Citalopram

Registered South African indications:

• Depression and prevention of relapse
• Panic disorder with or without agoraphobia
• Obsessive-compulsive disorder (OCD)

Contraindications 

South African recommendations

• Hypersensitivity to the active ingredient or any of its excipients 
• Children and adolescents <18yrs 
• Monoamine oxidase inhibitors (MAOIs)
  - Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the selective MAO-B inhibitor selegiline and the reversible MAOI (RIMA), moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI
  - Some cases presented with features resembling serotonin syndrome
  - Citalopram must not be used in combination with a MAOI, including selegiline in doses above 10mg daily
  - Within 14 days of discontinuing a non-selective MAOIs. Treatment with citalopram may be instituted 14 days after discontinuation
  -Within 1 day of discontinuing moclobemide. Treatment with citalopram may be instituted a minimum of 1 day after discontinuation
  - Treatment with MAOIs may be introduced 7 days after discontinuation of citalopram
• Concomitant treatment with pimozide
• In combination with linezolid
• Severely impaired renal function (creatinine clearance less than 30ml/min)
• In patients with known QT interval prolongation or congenital long QT syndrome
• Coadministration with medicines that are known to prolong the QT-interval

Recommendations in other jurisdictions

• Hypersensitivity to citalopram or to any of the excipients
• Monoamine oxidase inhibitors (MAOIs)
  - Some cases presented with features resembling serotonin syndrome
  - Patients receiving (MAOIs), including selegiline, in daily doses exceeding 10mg/day
  - Citalopram should not be given for 14 days after discontinuation of an irreversible MAOI or for the time specified after discontinuation of a reversible MAOI (RIMA) as stated in the prescribing text of the RIMA
  - MAOIs should not be introduced for 7 days after discontinuation of citalopram
• Citalopram is contraindicated in the combination with linezolid unless there are facilities for close observation and monitoring of blood pressure
• Patients with known QT-interval prolongation or congenital long QT syndrome
• Citalopram is contraindicated together with medicinal products that are known to prolong the QT-interval 

Cautions 

South African recommendations

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment (CrCl≥30ml/min)
• Hepatic impairment 
• Elderly
• Females 
• Other psychiatric and non-psychiatric disorders
• History of suicide-related events
• Significant degree of suicidal ideation prior to commencement of treatment
• Pre-existing QT interval prolongation
• Conditions of altered metabolism with increased peak levels
• Hypokalaemia
• Hypomagnesaemia
• Abrupt discontinuation (See additional prescribing points)
• Higher doses
• Hyponatraemia 
• Seizures
  - Seizure history
  - Controlled epilepsy
  - Poorly controlled epilepsy 
• Mania
  - Manic depressive illness
• Pre-existing slow heart rate
• Diabetes mellitus
• History of Glaucoma
  - Angle closure glaucoma
• Cardiac disease 
• Significant bradycardia
• Recent acute myocardial infarction
• Uncompensated heart failure
• History of bleeding disorders
  - Von Willebrand disease 
  - Haemophilia 
  - Deficiency in F VIII
• Comorbid bleeding disorders
  - Multiple pregnancy
  - Gestational hypertension
  - Preeclampsia
• Electroconvulsive therapy
• Psychosis 
• Coadministration with medicinal agents with serotonergic effects
• Coadministration with active substances known to affect platelet function (e.g. warfarin) or other active substances that can increase the risk of haemorrhage
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Pregnancy 
• Breastfeeding 
• Renal impairment 
• Hepatic impairment 
• Elderly
• Other psychiatric disorders
• History of suicidal-related events 
• Significant degree of suicidal ideation
• Mania
  - Manic depressive illness
• Pre-existing QT interval prolongation
• Poor metabolisers of  CYP2C19 (See additional prescribing points)
• Females
• Hypokalaemia
• Hypomagnesaemia
• Abrupt discontinuation (See additional prescribing points) 
• Higher doses
• Hyponatraemia 
• Epilepsy
  - Unstable epilepsy
  - Controlled epilepsy
• Diabetes mellitus
• Glaucoma 
  - Angle-closure glaucoma
• Cardiac disease
• Significant bradycardia
• Recent acute myocardial infarction
• Uncompensated heart failure
• History of bleeding disorders
• Comorbid bleeding disorders with SSRIs
  - Ecchymoses
  - Gynaecological haemorrhages
  - Gastrointestinal bleeding
  - Other cutaneous or mucous bleedings
• Electroconvulsive therapy
• Psychosis 
• Coadministration with medicinal agents with serotonergic effects
• Coadministration with active substances known to affect platelet function or other active substances that can increase the risk of haemorrhage
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• 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
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Depression and prevention of relapse

• Oral (fct, tab): Initial: 20mg, dly; Maintenance: 20-40mg, dly depending on patient response; Treatment duration: Up to 6 months after recovery in order to prevent relapse; Max: 40mg/24hrs

Obsessive-compulsive disorder (OCD)

• Oral (fct, tab): Initial: 20mg, dly; Maintenance: 20-40mg, dly depending on patient response; Treatment duration: Onset of action is 2-4 weeks with further improvement over time; Max: 40mg/24hrs

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Depression and OCD: The onset of effect usually sets in after 2-4 weeks

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Depression: Treatment with citalopram is symptomatic and must therefore be continued for an appropriate length of time, usually up to 6 months after recovery in order to prevent relapse

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Panic disorder with or without agoraphobia

• Oral (fct, tab): Initial: 10mg, dly for the first week; Then: Titrate to 20mg, dly; Maintenance: 20-40mg, dly depending on patient response; Max: 40mg/24hrs

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All indications: Abrupt discontinuation should be avoided. When stopping treatment with citalopram the dose should be gradually reduced over a period of at least 1-2 weeks in order to reduce the risk 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 medical practitioner may continue decreasing the dose, but at a more gradual rate

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Citalopram tablets can be taken any time of the day without regard to food intake

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Indications and dosages registered in other jurisdictions

Major depressive episodes
- Initial phase
- Maintenance against potential relapse/recurrence

• Oral (fct, tab): Initial: 20mg, dly; Maintenance: 20-40mg, dly depending on patient response; Treatment duration: ≥6 months to ensure that they are free from symptoms; Max: 40mg/24hrs

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In general, improvement starts after one week, but may only become evident from the second week of therapy

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Dosage should be reviewed and adjusted if necessary within 3-4 weeks of initiation of therapy and thereafter as judged clinically appropriate

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Panic disorder with or without agoraphobia

• Oral (fct, tab): Initial: 10mg, dly for the first week; Then: Titrate to 20mg, dly; Titrate in 10mg steps according to the patient's response up to the recommended dose; Maintenance: 20-40mg, dly depending on individual patient response; Max: 40mg/24hrs

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A low initial starting dose is recommended to minimise the potential worsening of panic symptoms, which is generally recognised to occur early in the treatment of this disorder

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Patients with panic disorder should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months or even longer

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All indications: Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen some patients may benefit from having their dose increased up to a maximum of 40mg. Dosage adjustments should be made carefully on an individual patient basis, to maintain the patients at the lowest effective dose

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Abrupt discontinuation should be avoided. When stopping treatment with citalopram the dose should be gradually reduced over a period of at least 1-2 weeks in order to reduce the risk of withdrawal reactions. 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 medical practitioner may continue decreasing the dose, but at a more gradual rate

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Citalopram tablets are administered as a single daily dose. Citalopram tablets can be taken at any time of the day without regard to food intake

Paed. dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

• Contraindicated

Indications and dosages registered in other jurisdictions

• Not established for use in children below 18 years

Pregnancy 

South African recommendations

• Caution; positive evidence of risk
• Safety in pregnancy has not been established
• The following symptoms may occur in neonates after maternal selective serotonin reuptake inhibitors (SSRI) 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 such as citalopram in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN)
• Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/ serotonin non-selective reuptake inhibitors (SNRI) exposure within the month prior to birth. Neonates should be observed if maternal use of citalopram continues into the later stages of pregnancy, particularly in the third trimester
• Abrupt discontinuation should be avoided during pregnancy

Recommendations in other jurisdictions

• Caution; not recommended
• Published data on pregnant women (more than 2500 exposed outcomes) indicate no malformative foeto/neonatal toxicity, however, citalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of risk/benefit
• Neonates should be observed if maternal use of citalopram 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 neonates after maternal selective serotonin reuptake inhibitors (SSRIs)/serotonin non-selective reuptake inhibitors (SNRIs) 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
• Safety in lactation has not been established
• Citalopram is excreted into breast milk

Recommendations in other jurisdictions

• Caution; not recommended  
• Citalopram is excreted into breast milk. It is estimated that the breastfeeding infant will receive about 5% of the weight related maternal daily dose (in mg/kg). No or only minor events have been observed in the infants. However, the existing information is insufficient for assessment of the risk to the child
• Caution is recommended. If treatment with citalopram is considered necessary, discontinuation of breastfeeding should be considered

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 

South African recommendations

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

Recommendations in other jurisdictions

• Mild to moderate (CrCl≥20ml/min): Caution; no dose adjustment recommended 
• Severe (CrCl<20ml/min): Caution; no information available 

Hepatic Impairment

• Caution; dose adjustment recommended 

Hepatic Impairment	Dose
Mild to moderate	Oral (tab): Initial: 10mg, dly; Maintenance: 10-20mg, dly; Max: 20mg/24hrs
Severe	Caution and extra careful dose titration are advised

Elderly 

• Caution; dose adjustment recommended 
  Decrease to half the recommended dose; Max: 20mg/24hrs

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Sleep disorder
• Agitation
• Decreased libido
• Anxiety
• Nervousness
• Confusional state
• Abnormal dreams
• Apathy
• Aggression
• Depersonalisation
• Hallucination
• Mania
• Panic attack
• Bruxism
• Restlessness
• Suicidal ideation
• Suicidal behaviour
• Somnolence
• Insomnia
• Headache
• Tremor
• Paraesthesia
• Dizziness
• Attention disturbance
• Migraine
• Amnesia
• Syncope
• Grand mal seizure
• Dyskinesia
• Seizures 
• Serotonin syndrome
• Extrapyramidal disorder
• Movement disorder
• Akathisia
• Asthenia

Cardiovascular Disorders 

• Palpitations
• Bradycardia
• Tachycardia
• QT prolongation
• Ventricular arrhythmia including torsade de pointes
• Haemorrhage
• Orthostatic hypotension

Respiratory Disorders 

• Yawning
• Rhinitis
• Coughing
• Epistaxis

Gastrointestinal Disorders 

• Dry mouth
• Nausea and vomiting
• Diarrhoea
• Constipation
• Dyspepsia
• Abdominal pain
• Flatulence
• Salivary hypersecretion
• Gastrointestinal haemorrhage 
  - Rectal haemorrhage

Hepatobiliary Disorders 

• Hepatitis
• Abnormal hepatic function test

Genitourinary Disorders 

• Urinary retention
• Impotence
• Ejaculation disorder
• Ejaculation failure 
• Menorrhagia
• Metrorrhagia
• Postpartum haemorrhage (See additional prescribing points)
• Increased libido
• Abnormal orgasm (female)
• Priapism

Endocrine and Metabolic Disorders 

• Inappropriate antidiuretic hormone secretion 
• Decreased appetite
• Increased appetite 
• Decreased weight
• Increased weight 
• Hyponatraemia
• Hypokalaemia
• Galactorrhoea (in males)

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Bone fractures

Skin and Subcutaneous Tissue Disorders 

• Increased sweating
• Pruritus
• Urticaria
• Alopecia
• Rash
• Purpura
• Photosensitivity reaction
• Ecchymosis
• Angioedema

Immune, Blood and Lymphatic System Disorders 

• Thrombocytopenia
• Hypersensitivity
• Anaphylactic reaction 
• Pyrexia
• Oedema

Sensory Disorders 

• Mydriasis (may lead to acute narrow angle glaucoma) 
• Visual disturbance
• Tinnitus
• Taste disturbance

• Moclobemide 
• Buspirone 
• Monoamine oxidase inhibitors 
• Selegiline 
• Linezolid
• QT prolonging agents 
• Class IA and III antiarrhythmics
• Antipsychotics (including atypical antipsychotics)
• Phenothiazine derivatives
• Pimozide
• Haloperidol
• Tricyclic antidepressants
• Antimicrobial agents
• Sparfloxacin
• Moxifloxacin
• Erythromycin IV
• Pentamidine
• Antimalarials
• Halofantrine
• Antihistamines
• Astemizole
• Mizolastine
• Serotonergic agents 
• Lithium 
• Tryptophan 
• Tramadol
• Sumatriptan
• Oxitriptan
• Triptans
• Agents that induce hypokalaemia 
• Agents that induce hypomagnesaemia 
• Agents that lower the seizure threshold 
• Antidepressants (selective serotonin reuptake inhibitors)
• Neuroleptics 
• Thioxanthenes
• Butyrophenones
• Mefloquin
• Bupropion
• Anticoagulants  
• Agents that affect platelet function
• Non-steroidal anti-inflammatory drugs
• Acetylsalicylic acid
• Dipyridamole
• Ticlopidine
• Agents that increase risk of haemorrhage
• Cimetidine 
• CYP2C19 inhibitors
• Omeprazole
• Esomeprazole
• Fluconazole
• Fluvoxamine
• Lansoprazole
• CYP2D6 substrates
• Flecainide
• Propafenone
• Metoprolol
• Desipramine
• Clomipramine
• Nortriptyline
• Risperidone
• Thioridazine
• Desipramine

Other interactions

• Electroconvulsive therapy 
• Alcohol  
• St. John's wort  

• Hepatic function
• Renal function
• Electrolytes 
  - Potassium 
  - Magnesium 

Specific cases may require

• Full blood count
• Electrocardiogram (ECG)
• Sodium 
• Vital signs

Additional observations

• 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 behaviour (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 change (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

Poor metabolisers of CYP2C19

• An initial dose of 10mg daily during the first two weeks of treatment is recommended for patients who are known to be poor metabolizers with respect to CYP2C19. The dose may be increased to a maximum of 20mg daily depending on individual patient response

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)

QT-interval prolongation

• Citalopram has been found to cause a dose-dependent prolongation of the QT-interval
• Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalemia, or with pre-existing QT prolongation or other cardiac diseases
• In a double-blind, placebo-controlled ECG study in healthy subjects, the change from baseline in QTc (Fridericia- correction) was 7.5 (90%CI 5.9-9.1) msec at the 20mg/day dose and 16.7 (90%CI 15.0-18.4) msec at the 60mg day/dose

Biochemical and behavioural studies have shown that citalopram is a potent inhibitor of the serotonin (5-HT)-uptake. Tolerance to the inhibition of 5-HT-uptake is not induced by long-term treatment with citalopram. Citalopram is a very selective serotonin reuptake inhibitor (SSRI), with no, or minimal, effect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake.

In contrast to many tricyclic antidepressants and some of the newer SSRI's, citalopram has no or very low affinity for a series 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. A series of functional in vitro tests in isolated organs as well as functional in vivo tests have confirmed the lack of receptor affinity. This absence of effects on receptors could explain why citalopram produces fewer of the traditional side effects such as dry mouth, bladder and gut disturbance, blurred vision, sedation, cardiotoxicity and orthostatic hypotension. The main metabolites of citalopram are all SSRIs although their potency and selectivity ratios are lower than those of citalopram. However, the selectivity ratios of the metabolites are higher than those of many of the newer SSRIs. The metabolites do not contribute to the overall antidepressant effect.

Tablet 10mg

• Austell Citalopram (Austell)
• Bio Citalopram 10 (Biotech Laboratories)

Tablet 20mg

• Acti-Lift (Activo)
• Adco-Talomil (Adcock Ingram)
• Arrow Citalopram (Arrow)
• Austell Citalopram (Austell)
• Bio Citalopram (Biotech Laboratories)
• Cilate (Unicorn Pharmaceuticals)
• Cilift (Pharmacare)
• Ciloram (Novagen)
• Cipramil (H.Lunbeck) originator
• Citalopram Actor (Cipla)
• Citalopram 20 Oethmaan (Oethmaan Biosims)
• Citalopram Winthrop (Zentiva)
• Depramil (Cipla Medpro)
• Gulf Citalopram 20 (Gulf)
• Recita (Aurobindo)
• Ran-Citalopram (Ranbaxy)
• Sandoz Citalopram (Sandoz)
• Simayla Citalopram (Ranbaxy)
• Tamomilt 20 ( Trinity Pharma)

Tablet 40mg

• Arrow Citalopram (Arrow)
• Austell Citalopram (Austell)
• Depramil (Cipla Medpro)
• Ran-Citalopram (Ranbaxy)
• Sandoz Citalopram (Sandoz)