Mass Tort Update- |
- Philadelphia, PA 215-567-3500
- |
- Red Bank, NJ 732-747-9003
Mass Tort Update
Adverse event information for Lexapro was collected from 715 patients with major depressive disorder who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind, placebo-controlled trials. An additional 284 patients with major depressive disorder were newly exposed to escitalopram in open-label trials. The adverse event information for Lexapro in patients with GAD was collected from 429 patients exposed to escitalopram and from 427 patients exposed to placebo in double-blind, placebo-controlled trials.
Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events.
The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Adverse Events Associated with Discontinuation of Treatment
Major Depressive Disorder
Among the 715 depressed patients who received Lexapro in placebo-controlled trials, 6% discontinued treatment due to an adverse event, as compared to 2% of 592 patients receiving placebo. In two fixed-dose studies, the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro was not significantly different from the rate of discontinuation for adverse events in patients receiving placebo. The rate of discontinuation for adverse events in patients assigned to a fixed dose of 20 mg/day Lexapro was 10%, which was significantly different from the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro (4%) and placebo (3%). Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients).
Generalized Anxiety Disorder
Among the 429 GAD patients who received Lexapro 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due to an adverse event, as compared to 4% of 427 patients receiving placebo. Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and fatigue (1%).
Incidence of Adverse Events in Placebo-Controlled Clinical Trials
Major Depressive Disorder
Table 1 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 715 depressed patients who received Lexapro at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients.
The prescriber should be aware that these figures can not be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.
The most commonly observed adverse events in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue, and somnolence (see TABLE 1).
TABLE 1
Treatment-Emergent Adverse Events: Incidence in Placebo-Controlled Clinical Trials for Major Depressive Disorder*
| (Percentage of Patients Reporting Event) | ||
| Body System / Adverse Event |
Lexapro (N=715) |
Placebo (N=592) |
| Autonomic Nervous System Disorders | ||
| Dry Mouth | 6% | 5% |
| Sweating Increased | 5% | 2% |
| Central & Peripheral Nervous System Disorders | ||
| Dizziness | 5% | 3% |
| Gastrointestinal Disorders | ||
| Nausea | 15% | 7% |
| Diarrhea | 8% | 5% |
| Constipation | 3% | 1% |
| Indigestion | 3% | 1% |
| Abdominal Pain | 2% | 1% |
| General | ||
| Influenza-like Symptoms | 5% | 4% |
| Fatigue | 5% | 2% |
| Psychiatric Disorders | ||
| Insomnia | 9% | 4% |
| Somnolence | 6% | 2% |
| Appetite Decreased | 3% | 1% |
| Libido Decreased | 3% | 1% |
| Respiratory System Disorders | ||
| Rhinitis | 5% | 4% |
| Sinusitis | 3% | 2% |
| Urogenital | ||
| Ejaculation Disorder1,2 | 9% | <1% |
| Impotence² | 3% | <1% |
| Anorgasmia3 | 2% | <1% |
| *Events reported by at least 2% of patients treated with Lexapro are reported, except for the following events which had an incidence on placebo ≥Lexapro: headache, upper respiratory tract infection, back pain, pharyngitis, inflicted injury, anxiety. 1Primarily ejaculatory delay. ²Denominator used was for males only (N=225 Lexapro; N=188 placebo). 3Denominator used was for females only (N=490 Lexapro; N=404 placebo). |
||
Generalized Anxiety Disorder
Table 2 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse events that occurred among 429 GAD patients who received Lexapro 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients.
The most commonly observed adverse events in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay), insomnia, fatigue, decreased libido, and anorgasmia (see TABLE 2).
TABLE 2
Treatment-Emergent Adverse Events: Incidence in Placebo-Controlled Clinical Trials for Generalized Anxiety Disorder*
| (Percentage of Patients Reporting Event) | ||
| Body System / Adverse Event |
Lexapro (N=429) |
Placebo (N=427) |
| Autonomic Nervous System Disorders | ||
| Dry Mouth | 9% | 5% |
| Sweating Increased | 4% | 1% |
| Central & Peripheral Nervous System Disorders | ||
| Headache | 24% | 17% |
| Paresthesia | 2% | 1% |
| Gastrointestinal Disorders | ||
| Nausea | 18% | 8% |
| Diarrhea | 8% | 6% |
| Constipation | 5% | 4% |
| Indigestion | 3% | 2% |
| Vomiting | 3% | 1% |
| Abdominal Pain | 2% | 1% |
| Flatulence | 2% | 1% |
| Toothache | 2% | 0% |
| General | ||
| Fatigue | 8% | 2% |
| Influenza-like Symptoms | 5% | 4% |
| Musculoskeletal | ||
| Neck/Shoulder Pain | 3% | 1% |
| Psychiatric Disorders | ||
| Somnolence | 13% | 7% |
| Insomnia | 12% | 6% |
| Libido Decreased | 7% | 2% |
| Dreaming Abnormal | 3% | 2% |
| Appetite Decreased | 3% | 1% |
| Lethargy | 3% | 1% |
| Yawning | 2% | 1% |
| Urogenital | ||
| Ejaculation Disorder1,2 | 14% | 2% |
| Anorgasmia3 | 6% | <1% |
| Menstrual Disorder | 2% | 1% |
| *Events reported by at least 2% of patients treated with Lexapro are reported, except for the following events which had an incidence on placebo ≥Lexapro: inflicted injury, dizziness, back pain, upper respiratory tract infection, rhinitis, pharyngitis. 1Primarily ejaculatory delay. ²Denominator used was for males only (N=182 Lexapro; N=195 placebo). 3Denominator used was for females only (N=247 Lexapro; N=232 placebo). |
||
Dose Dependency of Adverse Events
The potential dose dependency of common adverse events (defined as an incidence rate of ≥5% in either the 10 mg or 20 mg Lexapro groups) was examined on the basis of the combined incidence of adverse events in two fixed-dose trials. The overall incidence rates of adverse events in 10 mg Lexapro-treated patients (66%) was similar to that of the placebo-treated patients (61%), while the incidence rate in 20 mg/day Lexapro-treated patients was greater (86%). Table 3 shows common adverse events that occurred in the 20 mg/day Lexapro group with an incidence that was approximately twice that of the 10 mg/day Lexapro group and approximately twice that of the placebo group.
TABLE 3
Incidence of Common Adverse Events* in Patients with Major Depressive Disorder Receiving Placebo, 10 mg/day Lexapro, or 20 mg/day Lexapro
| Adverse Event | Placebo (N=311) |
10 mg/day Lexapro (N=310) |
20 mg/day Lexapro (N=125) |
| Insomnia | 4% | 7% | 14% |
| Diarrhea | 5% | 6% | 14% |
| Dry Mouth | 3% | 4% | 9% |
| Somnolence | 1% | 4% | 9% |
| Dizziness | 2% | 4% | 7% |
| Sweating Increased | <1% | 3% | 8% |
| Constipation | 1% | 3% | 6% |
| Fatigue | 2% | 2% | 6% |
| Indigestion | 1% | 2% | 6% |
| *Adverse events with an incidence rate of at least 5% in either of the Lexapro groups and with an incidence rate in the 20 mg/day Lexapro group that was approximately twice that of the 10 mg/day Lexapro group and the placebo group. | |||
Male and Female Sexual Dysfunction with SSRIs
Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences.
Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence.
Table 4 shows the incidence rates of sexual side effects in patients with major depressive disorder and GAD in placebo-controlled trials.
TABLE 4
Incidence of Sexual Side Effects in Placebo-Controlled Clinical Trials
| Adverse Event | Lexapro In Males Only (N=407) |
Placebo (N=383) |
| Ejaculation Disorder (primarily ejaculatory delay) | 12% | 1% |
| Libido Decreased | 6% | 2% |
| Impotence | 2% | <1% |
| In Females Only (N=737) |
(N=636) | |
| Libido Decreased | 3% | 1% |
| Anorgasmia | 3% | <1% |
There are no adequately designed studies examining sexual dysfunction with escitalopram treatment.
Priapism has been reported with all SSRIs.
While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.
Vital Sign Changes
Lexapro and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with Lexapro treatment. In addition, a comparison of supine and standing vital sign measures in subjects receiving Lexapro indicated that Lexapro treatment is not associated with orthostatic changes.
Weight Changes
Patients treated with Lexapro in controlled trials did not differ from placebo-treated patients with regard to clinically important change in body weight.
Laboratory Changes
Lexapro and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with Lexapro treatment.
ECG Changes
Electrocardiograms from Lexapro (N=625), racemic citalopram (N=351), and placebo (N=527) groups were compared with respect to (1) mean change from baseline in various ECG parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed (1) a decrease in heart rate of 2.2 bpm for Lexapro and 2.7 bpm for racemic citalopram, compared to an increase of 0.3 bpm for placebo and (2) an increase in QTc interval of 3.9 msec for Lexapro and 3.7 msec for racemic citalopram, compared to 0.5 msec for placebo. Neither Lexapro nor racemic citalopram were associated with the development of clinically significant ECG abnormalities.
Other Events Observed During the Premarketing Evaluation of Lexapro
Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by the 1428 patients treated with Lexapro for periods of up to one year in double-blind or open-label clinical trials during its premarketing evaluation. All reported events are included except those already listed in Tables 1 & 2, those occurring in only one patient, event terms that are so general as to be uninformative, and those that are unlikely to be drug related. It is important to emphasize that, although the events reported occurred during treatment with Lexapro, they were not necessarily caused by it.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients.
Cardiovascular
Frequent: palpitation, hypertension. Infrequent: bradycardia, tachycardia, ECG abnormal, flushing, varicose vein.
Central and Peripheral Nervous System Disorders
Frequent: light-headed feeling, migraine. Infrequent: tremor, vertigo, restless legs, shaking, twitching, dysequilibrium, tics, carpal tunnel syndrome, muscle contractions involuntary, sluggishness, coordination abnormal, faintness, hyperreflexia,
Gastrointestinal Disorders
Frequent: heartburn, abdominal cramp, gastroenteritis. Infrequent: gastroesophageal reflux, bloating, abdominal discomfort, dyspepsia, increased stool frequency, belching, gastritis, hemorrhoids, gagging, polyposis gastric, swallowing difficult.
General
Frequent: allergy, pain in limb, fever, hot flushes, chest pain. Infrequent: edema of extremities, chills, tightness of chest, leg pain, asthenia, syncope, malaise, anaphylaxis, fall.
Hemic and Lymphatic Disorders
Infrequent: bruise, anemia, nosebleed, hematoma, lymphadenopathy cervical.
Metabolic and Nutritional Disorders
Frequent: increased weight. Infrequent: decreased weight, hyperglycemia, thirst, bilirubin increased, hepatic enzymes increased, gout, hypercholesterolemia.
Musculoskeletal System Disorders
Frequent: arthralgia, myalgia. Infrequent: jaw stiffness, muscle cramp, muscle stiffness, arthritis, muscle weakness, back discomfort, arthropathy, jaw pain, joint stiffness.
Psychiatric Disorders
Frequent: appetite increased, lethargy, irritability, concentration impaired. Infrequent: jitteriness, panic reaction, agitation, apathy, forgetfulness, depression aggravated, nervousness, restlessness aggravated, suicide attempt, amnesia, anxiety attack, bruxism, carbohydrate craving, confusion, depersonalization, disorientation, emotional lability, feeling unreal, tremulousness nervous, crying abnormal, depression, excitability, auditory hallucination, suicidal tendency.
Reproductive Disorders/Female
Frequent: menstrual cramps, menstrual disorder. Infrequent: menorrhagia, breast neoplasm, pelvic inflammation, premenstrual syndrome, spotting between menses.
Respiratory System Disorders
Frequent: bronchitis, sinus congestion, coughing, nasal congestion, sinus headache. Infrequent: asthma, breath shortness, laryngitis, pneumonia, tracheitis.
Skin and Appendages Disorders
Frequent: rash. Infrequent: pruritus, acne, alopecia, eczema, dermatitis, dry skin, folliculitis, lipoma, furunculosis, dry lips, skin nodule.
Special Senses
Frequent: vision blurred, tinnitus. Infrequent: taste alteration, earache, conjunctivitis, vision abnormal, dry eyes, eye irritation, visual disturbance, eye infection, pupils dilated, metallic taste.
Urinary System Disorders
Frequent: urinary frequency, urinary tract infection.
Infrequent: urinary urgency, kidney stone, dysuria, blood in urine.
Events Reported Subsequent to the Marketing of Escitalopram
Although no causal relationship to escitalopram treatment has been found, the following adverse events have been reported to have occurred in patients and to be temporally associated with escitalopram treatment during post marketing experience and were not observed during the premarketing evaluation of escitalopram: abnormal gait, acute renal failure, aggression, akathisia, allergic reaction, anger, angioedema, atrial fibrillation, choreoathetosis, delirium, delusion, diplopia, dysarthria, dyskinesia, dystonia, ecchymosis, erythema multiforme, extrapyramidal disorders, fulminant hepatitis, hepatic failure, hypoaesthesia, hypoglycemia, hypokalemia, INR increased, gastrointestinal hemorrhage, glaucoma, grand mal seizures (or convulsions), hemolytic anemia, hepatic necrosis, hepatitis, hypotension, leucopenia, myocardial infarction, myoclonus, neuroleptic malignant syndrome, nightmare, nystagmus, orthostatic hypotension, pancreatitis, paranoia, photosensitivity reaction, priapism, prolactinemia, prothrombin decreased, pulmonary embolism, QT prolongation, rhabdomyolysis, seizures, serotonin syndrome, SIADH, spontaneous abortion, Stevens Johnson Syndrome, tardive dyskinesia, thrombocytopenia, thrombosis, torsade de pointes, toxic epidermal necrolysis, ventricular arrhythmia, ventricular tachycardia and visual hallucinations.
Drug Abuse And Dependence
Controlled Substance Class
Lexapro is not a controlled substance.
Physical and Psychological Dependence
Animal studies suggest that the abuse liability of racemic citalopram is low. Lexapro has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. The premarketing clinical experience with Lexapro 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. Consequently, physicians should carefully evaluate Lexapro patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).
| Enter any relevant background information or case specifics so that we can best understand your situation: | ||
|
To Prevent Automated Submissions, Enter the 4 Digit Number Shown Below
(OR YOU MAY CALL US DIRECTLY AT 888-375-7600) |
||
 1473
|
||