Lexapro (Escitalopram) Adverse Reactions
- abdominal pain
- agitation
- akathisia
- anaphylactoid reactions
- angioedema
- anxiety
- arrhythmia exacerbation
- bleeding
- choreoathetosis
- constipation
- delirium
- diaphoresis
- diarrhea
- dizziness
- drowsiness
- dysgeusia
- dyskinesia
- dyspepsia
- ecchymosis
- ejaculation dysfunction
- erythema multiforme
- fatigue
- fetal abortion
- GI bleeding
- headache
- hemolytic anemia
- hepatic necrosis
- hostility
- hyperprolactinemia
- hyponatremia
- hypoprothrombinemia
- impotence
- insomnia
- irritability
- libido decrease
- mania
- menstrual irregularity
- myoclonia
- nausea/vomiting
- neonatal abstinence syndrome
- neuroleptic malignant syndrome
- nystagmus
- orgasm dysfunction
- pancreatitis
- polyuria
- priapism
- QT prolongation
- renal failure (unspecified)
- rhabdomyolysis
- seizures
- serotonin syndrome
- SIADH
- suicidal ideation
- thrombocytopenia
- thrombosis
- torsade de pointes
- toxic epidermal necrolysis
- weight gain
- weight loss
- withdrawal
- xerostomia
- yawning
Lexapro (Escitalopram) Adverse Reactions
In general, escitalopram 10 mg has been shown to be well tolerated in clinical trials. The 20 mg dose of escitalopram has a markedly higher incidence of adverse events compared to the 10 mg dose or placebo. Studies suggest that escitalopram exhibits similar types of adverse events compared to citalopram. The most common ADRs included nausea, difficulty sleeping (insomnia), ejaculation disorder, somnolence (drowsiness), increased sweating (diaphoresis) and tiredness (fatigue). Central nervous system or psychiatric side effects with escitalopram 10 mg included drowsiness (4%), dizziness (4%), fatigue (2%), and insomnia (7%). CNS events noted with escitalopram 20 mg include insomnia (14%), drowsiness (9%), dizziness (7%), and fatigue (6%). Most notably, the incidence of insomnia doubles with the 20 mg dose of escitalopram. Diaphoresis has been reported in roughly 3% of patients receiving escitalopram 10 mg. Typically, diaphoresis is a dose-related effect with SSRIs; the incidence of diaphoresis (8%) at least doubled in incidence when the 20 mg dose was utilized. In GAD studies, headache was reported in 24% vs. 17% of patients receiving active vs. placebo agent. New onset headaches, especially with initial treatment of SSRIs, is an expected but transient side effect, with headaches usually resolving within 2 weeks. Adverse effects occurred in 86% of patients receiving either escitalopram 20 mg daily or citalopram 40 mg daily. In fixed-dose studies, therapy discontinuations were roughly 3%, 4%, 10% and 9% for placebo, escitalopram 10 mg, escitalopram 20 mg, and citalopram 40 mg daily, respectively. The rate of discontinuation in the escitalopram 10 mg group was similar to placebo but statistically less than the escitalopram 20 mg group, suggesting that many adverse events are dose-related. Adverse events most commonly associated with discontinuation of therapy included nausea (2%) and ejaculation disorder (2% of male patients). In pivotal escitalopram trials, 6% of all patients receiving escitalopram (n=715) discontinued treatment due to an adverse event, compared to 2% of all patients in the placebo group (n=592).
Xerostomia occurred in 4% of patients receiving 10 mg, versus 3% on placebo. Xerostomia (9%) at least doubled in incidence when the 20 mg dose was utilized. Gastrointestinal effects with escitalopram vs. placebo have included abdominal pain (2 vs.1%), constipation (3 vs. 1%), diarrhea (6 vs. 5%), indigestion (2% vs. 1%) and nausea/vomiting (15% vs. 7%). Nausea has been noted as the most common adverse effect with escitalopram. Weight gain and weight loss have been reported frequently with escitalopram, but overall, escitalopram groups did not differ significantly from placebo with regard to clinically important weight changes. Dysgeusia (altered taste) and decreased appetite have occurred infrequently. GI adverse events occurring with the escitalopram 20 mg dose that have been shown to be dose-related include: constipation (6%), diarrhea (14%), and indigestion (dyspepsia, 6%). Events at least doubled in incidence when the 20 mg dose was utilized.
In the escitalopram male groups (n=225) vs. placebo (n=188), ejaculation dysfunction (primary ejaculatory delay), decreased libido and impotence have been described in 9%, 4%, and 3% of men, respectively. Ejaculation dysfunction was reported at a higher rate in GAD studies (14 vs. 2% placebo). In roughly 2-3% of female patients (n=490), libido decrease and orgasm dysfunction (anorgasmia) have been reported. Libido decrease was reported at a higher rate in GAD studies (7 vs. 2% placebo). In both male and female placebo groups, all reported sexual side effect incidences were <1% except for decreased libido in males (2%). Notably, ejaculation disorder was one of the most common reasons men dropped out of pivotal studies. Although sexual dysfunction is often part of depression and other psychiatric disorders, there is increasing evidence that treatment with SSRIs may induce sexual side effects. Post-marketing experience has suggested that the frequency of sexual adverse events is actually much higher than reported during initial clinical trials. In fact, many physicians report an incidence of up to 90% based on their clinical experience. Priapism has been reported with an unintentional citalopram overdose (roughly 100 mg) in a patient with a history of trazodone-associated priapism. The mechanism in this case is proposed to be due to stimulation or inhibition of CNS serotonin receptors, and this rare side effect has been reported with many of the SSRIs. Priapism has also been reported in spontaneous adverse event reports with escitalopram.
Respiratory system disorders, while not differing much incidence from the placebo group, have been reported. Rhinitis and sinusitis have occurred in 5% and 3% of all escitalopram patients, respectively.
Use caution when combining SSRIs with NSAIDs, including aspirin. GI bleeding has been noted in 2 epidemiological studies when SSRIs were combined with NSAIDs (see Drug Interactions). Bleeding may occur at other sites. GI hemorrhage has been reported in escitalopram post-marketing reports.
Withdrawal symptoms have been reported with abrupt or rapid discontinuation of short-acting SSRIs (e.g., sertraline). The most commonly reported SSRI withdrawal symptoms include fatigue, stomach pain or nausea, dizziness/light-headedness, tremor, chills, diaphoresis, and incoordination. Other reported symptoms include dysphoric mood, impaired memory, insomnia, irritability, shock sensations, headache, paresthesia and aggression. Withdrawal symptoms usually begin 1-3 days after abrupt discontinuation of the SSRI and remit within 1-2 weeks. Significant withdrawal symptoms have been reported in only 3 out of 8 million patients treated with citalopram, while none have been reported with fluoxetine. The difference in the incidence of withdrawal symptoms among SSRIs is most likely due to differences in the half-lives of the active moieties. Nevertheless, gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of withdrawal symptoms. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
All SSRIs can cause a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) that presents as hyposmolarity of serum and urine, and hyponatremia. Older patients and those receiving diuretics or who are otherwise predisposed to dehydration appear to be more at risk. Discontinuation of the drug and/or medical intervention resolves these events. Polyuria has also been reported with citalopram.
Serotonin syndrome has been reported when SSRIs are administered concomitantly with other medications known to increase CNS or peripheral serotonin levels or during SSRI overdose. Symptoms may include nausea, vomiting, sedation, dizziness, diaphoresis (sweating), facial flush, mental status changes, myoclonia, restlessness, shivering, and hypertension. In post-marketing studies, serotonin syndrome has been reported with escitalopram.
Escitalopram has been associated with changes in electrocardiograms. In post-marketing spontaneous ADR reports with escitalopram, QT prolongation, torsade de pointes, and ventricular arrhythmia exacerbation have been reported; however a causal association with escitalopram has not been made.
Suicidal ideation has been reported in antidepressant clinical trials. The symptoms of aggressiveness, akathisia (psychomotor restlessness), agitation, anxiety, insomnia, irritability, hostility, mania, hypomania, impulsivity, and panic attacks 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 concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidal ideation. A change or discontinuation of the therapeutic regimen should especially be considered if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Many of these adverse symptoms have been reported in clinical trials and have not always been associated with suicidality. Rapid discontinuation of SSRIs may also result in many of these adverse CNS events.
The following list includes adverse events that were reported frequently (occurring in >= 1/100 patients) in escitalopram studies; however, a causal association with escitalopram has not been established: Adverse events are listed by body system in decreasing order of frequency. For a complete listing of infrequent adverse events (occurring in <= 1/100 but >= 1/1000 patients), consult the manufacturers package labeling. Cardiovascular system: palpitation, hypertension, paresthesia; CNS and peripheral nervous system: light-headed feeling, migraine, tremor, vertigo; GI: vomiting, flatulence, heartburn, toothache, gastroenteritis, abdominal cramp, GERD; General: allergy, pain in limb, hot flushes, fever, chest pain; Metabolic and Nutritional disorders: increased weight, decreased weight; Musculoskeletal system: arthralgia, neck/shoulder pain, muscle cramp, myalgia; Psychiatric disorders: abnormal dreaming, yawning (commonly associated with SSRIs), appetite increase, lethargy, irritability, concentration impaired; Reproductive disorders/females: menstrual cramps, menstrual irregularity or disorder; Respiratory system disorders: bronchitis, sinus congestion, coughing, sinus headache, nasal congestion; Skin and Appendages disorders: rash; Special senses: blurred vision, ear ache, tinnitus; Urinary System Disorders: UTI, urinary frequency.
The following events were noted in post-marketing reports to have a temporal association with the use of escitalopram, although causality has not been determined; incidences of these events were not reported: acute renal failure (unspecified), akathisia, allergic reaction, anaphylactoid reactions, angioedema, choreoathetosis, delirium, dyskinesia, ecchymosis, epidermal necrolysis, erythema multiforme, gastrointestinal hemorrhage, hemolytic anemia, hepatic necrosis, myoclonus, neuroleptic malignant syndrome, nystagmus, pancreatitis, priapism, hyperprolactinemia, hypoprothrombinemia, QT prolonged, rhabdomyolysis, seizures, serotonin syndrome, spontaneous fetal abortion, thrombocytopenia, thrombosis, Torsade de pointes, toxic epidermal necrolysis, ventricular arrhythmia exacerbation, withdrawal syndrome.
A neonatal abstinence syndrome has been reported in infants exposed to serotonergic agents in utero. After birth, symptoms consistent with withdrawal (i.e., poor feeding, hypoglycemia, hypothermia, lethargy or irritability, vomiting, etc.) were noted. Such complications can arise immediately upon delivery. Other symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, and constant crying. Serum concentrations of the serotonergic agent were measurable in the infants affected. Several other symptoms (bloody stools, necrotizing enterocolitis) may have been attributable to rebound platelet activation on withdrawal of the exposure to the SSRI. Neonatal symptoms generally improved over several days. Additionally, a cohort study of 55 women revealed that 22% (12/55) of neonates exposed to an SSRI in the third trimester had complications requiring treatment or extended hospitalization compared with 6% in comparison groups. Complications included respiratory distress (n=9), hypoglycemia (n=2) and jaundice (n=1). The incidence of prematurity in the third trimester SSRI group was significant at 20% vs. 3.7% of controls. These features are consistent with either a direct toxic effect of serotonergic agents, 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 other serotonergic agent during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, and taking the drug half-life into consideration, tapering of the serotonergic agent prior to delivery may be considered as an alternative.
[ Last revised: 11/9/2005 2:10:00 PM ]
References
. Stiskal JA, Kulin N, Koren G, et al. Neonatal paroxetine withdrawal syndrome. Arch Dis Child Fetal Neonatal Ed 2001;84:F134-5.
. Dent LA, Brown WC, Murney JD. Citalopram-induced priapism. Pharmacotherapy 2002;22:538-41.
. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 2002;63:331-6.
. Costei AM, Kozer E, Ho T, et al. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med. 2002;156:1129-32.
. Spigset O, Adielsson G. Combined serotonin syndrome and hyponatraemia caused by a citalopram-buspirone interaction. Int Clin Psychopharmacol. 1997;12:61-3.
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