TRIPASS XR تري باس

 

women disappears after menopause, which may necessitate the use of lower

benzodiazepine dosages during the postmenopausal period. Women have slower

glucuronidation metabolic processes than men, resulting in lower clearance of agents

such as temazepam and oxazepam.

57,77

Obesity and liver impairment are other physiologic factors relevant to B.G.’s case.

Obesity increases the volume of distribution of benzodiazepines and the extent of

accumulation of long-acting agents. Significant changes in the elimination half-lives

of lorazepam and oxazepam are not observed in obese patients. Liver dysfunction can

reduce benzodiazepine elimination rates and prolong their half-lives, resulting in

recommendations for decreased dosages. The pharmacokinetics of lorazepam,

oxazepam, and temazepam are unaffected by liver disease.

Decreased protein binding of benzodiazepines can occur in patients with renal

insufficiency, which may lead to increased free fractions of highly protein-bound

agents. However, no significant changes in clearance or volume of distribution of

free drug have been noted. Regarding ethnicity, up to 25% of Asians are CYP2C19

poor metabolizers. Decreased clearance of a variety of CYP2C19 substrates,

including diazepam, has been reported in Asian subjects.

98

In summary, the physiologic factors that can alter benzodiazepine disposition in

B.G. are his age, obesity, male sex, and liver disease. Accumulation of clonazepam

owing to these combined effects probably led to his mental status changes. In

addition to these factors, cimetidine and omeprazole can both increase the exposure

of clonazepam, resulting in decreased clearance and increased side effects.

If continued benzodiazepine therapy is deemed necessary for B.G., lorazepam or

oxazepam would be preferred agents because they are least affected by aging,

obesity, liver disease, or drug interactions. Benzodiazepine dosage equivalencies,

which are based on relative potencies, can be used to determine an equivalent dose

for the selected agent (Table 83-4). However, these equivalencies are inexact, and

dosing conversions should take patient variables and usual dosage ranges into

consideration. For example, B.G. had been taking 1 mg/day of clonazepam, so the

calculated equivalent lorazepam dosage is 3 to 4 mg/day. Because of his age and

recent reaction at this dose, a somewhat lower initial dose of 0.5 to 1 mg BID would

be indicated, accompanied by careful monitoring for adverse effects or withdrawal

symptoms. However, switching to a nonbenzodiazepine agent should be considered

because this may be a better treatment option for B.G.

Buspirone Therapy

CASE 83-6, QUESTION 2: Several days after recovery from clonazepam intoxication, B.G. expresses a

desire to discontinue benzodiazepine use. He is being criticized by his fellow Alcoholics Anonymous program

members for taking a drug associated with dependency. The decision is made to switch B.G. from clonazepam

to buspirone. How does the clinical profile of buspirone compare with benzodiazepines?

Buspirone lacks CNS depressant effects, sedation, cognitive or psychomotor

impairment, respiratory depression, and muscle relaxant or anticonvulsant effects.

46

This makes buspirone useful in older patients who may have a variety of chronic

medical conditions. Buspirone is generally well tolerated, and possible side effects

include mild nausea, dizziness, headache, and initial nervousness.

99 Unlike many

antidepressants, buspirone does not adversely affect sexual functioning and has

actually improved sexual functioning in some patients with GAD.

47 Buspirone has

minimal potential for abuse and is not classified as a controlled substance. It does not

produce physical dependence or withdrawal syndromes on discontinuation, even

after long-term therapy.

46,100

It also does not interact with alcohol or other CNS

depressants and is relatively safe in overdose.

46

Buspirone is a 5-HT1a receptor agonist/antagonist and is as effective as

benzodiazepines such as alprazolam, oxazepam, lorazepam, diazepam, and

clorazepate in the treatment of GAD.

99,100 Like antidepressants, buspirone is more

effective than benzodiazepines in treating the cognitive symptoms of anxiety.

However, the anxiolytic effects of buspirone have a more gradual onset than

benzodiazepines. Initial effects are observed within the first 7 to 10 days, but 3 to 4

weeks may be needed for optimal results. Buspirone must be taken on an ongoing

basis if it is effective, and the drug should not be taken “as needed.”

SWITCHING FROM BENZODIAZEPINE TO BUSPIRONE THERAPY

CASE 83-6, QUESTION 3: How should B.G. be switched from benzodiazepine to buspirone therapy?

Because buspirone has no CNS depressant effects and is not cross-tolerant with

the benzodiazepines, it is not effective in preventing or treating benzodiazepine

withdrawal. Thus, when patients are converted from benzodiazepine to buspirone

therapy, the benzodiazepine must be discontinued gradually. Because it takes several

weeks for full therapeutic effects of buspirone to occur, it can be initiated before the

benzodiazepine taper begins. This may indirectly ease benzodiazepine withdrawal by

providing extra anxiolytic coverage during the benzodiazepine taper period.

101

Administration with food may significantly increase bioavailability by decreasing

the first-pass effect. Some of the side effects of buspirone, such as nervousness, are

attributed to its active metabolite, 1-pyrimidinylpiperazine (1-PP).

46,102 The mean

elimination half-life of buspirone is short, approximately 2 to 3 hours, but 1-PP is

longer acting.

The clearance of buspirone is significantly reduced in patients with kidney or liver

disease, but there is little change in side effects or tolerability.

46 Nevertheless, it is

recommended that buspirone dosages be lowered in patients with compromised renal

or hepatic function and that use of the drug be avoided in cases of severe impairment.

Buspirone is metabolized by CYP3A4, and coadministration of CYP3A4

inhibitors, including grapefruit juice, can result in significant increases in buspirone

levels.

46 Because of buspirone’s extremely wide margin of safety and tolerability,

even very large increases in its plasma levels may be clinically insignificant.

Buspirone should be avoided in patients taking MAOIs and used cautiously in

combination with high-dose antidepressants because of the risk of serotonin

syndrome.

Some studies suggest patients previously treated with benzodiazepines will not

respond favorably to buspirone.

72,100 However, buspirone may provide benefit in this

population as long as the benzodiazepine is tapered slowly enough to prevent

withdrawal effects.

22 B.G. has been taking diazepam for several months and the drug

needs to be withdrawn gradually during a period of at least several weeks. B.G. can

be started on buspirone at this time. The usual recommended starting dosage of

buspirone is 15 mg/day given in two to three divided doses, but a lower dosage (10

mg/day) is indicated in B.G. because of his liver disease. Twice-daily dosing is

preferred to facilitate compliance and is comparable in efficacy and tolerability to

three-times-daily dosing.

103 The daily dosage may be increased in 5-mg/day

increments every 3 to 4 days. Optimal anxiolytic doses generally range from 20 to 30

mg/day, with 60 mg/day being the recommended maximum. There are no specific

guidelines for adjusting dosages in patients with liver impairment; therefore, dosage

titrations in B.G. should be made slowly, according to his response and side effects.

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PANIC DISORDER

Diagnostic Criteria

The hallmark characteristic of panic disorder is the occurrence of sudden and distinct

panic attacks, which are marked by an overwhelming wave of symptoms and feelings

reaching their peak within 10 minutes. Symptoms are listed in Table 83-9. To meet

diagnostic criteria, at least one of the attacks must be followed by symptoms lasting

at least 1 month, including persistent worry or concern about the consequences of the

attack or significant behavior change related to the attack.

1 Experiencing less than the

four required symptoms to fulfill diagnostic criteria is termed a “limited symptom

attack.” Three types of panic attacks have been defined with regard to the context in

which they occur: unexpected or uncued panic attacks (the attack is not associated

with a situational trigger); situationally bound panic attacks (the attacks invariably

occur on exposure to a situational trigger); and situationally predisposed panic

attacks (the attacks are more likely to, but do not invariably, occur on exposure to a

situational trigger).

1

Although panic attacks are the hallmark symptom of panic disorder, their

occurrence can also be associated with depressive and other anxiety disorders.

1 For

example, situationally predisposed panic attacks may occur in either panic or phobic

disorders. Nocturnal panic attacks, which awaken a person from sleep, are almost

always indicative of panic disorder. Because panic attacks occur unpredictably, they

often lead to generalized anxiety or constant fear of sudden attacks.

Epidemiology and Clinical Course

Although the estimated lifetime prevalence of panic disorder is 6.8%, approximately

10% of persons experience recurrent panic attacks that do not fulfill the diagnostic

criteria for panic disorder and nearly 30% experience a single isolated panic attack

at some point in their lives.

14 The onset of panic disorder often occurs during

stressful periods, usually in the late teens to mid-30s, with rare first onset in the

elderly population.

8,77 Women are affected two to three times more often than men.

77

Panic disorder, like other anxiety disorders, is accompanied by marked degrees of

psychiatric comorbidity. Common comorbidities include other anxiety disorders,

affective disorders, personality disorders, and alcohol/substance use disorders with

the majority of patients suffering a major depressive episode at some point.

1,14,104,105

Patients with psychiatric and medical comorbidities have more severe symptoms,

respond more slowly to treatment, have a lower chance of reaching remission, and

have a greater suicide risk (particularly when depression or substance abuse are

present) than those with panic disorder alone.

106 Although most patients experience

episodic periods of remission and relapse, nearly one in five suffer almost

continuously.

107

Table 83-9

Symptoms of Panic Disorder

1

Palpitations, pounding heart, or increased heart rate

Sweating

Trembling or shaking

Sensations of shortness of breath or smothering

Feeling of choking

Chest pain or discomfort

Nausea or abdominal distress

Feeling dizzy, unsteady, lightheaded, or faint

Derealization or depersonalization

Fear of losing control or going crazy

Fear of dying

Paresthesias

Chills or hot flushes

Panic disorder is associated with very high rates of healthcare service

utilization.

106 The vast majority of patients with panic disorder do not complain of

feeling anxious and report only physical symptoms, such as chest pain, GI problems,

headache, dizziness, and shortness of breath, which contributes to misdiagnosis.

108

The poor recognition of panic disorder in primary-care settings further increases use

of medical services. Panic disorder is the underlying cause of symptoms in an

estimated 10% to 30% of patients referred to specialty vestibular, respiratory, or

neurology clinics, and up to 60% of those referred for cardiology consultation.

1

It is

not uncommon for patients to have been in the healthcare system for up to 10 years

before they are correctly diagnosed.

Etiology and Pathophysiology

A neurobiologic model for panic disorder has been proposed in which the amygdala

is the central hub of the fear circuit.

5,109 Various projections from the amygdala,

including the hypothalamus and the locus coeruleus, trigger autonomic and

neuroendocrine responses resulting in anxiety and panic attacks. Patients with panic

disorder have a heightened anxiety sensitivity (fear of anxiety-related sensations),

and a variety of substances and situations may activate the anxiety and panic

response.

109 Acute panic attacks are believed to be caused by dysregulated firing in

the LC as described previously (see Neurobiology of Anxiety section), and

hyperresponsiveness of the NE system may be an underlying cause for panic

disorder.

110

Other neurobiologic research suggests patients with panic disorder have abnormal

patterns of cerebral glucose metabolism in certain brain areas; abnormalities in

GABA-A receptor, NE, 5-HT, and CCK functioning; decreased GABA-A

benzodiazepine binding sites; abnormal regulation of neuroactive steroids that

modulate GABA-A receptors; hyperactivation of the HPA axis; CCK-B receptor

gene polymorphism; and are hypersensitive to carbon dioxide. These findings seem

to predispose patients to panic attacks and require further study.

105,109–111

Genetic and environmental influences both contribute to a familial pattern where

people are 8 to 21 times more likely to develop panic disorder if they have a firstdegree relative with the disorder.

1,17 The vulnerability is believed to involve

heightened anxiety sensitivity whereby harmless normal physical sensations are

misinterpreted as being dangerous and cause fear.

112 Several studies have shown

distressing childhood events (e.g., separation from parents and abuse) and behavioral

inhibition during childhood (e.g., excessive fear and avoidance of novel stimuli) are

associated with markedly increased risks of developing panic disorder later in

life.

109 No single biologic abnormality can explain panic disorder, and further

research is needed to define the complex interplay of the various pathophysiological,

genetic, and environmental findings in this illness.

Treatment of Panic Disorder

Approximately 70% to 90% of patients with panic disorder can experience

substantial relief with currently available treatments, which include both

pharmacologic therapies and CBT.

1,105 Medications and CBT both are beneficial for

reducing panic attacks initially, and their effects on phobic avoidance generally occur

later. First-line medication treatments for panic disorder are SSRIs and venlafaxine

as TCAs are less tolerable and possess more safety and drug–drug interaction

concerns.

20,25,112,113 Benzodiazepines also are effective but no longer recommended as

first-line treatment given their abuse liability, cognitive and psychomotor

impairments, and lack of efficacy at treating common comorbidities. The

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heightened anxiety sensitivity common in panic disorder makes patients especially

vulnerable to initial SSRI and TCA side effects, such as anxiety and agitation. For

this reason, lower-than-usual starting doses of antidepressants are recommended in

patients with panic disorder.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS

Paroxetine, sertraline, fluoxetine, and venlafaxine are FDA-approved for treating

panic disorder although other SSRIs (fluvoxamine, citalopram, escitalopram) are

also effective in reducing the frequency of panic attacks, anticipatory anxiety, and

associated depression.

20,25,113 Although low starting dosages are recommended (10

mg/day for paroxetine and citalopram, 25 mg/day for sertraline, 5–10 mg/day for

fluoxetine and escitalopram) to minimize side effects, higher doses relative to

antidepressant doses are usually required for response. The recommended target

dosage range is 20 to 40 mg/day for paroxetine, citalopram, and fluoxetine, 100 to

200 mg/day for sertraline and fluvoxamine, and 10 to 20 mg/day for escitalopram for

panic disorder.

112 The initial dose of venlafaxine XR should be 37.5 mg/day with a

recommended therapeutic dose of 150 to 225 mg/day.

112

Response to SSRIs and other antidepressants in panic disorder occurs gradually,

over the course of several weeks. Reduced frequency of panic attacks usually begins

within 1 to 2 weeks. A trial period of at least 6 weeks should be allowed to fully

assess response, and continued improvements may be seen during a treatment period

of 6 months or longer.

112

BENZODIAZEPINES

The benzodiazepines alprazolam and clonazepam are FDA-approved for treating

panic disorder and are the most extensively studied agents of this class although

lorazepam and diazepam, when used in equivalent doses, also appear effective.

108,112

Optimal benzodiazepine dosing is an important issue in treating patients with panic

disorder because these individuals may need higher doses for response than patients

with other anxiety disorders.

114 This may be related to reduced sensitivity of

benzodiazepine binding sites in panic disorder.

115 An alprazolam dosage range of 4

to 6 mg/day is effective for most panic disorder patients, but others may require up to

10 mg/day for optimal response. The total daily dose usually needs to be taken in

three or four divided doses to minimize breakthrough anxiety or panic attacks before

the next scheduled dose because of fluctuating serum levels given its relatively short

duration of action. The extended-release alprazolam formulation (alprazolam XR)

was developed to address this problem.

56

It may have a lower abuse liability than

immediate-release alprazolam, but this remains unproven. Patients with panic

disorder are especially sensitive to benzodiazepine withdrawal effects. For these

reasons, using the longer-acting benzodiazepine clonazepam (1–2 mg/day dosed

twice daily) may be preferred over alprazolam.

114

TRICYCLIC ANTIDEPRESSANTS, MONOAMINE OXIDASE INHIBITORS,

AND OTHER ANTIDEPRESSANTS

TCAs were the first medications widely used in the treatment of panic disorder.

Imipramine (100–300 mg/day) and clomipramine (50–150 mg/day) are as effective

as alprazolam, but are less well tolerated.

116 Evidence for most other TCAs is

lacking.

20,25,112,113 Clomipramine appears to be more effective than other TCAs for

panic disorder, perhaps because of its greater serotonergic effects.

117 Despite using

lower initial doses to minimize anxiety-like side effect, many patients discontinue

therapy because of poor tolerability.

Among the MAOIs, phenelzine is often heralded as being remarkably effective in

the treatment of panic disorder, but this claim is based on studies conducted before

the publication of the initial diagnostic criteria for panic disorder in 1980.

112 No

recent MAOI studies are available to assess phenelzine’s efficacy within the context

of current diagnostic and treatment standards. It is generally an option of last resort

for treatment-refractory cases because of the many clinical disadvantages of MAOIs

relative to other antidepressants (see Chapter 86, Depression).

Preliminary reports suggest mirtazapine may also be beneficial in treating panic

disorder.

20,112 This agent may be useful in patients who do not respond to SSRI

therapy.

112

MISCELLANEOUS AGENTS

Other medications that are reportedly effective in treating panic disorder include

anticonvulsants (valproic acid and levetiracetam) and antipsychotics (primarily

risperidone and olanzapine) as either monotherapy or adjunctive therapy used in

combination with an SSRI.

20,112 More information is needed before any of these can

be routinely recommended for treating panic disorder.

NONPHARMACOLOGIC TREATMENTS

CBT, including exposure treatment and relaxation training, is also established as

being effective in panic disorder.

105,112 The cognitive theory of panic disorder is

based on the observed heightened anxiety sensitivity in these patients and asserts that

physical anxiety sensations are misinterpreted as being serious or life-threatening.

These fears trigger a cycle of further worsening anxiety symptoms that finally

progress to a panic attack. Reversing the cognitive component of this vicious cycle is

an integral part of CBT and is important in producing lasting therapeutic effects of

treatment.

112 Breathing retraining and exposure to fear cues are key components of

behavioral therapy.

Some studies have found medications to be superior to CBT in the treatment of

panic disorder, whereas others report opposite results.

112,118 Combining medication

with CBT can be useful to increase response/remission rates in those with severe

symptoms or a partial response as well as to improve relapse rates during

pharmacotherapy discontinuation attempts.

20,114,119

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Clinical Presentation and Differential Diagnosis of

Panic Disorder

CASE 83-7

QUESTION 1: S.K., a 24-year-old female graphic artist, presents to the ED complaining of chest pain,

difficulty breathing, dizziness, and nausea. She describes feeling “as if my head is going off in space and I am

outside my body.” These attacks often escalate quickly peaking within 10 minutes and then start to subside

within 30 minutes. She states she has been under extreme stress lately because of the poor economy and has

conflicts with her landlord as a result of nonpayment of the rent on her art studio. S.K. fears she has had a

heart attack or stroke brought on by her stressful life. S.K. recently visited her family physician for the same

symptoms; however, a complete physical examination and laboratory workup yielded no abnormalities. She

states her first “attack” occurred out of the blue about 5 months ago while she was shopping for oil paints at the

art supply store, and she can never predict when they will occur. Since then, her symptoms have become more

severe and frequent, and she has started isolating herself in her studio for fear they will return when she is in

public. S.K. uses marijuana “to relax” and occasionally drinks alcohol (but only rarely). She has suffered from

depression in the past and was hospitalized for one severe episode 2 years ago. An ECG is performed and

found to be normal. The physician’s diagnosis is panic disorder with agoraphobia. What clinical features of

panic disorder does S.K. display, and what are the important factors in the differential diagnosis of panic

disorder?

S.K. exhibits many typical characteristics of panic disorder. As illustrated in this

case, the first panic attack typically occurs without warning while the person is

involved in a normal everyday activity and lasts 10 to 30 minutes. Panic attacks are

extremely terrifying and usually leave the sufferer feeling anxious and convinced

something is medically wrong. As with S.K., it is not uncommon for persons to make

ED visits after or during panic attacks, believing they have had a heart attack or other

serious event. Unfortunately, panic disorder is often not recognized in primary-care

settings, and no medical cause for the symptoms can be identified. Faced with

findings that they are apparently healthy, persons may make repeated ED visits and

consult different doctors and specialists in an attempt to uncover a physical

explanation for their frightening symptoms.

S.K. exhibits the following target symptoms of panic disorder: chest pain,

shortness of breath, dizziness, abdominal distress, and loss of control. Agoraphobia

is present because she avoids leaving her studio because of her fear of having panic

attacks. Other factors consistent with a diagnosis of panic disorder include her young

age, female sex, and lack of abnormal physical findings. This case also illustrates the

association between onset of panic disorder and stressful life events, its common

association with depression, and the frequent lack of recognition of panic disorder in

primary-care settings.

Because different substances or medical conditions can cause severe anxiety and

panic, it is necessary to rule out these potential causes for panic attacks.

108 Notable

triggers of panic attacks include caffeine, alcohol, nicotine, nonprescription cold

preparations, cannabis, amphetamines, and cocaine (Table 83-2).

108 S.K. uses

marijuana, which can be associated with panic symptoms. Although chronic

moderate-to-severe use of marijuana may complicate the treatment of panic disorder,

it appears infrequent marijuana use does not adversely affect treatment.

120,121 S.K.

does not endorse chronic, severe marijuana abuse, but if she does not adequately

respond to treatment, this might be further explored. Medical illnesses that can cause

panic attacks include thyroid dysfunction, asthma, COPD, mitral valve prolapse, and

seizure disorders.

122 Panic attacks can also occur with other anxiety disorders.

However, in these cases, the panic attacks usually occur on exposure to a feared

object or situation (in phobic disorders), an object of obsession (in OCD), or a

stimulus associated with a traumatic stressor (in PTSD). S.K. reports her panic

attacks occur unexpectedly, and situationally bound or predisposed attacks are not

evident; therefore, the features are consistent with panic disorder.

Treatment Selection for Panic Disorder, Selective

Serotonin Reuptake Inhibitor Dosing Issues, and

Combination Selective Serotonin Reuptake Inhibitor–

Benzodiazepine Therapy

CASE 83-7, QUESTION 2: S.K. is referred to a psychiatrist who decides to initiate treatment with

paroxetine 20 mg every morning. Three days later, S.K. calls the doctor complaining that her anxiety and panic

attacks have greatly increased since she started taking paroxetine. The psychiatrist prescribes alprazolam 0.5

mg (tablets) and instructs S.K. to take one tablet as needed for the anxiety. What factors should be considered

in the selection of an initial medication treatment for panic disorder? Why is the prescribed treatment for S.K.

inappropriate?

An SSRI is an appropriate first-line treatment for most panic disorder patients.

20

In

patients such as S.K. who have a history of depression, SSRIs may also help prevent

relapse of depression. Patients with severe or distressing symptoms may initially

require concurrent benzodiazepine therapy, which provides quick relief from anxiety

and panic attacks until the therapeutic effects of SSRIs are evident. At that time,

usually after several weeks, the benzodiazepine can be gradually discontinued. An

SSRI–benzodiazepine combination is still the most commonly prescribed initial

treatment, even though guidelines recommend monotherapy unless initial anxiety is

extremely high.

123 Although benzodiazepines are generally avoided in patients with a

history of substance abuse, use of low doses for a limited time may be appropriate

for some patients with disabling symptoms, as long as there is no current substance

(especially alcohol) abuse.

20,69,112 Because of the levels of distress and impairment

caused by S.K.’s panic disorder, combined SSRI–benzodiazepine therapy would

have been the preferred initial treatment. Because panic attacks peak quickly and

generally last less than 30 minutes, an as-needed benzodiazepine is not helpful to

prevent panic attacks. As such, scheduled benzodiazepine dosing is preferred over

as-needed dosing schedule during initial therapy.

112

In choosing among SSRIs for the treatment of panic disorder, paroxetine or

sertraline may be less anxiety provoking in some patients than a more activating SSRI

such as fluoxetine.

26 When paroxetine is used, a very low initial dose of 10 mg/day

should be used. In S.K.’s case, the prescribed 20-mg/day starting dose was too high.

Also, scheduled versus as-needed benzodiazepine dosing would have been

preferred. After 2 to 4 weeks, the benzodiazepine can be gradually discontinued

while the SSRI therapy is continued and gradually titrated to the target effective dose.

The potential for drug interactions must also be kept in mind when SSRI–

benzodiazepine combinations are used because certain SSRIs can inhibit

benzodiazepine metabolism, leading to increased benzodiazepine side effects (see

Benzodiazepine Drug Interactions section).

Patient Counseling Information

Patients such as S.K. who are beginning SSRI therapy for the treatment of panic

disorder should be counseled about possible increased anxiety during the first 1 or 2

weeks of treatment, as well as other common SSRI side effects, including nausea,

headache, sexual dysfunction, and either insomnia or sedation. Because these are

dose-related effects, patients should inform their clinician of any problems, and a

dosage reduction may be indicated. These adverse effects (with the possible

exception of sexual dysfunction) usually subside after 1 to 3 weeks of continued

treatment. It is also important to inform patients it may take several weeks before

beneficial effects of antidepressant treatment are seen, and 6 to 12 weeks or longer

may be required for full response. Patients receiving benzodiazepines should be

counseled about their use in providing anxiolytic coverage during the initial weeks of

SSRI therapy, as well as their limited utility as long-term therapy. Other pertinent

counseling information for benzodiazepine treatment should also be included (see

Case 83-2, Question 4). The desired goals of therapy and likely duration of treatment

should also be explained. Providing information about the nature of panic disorder,

including reassurance that panic attacks are not life-threatening, is also important.

Many clinicians recommend patients keep a “panic diary” in which they record

frequency of panic attacks, along with symptoms experienced during attacks.

Clinical Assessment and Goals of Therapy

CASE 83-7, QUESTION 3: S.K. refuses to continue paroxetine, so escitalopram is prescribed instead. After

1 week of escitalopram therapy at the initial dosage of 5 mg/day, S.K. is tolerating the

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medication well. The plan is to gradually increase escitalopram to 10 mg, then to 20 mg/day during the next

several weeks. S.K. is also taking alprazolam, 0.5 mg BID to TID. What are the desired goals of treatment in

this case, and how can S.K.’s response to treatment be assessed?

Five domains in panic disorder have been identified in which treatment outcomes

should be assessed: (a) frequency and severity of panic attacks, (b) anticipatory

anxiety, (c) phobic avoidance behaviors, (d) overall well-being, and (e) illnessrelated disability in various areas (work, school, family).

112 The treatment goals in

this case are first to stop S.K.’s panic attacks, then to reduce her anticipatory anxiety,

followed by reversal of phobic avoidance.

54 These outcomes should allow her to

more comfortably leave her studio when required and, secondarily, improve her

overall functioning and quality of life.

Several different instruments have been used to assess outcomes of treatment in

panic disorder.

54

In addition to the panic diary, others include the Fear Questionnaire,

the Panic Appraisal Inventory, and the Panic Disorder Severity Scale. The latter is

currently considered by many experts to be the most useful because it evaluates

outcomes in all five identified target domains of panic disorder.

54,112

Course and Duration of Therapy

CASE 83-7, QUESTION 4: After 3 months of escitalopram therapy, S.K. reports she has had no panic

attacks in the past month and her functioning has improved dramatically. She is currently taking 20 mg/day of

escitalopram and gradually stopped taking the alprazolam 3 to 4 weeks ago. S.K. reveals she is painting

regularly, selling some of her paintings, paying her rent, and she has begun dating again. S.K. is experiencing no

significant side effects from escitalopram except for some decrease in her sexual drive. She wonders how long

she should continue taking it since she is doing so well. What is the recommended duration of treatment for

panic disorder?

Long-term medication trials in panic disorder support the recommendation that

treatment should continue for at least 6 to 12 months after acute response.

20,112 The

benefits of maintenance pharmacotherapy in preventing relapse are well documented

although the optimal duration of treatment is a subject of continued debate among

panic researchers. Maintenance treatment gives patients time to resume normal

lifestyles and to re-establish daily activities after acute cessation of panic attacks.

In this case, S.K.’s current escitalopram dosage of 20 mg/day is appropriate

because this is within the effective dosage range for panic disorder. Escitalopram

therapy should be continued at the current dosage for 3 to 6 more months. S.K.’s

sexual dysfunction is not likely to decrease with continued treatment; therefore,

specific remedies for SSRI-induced sexual dysfunction may be tried (see Chapter 86,

Depression). After a successful period of full remission, a trial of medication

discontinuation may be attempted to determine whether continued treatment is

necessary. Medication should not be stopped in patients who are experiencing

stressful life events or substantial residual problems in any of the five domains

(frequency and severity of panic attacks, anticipatory anxiety, phobic avoidance

behaviors, overall well-being, and illness-related disability in work, school, and

family).

112 When a medication is discontinued, it should be withdrawn gradually over

several months, regardless of the class. Because of the devastating impact panic

disorder can have, reinstitution of drug treatment is indicated if relapse occurs. Long-

term treatment with antidepressants, and benzodiazepines if necessary, is generally

successful in maintaining treatment benefits without detrimental effects or dosage

escalations.

SOCIAL ANXIETY DISORDER AND SPECIFIC

PHOBIAS

Classification and Diagnosis of Phobic Disorders

The DSM-5 includes two primary types of phobic disorders: specific phobia and

social anxiety disorder (formerly social phobia) with symptoms presented in Table

83-10.

1 These disorders involve excessive or unreasonable fears and lead to

avoidance behavior to minimize anxiety for a duration of at least 6 months. The main

difference between specific phobias and social anxiety disorder is that the former

involves fear and avoidance of specific stimuli and not a general fear of social

situations.

SOCIAL ANXIETY DISORDER

Social anxiety disorder manifests as intense irrational fear, anxiety, or avoidance of

scrutiny or evaluation by others in social situations because of concerns about

humiliation or being made to appear ridiculous.

1 A defining feature is that the fears

and anxiety are confined to social situations (e.g., speaking to people, attending

social gatherings, eating or drinking in public, using public restrooms, public

speaking), and patients are usually symptom-free when alone. If the fear is strictly

confined to speaking or performing in public, a performance-only specifier is applied

to the diagnosis. Common symptoms seen in social anxiety disorder include blushing,

muscle twitching, and stuttering, in addition to other typical symptoms of anxiety.

Panic attacks may also occur in either specific phobia or social anxiety disorder on

exposure to the feared object or situation. However, social anxiety disorder is

differentiated from panic disorder in that it involves the fear of scrutiny by others,

rather than the fear of having a panic attack.

SPECIFIC PHOBIAS

Specific phobias are coded by one of five specifiers: animal (e.g., insects, dogs,

spiders), natural environment (e.g., heights, water, storms), blood–injection–injury

(e.g., blood, injury, medical procedures), situational (e.g., flying, bridges, elevators),

or other.

1 Significant impairment of functioning or marked distress must be present

for a diagnosis of specific phobia to be warranted. For example, fear of flying might

constitute a diagnosis of specific phobia in a person whose job requires airplane

travel, but it would not impair functioning in someone who never has occasion to fly.

First-line management of specific phobias involves avoidance of the stimuli or

1.

2.

3.

4.

5.

exposure-based psychotherapy, such as CBT or virtual reality exposure. Medications

are not generally considered beneficial, as pharmacotherapy for specific phobia is

largely understudied and psychotherapy is extremely successful. Benzodiazepines

effectively reduce anxiety associated with a phobic trigger, but they may also

interfere with the efficacy of these exposure therapies.

20,25,113

Table 83-10

Symptoms of Social Anxiety Disorder (Social Phobia) (Items 1–5) and Specific

Phobia (Items 2–5)

1

Marked and constant fear of one or more socialsituations in which the person is exposed to unfamiliar people

or possible scrutiny by others and the person fears humiliation or embarrassment

Experiencing the situation causes an immediate anxiety response

Feared situation is avoided or experienced with intense anxiety or distress

Feared situation exceeds the true risk associated with the socialsituation according to sociocultural norms

Fear or avoidance significantly interferes with the person’s normal routine or activities or causes marked

distress

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