Citalopram is an antidepressant that belongs to the group of selective serotonin reuptake inhibitors (SSRIs). It has a pronounced ability to suppress serotonin reuptake, does not have or has a very weak ability to bind to a number of receptors, including receptors for gamma-aminobutyric acid (GABA), H1-histamine, D1- and D2-dopamine; α1-, α2-, beta-adrenergic; benzodiazepine and m-cholinergic receptors, which leads to the almost complete absence of such undesirable effects 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, practically does not interact with drugs metabolized by this enzyme. Thus, side effects and toxic effects are manifested to a much lesser extent. The antidepressant effect usually develops after 2-4 weeks of treatment.
Citalopram has no effect on serum prolactin and growth hormone levels.
Citalopram does not impair cognitive / intellectual functions and psychomotor function and has practically no sedative effect.
Citalopram in doses exceeding 40 mg per day can cause abnormal changes in the electrical activity of the heart (prolongation of the QT interval on the ECG).
Bioavailability of citalopram is 80% and practically does not depend on food intake. Cmax in plasma is reached on average after 3 hours. Pharmacokinetics has a linear dose-dependent character 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. Penetrates into breast milk. It is 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 the 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.
Children under 18 years of age is a contraindication for the use of citalopram, since the effectiveness and safety of its use at this age has not been established.
Pregnancy and lactation
Citalopram should not be administered to pregnant or breastfeeding women unless the potential clinical benefit outweighs the theoretical risk. the safety of the drug during pregnancy and lactation in a woman has not been established.The use of citalopram in the third trimester of pregnancy can adversely affect the psychophysical development of the newborn. The following disorders are possible in newborns whose mothers took selective serotonin reuptake inhibitors until childbirth: respiratory failure, cyanosis, shortness of breath, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, muscle hypertension or hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, constant crying, drowsiness and insomnia.Epidemiological evidence suggests that the use of SSRIs during pregnancy, especially in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. 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 abnormalities may indicate serotonergic effects or the onset of a withdrawal syndrome. In the case of using citalopram during pregnancy, its intake should not be abruptly interrupted.
As in the case of the use of other drugs of the SSRI group, against the background of the use of citalopram, undesirable side reactions are noted, however, they are of a transient nature and are weakly expressed.
Adverse reactions associated with the use of citalopram are observed during the first one to two weeks of treatment and usually subside significantly as the patient's condition improves.
Frequency of adverse reactions: very often - ≥10%; often - ≥1%, but <10%; infrequently - ≥0.1%, but <1%; rarely - ≥0.01%, but <0.1%; very rarely - <0.01%.
The following adverse reactions may occur.
Allergic reactions: infrequently - hypersensitivity; very rarely - anaphylactic reactions.
From the side of the central nervous system: very often - drowsiness, headache, tremors, dizziness; often - migraine, paresthesia, sleep disorder; infrequently - extrapyramidal disorders, convulsions; rarely - serotonin syndrome (a combination of excitement, tremor, myoclonus and hyperthermia); frequency is unknown - psychomotor agitation, akathisia. From the side of the mental sphere: very often - agitation, nervousness; often - decreased libido, disturbed 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 side of 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. On the part of the hematopoietic system: rarely - hemorrhages (for example, gynecological bleeding, bleeding of the gastrointestinal tract, ecchymosis and other forms). From the senses: very often - violation of accommodation; often - taste disturbance, visual impairment, infrequently - ringing in the ears.
From the respiratory system: often - rhinitis, sinusitis; infrequently - cough; rarely - dyspnea.
On the part of the reproductive system: often - violation of sexual function, namely, violation of ejaculation, decreased libido, impotence, menstrual irregularities; rarely galactorrhea.
From the urinary system: often - painful urination, polyuria.
Metabolic disorders: often - decreased appetite, weight loss, increased appetite; rarely - insufficient secretion of antidiuretic hormone (ADH), weight gain, hyponatremia; hypokalemia.
On the part of the skin: very often - increased sweating, often - skin rash, itching; infrequently - photosensitivity, urticaria, alopecia, purpura; frequency is unknown - angioedema, bruising.
On the part of 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.
Others: rarely - hyperthermia, yawning, increase or decrease in body weight.
Joint 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 them. Treatment with MAO inhibitors can be started no earlier than 7 days after stopping the intake of citalopram.
With QT-prolonging agents It is unacceptable to 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 (fluoxidine), antibiotics and their analogs, 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 can cause abnormal changes in the electrical activity of the heart (prolongation of the QT interval on the ECG) and lead to a violation of the heart rhythm (including the development of arrhythmias like "pirouette"), which can be fatal. Pimozide
The simultaneous use of pimozide and citalopram is contraindicated, since their combined use lengthens the QT interval. This also applies to drugs such as amitriptyline, maprotiline, venlafaxine, terfenadine, haloperidol, droperidol, chlorpromazine, thioridazine.
The combined use of Citalopram should be performed with caution:
Citalopram may lower the seizure threshold. It is required to exercise caution while taking other drugs that reduce the seizure threshold (tricyclic antidepressants, SSRIs, neuroleptics - derivatives of phenothiazine, thioxanthene and butyrophenone; mefloquine and tramadol).
With the simultaneous use of citalopram and tryptophan, cases of increased action 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 preparations containing St. John's wort (Hypericum perforatum) may lead to an increase in side effects.
With the simultaneous use of cimetidine causes a moderate increase in the equilibrium concentration of citalopram in the blood. Therefore, it is recommended to exercise caution when prescribing maximum doses of citalopram concurrently with the use of high doses of cimetidine. With the simultaneous use of citalopram with indirect anticoagulants and other agents that affect blood coagulation (atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, ticlopidine and dipyridamole), blood clotting disorders may occur. In such cases, at the beginning or end of therapy with citalopram, regular monitoring of blood clotting is necessary. When administered simultaneously with warfarin, the prothrombin time increases by 5%.
No interaction of citalopram with alcohol has been identified. 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 CYP2C19 and CYP3A4 isoenzymes, as well as with a small contribution of the CYP2D6 isoenzyme. It has been proven that inhibition of one of the enzymes can be compensated for by other enzymes.
The inhibitory effect of citalopram on these and other cytochrome P450 isoenzymes is weak or insignificant, therefore, citalopram has a low ability for clinically significant drug interactions known for this situation. However, caution is needed if citalopram is prescribed in conjunction with drugs that are metabolized mainly by the CYP2D6 isoenzyme and have a low therapeutic index.
Although clinical data on multiple dose pharmacokinetic studies are not available, there are in vitro data (human liver microsome model) that show a 45-60% slowdown in the formation of demethylated citalopram derivatives and 75-85% compared to controls 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, such as lansoprazole, significantly reduce the clearance of citalopram. Therefore, the maximum recommended dose of citalopram for patients taking CYP2C19 isoenzyme inhibitors together should not exceed 20 mg / day, incl. and due to the fact that the risk of prolongation of the QT interval is increased.
The combined use of citalopram with imipramine or desipramine does not affect the concentration of imipramine and citalopram, but increases the concentration of desipramine; dose adjustment of desipramine may be necessary.
Dosage and administration
Citalopram is taken orally once a day (without chewing, with a small amount of liquid). The drug can be used at any time of the day, regardless of food intake, it is advisable to take the drug at the same time of the day.
Depression therapy begins with the intake of 20 mg of citalopram per day. Depending on the patient's individual response and the severity of depression, the dose may be increased to a maximum of 40 mg per day.
For panic disorder, the recommended dose is 10 mg per day for 1 week, then the dose is increased to 20 mg per day. The daily dose, depending on the patient's individual response, can be further increased to 40 mg per day.
Duration of treatment
The effect is manifested after 2-4 weeks, the duration of the course of treatment is determined by the patient's condition, the effectiveness and tolerance of the therapy and is on average 6 months.
Peculiarities of the drug action when canceling
Symptoms that may occur with abrupt withdrawal of citalopram are not typical. These are most often dizziness, headache, paresthesia, sleep disturbance, asthenia, nervousness, tremors, nausea and / or vomiting.
If treatment is completed, citalopram should be withdrawn gradually over several weeks to avoid "withdrawal" syndrome. In most cases, about 2 weeks is enough for this, but in each case the doctor decides this issue individually: for some patients, it may take 2-3 months or more.
Overdose symptoms: convulsions, drowsiness, tachycardia, bradycardia, muscle hypotension or hypertension, nausea, vomiting, tremor, serotonin syndrome, agitation, dizziness, dilated pupils, stupor, sweating, cyanosis of the skin, heart failure, pulmonary blockage, hyperventilation , atrial arrhythmia, ventricular arrhythmia, coma. Coma and fatal cases of citalopram overdose are extremely rare, most of them involve concurrent overdose with other drugs. Overdose treatment: there is no specific antidote. In case of overdose, gastric lavage should be performed as soon as possible. Treatment is symptomatic and supportive. Medical supervision is recommended, in case of loss of consciousness and respiratory failure - intubation, as well as careful monitoring of the ECG and other vital functions, since there is a high risk of fatal arrhythmias accompanied by sinus tachycardia, nodal rhythm, prolongation of the QT interval, in particular, it is possible to develop arrhythmias of the "pirouette" type , ventricular arrhythmias.
Children under the age of 18 are contraindications for the use of citalopram, since the effectiveness and safety of its use at this age has not been established. Due to the possibility of suicidal attempts, patients with depression should be closely monitored at the beginning of treatment and the appointment of the lowest effective doses to reduce the risk of overdose. This precaution must be observed when treating other mental disorders because of the potential for a depressive episode at the same time. Severe depression is characterized by the risk of suicidal actions, which can persist until significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the benzodiazepine group or antipsychotic drugs and constant medical supervision (entrusting authorized persons with the storage and issuance of drugs) may be indicated. When treating panic disorder with antidepressants and / or benzodiazepines, some patients may experience significant increases in anxiety or anxiety in response to treatment. This condition (called by specialists "pathological disinhibition" or simply "paradoxical anxiety", the term itself has not yet been approved) is considered as a rare occurrence, although this pathological reaction has been repeatedly documented in the scientific literature. This "paradoxical anxiety" usually diminishes within the first few weeks after starting treatment. It is recommended to start at a low dose to reduce the risk of paradoxical anxiety. Cancellation of the drug in this case is recommended if such a paradoxical reaction does not disappear for a long time, and if such complications of therapy exceed the benefits of the treatment. In children, adolescents and young people (under 24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing citalopram or any other antidepressants in this category of patients, the risk of suicide and the benefits of their use should be correlated. In short-term studies, the risk of suicide did not increase in people over 24 years old, and in people over 65 years old it decreased slightly. During treatment with antidepressants, all patients should be monitored for early detection of suicidal tendencies. Citalopram should be used with caution in renal failure (creatinine clearance below 30 ml / min), hypomania, mania, pharmacologically uncontrolled epilepsy, depression with suicidal attempts, diabetes mellitus, liver cirrhosis, tendency to bleeding; simultaneous administration with drugs that reduce the threshold of convulsive readiness and cause hyponatremia, with ethanol, as well as with drugs metabolized by the isoenzyme CYP2C19. Citalopram can cause a dose-dependent prolongation of the QT interval, which can lead to an irregular heartbeat.
Hyponatremia develops due to impaired secretion of antidiuretic hormone, especially a high level of risk in older women.
Treatment with Citalopram can alter glycemic control in patients with diabetes. The dose of insulin and / or oral hypoglycemic agents should be adjusted.
Rarely is the development of akathisia, characterized by a constant or recurrent feeling of internal motor restlessness and manifested in the inability to sit quietly in one position for a long time or remain motionless for a long time. It takes place during the first weeks of treatment. Patients with bipolar disorder may experience mania. Then treatment with citalopram must be discontinued.
It is necessary to use citalopram with caution in the presence of drug dependence (including a history) and a history of epileptic seizures. Citalopram should not be used in combination with monoamine oxidase (MAO) inhibitors is required; in severe renal impairment, caution is required. In case of impaired liver function, the drug is limited to the minimum recommended doses. In elderly patients, a dose reduction of citalopram is required. With the development of a manic state, the drug should be canceled.
Clinical experience with the simultaneous use of SSRIs and electroconvulsive therapy is insufficient, therefore, caution is required.
At the beginning of treatment, insomnia and anxiety may occur, which can be resolved by adjusting the starting dose. Abrupt cessation of therapy with Citalopram may lead to withdrawal syndrome. Undesirable reactions such as dizziness, headaches, nausea may occur. To avoid the onset of withdrawal syndrome, gradual withdrawal of the drug over several weeks is necessary. Influence on the ability to drive vehicles and use mechanisms. Citalopram should be used with caution in persons whose activities are related to the mechanisms or control of moving vehicles. Citalopram does not reduce intellectual abilities and the speed of psychomotor reactions, however, patients can expect some decrease in attention and concentration due to the existing disease, adverse reactions from the treatment, or from both together.