Escitalopram

Registered South African indications:

• Major depressive episodes
• Panic disorder with or without agoraphobia
• Social anxiety disorder (social phobia)
• Generalised anxiety disorder
• Obsessive-compulsive disorder

Contraindications

South African recommendations

• Hypersensitivity to escitalopram, or to any of the excipients
• Children and adolescents under the age of 18 years
• Concomitant use with monoamine oxidase inhibitors
  - Cases of serious reactions have been reported in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued an SSRI and have been started on an MAOI. Some cases presented with features resembling serotonin syndrome
  - Escitalopram should not be used in combination with an MAOI
  - Escitalopram may be started 14 days after discontinuing treatment with an MAOI
  - At least 7 days should elapse after discontinuing escitalopram treatment before starting an MAOI
• Concomitant treatment with linezolid
• Concomitant treatment with pimozide as the combination may lead to clinically significant QT interval prolongation
• Patients with known QT interval prolongation or congenital long QT syndrome

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAO-inhibitors) is contraindicated due to the risk of serotonin syndrome with agitation, tremor, hyperthermia, etc
• Combination of escitalopram with reversible MAO-A inhibitors (e.g. moclobemide) or the reversible non-selective MAO-inhibitor linezolid is contraindicated due to the risk of onset of a serotonin syndrome
• Patients with known QT interval prolongation or congenital long QT syndrome
• Escitalopram is contraindicated together with medicinal products that are known to prolong the QT interval

Cautions

South African recommendations

• Pregnancy
• Breastfeeding
• Severe renal impairment (CrCl<30ml/min)
• Hepatic impairment
• Elderly
• Females
• Seizures
  - Seizure history
  - Controlled epilepsy
  - Poorly controlled epilepsy 
• History of suicide-related events
• Significant degree of suicidal ideation prior to commencement of treatment
• Other psychiatric and non-psychiatric disorders
• Abrupt discontinuation (See additional prescribing points)
• Higher doses
• Conditions of altered metabolism
• History of mania/hypomania
• Diabetes mellitus
• Hyponatraemia 
• Cirrhosis 
• Other cardiac diseases 
• Significant bradycardia
• Coronary heart disease 
• Pre-existing slow heart rate
• Recent acute myocardial infarction
• Uncompensated heart failure
• Electroconvulsive therapy
• History of glaucoma
  - Angle closure glaucoma
• Hypokalaemia
• Hypomagnesaemia
• Known bleeding tendencies 
• History of bleeding disorders
  - Von Willebrand disease
  - Haemophilia  
  - Deficiency in F VIII
• Comorbid bleeding disorders
  - Multiple pregnancy
  - Gestational hypertension
  - Preeclampsia
• Coadministration with medicinal agents known to affect platelet function
• Coadministration with medicinal agents with serotonergic effects
• Coadministration with agents which may cause hyponatraemia 
• Galactose intolerance (certain formulations)
• Total lactase deficiency (certain formulations)
• Glucose-galactose malabsorption (certain formulations)
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Pregnancy
• Breastfeeding
• Severe renal impairment (CrCl<30ml/min)
• Hepatic impairment
• Elderly
• Females
• Epilepsy
  - Unstable epilepsy
  - Controlled epilepsy
• Other psychiatric disorders
• History of suicide-related events
• Significant degree of suicidal ideation prior to commencement of treatment
• Abrupt discontinuation (See additional prescribing points)
• Higher doses
• Conditions of altered metabolism
• History of mania/ hypomania
• Diabetes mellitus
• Cirrhosis
• Hypokalaemia
• Other cardiac diseases
• Significant bradycardia
• Coronary heart disease
• Recent acute myocardial infarction
• Uncompensated heart failure
• Electroconvulsive therapy
• History of glaucoma
  - Angle closure glaucoma
• Hypokalaemia
• Hypomagnesaemia
• Poor metabolisers of CYP2C19 (See additional prescribing points)
• Known bleeding tendencies
• Coadministration with medicinal agents known to affect platelet function
• Coadministration with medicinal agents with serotonergic effects
• Coadministration with agents which may cause hyponatraemia 
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: fct, tab

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Major depressive episodes

• Oral (fct, tab): Initial: 10mg, dly; Maintenance: 10-20mg, dly depending on patient response; Max: 20mg/24hrs 

---

Usually, 2-4 weeks are necessary to obtain an antidepressant response 

---

Panic disorder with or without agoraphobia

• Oral (fct, tab): Initial: 5mg, dly for the first week; Then; Titrate to 10mg, dly; Maintenance: 10-20mg, dly depending on patient response; Max: 20mg/24hrs

---

Maximum effectiveness is reached after about 3 months. The treatment lasts several months

---

Social anxiety disorder 

• Oral (fct, tab): Initial: 10mg, dly; Maintenance: 10-20mg, dly depending on patient response; Max: 20mg/24hrs

---

Usually, 2-4 weeks are necessary to obtain symptom relief 

---

Treatment for 3 months is recommended to consolidate response

---

Long-term treatment of responders for 6 months has been shown to prevent relapse and can be considered on an individual basis

---

Treatment benefits should be re-evaluated at regular intervals

---

Generalized anxiety disorder

• Oral (fct, tab): Initial: 10mg, dly; Maintenance: 10-20mg, dly depending on patient response; Max: 20mg/24hrs 

---

Long term treatment of responders has been studied for at least 6 months and can be considered on an individual basis to prevent relapse

---

Obsessive-compulsive disorder (OCD) 

• Oral (fct, tab): Initial: 10mg, dly; Maintenance: 10-20mg, dly depending on patient response; Max: 20mg/24hrs 

---

Long-term treatment of patients responding to a 16-week open treatment phase has been studied for at least 24 weeks in patients receiving 10 or 20mg/day

---

As OCD is a chronic disease, patients should be treated for a sufficient period to ensure that they are symptom free. This period may be several months or even longer

---

All indications: Administered as a single daily dose without regard to food intake

Contraindicated

Pregnancy

South African recommendations

• Caution; not recommended 
• Should not be used during pregnancy
• Limited clinical data are available regarding exposure to escitalopram during pregnancy. In reproductive toxicity studies performed in rats, embryo-fetotoxic effects (reduced foetal weight and minor delay in ossification) were observed with exposure to escitalopram, but there was no effect on foetal viability and no increased incidence of malformations
• If used until or shortly before birth, discontinuation effects in the newborn are possible. Using escitalopram in the third trimester may result in effects, including neurobehavioral disturbances, in the newborn infant
• The following symptoms may occur in the newborn after maternal selective serotonin reuptake inhibitors (SSRI)/serotonin norepinephrine reuptake inhibitors (SNRI) use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either discontinuation effects or excess serotonergic activity. In a majority of instances, such complications begin immediately or soon (<24 hours) after delivery
• Epidemiological data have suggested that the use of SSRIs such as escitalopram in pregnancy, particularly in late pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (PPHN)
• There is data of an increased risk (less than 2-fold) of postpartum haemorrhage following exposure to an SSRI or SNRI within the month prior to birth.  Although no studies have investigated an association between escitalopram, treatment and postpartum haemorrhage, there is a potential risk, considering the related mechanism of action

Recommendations in other jurisdictions

• Caution; not recommended 
• Only limited clinical data are available regarding exposed pregnancies 
• Animal studies have shown reproductive toxicity.  Escitalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit
• Neonates should be observed if maternal use continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided during pregnancy
• The following symptoms may occur in the neonate after maternal selective serotonin reuptake inhibitors (SSRI)/serotonin norepinephrine reuptake inhibitors (SNRI) use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery
• Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur
• Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth

Breastfeeding 

South African recommendations

• Caution; not recommended 
• Escitalopram is excreted in breastmilk. Breastfeeding is not recommended during treatment

Recommendations in other jurisdictions

• Caution; not recommended 
• It is expected that escitalopram will be excreted into human milk. Consequently, breastfeeding is not recommended during treatment

Fertility

• Animal data have shown that citalopram may affect sperm quality
• Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far

Renal Impairment 

• Mild to moderate (CrCl≥30ml/min): No dose adjustment recommended
• Severe (CrCl<30ml/min): Caution; no information available  

Hepatic Impairment

• Caution; dose adjustment recommended 
  Dosages should be halved to the lower end of the dose range
  Initial dose: 5mg, dly, for 2 weeks; Titrate gradually depending on individual patient response; Max: 10mg/24hrs 
  Careful dose titration is advised in severely reduced hepatic function 

Elderly

• Caution; dose adjustment recommended 
  Lower initial and maximum dose should be considered
  Initial dose: 5mg, dly; Titrate gradually depending on individual patient response; Max: 10mg/24hrs 
  The efficacy of escitalopram in social anxiety disorder has not been studied in elderly patients 

Porphyria Information

• Probably not porphyrinogenic (PNP)   

Drugs in Sport

• Permitted - No warnings 

Central Nervous System Disorders

• Headache 
• Insomnia 
• Somnolence
• Dizziness 
• Paraesthesia 
• Tremor 
• Sleep disorder 
• Syncope 
• Serotonin syndrome 
• Dyskinesia 
• Movement disorder 
• Seizures 
• Psychomotor restlessness 
• Akathisia 
• Fatigue 
• Anxiety 
• Restlessness 
• Abnormal dreams
• Decreased libido
• Anorgasmia (female)
• Bruxism 
• Agitation 
• Nervousness
• Panic attacks 
• Confusional state 
• Aggression 
• Depersonalisation  
• Hallucination 
• Mania 
• Suicidal ideation
• Suicidal behaviour 

Cardiovascular Disorders

• Tachycardia 
• Bradycardia 
• Prolonged QT electrocardiogram 
• Ventricular arrhythmias, including torsade de pointes 
• Orthostatic hypotension 

Respiratory Disorders

• Sinusitis 
• Yawning 
• Epistaxis

Gastrointestinal Disorders

• Nausea and vomiting 
• Diarrhoea 
• Constipation 
• Dry mouth 
• Gastrointestinal haemorrhages
  -  Rectal haemorrhage

Hepatobiliary Disorders

• Hepatitis 
• Abnormal hepatic function tests 

Genitourinary Disorders

• Urinary retention 
• Ejaculation disorder (male)
• Impotence (male)
• Metrorrhagia (female)
• Menorrhagia (female)
• Postpartum haemorrhage 
• Priapism 

Endocrine and Metabolic Disorders

• Inappropriate antidiuretic hormone secretion 
• Increased appetite 
• Decreased appetite 
• Increased weight 
• Decreased weight 
• Hyponatraemia 
• Anorexia 
• Galactorrhoea 

Musculoskeletal Disorders

• Arthralgia 
• Myalgia 

Skin and Subcutaneous Tissue Disorders

• Increased sweating 
• Urticaria
• Alopecia 
• Rash
• Pruritus 
• Ecchymosis 
• Angioedemas 

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia 
• Anaphylactic reaction 
• Fever 
• Oedema 

Sensory Disorders

• Taste disturbance
• Mydriasis 
• Visual disturbance 
• Tinnitus 

• Irreversible non-selective monoamine oxidase inhibitors (MAO-inhibitors)
• Reversible, selective monoamine oxidase-A inhibitors
• Moclobemide
• Reversible, non-selective MAO-inhibitors
• Linezolid
• Irreversible, selective monoamine oxidase-B inhibitors 
• Selegiline
• QT-prolonging agents
• Class IA and III antiarrhythmics
• Antipsychotics
• Phenothiazine derivatives
• Pimozide
• Haloperidol
• Tricyclic antidepressants
• Antimicrobial agents
• Sparfloxacin
• Moxifloxacin
• Erythromycin IV
• Pentamidine
• Anti-malarial treatment
• Halofantrine
• Antihistamines
• Astemizole
• Hydroxyzine
• Mizolastine
• Serotonergic agents
• Opioids
• Tramadol
• Triptans 
• Sumatriptan
• Agents that lower the seizure threshold
• Antidepressants
• Other selective serotonin reuptake inhibitors
• Neuroleptics
• Thioxanthenes
• Butyrophenones
• Mefloquine
• Bupropion
• Lithium
• Tryptophan
• Oral anticoagulants
• Non-steroidal anti-inflammatory drugs 
• Agents that induce hypokalaemia 
• Agents that induce hypomagnesaemia 
• CYP2C19 inhibitors
• Omeprazole
• Cimetidine
• Esomeprazole
• Fluconazole
• Fluvoxamine
• Lansoprazole
• Ticlopidine
• CYP2D6 substrates
• Flecainide
• Propafenone
• Metoprolol 
• Desipramine
• Clomipramine
• Nortriptyline
• Risperidone
• Thioridazine

Other interactions

• St John's wort
• Alcohol

• Eletrolytes
  - Potassium
  - Magnesium 
• Hepatic function
• Renal function

Specific cases may require

• Electrocardiogram
• Sodium 
• Full blood count 
• Vital signs

Additional observations

• Personal or family history of bipolar disorder, hypomania, or mania
• Depression (particularly during initial 1-2 months of therapy or during periods of dosage adjustments)
• Clinical worsening (particularly during initial 1-2 months of therapy or during periods of dosage adjustments)
• Suicidality (particularly during initial 1-2 months of therapy or during periods of dosage adjustments)
• Psychosis (particularly during initial 1-2 months of therapy or during periods of dosage adjustments)
• Unusual changes in behavior (e.g. anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania) (particularly during initial 1-2 months of therapy or during periods of dosage adjustments)
• Signs/symptoms of serotonin syndrome
  - Mental status changes (e.g. agitation, hallucinations, delirium, coma)
  - Autonomic instability e(.g. tachycardia, labile blood pressure, diaphoresis)
  - Neuromuscular changes (e.g. tremor, rigidity, myoclonus)
  - Gastrointestinal symptoms (e.g nausea, vomiting, diarrhoea)
  - Seizures
• Blood loss
• Signs of anaemia
  - Fatigue
  - Shortness of breath
  - Chest pain
  - Breastfeeding problems

Risk of postpartum haemorrhage (PPH)

• PPH is a leading cause of maternal mortality. Treatment with SSRIs and SNRIs within one month prior to birth may increase the risk of PPH 
• Observational data indicate an increased risk of PPH following SSRI/ SNRI exposure within the month prior to delivery 
• Healthcare professionals should be aware of the potential risk of PPH while making treatment decisions for prescribing SSRI/ SNRI towards the end of pregnancy
• Patients should be advised to inform their doctors before taking SSRI/ SNRI containing medicines if they have history of bleeding disorders (e.g von Willebrand disease, haemophilia A, deficiency in F VIII, and haemophilia B); and comorbid bleeding disorders (e.g multiple pregnancy, gestational hypertension or preeclampsia)

Poor metabolisers of CYP2C19 

• For patients who are known to be poor metabolisers of CYP2C19, an initial of dose 5mg daily during the first two weeks of treatment is recommended. Depending on individual patient response, the dose may be increased to 10mg daily 

Discontinuation symptoms seen when stopping treatment

• Abrupt discontinuation should be avoided
• When stopping treatment with escitalopram the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of discontinuation 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
• Discontinuation of SSRIs/SNRIs (particularly when abrupt) commonly leads to discontinuation symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally, these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged
• It is therefore advised that when treatment is no longer required, gradual discontinuation by dose tapering should be carried out

Escitalopram is a selective inhibitor of serotonin (5-HT) re-uptake with high affinity for the primary binding site. It also binds to an allosteric site on the serotonin transporter, with a 1000 fold lower affinity. Escitalopram has no or low affinity for a number of receptors including 5-HT_1A, 5-HT₂, DA D₁ and D₂ receptors, α₁-, α₂-, β-adrenoceptors, histamine H₁, muscarine cholinergic, benzodiazepine, and opioid receptors. The inhibition of 5-HT re-uptake is the only likely mechanism of action explaining the pharmacological and clinical effects of escitalopram. 

Tablet 5mg

• Escitalopram Winthrop (Winthrop)
• Lexamil (Cipla Medpro)

Tablet 10mg

• Accord Escitalopram (Accord)
• Aspen Escitalopram (Pharmacare)
• Cipralex (H.Lundbeck) originator
• Citraz (Dr Reddy's)
• Dolin (Aurobindo)
• Emerdyne 10 (Macleods Pharmaceuticals)
• Escitalopram Be Tabs (Cipla Medpro)
• Escitalopram Unicorn (Unicorn)
• Escitalopram Winthrop (Winthrop)
• Esetam 10 (RX Medicals)
• Ficali 10 (Trinity Pharma)
• Lexamil (Cipla Medpro)
• Marprem (Novagen)
• Nexito fct (Ranbaxy)
• Zitolex (Arrow)
• Zydus Escitalopram (Zydus)
• Zyescito 10mg (Aurobindo Pharma)
• Zytomil (Pharma Dynamics)

Tablet 20mg

• Accord Escitalopram (Accord)
• Cipralex (H.Lundbeck) originator
• Citraz (Dr Reddy's)
• Dolin (Aurobindo)
• Escitalopram Be-Tabs (Cipla Medpro)
• Escitalopram Unicorn (Unicorn)
• Escitalopram Winthrop (Winthrop)
• Esetam 20 (RX Medicals)
• Ficali 20 (Trinity Pharma)
• Lexamil (Cipla Medpro)
• Macleods Escitalopram 20 (Macleods Pharmaceuticals)
• Marprem (Novagen)
• Zitolex (Arrow)
• Zyescito 20mg (Aurobindo Pharma)
• Zytomil (Pharma Dynamics)