Citalopram

Pharmacological properties

Citalopram is a potent serotonin reuptake inhibitor (5-hydroxytryptamine). with prolonged use of citalopram, there is no attenuation of the serotonin reuptake effect. citalopram is an exceptionally selective serotonin reuptake inhibitor (syoses); there is no or minimal effect on the reuptake of norepinephrine, dopamine and gamma.

Unlike many tricyclic antidepressants and some SSRIs, citalopram does not have or has a very low degree of affinity for other receptors, including serotonin 5-HT_1A-, 5-HT₂receptors, dopamine D₁- and D₂receptors, α₁— , α₂-, β-adrenergic receptors, histamine H₁-, muscarinic cholinergic, benzodiazepine and opiate receptors, which explains the fewer side effects when using citalopram, such as dry mouth, impaired urination, gastrointestinal tract function, vision, drowsiness, cardiotoxicity and orthostatic hypotension.

Pharmacodynamics A sign of antidepressant activity is the inhibition of the sleep phase of rapid eye movement. As well as tricyclic antidepressants, other SSRIs, and MAO inhibitors, citalopram inhibits the phase of rapid eye movement and enhances deep, slow-wave sleep.

Citalopram does not bind to opiate receptors, but enhances the antinociceptive effect of opioid analgesics. Citalopram does not affect cognitive and psychomotor activity and does not have or has minimally pronounced sedative properties, even in combination with alcohol. Citalopram in the study did not affect the activity of the cardiovascular system. Citalopram does not affect the level of growth hormone in blood plasma. Like other SSRIs, citalopram can increase plasma prolactin levels due to the stimulating effect of serotonin, but without clinically significant consequences.

Pharmacokinetics Absorption is almost complete and does not depend on food intake. The maximum plasma concentration is reached 3 hours after administration. The bioavailability of escitalopram is approximately 80%. Protein binding 80%. Metabolism occurs through demethylation, deamination and oxidation. The kinetics of unchanged citalopram is linear. Metabolites remain active. T_½ the drug is 1.5 days. It is excreted in urine and feces. The equilibrium concentration in the blood plasma is reached after 1-2 weeks from the start of treatment.

In elderly patients, T_½ increases to 1.5–3.75 days due to the lower metabolic rate, and the equilibrium concentration is approximately 2 times higher in comparison with young patients.

In case of impaired liver function, citalopram is eliminated more slowly. T indicators_½ and equilibrium concentration is approximately 2 times higher than those in patients with normal liver function when taking an equivalent dose of the drug.

In patients with impaired mild or moderate renal function, citalopram is eliminated more slowly, without a significant change in pharmacokinetics. Information on the treatment of patients with severe renal impairment (creatinine clearance of 20 ml / min) is not available today.

Indications

Depression of various etiologies and types, panic disorders with / without agoraphobia, obsessive-compulsive disorders.

Application

Cipramil is taken daily 1 time per day at any time during the day, regardless of food intake.

Treatment for depression. At the beginning of treatment, adults are prescribed 20 mg of the drug inside 1 time per day. Depending on the individual sensitivity and severity of the disease, the dose may be increased to 60 mg / day.

The antidepressant effect usually occurs after 2–4 weeks. Treatment of depression is symptomatic, therefore, it should last for 6 months in order to prevent relapse.

Panic disorder.At the beginning of treatment, adults are recommended to take 10 mg of the drug inside 1 time per day for 1 week, increasing the dose to 20 mg 1 time per day. The dose can be further increased to 60 mg / day, depending on the individual sensitivity of the patient.

Some patients noted an increase in the severity of anxiety symptoms at the beginning of antidepressant therapy. Such a paradoxical reaction eventually disappeared during 2 weeks of continuous treatment. An initial minimum dose is recommended to reduce the likelihood of a paradoxical anxiety reaction.

The therapeutic efficacy of citalopram in the treatment of panic disorders is achieved after 3 months of continuous use of the drug.

Treatment of obsessive-compulsive disorders. The recommended starting dose is 20 mg. Depending on the clinical assessment, the dose may be increased to 60 mg.

Elderly patients. The recommended daily dose for the elderly is 20 mg.

Depending on the individual sensitivity and severity of depression, the dose can be increased to a maximum of 40 mg / day.

Dosage for impaired liver function. With liver failure, the dose can be reduced to the minimum daily dose.

Dosage for impaired renal function. Dose reduction is not necessary for mild or moderate renal failure.

The antidepressant effect usually occurs 2-4 weeks after the start of treatment. Reception of antidepressants should be continued for a certain time, usually up to 6 months after recovery to prevent relapse. In patients with recurrent depression (unipolar), maintenance therapy may be needed for several years to prevent new episodes.

The maximum effectiveness of citalopram in the treatment of panic disorders is achieved after 3 months of use of the drug and is supported by continued treatment.

Drug withdrawal should be carried out gradually, over several weeks.

Contraindications

Hypersensitivity to the active substance or any component of the drug. combined use with MAO inhibitors and the first 2 weeks after their withdrawal. treatment with MAO inhibitors should begin no earlier than 7 days after cipramil is discontinued. simultaneous use of pimozide. conditions with signs of serotonin syndrome.

Side effects

Transient and slightly pronounced. noted during the 1-2 weeks of treatment and gradually disappear.

The dependence of the severity of the following symptoms on the dose of the drug was established: hyperhidrosis, dry mouth, insomnia, drowsiness, diarrhea, nausea and fatigue.

The frequency of side effects listed in the table below is defined as: very often (≥1 / 10); often (≥1 / 100, but 1/10); rarely (≥1 / 1000, but 1/100); sometimes (≥1 / 10,000, but 1/1000); isolated cases (1/10 000) or frequency cannot be set.

special instructions

Hyponatremia

When using SSRIs, it is sometimes possible to develop such a side effect as hyponatremia, which is possibly associated with a violation of the secretion of antidiuretic hormone. The risk group includes mainly elderly women.

Suicide risk

Depression causes an increased risk of suicidal thoughts, attempts, self-harm and suicide. Such a risk exists until a stable remission is achieved. Since the improvement of the condition may not occur during the first weeks of treatment, you should carefully monitor the patient until a marked improvement in the condition. Based on clinical experience, the risk of suicide may increase in the initial stages of recovery.

Other mental disorders for which citalopram is prescribed may also be associated with an increased risk of suicidal cases. In addition, such conditions can accompany severe depressive disorder. Therefore, the features of the use of citalopram also apply to other mental disorders.

Patients with a history of suicidal attempts or expressed suicidal ideations even before treatment have a high risk of suicidal attempts and thoughts, so their condition should be carefully monitored throughout therapy. In addition, there is a significant increase in the risk of suicidal behavior in young people.

Patients and their families should be warned about the need to carefully monitor such cases and seek immediate medical attention if these symptoms develop.

Akathisia

The use of SSRIs is associated with the development of akathisia, which is characterized by an unpleasant debilitating feeling of anxiety and injustice at the same time as the inability to stand or sit in one place. This condition is possible during the first few weeks of treatment. Increasing the dose in patients with akathisia may be unfavorable.

Mania

In patients with manic-depressive disorder, a phase change is possible. The use of the drug should be discontinued if the patient is in the manic stage of the underlying disease.

Cramps

Like other antidepressants, citalopram should be used with caution in patients with a history of seizures.

Diabetes

Like other psychotropic drugs, citalopram can change the sensitivity of tissues to insulin and glucose, which requires the correction of antidiabetic therapy in patients. In addition, depression can affect glucose balance.

Serotonin syndrome

It is necessary to use citalopram with serotonergic agents, for example, sumatriptan and other triptans, tramadol and tryptophan with caution.

Serotonin syndrome can manifest as anxiety, confusion, tremors, myoclonus, and hyperthermia.

Hemorrhage

When taking SSRIs, hemorrhages (ecchymosis and purpura) may develop. It is necessary to carefully prescribe this group of drugs to patients with a tendency to bleeding, as well as the combined use of anticoagulants and drugs that affect blood coagulation (for example, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and other NSAIDs, ticlopidine and dipyridamole).

Electroconvulsive