Jovia Special Precautions

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 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 less than 12 years old.
Clinical Worsening and Suicide Risk: The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. This risk much be considered in all depressed patients.
Patients with 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 drugs, and this risk may persist until significant remission occurs.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, particularly during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. Close supervision of patients and in particular those at high risk should accompany drug therapy particularly in early treatment and following dose changes.
There has been a 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. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the drug, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Generally, when stopping an antidepressant, doses should be tapered rather than stopped abruptly.
Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increased the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with MDD and other psychiatric disorders. 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 with antidepressants compared to placebo in adults 65 years and older.
The following symptoms have been reported in adult and pediatric patients being treated with antidepressants for MDD as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness, hypomania, and mania. Although a causal link between the emergence of such symptoms and either worsening of depression and/or emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing the drug, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Other psychiatric condition for which escitalopram is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with MDD. The same precautions observed when treating patients with MDD should therefore be observed when treating with other psychiatric disorders.
Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and non-psychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior and other symptoms described previously, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. It is particularly important that monitoring be undertaken during the initial few months of antidepressant treatment or at times of dose increase or decrease.
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.
Paradoxical anxiety: Some patients with panic disorder may experience increased anxiety symptoms at the beginning of treatment with antidepressants. This paradoxical reaction usually subsides within two weeks during continued treatment. A low starting dose is advised to reduce the likelihood of an anxiogenic effect.
Screening Patients for Bipolar Disorder: 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 previously represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk of bipolar disorder; such screening should include a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. It should be noted that escitalopram is not approved for use in treating bipolar depression.
Abuse and Dependence: Escitalopram has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. The premarketing clinical experience with escitalopram did not reveal any drug-seeking behavior. However, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Likewise, physicians should carefully evaluate escitalopram patients for history of drug abuse and follow such patients closely, observing them for sign of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).
Activation of Mania/Hypomania and Bipolar Disorder: As with other antidepressants, escitalopram should be used with caution in patients with a history of mania/hypomania.
A major depressive episode may be initial presentation of bipolar disorder. Patients with bipolar disorder may be at an increased risk of experiencing manic episodes when treated with antidepressants alone. Therefore, the decision to initiate symptomatic treatment of depression should only be made after patients have been adequately assessed to determine if they are at risk for bipolar disorder.
Electroconvulsive Therapy (ECT): The safety and efficacy of the concurrent use of either escitalopram or racemic citalopram and ECT have not been studies, and therefore, caution is advisable.
Akathisia/Psychomotor Restlessness: The use of SSRIs/SNRIs has been associated with the development of akathisia, characterized by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Seizures: Like other antidepressants, escitalopram should be used with caution in patients with a history of seizure disorder. Escitalopram should be discontinued if a patient develops seizures for the first time, or if there is an increase in seizure frequency (in patients with a previous diagnosis of epilepsy). SSRIs should be avoided in patients with uncontrolled epilepsy, and patients with controlled epilepsy should be closely monitored.
Serotonin Syndrome Neuroleptic Malignant Syndrome (NMS)-Like Events: On rare occasions, serotonin syndrome or NMS-like events have occurred in association with treatment with SSRIs, including escitalopram, particularly when given in combination with other serotonergic and/or neuroleptic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with escitalopram should be discontinued if such events (characterized by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Escitalopram should not be used in combination with MAOI or serotonin-precursors (such as L-tryptophan, oxitriptan) and should be used with caution in combination with other serotonergic drugs (triptans, certain tricyclic antidepressants, lithium, tramadol, St. John's wort) due to the risk of serotonergic syndrome.
Reversible Cerebral Vasoconstriction Syndrome: Reversible cerebral vasoconstriction syndrome (thunderclap headache) has been associated with serotonergic agents such as SSRIs or triptans.
Abnormal bleeding: SSRIs and SNRIs, including escitalopram, may increase the risk of bleeding events by causing abnormal platelet aggregation. Concomitant use of acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to the risk. Studies have shown an association between use of drugs that interfere with serotonin reuptake and the occurrence gastrointestinal (GI) bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
Patients should be cautioned about the risk of bleeding associated with the concomitant use of escitalopram and NSAIDs, ASA, or other drugs that affect coagulation. Caution is advised in patients with a history of bleeding disorder or predisposing conditions (e.g., thrombocytopenia).
Angle-Closure Glaucoma: SSRIs including escitalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure ang angle-closure glaucoma, particularly in predisposed patients. Therefore, escitalopram should be used with caution in patients with angle-closure glaucoma or history of glaucoma.
Bone Fracture Risk: Epidemiological studies shown an increased risk of bone fractures following exposure to some antidepressants, including SSRIs/SNRIs. The risk appears to be greater at the initial stages of treatment, but significant increased risks were also observed at later stages of treatment. The possibility of fracture should be considered in the care of patients treated with escitalopram. Elderly patients and patients with important risk factors for bone fractures should be advised of possible adverse events which increase the risk of falls such as dizziness and orthostatic hypotension, particularly at the early stages of treatment but also soon after withdrawal. Preliminary data from observational studies show association of SSRIs/SNRIs and low bone mineral density in older men and women. Until further information becomes available, a possible effect on bone mineral density with long term treatment with SSRIs/SNRIs, including escitalopram, cannot be excluded, and may be a potential concern for patients with osteoporosis or major risk factors for bone fractures.
Hyponatremia: As with other antidepressants, cases of hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported with escitalopram and racemic citalopram as a rare adverse event. The majority of these occurrences have been in elderly individuals, some in patients taking diuretics or who were otherwise volume-depleted. Elderly female patients in particular seem to be a group at risk. Caution should be exercised in patients at risk, such as the elderly, or patients with cirrhosis, or if used in combination with other medications which may cause hyponatremia.
Use in Patients with Concomitant Illness: Patients with cardiac disease: In line with other SSRIs, including racemic citalopram, escitalopram causes statistically significant, but clinically unimportant decrease in heart rate. In patients <60 years old, the mean decrease with escitalopram oxalate was approximately 2.3 bpm, while in patients ≥60 years old, the mean decrease was approximately 0.6 bpm. Consequently, caution should be observed when escitalopram is initiated in patients with pre-existing slow heart rate.
QT interval prolongation and torsade de pointes: Escitalopram has been found to cause a dose- dependent prolongation of the QT interval. In addition, there have been cases of QTc interval prolongation and torsade de pointes reported during the post-marketing period, predominantly in patients with risk factors for QTc prolongation.
Escitalopram should be used with caution in patients with risk for QTc prolongation/torsade de pointes. Risk factors include congenital long QT syndrome, >65 years old, female sex, structural heart disease/left ventricular dysfunction, hypokalemia, and severe hypomagnesemia, high plasma levels of escitalopram (e.g., high doses, medical conditions such as hepatic or renal disease, or use of medicines that inhibit the metabolism of escitalopram), and concomitant use of other QTc prolonging drugs.
In high risk patients (i.e., congenital long QT syndrome, pre-existing QT prolongation or multiple risk factors), an electrocardiogram (ECG) should be done prior starting treatment, at steady state, after dose increases or after starting any potentially interacting drugs. Electrolytes should be monitored periodically and any abnormalities should be corrected prior to starting escitalopram. An ECG should also be done in all patients experiencing symptoms that could indicative of an arrhythmia (e.g., dizziness, palpitations, syncope, or new onset seizure).
Consideration should be given to stopping escitalopram treatment or reducing the dose if the QTc interval is >500 ms or increases by >60 ms.
Diabetic patients: Treatment with an SSRI in patients with diabetes may alter glycemic control (hypoglycemia and hyperglycemia). Escitalopram should be used with caution in diabetic patients on insulin or oral hypoglycemic drugs.
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 including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paresthesia and electronic shock sensations), sleep disturbances (including 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 (2 to 3 months or more). Therefore, it is advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's need.
Effects On Ability To Drive And Use Machine: Although escitalopram has been shown not to affect intellectual function or psychomotor performance, any psychoactive drug may impair judgment of skills. Patients should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.
Hepatic Impairment: Based on a study conducted with escitalopram in patients with mild to moderate hepatic impairment, the t_¹/2 was approximately doubled and the exposure was increased by approximately two thirds, compared to subjects with normal liver function. Therefore, the use of escitalopram in hepatically impaired patients should be approached with caution and a lower dosage is recommended. Escitalopram should be used with additional caution in patients with severe hepatic impairment.
Renal Impairment: No information is available on the pharmacokinetic or pharmacodynamic effects of escitalopram in patients with renal impairment, particularly in patients with severely reduced function. Since no information is available on the pharmacokinetic or pharmacodynamic effects of either escitalopram in patients with severely reduced function (creatinine clearance <30 mL/min), escitalopram should be used with caution in these patients.
Use in Children: The safety and effectiveness of escitalopram have been established in adolescents (12 to 17 years old) for the treatment of MDD. Although maintenance efficacy in adolescent patients with MDD has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.
The safety and effectiveness of escitalopram have not been established in pediatric (younger than 12 years old) patients with MDD.
Safety and effectiveness of escitalopram has not been established in pediatric patients less than 18 years old with GAD.
Decreased appetite and weight loss have been observed in association with the use of SSRIs. Likewise, regular monitoring of weight and growth should be done in children and adolescents treated with an SSRI such as escitalopram.
Use in Elderly: SSRIs and SNRIs, including escitalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event.