Pharmacotherapy for specific phobia in adults.pdf

Official reprint from UpToDatewww.uptodate.com ©2013 UpToDate

AuthorsRichard Swinson, MDRandi E. McCabe, PhD

Section EditorMurray B Stein, MD, MPH

Deputy EditorRichard Hermann, MD

Pharmacotherapy for specific phobia in adults

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Oct 2013. | This topic last updated: Abr 12, 2012.

INTRODUCTION — Specific phobia is an anxiety disorder characterized by clinically-significant fear of a particularobject or situation that typically leads to avoidance behavior. Phobic fears include animals, insects, heights, water,enclosed places, driving, flying, seeing blood, getting an injection, and choking or vomiting.

Specific phobias are among the most common mental disorders and can be highly disabling [1,2]. However, theyare also among the most treatable mental disorders [3-6]. Despite availability of efficacious treatments, themajority of individuals with specific phobias are hesitant to seek treatment [7]. This may be due to lack ofknowledge that the phobia is treatable, embarrassment to disclose the phobia to a health professional,accommodation of the phobia through avoidance, or fear of increased anxiety or discomfort in the course oftreatment [5].

Pharmacotherapy for specific phobia in adults is discussed here. The epidemiology, pathogenesis, clinicalmanifestations, course, and diagnosis of specific phobia in adults are discussed separately. Psychotherapy forspecific phobia in adults is discussed separately. Specific phobias relating to clinical procedures (eg, blood-injection-injury phobia) and other manifestations of acute procedural anxiety are discussed separately. Specificphobia and other fears in children are also discussed separately. (See "Specific phobia in adults: Epidemiology,clinical manifestations, course and diagnosis" and "Psychotherapy for specific phobia in adults" and "Acuteprocedure anxiety in adults: Epidemiology and clinical presentation" and "Treatment of acute procedure anxiety inadults" and "Overview of fears and specific phobias in children".).

TREATMENT OVERVIEW — First-line treatment for specific phobia is cognitive-behavior therapy (CBT) thatincludes exposure treatment [8]. (See "Psychotherapy for specific phobia in adults".)

Pharmacotherapy, including benzodiazepines and serotonergic reuptake inhibitors, has a limited role in treatment ofspecific phobia. Medications are used when CBT is not available or when patients prefer medication to CBTdespite the lack of comparably robust supporting evidence from clinical trials.

Benzodiazepines

Indications — Among medications, benzodiazepines are most often used in the treatment of specific phobiawhen the phobic stimulus is infrequently encountered and unavoidable, such as in the treatment of a flying phobia orblood-injection-injury phobia. Patients who have experienced intense fear on previous occasions when undertakingthese activities may wish to have a reasonable certainty that their anxiety can be lessened if they were toexperience the feared stimulus again. (See "Treatment for specific phobias of medical and dental procedures",section on 'Blood-injection-injury phobia'.)

Efficacy — There are no rigorous data from clinical trials suggesting that benzodiazepines are effective forspecific phobia [9].

A randomized trial of 28 women with flying phobia who traveled on two flights over a one week period foundthat alprazolam led to reduced anxiety but a greater physiologic response on the first flight, compared toplacebo, and increased anxiety, physiologic response, and panic on the second flight [10].

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A non-randomized trial of 91 patients with dental phobia allowed participants to select whether to receivepretreatment with midazolam, a one-session stress management training, or no intervention prior to asurgical dental procedure [11]. In an analysis of only the 50 patients completing the procedure andsubsequent assessment, both interventions led to reduced fear at the time of the procedure compared tothe control group. The effects of the stress management training, but not the medication, were sustained attwo-month follow-up.

Substantial clinical experience suggests that flying phobia can be effectively treated with benzodiazepines.However, well-designed randomized trials are needed to determine efficacy [12].

Other trials of sedative medications have suggested that generalized anesthesia and nitrous oxide are effectivetreatments for dental phobia, though evidence comparing these agents to cognitive and behavioral therapies ismixed [13-15]. Sedating medications are most useful for treating phobias that do not involve performance thatcould be adversely affected by the medication. (See "Treatment for specific phobias of medical and dentalprocedures", section on 'Dental phobia'.)

Administration — A benzodiazepine with a relatively short onset (eg, lorazepam 0.5 to 2 mg) can be taken 30minutes before the stimulus is encountered. Patients should be advised to take a test dose prior to using it for thephobic situation to ensure it does not lead to oversedation. Patients should be warned not to consume alcohol andthe drug together due to the risk of additive side effects such as sedation, confusion, and impaired coordination.

The risk of abuse of benzodiazepines is largely confined to individuals with a substance abuse history or problem,though a family history of substance abuse may be a risk factor for some individuals [16]. Treating patients whoare no longer currently abusing substances with benzodiazepines is not absolutely contraindicated, but wouldrequire closer monitoring and, in some cases, the use of longer-acting benzodiazepines with slower onset of action(eg, clonazepam) that may reduce abuse liability. Dose escalation can be discouraged by prescribing a minimalsupply of pills for infrequent use.

Selective serotonin reuptake inhibitors

Indications — In cases where medications have been selected for treatment of specific phobia and abenzodiazepine is ineffective, a serotonin reuptake inhibiting antidepressant can be used. Given the time course ofresponse to a serotonin reuptake inhibiting antidepressant (ie, weeks to months), an SRI is indicated only whenthere is sufficient time to attain therapeutic benefit and only in instances where repeated exposure to the phobicstimulus is anticipated over a prolonged time period. A serotoninergic agent may be more suitable than abenzodiazepine when the patient is repeatedly exposed to the phobic stimulus (eg, an individual with claustrophobiawhose job requires him or her to ride as a passenger in a car).

Efficacy — Two very small trials and some case reports suggest that selective serotonin reuptake inhibitors(SSRIs) may be effective for specific phobia, though larger trials of these agents are needed.

A randomized trial compared 12 weeks of treatment with escitalopram (5 to 20 mg/day) to placebo in 12patients with specific phobia (types included enclosed spaces, flying, heights, dentist, and animals) [17]. Astatistically-significant difference was not seen between the two groups, though a trend in favor ofmedication was observed in this small trial.

A randomized trial compared four weeks of treatment with paroxetine (20 mg/day) to placebo in 11 patientswith specific phobia (types included confined spaces, storms, flying, animals, heights, driving) [18]. Patientstreated with paroxetine showed greater reductions in fear and avoidance compared to the placebo group.

Two case reports described the resolution of a pre-existing flight phobia associated with treatment of aco-occurring mood disorder with fluoxetine [19]. A third case report described remission of a storm phobiaassociated with fluvoxamine treatment [20].

Administration — SSRIs are typically started at the low end of their therapeutic range and titrated upgradually until response is achieved. As examples, the starting dose of escitalopram in specific phobia is as low as5 mg daily with upward titration over two to three weeks to 20 mg daily. Sertraline starting dose is 50 mg daily andincreasing to 200 mg daily in the same time period. The duration of a therapeutic trial of an SSRI should be a


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minimum of six to eight weeks before concluding that the medication has failed. (See "Selective serotonin reuptakeinhibitors: Pharmacology, administration, and side effects".)

COMPARING CBT AND MEDICATION — There are no clinical trials comparing the efficacy of cognitive-behavioraltherapy (CBT) to benzodiazepines or serotonin reuptake inhibitors for specific phobia. However, multiple trials showCBT to be effective versus placebo, while studies of SSRIs and benzodiazepines are of insufficient number andquality to clearly determine benefit over placebo. (See "Psychotherapy for specific phobia in adults".)

COMBINING CBT AND MEDICATION — There are no clinical trials comparing combinations of SSRIs orbenzodiazepines with CBT in specific phobia to either medications or CBT as monotherapy. If an SSRI is used totreat specific phobia, it should ideally be paired with exposure therapy and then gradually withdrawn as the fearand avoidance are reduced.

Augmentation of cognitive-behavioral therapy (CBT) with cycloserine and hydrocortisone has shown promise in thetreatment of specific phobia. However, the use of these medications for specific phobia is still experimental andcannot be recommended at present.

Cycloserine — Cycloserine, a partial N-methyl-d-aspartate (NMDA) receptor agonist, has been found toeffectively augment CBT in the treatment of specific phobia [21] and other anxiety disorders [22,23]. Themedication’s hypothesized mechanism of action is through facilitation of extinction learning.

In a randomized trial, 28 subjects with a height phobia were randomly assigned to receive cycloserine or placebo inaugmentation of virtual reality exposure [21]. A single dose of the medication (either 50 mg or 500 mg) or placebowas administered 30 to 60 minutes prior the exposure session. Patients who received either dosage of cycloserineplus exposure experienced greater reduction in anxiety symptoms of height phobia than patients who receivedplacebo plus exposure; the difference between groups was seen following each treatment session and onassessment three months following treatment.

Hydrocortisone — Two trials have found hydrocortisone, a glucocorticoid, to effectively augment CBT in thetreatment of specific phobia [24,25]. While the mechanism of action is not known, endogenous glucocorticoids havebeen found to be released in persons experiencing fearful situations.

Forty patients with a height phobia were randomly assigned to receive hydrocortisone 20 mg taken orally orplacebo one hour before each of two sessions of virtual reality exposure-based CBT [24]. Exposure therapyaugmented by hydrocortisone led to a greater reduction in fear of heights compared to placebo-augmentedexposure, as assessed following treatment and at a one-month post-treatment. The reduction in anxiety wasaccompanied by lowered physiological arousal measured by skin conductance (sweating) during theexposure task.

Twenty patients with a spider phobia were randomly assigned to receive hydrocortisone 10 mg taken orallyor placebo one hour prior to exposure to a picture of a spider [25]. Patients receiving hydrocortisoneexperienced a greater reduction in stimulus-induced fear compared to placebo.

SUMMARY AND RECOMMENDATIONS

For most presentations of specific phobia, we recommend first-line treatment with a cognitive-behavioraltherapy (CBT) that includes exposure treatment over other psychotherapeutic or pharmacologicinterventions (Grade 1B). (See "Psychotherapy for specific phobia in adults".)

When CBT/exposure is unavailable or when patients prefer medication to psychotherapy, we suggesttreatment of specific phobia with an infrequently encountered phobic stimulus with a benzodiazepine.(Grade 2C). Benzodiazepine are best suited for patients who lack a history of a substance-use disorder andfor situations where the drug’s sedating effects do not interfere with functioning (eg, as a passenger on aplane flight).

A benzodiazepine such as lorazepam 0.5 to 2 mg can be taken 30 minutes before encountering thesituation. The patient should take a test dose prior to using the medication for the phobic situation toensure it does not lead to oversedation. Patients should be warned not to consume alcohol and the drugtogether due to the risk of additive side effects such as sedation, confusion, and impaired coordination.


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(See 'Benzodiazepines' above.)

When CBT/exposure is unavailable or when patients prefer medication to psychotherapy, we suggesttreatment of specific phobia with a frequently encountered phobic stimulus with a selective serotoninreuptake inhibitor (SSRI) (Grade 2C). As an example, sertraline can be started at 50 mg/day and titratedup to a therapeutic dose over two to three weeks. (See 'Selective serotonin reuptake inhibitors' above.)

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