Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

Насырова, Р. Ф.; Толмачев, М. Ю.; Сычев, Д. А.; Яхин, К. К.; Neznanov, N.

doi:10.20538/1682-0363-2017-4-30-41

Cited by 3 publications

(1 citation statement)

References 76 publications

(105 reference statements)

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“…(5) FGAs are characterized by extrapyramidal symptoms, and hyperprolactinemia and, to a lesser extent, metabolic disorders; SGAs are more associated with weight gain, the appearance of type 2 diabetes, cardiovascular diseases, and the development of MetS. (6,7) Results of numerous studies show that antipsychotic induced weight gain occurs in 12-16 weeks. (8) It was found that patients with psychotic disorders are more likely to suffer from obesity than the general population.…”

Section: Introductionmentioning

confidence: 99%

Association of the HTR2A T102C SNP with Weight Gain and Changes in Biochemical Markers in Patients Receiving Antipsychotics

Tolmachev¹,

Akhmetova²,

Shnayder³

et al. 2018

IJBM

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The purpose of our research was to study the association of the HTR2A T102C (rs6313) SNP with anthropometric and biochemical markers in patients treated with typical and atypical antipsychotics in monotherapy mode.Materials and methods: One hundred and seventeen white inpatients (95 men and 22 women) with F2 disorders (ICD-10, 1995) were enrolled in the study. All patients were divided into two groups by the antipsychotic class with which they were treated (Group 1 included 40 patients treated with typical antipsychotics; Group 2 included 77 patients treated with atypical antipsychotics) and two subgroups by weight change criteria during the study (Subgroup 1 included patients with weight change >6%; Subgroup 2 included patients with weight change <6%). The following examinations were performed: physical examination, anthropometric measurements (BMI. WC, TC), clinical examination, blood test, and genotyping for the HTR2A T102C (rs6313) SNP.Results: There were no statistically significant differences in the distribution of genotypes of the HTR2A T102C (rs6313) SNP between Group 1 and Group 2 (P>0.05). Kruskal-Wallis one-way analysis of variance between subgroups showed statistically significant differences between carbamide levels in the second visit in Group 2 (P=0.02). We showed statistically significant differences between TT and CT genotypes of the HTR2A T102C SNP: carbamide level was greater in TT carriers (P=0.02). The strength of associations and risks between alleles of the HTR2A T102C SNP and antipsychotic-induced weight change were as follows: OR C =0.49; CI C [0.25; 0.95]; RR C =0.58 CI C [0.35; 0.97]; OR T =2.03; CI T [1.05; 3.94]; RR T =1.7 CI T [1.02; 2.81]. Conclusion: Our results of the pilot pharmacogenetic studies show an association of the T allele carriage of the HTR2A T102C (rs6313) SNP with risk of antipsychotic-induced weight gain. The continuation of this study and an increase in the sample size will allow establishing valid pharmacogenetic markers for the risk of antipsychotic-induced weight gain. (International Journal of Biomedicine. 2018;8(3):186-191.)

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Section: Introductionmentioning

confidence: 99%

Association of the HTR2A T102C SNP with Weight Gain and Changes in Biochemical Markers in Patients Receiving Antipsychotics

Tolmachev¹,

Akhmetova²,

Shnayder³

et al. 2018

IJBM

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Metabolic adverse effects of antipsychotics: the state of the problem and management options

et al. 2023

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Antipsychotic drugs are widely used for many psychiatric disorders, such as schizophrenia, bipolar affective disorder, delusions and hallucinations due to neurological disorders, depression with severe psychotic symptoms. Metabolic disorders including weight gain, dyslipidemia and hyperglycemia are one of the most common side effects of antipsychotic therapy. Psychiatric patients have higher risk of cardiovascular disease, so that the development of metabolic side effects is an important clinical problem that should be solved. Antipsychotic-induced weight gain may cause distress that leads to antipsychotics withdraw and repeated hospitalizations.Lifestyle changes, correction of the antipsychotic treatment, additional medications and their combination are the possible solutions of antipsychotic metabolic side effects. Lifestyle modification is a first-line therapy that should complement other options, when it feasible. At the same time, it can be extremely difficult for patients receiving antipsychotic to adhere dietary and physical activity recommendations. Replacing an antipsychotic with a milder drug is not always possible and may not be enough effective. Metformin seems to be the most well-studied, safe and effective agent that is prescribed to deal with antipsychotic-induced weight gain and associated metabolic disorders. Glucagon-like peptide type 1 receptor agonists and thiazolidinediones are mentioned as alternative medications, but clinical data on their efficacy and safety in this patient group are extremely limited. Dyslipidemia can develop as an independent antipsychotic side effect even without an increase in body weight. The most effective treatment, as in the general population, is statin therapy. However, the joint appointment of statins and antipsychotic significantly increases the risk of adverse reactions, such as myalgia, myopathy, increased creatine kinase levels, due to the competition of drugs for the cytochrome system.It is still unknown what scales should be used for cardiovascular risk stratification in patients taking antipsychotic and whether it is possible to use metformin to prevent antipsychotic-induced weight gain, and if so, how to select patients for whom such therapy can be indicated. Finally, more clinical trials are needed to evaluate the efficacy and safety of other classes of hypoglycemic and lipid-lowering drugs in patients on antipsychotics.

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Pharmacogenetics of schizophrenia in real clinical practice: a clinical case

Насырова

Shnayder

Миронов

et al. 2018

Nevrologiâ, nejropsihiatriâ, psihosomatika

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Schizophrenia is a socially significant mental disorder characterized by early onset and high time and financial expenditure on treatment. The basic drugs in these patients are antipsychotics that are highly effective against the positive and negative symptoms of schizophrenia, but at the same time have a wide range of adverse reactions (ARs). The clinical effect and tolerability of antipsychotics are variable and depend on the characteristics of genetically determined mechanisms (transportation, biotransformation, and elimination).The paper describes a clinical case of a female patient with schizophrenia who has been noted to be unresponsive to antipsychotic therapy for some years after the onset of the disease. After pharmacogenetic testing, she was found to be homozygous for the nonfunctional allelic variant CYP2D6*4 (1934 G>A, rs3892097), which was the reason for the complete shutdown of isoenzyme 2D6 activity and the development of ARs in the use of initial doses of antipsychotic drugs, as well as for an increase in the severity of ARs with aggravation of psycho-producing symptoms with an even slow titration of the daily dose.

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Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

Cited by 3 publications

References 76 publications

Association of the HTR2A T102C SNP with Weight Gain and Changes in Biochemical Markers in Patients Receiving Antipsychotics

Association of the HTR2A T102C SNP with Weight Gain and Changes in Biochemical Markers in Patients Receiving Antipsychotics

Metabolic adverse effects of antipsychotics: the state of the problem and management options

Pharmacogenetics of schizophrenia in real clinical practice: a clinical case

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