Serdolect, 20 mg, film-coated tablets, 28 pcs.
Due to precautions related to QT prolongation and ECG monitoring, Serdolect should be prescribed only in cases where there is already intolerance to at least one other antipsychotic.
The risk of QT prolongation increases with higher doses of sertindole (20–24 mg/day). Prolongation of the QT interval, which occurs when using a number of drugs, can lead to the development of paroxysmal ventricular tachycardia and sudden death.
Blood pressure control is necessary during the dose selection period and at the beginning of the maintenance therapy period.
SSS.
Before prescribing the drug Serdolect, it is necessary to conduct an ECG study. When the QT interval exceeds 450 ms in men and 470 ms in women, Serdolect should not be prescribed. An ECG study should be carried out before prescribing the drug, when Css is reached approximately 3 weeks after the start of administration or a daily dose of 16 mg, as well as 3 months after the start of treatment. During maintenance therapy, an ECG examination must be performed every 3 months.
During maintenance treatment, an ECG study should be performed before and after increasing the dose of sertindole or after adding/increasing the dose of a drug that may increase the concentration of sertindole in the blood.
If the QT interval prolongs beyond 500 ms, sertindole should be discontinued.
If a patient develops symptoms such as palpitations, convulsions, fainting, indicating the possibility of an arrhythmia, the attending physician should immediately begin examining the patient, including an ECG. It is preferable to carry out an ECG study in the morning.
Electrolyte disturbances.
In patients at risk of developing severe electrolyte disturbances, serum potassium and magnesium levels should be measured before starting treatment with Serdolect. Hypokalemia and hypomagnesemia should be corrected before starting sertindole. It is recommended to monitor the concentration of potassium in the blood plasma in patients with vomiting and diarrhea, in patients taking potassium-sparing diuretics, as well as in other electrolyte disturbances.
Parkinson's disease.
Antipsychotics may inhibit the effects of dopamine agonists. Serdolect should be used with caution in patients with Parkinson's disease.
Decreased liver function.
With a slight or moderate degree of liver dysfunction, careful monitoring of the patient's condition is necessary. A slower dosage increase and a lower maintenance dose are recommended.
Convulsive seizures.
Serdolect should be prescribed with caution in patients with a history of seizures.
Tardive dyskinesia.
Long-term use of antipsychotic drugs, especially in high doses, is associated with the risk of developing tardive dyskinesia. If symptoms appear while taking sertindole, the dosage should be reduced or the drug should be discontinued completely.
ZNS.
In cases of development of NMS, immediate discontinuation of the drug is necessary.
Withdrawal syndrome.
Abrupt withdrawal of antipsychotics may cause nausea, vomiting, increased sweating, and insomnia. The return of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) are also possible. Gradual withdrawal of the drug is necessary.
Excipients.
The tablets contain lactose monohydrate. Patients with hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose and galactose should not be prescribed the drug.
Pregnancy and breastfeeding.
Since the safety of Serdolect during pregnancy in humans has not been studied, this drug should not be prescribed to pregnant women. The safety of Serdolect in breastfeeding women has not been studied. In cases where the use of sertindole is considered necessary, breastfeeding should be discontinued.
Children and youth (up to 18 years).
The safety and effectiveness of Serdolect in children and adolescents has not been studied, so the drug should not be used in children and adolescents.
Impact on the ability to drive vehicles or operate other machinery.
Although Serdolect does not have a sedative effect, patients are not recommended to drive a car or use other machinery while taking it until individual tolerance to the drug has been established.
Instructions for use SERDOLECT
Due to precautions related to QT prolongation and ECG monitoring, Serdolect should be prescribed only in cases where there is already intolerance to at least one other antipsychotic drug.
An ECG study should be performed before prescribing the drug and during therapy:
- upon reaching a steady state (approximately 3 weeks from the start of therapy) or a daily dose of 16 mg, as well as 3 months after the start of treatment.
During maintenance therapy, ECG examinations should be performed every 3 months. An ECG study should be performed before and after changing the dose of sertindole or when adding/increasing the dose of a drug that can cause an increase in the concentration of sertindole in the blood plasma.
If the QT interval prolongs beyond 500 ms, sertindole should be discontinued. If a patient experiences palpitations, seizures, fainting, or other symptoms indicating the possibility of an arrhythmia, the patient should be immediately examined (including an ECG). It is preferable to conduct an ECG study in the morning.
The risk of QT prolongation increases when taken at higher doses (20-24 mg/day). Prolongation of the QT interval, which occurs when using a number of drugs, can lead to the development of paroxysmal ventricular tachycardia and sudden death.
Blood pressure monitoring is necessary during dose titration and at the beginning of maintenance therapy.
In patients with an increased risk of developing electrolyte disturbances, the concentration of potassium and magnesium in the blood serum should be determined before starting therapy with Serdolect. Correction of electrolyte metabolism must be carried out before prescribing an antipsychotic. Regular monitoring of serum potassium concentrations is recommended in patients with vomiting and diarrhea, when using potassium-sparing diuretics, and in other electrolyte disturbances.
If neuroleptic malignant syndrome develops, immediate discontinuation of the drug is necessary.
Long-term use of antipsychotic drugs (especially in high doses) increases the risk of developing tardive dyskinesia. If symptoms of tardive dyskinesia appear while using Serdolect, the dose of the antipsychotic should be reduced or the drug should be completely discontinued.
Abrupt withdrawal of antipsychotic drugs may cause nausea, vomiting, increased sweating, and insomnia. The return of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) are also possible. Gradual withdrawal of the drug is necessary.
Antipsychotics may inhibit the effects of dopamine receptor agonists. Serdolect should be used with caution in patients with Parkinson's disease.
Careful monitoring of the condition of patients with mild or moderate hepatic impairment is necessary.
Serdolect should be prescribed with caution to patients with a history of seizures.
The tablets contain lactose monohydrate. The drug is not prescribed to patients with hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose and galactose.
Use in pediatrics
Safety and effectiveness of the drug in children and adolescents under 18 years of age
have not been studied, the use of Serdolect in this category of patients is not recommended.
Impact on the ability to drive vehicles and operate machinery
While using the drug, patients are not recommended to engage in potentially hazardous activities that require increased attention until the patient’s individual response to the drug is established.
Serdolect tablet p/o 16mg N28 (H. Lundbeck A/O)
Due to precautions related to QT prolongation and ECG monitoring, sertindole should be prescribed in cases where at least one other antipsychotic is already intolerant. The risk of QT interval prolongation is greater when taking higher doses (20-24 mg/day). Prolongation of the QT interval when taking a number of drugs can lead to the development of paroxysms of ventricular tachycardia and sudden death. Blood pressure monitoring is necessary during the dose titration period and at the beginning of the maintenance therapy period. Cardiovascular system Before prescribing Serdolect, it is necessary to conduct an ECG study. When the QT interval exceeds 450 ms in men and 470 ms in women, Serdolect should not be prescribed. An ECG study should be carried out before prescribing the drug, when equilibrium concentration is reached approximately 3 weeks after the start of administration or a daily dose of 16 mg, as well as 3 months after the start of treatment. During maintenance therapy, ECG examinations must be performed every 3 months. During maintenance treatment, an ECG study should be performed before and after increasing the dose of sertindole or after adding/increasing the dose of a drug that may increase the concentration of sertindole in the blood. If the QT interval prolongs beyond 500 ms, sertindole should be discontinued. If a patient develops symptoms such as palpitations, convulsions, fainting, indicating the possibility of an arrhythmia, the attending physician should immediately begin examining the patient, including an ECG. It is preferable to carry out an ECG study in the morning. Electrolyte disturbances In patients at risk of developing severe electrolyte disturbances, the level of potassium and magnesium in the blood serum should be measured before starting treatment with Serdolect. Hypokalemia and hypomagnesemia should be corrected before starting sertindole. It is recommended to monitor plasma potassium concentrations in patients with vomiting and diarrhea, in patients taking potassium-sparing diuretics, and in other electrolyte disturbances. Parkinson's disease Antipsychotics may inhibit the effects of dopamine agonists. Serdolect should be used with caution in patients with Parkinson's disease. Reduced liver function If liver function is slightly or moderately impaired, careful monitoring of the patient's condition is necessary. A slower dosage increase and a lower maintenance dose are recommended. Seizures Serdolect should be prescribed with caution in patients with a history of seizures. Tardive dyskinesia Long-term use of antipsychotic drugs, especially in high doses, is associated with the risk of developing tardive dyskinesia. If symptoms appear while taking sertindole, you should reduce the dosage or completely discontinue the drug. Neuroleptic malignant syndrome (NMS) In cases of NMS development, immediate discontinuation of the drug is necessary. Withdrawal syndrome When antipsychotics are abruptly discontinued, nausea, vomiting, increased sweating, and insomnia may occur. The return of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) are also possible. Gradual withdrawal of the drug is necessary. Excipients Tablets contain lactose monohydrate. The drug should not be prescribed to patients with hereditary galactose intolerance, lactase deficiency or impaired absorption of glucose and galactose. Pregnancy and breastfeeding Since the safety of Serdolect during pregnancy in humans has not been studied, this drug should not be prescribed to pregnant women. The safety of Serdolect in breastfeeding women has not been studied. In cases where the use of sertindole is considered necessary, breastfeeding should be stopped. Children and adolescents (up to 18 years) The safety and effectiveness of Serdolect in children and adolescents has not been studied, therefore the drug should not be used in children and adolescents. Effect on the ability to drive a car or other mechanisms Although Serdolect does not have a sedative effect, patients are not recommended to drive a car or use other mechanisms while taking it until individual tolerance to the drug has been established.
Psychiatry Psychiatry and psychopharmacotherapy named after. P.B. Gannushkina No. 02 2008
Introduction
Despite the avalanche-like growth of modern psychotropic drugs from the class of antidepressants in the arsenal of a practicing physician, the problem of resistance in the treatment of depressive conditions remains relevant to this day. About 30% of patients with major depression do not respond to treatment with a single antidepressant prescribed in an adequate dose for a period sufficient to obtain a therapeutic effect (P. Cowen, 1998). The main strategies for overcoming therapeutic resistance by pharmacological means are: replacing an ineffective antidepressant with another, combination therapy (simultaneous use of two antidepressants) and augmentation strategies (adding an additional drug agent not belonging to this class of drugs to antidepressant therapy). If the tactic of sequential replacement of antidepressants of various pharmacological groups and their combined use is widely used in the clinic, then augmentation strategies raise multiple questions. This is primarily due to the fact that a number of drugs that are used for augmentation (thyroid hormones, antipsychotics, etc.) do not have officially registered indications for use in endogenous depression. At the same time, data from controlled studies, convincing from the point of view of evidence-based medicine (J. John, 2002), allow us to consider this approach as one of the methods of overcoming resistance to antidepressants.
Description of a clinical case
Patient G., born in 1983, was repeatedly hospitalized at the NIPNI named after. V.M. Bekhtereva with a diagnosis of recurrent depressive disorder, current depressive episode of moderate severity. The patient's heredity is clearly not psychopathologically burdened, but among the characterological characteristics of the parents, the manifestations of emotional imbalance and irascibility attract attention. The patient was born from an uncomplicated pregnancy, the only child in the family. Among childhood disorders, manifestations of increased motor activity were identified; sleepwalking and stuttering were noted at 4–5 years of age. I went to school at the age of 7, my academic performance and adaptation to the school environment were good. After graduating from high school, he entered a technical university. Premorbidly he was impressionable, with sensitive traits. She has considered herself sick since 2003, when after a traffic accident her mood sharply decreased, accompanied by manifestations of anxiety and internal tension; isolation and decreased performance increased. At the same time, appetite worsened and sleep disturbances such as early and late insomnia arose. Once, at the height of an anxiety attack, he made a superficial cut in the area of the wrist joint, but these actions did not have a clear suicidal motivation. In the fall of 2003, he received inpatient treatment for about a month in the border psychiatry department using Coaxil, from where he was discharged without signs of depression. The patient successfully continued his studies at the university, was socially active, participated in student life, and went abroad for several months on a competitive exchange between educational institutions. A repeated episode developed in January 2005, acutely, according to the “cliché” type. He sought medical help only in August 2005. On an outpatient basis he took Sonapax 75 mg/day and Finlepsin 1000 mg/day without clear clinical dynamics. In October 2005, he was readmitted to the clinic for borderline disorders to adjust the therapy. Coaxil, phenibut and amitriptyline were sequentially added to the therapy already carried out at the outpatient stage, against the background of which the condition improved. He was discharged with maintenance therapy: phenibut (2500 mg/day), amitriptyline (75 mg/day), finlepsin (800 mg/day), Sonapax (75 mg/day), Coaxil (25 mg/day). He calls his condition during this period “unsatisfactory.” Dyssomnia disorders of moderate severity, high levels of anxiety, and fears about the safety of loved ones persisted, which, however, did not affect the patient’s behavior. 3 weeks after discharge, despite compliance with the maintenance therapy regimen, inclusions of a depersonalization nature appeared in the clinical picture: “sounds became quieter, colors became duller, smells lost intensity, etc.”, the severity of depressive symptoms returned to the prehospital level. I independently contacted NIPNI named after. V.M. Bekhterev for help and began receiving therapy with cipramil at a dose of 60 mg/day. Due to the absence of a positive effect within 4 weeks, drug interventions were used to overcome manifestations of therapeutic resistance. Initially, cipramil was replaced with melipramine at a dose of 300 mg/day, which did not cause a reduction in actual symptoms. Then a course of combination therapy with remeron at a dose of 30 mg/day and amitriptyline at a dose of 250 mg/day was carried out, but also without a significant effect. At the next stage of treatment, drugs from other pharmacological groups are added to antidepressants as augmentation: finlepsin (800 mg/day) and rispolept (4 mg/day). Negative dynamics were noted in the form of increased depersonalization and the anxiety component of the state. Taking into account resistance to monotherapy with antidepressants of various groups, combinations of drugs and augmentation with antipsychotics, the patient was offered a course of electroconvulsive therapy (ECT). After 11 ECT sessions, the patient’s condition reached the level of clinical remission with a reduction in depressive and depersonalization disorders. Upon discharge, maintenance therapy included the use of finlepsin (800 mg/day). For 5 months the condition remained good. The last deterioration began in the fall of 2006, when weakness, apathy appeared, sleep was disturbed by the type of early and late insomnia, distinct episodes of unmotivated anxiety, low mood with vital inclusions, obsessive thinking about one’s own inferiority appeared, and he blamed himself for the inability to continue his studies. I lost my appetite and lost 7 kg in 1 month. He returned to the institute for inpatient treatment. Upon admission, he maintained correct orientation. Outwardly he was inhibited, with an impoverished facial and pantomimic pattern, with an erased orientation to the reaction of his interlocutor. In contact he was formal and emotionally distant. Attention is unstable and highly distractible. Self-reported memory loss. In the mental status, manifestations of hypothymia of an asthenoanergic nature with elements of autopsychic depersonalization were determined, with an emphasis on objectively recorded symptoms of total insomnia and loss of appetite. There were suicidal thoughts without attempts to implement them. The patient remained critical of his condition. When developing a therapeutic strategy, a number of clinical, psychopathological and psychopharmacological features of this case were taken into account. Thus, the appearance of depersonalization symptoms in the status of a patient against the background of long-term anxiety is traditionally one of the factors that worsens the prognosis in terms of the speed and severity of reduction of depressive symptoms proper during antidepressant therapy. In addition, the pathomorphosis of depression with a development vector directed towards negative affectivity with the formation of apathetic affect, extinction of the cognitive component of depersonalization and transition to the structure of the defect, was also considered as a sign of an unfavorable course. Taking into account the peculiarities of previous therapy (the lack of a therapeutic effect when prescribing Ixel with Finlepsin, as well as when using a combination of antidepressants from various groups), it was decided to use augmentation tactics. Finlepsin was discontinued, the dose of Ixel was increased to 150 mg/day. Serdolect (sertindole) was chosen as an augmentation agent, the maximum dose of which was 16 mg/day. Quite quickly, during the first 2 weeks of therapy, the picture of depression became stratified. Among the first signs of positive dynamics of the condition, a disinhibitory effect with a pronounced reduction in asthenoanergic manifestations was noted. The patient's condition returned to normal within 5 weeks of therapy. Additional symptoms, represented in the patient status by phenomena of a depersonalization nature, lost their former severity 6 weeks after the start of therapy, and completely disappeared after 3 months. Side effects of therapy included nausea during the 1st week of therapy and difficulty in nasal breathing within 22 days from the start of combined use. No extrapyramidal phenomena, neuroendocrine dysfunctions, or clinically significant deviations in the functioning of other systems and organs were noted. A high-quality pharmacogenic remission was formed with a smooth extinction of the phenomena of mental alienation during the first months of outpatient observation. The post-hospital observation period in this case was 11 months. During this time, the patient's condition remained stable, without signs of any deterioration or social decline. He continues to take Ixel 150 mg/day and Serdolect 16 mg/day.
Discussion of the given clinical case
Analysis of the patient's drug history makes it possible to register resistance to monotherapy with antidepressants of various chemical groups. The basis for this is data on adequate courses of antidepressant therapy (taking drugs in the maximum recommended doses, duration of therapy for at least 4 weeks). In addition to the use of sequential changes of two or more antidepressants, the combined use of drugs (selective serotonin reuptake inhibitors - SSRIs and tricyclic antidepressants - TCAs) has also not demonstrated effectiveness. Taking this into account, the tactics of augmenting therapy with antidepressants – atypical antipsychotics – were used, which is consistent with the recommendations for taking anti-resistant measures in patients with depression (M.V. Ivanov, G.E. Mazo, 2007). To optimize the treatment of drug-resistant depression, preference is currently given to atypical antipsychotics, which, unlike traditional antipsychotics, have antidepressant activity. The latter position is probably due to the peculiarities of the spectrum of receptor activity of atypical antipsychotics, blockade of 5-HT2A/2C receptors, which enhances the release of dopamine and norepinephrine in cortical areas (G. Marek et al., 2003). The use of atypical antipsychotics to enhance the effects of SSRIs allows the use of lower doses than those typically used in the treatment of schizophrenia. This may be due to the fact that effective blockade of 5-HT2A/2C receptors occurs at lower doses than blockade of dopamine D2 receptors.). The literature discusses the use of risperidone (R.Ostroff, J.Nelson, 1999), quetiapine (B.Baune, S.Caliskan, D.Todder, 2007), and olanzapine (R.Shelton et al., 2001) for augmentation. In the presented clinical case, when choosing an antipsychotic to augment the action of antidepressants, we primarily took into account the psychopathological structure of the patient’s condition, i.e. the presence of pronounced apatoanergic disorders. Taking this into account, when choosing, we gave preference to antipsychotics with less pronounced sedative effects. The use of risperidone was questionable given the patient's history of unsuccessful use of this drug. The choice of serdolect was associated with the disinhibitory effect, lack of sedation, and low incidence of neurological side effects noted in the literature (T. Steinert, 2005; D. Murdoch, 2006). In the literature available to us, we did not find data on the use of serdolect for the augmentation of antidepressants, but the spectrum of its psychotropic activity and safety profile suggest a potential possibility that requires further study. This is evidenced by the presented clinical case.
The clinical case presented by the St. Petersburg authors is of significant interest to practicing doctors, both in itself and due to the precise and vivid characteristics presented by the researchers. Moreover, the observation in question is a drop of water that reflects the transitional state of modern psychiatry. On the one hand, when describing the case, the authors use almost the entire terminological arsenal inherent in both ICD-10 and domestic psychiatric schools. Here there is a recurrent depressive disorder, and symptoms of a defect, episodes of unmotivated anxiety, and vital inclusions, and finally, “manifestations of hypothymia of an asthenoanergic nature with elements of autopsychic depersonalization with an emphasis on objectively recorded symptoms,” as well as “apatoanergic” disorders and the phenomena of “negative affectivity.” On the other hand, the prescription of treatment, at least at its current stage, is carried out entirely in the spirit of so-called functional psychopathology. According to this trend in modern psychiatry, the clinical manifestations of mental disorders are based on an excess or deficiency of monoamines in critical structures of the central nervous system (CNS). For example, the occurrence of delusions and hallucinations is associated with an excess of dopamine in the nucleus accumbens (n. accumbence). A significant number of mental disorders are associated with so-called monoamine deficiency syndromes (MDS). In particular, dopamine deficiency syndrome (DDS) is manifested by anhedonia, apathy, aspontaneity, flattened affect, emotional withdrawal, difficulty in abstract thinking, and impaired fluency and meaningfulness of thinking. Serotonin deficiency syndrome (SDS) is associated with hypothymia (in its various manifestations, including melancholy), anxiety, panic attacks, phobias, obsessions and compulsions, food cravings, bulimia, and pain. Norepinephrine deficiency syndrome (NDS) is manifested by difficulties with concentrating attention, decreased working memory capacity, slowed down information processes, hypothymia (in its various manifestations), motor retardation, fatigue, and pain. I don’t know whether the authors had the indicated scheme in mind, but they make it absolutely clear that when prescribing therapy they directly counted on an increase in the content of dopamine and norepinephrine in the brain. At the same time, they use the properties of the atypical antipsychotic serdolect, by blocking serotonin 2A receptors, to increase the content of dopamine in the mesocortical pathways of the brain, which are responsible, in particular, for the formation of negative disorders and symptoms of cognitive deficit (serdolect is also a possible source of additional norepinephrine for them, however, Most likely, this is the effect of Ixel, which is a serotonin- and noradrenergic antidepressant). Despite the apparent lapidary nature, “functional” psychopathology makes it possible to facilitate communication between psychiatrists who hold different views on the nosology of psychoses and the diagnostic boundaries of schizophrenia. Indeed, both SDD and SDN can be observed in both affective disorders and schizophrenia. Accordingly, instead of a field for discord, a space for consensus is created. Thus, the prescription of Serdolect for clearly increasing severity of negative disorders and symptoms of cognitive deficit within the limits of functional psychopathology may not be associated with the patient’s diagnosis of schizophrenia. It is also possible to use an atypical antipsychotic if there is a corresponding clinical picture of recurrent depressive disorder. In conclusion, a number of inaccuracies should be pointed out, which, however, do not in any way reduce the value of the presented observation. Thus, in a clinical case, there is very little data on the patient’s condition (including his performance, social functioning) during outpatient treatment, especially after the last hospitalizations, and information on the duration of courses of therapy is very limited. Data from a pathopsychological study are not presented, as well as from imaging techniques (computer and magnetic resonance imaging, etc.) that are quite relevant when analyzing the origin of negative and cognitive disorders. It is erroneously stated that the patient was receiving a combination of SSRIs and TCAs, when in fact it is mentioned that the combination of Coaxil (which is a selective serotonin reuptake stimulant - SSR) and amitriptyline (TCA) was used.
