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Citalopram

Citalopram
Citalopram is an antidepressant. It is prescribed during depression of various origins, panic disorder (including agoraphobia), obsessive-compulsive disorder.

Brand: Citalopram

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Average Delivery Time: 9 Days
Exp. Date: September 2023
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Product description

Pharmacological action of Citalopram 

Buy Citalopram in Canada

Citalopram is an antidepressant belonging to the group of selective serotonin reuptake inhibitors (SSRIs). It has a pronounced ability to suppress the reuptake of serotonin, has no or 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).

Pharmacokinetics

Citalopram drugs in Canada

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.

Patients over 65 years of age

There is a longer T1/2 and lower clearance values ​​due to a decrease in metabolism.

Lack of liver function

In patients with reduced liver function, citalopram is excreted more slowly. T1/2 of citalopram is almost doubled and the equilibrium plasma concentrations of citalopram are almost twice as high as compared with patients with normal liver function after taking a similar dose.

Lack of renal function

In patients with mild to moderate decline in renal function, the elimination of citalopram proceeds more slowly without a significant effect on pharmacokinetics. In patients with severe renal impairment (creatinine clearance below 30 ml / min), caution is required.

Indications of the drug Citalopram

Depression treatment with Citalopram

  • depressive episodes of moderate and severe degree;

  • panic disorder.

Dosage regimen of Citalopram

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 

Depression therapy is started with citalopram 20 mg per day. Depending on the individual patient's response and the severity of depression, the dose may be increased to a maximum of 40 mg per day.

Panic disorder

In 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.

Patients over the age of 65 

The recommended daily dose for the elderly is 10-20 mg. Depending on the individual reaction and the severity of depression, the dose may be increased to a maximum of 20 mg per day.

Impaired liver function

In patients with mild to moderate hepatic impairment, the initial dose is 10 mg per day for the first two weeks. Depending on the reaction, the dose can be increased to 20 mg per day. In patients with severe hepatic impairment, extreme caution is required in dose selection.

Patients with low activity of the isoenzyme CYP2C19

In patients with low activity of the isoenzyme CYP2C19, the initial dose is 10 mg per day for two weeks. Depending on the reaction, the dose can be increased to 20 mg per day.

Duration of treatment

The effect is manifested in 2-4 weeks, the duration of the course of treatment is determined by the patient's condition, the effectiveness and tolerability of the therapy and is on average 6 months.

Peculiarities of the drug's action when it is canceled

Symptoms, which can be observed with a sharp cancellation 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.

Contraindications for use

  • hypersensitivity to citalopram or to any of the excipients that make up this drug;

  • Citalopram should not be used in combination with monoamine oxidase (MAO) inhibitors, including selegiline, moclobemide, linezolid (antibiotic), or within 14 days after stopping them. Treatment with MAO inhibitors can be started no earlier than 7 days after discontinuation of citalopram;
  • citalopram is contraindicated when used simultaneously with drugs that lengthen the QT interval on the ECG (in particular, with pimozide), as well as with congenital prolongation of the QT interval;
  • 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 and lactating 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, convulsions, 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 neonates. 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.

Application for violations of liver function

In patients with mild to moderate hepatic impairment, the initial dose is 10 mg per day for the first two weeks. Depending on the reaction, the dose can be increased to 20 mg per day. In patients with severe hepatic impairment, extreme caution is required in dose selection.

Application for impaired renal function

In chronic renal failure of mild and moderate severity, correction of the dosage regimen is not required. In patients with severe renal impairment (creatinine clearance below 30 ml / min), caution is required in dose selection.

The use of 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.

Use in elderly patients 

The recommended daily dose for the elderly is 10-20 mg. Depending on the individual reaction and the severity of depression, the dose may be increased to a maximum of 20 mg per day.

Special instructions

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.

In connection with the possibility of suicidal attempts, patients with depression should be closely monitored at the beginning of treatment and the appointment of the minimum effective doses to reduce the risk of overdose. This precaution must be observed when treating other mental disorders because of the possibility of a depressive episode at the same time.

Severe depression is characterized by the risk of suicidal actions, which can persist until a significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptic drugs and constant medical supervision (entrusting authorized persons with the storage and issuance of drugs) may be indicated. When treating panic disorder with the prescription of antidepressants and / or benzodiazepines, anxiety or anxiety increases significantly in some patients in response to treatment. This condition (called by experts "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 was not increased in people over 24 years old, and in people over 65 years old it was slightly reduced. During antidepressant treatment, all patients should be monitored for early detection of suicidal tendencies.

Citalopram should be used with caution in case of 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 CYP2C19 isoenzyme.

Citalopram can cause a dose-dependent prolongation of the QT interval, which can lead to irregular heart rhythms.

Hyponatremia develops due to impaired secretion of antidiuretic hormone, especially a high 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 for a long time in one position 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; in severe renal impairment, caution is required. In case of impaired liver function, taking 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 a 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 control mechanisms

Citalopram should be used with caution in persons whose activities are associated with mechanisms or control of moving vehicles. Citalopram does not reduce intellectual abilities and the speed of psychomotor reactions, however, in patients, one can expect some decrease in attention and concentration due to the existing disease, adverse reactions from the treatment, or from both together.

Overdose 

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, cardiac tuberculosis, heart block lungs, 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.

Drug interactions

Combined 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 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 (fluoxetine) , antimicrobial drugs (macrolide antibiotics and their analogs, for example, erythromycin, clarithromycin; quinolone and fluoroquinolone derivatives: sparfloxacin, moxifloxacin; pentamidine), blockers of H1-histamine receptors (astemizole, mizolastine), antifungal agents of azocolazole series 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 heart rhythm disturbances (including the development of pirouette-type arrhythmias), which can prove 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 lower 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 high doses of cimetidine.

With the simultaneous use of citalopram with indirect anticoagulants and other drugs 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, when starting or ending therapy with citalopram, regular monitoring of blood clotting is necessary.

With simultaneous administration with warfarin, 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 to 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% in comparison with controls after adding ketoconazole and omeprazole , respectively. This may justify the necessary caution 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.


Side effect

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.

On the part of the mental sphere: very often - agitation, nervousness; often - decreased libido, orgasm disturbance (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.

From the side of hematopoietic organs: 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 unknown - angioedema, bruising.

From the side 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.