Escitalopram oxalate, often marketed as Lexapro, is the quintessential Selective Serotonin Reuptake Inhibitor (SSRI) used primarily for the management of symptoms associated with Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). Lexapro drug class through its actions increases serotonergic transmission in the central nervous system, which alleviates the symptoms and signs of Major Depression and Generalized Anxiety. Unfortunately, Serotonin doesn’t only act on receptors that regulate functions related to depression and anxiety. It also interacts with receptors that regulate appetite, sexual function, and sleep. Therefore, the increased serotonergic activity affects the regulation of all of the aforementioned physiologic processes within our bodies and produces the associated side effects of escitalopram use. This article will delve into the common Lexapro Side Effects, as well as several warnings and precautions patients should be aware of when taking Escitalopram.
If experienced, Lexapro side effects in the first week tend to be the worst as the body has not had the time to undergo physiological adaptation to the newly elevated levels of Serotonin.
The Most Common Lexapro Side Effects
Escitalopram is derived from a slightly older SSRI, Citalopram. The differentiating factor between these two drugs is their composition. Escitalopram contains the most functional and most serotonin-selective enantiomer. Why is this important? This means that the Escitalopram side effects are not related to actions of the drug itself as it only affects Serotonin, but rather to the elevated levels of Serotonin brought about by its therapeutic effect. Thus making most of the Escitalopram side effects dose-dependent. Furthermore, if experienced, Lexapro side effects in the first week tend to be the worst as the body has not had the time to undergo physiological adaptation to the newly elevated levels of Serotonin. However, as the body adjusts, many of the most common Lexapro side effects will abate or at the least become significantly more tolerable.
The Most Common (>2%) Escitalopram Side Effects Include:
- Constitutional: Fatigue, Flu-like Symptoms
- Autonomic Nervous System: Xerostomia/Dry mouth, Hyperhidrosis
- Central and Peripheral Nervous System: Headache, Dizziness, Paraesthesia
- Gastrointestinal: Nausea, Diarrhea, Constipation, Indigestion, Abdominal pain, Vomiting, Flatulence, Toothache
- Psychiatric Disorders: Insomnia, Somnolence, Tinnitus, Loss of appetite, Loss of libido
- Respiratory Disorders: Rhinitis, Sinusitis, Yawning
- Urogenital: Ejaculation Disorder, Impotence, Anorgasmia, Menstrual Disorder
As per the prescribing information for Lexapro provided by the Food and Drug Association (FDA), there are various other Lexapro side effects as reported by patients in premarketing and marketing time periods. However, as these adverse reactions occur with very low frequencies (<1%) and are self-reported, the reliable estimation of their frequency and establishment of a causal connection cannot be done.
Serious Escitalopram Side Effects
Life-threatening emergent Lexapro side effects are fortunately rare. The symptoms and signs of these adverse reactions are associated with various conditions and syndromes that can arise as a result of Lexapro therapy and are discussed in the section below on Escitalopram Warnings and Precautions.
If the Following Symptoms Are Experienced, The Patients Should Immediately Contact Their Physician or Emergency Medical Services:
- Priapism: painful erection lasting >4 hours.
- Extreme dizziness or syncope
- Irretractable (>10mins) bleeding from nose, gums, or cuts; Easy Bruising
- Coughing up blood; Vomiting blood; Blood in stool or urine
- Hyponatremia presenting with a constant headache, confusion, weakness, muscle cramps, or even seizures
- Suicidal thoughts
- High temperature (>38°C/>100.4°F), agitation, confusion, twitching, trembling
- Serious Allergic Reactions presenting with an itchy, red, swollen, or blistering rash; Trouble breathing and wheezing: Tightness in the chest or throat; Swelling in the mouth, tongue, lips, face, or throat.
Additional life-threatening side effects of Escitalopram can arise when Lexapro use is suddenly stopped or too much is taken. These two conditions will result in the development of Escitalopram Withdrawal Syndrome and Overdose of Escitalopram. Patients should always remember to take Escitalopram exactly as directed and not to make alterations to their dosage without first consulting their physicians.
Lexapro Weight Loss
As previously mentioned, Serotonin does not only regulate physiological processes related to depression and anxiety. It also regulates physiological processes related to appetite and satiety (a state of being “full” after eating). This Serotonergic regulation, in short, suppresses appetite and curbs hunger. According to the Monoamine Hypothesis in Major Depressive Disorder(MDD), there is a deficiency in the levels of Serotonin, which disrupts the regulation of appetite and hunger. This could explain why certain subsets of Major Depression are associated with increased appetite, hyperphagia, and weight gain. Therefore, it is understandable that Escitalopram therapy, which restores and even elevates the levels of Serotonin within our bodies, would lead to suppressed appetite and decreased hunger leading to weight loss. As such, Lexapro weight loss has been reported during the initial therapy in subsets of patients. Unfortunately, this is only temporary and most patients regain the lost weight within 6 months.
Lexapro Weight Gain
As we have established, Serotonin has definite effects on appetite and hunger regulation. In contrast to the weight loss seen with initial therapy, long-term use of SSRIs has been associated with additional weight gain. The United States National Library of Medicine recognizes increased appetite as one of Escitalopram’s adverse reactions, which could explain the associated Lexapro Weight Gain. However, as Serotonin is a natural suppressor of appetite and hunger, this increase in appetite must be brought on by a different mechanism. Furthermore, peripheral rather than central effects of elevated serotonin levels in the body could better explain why certain patients experience weight gain with continued SSRI therapy.
Possible Causes of Weight Gain Associated with Lexapro Use
Appetite Increase: this is thought to be related more to the patient feeling better with alleviation of depressive symptoms rather than a direct effect of the medication or its therapeutic effect, due to Lexapro mechanism of action.
Peripheral effects of Serotonin on the gastrointestinal tract could explain why patients could experience some weight gain. Although the mechanism of these effects is complicated below are listed some of the effects serotonin has on various gastrointestinal organs that could lead to weight gain:
- In the gut, Serotonin promotes intestinal motility for increased absorption of lipids along the entire length of the gut apical membrane. This increases the total fat absorption.
- In the pancreas, Serotonin promotes the release of insulin, which increases adipogenesis (fat tissue synthesis), lipogenesis (fatty acid synthesis), while also suppressing lipolysis (catabolism of fatty acids in fatty tissues).
- In the liver, Serotonin promotes Gluconeogenesis, Lipogenesis, and fat deposition
- Serotonin promotes the synthesis of White Adipose Tissue (WAT), which is the storage form of fats and prevents the catabolism of the same WAT.
Collectively, Serotonin promotes lipid synthesis and fatty tissue deposition which could account for the Lexapro weight gain seen in some patients with prolonged use.
Stopping Lexapro Due to Adverse Reactions
Previously, the topic of Lexapro Withdrawal Syndrome was mentioned. This syndrome occurs in those patients who have been taking Escitalopram, or other SSRIs, for a prolonged period of time, and in whom physiologic adaptations have occurred. As a result, sudden cessation of Escitalopram would cause a transient deficiency of serotonin and its activity resulting in the characteristic signs and symptoms of Escitalopram Withdrawal. Patients wishing to discontinue Escitalopram because of its adverse reactions should remember to never discontinue use on their own and should consult their physician for information on how to best discontinue Lexapro use.
Coping Strategies: Managing Weight Change From Taking Lexapro
It is worth noting that experiencing adverse reactions associated with SSRI use is quite variable and not all patients will experience weight changes during therapy. However, if patients do experience weight changes that are distressing to them, the following recommendations can be taken to cope with them:
- Dietary Changes: Restrict high-fat and high-calorie foods; Eat smaller portions; Low- and very-low-calorie diets; Exercise
- Cognitive Behavioral Therapy: identifying lifestyle behaviors to be modified, setting goals, modifying triggers of excessive eating
- Switching: Ask your medical doctor about the possibility of switching to another type of antidepressant which has little to no weight-related reactions.
Due to Lexapro Withdrawal, patients wishing to discontinue Escitalopram because of its adverse reactions should remember to never discontinue use on their own and should consult their physician for information on how to best discontinue Lexapro use.
Sexual Dysfunction as a Side Effect of Escitalopram Use
Sexual Dysfunction is one of the most common, yet under-discussed and reported side effects of Selective Serotonin Reuptake Inhibitors (SSRIs) such as Lexapro. The cause of the sexual dysfunction associated with Selective Serotonin Reuptake Inhibitor use is unknown. However, the effects of elevated levels of Serotonin on other hormones (testosterone), peptides (Nitric Oxide), and Neurotransmitters (Dopamine) are thought to play a role as these molecules play an important role in sexual desire, arousal, and orgasm.
As high as 40-65% of patients taking SSRIs report experiencing sexual dysfunction as a side effect within days to weeks from starting therapy.
The Various Reported Adverse Reactions Include:
- Lexapro Side Effects in Men: Delayed ejaculation; Delayed orgasm; Anorgansmia; Erectile Dysfunction; Reduced Libido; Reduced sexual satisfaction; Priapism
- Lexapro Side Effects in Women: Reduced lubrication; Reduced sexual satisfaction, Reduced Libido; Anorgasmia
Whatsmore, the kind and severity of sexual dysfunction are purported to vary by gender. Meaning that sexual Lexapro side effects in men differ from the sexual Lexapro side effects in women.
Women with Major Depression are more likely to have a greater reduction of sexual desire and difficulties with orgasm than men. Women tend to experience a variable degree of remission of these effects with continued therapy with SSRIs. By comparison, men are more likely to experience anorgasmia, delayed ejaculation, and erectile dysfunction. Also, these effects in men are less likely to remit with continued therapy with SSRIs.
Coping Strategies: Managing Escitalopram Sexual Side Effects
The acknowledgment of Escitalopram-induced sexual dysfunctions is important, as 41.7% of men and 15.4% of women have been purported to stop taking psychiatric medications as a result of sexual side effects. This is especially alarming as the sexual dysfunction may itself act as an instigator of Major Depression and act as an impediment to long-term therapy adherence, which is ever so important for SSRIs.
Effective management should begin with an assessment to ascertain whether the sexual dysfunction reported is caused by the antidepressant treatment itself or rather attributed to Major Depression, as it too can have similar effects. Thus, establishing a baseline level of sexual functioning prior to the initiation of SSRIs is optimal. Once this is established, the next big challenge is to manage the dysfunction without causing undesirable mental consequences on the patient.
There Are five general approaches to Managing the Sexual Dysfunction Associated With Escitalopram Use:
- Wait and See: Patients, especially women, may elect to endure these effects as they may be transient and remit with continued use of SSRIs. It is worthwhile to point out that, concomitant alcohol consumption while taking Lexapro can slow the physiological adaptation process and lengthen the duration of sexual dysfunction of SSRIs.
- Reducing Drug Dosage: As previously mentioned, the majority of the Lexapro side effects are related to the therapeutic elevation of serotonin levels and are thus dose-dependent. This means that lowering the dose of Escitalopram can possibly alleviate some of the sexual dysfunction experienced by some patients. However, patients should always remember to never make any alterations to the dosage of their antidepressant medication without consulting their health care provider as this can have serious adverse consequences to their health and wellbeing.
- Drug Holidays: In general, a “drug holiday” refers to a break from any medication for some duration of time. Patients must again consult their health care providers first to see if they are candidates for a drug holiday and if so, to determine the best regimen for the holiday. Always remember that it is of paramount importance to never stop taking or make alterations to the dosage of antidepressants without consulting your doctor first.
- Switching medications: Alternative medications may be a solution for some patients. Antidepressants such as Bupropion, Mirtazapine, and the novel antidepressants, Vilazodone and Vortioxetine have different mechanisms of action than SSRIs and are reported to lower the risk of sexual dysfunction. Patients can ask their doctors about the possibility of switching to one of these agents.
- Adjuncts: Addition of a Phosphodiesterase (PDE) 5 Inhibitors such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) may be an option as well. These agents prevent the degradation of Nitric Oxide and may improve Erectile Dysfunction in men. Their role in alleviating sexual dysfunction in women taking SSRIs is unclear.
Beyond the aforementioned five strategies, patient education about the sexual adverse reactions of antidepressants like SSRIs remains one of the most important strategies to successful treatment and long-term adherence.
Regardless of the side effects and no matter its severity, it is of paramount importance for patients to remember to never stop taking or alter the dose of Escitalopram on their own.
Lexapro And Pregnancy
Escitalopram oxalate is listed as a Pregnancy Category C which means that “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans to provide conclusive information, but potential benefits may warrant use of the drug in pregnant women despite potential risks.” Regardless, it is generally viewed that there is no need to discontinue antidepressants, including Escitalopram, during pregnancy as they are not teratogenic (causing birth defects).
Furthermore, very rare reports of non-teratogenic symptoms of SSRI use in pregnancy have been reported following delivery. However, it is unknown whether these symptoms are caused by the toxic effects of SSRIs on the newborn’s health or are related to SSRI withdrawal syndrome.
Regardless, the Symptoms Include:
- Respiratory Distress, Cyanosis, Apnea
- Seizures, Fluctuating temperature
- Difficulty with feeding, vomiting, hypoglycemia
- Hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, inconsolable crying
- Rare: Persistent Pulmonary Hypertension of the Newborn (PPHN) is a condition which in short will result in insufficient oxygenation of the newborn’s blood and subsequent development of hypoxia and cyanosis.
Breastfeeding while taking Escitalopram
As with most medications, a small percentage of Escitalopram is secreted in breast milk. Regardless, no information regarding contraindication between Escitalopram use and breastfeeding is currently provided by the United States Food and Drug Administration. However, caution should still be utilized and breastfed infants whose mothers are taking Lexapro should be monitored as a precaution for increased somnolence, decreased feeding, and weight loss.
Escitalopram Warnings and Precautions
Patients taking antidepressants, including Escitalopram, may experience worsening of the clinical signs and symptoms of Major Depression, causing the development of suicidality during the early phases of treatment. Lexapro can also trigger rapid cycling of manic/depressive episodes, the development of serotonin syndrome, hyponatremia, and other complications that can be dangerous.
Black Box Warning: Worsening of Symptoms of Depression and Increased Risk of Suicidality
Worsening of the symptoms of Major Depression and suicidal thoughts in patients who use Lexapro seem to be more prominent in adolescents (<18) and young adults (18-24), whereas in the elderly populations (>65) they seem to be less prominent. Family members and caregivers of patients receiving SSRIs should be given adequate information regarding this phenomenon and should be instructed to monitor their loved ones for new and sudden changes in mood, behavior, actions, thoughts, or feeling, especially when Lexapro is just started or dose is altered.
Furthermore, They Should Be Instructed to Contact Emergency Medical Services if the Following Symptoms and Signs Develop:
- Attempt to commit suicide or thoughts about suicide
- Impulsivity and risk-taking behavior
- Acting agitated, aggressive, irritable, or hostile
- Increased restlessness or increased in the amount of talking
- New or worsening symptoms of depression
- Panic attacks
- Hypomania or Mania
SSRIs, like Escitalopram, if incorrectly used to treat the depressive phase of Bipolar disorder, have the propensity to trigger rapid cycling of manic/depressive episodes which can be detrimental to the patient’s health. Therefore, before starting treatment, all patients with episodes of major depression should be screened for Bipolar disorder.
Serotonin Syndrome refers to a life-threatening syndrome of excessive serotonergic signaling that can result if Escitalopram is used concomitantly with other serotonergic medications such as Selective Serotonin Norepinephrine Reuptake Inhibitors (SSNRIs), Monoamine Oxidase Inhibitors (MAOIs), Cyclobenzaprine, Tramadol, Vilazodone, Trazodone, Buspirone, Vortioxetine, Ondansetron, MDMA, Dextromethorphan, Meperidine, Triptans, or Linezolid. Patients and their families should receive information about this syndrome, and be told that if any of the following symptoms are experienced they should immediately discontinue their medications and contact emergency medical services:
- Altered consciousness: delirium, agitation, hallucinations
- Autonomic instability: fever, sweating, tachycardia, variable blood pressure
- Neuromuscular excitability: muscle rigidity, tremor, ataxia, clonus, and hyperreflexia
- Gastrointestinal symptoms: diarrhea, nausea, emesis
Hyponatremia, or low sodium levels, are commonly seen in elderly patients using Lexapro. The low sodium levels seem to be related to an inappropriate release of a hormone called Vasopressin/Antidiuretic Hormone in response to Escitalopram therapy, which causes increased resorption of sodium from urine by the kidneys.
Symptoms and Signs Include:
- Severe Acute Hyponatremia can present with headaches, nausea, seizures, coma, and even death.
- Slowly developing hyponatremia which is mild to moderate can cause anorexia, nausea, vomiting, headache, muscle cramps, weakness, lethargy, and confusion.
All SSRI antidepressants, which include escitalopram, can increase the risk of both internal and external bleeding. As such, any abdominal pain and nausea should be taken seriously. Furthermore, patients should be counseled not to use Escitalopram concomitantly with Aspirin, NSAIDs, or other medication (warfarin) with effects on coagulation.
Severe, life-threatening allergic reactions may occur in a subset of patients. These reactions often occur shortly after taking the drug for the first time, but in some cases, it may be delayed.
Signs of Symptoms of an Allergic Reaction to Escitalopram Include:
- Dyspnea (Difficulty breathing) and wheezing
- Angioedema (Swelling of face, tongue, eye, mouth, or throat)
- Rash, Hives, Blisters, Itching
- Joint pain
If any of these symptoms present in a patient, they should seek immediate emergency medical attention.
Factors That Impact Side Effect Emergence
Lexapro side effects are idiosyncratic and their emergence in every patient is variable. This is because there are many factors at play that impact the emergence of side effects.
Factors That Can Impact Side Effect Emergence Include:
- Dose of medication
- Frequency of administration
- Genetic variations
- Comorbid organ disease especially of the heart, liver, and kidney
The majority of these variables are “unmodifiable”, meaning that they cannot be altered by the patient or their physician, and thus the ability to limit Escitalopram side effects is limited.
However, there are still some steps that can be taken that can make the side effects more tolerable or eliminate them in certain situations.
How To Reduce Lexapro Side Effects
There Are Only a Few Side Effects That Can Be Reduced and Mitigated:
- Xerostomia (Dry mouth) – sugar-free gum or candies which stimulate salivation due to their osmotic effects
- Hyperhidrosis (Excessive sweating) – strong antiperspirants, keeping cool. If conservative measurements do not work, patients can consult their physicians regarding laser treatment or as a last resort switching the class of antidepressant used.
- Insomnia (Inability to sleep) – try to take Escitalopram as early as possible before sleep
- Nausea – this can be combated by staying hydrated and consuming small meals at more frequent intervals.
- Cognitive Behavioral Therapy – this can help combat undesired thoughts and behaviors and find ways to alter them.
Regardless of the side effects and no matter its severity, it is of paramount importance for patients to remember to never stop taking or alter the dose of Escitalopram on their own. If the patients desire to discontinue Escitalopram due to experiencing intolerable side effects, they should consult their physician.
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