The European Study of the Epidemiology of Mental Disorders (commonly referred to as ESEMeD) investigated the
use of ADs and BDZs in 21 425 respondents from 6 countries.
In the nonhelp-seeking population, BDZs were used more
commonly than ADs, while in the help-seeking population,
with a 12-month prevalence of major depressive disorder or
anxiety disorder, BDZs were used as commonly as ADs.^ In
an Australian study,'' 16% of the adults aged 65 years and
older (n = 3970) had at least 1 BDZ prescription and the prescription prevalence increased with age.

Abbreviations used in this article

AD

antldepressant

APA

American Psychiatric Association

BDZ

benzodiazepine

BDZs' sedative, hypnotic, and anxiolytic properties are used

for various psychiatric and medical conditions including
anxiety disorders, sleep disorders, seizure disorders, movement disorders, and muscle spasticity. They are used in
anaesthesiology and for the symptomatic treatment of agitation associated with other psychiatric and neurological disorders including psychotic, mood, and cognitive disorders.'' In
emergencies they are the preferred treatment of withdrawal
from alcohol and sedative-hypnotics as well as agitation from
stimulants.
Tolerance to sedative effects usually develops among people
receiving maintenance therapy with a stable dose of BDZs;
by contrast, the memory-impairing effects can persist after
several years of daily administration,^ Overdoses are almost
never fatal unless occurring in combination with other sedative agents such as alcohol or opiates.
The reinforcing effects of BDZs may not only be mediated
through binding of the alpha 1 or lambda 2 subtypes of
GABA receptors but also via an opioid mechanism, A partial
mu receptor antagonist such as naltrexone may reduce anxiolytic and positive subjective effects of BDZs. This may
explain the high level of co-occurrence of BDZs and opioid
dependence. Of interest, BDZs are the only major class of
drugs with abuse liability that decrease dopamine levels in
the mesolimbic system,""

CBT

cognitive-behavioural therapy

From Physiologic Dependence to Loss of Control

CME

continuing medical education

GABA

gamma-aminobutyric acid

GAD

generalized anxiety disorder

NiCE

National Institute for Health and Clinical Excellence

The dose and duration of exposure to BDZs determines the

development of physiological dependence. It is almost never
seen in patients treated for less than 2 weeks but occurs in
about 50% of patients treated daily for more than 4 months.
Short- and long-acting BDZs produce comparable severity of
withdrawal. The development of physiological dependence
is reduced with intermittent, eompared with continuous,
exposure to BDZs,

OCD

obsessive-compulsive disorder

prn

pro re nata

PTSD

posttraumatic stress disorder

RCT

randomized controlled trial

SNRI

serotonin and norepinephrine reuptake inhibitor

SSRI

selective serotonin reuptai<e inhibitor

The Canadian Journal of Psychiatry, Vol 55, No 11, November 2010

Among people exposed to BDZs, a small subset, likely

among those who have abused other substances, will develop
compulsive drug-seeking behaviour with loss of control and
an inability to stop. The same may apply to people with a
709

In Debate

positive family history of drug or alcohol dependence, given

that some of the risk may be hereditary.^ Most patients treated
chronically with BDZs, who presumably may have physiological dependence, do not develop compulsive substance
use,^ and some patients present with compulsive substance
use without physiological dependence. The abuse potential of
BDZs depends not only on the drug receptor selectivity but
also on the characteristics of the individual and environmental
circumstances.
BDZs as a primary substance of abuse in people admitted for
addiction treatment make up less than 1% of all admissions.
Most of these people report abuse of alcohol or opioids in
addition to BDZs.^ The presence of another co-occurring psychiatric disorder (mood, anxiety, and Cluster C personality)
occurs in up to 50% of these admissions. Among patients on
methadone maintenance treatment, 40% to 50% abuse BDZs.
These rates are not significantly reduced by methadone maintenance alone.
Guidelines for Responsible Prescription
APA and NICE. The APA guideline for the treatment of panic
disorder'" and the NICE guideline" on the management of
panic disorder and GAD recommend SSRIs and not BDZs as
the best choice of medication, alongside CBT and self-help
based on CBT principles. BDZs are associated with a less
good outcome in the long term and should not be prescribed
beyond 2 to 4 weeks in GAD and are not recommended for
panic disorder.
BDZs, Compared With non-BDZ Antianxiety Medication and
CBT. Non-BDZ antianxiety medication and CBT often take
weeks before there is any beneficial effect, thus the short-term
prescription of high-potency BDZs may remain an option
when patients express an urgent need for the reduction of high
levels of anticipatory anxiety and the reduction in the severity
of panic attacks. BDZs with slower onset and longer action
may be safer than fast-acting agents.
BDZs, Compared With SSRIs and SNRIs. In the case of
comorbid anxiety and depression, SSRIs and (or) SNRIs are
the first-line medication but BDZs may also provide benefits
both for speed of response and for overall response. ADs
should also be started early as the shorter the time elapsed
between the onset of GAD and first adequate pharmacological
treatment the better the prognosis.'^
Coneerns Associated With the Prescription of BDZs.
Concerns include:
1. BDZs mainly have a favourable side effect profile;
however, patients, the elderly in particular, may
experience sedation, fatigue, slurred speech, memory
impairment, and weakness.
2. Even when the SSRI and (or) CBT has started to work,
the patient may still believe that the BDZ is the
effective agent and then have difficulty discontinuing
710

it. Provided with short-term symptomatic relief, the

patient may also lose motivation to follow all the CBT
steps.
3. Even after a few weeks of BDZ treatment, some
patients will experience withdrawal reactions on
discontinuation similar to an anxiety relapse, resulting
in their reluctance to discontinue the BDZ.
Identifying and Targeting High-Risk People.
This includes:
1. Screening for sedative-hypnotic use through a
nonthreatening personal and family history and
possibly urine toxicology.
2. Regular monitoring for signs of abuse or dependence
as well as concurrent abuse of alcohol or other drugs.
3. Individual reassessment of risks and benefits of
prescription at regular intervals.
4. Reduction of physiological dependence, through:
Use of adequate doses over a few weeks only.
Drug holidays; that is, intermittent use of medication
only in the case of high-anxiety situations, for
example, in a GAD.
5. Differentiation of common physiological dependence,
compared with rarer iatrogenic addiction.
The Management of Cessation of Use. Cessation requires a
detailed understanding by the patient of the options involved.
In our experience, it is critical for a fearful patient to perceive
that he or she retains a measure of control over the process.
Strategies for patients with comorbid anxiety or mood disorders and sedative-hypnotic use disorders will include:
1. Very gradual taper of medication during several
months. Referring the patient to a website such as the
Ashton manual'^ may be of help.
2. Conversion to, and stabilization on, equivalent dose of
alternative BDZ with a slower onset and a longer
duration of effect; that is, conversion from alprazolam
to clonazepam.
3. Discontinuation of BDZ and stabilization on an
alternate GABAergic agent with a higher safety
profile; that is, carbamazepine or valproate.
4. Implementation of CBT, typically for several weeks or
months, helps the patient to recognize and manage
symptoms of withdrawal and rebound anxiety, while
helping the transition in developing symptom control
and self-efficacy.
5. In the case of recurrence of mood or anxiety problems
that may or may not mimic withdrawal symptoms,
alternate pharmacotherapy such as trazodone
combined with CBT can improve the tolerability of
medication change. The resumption of BDZs or a
La Revue canadienne de psychiatrie, vol 55, no 11, novembre 2010

Are There Guidelines for the Responsible Prescription of Benzodiazepines?

return to a higher dose is not recommended. Sleep

disturbances have been alleviated by adding melatonin.
Patient With Primary Substance Use Comorbidity. Very often
a pattern of polysubstance abuse is evident. Admission to an
inpatient admission with a rapid 2- to 3-week detoxification
followed by an abstinence-based outpatient treatment has
been recommended.''' To maintain the gains of detoxification,
a relapse strategy is required to help further recovery, preferably with the help of psyehosocial approaches including
mutual help groups.
The Elderly. BDZs are still widely prescribed among the
elderly, most of whom are women.^ Both duration and cumulative exposure to BDZs may have negative effects on their
cognitive performance and anctioning in the community, and
long-term prescriptions may lead to secondary driving problems as well as falls. There is a need to inform older adults
about the risks of BDZs, offering effective discontinuation
and managing their somatic, sleep, and anxiety problems by
providing alternate pharmacological and psychological
treatments.
Is BDZ Prescription a Necessary Evil?
Most BDZ users, particularly those with a comorbid psychiatric disorder, are receiving their medication from physicians,
including psychiatrists, creating a unique opportunity for the
medical profession to prevent the potential problems.
Practitioners feel both overwhelmed and empathie toward
their patients' psyehosocial problems and consider the prescription of BDZ as facilitating a coping strategy. Consulting
psychiatrists may also perceive the prescription guidelines of
BDZ as too narrow for complex cases. The answer may be in
the diversification of more specific treatments for patients'
refraetory to current first-line recommendations. Long-term
management plans must include strategies for acute or
short-term care, long-term maintenance, and episodic or
breakthrough symptoms. Although the statistical risk for
dependence is relatively low, those unfortunate enough to
develop it will experience a clinically challenging withdrawal
course. Novel pharmacological factors, modulating particularly GABA receptors, ion channels, or glutamatergic transmission, are under various phases of investigation; their ease
of discontinuation must also be assessed.
The implication is that newer medications with partial agonist
effeets at selected GABA receptor subtypes may result in
more selective behavioural effects and better safety profiles.

References
1. Ncutcl CI. The epidemiology of long-tenn benzodiazeopitie use. Int Rev
Psychiatry. 2005;17:189-197.
2. Demyttenaerc K, Bonnewyn A, Bruffaeils R, et al. Clinical factors influencing
the prescription of antidepressants and benzodiazepines; results from the
European Study of the Epidemiology of Mental Disorders (ESEMeD). J Affeet
Disord. 2008;110(l-2):84-93.

The Canadian Journal of Psychiatry, Vol 55, No 11, November 2010

3. Windle A, Elliot E, Duszynski K, et al. Benzodiazepine prescribing in elderly

Australian general practice patients. Aust N Z J Public Health.
2007;31:379-381.
4. Hollister LE, Muller-Oerlinghausen B, Riekcis K, et al. Clinical uses of
benzodiazepines. J Clin Psychophannacol. 1993;13:1S-169S.
5. Lister RG. The amnesic action of benzodiazepines in man. Neurosci Biobehav
Rev. 1985;9:87-94.
6. Bisaga A. Benzodiazepines and other sedatives and hypnoties. In: Galanter M,
Kleber HD, editors. Textbook of substance abuse treatment. Washington (DC):
Ameriean Psychiatric Publishing, Inc; 2008. p 215-235.
7. Kendler KS, Karkowski LM, Neale MC, ct al. Illieit psychoactive substance
use, heavy use, abuse and dependcnee in a US population-based sample of male
twins. Arch Gen Psyehiatry. 2000;57:261-269.
8. Soumerai SB, Simoni-Wastila L, Singer C, et al. Lack of relationship between
long-term use of benzodiazepines and escalation to high dosages. Psychiatr
Serv. 2003;54:1006-10I1.
9. Substance Abuse and Mental Health Services Administration (SAMHSA).
Treatment Episode Data Set (TEDS): 1995-2005; national admissions to
substance abuse treatment serviees. Series S-37 (DI-IHS no SMA-07-4234).
Rockville (MD): SAMHSA; 2007.
10. American Psychiatric Association. Practice guideline for the treatment of
patients with panie disorder. Atn J Psyehiatry. 1998; 155(5 Suppl):l-34.
11. National Institute for Health and Clinieal Exeellenee. Management of anxiety
(panic disorder with or without agoraphobia, and generalized anxiety disorder)
in adults in primary, secondary and eotntnunity care [Internet]. London (GB):
NICE; 2004 [updated 2007; cited 2009 Oet 19]. Available frotn:
http://www.nice.org.uk/guidance/CG22.
12. Dunlop BW, Davis PG. Combination treatment with benzodiazepines and
SSRls for comorbid anxiety and depression: a review. Prim Care Companion J
Clin Psychiatry. 2008;10:222-228.
13. Ashton CH. Benzodiazepines: how they work and how to withdraw [Internet]
[also known as the Ashton manual]. [Updated 2002 Aug; cited 2008 Oct 20].
Available from: http://www.benzo.org.uk/manual/indcx.htm.

Nady el-Guebaly

BDZs Should Be Considered in the

Long-Term Treatment of Mood and
Anxiety Disorders
enzodiazepines are one of the oldest classes of
pharmaco- therapeutic medications.' Discovered in
1955 by Stembach, they have been widely used in many areas
of medicine. Most experts and regulatory guidelines recommend the short-term use of BDZs in the treatment of tnood
and anxiety disorders.^ However, the long-term use of BDZs
in treating mood and anxiety disorders has been controversial. Some have argued that the long-term use of BDZs will
be associated with increased risk for tolerance, dose escalation, and dependence.' We argue here that the benefits of
long-term BDZ use outweigh the potential adverse effects for
most patients.

We suggest that there are 4 specific reasons to consider the

use of BDZs as part of the overall treatment of mood and anxiety disorders. First, they work! BDZs rapidly, reliably, and
robustly relieve anxiety symptoms and improve sleep. As
there is clear evidence that mood and anxiety disorders are
chronic, long-term conditions, there is often a relapse of
symptoms when there is a reduction in dose or discontinuation of BDZs. This is sometimes interpreted as evidenee that
dependence has occurred (which may be the case) but the
most parsimonious explanation is that the condition has not
spontaneously remitted and further treatment is indicated.
Second, the fear of dose escalation with BDZs, presumably
711

In Debate

owing to tolerance, has been exaggerated. The little available

evidence in this area suggests that a very small minority of
patients have dose escalation (which could be due to tolerance). We will suggest some methods to minimize the risk of
dose escalation. Third, BDZs are often better tolerated than
SSRIs, atypical antipsychotics, or other classes of medications employed to treat anxiety that have side effects of weight
gain and sexual dysfunction. Fourth, absence of recent evidence on the clinical usefulness of BDZs does not equal ineffectiveness. As there have been no new BDZs available on the
market in the last 2 decades, there has been little financial
motivation among pharmaceutical companies to conduct
large-scale RCTs of BDZs in the treatment of mood and anxiety disorders. In summary, we suggest that clinicians need to
carefully consider the use of BDZs in the long-term management of mood and anxiety symptoms, and researchers need to
conduct large-scale RCTs in this area.
BDZs Are Efficacious
BDZs reduce anxiety symptoms among patients with primary
anxiety disorders, and anxiety symptoms among patients with
a mood disorder. The strongest evidence for the effectiveness
of BDZs has been among patients with social phobia, GAD,
and panic disorder.^ RCTs have demonstrated that BDZs are
effective in treating each of these anxiety disorders. There has
been a dearth of studies that have examined the use of BDZs
among patients with OCD" and PTSD.^ Although the few
studies examining the use of BDZs among patients with OCD
and PTSD have not found strong evidence for their use. North
American psychiatrists commonly use BDZs in the treatment
of these
In patients with mood disorders, anxiety symptoms often are
substantial and associated with poor outcomes (for example,
increased suicidality^ and functional impairment). Some studies have shown that addition of regularly dosed (that is, not
pm) clonazepam to ADs can accelerate the response among
depressed patients, compared with those who receive ADs
alone.' The treatment of anxiety symptoms among patients
with bipolar disorder is especially important. However, as
SSRIs may heighten the risk of mania and rapid cycling, we
suggest that BDZs may be especially beneficial for these
patients. There is a need for further study in this area.
The Dangers of Tolerance and Dependence on BDZs
Have Been Catastrophized
Is a diabetic patient addicted to insulin? What about asthmatics; are they addicted to salbutamol? In our opinion, the dangers of developing tolerance and dependence on BDZs have
been exaggerated. Long-term follow-up studies have shown
that the incidence of dose escalation (a possible indicator of
tolerance) occurs in only a small minority of patients. In a
large population-based study' that followed over 2000
patients treated with BDZs for more than 2 years, the incidence of dose escalation was small (1.6%). Physical dependence on BDZs does, of course, occur in patients who have
712

been taking therapeutic doses for any prolonged time period.

This is to be expected, and is neither an indication of an untoward effect nor evidence of abuse or misuse. Some patients
do abuse BDZs, and clinicians need to be wary of such people
who are often expert at pulling the wool over prescribers'
eyes. Patients who call for early refills, lose their medication
and need a refill, or obtain their medication from multiple
prescribers are to be carefully scrutinized in this regard. As
clinicians, we need to use medications judiciously. Nonetheless, we should also make sure that we are treating patients
adequately.
To minimize the small risk of dose escalation, we suggest that
clinicians should consider the following. First, carefully
assess a history of impulsivity (for example, concurrent or
past alcohol and [or] substance use problem, antisocial personality disorder, and borderline personality disorder).
Although anxiety symptoms and disorders are highly prevalent in these subgroups, our experience is that BDZs are not
likely to be enormously helpful. Second, minimize the use of
pm BDZs and use of short-half life BDZs (for example,
alprazolam). As-needed use of short-term BDZs leads to a
cycle of taking BDZs at the peak of anxiety. In our opinion,
this cycle leads to a higher likelihood of dose escalation. Regular dose, long-acting BDZs such as clonazepam work well
in treating anxiety symptoms without the risk of dose
escalation.
BDZs Do Not Cause Sexual Dysfunction and Metabolic
Syndrome
BDZs are well tolerated. However, SSRIs (and SNRIs) are
associated with sexual dysfunction, and atypical
antipsychotics are associated with metabolic syndrome and
the risk (although smaller than for typical antipsychotics) of
movement disorders. These side effects can have substantial
negative consequences on intimate partner relationships and
cardiovascular health. Moreover, they can have a substantially negative impact on adherence to treatment. BDZs are
generally safe and well tolerated by patients.
Industry's Influence on BDZ Use?
We wonder whether one of the reasons for the lack of recent
studies in this area is that there are no new BDZs on the market. All the BDZs are generic and there has been little financial incentive among pharmaceutical companies in
conducting large-scale studies to examine the efficacy of
BDZs among patients with mood and anxiety disorder. In
contrast, marketing strategies and CME events sponsored by
the pharmaceutical industry typically have highlighted the
novelty of ADs and antipsychotics in treating mood and anxiety disorders over the less costly use of BDZs. Industrysponsored CME events that are focused on new treatments of
mood and anxiety disorders often remind clinicians of the
potential risk of tolerance and dependence of BDZs, and
make a point of telling clinicians that BDZs are
La Revue canadienne de psyehiatrie, vol 55, no 11, novembre 2010

Are There Guidelines for the Responsible Prescription of Benzodiazepines?

recommended only for short-term use by clinical practice

guidelines.
An example of this issue is specifically in the treatment of
GAD. Bemey et al' reviewed the literature and found that
there were 22 RCTs comparing ADs to BDZs. None of them
showed superiority of ADs over BDZs in the treatment of
GAD. They concluded that there has been a shift in prescribing ADs instead of BDZs for GAD without any evidence to
support this shift.
In summary, judicious long-term use of BDZs should be
thoughtfully considered in treating patients with mood and
anxiety disorders. We also suggest that there is a need for
long-term studies comparing the safety and efficacy of BDZs
to newer ADs and antipsychotics.

References
1. Soumerai SB, Simoni-Wastila L, Singer C, et al. Laek of relationship between
long-term use of benzodiazepines and escalation to high dosages. Psyehiatr Serv.
2003;54(7); 1006-1011.
2. Swinson RD, Antony MM, Bleau P, et al. Clinieal praetiee guidelines.
Management of anxiety disorders. Can J Psyehiatry. 2006;51(8 Suppl 2);9S-91S.
3. Stein MB, Stein DJ. Soeial anxiety disorder. Laneet.2008;371(9618);l 115-1125.
4. Abramowitz JS, Taylor S, MeKay D. Obsessive-compulsive disorder. Laneet.
2009;374(9688);491-499.
5. Ravindran LN, Stein MB. Phannaeotherapy of PTSD; premises, prineiples, and
priorities. Brain Res. 2009;l239;24-39.
6. Blaneo C, Olfson M, Stein DJ, et al. Treatment of obsessive-compulsive
disorder by US psychiatrists. J Clin Psyehiatry. 2006;67(6);946-951.
7. Mohamed S, Rosenheek RA. Pharmaeotherapy of PTSD in the US Department
of Veterans Affairs; diagnostic- and symptom-guided drug seleetion. J Clin
Psyehiatry. 2008;69(6);959-965.
8. Sareen J, Cox BJ, Afifi TO, et al. Anxiety disorders and risk for suicidal ideation
and suicide attempts; a population-based longitudinal study of adults. Areh Gen
Psychiatry. 2005;62; 1249-1257.
9. Stnith WT, Londborg PD, Glaudin V, et al. Short-term augtnentation of
fluoxetine with elonazepam in the treatment of depression; a double-blind study.
Am J Psyehiatry. 1998; 155(10); 1339-1345.
10. Bemey P, Halpcrin D, Tango R, et al. A major ehange of preseribing pattern in
absence of adequate evidenee; benzodiazepines versus newer antidepressants in
anxiety disorders. Psyehophanrtacol Bull. 2008;41(3);39-47.

Jitender Sareen and Murray B Stein

Rebuttals

Should the Prescription of BDZs Be

Based on an Act of Faith?
My esteemed colleagues and I agree that BDZs are a useful
group of medications, and we do not seem to differ as to their
short-term use. Dr Sareen and Dr Stein advocate for the
long-term use of BDZs in treating mood and anxiety disorders, and, in support of their argument, they note that a reduction in the dose of BDZs may lead to symptomatic relapse, a
small sample subset will develop dose escalation (tolerance or
dependence?), and that BDZs are often better tolerated than
SSRls. So far, so good!
My initial quandary starts with their fourth reason; that is.
The Canadian Journal of Psychiatry, Vol 55, No 11, November 2010

absence of recent evidence on the clinical usefulness

of BDZs does not equal ineffectiveness . . .
clinicians need to carefully consider the use of BDZs
in the long-term management of mood and anxiety
symptoms and researchers need to eonduct
large-scale RCTs.
Is the latter to be considered before the studies?
In the case of panic disorder, where standard professional
guidelines consistently recommend the prescription of SSRls
over BDZs, Roy-Byrne et al' state that BDZs work rapidly
but are restricted by their narrow range of efficacy across disorders, the risk of physiological dependence and withdrawal,
and the risk of abuse. While the co-prescription of BDZs to
anxious patients treated with ADs is common, "no placebocontrolled studies have yet been done . . . [on] the effectiveness of augmenting SSRls with benzodiazepines."''' '^^ The
same could be said about the treatment of comorbid anxiety
and depression. Therefore, in summary, while there is evidence to support initial select co-prescription of BDZs with
SSRls, the wide open questions remain: For how long? And
at what cost?
My second surprise is that in an argument about long-term
treatment and, presumably, treatment resistance, the role of
psychotherapy, and CBT in particular, is not mentioned.
Surely, the long-term treatment of mood and anxiety disorders is not solely adequate pharmacology. Is not combined
psychotherapeutic connection with the patient as important?
Lastly, as an addiction specialist, I am taken aback with the
suggestion that anxiety could be a "BDZ-deficiency syndrome" similar to "diabetes and its insulin deficiency." While
the incidence of dose escalation is relatively small in samples
at low risk for addiction, this in no way negates the higher
biopsychosocial risks of BDZ dependence and other substance misuses in anxious and (or) depressed patients, as evidenced by the recent large-scale epidemiologic studies of
comorbidities. The vicious cycle between the misuse of
drugs, including BDZs, and the occurrence of anxiety and
(or) mood disorders is a common clinical presentation.
In summary, at issue is the risk-benefit analysis of the
long-term prescription of BDZs in mood or anxiety disorders
in the absence of adequate research. I fully support the search
for newer medication with improved safety profiles. A careful risk analysis before the prescription of BDZs is required.
CBT, as a widely studied and validated psychotherapeutic
treatment, should also be considered as a first-line augmentation strategy or alternative to limited pharmacological
response. The complexity of the withdrawal syndrome
resulting from BDZ dependence precludes me to advocate
their long-term prescription in the absence of adequate
research. It should not be based on an act of faith!
713

In Debate

Reference

inferred, these findings are interesting and suggest that BDZs

may not be a strong contributor to falls in the elderly.

1, Roy-Byme PP, Craske MG, Stein MB. Panic disorder. Lancet.

2006;368(9540): 1023-1032.

Nady el-Guebaly

Emerging Evidence That Risk of

Fractures Is Not Only Associated
With BDZs But Also Other
Psychotropic Medications in the
Elderly

e thank Dr el-Guebaly for his thoughtful comments on

the risks of BDZ use and his recommendations for
methods to reduce these risks. We agree with many of his
comments.

Specifically, we agree with Dr el-Guebaly that the risk of dose

escalation and tolerance with BDZs is low. Nonetheless, physicians should prescribe these medications judiciously and in
a responsible manner. There is also a need for further research
to guide clinicians in understanding which patients are specifically at risk of dose escalation and abuse of BDZs,
Anecdotally, we often have patients who are struggling with
severe anxiety and report worry about becoming addicted to
medications. In our experience, these patients are at low risk
of abusing BDZs, Conversely, patients with anxiety disorders
who have comorbid Cluster B personality traits, impulsivity,
aggression, or somatization problems often do not do well
with BDZs, in our experiences. In such patients, we prefer
ADs and, if necessary, small doses of antipsyehotics for management of anxiety symptoms.
We disagree with 2 specific points made by Dr el-Guebaly,
First, Dr el-Guebaly mentions one of the common concerns
about BDZs' is that they are associated with increased risk of
falls in the elderly. We point to recent emerging data that show
an association between SSRIs and risk for fractures. Also, a
recent metaanalysis^ examining the impact of 9 medication
classes on falls in the elderly also shows that the increased risk
for falls is not only associated with BDZs but also ADs and
neuroleptics. Interestingly, in 1989 the state of New York
changed policies such that BDZs would require triplicate prescriptions. This policy had a substantial impact on reducing
the prescription of BDZs in New York, However, this reduction in prescriptions did not have an impact on the prevalence
of hip fractures,-' Although the latter study^ used
quasiexperimental data, and causal inferences cannot be

714

Second, Dr el-Guebaly comments that the APA guidelines on

panic disorder, first edition, do not recommend the use of
BDZs for the treatment of panic disorder. Please note that the
updated guidelines published by the APA in 2009"* recommend the use of BDZs in certain patients with panic disorder.
These guidelines suggest that monotherapy with BDZs for
panic disorder can be used when comorbid depression is not a
major issue.
In summary, we believe that BDZs, when prescribed with full
awareness of their risks and benefits, have an important role
to play in the treatment of patients with mood and anxiety
disorders.

References
1. Bolton JM, Metge C, Lix L, et al. Fracture risk from psychotropic medications:
a population-based analysis. J Clin Psychophannacol. 2008;28(4):384-39l.
2. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the ittipact of 9
medication classes on falls in elderly persons. Arch Intern Med.
2009;169(21):1952-1960.
3. Wagner AK, Ross-Degnan D, Gurwitz JH, et al. Effect of New York State
regulatory action on benzodiazepine prescribing and hip fracture rates. Ann
Intem Med. 2007;146(2):96-103.
4. American Psychiatric Association. Practice guidelines for the treatment of panic
disorder seeond edition. Am J Psychiatry. 2009;166(2):sl-s68.

Jitender Sareen and Murray B Stein

Acknowledgements
No funding or support was received by Dr el-Guebaly in the
preparation of this article.
Preparation of this article was supported by grants awarded to
Dr Sareen and Dr Stein from the Canadian Institutes of Health
Research New Investigator Award and from the Manitoba Health
Researeh Council Chair award. Dr Sareen and Dr Stein
acknowledge Dr Rick Hawe for his assistance in manuscript
preparation.

' Professor and Head, Addiction Division, University of Calgary, Calgary,

Alberta; Consultant, Addiction Centre and Program, Alberta Health
Services, Calgary, Alberta.
Address for correspondence: Dr N el-Guebaly, Foothills Medical Centre,
Addiction Centre, 1403-29 STNW, Calgary, AB T2N 2T9;
nady.el-Guebaly@albet1ahealthservices.ca
^ Professor of Psychiatry, Psychology, and Community Health Sciences,
University of Manitoba, Winnipeg, Manitoba; Consulting Psychiatrist,
Operational Stress Injury Clinic, Deer Lodge Hospital, Winnipeg,
Manitoba.
' Professor of Psychiatry, and Family and Preventive Medieine,
University of California, San Diego, California.
Address for correspondence: Dr J Sareen, Director of Research and
Anxiety Services, Department of Psychiatry, University of Manitoba,
PZ-430 771 Bannatyne Avenue, Winnipeg, MB R3E 3N4;
sareen@cc.umanitoba.ca

La Revue canadienne de psychiatrie, vol 55, no 11, novembre 2010

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