Indications
Ministry of Health of Russia
F32 Depressive episode
F33 Recurrent depressive disorder
F40.0 Agoraphobia
F41.0 Panic disorder [episodic paroxysmal anxiety]
F42 Obsessive-compulsive disorder
FDA recommendations
Depression
UK Medicines and Healthcare Products Regulatory Agency guidelines
Depression
Panic disorder with/without agoraphobia
Drug interactions Citalopram
Taking citalopram simultaneously with MAO inhibitors can lead to the development of a hypertensive crisis (serotonin syndrome). Citalopram enhances the effect of sumatriptan and other serotonergic drugs. Cimetidine causes a moderate increase in the average steady-state concentration of citalopram in the blood plasma; this should be taken into account when prescribing these drugs in high doses simultaneously. There is no evidence of interaction of citalopram with lithium or alcohol, or clinically significant interaction of citalopram with phenothiazines or tricyclic antidepressants. Clinical studies have not established the interaction of citalopram with concomitantly prescribed benzodiazepines, neuroleptics, analgesics, lithium, antihistamines, antihypertensive drugs, beta-adrenergic receptor blockers and other drugs acting on the cardiovascular system.
Treatment regimen
Dosage and dose selection
- 20-40 mg/day
- Start with 20 mg/day, increase to 40 mg after a few weeks
- Take the daily dose at one time: morning or evening
- Treatment with a dose higher than 40 mg increases the risk of cardiac complications [1].
- If anxiety, insomnia, agitation, or akathisia occur at the beginning of treatment or after interruption of treatment, the possibility of bipolar disorder should be considered and switched to a mood stabilizer or an atypical antipsychotic
How quickly does it work?
Begins to act after 2-4 weeks
If there is no effect after 6-8 weeks, you need to increase the dose or switch to another drug
To prevent relapse, it can be taken for many years.
Expected Result
Complete remission.
After the symptoms of depression disappear, you should continue taking it for one year if this was the treatment of the first episode. If this is to treat a recurrent episode, treatment can be extended indefinitely.
Use in the treatment of anxiety is indefinite [1].
If it doesn't work
Change the dose, switch to another medicine or add an auxiliary drug;
Connect psychotherapy;
Review the diagnosis by identifying comorbid conditions;
In patients with undiagnosed bipolar affective disorder, the effectiveness of treatment may be low, in which case it is necessary to switch to a mood stabilizer [1].
How to stop taking it
There is no need to reduce it gradually, but to be sure to avoid withdrawal symptoms, you can reduce it gradually. Gradual reduction scheme: dose reduced by 50% - 3 days, again reduced by 50% - 3 days, complete cessation. If withdrawal symptoms appear, increase the dose, wait for withdrawal symptoms to subside, and continue decreasing [1].
Treatment combinations
- For insomnia: trazadone
- For fatigue, drowsiness, loss of concentration: modafinil [3].
- Combinations with other antidepressants may activate bipolar disorder and suicidal ideation
- For bipolar depression, psychotic depression, treatment-resistant depression, treatment-resistant anxiety disorder: mood stabilizers, atypical antipsychotics
- For anxiety disorder: gabapentin, tiagabine
Citalopram tablets ppo 10 mg No. 30
Compound
Active substance: citalopram (in the form of hydrobromide) - 10 mg. Excipients: microcrystalline cellulose 46.90 mg, pregelatinized starch 20.20 mg, magnesium stearate 0.40 mg.
Pharmacokinetics
The bioavailability of citalopram is 80% and is practically independent of food intake. Cmax in plasma is achieved on average after 3 hours. Pharmacokinetics is linear and dose-dependent when taking single and multiple doses (doses in the range of 10-60 mg per day). When taken once a day, Css in plasma is established after 7-14 days of therapy. Vd – about 12-17 l/kg. Plasma protein binding - no more than 80%. It is present in plasma unchanged. Passes into breast milk.
Metabolized by demethylation, deamination and oxidation with the participation of cytochrome P450 (isoenzymes CYP3A4 and CYP2C19, to a lesser extent CYP2D6) with the formation of pharmacologically less active metabolites. Inhibition of one of these enzymes can be compensated for by other enzymes. T1/2 of citalopram is 1.5 days (36 hours). Excretion is carried out by the kidneys (15%) and liver (85%). 12-23% of citalopram is excreted unchanged through the kidneys. Hepatic clearance is about 0.3 l/min, renal clearance is 0.05-0.08 l/min.
Patients over 65 years of age
A longer T1/2 and lower clearance values are observed due to decreased metabolism.
Liver failure
In patients with reduced liver function, citalopram is eliminated more slowly. T1/2 of citalopram is almost doubled and steady-state plasma concentrations of citalopram are almost twice as high compared to patients with normal liver function after taking a similar dose.
Kidney failure
In patients with mild to moderate reduction in renal function, citalopram elimination occurs more slowly without a significant effect on pharmacokinetics. Caution is required in patients with severe renal impairment (creatinine clearance below 30 ml/min).
Indications for use
- Moderate to severe depressive episodes and preventing their relapse.
- Panic disorder with/without agoraphobia.
Contraindications
- Hypersensitivity to citalopram or any of the excipients.
- Concomitant use with monoamine oxidase inhibitors (MAO) (including selegiline at a dose above 10 mg/day). The time interval between stopping taking irreversible MAO inhibitors and starting citalopram should be at least 14 days. In the case of using reversible MAO A inhibitors, the duration of the break is determined in accordance with the instructions for medical use of these drugs. Treatment with MAO inhibitors can be started no earlier than 7 days after stopping citalopram.
- Concomitant use with linezolid, if it is impossible to closely monitor the patient and monitor blood pressure.
- Concomitant use with pimozide.
- Established prolongation of the QT interval or congenital long QT interval.
- Concomitant use with drugs that prolong the QT interval.
- Children and adolescents (up to 18 years) (efficacy and safety of use have not been confirmed).
With caution:
history of QT interval prolongation; ventricular arrhythmia, including torsade de pointes; significant bradycardia; recent acute myocardial infarction; decompensated heart failure; hypokalemia and/or hypomagnesemia (electrolyte imbalances should be corrected before starting treatment with citalopram); severe renal failure (creatinine clearance below 30 ml/min); severe liver failure (careful dose selection is recommended); severe suicidal behavior (careful monitoring of patients is required until the condition improves several weeks after the start of treatment); diabetes mellitus (dosage adjustment of insulin and/or oral hypoglycemic drugs may be required); tendency to bleeding (especially when used simultaneously with drugs that affect platelet function or drugs that may increase the risk of bleeding); simultaneous use with the MAO B inhibitor selegiline, serotonergic drugs; drugs that lower the seizure threshold; cimetidine (increased equilibrium concentration of citalopram), metoprolol (increased concentration of metoprolol), lithium and tryptophan (increased effect), drugs containing St. John's wort (increased side effects); oral anticoagulants and medications that affect blood clotting (increasing the risk of bleeding); drugs that are weak metabolites of the CYP2C19 isoenzyme (it is necessary to reduce the initial dose); ethanol; electroconvulsive therapy; elderly people over 65 years of age (dose reduction required); pregnancy, breastfeeding period.
More detailed information about the instructions and precautions is provided in the sections “Interaction with other drugs”, “Special instructions”, “Use during pregnancy and breastfeeding”.
Directions for use and doses
Citalopram is prescribed orally once a day. The drug can be taken at any time of the day, regardless of meals. Tablets should not be divided in half.
Depression:
Citalopram is prescribed once a day 20 mg. Depending on the patient's individual response, the dose can be increased to a maximum of 40 mg per day.
The antidepressant effect usually develops 2-4 weeks after the start of treatment.
Antidepressant therapy is symptomatic and should be continued for a sufficient period of time, usually at least 6 months after complete elimination of depressive symptoms, to avoid relapse.
In patients with recurrent (unipolar) depression, the necessary maintenance therapy may be continued for several years to prevent the development of new episodes.
Panic disorder:
During the first week of treatment, the recommended single dose is 10 mg/day orally, then the dose is increased to 20 mg/day. Depending on the patient's individual response, the dose can be increased to a maximum of 40 mg/day.
When treating panic disorder, the maximum therapeutic effect of citalopram is achieved approximately 3 months after the start of treatment and persists with continued therapy.
Elderly patients (over 65 years):
The daily dose for elderly patients should be reduced to half the recommended dose, i.e. up to 10-20 mg. The recommended maximum dose for elderly patients is 20 mg/day.
Children and teenagers (under 18 years):
Citalopram should not be used in children and adolescents under 18 years of age (see section "Special instructions"). In addition, there is insufficient long-term data from long-term studies on the safety of the drug in children and adolescents regarding growth, maturation, cognitive and behavioral development.
Reduced kidney function:
For mild to moderate renal failure, no dose adjustment is required.
Patients with severe renal failure (creatinine clearance below 30 ml/min) should use Citalopram-ALSI with caution.
Decreased liver function:
For mild to moderate liver failure, the recommended initial dose during the first two weeks of treatment is 10 mg/day.
Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg/day.
Patients with severe liver failure should use the drug with caution; careful dose titration is required.
Reduced activity of the CYP2C19 isoenzyme:
For patients with weak activity of the CYP2C19 isoenzyme, the recommended initial dose during the first two weeks of treatment is 10 mg/day. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg/day.
Stopping treatment:
Abrupt cessation of treatment should be avoided. When discontinuing therapy with Citalopram-ALSI, the dose should be gradually reduced over a period of at least 1-2 weeks in order to avoid the occurrence of reactions.
QT prolongation
Citalopram has been found to cause dose-dependent prolongation of the QT interval. Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes, have been reported post-marketing, predominantly in female patients with hypokalemia or pre-existing QT prolongation or other cardiac disease.
The drug is recommended to be used with caution in patients with significant bradycardia, in patients who have recently suffered a myocardial infarction, or with decompensated heart failure.
Electrolyte disturbances, such as hypokalemia and hypomagnesemia, increase the risk of malignant arrhythmias and should therefore be corrected before initiating citalopram therapy.
In patients with compensated heart disease, an ECG study should be performed before starting treatment.
If any signs of cardiac arrhythmias occur during treatment with citalopram, the latter should be discontinued and an ECG study performed.
Description
Antidepressant.
Dosage form
White film-coated tablets, round, biconvex; on a cross section, the inner layer is white or white with a yellowish tint.
Use in children
Children under 18 years of age are a contraindication for the use of citalopram, since the effectiveness and safety of its use at this age have not been established.
Pharmacodynamics
Citalopram is an antidepressant belonging to the group of selective serotonin reuptake inhibitors (SSRIs). It has a pronounced ability to inhibit serotonin reuptake, has no or very weak ability to bind to a number of receptors, including gamma-aminobutyric acid (GABA), H1-histamine, D1- and D2-dopamine receptors; α1-, α2-, beta-adrenergic; benzodiazepine and m-cholinergic receptors, which leads to the almost complete absence of undesirable effects such as negative chrono-, dromo- and inotropic effects, orthostatic hypotension, sedation and dry mouth. Citalopram inhibits the CYP2D6 isoenzyme only to a very small extent, and therefore has virtually no interaction with drugs metabolized by this enzyme. Thus, side effects and toxic effects occur to a much lesser extent.
The antidepressant effect usually develops after 2-4 weeks of treatment.
Citalopram has no effect on serum levels of prolactin and growth hormone.
Citalopram does not impair cognitive/intellectual function and psychomotor function and has virtually no sedative effect.
Citalopram in doses exceeding 40 mg per day may cause abnormal changes in the electrical activity of the heart (prolongation of the QT interval on the ECG).
Side effects
As with the use of other drugs of the SSRI group, undesirable side reactions are observed with the use of citalopram, but they are transient in nature and mildly expressed.
Adverse reactions associated with the use of citalopram are observed during the first one to two weeks of treatment and usually significantly weaken as the patient’s condition improves.
Frequency of adverse reactions: very often - ≥10%; often - ≥1%, but <10%; uncommon - ≥0.1%, but <1%; rarely - ≥0.01%, but <0.1%; very rare - <0.01%.
The following adverse reactions may occur.
Allergic reactions: uncommon – hypersensitivity; very rarely - anaphylactic reactions.
From the central nervous system: very often - drowsiness, headache, tremor, dizziness; often – migraine, paresthesia, sleep disorder; uncommon – extrapyramidal disorders, convulsions; rarely – serotonin syndrome (a combination of agitation, tremor, myoclonus and hyperthermia); frequency unknown – psychomotor agitation, akathisia.
From the mental sphere: very often – agitation, nervousness; often - decreased libido, impaired orgasm (in women), anxiety, confusion, drowsiness, impaired concentration, strange dreams, amnesia; infrequently – aggression, depersonalization, hallucinations, mania, euphoria, increased libido; frequency unknown - panic attacks, bruxism, suicidal thoughts.
From the digestive system: very often - dry mouth, nausea, constipation; often - vomiting, flatulence, diarrhea, abdominal pain, hepatitis; frequency unknown - gastrointestinal bleeding.
From the cardiovascular system: very often – palpitations; often – tachycardia, arterial hypertension, orthostatic hypotension; rarely - bradycardia, decreased blood pressure, arrhythmia; frequency unknown – prolongation of the QT interval on the ECG.
From the hematopoietic organs: rarely - hemorrhages (for example, gynecological bleeding, bleeding of the gastrointestinal tract, ecchymosis and other forms).
From the senses: very often - disturbance of accommodation; often - taste disturbance, visual disturbances, infrequently - ringing in the ears.
From the respiratory system: often – rhinitis, sinusitis; infrequently – cough; rarely – dyspnea.
From the reproductive system: often - impaired sexual function, namely impaired ejaculation, decreased libido, impotence, menstrual irregularities; rarely - galactorrhea.
From the urinary system: often – painful urination, polyuria.
Metabolic disorders: often - loss of appetite, weight loss, increased appetite; rarely - insufficient secretion of antidiuretic hormone (ADH), weight gain, hyponatremia; hypokalemia.
From the skin: very often - increased sweating, often - skin rash, itching; uncommon – photosensitivity, urticaria, alopecia, purpura; frequency unknown - angioedema, bruising.
From the musculoskeletal system: infrequently – myalgia, arthralgia, increased risk of injuries and fractures.
Laboratory indicators: often - changes in laboratory indicators of liver function; infrequently - increased activity of liver enzymes, changes in the electrocardiogram (prolongation of the QT interval), hyponatremia.
Other: rarely - hyperthermia, yawning, weight gain or loss.
Use during pregnancy and breastfeeding
Citalopram should not be prescribed to pregnant and breastfeeding women unless the potential clinical benefit outweighs the theoretical risk, because The safety of the drug during pregnancy and lactation in women has not been established.
The use of citalopram in the third trimester of pregnancy can negatively affect the psychophysical development of the newborn. The following disorders are possible in newborns whose mothers took selective serotonin reuptake inhibitors until birth: respiratory failure, cyanosis, shortness of breath, convulsions, temperature instability, feeding difficulties, vomiting, hypoglycemia, muscle hypertension or hypotonia, hyperreflexia, tremor, nervousness, irritability, lethargy, constant crying, drowsiness and insomnia.
Epidemiological evidence suggests that use of SSRIs during pregnancy, especially late in pregnancy, may increase the risk of persistent neonatal pulmonary hypertension. The observed risk was 5 per 1000 pregnancies. In the general population, the risk is 1 to 2 cases of persistent pulmonary hypertension of the newborn per 1000 pregnancies.
Such disturbances may indicate serotonergic effects or the occurrence of a withdrawal syndrome. If citalopram is used during pregnancy, its use should not be abruptly interrupted.
Interaction
Concomitant use is contraindicated
- With MAO inhibitors
Concomitant treatment with MAO inhibitors is contraindicated (both non-selective and selective) due to the risk of serious side effects, incl. serotonin syndrome. Citalopram should not be used in combination, incl. with selegiline, moclobemide, linezolid (antibiotic), etc., as well as within 14 days after stopping their use. Treatment with MAO inhibitors can be started no earlier than 7 days after stopping citalopram.
- With drugs that prolong the QT interval
Do not use with drugs that prolong the QT interval, such as antiarrhythmics (procainamide, amiodarone, etc.), antipsychotics/neuroleptics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants and SSRIs (fluoxetine), antimicrobials (macrolide antibiotics) and their analogues, for example, erythromycin, clarithromycin; quinolone and fluoroquinolone derivatives: sparfloxacin, moxifloxacin; pentamidine), H1-histamine receptor blockers (astemizole, mizolastine), azole antifungals (ketoconazole, fluconazole), domperidone, ondansetron, since citalopram in Doses exceeding 40 mg per day may cause abnormal changes in the electrical activity of the heart (prolongation of the QT interval on the ECG) and lead to cardiac arrhythmias (including the development of arrhythmias), which can be fatal.
- Pimozide
Concomitant use of pimozide and citalopram is contraindicated as their combined use prolongs the QT interval. This also applies to drugs such as amitriptyline, maprotiline, venlafaxine, terfenadine, haloperidol, droperidol, chlorpromazine, thioridazine.
Concomitant use of Citalopram should be done with caution:
Citalopram may lower the seizure threshold. Caution is required when taking other drugs that lower the seizure threshold (tricyclic antidepressants, SSRIs, antipsychotics - phenothiazine derivatives, thioxanthene and butyrophenone; mefloquine and tramadol).
With the simultaneous use of citalopram and tryptophan, cases of increased effect of the drug have been reported. It is advisable not to combine serotonergic drugs such as sumatriptan or other triptans, as well as tramadol, with citalopram.
The simultaneous use of citalopram and drugs containing St. John's wort (Hypericum perforatum) may lead to increased side effects.
With simultaneous use, cimetidine causes a moderate increase in the steady-state concentration of citalopram in the blood. Therefore, caution is recommended when prescribing maximum doses of citalopram concomitantly with the use of high doses of cimetidine.
With simultaneous use of citalopram with indirect anticoagulants and other drugs that affect blood coagulation (atypical neuroleptics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, ticlopidine and dipyridamole), a blood clotting disorder may occur. In such cases, regular monitoring of blood clotting is necessary when starting or ending therapy with citalopram.
When administered simultaneously with warfarin, the prothrombin time increases by 5%.
There was no interaction between citalopram and alcohol. However, as with other psychotropic drugs, the simultaneous use of citalopram and alcohol is not recommended.
In vitro studies revealed that citalopram is converted into its demethylated derivatives with the participation of the CYP2C19 and CYP3A4 isoenzymes, as well as with a small contribution from the CYP2D6 isoenzyme. It has been proven that inhibition of one enzyme can be compensated by other enzymes. The inhibitory effect of citalopram on these and other cytochrome P450 isoenzymes is weak or non-significant, therefore citalopram has low potential for clinically significant drug interactions known in this setting. However, caution is needed if citalopram is prescribed together with drugs that are metabolized mainly by the CYP2D6 isoenzyme and have a low therapeutic index. Although clinical data from multiple-dose pharmacokinetic studies are not available, there is in vitro data (human liver microsomal model) that show a reduction in the formation of demethylated citalopram derivatives by 45-60% and 75-85% compared to control after the addition of ketoconazole and omeprazole , respectively. This may justify the caution necessary in these cases when prescribing, together with citalopram, such strong CYP3A4 inhibitors as ketoconazole, itraconazole, fluconazole, or such strong CYP2C19 inhibitors as omeprazole, esomeprazole, fluvoxamine, ticlopidine, lansoprazole, since their combined use with citalopram may cause significantly reduce the clearance of citalopram. Therefore, the maximum recommended dose of citalopram for patients taking drugs that are inhibitors of the CYP2C19 isoenzyme together should not exceed 20 mg/day, incl. and because there is an increased risk of QT prolongation.
Concomitant use of citalopram with imipramine or desipramine does not affect the concentrations of imipramine and citalopram, but increases the concentration of desipramine; Desipramine dose adjustment may be necessary.
Overdose
Symptoms of overdose: convulsions, drowsiness, tachycardia, bradycardia, muscle hypotension or hypertension, nausea, vomiting, tremor, serotonin syndrome, agitation, dizziness, dilated pupils, stupor, sweating, bluish skin, heart failure, bundle branch block, hyperventilation , atrial arrhythmia, ventricular arrhythmia, coma.
Coma and fatal cases of citalopram overdose are extremely rare, most of them involve concomitant overdose with other drugs.
Treatment of overdose: there is no specific antidote. In case of overdose, gastric lavage should be performed as soon as possible. Treatment is symptomatic and supportive. Medical observation is recommended, in case of loss of consciousness and breathing problems - intubation, as well as careful monitoring of ECG and other vital functions, since the risk of fatal arrhythmias is high, accompanied by sinus tachycardia, junctional rhythm, prolongation of the QT interval, in particular, the development of arrhythmias and ventricular arrhythmia is possible.
Release form
Film-coated tablets, 10 mg No. 30.
Impact on the ability to drive vehicles and operate machinery
Citalopram has a minimal or moderate ability to affect the ability to drive vehicles and operate machinery.
Psychoactive drugs can affect decision making and the ability to respond to emergencies. Patients should be warned about the potential effect on the ability to drive vehicles and operate machines.
Special patient groups
Patients with kidney problems
Use caution if the patient has severe kidney disease [1].
Patients with liver disease
Do not increase the dose above 20 mg [1].
Patients with heart disease
Exceeding the dose of 40 mg is dangerous [1].
Elderly patients
In patients over 60, the dose should not be raised above 20 mg;
Citalopram is one of the best-tolerated antidepressants in elderly patients [1].
Children and teenagers
- It is necessary to regularly and personally check the patient's condition, especially in the first weeks of treatment.
- Use with caution due to the risk of undiagnosed bipolar disorder and suicidality.
- Inform adults about the risks.
Pregnant
- There have been no adequate studies in pregnant women [1].
- Not recommended for pregnant women, especially in the first trimester
- All risks should be weighed and compared
- Bleeding can be expected during childbirth
Breast-feeding
- The medicine passes into breast milk.
- If the infant shows signs of irritation or sedation, discontinue feeding or citalopram
- However, treatment after childbirth may be necessary, so the risks should be weighed.
Special instructions for the use of Citalopram
The safety of taking citalopram during pregnancy or breastfeeding has not been established, so citalopram is not recommended to be prescribed unless the expected therapeutic effect for the patient outweighs the potential risk to the fetus or newborn. Citalopram should be prescribed with caution to patients driving vehicles or servicing potentially dangerous machinery. Citalopram does not affect intellectual activity or psychomotor activity, but some loss of attention may be observed when taking it.
Side effects and other risks
Mechanism of side effects
Side effects are caused by an increase in serotonin. Most side effects occur immediately after starting treatment and go away over time.
Side effects
- Gastroenterological (reduced appetite, nausea, diarrhea, constipation)
- Insomnia, sedation, agitation, tremor
- Sweating
- Urinary dysfunction
- Dry mouth
- Dangerous side effects: seizures, mania, suicidal ideation
- Weight gain: very rare
- Sedation: yes, but infrequently
- Sexual dysfunction: yes
What to do about side effects
- Wait;
- For insomnia, take the drug in the morning;
- For sedation, take at night;
- Switch to another antidepressant [1].
Long term use
Safely
addictive
No.
Overdose
Very rare cases of fatal overdoses.
Vomiting, sedation, cardiac arrhythmia, dizziness, tremor
Pharmacological properties of the drug Citalopram
Citalopram is an antidepressant, a selective inhibitor of neuronal serotonin reuptake. The ability to bind to a number of receptors (including histamine, muscarinic and adrenergic receptors) is absent or very low, therefore citalopram is devoid of cardiotoxicity, sedative properties, does not cause orthostatic hypotension and some other side effects. It inhibits cytochrome P450 IID6 extremely slightly, and therefore does not interact with those drugs that are metabolized with the participation of this enzyme. It has no effect on intracardiac conduction, blood pressure, hematological parameters, liver function, kidney function, and does not contribute to weight gain. The antidepressant effect is usually achieved 2–4 weeks after the start of treatment. Oral bioavailability is about 80%. The maximum concentration in blood plasma is achieved 2–4 hours after oral administration. Binding to plasma proteins is less than 80%. Metabolized by demethylation, deamination and oxidation. It is found predominantly unchanged in blood plasma and changes in its concentration are characterized by linear kinetics. Constant plasma concentrations are achieved 1–2 weeks after the start of treatment. The half-life is 1.5 days. Excreted in urine and feces.
