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Psychotic disorders are relatively rare but serious comorbidities in patients with epilepsy.
The first step in management is to clarify the scene of psychotic symptoms, especially whether these symptoms are clearly related to epilepsy activities and the use of anti-epileptic drugs.
Risperidone has a lower risk of drug interaction and inducing epilepsy, and may be regarded as a first-line drug for epilepsy with psychotic disorders.
The metabolism of quetiapine is largely dependent on CYP3A4, and blood drug levels are easily affected by the enzymatic effects of antiepileptic drugs (AED) on the liver.
Clozapine may be the antipsychotic with the highest risk of inducing epilepsy, and the risk is dose-dependent.
The combined use of antipsychotics and antiepileptic drugs with similar side effects may cause intolerable side effects to patients and should be avoided as much as possible.
For post-epilepsy psychosis, the combination of benzodiazepines, especially clobazam, and antipsychotics may be beneficial, but evidence is still lacking.
It is necessary to pay attention to the potential risks of lithium salt in combination with certain AEDs.
Psychotic disorder is a relatively rare but serious comorbidity of epilepsy.
It has not only attracted the attention of clinicians and researchers, but also aroused the creative interest of artists.
For example, Shakespeare and Dostoevsky (the latter suffers from epilepsy) both described similar conditions in their works.
Meta-analysis showed that 5.
6% of patients with epilepsy had comorbid psychotic disorders and 7% of patients with temporal lobe epilepsy; overall, the risk of comorbid psychotic disorders in epilepsy patients was 7.
8 times that of the general population.
The problem is that the treatment of such comorbidities is very challenging.
For example, antipsychotics may interact with antiepileptic drugs (AED), and certain antipsychotics themselves can affect the convulsive threshold, which can induce or aggravate seizures.
Table 1 The relationship between psychotic symptoms and epileptic seizures (Agrawal N, et al.
2019).
In a review published in Ther Adv Psychopharmacol.
, researchers from the UK based on the latest evidence to manage epilepsy comorbid psychotic disorders Discussed.
The following is a brief introduction to the drug treatment part-there are few studies on the treatment of epilepsy with psychotic disorders.
In the past ten years, some regional expert consensus has been published, providing some guidance for clinicians; but at present, it seems that we may be able to refer to the international guidelines for psychotic disorders other than epilepsy and apply them flexibly to patients with epilepsy.
Whether the treatment efficiency and cure rate of epilepsy with psychotic disorders are equivalent to those of schizophrenia is not yet clear, and close monitoring is required during treatment.
Investigation of antipsychotics There is little high-quality evidence for the use of antipsychotics in patients with epilepsy.
The 2015 Cochrane systematic review showed that there was only one randomized controlled study on this topic, comparing olanzapine (10mg/d) and haloperidol (12mg/d) in 16 patients with epilepsy comorbid schizophrenia-like psychosis.
The results suggest that olanzapine performs better.
However, the research has been more than 15 years old, and it is only a conference abstract and has never been published in a peer-reviewed journal.
The author of this article recommends that for psychotic disorders in patients with epilepsy, on the one hand, it is necessary to follow universal evidence-based guidelines (such as NICE and WFSBP guidelines), including the selection of first-line antipsychotics, adequate treatment in the acute phase, and maintenance Treatment, etc.
; on the other hand, it is necessary to consider the special characteristics of the symptoms of epilepsy patients, the interaction between antipsychotics and AED, and the possibility of increased risk of side effects.
Pharmacokinetic interaction with AED Some AEDs can strongly induce liver drug enzymes, such as phenytoin, carbamazepine, and barbiturates; these drugs can reduce the blood concentration of almost all antipsychotic drugs, and are most affected by this The most significant may be quetiapine.
Quetiapine is mainly metabolized by CYP3A4.
When combined with carbamazepine, even if a high dose of 700 mg/d is used, the blood concentration may be undetectable. Oxcarbazepine is a ketone analogue of carbamazepine, but it has a milder inducing effect on CYP3A4, and its pharmacokinetic interaction with antipsychotics is also softer, which often does not have clinical significance.
Other AEDs seem to have little effect on the metabolism of second-generation antipsychotics (SGA), but the possibility of individual differences cannot be completely ruled out, especially when using olanzapine and clozapine with complex and diverse antipsychotics.
Valproate is often regarded as a liver drug enzyme inhibitor, but there is no definitive report showing that this type of drug can increase the blood concentration of the latter when combined with antipsychotic drugs.
In contrast, valproate seems to mildly induce liver drug enzymes in certain patients and promote the metabolism of certain SGAs (such as olanzapine, aripiprazole, clozapine, and quetiapine).
Such drug interactions rarely cause clinically significant consequences and should be analyzed on a case-by-case basis and should not be regarded as a general phenomenon.
Conversely, all antipsychotics do not seem to significantly affect the metabolism of AEDs, and therefore theoretically do not affect their blood drug concentrations.
Pharmacodynamic interactions with AEDs There are limited data on the pharmacodynamic interactions of antipsychotics with AEDs.
However, caution should be exercised when combining antipsychotics with similar side effects with AED, as shown in Table 2.
Table 2 Overlap of common side effects of antipsychotics and AEDs (Agrawal N, et al.
2019) For example, the sedative side effects of antipsychotics can have a synergistic effect with many AEDs.
When olanzapine is used in combination with valproate, pregabalin, gabapentin, or carbamazepine, the patient's weight gain may be particularly significant.
In view of the potential risk of neutrophil deficiency, the combination of clozapine and carbamazepine is not recommended; for similar considerations, caution should also be exercised when valproate is combined with clozapine or olanzapine.
The risk of inducing epilepsy is well known and clozapine is closely related to epilepsy: Compared with placebo, the standardized incidence rate of clozapine-related seizures is 9.
5 (95% CI 7.
2-12.
2), which may be the highest among mainstream antipsychotics of. The other two drugs, olanzapine and quetiapine, also seem to have certain risks, but to a lesser degree than clozapine.
Other commonly used antipsychotics, such as risperidone, were not significantly different from placebo.
A large-scale study based on community populations showed that first-generation antipsychotics (FGA) such as chloroprothixol, thioridazine, and haloperidol seem to have a slightly higher risk of inducing epilepsy than SGA.
Specifically for clozapine, the risk of inducing epilepsy is clearly dose-dependent, and the larger the dose, the higher the risk.
A set of data in the United States showed that the average rate of seizures in clozapine patients was 2.
9%, and the rates of clozapine doses <300 mg, 300-600 mg, and >600 mg were 1%, 2.
7%, and 4.
4, respectively.
%.
However, the above data are from patients with primary mental disorders, and it is still unclear whether it can be extended to patients with epilepsy.
There is evidence that compared with patients without a history of seizures, those with a history of seizures are more likely to have seizures when using clozapine; however, it is not clear that compared with the general population, patients without seizures under stable AED treatment Whether the patient is more prone to seizures when using clozapine.
In addition, clozapine is also associated with epileptiform abnormalities on the EEG, even if the patient does not have a clear seizure.
According to reports, the incidence of this phenomenon is 5%, but it is still unclear whether epileptic seizures can be predicted.
Duration of treatment with antipsychotics Compared with schizophrenia, psychotic episodes between seizures are more likely to recur, and many patients require long-term treatment.
However, in view of the lack of research evidence and 15% of interictal psychosis are self-limiting and do not require antipsychotic maintenance treatment, the author of this article suggests that the duration of antipsychotic treatment for such patients should follow that of psychotic disorders other than epilepsy guide.
Injection Forms So far, no research has specifically explored the use of antipsychotic injections or long-acting injections in patients with epilepsy, and whether such formulations increase the risk of epilepsy worsening compared with oral dosage forms.
In clinical scenarios other than epilepsy with benzodiazepines, benzodiazepines themselves are not usually regarded as conventional treatments for psychotic disorders.
In fact, such drugs may also cause paradoxical excitement, and may not be as effective as antipsychotic drugs in terms of rapid sedation.
However, for post-epilepsy psychosis, certain benzodiazepines, especially isopazim (clobazam), are a very popular treatment, although there is no evidence-based evidence for this use.
Lithium salt Generally speaking, the possibility of epilepsy patients using lithium salt is very low, because lithium salt is mainly used to treat bipolar disorder, and many AEDs are also first-line treatments for bipolar disorder, which can replace the role of lithium salt.
However, lithium salt is occasionally used as a potent drug for the treatment of refractory schizophrenia.
If a patient with epilepsy comorbid psychotic disorder happens to use lithium, doctors must know: ▲ When lithium salt is used in combination with carbamazepine, it causes an increased risk of thyroid toxicity and may also mask the low sodium associated with carbamazepine or oxcarbazepine.
▲ When lithium salt is used in combination with valproate, the risk of tremor, sedation and weight gain is increased; ▲ When lithium salt is used in combination with topiramate, the latter may reduce the clearance rate of lithium salt and increase the risk of overdose poisoning.
risk.
In addition, lithium salt itself also has a convulsive effect, but the blood lithium level at this time has often reached the level of poisoning (>3mmol/L).
Conclusion Psychotic disorders are relatively rare but serious comorbidities in patients with epilepsy.
The first step in the management of such psychotic symptoms is to clarify the occurrence of these symptoms, especially whether these symptoms are clearly related to epileptic activities and the use of anti-epileptic drugs.
As far as antipsychotic treatment is concerned, risperidone may be regarded as a first-line treatment; the drug has a lower risk of drug interaction and a lower risk of inducing epilepsy.
The metabolism of quetiapine is largely dependent on CYP3A4, and blood levels are easily affected by the enzymatic effects of AED liver drugs.
Clozapine may be one of the antipsychotic drugs with the highest risk of inducing epilepsy; if the patient needs to use the drug due to the disease, it is recommended to increase the dose slowly and closely monitor it.
Combining antipsychotics and antiepileptic drugs with similar side effects may cause a lot of trouble to patients.
Both psychiatrists and neurologists need to understand the common side effects of these two types of drugs.
For post-epilepsy psychosis, the combination of benzodiazepines, especially clobazam, and antipsychotics may be beneficial, but evidence is still lacking.
It is necessary to pay attention to the risks when lithium salt is used in combination with certain AEDs.
Literature index: Agrawal N, Mula M.
Treatment of psychoses in patients with epilepsy: an update.
Ther Adv Psychopharmacol.
2019 Jul 10;9:2045125319862968.
Click "Read Original" to view and retrieve historical articles.
The first step in management is to clarify the scene of psychotic symptoms, especially whether these symptoms are clearly related to epilepsy activities and the use of anti-epileptic drugs.
Risperidone has a lower risk of drug interaction and inducing epilepsy, and may be regarded as a first-line drug for epilepsy with psychotic disorders.
The metabolism of quetiapine is largely dependent on CYP3A4, and blood drug levels are easily affected by the enzymatic effects of antiepileptic drugs (AED) on the liver.
Clozapine may be the antipsychotic with the highest risk of inducing epilepsy, and the risk is dose-dependent.
The combined use of antipsychotics and antiepileptic drugs with similar side effects may cause intolerable side effects to patients and should be avoided as much as possible.
For post-epilepsy psychosis, the combination of benzodiazepines, especially clobazam, and antipsychotics may be beneficial, but evidence is still lacking.
It is necessary to pay attention to the potential risks of lithium salt in combination with certain AEDs.
Psychotic disorder is a relatively rare but serious comorbidity of epilepsy.
It has not only attracted the attention of clinicians and researchers, but also aroused the creative interest of artists.
For example, Shakespeare and Dostoevsky (the latter suffers from epilepsy) both described similar conditions in their works.
Meta-analysis showed that 5.
6% of patients with epilepsy had comorbid psychotic disorders and 7% of patients with temporal lobe epilepsy; overall, the risk of comorbid psychotic disorders in epilepsy patients was 7.
8 times that of the general population.
The problem is that the treatment of such comorbidities is very challenging.
For example, antipsychotics may interact with antiepileptic drugs (AED), and certain antipsychotics themselves can affect the convulsive threshold, which can induce or aggravate seizures.
Table 1 The relationship between psychotic symptoms and epileptic seizures (Agrawal N, et al.
2019).
In a review published in Ther Adv Psychopharmacol.
, researchers from the UK based on the latest evidence to manage epilepsy comorbid psychotic disorders Discussed.
The following is a brief introduction to the drug treatment part-there are few studies on the treatment of epilepsy with psychotic disorders.
In the past ten years, some regional expert consensus has been published, providing some guidance for clinicians; but at present, it seems that we may be able to refer to the international guidelines for psychotic disorders other than epilepsy and apply them flexibly to patients with epilepsy.
Whether the treatment efficiency and cure rate of epilepsy with psychotic disorders are equivalent to those of schizophrenia is not yet clear, and close monitoring is required during treatment.
Investigation of antipsychotics There is little high-quality evidence for the use of antipsychotics in patients with epilepsy.
The 2015 Cochrane systematic review showed that there was only one randomized controlled study on this topic, comparing olanzapine (10mg/d) and haloperidol (12mg/d) in 16 patients with epilepsy comorbid schizophrenia-like psychosis.
The results suggest that olanzapine performs better.
However, the research has been more than 15 years old, and it is only a conference abstract and has never been published in a peer-reviewed journal.
The author of this article recommends that for psychotic disorders in patients with epilepsy, on the one hand, it is necessary to follow universal evidence-based guidelines (such as NICE and WFSBP guidelines), including the selection of first-line antipsychotics, adequate treatment in the acute phase, and maintenance Treatment, etc.
; on the other hand, it is necessary to consider the special characteristics of the symptoms of epilepsy patients, the interaction between antipsychotics and AED, and the possibility of increased risk of side effects.
Pharmacokinetic interaction with AED Some AEDs can strongly induce liver drug enzymes, such as phenytoin, carbamazepine, and barbiturates; these drugs can reduce the blood concentration of almost all antipsychotic drugs, and are most affected by this The most significant may be quetiapine.
Quetiapine is mainly metabolized by CYP3A4.
When combined with carbamazepine, even if a high dose of 700 mg/d is used, the blood concentration may be undetectable. Oxcarbazepine is a ketone analogue of carbamazepine, but it has a milder inducing effect on CYP3A4, and its pharmacokinetic interaction with antipsychotics is also softer, which often does not have clinical significance.
Other AEDs seem to have little effect on the metabolism of second-generation antipsychotics (SGA), but the possibility of individual differences cannot be completely ruled out, especially when using olanzapine and clozapine with complex and diverse antipsychotics.
Valproate is often regarded as a liver drug enzyme inhibitor, but there is no definitive report showing that this type of drug can increase the blood concentration of the latter when combined with antipsychotic drugs.
In contrast, valproate seems to mildly induce liver drug enzymes in certain patients and promote the metabolism of certain SGAs (such as olanzapine, aripiprazole, clozapine, and quetiapine).
Such drug interactions rarely cause clinically significant consequences and should be analyzed on a case-by-case basis and should not be regarded as a general phenomenon.
Conversely, all antipsychotics do not seem to significantly affect the metabolism of AEDs, and therefore theoretically do not affect their blood drug concentrations.
Pharmacodynamic interactions with AEDs There are limited data on the pharmacodynamic interactions of antipsychotics with AEDs.
However, caution should be exercised when combining antipsychotics with similar side effects with AED, as shown in Table 2.
Table 2 Overlap of common side effects of antipsychotics and AEDs (Agrawal N, et al.
2019) For example, the sedative side effects of antipsychotics can have a synergistic effect with many AEDs.
When olanzapine is used in combination with valproate, pregabalin, gabapentin, or carbamazepine, the patient's weight gain may be particularly significant.
In view of the potential risk of neutrophil deficiency, the combination of clozapine and carbamazepine is not recommended; for similar considerations, caution should also be exercised when valproate is combined with clozapine or olanzapine.
The risk of inducing epilepsy is well known and clozapine is closely related to epilepsy: Compared with placebo, the standardized incidence rate of clozapine-related seizures is 9.
5 (95% CI 7.
2-12.
2), which may be the highest among mainstream antipsychotics of. The other two drugs, olanzapine and quetiapine, also seem to have certain risks, but to a lesser degree than clozapine.
Other commonly used antipsychotics, such as risperidone, were not significantly different from placebo.
A large-scale study based on community populations showed that first-generation antipsychotics (FGA) such as chloroprothixol, thioridazine, and haloperidol seem to have a slightly higher risk of inducing epilepsy than SGA.
Specifically for clozapine, the risk of inducing epilepsy is clearly dose-dependent, and the larger the dose, the higher the risk.
A set of data in the United States showed that the average rate of seizures in clozapine patients was 2.
9%, and the rates of clozapine doses <300 mg, 300-600 mg, and >600 mg were 1%, 2.
7%, and 4.
4, respectively.
%.
However, the above data are from patients with primary mental disorders, and it is still unclear whether it can be extended to patients with epilepsy.
There is evidence that compared with patients without a history of seizures, those with a history of seizures are more likely to have seizures when using clozapine; however, it is not clear that compared with the general population, patients without seizures under stable AED treatment Whether the patient is more prone to seizures when using clozapine.
In addition, clozapine is also associated with epileptiform abnormalities on the EEG, even if the patient does not have a clear seizure.
According to reports, the incidence of this phenomenon is 5%, but it is still unclear whether epileptic seizures can be predicted.
Duration of treatment with antipsychotics Compared with schizophrenia, psychotic episodes between seizures are more likely to recur, and many patients require long-term treatment.
However, in view of the lack of research evidence and 15% of interictal psychosis are self-limiting and do not require antipsychotic maintenance treatment, the author of this article suggests that the duration of antipsychotic treatment for such patients should follow that of psychotic disorders other than epilepsy guide.
Injection Forms So far, no research has specifically explored the use of antipsychotic injections or long-acting injections in patients with epilepsy, and whether such formulations increase the risk of epilepsy worsening compared with oral dosage forms.
In clinical scenarios other than epilepsy with benzodiazepines, benzodiazepines themselves are not usually regarded as conventional treatments for psychotic disorders.
In fact, such drugs may also cause paradoxical excitement, and may not be as effective as antipsychotic drugs in terms of rapid sedation.
However, for post-epilepsy psychosis, certain benzodiazepines, especially isopazim (clobazam), are a very popular treatment, although there is no evidence-based evidence for this use.
Lithium salt Generally speaking, the possibility of epilepsy patients using lithium salt is very low, because lithium salt is mainly used to treat bipolar disorder, and many AEDs are also first-line treatments for bipolar disorder, which can replace the role of lithium salt.
However, lithium salt is occasionally used as a potent drug for the treatment of refractory schizophrenia.
If a patient with epilepsy comorbid psychotic disorder happens to use lithium, doctors must know: ▲ When lithium salt is used in combination with carbamazepine, it causes an increased risk of thyroid toxicity and may also mask the low sodium associated with carbamazepine or oxcarbazepine.
▲ When lithium salt is used in combination with valproate, the risk of tremor, sedation and weight gain is increased; ▲ When lithium salt is used in combination with topiramate, the latter may reduce the clearance rate of lithium salt and increase the risk of overdose poisoning.
risk.
In addition, lithium salt itself also has a convulsive effect, but the blood lithium level at this time has often reached the level of poisoning (>3mmol/L).
Conclusion Psychotic disorders are relatively rare but serious comorbidities in patients with epilepsy.
The first step in the management of such psychotic symptoms is to clarify the occurrence of these symptoms, especially whether these symptoms are clearly related to epileptic activities and the use of anti-epileptic drugs.
As far as antipsychotic treatment is concerned, risperidone may be regarded as a first-line treatment; the drug has a lower risk of drug interaction and a lower risk of inducing epilepsy.
The metabolism of quetiapine is largely dependent on CYP3A4, and blood levels are easily affected by the enzymatic effects of AED liver drugs.
Clozapine may be one of the antipsychotic drugs with the highest risk of inducing epilepsy; if the patient needs to use the drug due to the disease, it is recommended to increase the dose slowly and closely monitor it.
Combining antipsychotics and antiepileptic drugs with similar side effects may cause a lot of trouble to patients.
Both psychiatrists and neurologists need to understand the common side effects of these two types of drugs.
For post-epilepsy psychosis, the combination of benzodiazepines, especially clobazam, and antipsychotics may be beneficial, but evidence is still lacking.
It is necessary to pay attention to the risks when lithium salt is used in combination with certain AEDs.
Literature index: Agrawal N, Mula M.
Treatment of psychoses in patients with epilepsy: an update.
Ther Adv Psychopharmacol.
2019 Jul 10;9:2045125319862968.
Click "Read Original" to view and retrieve historical articles.
