Pharmacotherapy for social anxiety disorder

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Pharmacotherapy for social anxiety disorder Author Murray B Stein, MD, MPH 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: Jul 11, 2011. INTRODUCTION Social anxiety disorder (SAD), also known as social phobia, is a condition marked by extreme fear of situations that involve possible scrutiny by others. The individual is concerned that embarrassment or humiliation will result, and so he or she avoids such situations, or endures them with intense anxiety. SAD is a prevalent condition, estimated to affect between 4 and 10 percent of the adult United States population over a 12 month period. SAD typically begins in childhood or adolescence and, untreated, can be associated with the subsequent development of major depression, substance abuse, and other mental health problems. The disorder can be associated with extensive functional impairment and reduced quality of life [1]. This topic addresses the pharmacological treatment of SAD. Discussed separately are epidemiology, pathogenesis, clinical manifestations, and diagnosis of SAD; psychotherapy for SAD; and fears and specific phobias in children. (See "Social anxiety disorder: Epidemiology, clinical manifestations, and diagnosis" and "Psychotherapy for social anxiety disorder" and "Overview of fears and specific phobias in children".) SUBTYPES OF SOCIAL ANXIETY Social anxiety disorder (SAD) has two clinical subtypes, generalized and nongeneralized. In generalized SAD, distressing fears are experienced in multiple social situations that typically include social interactional situations (eg, engaging in a conversation, meeting new people, attending parties, relating to co-workers and bosses). In nongeneralized or circumscribed SAD, fears are limited to one or a few social situations, which tend to be social performance (rather than interactional) situations (eg, public speaking; writing in front of others). PHARMACOTHERAPY Several classes of drugs are used to treat SAD, including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), beta-blockers, and benzodiazepines. Pharmacologic treatment is quite different for generalized versus nongeneralized SAD. We suggest SSRIs or SNRIs be used as first-line medication treatment for generalized SAD based on a combination of efficacy, tolerability, and safety. We suggest beta-blockers or benzodiazepines as first-line medication treatment for nongeneralized SAD (most commonly performance anxiety). (See 'Generalized social anxiety disorder' below and 'Nongeneralized social anxiety disorder' below.) SSRIs, SNRIs, and MAOIs all require four to six weeks to achieve an effect, and up to 16 weeks to achieve full effect. They need to be taken on a regular, daily basis. Beta-blockers and benzodiazepines achieve their effects within 30 to 60 minutes, and are used on an "as needed" basis for non-generalized SAD. Long-acting benzodiazepines may also be used on a regular (not as needed) basis for generalized SAD, as discussed below. Based on findings from numerous clinical trials, approximately one-half of patients with SAD show significant clinical improvement in response to current treatments [2,3]. There are no consistently proven predictors of response to pharmacotherapy in general, or to specific medications. We suggest that treatment with SSRIs, SNRIs, or MAOIs be continued for at least 6 to 12 months to prevent Section Editor Peter P Roy-Byrne, MD Deputy Editor Richard Hermann, MD

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relapse [4,5]. Generalized social anxiety disorder Most clinical trials of SAD in the past decade have evaluated treatments for the generalized subtype of the disorder or do not specify the subtype of patients enrolled in the study. These trials, using regular daily dosing of medication, are described in this section. "As needed" dosing for situational or nongeneralized SAD is discussed separately. (See 'Nongeneralized social anxiety disorder' below.) Whenever pharmacotherapy is prescribed for generalized SAD, it is good clinical practice to recommend to the patient that he or she enter previously feared social situations to test out the effects of the medication and to learn that these situations are safe and can be tolerated. Although there are no research data to support this claim, there is some reason to believe that those patients who do the most practicing and expanding of their social horizons while on medication are the ones who have the best longer-term outcomes. Selective serotonin reuptake inhibitors (SSRIs) SSRIs are the best studied and the most commonly prescribed of the medication treatments for SAD [2]. The SSRI paroxetine was the first medication to receive US FDA approval for SAD [6], and numerous subsequent studies have gone on to confirm efficacy for this and other SSRIs. A meta-analysis of seven trials compared SSRIs to placebo in a total of 896 patients with SAD. SSRIs resulted in greater symptom reduction and had a moderate effect size [7]. As an example, 183 patients with SAD were randomly assigned to receive paroxetine (20 to 50 mg) or placebo for 11 weeks. Patients receiving paroxetine (55 percent) were more likely to be much improved or very much improved at the end of treatment compared to patients on placebo (24 percent). The mean score on the Liebowitz Social Anxiety Scale was reduced by 39 percent in the paroxetine group, compared to 17 percent in the placebo group. The clinical effects of SSRI treatment for SAD typically require four to six weeks to have a significant impact; maximal benefit can require as long as 16 weeks [5]. Patients should be encouraged to try out the medication by engaging in social situations that typically result in anxiety and to report back about their response. One of the first indications of response is the patients report of feeling less self-conscious in typical social situations. Higher doses of SSRI typically result in better outcomes, so the dose is usually pushed to the maximum tolerated by the individual (unless an excellent response is attained at a lower dose, at which point the dose would be held there to ascertain stability of the response). Although some SSRIs have been more extensively studied than others in the treatment of SAD, there is no evidence of superiority of one SSRI over another. As examples, paroxetine can be started at 20 mg/day taken orally and, if the patient does not respond after 6 weeks, can be increased in 10 mg increments every few weeks to a maximum of 60 mg/day. Sertraline can be started at 50 mg/day taken orally and, if the patients does not respond after 6 weeks, can be increased in 50 mg every few weeks to a maximum of 250 mg/day. Common side effects of SSRIs include restlessness, agitation, headache, diarrhea, nausea and insomnia. SSRIs also cause sexual dysfunction in as many as 50 percent of patients. (See "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects" and "Sexual dysfunction associated with selective serotonin reuptake inhibitor (SSRI) antidepressants: Management".) Many of the side effects can be reduced or avoided by starting the medication at lower doses and increasing it gradually. See table for standard and lower initial doses as well as the range of therapeutic doses for SSRIs (table 1). Serotonin norepinephrine reuptake inhibitors (SNRIs) Although less well studied than the SSRIs, the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine extended release is an equally effective treatment for SAD [8-10]. One trial randomly assigned 440 patients with SAD to treatment with venlafaxine (75 to 225 mg daily extended release), paroxetine (20 to 50 mg daily), or placebo [8]. After 12 weeks, response rates were similar in the venlafaxine and paroxetine groups, both of which were superior to placebo (59 and 63 versus 36 percent response, respectively). Medication discontinuation rates were similar with venlafaxine and paroxetine, but adverse events leading to a reduction in dosage were more common with venlafaxine (16 versus 8 percent). Venlafaxine can be started at 37.5 mg/day taken orally and increased to a dose within the therapeutic range,

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between 75 and 225 mg/day (table 1). SSRI recommendations regarding gradual titration, trial duration, and dose increases apply to SNRIs as well. The most common side effects of venlafaxine are nausea, dizziness, insomnia, sedation and constipation. Venlafaxine may cause elevations in blood pressure. Though usually small, the increases can be significant in some patients. The medication should be avoided in patients with hypertension, and blood pressure should be monitored during use. (See "Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects".) There are no published data from controlled trials on the use of another marketed SNRI, duloxetine, in the treatment of SAD. Monoamine oxidase inhibitors The monoamine oxidase inhibitors (MAOIs) have the longest track record of use for SAD, having been essentially the only pharmacotherapy available (though never FDA approved) for SAD prior to the advent of the SSRIs. However, side effects and dietary restrictions limit their use. MAOIs are generally reserved for SAD refractory to other treatments. Some practitioners feel that MAOIs are more effective than SSRIs or SNRIs, though no comparative efficacy trials have been conducted to substantiate this belief. (See "Monoamine oxidase inhibitors (MAOIs) for treating depressed adults".) Several randomized trials have found that phenelzine is an efficacious treatment for SAD, with approximately one-half of patients responding with a clinically significant reduction in symptoms [7]. A recent randomized trial that included a phenelzine arm found a response rate of 54 percent for phenelzine compared to 33 percent for placebo [11]. Phenelzine is typically started at 15 mg once or twice daily, and increased to a total dose of 60 to 90 mg/day based on response. It can take four to six weeks for a response to occur, and longer for maximal response to be attained. MAOIs cause inhibition of the MAO enzyme. Irreversible MAOIs, such as phenelzine, are incompatible with certain foods and medications (eg, cheese, aged meats, alcohol, OTC cold preparations). A potentially fatal hypertensive reaction can occur if users of MAOIs consume food containing tyramine; thus, use of irreversible MAOIs must be accompanied by a low tyramine diet. Their use is also contraindicated with other antidepressants, and over-thecounter or prescribed medications containing sympathomimetic stimulants or dextromethorphan. Other adverse effects common at therapeutic doses include postural hypotension, insomnia, paradoxical daytime sedation, sexual dysfunction, and weight gain. In many instances, these side effects can be dose limiting. Reversible inhibitors of monoamine type A Moclobemide, a reversible MAOI selective for inhibition of MAO-A has shown, at best, mixed results in randomized controlled trials of SAD [12-14]. Moclobemide is not marketed in the United States, but is available in many other countries. In contrast to non-reversible MAOIs (such as phenelzine or tranylcypromine), moclobemide does not require a low tyramine diet, and generally has fewer adverse effects overall. Although it had been hoped by practitioners that moclobemide would be as efficacious as MAOIs, its efficacy seems to be no better (perhaps even less) than that of SSRIs or SNRIs. Beta adrenergic blockers Beta-blockers are not an effective treatment for generalized SAD [15,16], but are effective for nongeneralized SAD (including performance anxiety). (See 'Nongeneralized social anxiety disorder' below.) Benzodiazepines Only two, small randomized controlled trials have been published, which found the high potency benzodiazepines, alprazolam [17] and clonazepam [18], to be efficacious as monotherapy in the reduction of SAD symptoms. Another study found modest evidence of superiority of an SSRI plus clonazepam compared to SSRI alone in the treatment of generalized SAD [19]. Sedation and the potential for abuse and dependence limit the usefulness of these agents. Benzodiazepines should generally be avoided in patients with a history of alcohol or other substance abuse; though judicious prescription of benzodiazepines can be undertaken in such patients when other treatments are ineffective. Clonazepam, a longer-acting agent with a slower rate of onset, seems to be more commonly used for generalized SAD than other benzodiazepines. Sedation, the principal dose-limiting adverse effect, can be minimized by starting with low doses and titrating upwards slowly until a satisfactory response is achieved. Clonazepam can be started at 0.25 to 0.50 mg twice daily, to a maximum of 2 mg twice daily.

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Other agents Gabapentin (an anticonvulsant) and the related compound pregabalin (marketed for certain types of neuropathic pain and for fibromyalgia), have demonstrated modest effectiveness (response rates <45 percent) for generalized SAD [20,21]. The role of these compounds in the treatment of SAD is unclear, but some practitioners will consider using either of them as monotherapy (in cases where a benzodiazepine is desired, but the patient has a substance abuse history) or, more commonly, as an adjunct to an SSRI or SNRI. Doses of gabapentin for SAD typically range from 900 mg to 3600 mg daily in three divided doses. Doses of pregabalin for SAD typically range from 150 to 600 mg per day. Mirtazapine (30 mg a day) was found to be efficacious for SAD in a randomized control trial of 66 women [22]. In a more recent randomized controlled trial of 60 men and women with generalized SAD randomized to either 30 to 45 mg/day (n= 30) or placebo (n= 30) for 12 weeks, mirtazapine was no more effective than placebo (13 percent versus 13 percent response rate). The tricyclic antidepressants (TCAs) have not been well studied in clinical trials of patients with SAD. A small open-label trial of imipramine suggested that it was not effective. It is possible that TCAs with more potent serotonergic reuptake blockade (eg, clomipramine) might be useful, but this is unknown. Very small randomized controlled trials of olanzapine and quetiapine suggested that these atypical (or secondgeneration) antipsychotics might be effective for SAD [23,24]. Considerable further study is needed as well as consideration of metabolic side effects of these agents [25]. The limited available data suggest that buspirone is ineffective as monotherapy for SAD [26]. Atomoxetine, a selective norepinephrine reuptake inhibitor (marketed for the treatment of attention deficit disorder/hyperactivity) was not shown to be effective for generalized SAD in a small randomized controlled trial [27]. However, there is some evidence from a trial in adults with comorbid ADHD and SAD [28] that atomoxetine may be helpful for both ADHD and SAD symptoms in patients who have both . Pharmacotherapy augmentation or switching A substantial number of patients respond only partially to monotherapy for generalized SAD [2], this has generated interest in strategies that combine SSRIs (or SNRIs) with other agents. Small trials yielded positive results augmenting SSRIs with buspirone [29], but equivocal results from augmentation with clonazepam [19] or and negative results from augmentation with pindolol [30]. MAOIs should not be combined with other antidepressants. (See "Serotonin syndrome".) There are no available data on whether switching from one SSRI to another, or from an SSRI to an SNRI, is useful in the treatment of non-responders to initial therapy. Nongeneralized social anxiety disorder In nongeneralized or circumscribed SAD, symptoms are limited to specific performances or circumstances, and are often described as performance anxiety. For this reason, medication treatment is often prescribed on an "as needed" basis. We suggest benzodiazepines or beta-blockers as first-line medication treatment. Administering a test dose prior to treatment can be useful to assess the drug's effects. Benzodiazepines Benzodiazepines can also be used on an "as needed" basis to treat nongeneralized SAD [3]. Clonazepam 0.25 to 1 mg or lorazepam 0.5 to 2 mg can be given 30 to 60 minutes before the performance. Tolerance and physical dependence are not a concern with occasional use. But the potential for abuse, highest in persons with a history of alcohol or other substance use, should also limit their use in this context. Sedation can be a side effect of benzodiazepines, particularly at higher doses. For this reason, the patient should be encouraged to try out the medication in advance of a potentially precipitating event to determine how well it is tolerated and to see if it is efficacious. The prescribing physician may need to fine-tune the dose for the individual. Patients may have used alcohol in the past to cope with similar situations and should be explicitly cautioned not to mix alcohol with benzodiazepines. Beta-adrenergic blockers Several small trials have found beta-blockers to reduce performance anxiety (including public speaking). However, these studies were conducted with normal or anxious volunteers rather than individuals diagnosed with SAD. Beta-adrenergic blockers may be most useful for patients who have prominent awareness of physiological symptoms such as tachycardia or tremor. Propranolol can be taken orally 30 to 60 minutes prior to the anxiety-inducing situation, at a dose of 20 to 60 mg.

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The patient should be encouraged to try out the medication in advance of a potentially precipitating event to determine how well it is tolerated and to see if it is efficacious. The prescribing physician may need to fine-tune the dose for the individual. Contraindications to the prescription of beta-blockers include: a history of beta-blocker intolerance or allergy, asthma, diabetes, and certain cardiac conditions (eg, conduction problems). (See "Major side effects of beta blockers".) COMBINED PSYCHOLOGICAL AND PHARMACOLOGICAL TREATMENT CBT and antidepressants Several trials have assessed clinical interventions combining antidepressant medication and CBT for generalized SAD, but evidence of an additive effect for combining the two modalities is mixed [11,29,31]. A randomized trial of 128 patients with generalized SAD found group CBT and phenelzine was more effective than either intervention individually or pill placebo [11]. The combination of CBT and phenelzine resulted in a higher response rate (71.9 percent) than placebo (33.3 percent), CBT alone (47.1 percent), or phenelzine alone (54.3 percent). In a trial of 295 patients with generalized SAD, patients were randomized to one of five groups: fluoxetine, group CBT, combined group CBT and placebo, combined group CBT and fluoxetine, or placebo [31]. A higher proportion of patients responded to fluoxetine (51 percent), group CBT (52 percent), combined group CBT and placebo (51 percent) and combined group CBT and fluoxetine (54 percent) than to placebo (32 percent). However, the group receiving combined medication and CBT did not differ significantly in response compared to groups receiving either monotherapy In addition, the combination sertraline and exposure therapy did not show greater effectiveness than either modality individually in a randomized trial [29]. CBT and d-cycloserine Two small randomized trials have found that d-cycloserine, a partial N-methyld-aspartate (NMDA) receptor agonist believed to enhance certain kinds of learning, enhanced the efficacy of CBT for SAD when the medication was provided prior to the exposures [32,33]. It is unclear if the effect of d-cycloserine is to accelerate response to CBT, thereby requiring fewer CBT sessions to achieve a response, or whether it can truly augment response, yielding a superior overall response rate than CBT alone. The use of d-cycloserine to augment CBT is still experimental, and cannot be recommended at present. TREATMENT SELECTION There are no empirically-derived algorithms for treating SAD. Based on available data and clinical experience, we approach the disorder as follows. Generalized social anxiety disorder We recommend either pharmacotherapy or CBT for initial treatment of SAD. Both treatments reduce social anxiety compared to placebo. The selection between pharmacotherapy and CBT should be made on the basis of informed patient preference and treatment availability. Randomized trials comparing CBT to pharmacotherapy for SAD have not demonstrated superiority of one treatment over the other [11,29,31]. (See 'CBT and antidepressants' above.) Onset of symptom response may be faster with pharmacotherapy, although CBT appears to result in a more durable response [5]. If medication is chosen for first-line treatment for generalized SAD, we suggest use of an SSRI or an SNRI. (See 'Selective serotonin reuptake inhibitors (SSRIs)' above and 'Serotonin norepinephrine reuptake inhibitors (SNRIs)' above.) If only a partial response is achieved from an SSRI or CBT, the addition of the other modality in a stepped care approach may be helpful, although this has not been adequately studied. If pharmacotherapy has been selected and an SSRI has not led to an adequate response after 12 weeks, an SNRI can be used (or vice-versa). With appropriate precautions (ie, restrictions on diet and certain medications), an irreversible MAOI such as phenelzine can be used to treat generalized SAD that has been refractory to treatment with other medications. The MAOI should be used in place of the previous antidepressant, not in conjunction with it. The prior antidepressant should be stopped at least two weeks before beginning an MAOI to avoid precipitating a hypertensive reaction or serotonin syndrome. This wash out would be longer, up to five weeks, for antidepressants that have a longer half

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life, eg, fluoxetine. (See 'Monoamine oxidase inhibitors' above and "Serotonin syndrome".) Nongeneralized social anxiety disorder We suggest treating SAD that is restricted to only a performance or another discrete circumstance with either CBT or a medication. CBT would be most useful when the feared situation will be regularly encountered by the individual, while an as needed dose of medication is better suited to situations that are only rarely or occasionally encountered, or where the patient prefers medication or where CBT is not available. When treating nongeneralized SAD with medication, we suggest treatment with a benzodiazepine for patients who lack a history of a substance use disorder and do not experience sedation. Clonazepam (0.25 to 1 mg) or lorazepam (0.5 to 2 mg) can be given 30 to 60 minutes before a performance. For patients without contraindications to their use, treatment with a beta-blocker is a reasonable alternative. Propranolol (20 to 60 mg) can be given 30 to 60 minutes before the anxiety-inducing situation. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topic (see "Patient information: Social anxiety disorder (The Basics)") SUMMARY AND RECOMMENDATIONS Social anxiety disorder (SAD), also known as social phobia, is characterized by an individual's unreasonable fear of embarrassment in social or performance situations, which he or she either avoids or experiences with intense anxiety. (See 'Introduction' above and 'Subtypes of social anxiety' above.) In generalized SAD, distressing fears are experienced in multiple social situations that typically include social interaction. In nongeneralized or circumscribed SAD, fears are limited to one or a few social situations, which tend to be performance rather than interactional situations. Generalized social anxiety disorder Whenever pharmacotherapy is prescribed for generalized SAD, it is good clinical practice to recommend to the patient that he enter previously feared social situations to test out the effects of the medication and to learn that these situations are safe and can be tolerated. (See 'Generalized social anxiety disorder' above.) We recommend first-line treatment of patients with generalized SAD with an antidepressant or cognitive behavioral therapy (CBT) (Grade 1A). Selection between them can be made on the basis of informed patient preference and treatment availability. (See 'Treatment selection' above.) When pharmacotherapy is preferred, we suggest selective serotonin reuptake inhibitors (SSRIs) or SNRIs for first-line medication treatment of generalized SAD (Grade 2B). Paroxetine, an SSRI, can be started at 20 mg/day taken orally and, if the patient does not respond after 6 weeks, can be increased to a maximum of 60 mg/day. (See 'Selective serotonin reuptake inhibitors (SSRIs)' above.) Venlafaxine, an SNRI, can be started at 37.5 mg/day taken orally and increased to a dose within the therapeutic range (between 75 and 225 mg/day). (See 'Serotonin norepinephrine reuptake inhibitors (SNRIs)' above.) Other agents with some (but considerably less) support for efficacy in SAD include gabapentin and

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pregabalin. SSRIs, SNRIs, and MAOIs may take four to six weeks for an initial response and 12 to 16 weeks to achieve their full effect. These or other medications for generalized SAD should be continued for at least 6 to 12 months to decrease the likelihood of relapse. Some patients may need continuing treatment to maintain the gains achieved. (See 'Pharmacotherapy' above.) Nongeneralized social anxiety disorder We suggest treating SAD that is restricted to a performance or another discrete circumstance, which is rarely or only occasionally encountered, with medication rather than psychotherapy ( Grade 2C). (See 'Nongeneralized social anxiety disorder' above.) For patients who lack a history of a substance use disorder and do not experience sedation, we suggest treatment with a benzodiazepine. (Grade 2C). Clonazepam (0.25 to 1 mg) or lorazepam (0.5 to 2 mg) can be given 30 to 60 minutes before a performance. (See 'Benzodiazepines' above.) For patients without contraindications to their use, a beta-blocker is a reasonable alternative. Propranolol (20 to 60 mg) can be given 30 to 60 minutes before the anxiety-inducing situation. (See 'Beta-adrenergic blockers' above.) We suggest treating SAD that is restricted to a performance or another discrete circumstance, which would be encountered more regularly, with cognitive behavioral therapy (CBT) rather than medication (Grade 2C); however, this choice can reasonably be made on the basis of treatment availability or patient preference. (See 'Nongeneralized social anxiety disorder' above and "Psychotherapy for social anxiety disorder".) Use of UpToDate is subject to the Subscription and License Agreement. Topic 505 Version 9.0

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GRAPHICS Antidepressant medications: dosing and half-life information

Trade name (US) Usual starting dose (mg)* Low starting dose (mg)* Usual daily dose (mg) Available oral doses (mg) Mean half-life, hours (active metabolites)

Generic drug name

Selective serotonin reuptake inhibitors Citalopram Escitalopram Fluoxetine Fluoxetine Weekly Fluvoxamine Paroxetine Paroxetine CR Sertraline Zoloft 50 12.5 to 25 Celexa Lexapro Prozac Prozac Weekly Luvox Paxil Paxil CR 20 10 20 90 50 20 25 25 5 to 10 5 to 10 5 20 to 40 10 to 20 20 to 60 NA 50 to 20 to 60 25 to 62.5 50 to 200 10, 20, 40, L 5, 10, 20, L 10, 20, 40, L 90 25, 50, 100 10, 20, 30, 40, L 12.5, 25, 37.5 25, 50, 100 26 (66) 15 to 20 35 27 to 32 72 (216) 15 20

300

Serotonin-norepinephrine reuptake inhibitors Duloxetine Venlafaxine Venlafaxine XR Cymbalta Effexor Effexor XR 30 37.5 37.5 60 to 90 75 to 225 75 to 225 20, 30, 60 25, 37.5, 50, 75, 100 37.5, 75, 150 12 5 (11) 5 (11)

L: liquid; NA: not applicable; CR: controlled release; XR: extended release. * Lower starting doses are recommended for elderly patients and patients with panic disorder, significant anxiety, or hepatic disease. Mean half-lives of active metabolites are given in parentheses. Dose varies with diagnosis. Refer to text for specific guidelines. Maximum recommended dose of citalopram is 20 mg for patients >60 years of age, with significant hepatic insufficiency, or taking interacting medications that can increase citalopram levels. Refer to topics on unipolar depression for more information. Specific interactions of citalopram with other medications may be determined using the drug interactions tool (Lexi-Interact Online) included in UpToDate. This tool can be accessed from the UpToDate online search page or through the individual drug information topics in the section on Drug interactions. Data from: Martinez M, Marangell LB, Martinez JM. Psychopharmacology. In: American Psychiatric Publishing Textbook of Psychiatry, 5th ed, Hales RE, Yudofsky SC, Gabbard, GO (Eds), American Psychiatric Publishing, Inc, 2008.

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