Sertraline is an antidepressant from the group of selective serotonin reuptake inhibitors (SSRIs).
History of creation
The drug was developed by the pharmaceutical company Pfizer. Initially, work was carried out on the drug "tametralin," which was an inhibitor of the reuptake of catecholamines. Tametralin did not establish itself as an effective anti-depressant, as it demonstrated the undesirable effects of prohibited psychostimulants.
Many years later, Tametralin research was resumed, with the result that Sertraline was created. Sertralin differs from tametraline in the presence of two chlorine atoms in the molecule. However, studies have shown that this substance is an extremely selective inhibitor of serotonin reuptake. At the time of the research, Pfizer considered other drugs as an antidepressant put forward to the wide market. However, scientists working on sertraline, without any motivation, insistently offered their invention. As a result of these actions, sertraline was on sale under the trade name Zoloft and Lyustral and for some time was the most prescribed remedy for depression in the United States.
An antidepressant, a specific serotonin reuptake inhibitor, enhances its effects, has a weak effect on the reuptake of norepinephrine and dopamine; at therapeutic doses, it blocks serotonin uptake in human platelets. Suppression of serotonin reuptake activity increases serotonergic transmission, which leads to subsequent inhibition of adrenergic activity in the blue nucleus (locus ceruleus). Sertralin also inhibits the excitation of serotonin neurons in the suture area (median line of the medulla oblongata); which leads to an initial increase in the activity of the blue nucleus with a subsequent decrease in the activity of postsynaptic beta-adrenergic receptors and presynaptic alpha2-adrenergic receptors.
Does not cause drug dependence, does not have m-holinoblokiruyuschego and cardiotoxic effects, does not change the psychomotor activity. Due to the selective inhibition of serotonin uptake, it does not enhance the activity of the sympathetic nervous system. Does not have affinity for m-choline, some serotonin (5-HT1A, 5-HT1B, 5-HT2), dopamine, adreno, histamine, GABA or benzodiazepine receptors; does not inhibit MAO. Unlike tricyclic antidepressants, in the treatment of depression or obsessive-compulsive disorders (obsessive-compulsive disorder) does not increase body weight. Unlike other representatives of SSRIs, to a lesser extent causes phase inversion: the development of a hypomaniacal or manic state. The initial effect develops by the end of the first week, is more pronounced in 2-4 weeks, the maximum therapeutic effect - after 3 months from the beginning of the regular intake of the drug.
Absorption (Absorption) - high (but at a slow rate). Bioavailability increases with food intake by 25%. Eating increases the maximum concentration (Cmax) by 25% and shortens the time to reach the maximum concentration (Tcmax). The concentration of the drug in the blood plasma reaches its peak peak (Cmax) by 14 days 4.5-8.4 hours after administration. Сmax and the area under the concentration-time curve (AUC) are proportional to the dose within 50-200 mg of sertraline 1 time per day for 14 days, thus revealing the linear nature of the pharmacokinetic dependence. The pharmacokinetic profile in adolescents and the elderly is not significantly different from that in patients aged 18 to 65 years. The average elimination half-life (T1 / 2) of sertraline is 22-36 hours. Accordingly, the final T1 / 2 has approximately double cumulation of the drug until equilibrium concentrations occur after 1 week of treatment (once-daily dose). Plasma protein binding is approximately 98%. The pharmacokinetics of sertraline in children with OCD has been shown to be similar to that in adults (although in children sertraline metabolism is somewhat more active). However, given the lower body weight in children (especially at the age of 6-12 years), the drug is recommended to be used in a lower dose in order to avoid excessive plasma concentrations.
Sertralin undergoes active biotransformation during the first passage through the liver. The main metabolite found in plasma, N-desmethyl sertraline, is significantly inferior (approximately 20 times) to sertraline in in vitro activity and is actually not active in in vivo depression models. T1 / 2 N-desmethyl sertraline varies in the range of 62-104 hours. Sertralin and N-desmethyl sertraline actively biotransform; The resulting metabolites are excreted in equal amounts with feces and urine. Unchanged sertraline is excreted in the urine in small amounts (<0.2%). In patients with cirrhosis of the liver, the T1 / 2 drug and AUC are increased in comparison with those in healthy people.
Indications for use
Depressive states (including those accompanied by anxiety); prevention of initial or chronic episodes of depression; obsessive compulsive disorder; panic disorders, social phobias.
With poorly treatable depressions, it may be used in combination with other drugs. You can combine only drugs belonging to different groups of antidepressants. Sertraline can be combined, for example, with bupropion or mirtazapine.
Dosage and administration
Inside, 50 mg, 1 time per day, in the morning or in the evening, regardless of the meal. In the absence of effect, a gradual (within a few weeks) increase in the dose to 200 mg / day (by 50 mg / week) is possible. Some clinicians recommend prescribing a dose of 25 mg / day at first for 1-2 days. Panic disorders: the initial dose is 25 mg / day, followed by an increase to 50 mg / day for 1 week. When conducting long-term maintenance therapy prescribed in the minimum effective dose, which subsequently change depending on the effect. Obsessive compulsive disorders and social phobias: in children and adolescents 13-17 years old, the initial dose is 50 mg / day, in children 6-12 years old, the initial dose is 25 mg / day, followed by an increase in 1 week to 50 mg / day . With insufficient effect, the dose can be increased in increments of 50 mg / day to 200 mg / day, with an interval of at least 1 week. In elderly patients, the initial dose is 25 mg / day (morning or evening), followed by a gradual increase.
Manic states, hypersensitivity, liver disease, alcohol poisoning, psychotropic drugs and other drugs, pregnancy, lactation, simultaneous administration of MAO inhibitors. With caution. Neurological disorders (including mental retardation), epilepsy, hepatic and / or renal failure, weight loss, childhood.
Treatment of Obsessive Compulsive Disorder with Sertraline
Studies have shown that sertraline is slightly more effective in the treatment of OCD than the antidepressant of the same class of SSRIs Fluoxetine (Prozac). With insufficient effect, increasing the dose above the recommended (50-200 mg) did not give results. Study participants confirmed the positive effect of sertraline treatment and the maintenance of this effect for a year or more of sertraline. Constant use of the drug is not required for everyone. However, when discontinuing the drug, exacerbations of OCD were often observed, which were the result of side effects or withdrawal syndrome. 48% of patients who stopped using the drug felt the same way as continued treatment. Sertralin is effective in treating OCD in adults and children. It is known that sertraline can also be used in OCD with concomitant Tourette syndrome, but it can cause an exacerbation of tics in Tourette syndrome.
Anxiety, affect inversion (development of mania or hypomania), tremor, hyperhidrosis, allergic reactions, bleeding (including epistaxis), palpitations, dry mouth, loss of appetite. Rarely - increased appetite (possibly as a consequence of depression), nausea, vomiting, unstable stools, diarrhea, cramps in the stomach or stomach, flatulence or pain, weight loss; headache, dizziness, insomnia, drowsiness, movement disorders (extrapyramidal symptoms, gait change), akathisia, convulsions, paresthesia, symptoms of depression, hallucinations, aggression, agitation, anxiety, psychosis, flushing of the skin or flushes of blood to the face, visual disturbances (including blurred vision), yawning, increased sweating, impaired sexual function (delayed ejaculation, priapism, reduced potency and / or libido, anorgasmia), dysmenorrhea, galactorrhea, hyponatremia (syndrome of inadequate secretion of ADH), hyperpr laktinemiya, withdrawal syndrome, erythema multiforme, skin rash and itching. In rare cases, serotonin syndrome.
May lead to emotional and behavioral changes, including an increased risk of suicide.
Symptoms: anxiety, drowsiness, ECG changes, mydriasis, nausea, vomiting, tachycardia. Treatment: ensuring the normal airway (oxygenation and ventilation of the lungs), gastric lavage, the appointment of emetic drugs, activated carbon with sorbitol. It is necessary to control the function of the heart and liver. Forced diuresis, dialysis, hemoperfusion, and exchange transfusion are not effective (given the large volume of distribution).
May lead to emotional and behavioral changes, including an increased risk of suicide.
During the period of treatment, it is necessary to exercise strict control over the behavior of patients in a state of depression (the risk of suicidal attempts) until there is a significant improvement as a result of the treatment being performed. Sertralin is prescribed no earlier than 14 days after discontinuation of MAO inhibitors. Women of childbearing age should use adequate methods of contraception during treatment. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed.
Interaction with other drugs
Able to displace other drugs from the association with plasma proteins: in particular, it increases the plasma level of the free fraction of anxiolytics, H2-histamine receptor blockers, warfarin, digoxin, sulfonylurea derivatives due to their displacement from the association with proteins.
It slows down the metabolism of desipramine (and also of imipramine) and increases the concentration of this antidepressant in the blood by 50%. Reduces plasma clearance of diazepam, slightly increases its concentration in the blood. Enhances the side effects of lithium salts (in particular, tremor). It enhances the effect of indirect anticoagulants (an increase in prothrombin time), blocks CYP2D6 cytochrome, increasing the concentration in plasma of simultaneously used drugs, in the metabolism of which this enzyme participates (tricyclic antidepressants, antiarrhythmic drugs Ic class - propafenone, flecainide). Reduces clearance of tolbutamide (requires control of blood glucose with simultaneous use).
Cimetidine reduces AUC, Cmax, and T1 / 2 sertraline by 50, 24, and 26%, respectively.
The combination of sertraline with digoxin increases the risk of side effects of both drugs. When combined with drugs that depress the central nervous system, the inhibitory effect on the central nervous system of both drugs is enhanced.
In order to avoid the risk of serotonin syndrome, it is necessary to avoid prescribing drugs of the SSRI group (in particular, sertraline) together with other serotonergic drugs. It is necessary to maintain an interval of 2 weeks between the cancellation of SSRIs and the prescription of MAO inhibitors, and a break of four weeks between the cancellation of MAO inhibitors and the appointment of SSRIs (according to other data, two weeks); when transferring from moclobemide to SSRIs, 24 hours is sufficient. In addition, serotonin syndrome can occur when a combination of anti-depressants of the SSRI group with buspirone, if required, herbal anti-depressant drugs containing St. John's wort, 5-hydroxytryptophan, S-adenosylmethionine (SAM, Heptral) and tryptophan, dextromethanfane, and antidepressant, S-adenosylmethionine (SAM, Heptral) and tryptophan, dextromethanphane, and when, for example, dextrophane, dextrophane, octosilmethionine (SAM) lithium drugs, metoclopramide and some other drugs.
When sertraline is combined with astemizole, terfenadine or cisapride, the QT interval lengthens, and fatal ventricular arrhythmias of the “pirouette” type can develop. When combined with warfarin, a small, but statistically significant increase in prothrombin time was noted.
Sertralin is incompatible with ethanol (this combination increases the inhibitory effect on the central nervous system).
In a 2009 study comparing 12 antidepressants of the new generation, it was shown that sertraline (along with escitalopram) is one of the best drugs for the treatment of major depressive disorder (MDD).
Some studies have questioned the effectiveness of sertraline. Thus, a comparative review of 42 clinical trials of 6 antidepressants (sertraline, fluoxetine, paroxetine, citalopram, nefazodone, and venlafaxine), including those tests whose data have not been published before, showed that the results of most of these 42 trials are negative. The difference between placebo and medications averaged only 1.8 on the Hamilton scale — a number that is statistically significant, but not clinically significant.