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In Debate

Are There Guidelines for the Responsible Prescription

of Benzodiazepines

Nady el-Guebaly, MD, DPH, DPsych, FR CP C'; Jitender Sareen, MD, FRCPC^;

M urray B Stein, MD, MPH , FRCPC^

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

The Prevalence of Prescriptions and

Their Indications

B

enzodiazepines are reportedly the most frequently pre-

scribed 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 Dis-

orders (commonly referred to as ESEMeD) investigated the

use of ADs and BDZs in 2 425 respon dents 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 BDZ prescription and the pre-

scription prevalence increased with age.

bbreviations used in this article

AD antldepressant

APA American Psychiatric Association

BDZ benzodiazepine

CBT cognitive-behavioural therapy

CME continuing medical education

GABA gamma-am inobutyric acid

GAD generalized anxiety disorder

NiCE National Institute for Health and Clinical Excellence

OCD obsess ive-comp ulsive disorder

prn pro re n t

PTSD posttraumatic stress disorder

RCT randomized controlled trial

SNRI serotonin and norepineph rine reuptake inhibitor

SSRI selective serotonin reuptai<e inhibitor

BD Zs' sedative, hypnotic, and anxiolytic properties are used

for various psychiatric and medical conditions including

anxiety disorders, sleep disorders, seizure disorders, move-

ment disorders, and muscle spasticity. They are used in

anaesthesiology and for the symptomatic treatment of agita-

tion associated with other psychiatric and neurological disor-

ders including psychotic, mood, and cognitive disorders.'' In

emergencies they are the preferred treatment of withdrawal

from alcohol and sedative-hypn otics as well as agitation from

stimulants.

Tolerance to sedative effects usually develops am ong p eople

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 seda-

tive agents such as alcohol or opiates.

The reinforcing effects of BDZs may not only be mediated

through bind ing of the alpha 1 or lambda 2 subtypes of

GABA receptors but also via an opioid m echanism, A partial

mu receptor antagonist such as naltrexone m ay reduce anxio-

lytic 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 m esolim bic system,

From Physiologic Dependence to Loss of ontrol

The dose and duration of exposure to BDZs determines the

developm ent of physiological depen dence. 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 BD Zs produce comparable severity of

withdrawal. The development of physiological dependence

is reduced with intermittent, eompared with continuous,

exposure to BDZs,

Among people exposed to BDZs, a small subset, likely

among those who have abused o ther substances, will develop

compulsive drug-seeking behaviour with loss of control and

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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 physio-

logical dependence, do not develop compulsive substance

use,^ and some patients present with compulsive substance

use without physiological depen dence. The abuse potential of

BDZs depends not only on the drug receptor selectivity but

also on the characteristics of the individual and environmen tal

circumstances.

BDZs as a primary substance of

buse

in people adm itted 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-occu rring psy-

chiatric disorder (mood, anxiety, and Cluster C personality)

occurs in up to 50% of these admissions. Among patients on

methadone maintenance treatment, 40% to 5 0% abuse BD Zs.

These rates are not significantly reduced by methado ne m ain-

tenance alone.

Guidelines for Respon sible Prescription

APA and NICE. The A PA 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 ith non-BD Z Antianxiety Medication and

CBT.

Non-BDZ antianxiety medication and CBT often take

week s before there is any beneficial effect, thus the sh ort-term

prescription of high-potency BDZs may remain an option

when patients exp ress an urgent need for the reduction of high

levels of anticipatory anx iety 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 BDZ s 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 p harmacolog ical

treatment the better the progn osis.'^

Coneerns Associated ith the Prescription of BDZs.

Concerns include:

1.

BDZs mainly have a favourable side effect profile;

howev er, 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,

it. Provided with short-term symptomatic relief the

patient may also lose motivation to follow all the CB

steps.

3.

Even after a few weeks of BDZ treatment, some

patients will experience withdrawal reactions on

discontinuation similar to an anxiety relapse, resultin

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 w eeks only.

• Drug holiday s; that is, intermittent use of medicatio

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 Managem ent of Cessation of Use. Cessation require

detailed understanding by the patient of the options involve

In our exp erienc e, it is critical for fearful patient to percei

that he or she retains a measure of control over the proces

Strategies for patients with comorbid anx iety or mood diso

ders 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

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

months, helps the patient to recognize and manage

symptoms of withdrawal and rebound anxiety, while

helping the transition in developing symptom contro

and self-efficacy.

5. In the case of recurrence of mood or anxiety problem

that may or may not mimic withdrawal sym ptoms,

alternate pharmacotherapy such as trazodone

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Are There G uidelines for the Responsible Prescription of Benzodiazepines?

return to a higher dose is not recommended. Sleep

disturbances have been alleviated by adding melatonin.

With

Primary Substance

se

C omorbidity

Very often

3 week detoxification

mend ed.''' To maintain the gains of detoxification,

BDZs are still widely prescribed among the

whom are women.^ Both duration and cum u-

and ñanctioning in the commun ity, and

DZ Prescription a Necessary Evil?

st BDZ u sers, particularly those with

a

comorbid psychiat-

on of BDZ as facilitating a coping strategy. Consulting

of

for complex cases. The answer m ay be in

hort-term care, long-term maintenance, and episodic or

reakthrough symptoms. Although the statistical risk for

ependence is relatively low, those unfortunate enough to

develop it will experience a clinically challenging withdrawal

course. Novel pharmacological factors, modulating particu-

larly GABA receptors, ion channels, or glutamatergic trans-

mission, are under various phases of investigation; their ease

of discontinuation m ust also be assessed.

The im plication is that newer medications w ith partial agon ist

effeets at selected GABA receptor subtypes may result in

more selective behavioural effects and better safety profiles.

References

1.

Ncutcl CI. The epidemiology o f 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 (ESEM eD). J Affeet

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-Oerlingh ausen 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 (D C):

Ameriean Psychiatric Pu blishing, Inc; 2008. p 215-23 5.

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 m ale

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 (SA MH SA).

Treatment Episode Data Set (TEDS): 1995-2 005; national admissions to

substance abuse treatment serviees. Series S-37 (DI-IHS no S MA -07-4 234 ).

Rockville (MD): SAMHSA; 2007.

10.

American Psychiatric Association. Practice guideline for the treatment of

patients with panie disorder. Atn J Psyehiatry. 1998; 155 5 Su ppl ) : 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. B enzodiazepines: how they w ork and how to withdraw [Internet]

[also known as the Ashton m anual]. [Updated 2002 Aug; cited 2008 Oct 20].

Available from: http://www.benzo.org.uk/manu al/indcx.htm.

Nady el-Guebaly

BDZs Should Be Considered in the

Long-Term Treatment of Mood and

Anxiety Disorders

B

enzodiazepines are one of the oldest classes of

pharmaco- therapeutic medications.' Discovered in

1955 by Stem bach, they have been widely used in many areas

of medicine. Most experts and regulatory guidelines recom-

mend the short-term use of BDZs in the treatment of tnood

and anxiety disorders.^ However, the long-term u se of BDZs

in treating mood and anxiety disorders has been controver-

sial. Some have argued that the long-term use of BDZs will

be associated with increased risk for tolerance, dose escala-

tion, and dependence.' We argue here that the benefits of

long-term BD Z 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 anx-

iety disorders. First, they work BDZ s 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 discontinua-

tion 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.

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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 toler-

ance). We w ill suggest some methods to minimize the risk of

dose escalation. Third, BDZs are often better tolerated than

SSRIs, atypical antipsychotics, or other classes of medica-

tions employed to treat anxiety that h ve side effects of weig ht

gain and sexual dysfunction. Fourth, absence of recent evi-

dence on the clinical usefulness of BDZs does not equal

inef

fectiveness. As there have been no new BD Zs available on the

market in the last 2 decades, there has been little financial

motivation among pharmaceutical companies to conduct

large-scale RCT s of BDZ s in the treatment of m ood and anxi-

ety disorders. In summary, we suggest that clinicians need to

carefully consider the use of BDZs in the long-term m anage-

ment of mood and anxiety symptoms, and researchers need to

conduct large-scale RCTs in this area.

BDZs Are Efficacious

BDZs reduce anxiety symptoms am ong patients with primary

anxiety disorders, and anxiety symptom s 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.^ RCT s have dem onstrated that BDZs are

effective in treating each of these anxiety disorders . There has

been a dearth of studies that have examined the use of BD Zs

among patients with OCD and PTSD.^ Although the few

studies examining the use of BDZ s among patients with OC D

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 exam ple,

increased suicidality^ and functional im pairm ent). Some stud-

ies 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.

h Dangers of Tolerance and Dependence on BDZ s

Have Been Catastrophized

Is a diabetic patient addicted to insulin? What about asthmat-

ics;

are they addicted to salbutamol? In our opinion, the dan-

gers 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 inci-

dence of

dose

escalation was small (1.6%). Physical depend-

been taking therapeutic doses for any prolonged time per

This is to be expected, and is neither an ind ication of an u

ward effect nor evidence of abuse or misuse. Some pati

do abuse BDZ s, and clinicians need to be wary of such peo

who are often expert at pulling the wool over prescrib

eyes.

Patients who call for early refills, lose their medica

and need a refill, or obtain their medication from mult

prescribers are to be carefully scrutinized in this regard.

clinicians, we need to use medications judiciously. Non e

less,

we should also make sure that we are treating pati

adequately.

To m inimize the small risk of dose escalation, we sugg est

clinicians should consider the following. First, caref

assess a history of impulsivity (for example, concurren

past alcohol and [or] substance use problem, antisocial p

sonality disorder, and borderline personality disord

Although anxiety sym ptoms and disorders are highly pre

lent in these subgroups, our experience is that BDZs are

likely to be enormously helpful. Second, minim ize the us

pm BDZs and use of short-half life BDZs (for exam

alprazolam). As-needed use of short-term BDZs leads t

cycle of taking BDZs at the peak of anxiety. In our opin

this cycle leads to higher likelihood of dose escalation. R

ular dose, long-acting BDZs such as clonazepam work w

in treating anxiety symptoms without the risk of d

escalation.

BDZs Do Not Cause Sexual Dysfunction and M etaboli

Syndrome

BDZs are well tolerated. However, SSRIs (and SNRIs)

a s soc ia ted wi th sexua l dys func t ion , and a typ i

antipsychotics are associated with metabolic syndrome

the risk (although smaller than for typical antipsychotics

movement disorders. These side effects can have substan

negative consequences on intimate partner relationships

cardiovascular health. Moreover, they can have a subst

tially negative impact on adherence to treatment. BDZs

generally safe and well tolerated by patients.

Industry s Influence on BDZ Use?

We w onder whether one of the reasons for the lack of rec

studies in this area is that there are no new BDZs on the m

ket. All the BDZ s are generic and there has been little fin

c ia l incent ive among pharmaceutica l companies

conducting large-scale studies to examine the efficacy

BDZs among patients with mood and anxiety disorder.

contrast, marketing strategies and CME events sponsored

the pharmaceutical industry typically have highlighted

novelty of ADs and antipsychotics in treating mood and an

ety disorders over the less costly use of BDZs. Indust

sponsored CM E events that are focused on new treatments

mood and anxiety disorders often remind clinicians of

potential risk of tolerance and dependence of BDZs, a

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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 com paring ADs to BD Zs. None of them

showed superiority of ADs over BDZs in the treatment of

GAD . They concluded that there has been a shift in prescrib-

ing 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 BDZ s

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 1 15-1125.

4.

Abramowitz JS, Taylor S, MeKay D. Obsessive-compulsive disorder. Laneet.

2009;374(9688);491-499.

5.

Ravindran LN, Stein M B. 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; 1249-125 7.

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

ebutt ls

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 disor-

ders, and, in support of their argument, they note that a reduc-

tion 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

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 SSR ls

over BDZs, Roy-Byrne et al' state that BDZs work rapidly

but are restricted by their narrow range of efficacy across dis-

orders, the risk of physiological dep endence and w ithdrawal,

and the risk of abuse. While the co-prescription of BDZs to

anxious patients treated with ADs is common, "no placebo-

controlled studies have yet been done ... [on] the effective-

ness of augmenting SSRls with ben zod iazepin es."'' '

'°^^

Th e

same could be said about the treatment of comorbid anxiety

and depression. Therefore, in summary, while there is evi-

dence 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 disor-

ders is not solely adequate pharmacology. Is not combined

psychotherapeu tic connection w ith the patient as important?

Lastly, as an addiction specialist, I am taken aback with the

suggestion that anxiety could be a "BDZ-deficiency syn-

drome" similar

to

"diabetes and its insulin deficiency." W hile

the incidence of dose escalation is relatively small in samp les

at low risk for addiction, this in no way negates the higher

biopsychosocial risks of BDZ dependence and other sub-

stance misuses in anxious and (or) depressed patients, as evi-

denced 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 BDZ s in mood or anxiety disorders

in the absence of adeq uate research.

fully support the search

for newer medication with improved safety profiles. A care-

ful risk analysis before the prescription of BD Zs is required.

CBT, as a widely studied and validated psychotherapeutic

treatment, should also be considered as a first-line augmenta-

tion 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

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In Debate

Reference

1,

Roy-Byme PP , Craske M G, 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

W

e thank Dr el-Guebaly for his thoughtful com ments 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 BDZ s is low. Noneth eless, phy-

sicians should prescribe these m edications judiciou sly and in

a responsible mann er. There is also a need for further rese arch

to guide clinicians in understanding wh ich patients are specif

ically 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 BDZ s, 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

AD s and, if necessary, small doses of antipsyehotics for man-

agement 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 BD Zs' is that they are associated with increased risk of

falls in the elderly. W e 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 po licies such that BDZs would require triplicate pre-

scriptions. This policy had a substantial impact on reducing

the prescription of BD Zs in New Y ork, How ever, this reduc-

tion in prescriptions did not have an impact on the prevalence

of hip f rac tures , - ' Al though the la t te r s tudy^ used

quasiexperimental data, and causal inferences cannot be

inferred, these findings are interesting and sugg est that BD

may not b e a strong contributor to falls in the elderly.

Second, Dr el-Guebaly com ments that the APA gu idelines

panic disorder, first edition, do not recommend the use

BDZ s for the treatment of panic disorder. Please note that

updated guidelines published by the APA in 2009 * reco

mend the use of BDZs in certain patients with panic disord

These guidelines suggest that monotherapy with BDZs

panic disorder can be used when com orbid depression is no

major issue.

In summary, we believe that BD Zs, when prescribed with

awareness of their risks and benefits, have an important r

to play in the treatment of patients with mood and anxi

disorders.

References

1.

Bolton JM, Metge C, Lix L, et al. Fracture risk from psychotropic medicatio

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

medication classes on falls in elderly persons. Arch Intern Med.

2009;169(21):1952-1960.

3. Wagner A K, Ross-Degnan D, Gurwitz JH, et al. Effect of N ew 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 p

disorder seeond edition. Am J Psychiatry. 2009;166(2):sl-s68.

Jitender Sareen and Murray B St

knowledgements

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 Heal

Researeh Council Chair award. Dr Sareen and Dr Stein

acknowledge Dr Rick H awe for his assistance in m anuscript

preparation.

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

Alberta; Consultant, Addiction Centre and Program, Alberta Health

Services, Calgary, Alberta.

Address for correspondence Dr N el-Guebaly, Foothills Medical Centr

Addiction Centre, 1403-29 STN W , Calgary, AB T2N 2T9;

[email protected]

Professor of Psychiatry, Psychology, and Community Health Science

University of Manitoba, Winnipeg, Manitoba; Consulting Psychiatris

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;

[email protected]

7/17/2019 57309193.pdf


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