Uses
Citalopram hydrobromide is used in the treatment of major depressive disorder. In addition, citalopram has been used for the treatment of obsessive-compulsive disorder, panic disorder, social phobia (social anxiety disorder), alcohol dependence, premenstrual dysphoric disorder, premature ejaculation, eating disorders, diabetic neuropathy, and posttraumatic stress disorder.
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Major Depressive Disorder
Citalopram hydrobromide is used in the treatment of major depressive disorder. A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks). According to DSM-IV criteria, a major depressive episode includes at least 5 of the following 9 symptoms (with at least one of the symptoms being either depressed mood or loss of interest or pleasure): depressed mood most of the day as indicated by subjective report (e.g., feels sad or empty) or observation made by others; markedly diminished interest or pleasure in all, or almost all, activities most of the day; significant weight loss (when not dieting) or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite; insomnia or hypersomnia; psychomotor agitation or retardation (observable by others, not merely subjective feelings of restlessness or being slowed down); fatigue or loss of energy; feelings of worthlessness or excessive or inappropriate guilt (not merely self-reproach or guilt about being sick); diminished ability to think or concentrate or indecisiveness (either by subjective account or as observed by others); and recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or specific plan for committing suicide.
Treatment of major depressive disorder generally consists of an acute phase (to induce remission), a continuation phase (to preserve remission), and a maintenance phase (to prevent recurrence). Various interventions (e.g., psychotherapy, antidepressant drug therapy, electroconvulsive therapy [ECT]) are used alone or in combination to treat major depressive episodes. Treatment should be individualized, and the most appropriate strategy for a particular patient is determined by clinical factors such as severity of depression (e.g., mild, moderate, severe), presence or absence of certain psychiatric features (e.g., suicide risk, catatonia, psychotic or atypical features, alcohol or substance abuse or dependence, panic or other anxiety disorder, cognitive dysfunction, dysthymia, personality disorder, seasonal affective disorder), and concurrent illness (e.g., asthma, cardiac disease, dementia, seizure disorder, glaucoma, hypertension). Demographic and psychosocial factors as well as patient preference also are used to determine the most effective treatment strategy.
While use of psychotherapy alone may be considered as an initial treatment strategy for patients with mild to moderate major depressive disorder (based on patient preference and presence of clinical features such as psychosocial stressors), combined use of antidepressant drug therapy and psychotherapy may be useful for initial treatment of patients with moderate to severe major depressive disorder with psychosocial issues, interpersonal problems, or a comorbid axis II disorder. In addition, combined use of antidepressant drug therapy and psychotherapy may be beneficial in patients who have a history of poor compliance or only partial response to adequate trials of either antidepressant drug therapy or psychotherapy alone.
Antidepressant drug therapy can be used alone for initial treatment of patients with mild major depressive disorder (if preferred by the patient) and usually is indicated alone or in combination with psychotherapy for initial treatment of patients with moderate to severe major depressive disorder (unless ECT is planned). ECT is not generally used for initial treatment of uncomplicated major depression, but is recommended as first-line treatment for severe major depressive disorder when it is coupled with psychotic features, catatonic stupor, severe suicidality, food refusal leading to nutritional compromise, or other situations when a rapid antidepressant response is required. ECT also is recommended for patients who have previously shown a positive response to or a preference for this treatment modality and can be considered for patients with moderate or severe depression who have not responded to or cannot receive antidepressant drug therapy. In certain situations involving depressed patients unresponsive to adequate trials of several individual antidepressant agents, adjunctive therapy with another agent (e.g., buspirone, lithium) or concomitant use of a second antidepressant agent (e.g., bupropion) has been used; however, such combination therapy is associated with an increased risk of adverse reactions, may require dosage adjustments, and (if not contraindicated) should be undertaken only after careful consideration of the relative risks and benefits.
(See Drug Interactions: Serotonergic Drugs ,Tricyclic and Other Antidepressants under Drug Interactions: Drugs Undergoing Hepatic Metabolism or Affecting Hepatic Microsomal Enzymes , andDrug Interactions: Lithium.) The efficacy of citalopram for the management of major depression has been established in short-term (4-6 weeks' duration), placebo-controlled studies in outpatients 18-66 years of age who met DSM-III or -III-R criteria for major depressive disorder. In a 6-week study in which patients received fixed citalopram dosages of 10, 20, 40, or 60 mg daily, the drug was effective at dosages of 40 and 60 mg daily as measured by the Hamilton Depression Rating Scale (HAM-D) Total Score, the HAM-D Depressed Mood Item (Item 1), the Montgomery Asberg Depression Rating Scale, and the Clinical Global Impression (CGI) Severity Scale. This study showed no clear antidepressant effect of the 10 or 20 mg daily dosages, and the 60 mg daily dosage was not more effective than the 40 mg daily dosage.
In a 4-week, placebo-controlled study in depressed adult patients, of whom 85% met criteria for melancholia, those who were treated with citalopram (at an initial dosage of 20 mg daily, titrated to the maximum tolerated dosage or to a maximum daily dosage of 80 mg) showed greater improvement than patients receiving placebo on the HAM-D Total Score, HAM-D Item 1, and the CGI Severity score. In 3 additional placebo-controlled depression trials, the difference in response to treatment between patients receiving citalopram and patients receiving placebo was not statistically significant, possibly due at least in part to a high spontaneous response rate, a high placebo response rate, small sample size, or, in the case of one study, too low a dosage.
In 2 placebo-controlled studies, depressed adult patients who had responded to an initial 6- to 8-week course of citalopram (fixed dosage of 20 or 40 mg daily in one study and flexible dosages ranging from 20-60 mg daily in the second study) were randomized to continue receiving citalopram or placebo for up to 6 months. In both of these studies, patients receiving citalopram experienced substantially lower relapse rates over the subsequent 6 months compared with those receiving placebo. In the fixed-dose study, the decreased rate of depression relapse was similar in patients receiving 20 or 40 mg daily of citalopram. An analysis of these data for possible age-, gender-, and race-related effects on treatment outcome did not suggest any difference in antidepressant efficacy based on the age, gender, and race of the patient. In a placebo-controlled trial, citalopram also was shown to help prevent recurrences of depression in patients with recurrent major depression receiving the drug for up to 6-18 months.
While the optimum duration of citalopram therapy has not been established, many experts state that acute depressive episodes require several months or longer of sustained antidepressant therapy. In addition, some clinicians recommend that long-term antidepressant therapy be considered in certain patients at risk for recurrence of depressive episodes (such as those with highly recurrent unipolar depression). In placebo-controlled studies, citalopram has been shown to be effective for the long-term (e.g., up to 18 months) management of depression. In addition, the drug has been used in some patients for longer periods (e.g., up to 28 months) without apparent loss of clinical effect or increased toxicity. However, when citalopram is used for extended periods, the need for continued therapy should be reassessed periodically.
(See Dosage and Administration: Dosage.) The manufacturer states that efficacy of citalopram as an antidepressant in hospital settings has not been studied adequately to date; however, the drug has been shown to be effective in hospitalized patients with depression, including severe depression, in several studies.
As with other antidepressants, the possibility that citalopram may precipitate hypomanic or manic attacks in patients with bipolar or other major affective disorder should be considered. Citalopram is not approved for use in treating bipolar depression.
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Considerations in Choosing an Antidepressant
A variety of antidepressant drugs are available for the treatment of major depressive disorder, including selective serotonin-reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs; e.g., desvenlafaxine, duloxetine, venlafaxine), tricyclic antidepressants (e.g., amitriptyline, amoxapine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine), monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine), and other antidepressants (e.g., bupropion, maprotiline, nefazodone, trazodone, vilazodone). Most clinical studies have shown that the antidepressant effect of usual dosages of citalopram in patients with depression is greater than that of placebo and comparable to that of usual dosages of tricyclic antidepressants (e.g., amitriptyline, imipramine, clomipramine), other SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline), and other antidepressants (e.g., mirtazapine, venlafaxine). Escitalopram, the active S-enantiomer of citalopram, also is commercially available for the treatment of depression. Although there is some evidence that escitalopram may offer some clinical advantages compared with citalopram or other SSRIs (e.g., increased efficacy, more rapid onset of therapeutic effect, fewer adverse effects), additional studies are needed to confirm these initial findings. The onset of antidepressant action of citalopram appears to be comparable to that of tricyclic antidepressants and other SSRIs, although there is some evidence that the onset of action may occur slightly earlier with citalopram than with some other antidepressants, including sertraline. However, additional study is needed to confirm these findings.
In general, response rates in patients with major depression are similar for currently available antidepressants, and the choice of antidepressant agent for a given patient depends principally on other factors such as potential adverse effects, safety or tolerability of these adverse effects in the individual patient, psychiatric and medical history, patient or family history of response to specific therapies, patient preference, quantity and quality of available clinical data, cost, and relative acute overdose safety. No single antidepressant can be recommended as optimal for all patients because of substantial heterogeneity in individual responses and in the nature, likelihood, and severity of adverse effects. In addition, patients vary in the degree to which certain adverse effects and other inconveniences of drug therapy (e.g., cost, dietary restrictions) affect their preferences.
In the large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR*D) effectiveness trial, patients with major depressive disorder who did not respond to or could not tolerate citalopram therapy were randomized to switch to extended-release (''sustained-release'') bupropion, sertraline, or extended-release venlafaxine as a second step of treatment (level 2). Remission rates as assessed by the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Quick Inventory of Depressive Symptomatology--Self Report (QIDS-SR-16) were approximately 21 and 26% for extended-release bupropion, 18 and 27% for sertraline, and 25 and 25% for extended-release venlafaxine therapy, respectively; response rates as assessed by the QIDS-SR-16 were 26, 27, and 28% for extended-release bupropion, sertraline, and extended-release venlafaxine therapy, respectively. These results suggest that after unsuccessful initial treatment of depressed patients with an SSRI, approximately 25% of patients will achieve remission after therapy is switched to another antidepressant, and either another SSRI (e.g., sertraline) or an agent from another class (e.g., bupropion, venlafaxine) may be reasonable alternative antidepressants in patients not responding to initial SSRI therapy.
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Patient Tolerance Considerations
Because of differences in the adverse effect profile between selective serotonin-reuptake inhibitors and tricyclic antidepressants, particularly less frequent anticholinergic effects, cardiovascular effects, and/or weight gain with selective serotonin-reuptake inhibitors, these drugs may be preferred in patients in whom such effects are not tolerated or are of potential concern. The decreased incidence of anticholinergic effects associated with citalopram and other selective serotonin-reuptake inhibitors compared with tricyclic antidepressants is a potential advantage, since such effects may result in discontinuance of the drug early during therapy in unusually sensitive patients. In addition, some anticholinergic effects may become troublesome during long-term tricyclic antidepressant therapy (e.g., persistent dry mouth may result in tooth decay). Although selective serotonin-reuptake inhibitors share the same overall tolerability profile, certain patients may tolerate one drug in this class better than another. Antidepressants other than selective serotonin-reuptake inhibitors may be preferred in patients in whom certain adverse GI effects (e.g., nausea, anorexia), nervous system effects (e.g., anxiety, nervousness, insomnia), and/or weight loss are not tolerated or are of concern, since such effects appear to occur more frequently with citalopram and other drugs in this class.
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Pediatric Considerations
The clinical presentation of depression in children and adolescents can differ from that in adults and generally varies with the age and developmental stages of the child. Younger children may exhibit behavioral problems such as social withdrawal, aggressive behavior, apathy, sleep disruption, and weight loss; adolescents may present with somatic complaints, self-esteem problems, rebelliousness, poor performance in school, or a pattern of engaging in risky or aggressive behavior.
Only limited data are available to date from controlled clinical studies evaluating various antidepressant agents in children and adolescents, and many of these studies have methodologic limitations (e.g., nonrandomized or uncontrolled, small sample size, short duration, nonspecific inclusion criteria). However, there is some evidence that the response to antidepressants in pediatric patients may differ from that seen in adults, and caution should be used in extrapolating data from adult studies when making treatment decisions for pediatric patients.
Results of several studies evaluating tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline) in preadolescent and adolescent patients with major depression indicate a lack of overall efficacy in this age group. Based on the lack of efficacy data regarding use of tricyclic antidepressants and MAO inhibitors in pediatric patients and because of the potential for life-threatening adverse effects associated with the use of these drugs, many experts consider selective serotonin-reuptake inhibitors, including citalopram, the drugs of choice when antidepressant therapy is indicated for the treatment of major depressive disorder in children and adolescents. However, the US Food and Drug Administration (FDA) states that, while efficacy of fluoxetine has been established in pediatric patients, efficacy of other newer antidepressants (i.e., citalopram, desvenlafaxine, duloxetine, escitalopram, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, venlafaxine) was not conclusively established in clinical trials in pediatric patients with major depressive disorder. In addition, FDA now warns that antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders.
(See Cautions: Pediatric Precautions.) FDA currently states that anyone considering using an antidepressant in a child or adolescent for any clinical use must balance the potential risk of therapy with the clinical need.(See Cautions: Precautions and Contraindications.)
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Geriatric Considerations
The response to antidepressants in depressed geriatric patients without dementia is similar to that reported in younger adults, but depression in geriatric patients often is not recognized and is not treated. In geriatric patients with major depressive disorder, SSRIs appear to be as effective as tricyclic antidepressants but may cause fewer overall adverse effects than these other agents. Geriatric patients appear to be especially sensitive to anticholinergic (e.g., dry mouth, constipation, vision disturbance), cardiovascular, orthostatic hypotensive, and sedative effects of tricyclic antidepressants. The low incidence of anticholinergic effects associated with citalopram and other SSRIs compared with tricyclic antidepressants is a potential advantage in geriatric patients, since such effects (e.g., constipation, dry mouth, confusion, memory impairment) may be particularly troublesome in these patients. However, SSRI therapy may be associated with other troublesome adverse effects (e.g., nausea and vomiting, agitation and akathisia, parkinsonian adverse effects, sexual dysfunction, weight loss, and hyponatremia). Some clinicians state that SSRIs including citalopram may be preferred for treating depression in geriatric patients in whom the orthostatic hypotension associated with many antidepressants (e.g., tricyclics) potentially may result ininjuries (such as severe falls). However, despite the fewer cardiovascular and anticholinergic effects associated with SSRIs, these drugs did not show any advantage over tricyclic antidepressants with regard to hip fracture in a case-control study. In addition, there was little difference in the rates of falls between nursing home residents receiving SSRIs and those receiving tricyclic antidepressants in a retrospective study. Therefore, all geriatric patients receiving either type of antidepressant should be considered at increased risk of falls and appropriate measures should be taken. In addition, clinicians prescribing SSRIs in geriatric patients should be aware of the many possible drug interactions associated with these drugs, including those involving metabolism of the drugs through the cytochrome P-450 system.
(See Drug Interactions.) Patients with dementia of the Alzheimer's type (Alzheimer's disease, presenile or senile dementia) often present with depressive symptoms, such as depressed mood, appetite loss, insomnia, fatigue, irritability, and agitation. Most experts recommend that patients with dementia of the Alzheimer's type who present with clinically significant and persistent depressive symptoms be considered as candidates for pharmacotherapy even if they fail to meet the criteria for a major depressive syndrome. The goals of such therapy are to improve mood, functional status (e.g., cognition), and quality of life. Treatment of depression also may reduce other neuropsychiatric symptoms associated with depression in patients with dementia, including aggression, anxiety, apathy, and psychosis. Although patients may present with depressed mood alone, the possibility of more extensive depressive symptomatology should be considered. Therefore, patients should be evaluated and monitored carefully for indices of major depression, suicidal ideation, and neurovegetative signs since safety measures (e.g., hospitalization for suicidal ideations) and more vigorous and aggressive therapy (e.g., relatively high dosages, multiple drug trials) may be needed in some patients.
Although placebo-controlled trials of antidepressants in depressed patients with concurrent dementia have shown mixed results, the available evidence and experience with the use of antidepressants in patients with dementia of the Alzheimer's type and associated depressive manifestations indicate that depressive symptoms (including depressed mood alone and with neurovegetative changes) in such patients are responsive to antidepressant therapy. In some patients, cognitive deficits may partially or fully resolve during antidepressant therapy, but the extent of response will be limited to the degree of cognitive impairment that is directly related to depression. SSRIs such as citalopram, escitalopram, fluoxetine, paroxetine, or sertraline generally are considered first-line agents in the treatment of depressed patients with dementia since they usually are better tolerated than some other antidepressants (e.g., tricyclic antidepressants, monoamine oxidase inhibitors). Some possible alternative agents to SSRIs include bupropion, mirtazapine, and venlafaxine. Some geriatric patients with dementia and depression may be unable to tolerate the antidepressant dosages needed to achieve full remission. When a rapid antidepressant response is not critical, some experts therefore recommend a very gradual dosage titration to increase the likelihood that a therapeutic dosage of the SSRI or other antidepressant will be reached and tolerated. In a controlled study comparing citalopram and placebo in elderly patients with dementia, citalopram was found to improve depression as well as cognitive and emotional functioning more than placebo. In an open study in a limited number of patients with dementia and behavioral disturbances, citalopram was found to improve the behavioral complications associated with dementia.
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Cardiovascular Considerations
Clinical studies of citalopram for the management of depression generally did not include individuals with cardiovascular disease (e.g., those with a recent history of myocardial infarction or unstable cardiovascular disease).
Citalopram causes dose-dependent QTc-interval prolongation, and torsades de pointes, ventricular tachycardia, and sudden death have been reported in postmarketing experience in patients receiving the drug. Patients with congenital long QT syndrome, uncompensated heart failure, bradyarrhythmias, recent acute myocardial infarction, or hypokalemia or hypomagnesemia or who are receiving other drugs that prolong the QT interval are at higher risk of developing torsades de pointes.
(See Cautions: Cardiovascular Effects ,Cautions: Precautions and Contraindications , andDrug Interactions: Drugs that Prolong the QT Interval .)
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Sedative Considerations
Because citalopram and other selective serotonin-reuptake inhibitors generally are less sedating than some other antidepressants (e.g., tricyclics), some clinicians state that these drugs may be preferable in patients who do not require the sedative effects associated with many antidepressant agents or in patients who are prone to accidents; however, an antidepressant with more prominent sedative effects (e.g., trazodone) may be preferable in certain patients (e.g., those with insomnia).
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Suicidal Risk Considerations
Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidal thinking and behavior (suicidality) in certain patients during the early phases of treatment. FDA states that antidepressants increased the risk of suicidality in short-term studies in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders.
(See Cautions: Pediatric Precautions.) An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age and a reduced risk was observed in adults 65 years of age or older. It currently is unknown whether the suicidality risk extends to longer-term antidepressant use (i.e., beyond several months); however, there is substantial evidence from placebo-controlled maintenance trials in adults with major depressive disorder that antidepressants can delay the recurrence of depression. Because the risk of suicidality in depressed patients may persist until substantial remission of depression occurs, appropriate monitoring and close observation of patients of all ages who are receiving antidepressant therapy are recommended.(See Cautions: Precautions and Contraindications.)
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Other Considerations
Citalopram has been effective in patients with moderate to severe depression, endogenous depression, post-stroke depression and pathologic crying, and depression associated with chronic hepatitis C virus infection.
In an open study in a limited number of patients with bipolar depression (mainly bipolar I disorder), citalopram was effective and well tolerated when added to monotherapy or combined therapy with lithium, divalproex sodium, and/or carbamazepine. Controlled studies are needed to confirm these preliminary findings. The manufacturer states that citalopram is not approved for use in treating bipolar depression, and that the possibility that the drug may precipitate hypomanic or manic attacks in patients with bipolar or other major affective disorder should be considered. For detailed information on bipolar disorder, including its management, .
In patients with refractory depression, citalopram was more effective when given in combination with buspirone in one placebo-controlled study. However, combined citalopram and buspirone therapy was not found to be more effective than citalopram monotherapy in another placebo-controlled study. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) level 2 trial, patients with major depressive disorder who did not respond to or could not tolerate citalopram therapy were randomized to receive either extended-release (''sustained-release'') bupropion or buspirone therapy in addition to citalopram. Although both extended-release bupropion and buspirone were found to produce similar remission rates, extended-release bupropion produced a greater reduction in the number and severity of symptoms and a lower rate of drug discontinuance than buspirone in this large-scale effectiveness trial. These results suggest that augmentation of SSRI therapy with extended-release bupropion may be useful in some patients with refractory depression. The addition of lithium to citalopram in depressed patients not responding to citalopram alone also has been found to be effective and well tolerated in a double-blind, placebo-controlled trial.
(See Drug Interactions: Lithium.) In a limited number of depressed patients not responding to citalopram alone, the addition of carbamazepine was effective and well tolerated in an open study. However, the possibility of serotonin syndrome and drug interactions should be considered pending further clinical experience with this combination.
(See Drug Interactions: Serotonergic Drugs andCarbamazepine under Drug Interactions: Drugs Undergoing Hepatic Metabolism or Affecting Hepatic Microsomal Enzymes.) Citalopram was found to improve personality disturbances (decrease in anxiety and aggression-related symptoms and increase in social desirability and socialization) in depressed patients in one study.
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Obsessive-Compulsive Disorder
Citalopram has been used in the treatment of obsessive-compulsive disorder. In a large, double-blind, placebo-controlled trial evaluating citalopram (20, 40, or 60 mg daily for 12 weeks) in adults with obsessive-compulsive disorder, the drug was more effective than placebo as measured by Yale-Brown Obsessive-Compulsive Scale score changes at all 3 dosages. The highest response rate (65%) was observed in those who received 60 mg daily; this compared with 52 or 57% in those receiving 40 or 20 mg daily, respectively. An analysis of predictors of response to citalopram therapy from this trial suggested that patients with a longer duration of obsessive-compulsive disorder, more severe symptoms, or a history of previous selective serotonin-reuptake inhibitor therapy were less likely to respond to therapy with citalopram. In an open trial, 76% of patients with obsessive-compulsive disorder receiving citalopram therapy (usually 40 or 60 mg daily) for 24 weeks demonstrated improved symptoms associated with this condition. In another open study, citalopram (40 mg daily) was effective in a limited number of patients with refractory obsessive-compulsive disorder who had failed to respond to therapy with other selective serotonin-reuptake inhibitors. Clinical experience to date indicates that citalopram is well tolerated in patients with obsessive-compulsive disorder. Additional study is needed to determine the long-term efficacy of citalopram in the treatment of this condition.
For additional information on the use of selective serotonin-reuptake inhibitors in the treatment of obsessive-compulsive disorder, .
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Panic Disorder
Citalopram has been used in the treatment of panic disorder with or without agoraphobia. In a randomized, single-blind study comparing citalopram and paroxetine in adults with panic disorder, both drugs were found to be effective and well tolerated, with 86% of the citalopram-treated patients and 84% of the paroxetine-treated patients responding well to 2 months of therapy. In a limited number of adults with panic disorder, citalopram therapy (20-60 mg daily) produced a full remission in 66% of the patients and improved symptomatology.
In a large, double-blind, placebo-controlled trial evaluating the efficacy and tolerability of long-term therapy (up to 1 year) with citalopram at 3 dosages (10-15 mg daily, 20-30 mg daily, 40-60 mg daily) or clomipramine in adult outpatients with panic disorder with or without agoraphobia, both drugs were more effective than placebo. Citalopram was more effective than placebo at all dosages studied, with a dosage of 20-30 mg daily being the most effective maintenance dosage in most patients.
For additional information on the use of selective serotonin-reuptake inhibitors in the treatment of panic disorder,
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Social Phobia
Like some other selective serotonin-reuptake inhibitors, citalopram has been used in the treatment of social phobia (social anxiety disorder). However, additional evidence from well-designed studies is needed to more fully elucidate the role of the drug in this disorder.
In an open study in a limited number of patients with social phobia, 86% of patients responded to citalopram 40 mg daily after 12 weeks as rated by the Clinical Global Impressions (CGI) score and the Liebowitz Social Anxiety Scale (LSAS).
In an open, flexible-dose study in patients with social anxiety disorder with comorbid major depression, response rates after 12 weeks of citalopram therapy (mean dosage: 38 mg daily) were approximately 67 and 76% for social anxiety disorder and depression, respectively. However, the depression symptoms responded more rapidly and completely than the social anxiety symptoms after 12 weeks of citalopram therapy, suggesting that a longer duration of therapy may be necessary to fully assess the clinical efficacy of the drug in such patients.
In a randomized, open trial comparing citalopram and moclobemide (not commercially available in the US) in patients with social phobia, similar improvements in the CGI-improvement score and LSAS were noted with these drugs. Clinical experience to date suggests that citalopram generally is well tolerated in patients with social phobia. However, well controlled studies are needed to confirm the efficacy and safety and to determine the optimal dosage of citalopram in patients with this condition.
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Alcohol Dependence
Like some other selective serotonin-reuptake inhibitors (fluoxetine, zimelidine [not commercially available in the US]), citalopram has been used in the management of alcohol dependence. In clinical studies, citalopram has been shown to reduce alcohol consumption in alcohol-dependent, nondepressed drinkers receiving short-term therapy with 40 mg of the drug daily. In clinical studies conducted to date with selective serotonin-reuptake inhibitors in alcoholic patients, considerable interindividual variability in response has been observed, with reduction in alcohol consumption ranging from 10 to more than 70%. Several factors, including gender, alcoholic subtype, presence or absence of depression, and extent of drinking, appear to affect the clinical efficacy of selective serotonin-reuptake inhibitors in the management of alcohol dependence. Additional study is required to fully determine the safety and efficacy of citalopram in the management of alcohol dependence.
(See Pharmacology: Effects on Alcohol Intake and alsosee Drug Interactions: Alcohol.)
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Premenstrual Dysphoric Disorder
Like some other selective serotonin-reuptake inhibitors (e.g., fluoxetine, paroxetine, sertraline), citalopram has been used in a limited number of women with premenstrual dysphoric disorder (previously late luteal phase dysphoric disorder). Clinical experience to date suggests that the onset of action of serotonin-reuptake inhibitors in women with premenstrual dysphoric disorder is more rapid than when used for other psychiatric conditions; therefore, administration only during the luteal phase of the menstrual cycle may potentially be effective in this condition.
In a placebo-controlled trial, intermittent administration of citalopram (10-30 mg daily during the luteal phase) for 3 menstrual cycles appeared to be more effective than continuous (10-30 mg daily throughout the menstrual cycle) or semi-intermittent administration (5 mg daily during the follicular phase and 10-30 mg daily during the luteal phase) of the drug and substantially more effective than placebo. Citalopram was well tolerated in all 3 regimens, and adverse effects generally were mild and transient. Additional controlled studies are needed to determine whether the efficacy of the drug is sustained during longer-term, maintenance therapy in women with this condition.
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Premature Ejaculation
Like some other selective serotonin-reuptake inhibitors, citalopram has been used for the treatment of premature ejaculation. However, studies with citalopram to date have only involved a limited number of patients and there is some evidence that the drug may be less effective than certain other selective serotonin-reuptake inhibitors (e.g., paroxetine). In a double-blind study in men with premature ejaculation, citalopram 20 mg daily delayed ejaculation to a slight degree (1. 8-fold increase in intravaginal ejaculation latency time) compared with a marked increase (8. 9-fold increase) with paroxetine 20 mg daily following 6 weeks of therapy. These preliminary findings suggest that paroxetine may be more effective than citalopram in the treatment of premature ejaculation.
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Eating Disorders
Citalopram has been used in a limited number of patients for the treatment of bulimia nervosa or anorexia nervosa. Although citalopram reportedly has been effective in some patients with these eating disorders, underweight patients with anorexia nervosa who received citalopram in conjunction with psychotherapy did worse (i.e., experienced greater weight loss) than those receiving psychotherapy alone in one open-label study. Because of limited evidence and experience to date, the role if any of citalopram in the management of eating disorders remains to be elucidated. For information on the use of selective serotonin-reuptake inhibitors in the treatment of eating disorders, .
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Diabetic Neuropathy
Tricyclic antidepressants generally have been considered a mainstay of therapy for the treatment of diabetic neuropathy. However, because of potentially improved patient tolerability, therapy with selective serotonin-reuptake inhibitors or selective serotonin- and norepinephrine-reuptake inhibitors (e.g., duloxetine, venlafaxine) has been attempted as an alternative. In a double-blind, placebo-controlled trial, citalopram (40 mg daily) substantially reduced the symptoms associated with diabetic neuropathy (pain, paresthesia, and dysesthesia) in a limited number of patients and generally was well tolerated. When compared with earlier results obtained with imipramine in the management of this condition, selective serotonin-reuptake inhibitors such as citalopram, fluoxetine, paroxetine, and sertraline appear to be less effective but better tolerated overall. Additional study and experience are needed to elucidate the relative roles of selective serotonin-reuptake inhibitors versus tricyclic antidepressants, selective serotonin- and norepinephrine-reuptake inhibitors, anticonvulsants (e.g., pregabalin, gabapentin), and other forms of treatment in the management of this condition.
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Posttraumatic Stress Disorder
Citalopram has been used in a limited number of adults with civilian- or combat-related posttraumatic stress disorder (PTSD). In an open study, patients treated with citalopram for 8 weeks showed marked improvement in PTSD manifestations (reexperiencing, hyperarousal, and avoidance) as well as in depression and anxiety. Well-designed, controlled studies are needed to confirm these preliminary findings.
For additional information on the use of selective serotonin-reuptake inhibitors in the treatment of PTSD, , and