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10 Psychiatric Disorders

Psychiatric Disorders

Chapter 2Anxiety DisordersR. P. Swinson, MD, FRCPsych, FRCPC

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) contains severalsignificant changes to the classification of anxiety disorder:1■ Panic disorder and agoraphobia are no longer linked in a single diagnosis. Each has separate criteria

and patients with both disorders are now coded with 2 diagnoses.■ Obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are reclassified as

separate disorders—obsessive-compulsive and related disorders, and trauma- and stressor-relateddisorders, respectively. Management of OCD and PTSD are discussed in separate chapters (seeChapter 9 and Chapter 10).

■ Two disorders, separation anxiety disorder and selective mutism, have been added to anxietydisorders. Both disorders were previously classified in “disorders usually first diagnosed in infancy,childhood, or adolescence”.

Goals of Therapy■ Eliminate or decrease symptomatic anxiety■ Eliminate or decrease anxiety-based disability■ Prevent recurrence■ Treat comorbid conditions

Investigations■ Thorough history with attention to:

– nature and onset of symptoms– nature and extent of disability– presence of comorbid medical or psychiatric conditions

Note: Treat comorbid mood disorders, especially depression, as the primary condition.■ Interview questions assist in obtaining an accurate diagnosis (Table 1, Table 2)■ Physical examination to exclude endocrine or cardiac disorders and to look for signs of substance use■ Laboratory tests:

– CBC, liver function tests, gamma-glutamyl transpeptidase (GGT to screen for alcohol use),thyroid indices (supersensitive TSH), ECG

Note: Treat physical disorders of recent onset before making a definitive diagnosis of an anxietydisorder.

Therapeutic ChoicesRelatively mild anxiety states in response to life circumstances are frequently time-limited; manypatients will respond to anxiety management strategies without medication. Support, problem-solvingand relaxation techniques or mindfulness may be helpful as the environmental crisis resolves.

Copyright © 2014 Canadian Pharmacists Association. All rights reserved. Compendium of Therapeutic Choices



Chapter 2: Anxiety Disorders 11However, specific anxiety or mood disorders may develop as a consequence of the original stressor.See Figure 1 for an illustration of the management of anxiety disorders.

Table 1: Classification of Anxiety Disorders1

Type of Anxiety Disorder Clinical Features

Separation anxiety disorder Childhood onset of fear of separation from attachment figures (parents, siblings) that isexcessive for the developmental stage.

Selective mutism Childhood onset of failure to speak in school or other social situations when the individualdoes speak in other settings. May impede academic progression.

Specific phobia Severe anxiety triggered by a specific feared object or situation (e.g., spiders, flying, heights)often leading to avoidance behaviour.

Social anxiety disorder (socialphobia)

Intense anxiety provoked by social or performance situations in which embarrassment mightoccur; often leads to avoidance behaviour.

Panic disorder Recurrent unexpected abrupt panic attacks with persistent anxiety concerning recurrence.

Agoraphobia Marked fear or anxiety of 2 or more situations: public transportation, open spaces, closedspaces, crowds, being outside of home alone. Leads to avoidance of these situations.

Generalized anxiety disorder Excessive worry and anxiety about a number of events or activities on more days than notover a period of ≥6 months.

Anxiety disorder due to anothermedical condition

Anxiety or panic attacks directly caused by a medical condition (e.g., thyroid dysfunction,hypoglycemia, heart failure, arrhythmia, COPD, vitamin B12 deficiency, encephalitis).

Substance/medication-inducedanxiety disorder

Anxiety or panic attacks directly caused by use or discontinuation of a substance (e.g.,alcohol, amphetamines, anticholinergics, caffeine, cannabis, cocaine, corticosteroids,hallucinogens), capable of producing the symptoms of anxiety.

Other specified anxiety disorder Symptoms of anxiety disorders not meeting full diagnostic criteria, e.g., limited-symptom panicattacks, generalized anxiety not occurring on more days than not.

Unspecified anxiety disorder Distressing anxiety symptoms that fail to meet diagnostic criteria for specific anxiety disorders.

Table 2: Interview Questions to Establish Specific Anxiety DiagnosisaQuestions Further Inquiry

Do you have sudden episodes of intense anxiety? Establish nature of attack.

Do you have difficulty going to places to which you used to be ableto go?

Inquire about crowded places, line-ups, movies, highways,distance from home.

Do you have difficulty talking to people in authority or speaking inpublic?

Establish situations (one-on-one or groups).

Are you afraid of blood, small animals or heights? Establish precise feared situation.

Do you have thoughts that keep going in your mind that you can'tstop?

Ask nature of thoughts (illness, harm, sex).

Do you worry a lot of the time? Ask about worries related to health, family, job and finances.a The order of asking the questions can be varied. The order represented in Table 2 reflects the sequence in the Diagnostic and statistical manual of mentaldisorders: DSM-51 in which panic attacks are diagnosed first, followed by phobic disorders, and generalized anxiety disorder. Anxiety disorders that donot fit into the above categories are atypical. Accurate diagnosis is recommended before instituting treatment.

Compendium of Therapeutic Choices Copyright © 2014 Canadian Pharmacists Association. All rights reserved.

Chapter 2: Anxiety Disorders



Nonpharmacologic Choices■ Specific cognitive behavioural therapy (CBT) tailored to the primary diagnosis may be required.

An online resource at McMaster University (www.pter.mcmaster.ca) provides more informationabout CBT.

■ Caffeine or other stimulant use should be reduced and controlled.■ Alcohol use should be minimal; it should not be used to control anxiety.■ Recommend aerobic exercise several times per week. Exercise has been found to reduce some

symptoms of panic and agoraphobia but CBT is significantly more effective.2■ Educate patient about regular sleep habits and sleep hygiene.■ Stress reduction, including relaxation training and time management, is often helpful initially.

Mindfulness meditation is increasingly used in anxiety disorders with good effect.

Figure 1: Management of Anxiety Disorders

Abbreviations: CBT = cognitive behavioural therapy; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor




Chapter 2: Anxiety Disorders 13Pharmacologic ChoicesThe role of drug therapies varies among anxiety disorders. Drug treatment is rarely required for specificphobias. In the other anxiety disorders, drug therapy is the most common intervention, especiallywhen intensity of symptoms and disability are moderate to severe. A psychiatric consultation isrecommended for any patient who does not improve with a trial of 2 separate antidepressants. A list ofdrug choices is provided in Table 3.

Available information on the treatment of panic disorder, agoraphobia and panic disorder withagoraphobia (PDA) is based on studies that did not separate patients into groups with either panicdisorder or agoraphobia.3 Although DSM-5 makes the distinction between the 2 separate conditionsor PDA, studies are needed to determine whether available pharmacologic agents differentially treateach condition.

Panic DisorderAntidepressants

The SSRIs citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are alleffective in reducing panic attacks. Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI),has also demonstrated efficacy. SSRIs and SNRIs are first-choice agents in treating panic disorder withor without agoraphobia.4,5 There is usually a delay in response to these agents that may be accompaniedby initial agitation. Augmenting the SSRI or SNRI with a brief course of a low-dose benzodiazepine(no longer than 8 weeks, to minimize risk of dependence/withdrawal) can increase adherence tomedication and produce a more rapid response than with antidepressants alone.6

The tricyclic antidepressants (TCAs) imipramine, desipramine and clomipramine have beenshown to reduce the frequency and severity of panic attacks7 and are inexpensive. The different sideeffect profiles of TCAs and SSRIs can be used to guide treatment choice. Mirtazapine has beeneffective in open-label trials.8,9 The older monoamine oxidase inhibitors (MAOIs) phenelzine andtranylcypromine are also effective but more difficult to use because of the dietary restrictions andpotential for serious drug interactions.10

The dosage requirements and length of treatment for antidepressants in panic disorder are similar tothose for major depression (see Chapter 6). However, the initial dose should be as low as possible(e.g., 10 mg daily for TCAs or fluoxetine), and then increased as tolerated to the usual antidepressantdose range; higher starting doses may cause patients to become agitated and discontinue treatmentabruptly. Determining the duration of drug treatment is of great importance; medication is usuallyrequired for months or years. Evidence has shown that a majority of patients will suffer relapse afterbenzodiazepines or antidepressants are discontinued.11

Taper doses gradually if antidepressants must be discontinued or dose-reduced. Abrupt dosage changesmay cause the patient to experience antidepressant discontinuation syndrome. More information aboutthis syndrome is included in the Depression chapter (see Chapter 6).

Benzodiazepines

Pharmacologic treatment is guided by the acuity of panic disorder at presentation. Low doses ofhigh-potency benzodiazepines can be used to abort initial panic attacks and may control high-frequencyattacks later in the development of the disorder. Clonazepam 0.25–0.5 mg BID frequently makes panicattacks more manageable. Lorazepam and diazepam can also be used.

Although there is considerable evidence for the efficacy of benzodiazepines as monotherapy for panicdisorder, they are best reserved for those cases where SSRI/SNRI treatment has not been successful orif the antidepressant response needs augmentation.

Short-term use of benzodiazepines is best. For patients who have been maintained on stable low dosesfor years, the potential benefits of discontinuing benzodiazepines (e.g., decreased risk of sedation/falls





or dependence/withdrawal) should be weighed against the potential increase in frequency or severity ofpanic attacks when benzodiazepines are stopped.11

Agoraphobia and Panic Disorder with AgoraphobiaThe pharmacologic treatment of agoraphobia with or without panic disorder is the same as for panicdisorder. Much of the disability in agoraphobia arises from avoidance behaviour rather than the panicattacks. The degree of avoidance is frequently under-reported by patients; careful questioning orstandardized questionnaires may be needed for a complete assessment. The avoidance can be addressedwith CBT, even if medication reduces or eliminates accompanying panic attacks. CBT is effectivealone or combined with medication.11,12 Access to specialized CBT is often limited by financial factors.

Social Anxiety Disorder (Social Phobia)This excessive fear of being criticized or negatively evaluated by others presents as shyness, avoidanceof social contact or difficulty dealing with authority figures. The disorder may be present fromchildhood and often becomes noticeable in adolescence. It is particularly important to rule outcomorbid major depression and alcohol use. CBT or other psychotherapy may be necessary to dealwith significant social anxiety, even when medication is used.

SSRI and SNRI antidepressants are the mainstay of medical treatment for social anxiety disorder.These agents are effective for generalized social anxiety and for milder cases manifesting as stagefright or fear of public speaking. Escitalopram,13,14 fluvoxamine,15,16 paroxetine,17,18 sertraline19,20and venlafaxine21 have demonstrated efficacy. Simple stage fright or fear of public speaking mayrespond to low-dose propranolol (10 mg) taken 30 minutes before the event; in generalized socialanxiety disorder propranolol is usually ineffective.22,23

Results for moclobemide vary but it may be effective, particularly in higher doses.24 When used atdoses above 600 mg/day, moclobemide loses its isoenzyme specificity for MAO-A. Caution patientstaking higher doses about consumption of tyramine-rich foods such as aged cheeses, smoked meats,beer and red wine.

There is some evidence to support a trial of gabapentin25 or pregabalin26 in patients not responding tofirst-line measures. Benzodiazepines, particularly clonazepam,27 are effective but should be used withthe same restrictions (i.e., short-term use of lowest effective dose) as in other anxiety disorders.

Specific PhobiaMedication is not usually indicated for the treatment of specific fear of heights, animals, injectionsor other common triggers. As little as 6 hours of CBT is often successful in producing marked,enduring change.

Generalized Anxiety DisorderGeneralized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry related toeveryday-life concerns such as safety of family members, financial/job security and health. Patientswith GAD frequently exhibit depressed mood and other anxiety symptoms. CBT is the most effectivepsychosocial treatment but often requires 20 or more sessions to be successful.28

SSRIs and SNRIs are established as first-line drug treatment for generalized anxiety disorder.Numerous studies demonstrate the efficacy of duloxetine29, escitalopram,30,31 paroxetine,32 sertralineor venlafaxine.33 Pregabalin is now an established first-line treatment for GAD with the advantage ofproviding rapid onset of relief.34,35,36 While effective in GAD, imipramine is limited by its side effectprofile and safety concerns in overdose. It is usually reserved for use in patients for whom first-lineagents are not effective. Bupropion is also an option.37




Chapter 2: Anxiety Disorders 15Quetiapine is effective in GAD both as monotherapy and to augment antidepressant medication.38 At adose of 150 mg daily, it has been shown to rapidly reduce many symptoms of GAD. Quetiapine isgenerally regarded as a second-line choice due to its side-effect profile of weight gain and potentialeffects on metabolic regulation.

Low-dose benzodiazepines (e.g., bromazepam, clonazepam, diazepam, lorazepam) can be used forsymptom relief for several weeks at a time; caution is advised regarding the risk of dependence anddiscontinuation symptoms.

Buspirone is an azapirone with a low potential for abuse and less sedation compared tobenzodiazepines. Like antidepressants, it has a relatively slow onset of effect. When switchingfrom long-term benzodiazepine therapy to buspirone, it is important that the benzodiazepine is notdiscontinued abruptly; there is no cross-tolerance between the 2 drug classes and benzodiazepinewithdrawal symptoms could be precipitated.

Choices during Pregnancy and BreastfeedingAnxiety Disorders and PregnancyAnxiety disorders have onset early in life, are frequently chronic in nature and their severity waxesand wanes in response to environmental events. Pregnancy may be accompanied by increased ordecreased anxiety.

It is important to screen for the presence of anxiety symptoms prior to conception if possible. Screeningcan be repeated during the pregnancy and in particular postpartum. If a woman is suffering frommarked anxiety related to pregnancy and breastfeeding, it is imperative to screen for the presenceof mood symptoms and suicidality.

In any circumstances where a woman experiences severe anxiety or mood disorder symptoms duringpregnancy or postpartum, referral to a psychiatrist may be necessary. In major centres, women's mentalhealth programs are usually available and are attuned to responding to consultation requests quickly.

Preconceptional treatment can be offered for anxiety disorders that are producing significant distress orinterfering with functioning. Panic disorder with agoraphobia may prevent a woman from attendingmedical appointments.

Management during PregnancyThere is good evidence that psychological treatments can have beneficial effects for more than half ofthose who persist with a treatment program. CBT can be administered without restriction throughoutpregnancy. Therapies based in meditative or relaxation techniques may be more acceptable thanpharmacologic approaches.39

If anxiety symptoms are severe and produce significant impairment, medications can be appropriateand effective.40 The 2 main classes of medications used for anxiety disorders are SSRI or SNRIantidepressants and benzodiazepines.

SSRIs or SNRIs may cause agitation, sweating, nausea, GI distress and weight gain. There havebeen reports of a slightly higher (but still low) risk of congenital abnormalities involving the heartor cleft lip/palate.41 When used in the third trimester, these drugs may be associated with neonatalwithdrawal symptoms such as tremors, increased muscle tone, feeding or digestive problems orrespiratory distress. Whether benzodiazepines confer an increased risk of congenital malformationsis controversial. Benzodiazepines administered shortly before delivery can result in floppy infantsyndrome or neonatal withdrawal symptoms.

The use of SSRIs, SNRIs or benzodiazepines may be warranted in patients with severe symptoms thatcould affect fetal or maternal safety or health. In general, the lowest effective dose should be used





for the shortest time necessary. General principles for management of depression during pregnancyare applicable to the management of anxiety disorders.42,43 See also Chapter 6 for information onmanagement of depression during pregnancy and breastfeeding.

Anxiety Disorders and BreastfeedingIn the postpartum period, severe anxiety can impede the mother's sleep and erode her confidence incaring for her child. If a woman refuses to be involved with caring for her child, an urgent psychiatricconsultation is needed and treatment considerations should include admitting the mother and childto hospital.

As in pregnancy, nonpharmacologic options should be used whenever possible in the postpartumperiod, particularly in breastfeeding women. If drug therapy is necessary, consider paroxetine orsertraline, since both have low concentrations in breast milk.44 When possible, avoid benzodiazepinesdue to potential accumulation, sedation and impaired temperature regulation in the infant.

A discussion of general principles on the use of medications in these special populations can befound in Appendix II and Appendix III. Other specialized reference sources are also provided inthese appendices.

Therapeutic Tips■ Short-term interventions such as psychological therapies, relaxation techniques and benzodiazepines

may be effective.■ Assess a drug's effectiveness after a trial of an adequate dosage taken for a sufficient length of time.■ If the first antidepressant at optimal dosage is not effective or not tolerated, switch to another

first-line antidepressant.■ If the second antidepressant is not effective, switch to an agent from a different drug class or

augment with an appropriate medication. See Figure 1.■ Restrict benzodiazepines to short-term use (i.e., 6–8 weeks) to assist with SSRI/SNRI-related

agitation.■ Limit the “as-needed” use of short-acting benzodiazepines as much as possible; ideally, such use

should not be continued for longer than 4 days.




Chapter 2: Anxiety Disorders 17

Table3:

Drugs

UsedfortheManagem

ento

fAnxiety

Disorders

Class

Drug

Type

ofAnxiety

Dose

Adverse

Effects

DrugInteractions

Com

ments

Costa

Antidepressants,

tricyclic

clom

ipramine

Anafranil,

generics

PD,A

G75–225

mg/daypo

CNSeffects

(agitationon

initiationof

therapy,confusion,

drow

siness,

headache),

anticholinergic

effects(drymouth,

blurredvision,

constipation,

etc.),

weightgain,nausea,

cardiovascular

effects(tachycardia,

arrhythm

ias,

orthostatic

hypotension),

anorgasm

ia,erectile

dysfunction.

May

increase

effect

ofanticholinergicdrugs,CNS

depressants,warfarin;donot

useMAOIsconcurrently.

May

take

2–3monthsfor

maximum

effect.

$-$$

desipram

ine

generics

PD,A

G,G

AD

75–300

mg/daypo

See

clom

ipramine.

See

clom

ipramine.

See

clom

ipramine.

$$-$$$$

imipramine

generics

PD,A

G,G

AD

75–300

mg/daypo

See

clom

ipramine.

See

clom

ipramine.

See

clom

ipramine.

$$-$$$$

Antipsychotics,

Second

-generation

quetiapine

Seroquel,

SeroquelX

R,

generics

GAD

Initial:5

0mgdaily

poTitrate

to150mg

daily

po,o

rhigherif

necessary.45

Usualmaximum

:400mgdaily

po

Sedation,dizziness,

weightgain,

orthostatic

hypotension,hepatic

aminotransferase

elevation,

headache,

anticholinergic

effects,increased

riskof

diabetes

anddyslipidem

ia,

movem

ent

disorders;may

lower

thyroidhormone

levels,m

odestQ

T cprolongation.

Additive

sedationwith

CNS

depressants;may

potentiate

antihypertensivedrug

effects;

inhibitors

ofCYP3A

4such

asclarithromycin,

erythrom

ycin,grapefruitjuice,

ketoconazoleor

prednisone

may

increase

quetiapine

levels;

inducersofCYP3A

4such

ascarbam

azepine,

phenytoin

orrifam

pinmay

decrease

quetiapine

levels.

Use

with

cautionwith

drugs

know

nto

prolongtheQT c

interval.

Usedas

augm

entation

therapywith

first-line

agentsinGAD,o

ras

monotherapy

afterfailure

offirst-line

therapies.

Advisepatientsabout

antipsychotic-associated

body

temperature

dysregulationand

preventionofheatstroke

(e.g.,hydration,

sun

protection).

$$

(cont'd)





Table3:

Drugs

Usedforthe

Managem

ento

fAnxiety

Disorders

(cont'd)

Class

Drug

Type

ofAnxiety

Dose

Adverse

Effects

DrugInteractions

Com

ments

Costa

Azapirones

buspirone

generics

GAD

Initial:5mgBID–TID

po Titrate

gradually

toeffectivedose.

Maximum

:60

mg/daypo

Nausea,headache,

dizziness,restless-

ness/insomnia.

Avoidusewith

MAOIs.

Onset

ofeffect

not

asrapidas

with

benzodiazepines.

$$$-$$$$$

Benzodiazepines

clonazepam

Rivotril,

generics

GAD,P

D,A

G0.25–0.5mgBID

poDrowsiness

(tolerance

develops

with

continuedtherapy),

dizziness,reduced

concentration,

retrograde

amnesia,

physical

dependence;rarely,

paradoxicalangeror

hostility.

Warnpatientsre:concom

itant

useof

alcohol,otherCNS

depressants(increasedeffect).

Discontinue

gradually

toavoidreboundanxiety;

avoidinpregnancy;

contraindicatedin

patientswith

know

nhistoryof

abuse;

dose

escalationis

rare

inpatientstaking

benzodiazepinesfor

chronicanxiety;

use

lower

dosesinelderly.

$

Beta 1-adrenergic

Antagon

ists

propranolol

generics

SAD(specific

task-related

anxiety)

10mgpo

30min

before

task

PRN

Hypotension.

Cautionre:increased

bradycardiawith

amiodarone.

Foroccasionalusein

situations

such

aspublic

speaking,p

erforming;

notusefulingeneralized

socialanxietydisorder.

$

GABADerivatives

gabapentin

Neurontin,

generics

SAD

See

Com

ments.

Initial:3

00mg/daypo

Usual:

900–1800

mg/daypo

in2divideddoses

Som

nolence,

dizziness,ataxia,

vision

changes.

Magnesium

-and

alum

inum

-containingantacids

may

decrease

theabsorption

ofgabapentin.

Not

afirst-line

agent;

may

beusefulinpatients

notresponding

tofirst-line

measures.

Not

anapproved

indication.

$-$$

pregabalin

Lyrica,

generics

GAD,S

AD

Initial:1

50mg/daypo

in2–3divideddoses

May

beincreasedto

150mgBID

poafter1

wkifnecessary

Dizziness,sedation,

peripheraledema.

Noknow

nsignificant

drug

interactions.

First-lineagentfor

GAD.

May

beusefulinpatients

notrespondingtoor

not

toleratingotherfirst-line

measures.

$$

Mon

oamine

Oxidase

Inhibitors

phenelzine

Nardil

PD,A

G45–90mg/daypo

Insomnia,dizziness,

orthostatic

hypotension,

edem

a,sexual

dysfunction.

Concurrentusewith

sympathom

imeticagents,

tyramineor

levodopa

may

resultinhypertensivecrisis;do

notuse

with

serotonergicdrugs

such

asSSRIs,S

NRIs,T

CAs,

meperidine,

tryptophandue

tohigh

riskforfatalserotonin

syndrome).

Stringentdietary

restrictions

are

necessary.

Avoid

tyramine-containing

foods.

$$-$$$




Chapter 2: Anxiety Disorders 19Class

Drug

Type

ofAnxiety

Dose

Adverse

Effects

DrugInteractions

Com

ments

Costa

tranylcypromine

Parnate

PD,A

G20–60mg/daypo

See

phenelzine.

See

phenelzine.

See

phenelzine.

$$-$$$

Reversible

Inhibitors

ofMon

oamine

Oxidase-A

moclobemide

Manerix,

generics

SAD

300–600mg/daypo

Nausea,insomnia.

Donotuse

with

meperidine,

TCAs,SSRIs.

Dietaryrestrictions

are

notrequiredat

usual

doses.

$

SelectiveSe

rotonin

ReuptakeInhibitors

citalopram

Celexa,

CTP

30,

generics

PD,A

G,S

AD

20–40mg/daypo

Upto60

mg/daypo

may

berequiredin

appropriatelyselected

patients.

Agitation(on

initiationof

therapy),n

ausea,

anorgasm

ia,

insomnia,diarrhea,

increasedrisk

ofGIbleeding;

dose-related

QT c

prolongation.

Serotoninsyndromewith

MAOIs(hypertension,tremor,

agitation,hypomania);caution

with

otherserotonergicdrugs

includingam

phetam

ine

derivatives,dextromethorphan,

dihydroergotam

ine,linezolid,

lithium

,meperidine,

pentazocine,

selegiline,

St.John'swort,trazodone,

triptans,tryptophan(increased

riskofserotoninsyndrome);

increasedriskofGIbleeding

with

NSAIDs,

antiplatelet

agents.

SSRIsaresubstratesand

inhibitorsofseveralcytochrom

eP450isoenzym

es.Thismay

resultinreducedclearanceof

manydrugs(e.g.,clozapine,

methadone,mexiletine,

phenytoin,

pimozide,

propafenone)

ordecreased

enzymaticconversion

ofa

prodrugto

itsactiveform

(e.g.,clopidogrel,codeine,

tamoxifen).

Avoidcombinedusewith

drugs

associated

with

prolonged

QT c

interval/torsades

depointes,such

asam

iodarone,

azithromycin,clarithrom

ycin,

domperidone,

erythrom

ycin,

haloperidol,methadone,

pimozide,

quinine,

sotalol,

ziprasidone.

May

take

2–3monthsfor

maximum

effect.

Discontinue

gradually.

$

(cont'd)





Table3:

Drugs

Usedforthe

Managem

ento

fAnxiety

Disorders

(cont'd)

Class

Drug

Type

ofAnxiety

Dose

Adverse

Effects

DrugInteractions

Com

ments

Costa

escitalopram

Cipralex,

CipralexMELTZ

PD,A

G,G

AD

10–20mg/daypo

See

citalopram

.See

citalopram

.See

citalopram

.$$$

fluoxetine

Prozac,

generics

PD,A

G,S

AD

20–80mg/daypo

Agitation(on

initiationof

therapy),n

ausea,

anorgasm

ia,

insomnia,

headache,reduced

appetite,

diarrhea,

increasedriskofGI

bleeding.

See

citalopram

.See

citalopram

.$-$$

fluvoxamine

Luvox,generics

PD,A

G,S

AD

150–300mg/daypo

Agitation(on

initiationof

therapy),n

ausea,

anorgasm

ia,

anticholinergic

effects,sedation,

increasedriskofGI

bleeding.

See

citalopram

.See

citalopram

.$-$$

paroxetine

immediate-

release

Paxil,generics

PD,A

G,S

AD

20–60mg/daypo

See

fluvoxamine.

See

citalopram

.See

citalopram

.$-$$

paroxetine

controlled-

release

PaxilCR

PD,A

G,S

AD

12.5–37.5mg/day

poSee

fluvoxamine.

See

citalopram

.See

citalopram

.$$$

sertraline

Zoloft,generics

PD,A

G,S

AD

50–200

mg/daypo

Agitation(on

initiationof

therapy),n

ausea,

anorgasm

ia,

insomnia,diarrhea,

increasedriskofGI

bleeding.

See

citalopram

.See

citalopram

.$-$$




Chapter 2: Anxiety Disorders 21Class

Drug

Type

ofAnxiety

Dose

Adverse

Effects

DrugInteractions

Com

ments

Costa

Serotonin-

Norepinephrine

ReuptakeInhibitors

duloxetine

Cym

balta

GAD

60–120

mgdaily

poNausea,

insomnia,

dizziness,asthenia.

Donotusewith

MAOIs;

cautionwith

otherserotonergic

drugsincludingam

phetam

ine

derivatives,dextromethorphan,

dihydroergotam

ine,linezolid,

lithium

,meperidine,

pentazocine,

selegiline,

St.John'swort,trazodone,

triptans,tryptophan(increased

riskofserotoninsyndrome).

Substrate

ofCYP1A

2and

CYP2D

6;cautionwith

inducers

orinhibitors

oftheseisoenzym

es.

May

take

2–3monthsfor

maximum

effect.

Discontinue

gradually.

Avoidinsevere

renal

dysfunction.

$125–240

venlafaxine

extended-

release

EffexorX

R,

generics

GAD,S

AD

37.5–225

mg/day

poSee

duloxetine.

Donotuse

with

MAOIs.

Substrate

ofCYP2D

6and

CYP3A

4;cautionwith

inducers

orinhibitors

oftheseisoenzym

es.

See

duloxetine.

$-$$

aCostof30-daysupply,

unless

otherwisespecified;includesdrug

costonly.

Dosageadjustmentm

aybe

requiredinrenalimpairm

ent;seeAppendixI.

Abbreviations:

AG=agoraphobia;GAD=generalized

anxietydisorder;M

AOI=

monoamineoxidaseinhibitor;PD=panicdisorder;S

AD=socialanxietydisorder;S

NRI=

serotonin-norepinephrinereuptake

inhibitor;

SSRI=

selectiveserotoninreuptake

inhibitor;TC

A=tricyclicantidepressant

Legend:

$<$25

$-$$

<$25–50

$$$25–50

$$-$$$

$25–75

$$$$50–75

$$-$$$$$25–100

$$$$

$75–100

$$$-$$$$$$50–125

$$$$$$100–125





Suggested Readings

American Psychiatric Association. Practice guidelines for the treatment of patients with panicdisorder. 2nd ed. Washington (DC): APA; 2009.

Baldwin DS, Anderson IM, Nutt DJ et al. Evidence-based guidelines for the pharmacological treatmentof anxiety disorders: recommendations from the British Association for Psychopharmacology. JPsychopharmacol 2005;19(6):567-96.

Bandelow B, Sher L, Bunevicius R et al. Guidelines for the pharmacological treatment of anxietydisorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int JPyschiatry Clin Pract 2012;16(2):77-84.

Ravindran H, Stein M. The pharmacologic treatment of anxiety disorders: a review of progress. J ClinPsych 2010;71(7):839-54.

Swinson R, Anthony M, Bleau P et al. Canadian Psychiatric Association. Clinical practice guidelines.Management of anxiety disorders. Can J Psychiatry 2006;51(8 Suppl 2):9S-91S.

U.K. National Institute for Health and Care Excellence. NICE clinical guidelines CG159.Social anxiety disorder: recognition, assessment and treatment. May 2013. Available from:publications.nice.org.uk/social-anxiety-disorder-recognition-assessment-and-treatment-cg159.

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panic disorder in a randomized controlled trial. Behav Cogn Psychother 2013;41(4):408-32.3. Van Apeldoorn FJ, Van Hout WJ, Timmerman ME et al. Rate of improvement during and across three treatments for panic disorder with or

without agoraphobia: cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined. J Affect Disord 2013;150(2):313-9.4. Swinson R, Anthony M, Bleau P et al. Canadian Psychiatric Association. Clinical practice guidelines. Management of anxiety disorders. Can J

Psychiatry 2006;51(8 Suppl 2):9S-91S.5. Boyer W. Serotonin uptake inhibitors are superior to imipramine in alleviating panic attacks: a meta-analysis. In: Darcourt G, ed. Current

therapeutic approaches to panic and other anxiety disorders. New York (NY): Karger; 1994.6. Goddard AW, Brouette T, Almai A et al. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry

2001;58(7):681-6.7. Mavissakalian MR, Perel JM. Long-term maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia.

Arch Gen Psychiatry 1999;56(9):821-7.8. Boshuisen ML, Slaap BR, Vester-Blokland ED et al. The effect of mirtazapine in panic disorder: an open label pilot study with a single-blind

placebo run-in period. Int Clin Psychopharmacol 2001;16(6):363-8.9. Sarchiapone M, Amore M, De Risio S et al. Mirtazapine in the treatment of panic disorder: an open-label trial. Int Clin Psychopharmacol

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multicenter trial on panic disorder with or without agoraphobia. Acta Psychiatr Scand 2008;117(4):260-70.13. Kasper S, Stein D, Loft H et al. Escitalopram in the treatment of social anxiety disorder: randomised, placebo-controlled, flexible-dosage

study. Br J Psychiatry 2005;186:222-6.14. Lader M, Stender K, Burger V et al. Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder:

randomised, double-blind, placebo-controlled, fixed-dose study. Depress Anxiety 2004;19(4):241-8.15. Davidson J, Yaryura-Tobias J, DuPont R et al. Fluvoxamine-controlled release formulation for the treatment of generalized social anxiety

disorder. J Clin Psychopharmacol 2004;24(2):118-25.16. Westenberg HG, Stein DJ, Yang H et al. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of

generalized social anxiety disorder. J Clin Psychopharmacol 2004;24(1):49-55.17. Baldwin D, Bobes J, Stein DJ et al. Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled

study. Paroxetine Study Group. Br J Psychiatry 1999;175:120-6.18. Liebowitz MR, Stein MB, Tancer M et al. A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of

generalized social anxiety disorder. J Clin Psychiatry 2002;63(1):66-74.19. Liebowitz MR, DeMartinis NA, Weihs K et al. Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind,

placebo-controlled study. J Clin Psychiatry 2003;64(7):785-92.20. Van Ameringen MA, Lane RM, Walker JR et al. Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled

study. Am J Psychiatry 2001;158(2):275-81.21. Rickels K, Mangano R, Khan A. A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with

generalized social anxiety disorder. J Clin Psychopharmacol 2004;24(5):488-96.22. Falloon IR, Lloyd GG, Harpin RE. The treatment of social phobia. Real-life rehearsal with nonprofessional therapists. J Nerv Ment

Dis 1981;169(3):180-4.23. Liebowitz MR, Schneier F, Campeas R et al. Phenelzine vs atenolol in social phobia. A placebo-controlled comparison. Arch Gen Psychiatry

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Chapter 2: Anxiety Disorders 2324. Stein DJ, Cameron A, Amrein R et al. Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder

with or without comorbid anxiety disorder. Int Clin Psychopharmacol 2002;17(4):161-70.25. Pande AC, Davidson JR, Jefferson JW et al. Treatment of social phobia with gabapentin: a placebo-controlled study. J Clin Psychopharmacol

1999;19(4):341-8.26. Pande AC, Feltner DE, Jefferson JW et al. Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled,

multicenter study. J Clin Psychopharmacol 2004;24(2):141-9.27. Otto MW, Pollack MH, Gould RA et al. A comparison of the efficacy of clonazepam and cognitive-behavioral group therapy for the treatment

of social phobia. J Anxiety Disord 2000;14(4):345-58.28. Borkovec TD, Ruscio AM. Psychotherapy for generalized anxiety disorder. J Clin Psychiatry 2001;62(Suppl 11):37-42.29. Mancini M, Perna G, Rossi A et al. Use of duloxetine in patients with an anxiety disorder, or with comorbid anxiety and major depressive

disorder: a review of the literature. Expert Opin Pharmacother 2010;11(7):1167-81.30. Davidson JR, Bose A, Korotzer A et al. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled,

flexible-dose study. Depress Anxiety 2004;19(4):234-40.31. Goodman WK, Bose A, Wang Q. Treatment of generalized anxiety disorder with escitalopram: pooled results from double-blind,

placebo-controlled trials. J Affect Disord 2005;87(2-3):161-7.32. Pollack MH, Zaninelli R, Goddard A et al. Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled,

flexible-dosage trial. J Clin Psychiatry 2001;62(5):350-7.33. Davidson JR, DuPont RL, Hedges D et al. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with

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placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 2005;62(9):1022-30.35. Feltner DE, Crockatt JG, Dubovsky SJ et al. A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin

in patients with generalized anxiety disorder. J Clin Psychopharmacol 2003;23(3):240-9.36. Baldwin S, Ajel K, Masdrakis VG et al. Pregabalin for the treatment of generalized anxiety disorder: an update. Neuropsychiatr Dis

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Neuropsychopharmacol 2005;30(Suppl 1):S101.38. Bandelow B, Chouinard G, Bobes J et al. Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in

generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. Int J Neuropsychopharmacol2010;13(3):305-20.

39. Olatunji BO, Cisler JM, Deacon BJ. Efficacy of cognitive behavioral therapy for anxiety disorders: a review of meta-analytic findings.Psychiatr Clin North Am 2010;33(3):557-77.

40. ACOG Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologistsnumber 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation.Obstet Gynecol 2008;111(4):1001-20.

41. Tuccori M, Montagnani S, Testi A et al. Use of selective serotonin reuptake inhibitors during pregnancy and risk of major and cardiovascularmalformations: an update. Postgrad Med 2010;122(4):49-65.

42. Yonkers KA, Wisner KL, Stewart DE et al. The management of depression during pregnancy: a report from the American PsychiatricAssociation and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry 2009;31(5):403-13.

43. Academy of Breastfeeding Medicine Protocol Committee. ABM clinical protocol #18: use of antidepressants in nursing mothers. BreastfeedMed 2008;3(1):44-52.

44. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants.Am J Psychiatry 2004;161(6):1066-78.

45. Bandelow B, Bobes J, Ahokas A et al. Results from a phase III study of once-daily extended release quetiapine fumarate (quetiapine XR)monotherapy in patients with generalized anxiety disorder. Presented at 7th International Forum of Mood and Anxiety Disorders 5–7December 2007; Budapest, Hungary.



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