Quetiapine
Chemical group: Quetiapine (Seroquel) is a dibenzothiazepine compound.
Release form: tablets 25, 100, 200, 300 mg
Pharmacokinetics: half-life - 7 hours, peak and stabilization of concentration 1.5 hours and 2 days, respectively.
Dosage regimen: Most psychiatrists recommend a gradual increase in quetiapine doses. Initially, the drug is prescribed 25 mg orally twice a day with meals or outside meals. If the drug is well tolerated, the dose is adjusted to 50 mg twice. on the second day, then up to 100 mg twice daily. by 150 mg twice daily on approximately the fourth day of therapy. The average effective daily dose is 300-450 mg in several doses, less often the drug is prescribed at a dose of 150-850 mg/day. If there is no effect within three weeks, the dose of the drug is increased to 600-800 mg per day or more and then, having achieved a positive effect, it is gradually reduced.
According to some researchers, the initial daily dose of quetiapine should not be high due to possible severe sedation and drowsiness. Quetiapine is believed to require a slower dose increase than risperidone and olanzapine. In this case, the daily dose for the first four days of therapy is 50 mg (day 1), 100 mg (day 2), 200 mg (day 3), 300 mg (day 4).
More recent work suggests that the initial daily dose of quetiapine may be higher for the treatment of an acute episode of schizophrenia. On the first day, this dose may correspond to 150-400 mg; 500 mg or more on the second day (Peuskens J. et al., 2007).
In the elderly and in patients with liver disease, the drug is used with caution, starting with 25 mg, with a daily dose increase of 25-50 mg.
Mechanism of action: the drug has relatively low affinity (compared to other atypical antipsychotics) for 5HT1A and 5HT2A receptors, moderate to high affinity for alpha1, alpha2 and H1 receptors and lower activity against D1, D2, D3, D4, D5 - dopamine receptors. As a result of the above, quetiapine does not cause significant dopaminergic side effects. At the same time, according to the results of some studies, quetiapine at a daily dose of 800 mg blocks up to 50% of dopamine receptors. Quetiapine, unlike risperidone and olanzapine, quickly binds to D2 receptors and is also quickly released from them (“fast dissociation constant”), hence the lack of effect in terms of the occurrence of extrapyramidal disorders. Some authors associate the future direction of the synthesis of new atypical antipsychotics with the effect of “rapid release of dopamine receptors”.
Indications: Compared to risperidone and olanzapine, the drug is considered a relatively weak antipsychotic, but its effect is dose dependent. According to a number of authors, quetiapine is better tolerated than risperidone and olanzapine; in addition, its use is recommended in the treatment of schizoaffective disorders and for the treatment of patients with schizophrenia who are prone to aggression and socially dangerous actions (Styazhkin V.D., Tarasevich L.A., 2007). According to a number of researchers, quetiapine is almost twice as effective as haloperidol in terms of reducing positive and negative symptoms.
Indications for treatment of schizophrenia with quetiapine:
- Poor tolerability of atypical antipsychotics such as risperidone and olanzapine
- Schizoaffective disorders, comorbid depressive spectrum disorders
- Aggressiveness
- Tendency to develop extrapyramidal symptoms
- First psychotic episode
- Maintenance therapy
Side effects: the most common side effects of quetiapine include dizziness, hypotension, tachycardia, and QT segment prolongation on the ECG.
Side effects of quetiapine:
- Cardiovascular disorders (orthostatic hypotension, tachycardia, QT segment prolongation)
- Neurological disorders (drowsiness, rarely: insomnia, epileptiform syndrome, extrapyramidal symptoms, myalgia)
- Mild gastroenterological, endocrine and metabolic disorders (dry mouth, constipation, dyspepsia, weight gain, decreased levels of thyroid hormones)
Orthostatic hypotension, less often hypertension, is more often observed in elderly and debilitated patients. The drug should be used with caution in persons suffering from cardiovascular pathology, as well as in patients with a history of seizures. Cases of cataracts have been reported in patients receiving quetiapine for a long time.
Side effects of the drug also include mild drowsiness and, less commonly, insomnia. Due to drowsiness, the drug is not recommended for patients who drive. There have been cases of increased severity of obsessive states when taking quetiapine.
When taking quetiapine, dizziness, constipation, dry mouth, changes in liver enzyme levels, mild asthenia, rhinitis, dyspepsia, limited weight gain, headache, and fever occasionally occur.
Extrapyramidal symptoms rarely develop when taking quetiapine. Peripheral edema, priapism, myalgia (pain in the abdomen, lower back) are also noted among the rare side effects of the drug.
In some cases, an increase in serum lipids was noted during treatment with quetiapine. Possible increase in cholesterol and serum triglyceride levels, decrease in thyroid hormone levels (total T4 and free T3).
Compared with other atypical antipsychotics, quetiapine is more likely to cause anticholinergic side effects.
As noted above, the medication can affect the QT segment, so caution is required when using it in conjunction with drugs that affect the conduction of the heart muscle.
Interaction with medications: quetiapine does not combine well with alcohol, thioridazine, phenytoin, carbamazepine, microsomal enzyme inducers, drugs with central activity (barbiturates), potential CYP3A4 inhibitors (ketoconazole and erythromycin).
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Quetiapine, 200 mg, film-coated tablets, 60 pcs.
Children and adolescents (ages 10 to 17 years)
Quetiapine is not indicated for use in children and adolescents under 18 years of age due to insufficient data on use in this age group. According to the results of clinical studies of quetiapine, some side effects (increased appetite, increased concentration of prolactin in the blood serum, vomiting, runny nose and fainting) were observed with a higher frequency in children and adolescents than in adult patients. Some adverse events (AEs) may have different consequences in children and adolescents compared to adult patients. An increase in blood pressure not observed in adult patients was also noted. Changes in thyroid function have also been observed in children and adolescents. The effects on growth, puberty, mental development and behavioral reactions with long-term use (more than 26 weeks) of quetiapine have not been studied.
In placebo-controlled studies in children and adolescents with schizophrenia and mania in bipolar disorder, the incidence of advanced EPS was higher with quetiapine compared with placebo.
Suicide/suicidal ideation or clinical worsening
Depression in bipolar disorder is associated with an increased risk of suicidal thoughts of self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. Because it may take several weeks or more for the patient's condition to improve from the start of treatment, patients should be under close medical supervision until improvement occurs.
According to generally accepted clinical experience, the risk of suicide may increase in the early stages of remission. Patients (especially those at increased risk for suicide) and their caregivers should be warned to monitor for clinical worsening of suicidal behavior or thoughts of unusual changes in behavior and to seek immediate medical attention if they occur.
According to clinical studies in patients with depression in bipolar disorder, the risk of suicide-related events was 30% (7/233) for quetiapine and 0% (0/120) for placebo in patients aged 18-24 years; 18% (19/1616) for quetiapine and 18% (11/622) for placebo in patients over 25 years of age.
Other psychiatric disorders treated with quetiapine are also associated with an increased risk of suicide-related events. In addition, such conditions may be comorbid with a depressive episode. Thus, the precautions taken when treating patients with a depressive episode should also be taken when treating patients with other mental disorders.
If quetiapine therapy is abruptly discontinued, the potential risk of suicide-related events should be taken into account.
Patients with a history of suicidal events, as well as patients who clearly express suicidal thoughts before starting therapy, are at increased risk of suicidal intentions and suicide attempts and should be carefully monitored during treatment.
An FDA meta-analysis of placebo-controlled studies of antidepressants summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders found an increased risk of suicidal behavior with antidepressants compared with placebo in child adolescents and adult patients. under the age of 25. This meta-analysis does not include studies where quetiapine was used.
In short-term, placebo-controlled studies across all indications and in all age groups, the incidence of suicide events was 08% for both quetiapine (76/9327) and placebo (37/4845).
In these studies in patients with schizophrenia, the risk of suicide-related events was 14% (3/212) for quetiapine and 16% (1/62) for placebo in patients aged 18–24 years; 08% (13/1663) for quetiapine and 11% (5/463) for placebo in patients over 25 years of age; 14% (2/147) for quetiapine and 13% (1/75) for placebo in patients under 18 years of age.
In patients with manic bipolar disorder, the risk of suicide-related events was 0% (0/60) for quetiapine and 0% (0/58) for placebo in patients aged 18–24 years; 12% (6/496) for quetiapine and 12% (6/503) for placebo in patients over 25 years of age; 10% (2/192) for quetiapine and 0% (0/90) for placebo in patients under 18 years of age.
Drowsiness
During quetiapine therapy, drowsiness and associated symptoms such as sedation may occur. In clinical studies involving patients with depression as part of bipolar disorder, somnolence typically developed during the first three days of therapy. The severity of this side effect was generally minor or moderate. If severe sleepiness develops, patients with depression as part of bipolar disorder may require more frequent visits to the doctor for 2 weeks after the onset of sleepiness or until symptoms improve. In some cases, discontinuation of quetiapine therapy may be necessary.
Patients with cardiovascular diseases
Caution should be exercised when prescribing quetiapine to patients with cardiovascular and cerebrovascular diseases and other conditions predisposing to hypotension.
Orthostatic hypotension may occur during quetiapine therapy, especially during dose titration at the beginning of therapy. Orthostatic hypotension and associated dizziness may increase the risk of accidental injury (fall), especially in older patients.
Patients should exercise caution until they adjust to these potential side effects. If orthostatic hypotension occurs, dose reduction or slower titration may be necessary.
Sleep apnea syndrome
Sleep apnea syndrome has been reported in patients taking quetiapine. Caution should be exercised when prescribing quetiapine to patients receiving drugs that have a depressant effect on the central nervous system, as well as patients with risk factors for sleep apnea (for example, overweight/obese male gender) or with a history of sleep apnea.
Seizures
There were no differences in the incidence of seizures in patients taking quetiapine or placebo. However, as with other antipsychotic drugs, caution is recommended when treating patients with a history of seizures with quetiapine.
Extrapyramidal symptoms
There was an increase in the incidence of EPS in adult patients with depression in the structure of bipolar disorder when taking quetiapine for depressive episodes compared to placebo.
While taking quetiapine, akathisia may occur, which is characterized by an unpleasant feeling of motor restlessness and the need to move and is manifested by the patient’s inability to sit or stand without moving. If such symptoms occur, the dose of quetiapine should not be increased.
Tardive dyskinesia
If symptoms of tardive dyskinesia develop, it is recommended to reduce the dose of the drug or gradually discontinue it. Symptoms of tardive dyskinesia may worsen or even occur after you stop taking the drug.
Neuroleptic malignant syndrome
While taking antipsychotic drugs, including quetiapine, neuroleptic malignant syndrome may develop. Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability of the autonomic nervous system, and increased creatine phosphokinase activity. In such cases, it is necessary to discontinue quetiapine and carry out appropriate treatment.
Severe neutropenia and agranulocytosis
In short-term, placebo-controlled clinical trials of quetiapine monotherapy, cases of severe neutropenia (neutrophil count <05 x 109/L) without infection were reported infrequently. The development of agranulocytosis (severe neutropenia associated with infections) has been reported in patients receiving quetiapine in clinical trials (rare) and during post-marketing use (including death). Most of these cases of severe neutropenia occurred several months after initiation of quetiapine therapy. No dose-dependent effect was found.
Leukopenia and/or neutropenia resolved after discontinuation of quetiapine therapy. A possible risk factor for the occurrence of neutropenia is a previous low white blood cell count and a history of drug-induced neutropenia. The development of agranulocytosis was also noted in patients without risk factors. The possibility of developing neutropenia in patients with infection must be considered, especially in the absence of obvious predisposing factors or in patients with unexplained fever; these cases should be managed in accordance with clinical guidelines.
In patients with a neutrophil count <10 x 109/L, quetiapine should be discontinued. The patient should be observed for possible symptoms of infection and the neutrophil level should be monitored (until the level exceeds 15 x 109/L).
Child and adolescent therapy
At this time, few descriptions of the practical use of Seroquel in child and adolescent psychiatry can be found in the specialized literature. But they describe in sufficient detail the specifics of using the drug for this category of patients.
Due to good treatment results and mild side effects, experts suggest more active use of the drug in child and adolescent psychiatry. Already at 3-6 weeks, minor patients with schizophrenia taking Quetiapine in doses from 100 to 800 mg per day demonstrated a decrease in the symptoms of this disease, “extinguishing” hyperactivity and aggression.
Some patients experienced dry mouth, mild tremor, dizziness and hypotension as side effects. However, there were only a few such patients, and such manifestations were very weak. The usual strong increase in body weight after taking atypical antipsychotics was not observed, as well as disturbances in the endocrine system and problems with motor functions.
Also safe for children and adolescents is treatment with Quetiapine for bipolar and schizoactive disorders, antisocial behavior, psychopathy, Gilles de la Tourette syndrome and generalized tics, and other mental disorders. At the same time, experts warn about the danger of an overdose of the drug, which can cause tachycardia, hypotension, and agitation.
Seroquel in general psychiatry
At the moment, there is a significant amount of data on the practical use of Quetiapine, accumulated by specialists over the past five years. As already mentioned, this atypical antipsychotic has been introduced as a treatment for schizophrenia. Its long-term use leads to an increase in the general activity of patients, a decrease in autistic manifestations, and an improvement in social adaptation. In this case, hyperprolactinemia and extrapyramidal disorders are not observed.
Seroquel has a positive effect on cognitive function in people with schizophrenia:
• after 3 months of use, attention improves significantly;
• after six months to a year, the quality of executive function and verbal productivity improves.
It should be clarified that this effect is achieved at an average dose of 517.9 mg/day of the drug per day. Long-term use of the drug is not dangerous, as it is well tolerated. Among other things, it reduces suicidal risks.
Experts who have used the atypical antipsychotic in practice indicate its positive results for depressive symptoms. It has a stronger antipsychotic effect than haloperidol, surpassing it and other drugs in antidepressant, anti-anxiety and anti-manic properties.
Such abilities of Quetiapine made it possible to use it and prove its effectiveness in the treatment of:
• anxiety states;
• affective disorders;
• behavioral disorders;
• bipolar disorders, etc.
The drug has also been successfully used to relieve hostility and aggression, in acute mania, and to reduce psychotic symptoms.
The following positive points can be mentioned:
1. Thanks to Seroquel, monotherapy has become possible, that is, treatment of mental disorders with excellent results without side effects is available using only one, maximum two drugs.
2. If we talk about obsessive-compulsive disorders, then Seroquel has also been tried to treat patients with strong resistance to antipsychotics such as selective serotonin reuptake inhibitors. However, a small dose of the drug in monotherapy was ineffective. But, in cases of combination of Quetiapine with SSRIs, patients experienced significant improvement in their condition.
3. They tried to use an atypical antipsychotic in the treatment of post-traumatic stress disorder. 18 war veterans with this problem took Seroquel for 6 weeks, 25-300 mg per day. By the end of therapy, the patients' condition improved significantly; no deterioration in neurological parameters or negative changes in internal organs were recorded. As a result, it was decided to expand research on the use of the drug in the treatment of this disorder.
4. There is evidence of success with this antipsychotic in elderly patients with psychotic symptoms, Parkinson's disease and Alzheimer's disease. Elderly patients had improved quality of life, motor functions, decreased behavioral disorders, and improved sleep. The attending physicians clarify that to achieve a positive effect, you should start with small doses of the drug and not increase them much.
5. There are isolated cases of effective use of Quetiapine for a patient with a mental illness aggravated by drug addiction and alcoholism.
