INTRODUCTION. Treatment-resistant schizophrenia (TRS) represents one of the most challenging clinical problems in psychiatry. Clozapine remains the only antipsychotic with proven efficacy for TRS; however, in real-world clinical practice, patients frequently receive combinations of antipsychotic medications, which increases the risk of adverse drug reactions (ADRs). Monitoring the safety of therapy in TRS is of high clinical significance.

AIM. To analyze the safety profile of psychopharmacotherapy in patients with TRS in real-world clinical practice using a custom panel of global triggers adapted for psychiatric inpatient settings, with the aim of optimizing treatment strategies for resistant cases and selecting triggers for inclusion in an active adverse drug reaction monitoring system.

MATERIALS AND METHODS. A retrospective pharmacoepidemiological study was conducted of 500 completed clinical cases of patients with TRS admitted to a psychiatric hospital between 2021 and 2024. ADRs were identified using the global triggers method and classified by type, severity, preventability, and probability of causal relationship. The rationality of pharmacotherapy (assessed using the Medication Appropriateness Index, MAI) and the positive predictive value (PPV) of the triggers were evaluated.

RESULTS. ADRs were identified in 48.8% of patients, most commonly extrapyramidal disorders (15.8%), tachycardia (9.6%), and increased sedation (8.8%). Potentially clinically significant drug interactions were noted in 58.4% of patients. Only 15.6% of patients received rational therapy, while 84.4% showed deviations from recommended pharmacotherapy regimens. Clozapine was prescribed in a timely manner in only 31.6% of patients; in 48.0%, documentation of prescription timing was absent. Maximum PPV values (80–100%) were characteristic of triggers reflecting clinical and laboratory changes: significant weight gain, decreased leukocyte levels, hyperprolactinemia, laxative prescription, and pronounced sedation. Moderate predictive value (36–51%) was demonstrated by triggers associated with concomitant therapy (β-blockers, antidiarrheal and antihistamine agents). Low specificity (PPV 2–20%) was noted for triggers reflecting pharmacotherapy changes (drug discontinuation or dose reduction, prescription and dose adjustment of extrapyramidal symptom correctors). The least informative trigger (PPV 2.0%) was “irrational drug combinations”.

CONCLUSIONS. Psychopharmacotherapy in patients with TRS in psychiatric inpatient settings was characterized by a high frequency of ADRs, substantial prevalence of clinically significant drug interactions, and low prescribing rationality. Triggers reflecting clinical-laboratory changes (significant weight gain, decreased leukocyte levels, hyperprolactinemia, laxative prescription, and pronounced sedation) demonstrated the greatest predictive value and may be recommended for prioritized inclusion in an active safety monitoring system for psychopharmacotherapy in TRS. To optimize treatment strategies for resistant cases, implementation of algorithms for early identification of treatment resistance is necessary, enabling timely clozapine prescription, alongside the use of standardized tools for assessing the rationality of combination therapy.

INTRODUCTION. Validated tools for assessing the quality and safety of pharmacotherapy, widely used for scientific and expert purposes, have proven effective in improving treatment quality and optimizing costs. However, their application in routine clinical practice is often limited by the complexity of the assessment procedure and interpretation of results, as well as the lack of adaptation to national clinical guidelines. Therefore, the development of a comprehensive method based on a qualitative and quantitative assessment of pharmacotherapy compliance with clinical guidelines and the criteria of efficacy, rationality, and safety remains relevant.

AIM. To develop and pilot-test an adapted tool, the Pharmacotherapy Assessment Card (the Card), for standardized qualitative and quantitative assessment of pharmacotherapy.

MATERIALS AND METHODS. The basis of the Card was Form No. 313/u, approved by Order No. 494 of the Ministry of Health of the Russian Federation dated October 22, 2003. For quantitative assessment of the criteria, additional tools were integrated into the Card: the modified Medication Appropriateness Index (MAI) and the GerontoNet scale. Evaluation of drug interactions was performed using the Drug-Drug Interactions database. Pilot testing of the Card was conducted using 80 medical records of patients in a multidisciplinary hospital.

RESULTS. The Pharmacotherapy Assessment Card includes 8 criteria for qualitative and quantitative assessment of pharmacotherapy, derived by comparing and integrating criteria from various international validated scales. For example, to objectively assess the criterion “risk of adverse drug reactions,” the GerontoNet scale was applied with a threshold value of ≥4 points. Pilot testing confirmed the applicability of most criteria. The mean assessment time was 90 minutes (decreasing with experience). The integral assessment showed that pharmacotherapy met the rationality criteria in 19.2% of cases (score 6–7), insufficient compliance with criteria was found in 45.2% (score 8–10), partial compliance with criteria in 35.6% (score 11–13), and there were no cases of complete non-compliance with criteria (score 14–16).

CONCLUSIONS. The developed Pharmacotherapy Assessment Card represents a practical tool that combines qualitative and quantitative metrics based on international standardized methods. The tool enables both a quantitative score-based result and a structured conclusion with recommendations for therapy optimization. Further prospective validation of the Pharmacotherapy Assessment Card is planned to confirm reliability and establish statistically justified threshold values for each criterion.

INTRODUCTION. Amfedazole, which belongs to the class of benzimidazole derivatives, exceeds quinidine, novocainamide, etmozine, and amiodarone in terms of antiarrhythmic activity in supraventricular rhythm disorders. Amfedazole increases the effective refractory period, affects transmembrane ion currents and prolongs the action potential, prolongs the QT and QTc intervals, and also produces anti-ischemic and antifibrillatory effects. Thus, conducting preclinical studies of this compound is promising.

AIM. To study the toxicokinetic properties, biotransformation, interaction with cytochrome P450 isoforms, and excretion of amfedazole to gain insight into its toxic effects.

MATERIALS AND METHODS. Toxicokinetic experiments were performed on 119 adult male white Wistar rats weighing 225±25 g and aged 4–5 months, and 54 adult male white outbred mice weighing 23±3 g and aged 2–3 months. Amfedazole was administered intraperitoneally as a single dose of 6 mg/kg (subtoxic dose). Blood, organ, tissue, and excreta samples were collected over 172 hours. Quantitative analysis was performed using a Shimadzu high-performance liquid chromatography (HPLC) system with a diode matrix (DM) detector. The possible metabolites of amfedazole were predicted using the PALLAS program (CompuDrug Chemistry Ltd.). The effect of amfedazole on the biotransformation enzyme system was studied using the test substrates hexobarbital, midazolam, alprazolam, and chloral hydrate (doses of 1.7 and 6 mg/kg).

RESULTS. When administered as a subtoxic dose, amfedazole was detected in the animals’ blood for up to 5 hours postdose, with C_max at 30 minutes after administration: AUC=24.39 µg/mL×h, t_1/2 =2.33 h. Amfedazole was extensively distributed into the studied organs and tissues and was excreted mainly via the kidneys. Amfedazole was biotransformed, presumably by the CYP3A isoenzyme. Amfedazole, administered at a subtoxic dose, was excreted mainly via the kidneys and, to a lesser extent, via the intestines within 72 hours.

CONCLUSIONS. The toxicokinetic study of amfedazole showed that it was detected in the blood almost immediately after administration. The peak concentration of the active substance was reached at 30 minutes, and by 5 hours its level decreased below the limit of quantification. Amfedazole was distributed into the liver, kidneys, and heart. Administered at a subtoxic dose, amfedazole was excreted within 72 hours, mainly via the kidneys.

INTRODUCTION. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are used for the treatment of type 2 diabetes mellitus, obesity, weight reduction, and weight control. Owing to their weight-loss and appetite-suppressant effects, information about these agents has spread widely in the mass media and social networks. A notable aspect of their use worldwide is the widespread practice of self-medication. We present a case of off-label self-medication with the prescription drug tirzepatide.

CASE REPORT. A 51-year-old woman (BMI 22.9 kg/m², without type 2 diabetes mellitus) self-injected 5 mg of tirzepatide to lose 2–3 kg of body weight. The subsequent self-administration of the prescription medications metoclopramide and furosemide without consulting a physician to relieve nausea, vomiting, and elevated blood pressure led to adverse drug interactions with fluoxetine and bisoprolol, which the patient was taking regularly, and resulted in multiple life-threatening conditions (extrapyramidal disorders, serotonin syndrome, severe electrolyte disturbances, QTc interval prolongation, and rhabdomyolysis) requiring hospitalization.

CONCLUSIONS. Self-medication with tirzepatide at an inadequately high starting dose of 5 mg was the trigger that initiated a cascade of predictable but severe adverse drug reactions. The subsequent uncontrolled use of prescription medications to relieve the symptoms without adherence to dosage regimens and frequency of administration, as well as without consideration of potential drug interactions, led to the development of life-threatening conditions. This clinical case highlights the problem of popularization of GLP-1/GIP receptor agonists in the mass media and underscores the need for physician supervision and proactive patient education about the risks, especially in the presence of concomitant pharmacotherapy.