Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of escitalopram or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond 24 years old; there was a reduction in risk with antidepressants compared to placebo in adults over 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Escitalopram is not approved for use in pediatric patients.
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
Symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is a concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, inpatients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression of suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms.
Prescriptions of escitalopram should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Screening Patients for Bipolar Disorder: Bipolar disorder may present initially as a major depressive episode. It is thought that treating such an episode with an antidepressant alone may precipitate a mixed/manic episode in patients at risk for bipolar disorder. Careful screening entails accurate recording of the patient's psychiatric history, especially family history of suicide, bipolar disorder and depression. Escitalopram is not approved for the treatment of bipolar depression.
Potential for Interaction with Monoamine Oxidase Inhibitors (MAOIs): There have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma inpatients receiving serotonin reuptake inhibitor drugs in combination with a MAOI. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that escitalopram should not be used in combination with a MAOI, or within 14 days of discontinuing treatment with a MAOI. Similarly, at least 14 days should be allowed after stopping escitalopram before starting a MAOI.
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: There have been reports of potentially life-threatening serotonin syndrome or NMS-like reactions with selective norepinephrine reuptake inhibitors (SNRIs) and SSRIs alone, including escitalopram treatment but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair serotonin metabolism (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucination, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberration (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS like signs and symptoms.
Discontinuation of Treatment: Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt. The risk of discontinuation symptoms may be dependent on several factors such as the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (e.g., paresthesia and electric shock sensations), sleep disturbances (e.g., insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances are the most commonly reported reactions. Generally, these symptoms are mild to moderate; however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally, these symptoms are self-limiting and usually resolve within two weeks, though in some individuals they may be prolonged (two to three months or longer). It is therefore advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs.
Abnormal bleeding: Cases of bleeding abnormalities of the skin and mucous membranes including purpura, ecchymoses, hematoma, epistaxis, vaginal bleeding and gastrointestinal bleeding were associated with the use of SSRIs.
Escitalopram should therefore be used with caution in patients concomitantly treated with oral anticoagulants, drugs known to affect platelet function (e.g., atypical antipsychotics and phenothiazines, most TCAs, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, ticlopidine, and dipyridamole) as well as in patients with a past history of abnormal bleeding or those with predisposing conditions. Pharmacological gastroprotection should be considered for high risk patients.
Hyponatremia: Hyponatremia has been reported as a rare adverse reaction with the use of SSRIs probably due to inappropriate antidiuretic hormone secretion (SIADH). Caution should be exercised in patients at risk, such as the elderly, cirrhotic patients or patients concomitantly treated with drugs known to cause hyponatremia.
Activation of Mania/Hypomania: Clinical trials have documented an activation of mania/hypomania in patients treated with escitalopram. Escitalopram should be used cautiously in patients with a history of mania.
Interference with Cognitive and Motor Performance: Patients should be warned that psychoactive drugs may impair judgment, thinking or motor skills. They should be advised to avoid tasks which require complete mental alertness such as operating hazardous machinery and driving vehicles until they are sure that their treatment does not significantly impede their ability to perform such activities.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycemic control possibly due to improvement of depressive symptoms. Insulin and/or oral hypoglycemic dosage may need to be adjusted.
Use in Patients with Concomitant Illness: Clinical experience with escitalopram in patients with certain concomitant systematic illnesses is limited. Caution should be exercised when giving escitalopram in patients with diseases or conditions that produce altered metabolism or hemodynamic responses.
Escitalopram has not been systematically evaluated in patients with recent history of myocardial infarction or unstable heart disease.
Use in Children: Safety and effectiveness of escitalopram in pediatric patients have not been established.
Use in Elderly: Experience in those 65 years or older is insufficient to determine whether they respond differently from younger adults; increased sensitivity cannot be ruled out.
A reduced risk of suicidality was observed in adults 65 years or older with antidepressant therapy compared with placebo.