Sample Chapter

SAMPLE CHAPTER

TO ORDER SEE DETAILS ON PAGE 19 OR GO TO WWW.PHARMACISTS.CA/CTCNURSE 3 10PsychiatricPsychiatric Disorders Disorders Psychiatric Disorders Chapter 2 Anxiety Disorders R. P. Swinson, MD, FRCPsych, FRCPC

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) contains several significant 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-related disorders, respectively. Management of OCD and PTSD are discussed in separate chapters (see Chapter 9 and Chapter 10). ■ Two disorders, separation anxiety disorder and selective mutism, have been added to anxiety disorders. 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 anxiety disorder.

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

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However, 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 is excessive for the developmental stage.

Selective mutism Childhood onset of failure to speak in school or other social situations when the individual does 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 (social Intense anxiety provoked by social or performance situations in which embarrassment might phobia) occur; 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, closed spaces, 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 not over a period of ≥6 months.

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

Substance/medication-induced Anxiety or panic attacks directly caused by use or discontinuation of a substance (e.g., anxiety disorder 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 panic attacks, 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 Diagnosisa Questions 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 beable Inquire about crowded places, line-ups, movies, highways, to go? distance from home.

Do you have difficulty talking to people in authority or speaking in Establish situations (one-on-one or groups). public?

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't Ask nature of thoughts (illness, harm, sex). stop?

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 mental disorders: DSM-51 in which panic attacks are diagnosed first, followed by phobic disorders, and generalized anxiety disorder. Anxiety disorders thatdo not fit into the above categories are atypical. Accurate diagnosis is recommended before instituting treatment.

Compendium of TherapeuticTO Choices ORDER SEE DETAILS ON PAGECopyright 19 OR © 2014GO CanadianTO WWW.PHARMACISTS.CA/CTCNURSE Pharmacists Association. All rights reserved. 5 Psychiatric Disorders 12 Psychiatric 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 information about 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

6 TOCopyright ORDER © 2014SEE CanadianDETAILS Pharmacists ON PAGE Association. 19 OR AllGO rights TO reserved. WWW.PHARMACISTS.CA/CTCNURSECompendium of Therapeutic Choices Chapter 2: Anxiety Disorders Chapter 2: Anxiety Disorders 13 Pharmacologic Choices The role of drug therapies varies among anxiety disorders. Drug treatment is rarely required for specific phobias. In the other anxiety disorders, drug therapy is the most common intervention, especially when intensity of symptoms and disability are moderate to severe. A psychiatric consultation is recommended for any patient who does not improve with a trial of 2 separate antidepressants. A list of drug choices is provided in Table 3. Available information on the treatment of panic disorder, agoraphobia and panic disorder with agoraphobia (PDA) is based on studies that did not separate patients into groups with either panic disorder or agoraphobia.3 Although DSM-5 makes the distinction between the 2 separate conditions or PDA, studies are needed to determine whether available pharmacologic agents differentially treat each condition. Panic Disorder Antidepressants The SSRIs citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are all effective 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 with or without agoraphobia.4,5 There is usually a delay in response to these agents that may be accompanied by 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 to medication and produce a more rapid response than with antidepressants alone.6 The tricyclic antidepressants (TCAs) imipramine, desipramine and clomipramine have been shown to reduce the frequency and severity of panic attacks7 and are inexpensive. The different side effect profiles of TCAs and SSRIs can be used to guide treatment choice. Mirtazapine has been effective in open-label trials.8,9 The older monoamine oxidase inhibitors (MAOIs) phenelzine and tranylcypromine are also effective but more difficult to use because of the dietary restrictions and potential for serious drug interactions.10 The dosage requirements and length of treatment for antidepressants in panic disorder are similar to those 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 antidepressant dose range; higher starting doses may cause patients to become agitated and discontinue treatment abruptly. Determining the duration of drug treatment is of great importance; medication is usually required for months or years. Evidence has shown that a majority of patients will suffer relapse after benzodiazepines or antidepressants are discontinued.11 Taper doses gradually if antidepressants must be discontinued or dose-reduced. Abrupt dosage changes may cause the patient to experience antidepressant discontinuation syndrome. More information about this 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 of high-potency benzodiazepines can be used to abort initial panic attacks and may control high-frequency attacks later in the development of the disorder. Clonazepam 0.25–0.5 mg BID frequently makes panic attacks more manageable. Lorazepam and diazepam can also be used. Although there is considerable evidence for the efficacy of benzodiazepines as monotherapy for panic disorder, they are best reserved for those cases where SSRI/SNRI treatment has not been successful or if the antidepressant response needs augmentation. Short-term use of benzodiazepines is best. For patients who have been maintained on stable low doses for 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 of panic attacks when benzodiazepines are stopped.11 Agoraphobia and Panic Disorder with Agoraphobia The pharmacologic treatment of agoraphobia with or without panic disorder is the same as for panic disorder. Much of the disability in agoraphobia arises from avoidance behaviour rather than the panic attacks. The degree of avoidance is frequently under-reported by patients; careful questioning or standardized questionnaires may be needed for a complete assessment. The avoidance can be addressed with CBT, even if medication reduces or eliminates accompanying panic attacks. CBT is effective alone 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, avoidance of social contact or difficulty dealing with authority figures. The disorder may be present from childhood and often becomes noticeable in adolescence. It is particularly important to rule out comorbid major depression and alcohol use. CBT or other psychotherapy may be necessary to deal with 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 stage fright or fear of public speaking. Escitalopram,13,14 fluvoxamine,15,16 paroxetine,17,18 sertraline19,20 and venlafaxine21 have demonstrated efficacy. Simple stage fright or fear of public speaking may respond to low-dose propranolol (10 mg) taken 30 minutes before the event; in generalized social anxiety disorder propranolol is usually ineffective.22,23 Results for moclobemide vary but it may be effective, particularly in higher doses.24 When used at doses above 600 mg/day, moclobemide loses its isoenzyme specificity for MAO-A. Caution patients taking 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 to first-line measures. Benzodiazepines, particularly clonazepam,27 are effective but should be used with the same restrictions (i.e., short-term use of lowest effective dose) as in other anxiety disorders. Specific Phobia Medication is not usually indicated for the treatment of specific fear of heights, animals, injections or other common triggers. As little as 6 hours of CBT is often successful in producing marked, enduring change. Generalized Anxiety Disorder Generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry related to everyday-life concerns such as safety of family members, financial/job security and health. Patients with GAD frequently exhibit depressed mood and other anxiety symptoms. CBT is the most effective psychosocial 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 sertraline or venlafaxine.33 Pregabalin is now an established first-line treatment for GAD with the advantage of providing rapid onset of relief.34,35,36 While effective in GAD, imipramine is limited by its side effect profile and safety concerns in overdose. It is usually reserved for use in patients for whomfirst-line agents are not effective. Bupropion is also an option.37

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Quetiapine is effective in GAD both as monotherapy and to augment antidepressant medication.38 At a dose of 150 mg daily, it has been shown to rapidly reduce many symptoms of GAD. Quetiapine is generally regarded as a second-line choice due to its side-effect profile of weight gain and potential effects on metabolic regulation. Low-dose benzodiazepines (e.g., bromazepam, clonazepam, diazepam, lorazepam) can be used for symptom relief for several weeks at a time; caution is advised regarding the risk of dependence and discontinuation symptoms. Buspirone is an azapirone with a low potential for abuse and less sedation compared to benzodiazepines. Like antidepressants, it has a relatively slow onset of effect. When switching from long-term benzodiazepine therapy to buspirone, it is important that the benzodiazepine is not discontinued abruptly; there is no cross-tolerance between the 2 drug classes and benzodiazepine withdrawal symptoms could be precipitated.

Choices during Pregnancy and Breastfeeding Anxiety Disorders and Pregnancy Anxiety disorders have onset early in life, are frequently chronic in nature and their severity waxes and wanes in response to environmental events. Pregnancy may be accompanied by increased or decreased anxiety. It is important to screen for the presence of anxiety symptoms prior to conception if possible. Screening can be repeated during the pregnancy and in particular postpartum. If a woman is suffering from marked anxiety related to pregnancy and breastfeeding, it is imperative to screen for the presence of mood symptoms and suicidality. In any circumstances where a woman experiences severe anxiety or mood disorder symptoms during pregnancy or postpartum, referral to a psychiatrist may be necessary. In major centres, women's mental health 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 or interfering with functioning. Panic disorder with agoraphobia may prevent a woman from attending medical appointments. Management during Pregnancy There is good evidence that psychological treatments can have beneficial effects for more than half of those who persist with a treatment program. CBT can be administered without restriction throughout pregnancy. Therapies based in meditative or relaxation techniques may be more acceptable than pharmacologic approaches.39 If anxiety symptoms are severe and produce significant impairment, medications can be appropriate and effective.40 The 2 main classes of medications used for anxiety disorders are SSRI or SNRI antidepressants and benzodiazepines. SSRIs or SNRIs may cause agitation, sweating, nausea, GI distress and weight gain. There have been reports of a slightly higher (but still low) risk of congenital abnormalities involving the heart or cleft lip/palate.41 When used in the third trimester, these drugs may be associated with neonatal withdrawal symptoms such as tremors, increased muscle tone, feeding or digestive problems or respiratory distress. Whether benzodiazepines confer an increased risk of congenital malformations is controversial. Benzodiazepines administered shortly before delivery can result in floppy infant syndrome or neonatal withdrawal symptoms. The use of SSRIs, SNRIs or benzodiazepines may be warranted in patients with severe symptoms that could 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 pregnancy are applicable to the management of anxiety disorders.42,43 See also Chapter 6 for information on management of depression during pregnancy and breastfeeding.

Anxiety Disorders and Breastfeeding In the postpartum period, severe anxiety can impede the mother's sleep and erode her confidence in caring for her child. If a woman refuses to be involved with caring for her child, an urgent psychiatric consultation is needed and treatment considerations should include admitting the mother and child to hospital. As in pregnancy, nonpharmacologic options should be used whenever possible in the postpartum period, particularly in breastfeeding women. If drug therapy is necessary, consider paroxetine or sertraline, since both have low concentrations in breast milk.44 When possible, avoid benzodiazepines due 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 be found in Appendix II and Appendix III. Other specialized reference sources are also provided in these 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 toanother 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.

10 TOCopyright ORDER © 2014 SEE Canadian DETAILS Pharmacists ON PAGE Association. 19 OR All GO rights TO reserved. WWW.PHARMACISTS.CA/CTCNURSECompendium of Therapeutic Choices Chapter 2: Anxiety Disorders Chapter 2: Anxiety Disorders 17 (cont'd) a $$-$$$$ Cost $$-$$$$ $$ $-$$ See clomipramine. Comments See clomipramine. Used as augmentation therapy with first-line agents in GAD, ormonotherapy after as failure of first-line therapies. Advise patients about antipsychotic-associated body temperature dysregulation and prevention of heat stroke (e.g., hydration, sun protection). May take 2–3 months for maximum effect. c interval. May increase effectanticholinergic of drugs, CNS depressants, warfarin; do not use MAOIs concurrently. Additive sedation with CNS depressants; may potentiate antihypertensive drug effects; inhibitors of CYP3A4 such as clarithromycin, erythromycin, grapefruit juice, ketoconazole or prednisone may increase quetiapine levels; inducers of CYP3A4 suchcarbamazepine, as phenytoin or rifampin may decrease quetiapine levels. Use with caution withknown drugs to prolong the QT c (agitation on initiation of therapy, confusion, drowsiness, headache), anticholinergic effects (dry mouth, blurred vision, constipation, etc.), weight gain, nausea, cardiovascular effects (tachycardia, arrhythmias, orthostatic hypotension), anorgasmia, erectile dysfunction. prolongation. Sedation, dizziness, weight gain, orthostatic hypotension, hepatic aminotransferase elevation, headache, anticholinergic effects, increased risk of diabetes and dyslipidemia, movement disorders; may lower thyroid hormone levels, modest QT Adverse Effects Drug Interactions 45 Usual maximum: 400 mg daily po Initial: 50 mg daily po Titrate to 150 mg daily po, or highernecessary. if PD, AG 75–225 mg/day po CNS effects PD, AG, GAD 75–300 mg/day po See clomipramine. See clomipramine. PD, AG, GAD 75–300 mg/day po See clomipramine. See clomipramine. Type of Anxiety Dose GAD imipramine generics Drug clomipramine Anafranil, generics desipramine generics quetiapine Seroquel, Seroquel XR, generics Drugs Used for the Management of Anxiety Disorders Class Antidepressants, tricyclic Antipsychotics, Second-generation Table 3:

Compendium of TherapeuticTO Choices ORDER SEE DETAILS ON PAGECopyright 19 OR © 2014 GO Canadian TO WWW.PHARMACISTS.CA/CTCNURSE Pharmacists Association. All rights reserved. 11 Psychiatric Disorders 18 Psychiatric Disorders a Cost $$$-$$$$$ $ $ $$-$$$ $-$$ $$ Comments as rapid asbenzodiazepines. with Discontinue gradually to avoid rebound anxiety; avoid in pregnancy; contraindicated in patients with known history of abuse; dose escalation is rare in patients taking benzodiazepines for chronic anxiety; use lower doses in elderly. For occasional use in situations such as public speaking, performing; not useful in generalized social anxiety disorder. Stringent dietary restrictions are necessary. Avoid tyramine-containing foods. Not a first-line agent; may be useful in patients not responding to first-line measures. Not an approved indication. First-line agent for GAD. May be useful in patients not responding to ortolerating not other first-line measures. Avoid use with MAOIs. Onset of effect not Warn patients re: concomitant use of alcohol, otherdepressants (increased CNS effect). Caution re: increased bradycardia with amiodarone. Concurrent use with sympathomimetic agents, tyramine or levodopa may result in hypertensive crisis; do not use with serotonergic drugs such as SSRIs, SNRIs,meperidine, TCAs, tryptophan due to high risk forsyndrome). fatal serotonin Magnesium- and aluminum-containing antacids may decrease the absorption of gabapentin. No known significant drug interactions. (cont'd) Adverse EffectsNausea, headache, Drugdizziness, Interactions restless- ness/insomnia. (tolerance develops with continued therapy), dizziness, reduced concentration, retrograde amnesia, physical dependence; rarely, paradoxical anger or hostility. Hypotension. Insomnia, dizziness, orthostatic hypotension, edema, sexual dysfunction. Somnolence, dizziness, ataxia, vision changes. Dizziness, sedation, peripheral edema. Initial: 5 mg BID–TID po Titrate gradually to effective dose. Maximum: 60 mg/day po 0.25–0.5 mg BID po Drowsiness 10 mg pobefore 30 task min PRN Initial: 300 mg/day po Usual: 900–1800 mg/day po in 2 divided doses in 2–3 divided doses May be increased to 150 mg BID po afterwk 1 if necessary Type of AnxietyGAD Dose GAD, PD, AG SAD (specific task-related anxiety) PD, AG 45–90 mg/day po SAD See Comments. GAD, SAD Initial: 150 mg/day po Drug buspirone generics clonazepam Rivotril, generics propranolol generics gabapentin phenelzine Nardil Neurontin, generics pregabalin Lyrica, generics Drugs Used for the Management of Anxiety Disorders -adrenergic 1 Class Azapirones Benzodiazepines Beta GABA Derivatives Monoamine Oxidase Inhibitors Antagonists Table 3:

12 TOCopyright ORDER © 2014SEE CanadianDETAILS Pharmacists ON PAGE Association. 19 OR AllGO rights TO reserved. WWW.PHARMACISTS.CA/CTCNURSECompendium of Therapeutic Choices Chapter 2: Anxiety Disorders Chapter 2: Anxiety Disorders 19 (cont'd) a Cost $$-$$$ $ $ Comments See phenelzine. May take 2–3 months for maximum effect. Discontinue gradually. Dietary restrictions are not required at usual doses. interval/torsades de c pointes, such as amiodarone, azithromycin, clarithromycin, domperidone, erythromycin, haloperidol, methadone, pimozide, quinine, sotalol, ziprasidone. Serotonin syndrome with MAOIs (hypertension, tremor, agitation, hypomania); caution with other serotonergic drugs including amphetamine derivatives, dextromethorphan, dihydroergotamine, linezolid, lithium, meperidine, pentazocine, selegiline, St. John's wort,triptans, trazodone, tryptophan (increased risk of serotonin syndrome); increased risk of GIwith bleeding NSAIDs, antiplatelet agents. SSRIs are substrates and inhibitors of several cytochrome P450 isoenzymes. This may result in reduced clearancemany of drugs (e.g., clozapine, methadone, mexiletine, phenytoin, pimozide, propafenone) or decreased enzymatic conversion of a prodrug to its active(e.g., form clopidogrel, codeine, tamoxifen). Avoid combined use with drugs associated with prolonged QT TCAs, SSRIs. c prolongation. Adverse Effects Drug Interactions Agitation (on initiation of therapy), nausea, anorgasmia, insomnia, diarrhea, increased risk of GI bleeding; dose-related QT Nausea, insomnia. Do not use with meperidine, Up to 60 mg/daymay po be required in appropriately selected patients. 300–600 mg/day po Type of Anxiety Dose PD, AG 20–60 mg/day po See phenelzine. See phenelzine. PD, AG, SAD 20–40 mg/day po SAD Drug citalopram Celexa, CTP 30, generics tranylcypromine Parnate moclobemide Manerix, generics Class Selective Serotonin Reuptake Inhibitors Reversible Inhibitors of Monoamine Oxidase-A

Compendium of TherapeuticTO Choices ORDER SEE DETAILS ON PAGECopyright 19 OR © 2014 GO Canadian TO WWW.PHARMACISTS.CA/CTCNURSE Pharmacists Association. All rights reserved. 13 Psychiatric Disorders 20 Psychiatric Disorders a $$$ $-$$ Cost $$$ $-$$ $-$$ $-$$ See citalopram. See citalopram. Comments See citalopram. See citalopram. See citalopram. See citalopram. See citalopram. See citalopram. See citalopram. (cont'd) initiation of therapy), nausea, anorgasmia, insomnia, headache, reduced appetite, diarrhea, increased risk of GI bleeding. initiation of therapy), nausea, anorgasmia, anticholinergic effects, sedation, increased risk of GI bleeding. initiation of therapy), nausea, anorgasmia, insomnia, diarrhea, increased risk of GI bleeding. Adverse Effects Drug Interactions See fluvoxamine. See citalopram. po PD, AG, GAD 10–20 mg/day po See citalopram. See citalopram. PD, AG, SAD 20–60 mg/day po See fluvoxamine. See citalopram. PD, AG, SAD 20–80 mg/day po Agitation (on PD, AG, SAD 150–300 mg/day po Agitation (on PD, AG, SAD 50–200 mg/day po Agitation (on Type of Anxiety Dose PD, AG, SAD 12.5–37.5 mg/day fluoxetine Prozac, generics paroxetine controlled- release Drug escitalopram Cipralex, Cipralex MELTZ Paxil, generics Paxil CR sertraline Zoloft, generics fluvoxamine Luvox, generics paroxetine immediate- release Drugs Used for the Management of Anxiety Disorders Class Table 3:

14 TO ORDERCopyright SEE © 2014 DETAILS Canadian PharmacistsON PAGE Association. 19 OR GO All TO rights WWW.PHARMACISTS.CA/CTCNURSE reserved. Compendium of Therapeutic Choices Chapter 2: Anxiety Disorders Chapter 2: Anxiety Disorders 21 a Cost $125–240 $-$$ Comments May take 2–3 months for maximum effect. Discontinue gradually. Avoid in severe renal dysfunction. See duloxetine. Do not usecaution with with MAOIs; other serotonergic drugs including amphetamine derivatives, dextromethorphan, dihydroergotamine, linezolid, lithium, meperidine, pentazocine, selegiline, St. John's wort,triptans, trazodone, tryptophan (increased risk of serotonin syndrome). Substrate of CYP1A2 and CYP2D6; caution with inducers or inhibitorsthese of isoenzymes. Substrate of CYP2D6 and CYP3A4; caution with inducers or inhibitorsthese of isoenzymes. Adverse Effects Drug Interactions dizziness, asthenia. See duloxetine. Do not use with MAOIs. 60–120 mg daily po Nausea, insomnia, po Type of Anxiety Dose GAD GAD, SAD 37.5–225 mg/day Drug duloxetine Cymbalta venlafaxine extended- release Effexor XR, generics Dosage adjustment may be required in renal impairment; see Appendix I. Cost of 30-day supply, unless otherwise specified; includes drug only. cost Class Serotonin- Norepinephrine Reuptake Inhibitors Abbreviations: AGSSRI = = agoraphobia; selective GAD = serotoninLegend: generalized reuptake anxiety inhibitor; disorder; TCA MAOI $ = = < tricyclic monoamine $25 antidepressant oxidase inhibitor; PD = $-$$ panic < disorder; $25–50 SAD = social anxiety disorder; $$ SNRI $25–50 = serotonin-norepinephrine reuptake inhibitor; $$-$$$ $25–75 $$$ $50–75 $$-$$$$ $25–100 $$$$ $75–100 $$$-$$$$$ $50–125 $$$$$ $100–125 a

Compendium of TherapeuticTO Choices ORDER SEE DETAILS ON PAGECopyright 19 OR © 2014GO CanadianTO WWW.PHARMACISTS.CA/CTCNURSE Pharmacists Association. All rights reserved. 15 Psychiatric Disorders 22 Psychiatric Disorders Suggested Readings American Psychiatric Association. Practice guidelines for the treatment of patients with panic disorder. 2nd ed. Washington (DC): APA; 2009. Baldwin DS, Anderson IM, Nutt DJ et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2005;19(6):567-96. Bandelow B, Sher L, Bunevicius R et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Pyschiatry Clin Pract 2012;16(2):77-84. Ravindran H, Stein M. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psych 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. References 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. Arlington (VA): APA; 2013. 2. Hovland A, Nordhus IH, Sjøbø T et al. Comparing physical exercise in groups to group cognitive behaviour therapy for the treatment of 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 2003;18(1):35-8. 10. Buigues J, Vallejo J. Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks. J Clin Psychiatry 1987;48(2):55-9. 11. Marks IM, Swinson RP, Basoglu M et al. Alprazolam and exposure alone and combined in panic disorder with agoraphobia. A controlled study in London and Toronto. Br J Psychiatry 1993;162:776-87. 12. van Apeldoorn FJ, van Hout WJ, Mersch PP et al. Is a combined therapy more effective than either CBT or SSRI alone? Results of a 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 1992;49(4):290-300.

16 TO ORDER SEE DETAILS ON PAGE 19 OR GO TO WWW.PHARMACISTS.CA/CTCNURSE Chapter 2: Anxiety Disorders Chapter 2: Anxiety Disorders 23

24. 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 generalized anxiety disorder. J Clin Psychiatry 1999;60(8):528-35. 34. Rickels K, Pollack MH, Feltner DE et al. Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, 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 Treat 2013;9:883-92. 37. Bystritsky A, Kerwin L, Eiduson S et al. A pilot controlled trial of bupropion vs. escitalopram in generalized anxiety disorder (GAD). 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 Neuropsychopharmacol 2010;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-gynecologists number 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 cardiovascular malformations: 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 Psychiatric Association 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. Breastfeed Med 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 5–7 December 2007; Budapest, Hungary.

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