Lexapro (Escitalopram) Contraindications and Precautions
- abrupt discontinuation
- bipolar disorder
- bleeding
- breast-feeding
- cardiac disease
- children
- CNS depression
- dehydration
- driving or operating machinery
- elderly
- electroconvulsive therapy (ECT)
- ethanol intoxication
- hepatic disease
- hyponatremia
- mania
- neonates
- pregnancy
- renal failure
- renal impairment
- seizures
- suicidal ideation
Lexapro (Escitalopram) Contraindications and Precautions
Escitalopram is contraindicated for use in those patients with a hypersensitivity to the drug, hypersensitivity to the related drug citalopram, or to any of the formulation components. Escitalopram is the active isomer of racemic citalopram; therefore the two drugs should not be taken together as this would constitute duplicative therapy.
Avoid abrupt discontinuation of any SSRI if possible. Gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of potential withdrawal-like symptoms (see Adverse Reactions).
All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. If a patient develops symptoms suggestive of mania or bipolar disorder, escitalopram should be held and the appropriate therapy to treat the manic symptoms initiated.
The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as obsessive-compulsive disorder (OCD). Patients with a history of suicidal ideation and who are at high risk for suicide attempt should be closely supervised during initial drug therapy with escitalopram. In addition, escitalopram should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n=4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: antidepressants increase the risk of suicidal thinking and behavior (suicidality) in pediatric patients with MDD and other psychiatric disorders (OCD, social anxiety disorder); anyone considering the use of an antidepressant in a pediatric patient for any clinical use must balance the risk of increased suicidality with the clinical need; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increases or decreases; such observation would generally include at least weekly face-to-face contact with patients, family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between face-to-face visits; adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes; families and caregivers should be advised to closely observe the patient (adult or child) on a daily basis for the emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality, and to communicate immediately with the prescriber. It is unknown if the suicidality risk in pediatric patients extends to longer-term therapy (i.e., beyond several months) or to adult patients. In patients who exhibit changes in symptoms (see Adverse Events), worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described represent such a conversion is unknown. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that escitalopram is not approved for use in treating bipolar depression.
Escitalopram is contraindicated for concomitant use in patients receiving MAO inhibitor (MAOI) therapy (see Drug Interactions).
Escitalopram effects during electroconvulsive therapy (ECT) have not been evaluated in clinical studies to date.
Escitalopram has not been evaluated in patients with seizures or seizure disorders. In clinical trials no seizures occurred in patients receiving escitalopram. As with all drugs used for depression, use escitalopram carefully in patients with seizure disorders.
In unpublished studies, escitalopram was not associated with significant effects on blood pressure, heart rate, or the ECG. The use of escitalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable cardiac disease. Torsades de pointes, QT prolongation, and ventricular arrhythmia have been reported rarely with the use of citalopram. Caution is advisable in patients with conditions that produce altered hemodynamic responses.
Excretion of unchanged escitalopram in the urine is a minor route of elimination. Ten percent of escitalopram is excreted unchanged in the urine. Escitalopram should be used with caution in patients with severe renal impairment (i.e., CrCl < 20 ml/min) until pharmacokinetic data are available for this population. There is no information on the use of escitalopram in patients with chronic renal failure who receive hemodialysis.
Escitalopram should be used with caution in patients with hepatic disease because the drug is extensively metabolized in the liver, resulting in decreased clearance and increased plasma concentrations in patients with hepatic dysfunction. A lower maximum dosage is recommended for such patients (see Dosage). Caution is advisable in patients with conditions that produce altered metabolism
CNS depression has been reported in up to 10% of patients using escitalopram. Because any psychoactive drug may impair judgment, thinking, or motor skills, patients should use caution when driving or operating machinery, until the full effect of escitalopram is determined. Citalopram has not been shown to potentiate the cognitive and motor effects of alcohol; however, studies with escitalopram have not been done. Ethanol intoxication or use should be avoided in patients using escitalopram as adverse CNS effects may be potentiated. Additionally, other co-administered centrally-acting drugs may augment cognitive impairment. The US Olympic committee has only banned the use of the SSRI-type antidepressants in sporting events that involve rifelry.
The number of elderly patients in escitalopram clinical trials was insufficient to assess a difference in safety and/or efficacy in this population. In clinical trials with escitalopram, 31% of patients were age 60 or older, 23% were 65 or older, and 10% were 75 or older. Greater sensitivity of the elderly patient should be considered when prescribing escitalopram. A lower dosage has been recommended for the elderly (see Dosage).
SSRIs can rarely precipitate a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) that presents as hypo-osmolarity of serum and urine, and hyponatremia. The incidence reported with other SSRIs was highest among elderly patients and/or patients on diuretics, or patients with significant dehydration. Therefore, such patients are at increased risk and should be monitored appropriately.
Escitalopram is classified in FDA pregnancy risk category C. Data detailing the use of escitalopram in human pregnancy are unavailable. In rat embryo/fetal developmental studies, escitalopram has been shown to have adverse effects on embryo/fetal and postnatal development when administered at doses >= 56 times the human maximum therapeutic dose (20 mg/m2/day). Decreased fetal body weight and delays in ossification were noted. Maternal toxicity (decreased feeding and decreased weight gain) was present at all dose levels. The developmental no effect dose of 56 mg/kg/day is roughly 28 times the recommended human dose. No teratogenicity was noted at any escitalopram dose; however, teratogenicity has been observed in citalopram animal studies. In general, animal studies have shown that SSRIs downregulate the serotonin receptors in the fetal cortex and that these changes can be present for a period of time after birth. One prospective, cohort study was conducted to evaluate the outcome of infants born to 267 women who took an SSRI during pregnancy. Compared with a neonatal control group, SSRI-exposed newborns had similar rates of major malformation, spontaneous and elective abortion, and stillbirth. Mean birth weight and gestational age were also similar. None of the patients in this study of the SSRIs were exposed to escitalopram. There are no well-controlled studies of escitalopram in pregnant women. Until further information is available from the manufacturer, escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The effect of escitalopram on labor and delivery is unknown.
Neonates exposed to escitalopram and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. When treating a pregnant woman with an SSRI or SNRI during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, tapering of the medication prior to delivery may be considered.
Specific data detailing the safety of escitalopram in breast-feeding are unavailable. However, it is recommended that escitalopram be used with caution in lactating women because the drug is excreted into human breast milk. With citalopram, a closely related drug, a few cases of somnolence, decreased feeding and weight loss in breast-feeding infants have been noted, and a case report has noted infant sleep disturbances. In some cases, the breast-milk concentrations of citalopram were comparable to those of the maternal serum and/or quantifiable levels of citalopram were noted in infant serum. In the case of the sleep disturbance, the effect subsided after dividing the mothers medication in 2 doses daily and replacing 2 of the daily infant feeds with formula. The American Academy of Pediatrics has suggested that SSRI use during breast-feeding may be of concern. Patients should advise their physician of their intention to breast-feed. If escitalopram must be continued during lactation due to the benefit of the drug to the mother, infant breast-feedings should be avoided during the times of maximum maternal serum concentrations (i.e., within 4 hours of the daily dose). If agreeable with the mother and health care provider, the mother may pump breast-milk during times of lowest maternal serum concentrations (right before the next dose) and use this breast milk for feedings during the times of maximum maternal serum concentrations. Also, substitution of formula during times of maximal escitalopram concentrations should help limit the potential for adverse effects in the infant. Alternatively, discontinuation of escitalopram during lactation or the use of formula for all feeds may be indicated.
There are no adequate and well-controlled studies of escitalopram use in children. Safety and efficacy have not been established. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients (see Contraindications, suicidal ideation). Pediatric patients should be monitored closely for the risk of suicide with any antidepressant medication. Among the antidepressants, only fluoxetine is approved for use in treating depression in pediatric patients. Fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children. Pediatric patients being treated with antidepressants for any indication should be observed daily by caregivers for clinical worsening, as well as agitation, irritability, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. If concerns arise, contact with health care providers should be made immediately. Antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. A patient Medication Guide about using antidepressants in children and adolescents is available. Health care providers should instruct patients and caregivers to read the guide and discuss any questions with them.
There have been several reports of abnormal bleeding associated with SSRI treatment, including reports of impaired platelet aggregation. While a causal relationship to escitalopram has not been established, impaired platelet aggregation may result from platelet serotonin depletion and may contribute to abnormal bleeding.
[ Last revised: 2/25/2005 2:21:00 PM ]
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