1.What are the principles of medication for pediatric seminarians? Is it better to use single medication or with medication?
The medication principles for children with schizophrenia are.
(1) Once a child is diagnosed with schizophrenia, medication should be started;
(2) Select an antipsychotic medication based on the manifestation of the child’s clinical symptom cluster, as well as the somatic condition. Treatment is individualized and varies from person to person;
(3) For pediatric patients, treatment should be started in small doses and gradually increased to the effective recommended dose. The rate of medication adjustment depends on the characteristics of the drug and the child’s physical condition;
(4) Drug therapy should follow the principle of full dosage and full course of medication.
If the treatment with one antipsychotic drug has reached the therapeutic dose and the full course of treatment is still ineffective, increase the dose or consider switching to another antipsychotic drug with a different chemical structure as appropriate, and still focus on single drug treatment. If the efficacy of the above treatment is still unsatisfactory, the combination of two drugs should be considered.
The combination of two drugs with different chemical structures and different pharmacological effects should be considered. Atypical antipsychotics are generally recommended as the first-line drugs. When treating with antipsychotic drugs, pay attention to monitoring the changes of clinical symptoms and functional impairment, carefully observe and evaluate the adverse drug reactions and make active treatment.
2. There have been three generations of antipsychotic drugs, is it true that the newer the drug, the better its efficacy?
The first generation of antipsychotic drugs are D2 blockers. It can act on four dopamine pathways in the central nervous system, of which D2 receptor blocking effect on the midbrain cortical and limbic systems is its main mechanism of action, but D2 receptor blocking effect on the nodal funnel and nigrostriatal pathways is associated with adverse drug reactions.
Second-generation antipsychotics have higher 5-hydroxytryptamine receptor blocking effects, are more selective in their effects on the limbic system of the midbrain than on the striatal system, and have a smaller or insignificant rate of extrapyramidal adverse effects.
Third-generation antipsychotics are 5-hydroxytryptamine-dopamine system stabilizers, such as aripiprazole. Second- and third-generation antipsychotics are collectively referred to as atypical antipsychotics.
According to the Chinese Guidelines for the Prevention and Treatment of Schizophrenia, atypical antipsychotics are preferred. There is no significant difference in efficacy between the various atypical antipsychotics, but there are individual differences, and the choice needs to be individualized according to the child’s different clinical symptom clusters and somatic conditions. However, haloperidol injections should be considered when the child is uncooperative or markedly excitable and agitated. In cases of poor efficacy with atypical antipsychotics, a switch to or combination with first-generation antipsychotics may be considered.
Therefore, it is not the case that the newer the drug, the better the efficacy.
3, we know that non-classical antipsychotic drugs such as: clozapine, olanzapine, risperidone, etc., the reason why the effect is good is that it acts on dopamine (DA) more inhibitory effect on 5hydroxytryptamine (5HT) receptors, but now there is a theory that inhibition of 5hydroxytryptamine receptors does not have a major effect on symptoms, “DA and 5HT dual receptors ” doctrine has been discredited, is it true?
Schizophrenia has its own pathological mechanisms, and antipsychotic drugs can block both dopamine D2 receptors and possibly 5hydroxytryptamine (5HT) receptors, perhaps acting simultaneously on both. A combined antagonistic effect of second-generation antipsychotics on dopamine and 5HT receptors has been proposed, a feature that also gives it some improvement of negative symptoms and antidepressant effects in children with schizophrenia.
Theoretically, a symptom can be said to be the “target symptom” of a drug if it has its own specific pathological mechanism and there is a drug that can target that pathological mechanism. Likewise, schizophrenia should not be treated with drugs that are specifically designed to treat hallucinations, as in the case of “treating the head when it hurts”. If the positive or negative symptoms do have their own specific pathological mechanisms, then it may be possible to find specific drugs that can treat the positive or negative symptoms separately, with one of them as the “target symptom”.
Unfortunately, it has not been possible to elucidate the specific mechanism of each of the positive or negative symptoms. If the negative symptom is indeed frontal hypofunction and a poor dopamine pathway in the frontal lobe, then a drug that selectively increases frontal dopamine would be a specific drug that could target the negative symptom as a “target symptom”. Unfortunately, all existing antipsychotic drugs have the same or similar pharmacological mechanisms, so it is theoretically impossible to have a variety of different “target symptoms. It seems that the problem is not so simple, the so-called dopamine and 5hydroxytryptamine dual receptor theory is not necessarily the truth.
4. In 2012, the US ruled that the manufacturer of Risperidone concealed the side effects of the drug, so what are the side effects of Risperidone?
Indications for child and adolescent psychiatric disorders: Risperidone can be used to treat schizophrenia and also short-term treatment of manic symptoms in patients with bipolar disorder – manic episodes/mixed episodes. Risperidone has been approved by the U.S. FDA for the treatment of schizophrenia in patients aged 13 to 17 years, bipolar disorder – manic episodes/mixed episodes in patients aged 10 to 17 years, and irritable symptoms in autistic patients aged 5 to 16 years.
In terms of chemical structure, risperidone is a combination of haloperidol and ritanserin (a 5-hydroxytryptamine receptor blocker), which retains the effects of haloperidol’s D2 receptors while adding the property of blocking 5-hydroxytryptamine receptors. It is thus understandable that risperidone may cause fewer extrapyramidal adverse reactions compared to haloperidol, but in fact it is not as few as early data suggest, and most patients still require benzedrine tablets to counteract them.
Common adverse reactions to risperidone therapy include extrapyramidal adverse effects, dizziness, drowsiness, nausea, and elevated pituitary lactogen, as well as weight gain, anxiety, agitation, insomnia, vomiting, nasal mucositis, erectile dysfunction, lack of orgasm, skin pigmentation, and cardiac conduction dysfunction (e.g., sinus bradycardia). It also predisposes to constipation, hepatotoxicity (including steatohepatitis, fatty liver, elevated transaminases), postural hypotension, elevated blood glucose, type 2 diabetes and depressed cardiac function reported in children and adolescents.
5.Is pentoxifylline a good drug with good efficacy, cheap price and few side effects? Can it be taken as a first-line drug for a long time?
Pentoxifylline is a long-acting antipsychotic with a half-life of 65-70 hours and a duration of action of up to one week. It does not increase body weight and has a low degree of blood sugar increase; although Pentoxifylline has the above characteristics, it does not mean that the drug is effective and has few side effects, and Pentoxifylline cannot be used as a first-line drug for all phases of treatment for psychiatric patients because Pentoxifylline is not effective for all patients.
Moreover, pentoxifylline is an older antipsychotic drug with more side effects, such as extrapyramidal side effects, especially delayed dyskinesia (TD), which usually occurs only after a longer period of time, but once it occurs, it is sometimes irreversible and a serious disabling side effect; and because of the long half-life of pentoxifylline, it can be very troublesome to deal with side effects once they occur. Because even if the drug is stopped immediately, its blood concentration decreases very slowly, which will delay the treatment time, so it is not recommended as the first-line treatment drug.
Of course, pentoxifylline also has its own applicability, because it is slowly absorbed and slowly acting, so it is difficult to use it to treat acute conditions, but it is more suitable for maintenance, to prevent relapse, but it is best to use it under the close examination of doctors.