Review Article

Anxiety
Address correspondence to
Dr Asim A. Shah,
Neuropsychiatric Center,
Second floor, Room 2.125,
1502 Taub Loop, Asim A. Shah, MD; Jin Y. Han, MD
Houston, TX 77030,
aashah@bcm.edu.
Relationship Disclosure:
Dr Shah has received personal ABSTRACT
compensation as a speaker Purpose of Review: This article provides an overview of anxiety disorders including the
from Otsuka Pharmaceutical.
Dr Han reports no disclosure. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic
Unlabeled Use of criteria with practical key features. The article discusses neurologic and other medical
Products/Investigational comorbidities as well as treatment strategies, keeping in mind the co-occurrence of
Use Disclosure:
Drs Shah and Han discuss
anxiety disorders with depression.
the unlabeled/investigational Recent Findings: Several studies have emphasized the high prevalence of comorbid
use of propranolol for the mental and medical conditions including, but not limited to, cardiovascular and neurologic
treatment of performance anxiety.
illnesses, making the overall management of these patients more costly and complex,
ultimately leading to decreased length and quality of life. However, several research
studies have suggested that appropriate and effective comanagement of anxiety and
depression improves overall outcomes of those individuals with chronic medical conditions.
Summary: Anxiety and depression are common psychiatric conditions that not only co-
occur, but also co-occur with other neurologic illnesses. Early recognition and treatment of
these comorbidities are imperative in order to achieve better health outcomes for patients.

Continuum (Minneap Minn) 2015;21(3):772–782.

INTRODUCTION United States during their lifetime. Like

Some studies have estimated that 17%
of the adult population have had comor-
bid mental and medical conditions within
a 12-month period.1,2 More than 68%
of patients with a mental disorder re-
ported having at least one medical con-
dition, and 29% of those with a medical
condition had a comorbid mental ill-
ness.1,3 Additionally, mental illnesses,
cardiovascular conditions, and neurologic
disorders are common comorbidities in
Medicaid beneficiaries.4 Several research
studies have suggested that appropri-
ate and effective comanagement of
anxiety and depression improves over-
all outcomes.5Y7
According to the National Comorbid-
ity Survey replication report, one in four
people meet criteria for any anxiety disor-
der, with a 1-year prevalence rate of
18.1%.8 Studies have suggested that anx-
iety disorders affect close to 30 million
people in the United States at some
point of their lives,9,10 while depression
affects 17 to 22 million people in the
depression, anxiety has a two to one ra-
tio of women to men who have the dis-
order. Anxiety usually presents in a
younger age group, although a slight
surge occurs in older adults due to their
medical comorbidities, financial stressors,
and even at times of ‘‘empty nest
syndrome.’’ Low socioeconomic status
is an important risk factor, as is the
presence of multiple medical comorbidities.
More than 50% of patients with depres-
sion have comorbid anxiety.11
Anxiety is a psychological and phys-
iologic state characterized by a constel-
lation of somatic, emotional, cognitive,
and behavioral symptoms. Whether or
not psychological stress exists, anxiety
creates feelings of fear, worry, uneasiness,
and dread,12 causing significant distress
or impairment in daily functioning.
PATHOPHYSIOLOGY
Serotonin, norepinephrine, and GABA
are the three main neurotransmitters
involved in anxiety disorders. Imaging

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 KEY POINTS
studies have implicated hyperactivity of Social anxiety disorder or social pho- h Appropriate and effective
the amygdala and other components of bia is a marked fear or out-of-proportion comanagement of anxiety
the limbic system in the pathogenesis anxiety about one or more social situa- and depression improves
of anxiety and depression.13Y15 Some tions in which an individual is exposed overall outcomes.
studies have suggested that the solute to possible scrutiny by others. Patients h Anxiety disorders affect
carrier family 6 (neurotransmitter trans- with social anxiety disorder fear either close to 30 million
porter), member 4 (SLC6A4) gene, and that their behavior or their anxiety people in the United
the catechol-O-methyltransferase (COMT) symptoms could be judged negatively States at some point of
gene influence the degree of amygdalar by those around them, causing embar- their lives.
response to anxiety.16 rassment or humiliation. Therefore, pa- h Serotonin, norepinephrine,
Studies with MRI have shown reduc- tients avoid these anxiety-provoking and GABA are the three
tion in volume of the amygdala and social situations. Symptoms of social main neurotransmitters
temporal lobes in patients with panic anxiety disorder are persistent, typically involved in
disorders.17,18 A positron emission to- lasting for 6 months or more. anxiety disorders.
mography (PET) imaging study found Although generalized anxiety disorder h Specific phobia is the
low density of the serotonin type 1A makes up a small percentage of anxiety most common form of
receptor in the anterior and posterior disorders in psychiatric practice, in pri- anxiety and can manifest,
cingulate areas in the midbrain raphe mary care, generalized anxiety disorder is for example, as fear of
in patients with panic disorders.19 found in up to 22% of the patients who heights (acrophobia)
In addition to the neurobiological view, experience anxiety symptoms.21 Since and fear of closed
other factors influence the development it is the most common of psychiatric spaces (claustrophobia).
of anxiety disorders, such as the genetic diagnoses seen by physicians other than h Social anxiety disorder
predisposition, temperament, or per- psychiatrists, making an early diagnosis or social phobia is a
sonality traits of the individual, as well and providing appropriate treatment marked fear or
as life experiences or traumatic events. is very important. Generalized anxiety out-of-proportion
disorder is defined as excessive worry, anxiety about one or
CLASSIFICATION more social situations in
occurring more days than not for at
which an individual is
The DSM-5 has the following common least 6 months, about a number of events
exposed to possible
subtypes of anxiety affecting adults in its or activities, which causes significant scrutiny by others.
diagnostic schema20: (1) specific phobia; distress or impairment in social, occu-
h In primary care,
(2) social anxiety disorder; (3) general- pational, or other important areas of
generalized anxiety
ized anxiety disorder; (4) panic disorder; daily functioning. Generalized anxiety
disorder is found in
and (5) agoraphobia. disorder presents with physical symp- up to 22% of the
Specific phobia is the most common toms such as fatigue, muscle tension, patients who report
form of anxiety and can manifest, for and restlessness. anxiety symptoms.
example, as fear of heights (acrophobia), The diagnosis of panic disorder has
h Generalized anxiety
fear of closed spaces (claustrophobia), been simplified in the DSM-5 since it is disorder is defined as
fear of cats (ailurophobia), or fear of dogs now a stand-alone diagnosis not associ- excessive worry,
(cynophobia) (Case 11-1). Specific pho- ated with agoraphobia. In prior versions occurring more days
bia is defined as a marked fear or anxiety of the DSM, panic disorder was diagnosed than not for at least
about either a specific object or situa- as presenting either with or without 6 months, about a
tion, in which the phobic object or situa- agoraphobia. Panic attacks present with number of events or
tion will almost always provoke immediate a wide range of symptoms including activities, which causes
fear or anxiety and cause significant dis- palpitations, tachycardia, diaphoresis, significant distress or
tress. The fear or anxiety is persistent and trembling, choking, shortness of breath, impairment in social,
is out of proportion to the danger the paresthesia, derealization, and fear of occupational, or other
important areas of
phobic object or situation objectively losing control or dying. An attack is fol-
daily functioning.
poses. Furthermore, the patient actively lowed by persistent concern about future
avoids the object or situation.20 attacks. Patients with agoraphobia are
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 Anxiety

KEY POINT
h The diagnosis of panic
disorder has been
Case 11-1
A 67-year-old widow presented to her primary care doctor after experiencing
simplified in the
anxiety and fear while driving. While the patient had driven all her life, she
Diagnostic and Statistical
had never previously driven on bridges or main highways as her husband
Manual of Mental
would drive her in these situations. The patient had been a homemaker her
Disorders, Fifth Edition
entire adult life, and since her husband’s death the previous year, she lived by
since it is now a
herself and financially supported herself on her social security income and
stand-alone diagnosis
savings. Her diabetes mellitus was well controlled on metformin, and she had
not associated
maintained a glycosylated hemoglobin around 6.5 for many years. Laboratory
with agoraphobia.
results showed normal thyroid-stimulating hormone (TSH) level and an
unremarkable complete blood count. She had no prior psychiatric history.
Further evaluation revealed that she had experienced worsening anxiety
before attempting to drive across a long high bridge. She became so anxious
that she had to stop driving and park her car on the shoulder. As a result, she
had limited her driving to surface roads only and had been continuing to avoid
bridges and highways. Visiting her only daughter, who lived 45 miles away,
would require her to drive on an interstate highway and cross many high
bridges and ramps. This anxiety had also led her to become depressed.
Comment. This patient was diagnosed with a fear of heights (acrophobia),
a variant of specific phobia. Due to her age, she was started on sertraline
while participating in weekly cognitive-behavioral therapy sessions.
Paroxetine, with its anticholinergic side effects, is not a treatment of choice
for patients over 65. Escitalopram is another good alternative due to its
negligible drug interaction profile. The patient was started on sertraline
25 mg daily, which was titrated up to 50 mg daily after 2 weeks. When she
was reevaluated 8 weeks later, her symptoms had improved, but not
completely resolved. She was able to drive on highways, but she was still
anxious about driving on tall bridges. Her sertraline was increased to 100 mg daily,
and 4 weeks later she was able to drive to her daughter without anxiety, fear,
or phobia about bridges.

fearful of certain situations where escape
could be difficult or help might not be
available in the event of a panic attack.20
DIAGNOSTIC KEY WORDS OR
HINTS FOR CLINICIANS
While taking a history from a patient suf-
fering from anxiety, the physician should
be particularly attentive to certain key
words patients use to describe their symp-
toms as these key words can serve to
help differentiate from among the dif-
ferent types of anxiety disorders and es-
tablish the correct diagnosis.
Phobia
Phobia is the fear or anxiety about a specific
object or situation such as animals, heights,
water, needles, or airplanes. The key words
or cues reported by patients that will help
guide the clinician’s diagnostic evaluation
are fear and avoidance of a specific object
or situation. The duration of these symp-
toms lasts for at least 6 months (Case 11-1).
Social Anxiety Disorder
Social anxiety disorder is the fear or
anxiety about social situations in which
scrutiny by others is possible. For this
disorder, fear and avoidance of social sit-
uations are the key words or cues re-
ported by patients that will help guide
the clinician’s diagnostic evaluation. The
duration of symptoms is at least 6 months.
Generalized Anxiety Disorder
Generalized anxiety disorder is identified
by the symptom of excessive worry about

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anything, lasting for at least 6 months.
For this disorder, the key diagnostic
cue is excessive worry (Case 11-2).
Panic disorder
Symptoms of panic disorder resemble
an acute coronary syndrome and is
frequently seen in the emergency de-
partment setting where a medical workup
is performed to exclude cardiac and
other possible medical etiologies. The
duration of a panic attack is usually very
short (5 minutes to less than 20 minutes,
but usually no more than 30 minutes).
The diagnostic key words or cues are
sense of impending doom, and panic
disorder is associated with other symp-
toms such as palpitations, sweating,
trembling, shortness of breath, choking
sensation, chest pain, abdominal dis-
comfort, dizziness, paresthesia, and
feeling of unreality or being detached
from self, losing control, or fear of
KEY POINT
dying. The patient may express con- h Anxiety disorders are
cerns for future panic attacks and may seen very commonly in
also avoid some situations that may neurologic conditions
trigger panic attacks. and are more commonly
comorbid with
Agoraphobia neurologic disorders
Agoraphobia is the fear or anxiety about than are
situations where escape might be diffi- mood symptoms.
cult or help might not be available. The
patient tries to avoid such situations.
The duration of symptoms is at least
6 months, and the key words are fear
and avoidance of ‘‘no escape’’ or ‘‘no
help’’ situations.
ANXIETY WORKUP AND
NEUROLOGIC COMORBIDITIES
Anxiety disorders occur very commonly
in neurologic conditions and are more
commonly comorbid with neurologic
disorders than are mood symptoms.
When anxiety is thought to be a direct
consequence of an underlying physical

Case 11-2
A 25-year-old woman presented to a psychiatrist for evaluation of ‘‘paranoia.’’ Her husband stated that
she had always been suspicious that something would go wrong, and, thus, he considered her paranoid.
The patient had been married for 6 years and had three daughters, one with congenital heart disease.
Although her two younger daughters attended preschool, the older daughter, who was 5 years old,
was too sick to attend school. The patient cared for her daughter at home and attended numerous
medical appointments. Her husband noted that she was always worried that something bad was going to
happen to their 5 year old. The patient also would become very worried if the other daughters came
home late for any reason, even if the carpool was late dropping them off due to traffic congestion. The
patient had no symptoms of psychosis (ie, no auditory or visual hallucinations, no paranoia, and no
thought-content abnormalities). It was noted that, while talking about her family, she would become
worried rather easily and could not control her worry in spite of all assurances. However, no paranoia
(false beliefs of persecution, threat, or conspiracy toward self) was noted. She was also noted to have a
constricted affect and had depressed mood associated with poor quality of sleep and fatigue.
Comment. This patient had generalized anxiety disorder. While her husband referred to the patient as
paranoid, her symptoms were truly ones of excessive worry and out of proportion to what one may
objectively expect. This patient’s anxiety had been occurring for more than 1 year and fit the diagnostic
criteria for generalized anxiety disorder. She was started on escitalopram 10 mg daily, which is a
US Food and Drug Administration (FDA)Yapproved treatment of generalized anxiety disorder. While the
patient responded to treatment and her anxiety and excessive worry decreased, her symptoms did not
fully resolve. Since she had some important social factors, such as her daughter’s illness, contributing to her
anxiety, weekly cognitive-behavioral therapy sessions were added to her treatment. After the completion of
cognitive-behavioral therapy, the patient improved tremendously. Her anxiety and worry were under control,
and the patient continued to take escitalopram 10 mg daily with good results.

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 Anxiety
KEY POINTS
h Patients with multiple
sclerosis are at
particularly high risk for
anxiety disorders,
especially if the patient
is a female, has a history
of depression, and has
poor social support.
h Patients with Parkinson
disease or epilepsy
are also at high risk
of anxiety.
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condition, DSM-5 codes the condition A comprehensive psychiatric inter-
as anxiety disorder due to another view as well as physical and neurologic
medical condition (Table 11-122).20 examinations should be part of the
initial evaluation, and collateral infor-
mation could provide further data to
TABLE 11-1 Nonpsychiatric
Causes of Anxietya
clarify the diagnosis. Considering the
high prevalence of comorbidities such
as chronic medical illnesses and depres-
b Neurologic
sion, a good review of physical and
Brain tumors
psychiatric symptoms is helpful. Most of
Encephalitis
the young patients without comorbidities
Migraines
only need basic laboratory tests such as
Multiple sclerosis and other a complete blood count, basic metabolic
demyelinating conditions
profile, thyroid-stimulating hormone (TSH),
Parkinson disease and other
and a urine drug screen, but older pa-
neurocognitive-movement
disorders tients with a higher risk of cardiovascular
Seizures
conditions will warrant an ECG and other
tests such as a Holter monitor, and even a
Strokes
referral to cardiology or other specialties
Traumatic brain injury
for further assessment if clinical suspicion
Vestibular dysfunction
of another medical condition is high.
b Endocrine/Secreting Tumors Patients with multiple sclerosis are
Carcinoid syndrome at particularly high risk for anxiety dis-
Cushing disease orders, especially if the patient is female,
Hyperthyroidism has a history of depression, and has poor
Hypoglycemia/insulinoma social support.23 In one study of patients
Pheochromocytoma with multiple sclerosis, the prevalence of
b Cardiopulmonary anxiety disorders was as high as 35.7%,
Angina with generalized anxiety disorder being
Arrhythmia the most common anxiety disorder, fol-
Asthma
lowed by panic disorder and obsessive-
compulsive disorder.23
Congestive heart failure
Patients with Parkinson disease are
Coronary artery disease
also at high risk for anxiety, with 19%
Pneumothorax
experiencing anxiety in one study.24
Pulmonary embolism Anxiety is also common among pa-
Syncope tients with epilepsy, and anxiety man-
Valvular disease ifests differently during postictal and
b Substances or Drugs interictal phases.25,26 Although some
Alcohol or benzodiazepine antiepileptic drugs may reduce depres-
withdrawal sion, none of them reduce anxiety.27,28
Amphetamines In some cases, seizure and anxiety
Bronchodilators both may present as fear, complicat-
Caffeine ing the diagnosis.29
Cocaine
a
TREATMENT
Data from Rosenbaum JF, N Engl J Med.22
www.nejm.org/doi/full/10.1056/ Pharmacologic Treatment
NEJM198202183060705. Treatment of anxiety disorders is inti-
mately tied to the neurotransmitters
June 2015

believed to mediate anxiety symptoms,
as described above. Benzodiazepines
bind to GABA-A receptors, enhancing
the effects of the main inhibitory neuro-
transmitter GABA; selective serotonin
reuptake inhibitors (SSRIs) increase the
availability of serotonin by inhibiting its
presynaptic reuptake, and serotonin
norepinephrine reuptake inhibitors
(SNRIs) work in similar fashion involv-
ing serotonin as well as norepineph-
rine. Monoamine oxidase inhibitors
(MAOIs) inhibit monoamine oxidase,
increasing the availability of neurotrans-
mitters such as serotonin, norepinephrine,
and dopamine. Tricyclic antidepres-
sants inhibit presynaptic reuptake of
serotonin and norepinephrine but also
antagonize histamine and muscarinic
acetylcholine receptors. Hydroxyzine
(H1 receptor inverse agonist) and bus-
pirone (5-HT1A receptor partial ago-
nist) are also common therapeutic
options used to treat anxiety. SSRIs
and SNRIs are the first-line treat-
ment of any kind of anxiety disorder
(Table 11-2). They are generally well
tolerated and are less toxic in over-
doses than tricyclic antidepressants.
Specific phobia. None of the SSRIs
or SNRIs are officially approved by the
FDA to treat specific phobias, and,
furthermore, no benzodiazepine, hy-
droxyzine, buspirone, or propranolol
have such approval, but it is a common
practice to utilize these medications as
needed while the patient undergoes
psychotherapy (Case 11-1).
Panic disorder. FDA-approved drugs
to treat panic disorder are fluoxetine,
paroxetine, sertraline, venlafaxine ex-
tended release, alprazolam, and clonaz-
epam (Table 11-2).
Social anxiety disorder or social
phobia. Paroxetine was the first SSRI to
receive FDA approval to treat social
phobia in 1999. In 2003, sertraline
received FDA approval for short-term
and long-term (20 weeks) treatment of
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KEY POINTS
social phobia in adults, followed by h Selective serotonin
venlafaxine extended release, which reuptake inhibitors and
was also approved in 2003 for the same serotonin norepinephrine
indication (Table 11-2).30 reuptake inhibitors
Generalized anxiety disorder. are the first-line treatment
FDA-approved SSRIs and SNRIs for the of any kind of
treatment of generalized anxiety disor- anxiety disorder.
der include escitalopram, paroxetine, h Many psychiatrists also
venlafaxine extended release, and favor hydroxyzine for
duloxetine (Case 11-2). Buspirone is a the treatment of
5-HT1A receptor partial agonist ap- anxiety. Unlike
proved for treating generalized anxiety buspirone, which takes
disorder as well. It does not have anti- 2 weeks to work,
convulsant or muscle-relaxant properties. hydroxyzine works
rather quickly.
It is nonsedating, does not have signif-
icant affinity for benzodiazepine recep-
tors, and does not affect GABA binding
at all.31
Many psychiatrists also favor hydroxy-
zine as an add-on medication for the
treatment of anxiety instead of classic
benzodiazepines. Unlike buspirone,
which takes 2 weeks to work, hydroxy-
zine works rather quickly and has some
calming and sedating properties, which
anxious patients often like. Hydroxy-
zine has been on the market since 1956
and is a first-generation antihistamine of
the diphenylmethane and piperazine
class. Hydroxyzine has shown to be as
effective as the benzodiazepine drug
bromazepam in the treatment of gener-
alized anxiety disorder.32 Hydroxyzine
can be administered either orally or via
IM injection, and its effect is notable in
30 minutes after oral administration.
Hydroxyzine is a potent H1 receptor
inverse agonist with a very low affinity
for the muscarinic acetylcholine recep-
tors. The medication, therefore, has a
low propensity for producing anticho-
linergic side effects (sedation is most
common, but dry mouth also frequently
occurs). The antiserotonergic (5-HT2A)
effects of hydroxyzine may be the rea-
son for its anxiolytic effects,33 as other
antihistamines without such proper-
ties are not effective in the treatment
of anxiety.34
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 Anxiety

TABLE 11-2 List of US Food and Drug AdministrationYApproved Drugs for Anxiety Disorders

Disorder and Medication Classa Dose Range Commentsa

Panic disorder
Fluoxetine Selective serotonin 10Y60 mg/d Activating
reuptake inhibitor (SSRI) Long half-life
Drug interaction is common
Paroxetine SSRI 10Y60 mg/d Somnolence
Short half-life
Anticholinergic effect
Drug interaction is common
Sertraline SSRI 25Y200 mg/d Gastrointestinal discomfort
Activating
Venlafaxine extended Serotonin norepinephrine 37.5Y225 mg/d Dose-dependent blood
release reuptake inhibitor (SNRI) pressure elevation
Activating
Alprazolam Benzodiazepine 0.5Y2 mg/d Potential for abuse
Short half-life
Potential for withdrawal
Clonazepam Benzodiazepine 0.25Y2 mg Long acting
2 times/d Potential for abuse
Social anxiety
Paroxetine SSRI 10Y60 mg/d Somnolence
Short half-life
Anticholinergic effect
Drug interaction is common
Sertraline SSRI 25Y200 mg/d Gastrointestinal discomfort
Activating
Venlafaxine extended SNRI 37.5Y225 mg/d Dose-dependent blood
release pressure elevation
Activating
Generalized anxiety disorder
Escitalopram SSRI 10Y20mg/d Negligible drug interaction
Good tolerability
Paroxetine SSRI 10Y60 mg/d Somnolence
Short half-life
Anticholinergic effect
Drug interaction is common
Venlafaxine extended SNRI 37.5Y225 mg/d Dose-dependent blood
release pressure elevation
Activating
Duloxetine SNRI 30Y120 mg/d FDA-approved for fibromyalgia,
diabetic neuropathy, chronic
musculoskeletal pain
Buspirone Azapirone 7.5Y30 mg No abuse potential
2 times/d
a
All SSRIs and SNRIs can cause gastrointestinal disturbance and sexual dysfunction.

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Benzodiazepines such as alprazolam,
clonazepam, oxazepam, chlordiazepoxide,
lorazepam, clorazepate, and diazepam
have been also approved for anxiety as
well as hydroxyzine, as described
above. Beta-blockers such as propran-
olol have been used with success in
cases of performance anxiety (eg,
before an examination, before making
a speech in front of people, or before
any presentation in public). The DSM-5
classifies performance anxiety under
social anxiety disorder with ‘‘performance
only’’ as a specifier.20
Benzodiazepine use in anxiety
disorders. Although benzodiazepines
can be useful short-term medications
for treating anxiety disorders, they have
enormous abuse potential. According
to the Centers for Disease Control and
Prevention (CDC), benzodiazepine use
has become a growing industry in the
last few decades, and prescriptions have
risen over 200% in the last few years.35
According to IMS Health’s National
Prescription Audit, which is the leading
audit system monitoring prescription
trends, alprazolam was the top psychi-
atric drug prescribed in the United States
with 45.3 million prescriptions in 2009
and 49.6 million prescriptions in 2013.
Most of these prescriptions were written
by nonpsychiatrists.36
More annual benzodiazepine pre-
scriptions were written than SSRI pre-
scriptions for either anxiety or depression
combined. These figures are not only
alarming, but also disappointing as
benzodiazepines will not treat the co-
morbidities of anxiety such as depression.
Alprazolam use is of special concern,
as withdrawal can cause seizures and
other serious effects.37,38
A 2012 International Narcotics Control
Board report notes that alprazolam is the
world’s most manufactured psychotropic
substance. Internationally, alprazolam is
included under the United Nations’
Convention on Psychotropic Substances
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KEY POINT
as a schedule IV medication.39 In the h A 2012 International
United Kingdom, alprazolam is not Narcotics Control Board
available through the National Health report notes that
Service and can only be obtained by a alprazolam is the world’s
private prescription.40 In Australia, alpraz- most manufactured
olam was originally a schedule IV (pre- psychotropic substance.
scription only) medication; however, as of Internationally, alprazolam
February 2014, it has become a schedule is included under
VIII medication, subjecting it to more the United Nations’
rigorous prescribing requirements.41 Convention on Psychotropic
Substances as a
Thailand’s Ministry of Public Health
schedule IV medication.
has banned alprazolam because of its
escalating use in sex crimes. According
to Oklahoma state drug overdose data
from 1994 to 2006, alprazolam was a
contributing factor in 15.2 deaths.42
When a benzodiazepine is indicated,
clonazepam and lorazepam are the drugs
of choice, usually at doses lower than
2 mg a day. Alprazolam is considered
to be a poor choice because of its short
half-life, potential for abuse, and with-
drawal symptoms. Benzodiazepines are
effective agents for treating anxiety dis-
orders; however, some significant chal-
lenges are associated with their use,
primarily concerns noted above about
abuse or dependence, as well as diver-
sion, falls, and memory loss, and alpraz-
olam has been the benzodiazepine of
most concern regarding these symptoms.
Physicians are divided on when to use
benzodiazepines, for how long, and at
what doses in patients with addictions.
In spite of all the concerns discussed
above, prescribing patterns of benzodi-
azepines have stayed fairly stable for more
than 13 years and actually may have in-
creased.43 Benzodiazepines are the most
common class of medications used to
treat anxiety disorders (these medica-
tions are not indicated or approved for
the treatment of depression), and even
after a decade of taking them, a third of
these patients were still taking them.43
According to another study, mentally
or physically vulnerable people are
most likely to be at a greater risk of
inappropriately using these agents.44
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 Anxiety
KEY POINTS
h Alprazolam is
considered to be a poor
choice because of its
short half-life, potential
for abuse, and
withdrawal symptoms.
h The most widely accepted
and most effective
nonpharmacologic
treatment of anxiety
disorders is cognitive-
behavioral therapy.
h Anxiety and depression
are common psychiatric
conditions which not
only co-occur, but also
co-occur with other
neurologic illnesses.
Early recognition and
treatment of these
comorbidities are
imperative in order to
reach better health
outcomes for patients.
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Nonpharmacologic Treatment
The most widely accepted and most ef-
fective nonpharmacologic treatment of
anxiety disorders is cognitive-behavioral
therapy.45,46 For highly motivated patients,
cognitive-behavioral therapy is an excel-
lent option. It should be noted, however,
that cognitive-behavioral therapy is usu-
ally performed by a trained cognitive-
behavioral therapy clinician. Therapy is
usually 10 to 20 weekly sessions.
CONCLUSION
In summary, anxiety disorders are often
chronic and relapsing. Anxiety and de-
pression are common psychiatric condi-
tions that not only co-occur, but also
co-occur with other neurologic illnesses.
Early recognition and treatment of these
comorbidities are imperative in order to
achieve better patient health outcomes.
While judicious use of a benzodiazepine is
considered appropriate, the medication
is most appropriately prescribed for
short-term use (eg, no longer than
6 weeks). SSRIs, SNRIs, and cognitive-
behavior therapy should be the treatments
of choice as these medications not only
show similar if not greater efficacy, but
also long-term data show promise that
these medications effectively treat anx-
iety and comorbid depression.
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