Schizophrenia is socially significant mental disorder characterized by early onset and high time and financial expenditure on treatment. Antipsychotics (APs) are highly effective against positive and negative symptoms, but at same time have a wide range of adverse drug reactions (ADRs). APs efficiency and safety are variable and depend on characteristics of genetically determined mechanisms (transportation, biotransformation, and elimination).

Investigation role of pharmacogenetic testing (PhGT) on example of clinical case of severe ADRs in 47-year-old woman with schizophrenia.

Patient’s medical history analysis; clinical observation; biochemical serum analysis; therapeutic drug monitoring; PhGT.

The clinical case of a woman with schizophrenia who has been noted to be unresponsive to APs for some years after schizophrenia onset. She was found to be homozygous for nonfunctional SNVs CYP2D6*4 and CYP2C9*2, heterozygous for CYP1A1*2A, which was reason for complete shutdown of isoenzymes 2D6, 2C9 and 1A1 activity and development of ADRs in use of initial doses of several APs, as well as for an increase in severity of ADRs with schizophrenia positive symptoms aggravation with an even slower titration of APs daily dose not only with polytherapy, but also with monotherapy. So, not recommented APs for patient: aripiprazole, haloperidol, zuclopenthixol, cariprazine, quetiapine, paliperidone, risperidone, thioridazine, sertindole, asenapine, alimemazine, chlorpromazine, etc. (CYP2D6); haloperidol, clozapine, olanzapine, perphenazine, promazine (CYP2C9); carefully: haloperidol, olanzapine, perospirone (СYP1A1).

This rare case demonstrates PhGT importance before APs therapy, because the patient had very high risk AP – induced ADRs. She needed PhGt before APs use, but not after severe ADRs during 12 years.

No significant relationships.

Chemical structure is a vital consideration early in the drug development process. Its role in analysis of safety and efficacy is relatively diminished after drugs are approved for clinical use. This interdisciplinary study explores a strategy by which readily available clinical data may be used along with structural features of drugs to identify associations with potential utility for both clinical decision-making and drug development.

Chemical functional groups and structural groups (SGs) of 261 drugs were manually classified in tiers, and their incidence of gastrointestinal (GI) and central nervous system (CNS) adverse drug reactions (ADRs) were obtained from a clinical database. Drugs with an GI or CNS ADR incidence of at least 10% were analyzed for correlations with their functional and SGs.

Eight statistically significant associations were detected by preliminary analysis: piperazine and methylene groups were associated with higher rate of CNS ADRs; while amides, secondary alcohols, and di-substituted phenyl groups were associated with lower rates of GI or CNS ADRs or both.

Although further study is necessary to understand these associations and build upon this strategy, this exploratory analysis establishes a methodology by which chemical properties of drugs may be used to aid in clinical decision-making when choosing between otherwise equivalent drug therapy options, as the presence of specific groups on drugs may be associated with increased or decreased risks of specific ADRs.