Citalopram (cipramil, Oprah)
Citalopram is a selective serotonin reuptake blocker (SSRI) and is used in the treatment of depression, generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder and cataplexy. Both citalopram (50:50 S-, R - enantiomer) and escitaloprom (S - enantiomer of citalopram) block serotonin reuptake, increase serotonin levels within a few hours, but the actual antidepressant effect of the drug appears after several weeks (usually 1-2 ) . Escitalopram is a more potent drug than its R enantiomer. When using citalopram together with other drugs, its doses should not be high; when used as monotherapy, higher dosages can be prescribed. Monitoring the safety of citalopram, especially when increasing its dose, involves periodic assessment of the electrocardiogram, in particular, monitoring of QTc segment prolongation. Due to the above, you should not prescribe this drug after myocardial infarction, in the presence of cardiac arrhythmia, hypokalemia, hypomagnesemia, or heart failure.
Among the side effects of the drug, it should be noted. insomnia, nausea, weakness, somnolence, hyperhidrosis, decreased libido, delayed ejaculation and anorgasmia. Serotonin syndrome, increased mania, suicidal thoughts (these manifestations are most likely in the first months of treatment with citalopram), angle-closure glaucoma, increased seizures, bleeding and hyponatremia are rare. The reduction in the dose of the drug is usually gradual over 3-4 days in order to exclude the occurrence of withdrawal syndrome (agitation, dry mouth, anxiety, dysphoria). Correction of sexual disorders is achieved by prescribing drugs that have an alpha-adrenergic antagonistic effect (buspirone, amantadine, mirtazapine, and gingo biloba. Citalopram is prescribed in a daily dose of 20 to 80 mg, for eating disorders - the recommended dose is 60 mg., for obsessive-compulsive disorder - 80 mg. When taking too high doses of the drug, the following may occur: convulsive syndrome, coma, dizziness, decreased blood pressure, insomnia, nausea, vomiting, sinus tachycardia, somnolence, ECG changes (QTc prolongation).
Citalopram is metabolized by the liver enzyme cytochrome oxidase P-450, in particular, CYP3A4, CYP2C19, CYP2D6 (to a lesser extent). Bioavailability - 80%, 20% is eliminated by the kidneys. Half-life is 20-40 hours, 56% is bound to proteins.
Serotonin syndrome develops when citalopram is co-administered with monoamine oxidase inhibitors (MAO) or other serotonergic drugs (a break of 1-2 weeks between doses is desirable). Co-administration of citalopram with drugs (inhibitors) metabolized by the CYP450 enzyme has little effect on drug concentration levels in the blood. When taking citalopram simultaneously with aspirin or warfarin, the bleeding time may be prolonged/changed. Citalopram should not be prescribed simultaneously with the serotonin precursor tryptophan. In case of liver dysfunction, as well as in older people, it is advisable to use low doses of citalopram (10 mg/day). When prescribing the drug to pregnant women, it should be borne in mind that it belongs to category C. If this drug is prescribed to pregnant women in the third trimester, then the fetus may experience complications requiring hospitalization: respiratory dysfunction, cyanosis, apnea, fever, hypoglycemia, convulsive syndrome, tremors, vomiting, eating problems. Citalopram is not recommended for use by nursing mothers. According to a Cochrane review, citalopram is more effective than paroxetine and reboxetine, and is better tolerated than tricyclic antidepressants, venlafaxine and reboxetine. In an experiment on animals, it turned out that escitalopram relieves the effects of stress somewhat faster than citalopram (1 and 2 weeks, respectively). Citalopram, like all drugs from the SSRI group, causes similar changes in sleep architecture: REM latency increases, the first and second phases of slow-wave sleep increase, and sleep fragmentation. Effective for cataplexy, but not narcolepsy. The drug at high doses can impair the quality of sleep in patients with obsessive-compulsive disorder.
Cipramil
Release form, composition and packaging
White film-coated tablets, oval, scored, marked “C” and “N” symmetrically near the score. 1 tab. citalopram (in the form of hydrobromide) 20 mg. Excipients: corn starch, lactose monohydrate, copovidone, glycerol 85%, microcrystalline cellulose, croscarmellose sodium, magnesium stearate. Shell composition: hypromellose 5, macrogol 400, titanium dioxide (E 171).
White film-coated tablets, oval, scored, marked “C” and “N” symmetrically near the score. 1 tab. citalopram (hydrobromide) 40 mg. Excipients: corn starch, lactose monohydrate, copovidone, glycerol 85%, microcrystalline cellulose, croscarmellose sodium, magnesium stearate. Shell composition: hypromellose 5, macrogol 400, titanium dioxide (E 171).
Clinical and pharmacological group: Antidepressant.
pharmachologic effect
Antidepressant, selective serotonin reuptake inhibitor. The antidepressant effect usually develops after 2-4 weeks of therapy. Tsipramil has virtually no or insignificant ability to bind to a number of receptors, including histamine, m-cholinergic receptors and adrenergic receptors. There is no sedative effect. It inhibits cytochrome P450 IID6 to a very small extent, and therefore does not interact with drugs metabolized by this isoenzyme. Tsipramil has no effect on the conduction system of the heart and blood pressure, does not change hematological parameters, liver and kidney functions; does not cause weight gain.
Pharmacokinetics
Suction
After oral administration, Cmax of citalopram in plasma is reached within 2-4 hours. Bioavailability when taken orally is about 80%.
Distribution
Changes in plasma concentrations of citalopram are linear. Css in plasma is established after 1-2 weeks of therapy. Plasma protein binding is less than 80%.
Metabolism
In blood plasma, citalopram is present mainly unchanged. Metabolized by demethylation, deamination and oxidation.
Removal
T1/2 is 1.5 days. Excreted by the kidneys and through the intestines.
Indications
- depression of various etiologies and structures (in adults);
- panic disorder with/without agoraphobia;
- obsessive-compulsive disorders (OCD).
Dosage regimen
The drug is prescribed 1 time/day. For depression, the drug is prescribed at a dose of 20 mg/day. Depending on the individual response of the patient and the severity of depression, the dose may be increased to a maximum of 60 mg/day. For panic disorders, during the first week of treatment the recommended dose is 10 mg/day, then the dose is increased to 20 mg/day.
Depending on the patient’s individual response to the drug, the daily dose may subsequently be increased. The maximum dose is 60 mg/day. For obsessive-compulsive disorders, the initial dose of the drug is 20 mg/day. If necessary, the dose can be increased. The maximum dose is 60 mg/day. In elderly patients, the recommended dose is 20 mg/day. Depending on the individual response and severity of depression, the dose may be increased to a maximum of 40 mg/day.
For patients with severe liver dysfunction, the drug is prescribed in the minimum recommended doses. Tsipramil can be taken regardless of meals, at any time of the day.
Side effect
- From the digestive system: dry mouth, nausea, diarrhea.
- From the side of the central nervous system: drowsiness, tremor, weakness, agitation, insomnia; in exceptional cases - convulsive seizures (when using the drug in high doses).
- From the cardiovascular system: a slight decrease in heart rate is possible, which usually has no clinical significance.
However, in patients with an initially low heart rate, the drug may cause bradycardia. Other: increased sweating, sexual dysfunction. Hyponatremia, manifestations of serotonin syndrome, withdrawal syndrome, extrapyramidal disorders, and purpura can occur extremely rarely. Side effects are usually transient and mild. They are observed mainly during the first 2 weeks of treatment and usually decrease significantly as the patient's condition improves.
Contraindications
- hypersensitivity to the drug.
Pregnancy and lactation
The safety of using Tsipramil during pregnancy and lactation has not been established. The use of the drug is justified only in cases where the potential benefit of therapy for the mother outweighs the possible risk to the fetus and child. Experimental studies did not reveal a teratogenic effect or any effect of Tsipramil on reproductive function and perinatal development of the fetus.
special instructions
Cipramil, like other selective serotonin reuptake inhibitors, should not be prescribed while using MAO inhibitors, or within 14 days after stopping their use. Treatment with MAO inhibitors can be started 7 days after stopping Cipramil.
For moderate renal impairment, no dosage adjustment is required. If the depression phase is inverted and a manic state develops, Cipramil should be discontinued.
Impact on the ability to drive vehicles and operate machinery
Tsipramil does not reduce the ability to think and the speed of psychomotor reactions. However, it should be borne in mind that patients with depression often experience a decrease in the ability to concentrate, which can be aggravated by the use of psychotropic drugs.
Taking this into account, when prescribing Tsipramil for depression, the patient should be warned about a possible decrease in the ability to concentrate and the speed of psychomotor reactions when driving a car and working with machinery.
Overdose
Symptoms: drowsiness, coma, articulation disorders, occasionally - grand mal seizures, sinus tachycardia, sometimes junctional rhythm, increased sweating, nausea, vomiting, cyanosis, hyperventilation. The clinical picture is not typical. Treatment: it is necessary to rinse the stomach as soon as possible after taking the drug. Conduct symptomatic and supportive therapy. Monitoring the patient's condition is recommended. There is no specific antidote.
Drug interactions
With the simultaneous use of Tsipramil and MAO inhibitors, the development of a hypertensive crisis (serotonin syndrome) is possible.
When used together, cimetidine causes a moderate increase in the average steady-state concentration of citalopram in the blood (therefore, Cipramil should be prescribed with caution in maximum doses while taking cimetidine in high doses). No clinically significant pharmacokinetic interaction of Tsipramil with phenothiazines and tricyclic antidepressants has been identified.
Clinical studies have not revealed pharmacodynamic interactions between Tsipramil and concomitantly used benzodiazepines, antipsychotics, analgesics, lithium preparations, antihypertensive drugs, antihistamines, beta-blockers and other cardiotropic drugs. There was no interaction between Tsipramil and ethanol. The effects of sumatriptan and other serotonergic drugs may be enhanced by citalopram.
Storage conditions and periods
List B. The drug should be stored at a temperature not exceeding 30°C.
