Description of the drug BRINTELLIX
Vortioxetine is extensively metabolized in the liver, primarily through oxidation catalyzed by CYP2D6 and to a lesser extent by CYP3A4/5 and CYP2C9.
Due to the risk of serotonin syndrome, vortioxetine is contraindicated in combination with irreversible non-selective MAO inhibitors. Vortioxetine can be prescribed no earlier than 14 days after discontinuation of irreversible non-selective MAO inhibitors. Vortioxetine must be discontinued at least 14 days before starting the use of irreversible non-selective MAO inhibitors.
Concomitant use of vortioxetine with reversible selective MAO A inhibitors, such as moclobemide, is contraindicated. If concomitant use is demonstrated to be necessary, the adjunctive drug should be used in minimal doses and with careful clinical monitoring for the occurrence of serotonin syndrome.
Concomitant use of vortioxetine with a weak, reversible, non-selective MAO inhibitor such as linezolid is contraindicated. If concomitant use is demonstrated to be necessary, the adjunctive drug should be used in minimal doses with close clinical monitoring for the occurrence of serotonin syndrome.
Although the risk of serotonin syndrome with concomitant use of vortioxetine and selective MAO B inhibitors is lower than with concomitant use of vortioxetine and selective MAO A inhibitors, the combined use of vortioxetine with irreversible MAO B inhibitors such as selegiline or rasagiline should be used with caution. In case of simultaneous use, the patient should be closely monitored for the occurrence of serotonin syndrome.
Concomitant use of vortioxetine and other drugs with serotonergic effects (for example, tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome. Concomitant use of antidepressants with serotonergic effects with drugs containing St. John's wort may lead to an increased incidence of adverse reactions, including serotonin syndrome.
Antidepressants with serotonergic effects may lower the seizure threshold. Concomitant use with drugs that lower the seizure threshold (for example, tricyclic antidepressants, SSRIs, SNRIs), antipsychotics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, tramadol) should be used with caution.
When vortioxetine was administered at a dose of 10 mg/day concomitantly with bupropion (a strong inhibitor of the CYP2D6 isoenzyme) at a dose of 150 mg 2 times/day for 14 days in healthy subjects, vortioxetine exposure increased by 2.3 times.
Adverse reactions were observed more frequently when bupropion was added to current vortioxetine therapy than when vortioxetine was added to current bupropion therapy. Depending on the individual patient's response, when adding a strong CYP2D6 inhibitor (e.g., bupropion, quinidine, fluoxetine, paroxetine) to current vortioxetine therapy, consider reducing the dose of vortioxetine.
Adding vortioxetine 6 days after starting the use of ketoconazole at a dose of 400 mg/day (inhibitor of the CYP3A4/5 isoenzymes and P-glycoprotein) or 6 days after starting the use of fluconazole at a dose of 200 mg/day (inhibitor of the CYP2C9, CYP2C19 and CYP3A4/5 isoenzymes ) in healthy subjects, vortioxetine exposure (AUC) increased 1.3-fold and 1.5-fold, respectively. No dose adjustment is required.
There have been no specific studies of the use of vortioxetine concomitantly with strong CYP3A4 inhibitors (such as itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, conivaptan and many HIV protease inhibitors) and CYP2C9 inhibitors (such as fluconazole and amiodarone) in patients with reduced CYP2D6 activity. However, in these patients, such use would be expected to result in greater exposure to vortioxetine than the moderate exposure described above. Taking a single dose of omeprazole 40 mg (CYP2C19 inhibitor) with repeated doses of vortioxetine did not change the pharmacokinetics of the latter in healthy subjects.
When a single dose of vortioxetine 20 mg was administered 10 days after initiation of rifampicin 600 mg/day (a broad-spectrum CYP isoenzyme inducer) in healthy subjects, vortioxetine exposure (AUC) was reduced by 72%. Depending on the individual response of the patient, when adding a strong inducer of broad-spectrum cytochrome P450 isoenzymes (for example, rifampicin, carbamazepine, phenytoin) to current vortioxetine therapy, the possibility of adjusting the dose of vortioxetine should be considered.
Antidepressants and alcohol: compatible?
Author: Pribytkov A.A.
Can you drink alcohol if you are taking antidepressants? The thought immediately arises: what kind of alcohol is there, if you get cured, then you will indulge in alcohol. But it's not that simple. The standard course of taking antidepressants is 6 months (in some cases it can be longer). Now let’s imagine: the symptoms have already gone away, the person feels well, there are still months of treatment ahead, and then there’s a wedding, a birthday, or the first vacation in two years...
So the question about the compatibility of antidepressants and alcohol is quite relevant and patients ask me this regularly at appointments. I have repeatedly come across the statement that alcohol is completely contraindicated during treatment with antidepressants. But I also saw people who drank alcohol “on top of” antidepressants without any consequences.⠀
Let's try to understand the compatibility of antidepressants and alcohol.
Let me start with the fact that antidepressants are a fairly large group of drugs and what is true for one may be completely wrong for another. And then in the text there will be specifics. I call antidepressants by international names, if you need to clarify about trade names (those written on the packaging), ask in the comments - I will answer, or Yandex to help.⠀
Tricyclic antidepressants (amitriptyline, clomipramine, imipramine) are the first generation, crude drugs, with a powerful effect, but a lot of side effects. They act on many receptors at once, hence the high probability of interaction with other substances. NOT compatible with alcohol (as stated in the instructions), they enhance its effect. With high doses of both, there are serious consequences, including the prospect of bouquets with an even number of flowers.⠀
A group with the complex name Selective Serotonin Reuptake Inhibitors - SSRIs (escitalopram, sertraline, paroxetine, fluoxetine, fluvoxamine). The drugs act on serotonin in isolation, there are few side effects, and interactions are rare. Escitalopram, sertraline, paroxetine, fluoxetine are stated to NOT affect the metabolism of alcohol and DO NOT enhance its effect. Immediately in the instructions there is a disclaimer that it is not recommended to take it together. I won’t recommend it either, but I can’t strictly prohibit it either. To patients taking these drugs, I say something like this: small amounts of alcohol can sometimes be tolerated, but only after the condition has normalized (that is, during the period of maintenance therapy).
Vortioxetine is a modern antidepressant with a minimal likelihood of interactions. It does NOT affect the metabolism of alcohol and does NOT enhance its effect on the psyche. The summary is similar to the SSRI group: it’s possible, just be careful.⠀
Mirtazapine and its “little brother” mianserin. They act through receptors, including histamine receptors. Hence their pronounced sedative (calming, inhibitory) effect and one can suspect that there will be an interaction with alcohol. We look at the instructions - exactly, they enhance the effect of alcohol. If the doctor prescribed Mirtazapine, then you should forget about adult drinks.⠀
“Double action” drugs. For those for whom the words receptor and neurochemistry do not cause an irresistible yawn, I inform you: they act on serotonin and norepinephrine. There are such substances in nerve cells and disturbances in their metabolism lead to depression and other problems. The likelihood of interactions is low, but still higher than with SSRIs. About venlafaxine it is indicated that it enhances the effect of alcohol, about the other two there are no direct instructions, only a warning that it should be avoided. My summary: there are unlikely to be serious consequences, but it’s better not to risk it.
Agomelatine. From the point of view of the effect on the nervous system when drinking alcohol, it is theoretically safe; I have not found any direct instructions. An extremely rare but dangerous effect on the liver has been described. Based on this, there is a reason for abstaining from alcohol.⠀
General summary. If you are taking antidepressants, it is best to avoid alcohol. Tricyclic antidepressants (amitriptyline, etc.) or mirtazapine - say a firm NO to alcohol. SSRIs (escitalopram, sertraline, etc.), as well as vortioxetine - sometimes a little bit is acceptable.⠀
And, of course, this entry is in no way a call to wash down an antidepressant with a glass of vodka or a glass of foam. We are talking about some rare significant cases and limited quantities. Let me make a reservation: no one has measured what a “small dose” is. Use common sense. A glass of wine or a bottle of beer with the mentioned “safe” antidepressants is acceptable, I can’t guarantee anything more.⠀
#antidepressants #alcohol #psychotherapistPenza #DoctorPribytkov #ColorsofLifePenza
Pharmacological properties
The mechanism of action of vortioxetine appears to be related to its direct modulating serotonergic activity and inhibition of the serotonin transport protein. Preclinical studies indicate that vortioxetine acts as an antagonist of the 5-HT3, 5-HT7 and 5-HT1D receptors, a partial agonist of the 5-HT1B receptor and a full agonist of the 5-HT 1A receptor, and also inhibits the 5-HT transporter, thereby modulating neurotransmission in several systems, primarily serotonergic, but probably also noradrenergic, dopaminergic, neurotransmission mediated by histamine, acetylcholine, GABA and glutamate. This multimodal pharmacological activity appears to underlie the antidepressant and anxiolytic properties of vortioxetine and is also responsible for the improvements in cognition, learning and memory observed in animal studies. However, since the individual contribution of each pharmacological target to the observed pharmacodynamic profile of vortioxetine remains unclear, extrapolation of the reported preclinical data to humans should be done with caution.
Two studies using positron emission tomography (PET) in humans to quantify the extent of 5-HT transporter occupancy (using ligands 11 C-MADAM or 11 C-DASB), at different dosage levels of vortioxetine, found the following data: mean number 5-HT transporters associated with vortioxetine were approximately 50% at a dose of 5 mg/day, 65% at a dose of 10 mg/day, and increased to 80% when the dose was increased to 20 mg/day.
Clinical efficacy and safety
The efficacy and safety of vortioxetine have been studied in a number of clinical studies involving more than 6,700 patients, of which more than 3,700 patients participated in short-term (≤12 weeks) studies in major depressive disorder (MDD). Twelve double-blind, placebo-controlled, 6/8-week, fixed-dose studies were conducted to determine the short-term effectiveness of vortioxetine for MDD in adult patients (including elderly patients). Efficacy of vortioxetine was demonstrated in at least the single-dose group in 9 of 12 studies, showing a change of at least 2 points from placebo on the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-). D24). This was clinically confirmed by the number of patients responding to therapy and achieving remission, as well as improvement on the Clinical Global Impression Scale (CGI-I). The effectiveness of vortioxetine increased with increasing dose.
Individual study efficacy was supported by a meta-analysis (MMRM) of mean changes in MADRS total score at 6/8 weeks in short-term placebo-controlled studies in adults. According to the results of a meta-analysis of these studies, the differences from placebo were statistically significant: -2.3 points (p = 0.007); -3.6 points (p Category: Other drugs
Brintellix (vortioxetine)
The drug vortioxetine (Brintellix) is an effective and safe antidepressant. The drug is used in psychiatric practice for the treatment of clinical depression at different stages - for active therapy, condition stabilization and maintenance therapy. The drug is well tolerated by patients suffering from depressive disorders. Psychotherapists at the Yusupov Hospital take an individual approach to choosing the dose of the drug vortioxetine (Brintellix) and the duration of the course of treatment.
Vortioxetine is the trade name of the drug Brintellix. It has the following clinical features:
- Its own pro-cognitive effect (improves memory, attention, thinking);
- Minimal negative impact on sexual function;
- No significant impact on the ability to drive;
- No significant effect on body weight with long-term use.
Reviews from patients who take the antidepressant vortioxetine (Brintellix) are positive. The drug does not cause sleep disturbances. The drug can be discontinued at the same time, since there is no withdrawal syndrome when stopping treatment. Doctors at the Yusupov Hospital take into account the indications, contraindications for the use of the drug Brintellix, and possible side effects.
Compound:
Active substance
– vortioxetine hydrobromide 6.355 mg / 12.710 mg / 19.065 mg / 25.420 mg, which is equivalent to 5 mg / 10 mg / 15 mg / 20 mg vortioxetine.
Excipients
– mannitol 110.645 mg/ 104.29 mg/ 97.935 mg/ 91.58 mg, microcrystalline cellulose 22.5 mg/ 22.5 mg/ 22.5 mg/ 22.5 mg, hyprolose 4.5 mg/ 4.5 mg / 4.5 mg/ 4.5 mg, sodium carboxymethyl starch (type A) 4.5 mg/ 4.5 mg/ 4.5 mg/ 4.5 mg, magnesium stearate 1.5 mg/ 1.5 mg/ 1 .5 mg/ 1.5 mg.
for tablets 5 mg – Opadry pink 4.5 mg (hypromellose 2.813 mg, titanium dioxide (E171) 1.375 mg, macrogol 400 0.281 mg, iron dye red oxide (E172) 0.032 mg);
for tablets 10 mg - Opadry yellow 4.5 mg (hypromellose 2.813 mg, titanium dioxide (E171) 1.350 mg, macrogol 400 0.281 mg, iron dye yellow oxide (E172) 0.056 mg);
for tablets 15 mg - Opadry orange 4.5 mg (hypromellose 2.813 mg, titanium dioxide (E171) 1.294 mg, macrogol 400 0.281 mg, iron dye yellow oxide (E172) 0.101 mg, iron dye red oxide (E172) 0.011 mg);
for tablets 20 mg - Opadry red 3.0 mg (hypromellose 1.875 mg, titanium dioxide (E171) 0.449 mg, macrogol 400 0.188 mg, iron dye red oxide (E172) 0.488 mg).
Description of the dosage form
5 mg tablets: almond-shaped, pink film-coated, embossed with “TL” on one side and “5” on the other.
10 mg tablets: almond-shaped, light yellow film-coated, embossed with “TL” on one side and “10” on the other.
15 mg tablets: almond-shaped, light orange film-coated, embossed with “TL” on one side and “15” on the other.
20 mg tablets: almond-shaped, brownish-red film-coated tablets, embossed with “TL” on one side and “20” on the other.
Indications, contraindications and application features
Brintellix, as stated in the instructions for use of the drug, is used to treat major depressive episodes in adults. A contraindication to the use of the drug is hypersensitivity to the active ingredient or auxiliary component of the drug, children and adolescents under 18 years of age. The drug is not used simultaneously with non-selective or selective monoamine oxidase inhibitors.
Doctors at the Yusupov Hospital are especially wary when prescribing the antidepressant Brintellix to patients suffering from severe renal and liver failure, mania and hypomania, and pharmacologically uncontrolled epilepsy. They collectively decide on the safety of therapy with the drug Brintellix for patients who have previously had seizures, severe suicidal behavior, and a tendency to bleed.
Brintellix should be prescribed with caution concomitantly with the following medications:
- Monoamine oxidase B inhibitors (selegiline, rasagiline);
- Serotonergic drugs;
- Drugs that lower the seizure threshold;
- Lithium;
- Tryptophan;
- Medicines that contain St. John's wort;
- Oral anticoagulants and pharmacological drugs that affect platelet function;
- Drugs that can cause a decrease in sodium concentration in blood plasma.
At a meeting of the Expert Council with the participation of professors, doctors of medical sciences, and doctors of the highest category, the issue of the safety of prescribing the antidepressant brintellix to patients undergoing electroconvulsive therapy and elderly patients is decided.
The drug has a toxic effect on the fetus. When using Brintellix in late pregnancy, newborns may develop the following symptoms:
- Respiratory distress;
- Apnea (stopping breathing);
- Cyanosis (bluish color of the skin);
- Convulsions;
- Temperature instability;
- Vomit;
- Difficulty eating;
- Increased blood pressure;
- Trembling of arms and legs;
- Irritability;
- Increased neuro-reflex excitability;
- Constant crying;
- Sopor;
- Drowsiness or poor sleep.
