scholarly journals Prognostic model of the risk of hyperprolactinemia in patients with schizophrenia receiving antipsychotic therapy

Author(s):  
Д.З. Падерина ◽  
М.Б. Фрейдин ◽  
О.Ю. Федоренко ◽  
В.Н. Стегний ◽  
С.А. Иванова

Использование антипсихотических средств ассоциировано с повышенным уровнем пролактина. Лекарственно-индуцированная гиперпролактинемия (ГП) имеет не только краткосрочные, но и долгосрочные последствия, которые могут серьезно повлиять на качество жизни пациента. Клинические проявления ГП включают гинекомастию, галакторею, нарушения менструального цикла, сексуальные дисфункции, бесплодие, а также значимый рост вероятности развития остеопороза и онкологических заболеваний. В развитии данного побочного эффекта антипсихотической терапии участвуют не только экзогенные, но и генетические факторы. Целью данной работы было исследование клинических и молекулярно-генетических факторов развития лекарственно-индуцированной ГП и создание прогностической модели риска развития ГП, которая в перспективе может быть использована для оптимизации и персонализации назначаемой терапии при лечении шизофрении. Исследование проведено в выборке русских, проживающих в Западно-Сибирском регионе России, больных шизофренией (n=446). Средний возраст пациентов составил 41,5 ± 13,4 года (возрастной диапазон - от 18 до 65 лет). Клиническая симптоматика оценивалась по шкалам позитивных и негативных синдромов (Positive and Negative Syndrome Scale - PANSS), общего клинического впечатления (Clinical Global Impression - CGI), оценки побочного действия (Udvalg for Kliniske Undersogelser Scale - UKU), на всех пациентов заполнялся модифицированный вариант карты стандартизированного описания больного шизофренией. На основании содержания гормона пролактина в сыворотке крови были выделены подгруппы пациентов с ГП (n=227) и с нормальным уровнем пролактина (n=219). Выполнен молекулярно-генетический анализ 88 полиморфных вариантов генов серотониновых (HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B) и дофаминовых (DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4) рецепторов, дофаминового транспортера SLC6A3, переносчика норадреналина SLC6A2, системы ферментов цитохромов P450 (CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2), катехол-О-метилтрансферазы СОМТ, p-глутатион S-трансферазы GSTP1, ATXN1, KREMEN1 и пролактина PRL. Получена прогностическая модель с включением генетических маркеров «rs1176744» (HTR3B), «rs10042486» (HTR1A), «rs936461» (DRD4), «rs179997» (ATXN1), «rs1076562» (DRD2), «rs3773678» (DRD3), «rs167771» (DRD3), «rs1587756» (DRD3), «rs134655» (KREMEN1),»rs3892097» (CYP2D6*4), «rs1341239» (PRL), «rs4975646» (SLC6A3), «rs13333066» (SLC6A2), а также негенетических факторов, таких как пол, возраст и доза антипсихотика в хлорпромазиновом эквиваленте (CPZeq). Разработанную фармакогенетическую панель можно рассматривать в качестве биологического предиктора развития антипсихотик-индуцированной ГП при шизофрении до назначения фармакотерапии. The use of antipsychotics is associated with elevated prolactin levels. Drug-induced hyperprolactinemia (HP) has not only short-term, but also long-term consequences, which can seriously affect the patient’s quality of life. Clinical manifestations of HP include gynecomastia, galactorrhea, menstrual irregularities, sexual dysfunctions, infertility, as well as a significant increase in the likelihood of developing osteoporosis and cancer. Not only exogenous, but also genetic factors are involved in the development of this side effect of antipsychotic therapy. The aim of this work was to study the clinical and molecular genetic factors of the development of drug-induced HP and the creation of a prognostic model of the risk of developing HP, which in the future can be used to optimize and personalize the prescribed therapy in the treatment of schizophrenia. The study was conducted in populations of russians with schizophrenia (n = 446), living in the West Siberian region of Russia. The average age of patients was 41,5 ± 13,4 years (18 - 65 age range). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI), the side effect rating scale (Udvalg for Kliniske Undersogelser Scale - UKU), and a modified version of the card of a standardized description of patient with schizophrenia. Based on the results on the serum prolactin level patients were divided into subgroups: with HP (n = 227) and with normal prolactin levels (n = 219). Molecular genetic analysis of 88 polymorphic variants of serotonin receptors genes (HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B) and dopamine receptors genes (DRD1, DRD2, DRD2 / ANKK1, DRD3, DRD4), dopamine transporter gene SLC6A3, noradrenaline transporter gene SLC6A2, genes of the cytochrome P450 enzymes (CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2), gene of catechol-O-methyltransferase COMT, gene of glutathione S-transferase P (GSTP1), genes ATXN1, KREMEN1 and prolactin gene PRL was performed. A prognostic model was obtained with the inclusion of the genetic markers “rs1176744” (HTR3B), “rs10042486” (HTR1A), “rs936461” (DRD4), “rs179997” (ATXN1), “rs1076562” (DRD2), “rs3773678” (DRD3), “rs167771” (DRD3), “rs1587756” (DRD3), “rs134655” (KREMEN1), “rs3892097” (CYP2D6*4), “rs1341239” (PRL),”rs4975646” (SLC6A3),”rs1333302” (SLC6A2), as well as non-genetic factors such as gender, age and dose of antipsychotic in chlorpromazine equivalent (CPZeq). The developed pharmacogenetic panel can be considered as biological predictors of the development of antipsychotic-induced HP in schizophrenia before the appointment of pharmacotherapy.

CNS Spectrums ◽  
2017 ◽  
Vol 23 (4) ◽  
pp. 284-290 ◽  
Author(s):  
Leslie Citrome ◽  
Robert Risinger ◽  
Andrew J. Cutler ◽  
Yangchun Du ◽  
Jacqueline Zummo ◽  
...  

ObjectiveAripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.MethodsPatients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.ResultsOf 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.ConclusionAL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.


2013 ◽  
Vol 28 (S2) ◽  
pp. 107-107
Author(s):  
P. Vidailhet ◽  
A. Schreiner ◽  
P. Bergmans ◽  
P. Cherubin ◽  
E. Rancans ◽  
...  

ObjectifsÉvaluer la tolérance, la sécurité d’emploi et la réponse à un traitement mensuel par palmitate de paliperidone (PP) à doses flexibles chez des patients adultes atteints de schizophrénie, non-aigus mais symptomatiques, après échec d’un traitement par antipsychotiques oraux.MéthodesAnalyse d’un groupe de patients atteints de schizophrénie, non-aigus mais symptomatiques, inclus dans une étude internationale, ouverte, prospective de six mois, évaluant la symptomatologie clinique : PANSS (Positive and Negative Syndrome Scale) et CGIS-S (Clinical Global Impression-Severity Scale), les événements indésirables (EIs) et le changement de poids.RésultatsCinq cent quatre-vingt-treize patients (population en intention de traiter) : 63,1 % d’hommes, âge moyen 38,4 ± 11,8 ans, 78,6 % souffrant de schizophrénie paranoïde. La principale raison de la substitution d’un antipsychotique oral par le PP était un manque d’efficacité (24,3 %). 74,5 % des patients ont terminé l’étude de six mois. Les raisons les plus fréquentes d’arrêt précoce étaient : le choix du patient (9,3 %), des effets indésirables (EIs) (6,1 %), les perdus de vue (3,0 %) et le manque d’efficacité (2,5 %). Le score total moyen à l’échelle PANSS a diminué de 71,5 ± 14,6 à l’inclusion à 59,7 ± 18,1 à la fin de l’étude (soit une différence de −11,7 ± 15,9 points ; 95 % IC 95 % [−13,0 ; −10,5] ; p <0,0001). 64,0 % des patients ont eu une amélioration supérieure ou égale à 20 % du score total à la PANSS et le pourcentage de patients légèrement malades ou moins (CGI-S) est passé de 31,8 à 63,2 %. Les EIs touchant plus de 5 % des patients sont : douleur au site d’injection (12,3 %), insomnie (8,6 %), anxiété (6,7 %), trouble psychotique (6,1 %) et céphalées (5,6 %). Le changement moyen de poids a été de 1,2 ± 5,0 kg (IC 95 % [0,7 ; 1,6]).ConclusionsCes résultats confirment la bonne tolérance et l’efficacité thérapeutique du PP à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par antipsychotiques oraux.


CNS Spectrums ◽  
2008 ◽  
Vol 13 (10) ◽  
pp. 898-905 ◽  
Author(s):  
George M. Simpson ◽  
Cedric J. O'Gorman ◽  
Antony Loebel ◽  
Ruoyong Yang

ABSTRACTIntroduction:The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies.Methods:These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data.Results:Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (−4.3 [P≤.01]), PANSS negative scores (−2.4 [P≤.0001]), and Clinical Global Impression of severity score (−0.3 [P≤.001]). Completers showed significant improvement in mean PANSS total scores (−10.2 [P<.0001]), PANSS positive scores (−2.7 [P<.0001]), PANSS negative scores (−2.7 [P<.001]), and Clinical Global Impression of severity scores (−0.6 [P<.0001]).Conclusion:Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval ≥500 msec.


2016 ◽  
Vol 7 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Nosa Godwin Igbinomwanhia ◽  
Sunday Osasu Olotu ◽  
Bawo Onesirosan James

Background: The study aimed to determine the prevalence, pattern and correlates of antipsychotic polypharmacy (APP) among outpatients with schizophrenia attending a tertiary psychiatric facility in Nigeria. Method: A cross-sectional study of 250 patients with schizophrenia attending the outpatient clinic of a regional tertiary psychiatric facility in Nigeria was undertaken. They were administered a sociodemographic questionnaire, the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Liverpool University Side Effects Rating Scale (LUNSERS). Results: Of the 250 subjects interviewed, 176 (70.4%) were on APP. APP was significantly associated with higher prescribed chlorpromazine equivalent doses of antipsychotics ( p < 0.001), increased frequency of dosing ( p < 0.001), negative symptoms ( p < 0.01), poorer functioning ( p = 0.04) and greater side-effect burden ( p = 0.04). Conclusion: The APP rate reported from this study is high. Clinicians should be mindful of its impact on dosage and side-effect profiles as APP use is associated with negative symptoms and poor psychosocial functioning.


2021 ◽  
Author(s):  
Aline Hajj ◽  
Souheil Hallit ◽  
Karam Chamoun ◽  
Hala Sacre ◽  
Sahar Obeid ◽  
...  

Aim: Explore the possible association between clinical factors and genetic variants of the dopamine pathways and negative symptoms. Materials & methods: Negative symptoms were assessed in 206 patients with schizophrenia using the Arabic version of the self-evaluation of negative symptoms scale and the Positive and Negative Syndrome Scale. Genotyping for COMT, DRD2, MTHFR and OPRM1 genes was performed. Results: Multivariable analysis showed that higher self-evaluation of negative symptoms scale scores were significantly associated with higher age, higher chlorpromazine-equivalent daily dose for typical antipsychotics and in married patients. Higher negative Positive and Negative Syndrome Scale scores were significantly associated with women and having the CT genotype for MTHFR c.677C>T (β = 4.25; p = 0.008) compared with CC patients. Conclusion: Understanding both clinical/genetic factors could help improve the treatment of patients.


2020 ◽  
Vol 7 (5) ◽  
pp. 817
Author(s):  
Unnati Saxena ◽  
Anuradha Nischal ◽  
Anil Nischal ◽  
Abbas Ali Mahdi ◽  
Manu Agarwal ◽  
...  

Background: Schizophrenia comprises a group of disorders with heterogeneous etiologies, it includes patients whose clinical presentations, treatment response, and courses of illness vary. This study was carried to study the clinical efficacy and safety of Lurasidone versus Risperidone on psychopathology and cognition in patients with first episode of schizophrenia.Methods: Patients diagnosed with first episode of schizophrenia were enrolled in the study. Patients were randomized to 80 mg/d (n = 27) of Lurasidone or 6mg/d (n = 27) of Risperidone. Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores, Schizophrenia cognition rating scale (SCoRS). IL-6 estimation was done and safety assessment was done using UKU side effect rating scale.Results: During the eight weeks of study; significant improvement was observed in PANSS total and all its subscale scores with both Lurasidone and Risperidone. Mean change in PANSS scores were not significant between the groups (-32.93 vs -35.33 p>0.05). Mean change in SCoRS scores were significantly higher in Lurasidone group as compared to risperidone group (-8.43 vs -2.34, p<0.001). Significant reduction in the IL-6 levels with both the groups but mean change in IL-6 levels were not significant between the group (-10.47 vs -8.31, p>0.05). UKU side effect rating scores were significantly higher with Risperidone as compared to Lurasidone (p<0.001).Conclusions: Lurasidone is as effective as Risperidone in improving psychopathology in patient of schizophrenia. Lurasidone proved more efficacious in improving cognition as compared to Risperidone. Both the treatment modalities are efficacious in lowering IL-6 levels. Lurasidone causes less adverse effects as compared to Risperidone.


2001 ◽  
Vol 10 (3) ◽  
pp. 186-193 ◽  
Author(s):  
Vittorio Di Michele ◽  
Francesca Bolino ◽  
Gabriella Di Zio ◽  
Paola Pincini

RIASSUNTOScopo – Verificare l'esistenza di correlazioni fra sintomatologia schizofrenica e variabili multidimensionali del funzionamento sociale e se tali correlazioni possano condurre ad una precisazione classificativa orientata sull'esito attraverso una metodica empirica. Disegno – Quaranta pazienti affetti da schizofrenia cronica con diagnosi accertata clinicamente e attraverso criteri diagnostici sono stati arruolati. Setting – I pazienti erano in carico ad un Centro di Salute Mentale ed erano in fase stabilizzata di malattia definita con criteri operativi. Principali misure utilizzate – Per la valutazione psicopatologica è stata utilizzata la Positive And Negative Syndrome Scale e la Clinical Global Impression. Il funzionamento sociale è stato valutato con la Life Skills Profile e la Scala di Valutazione del Funzionamento Globale. Risultati – Esiste una correlazione fra variabili sintomatologiche e psicosociali che suggerisce un costrutto unitario. A tali variabili soggiaciono 2 fattori principali in grado di spiegare il 79% della varianza che consentono di differenziare il campione in tre gruppi sulla base della Cluster analysis. Sia i sintomi positivi che negativi risultano embricati con alcune aspetti del funzionamento sociale, ma non con tutti. Conclusioni – I sintomi e le variabili psicosociali dei pazienti si aggregano in una struttura omogenea tripartitica. Tale dato suggerisce l'esistenza, nell'ambito di un concetto unitario, di una differenziazione sindromica derivabile con criteri empirici e orientata prognosticamente.


2005 ◽  
Vol 19 (5_suppl) ◽  
pp. 22-31 ◽  
Author(s):  
A. Mohl ◽  
K. Westlye ◽  
S. Opjordsmoen ◽  
A. Lex ◽  
A. Schreiner ◽  
...  

Oral and long-acting risperidone has been shown to be effective for acute and maintenance treatment of patients with schizoaffective disorders. The present analysis investigated the efficacy and tolerability of direct transition from other antipsychotics to risperidone long-acting injectable in patients with schizoaffective disorder. Patients aged ≥ 18 years with schizoaffective disorder (DSM-IV), who required a change of medication, received risperidone long-acting injectable 25mg (increased to 37.5 or 50mg, if necessary) every 2 weeks for 6 months. The analysis included 249 patients (47% male; mean age 43 years), of whom 74% completed the 6-month study. Mean scores for the total Positive and Negative Syndrome Scale (PANSS) and all three subscales were significantly reduced from baseline to week 4 (p < 0.001), with further improvements until treatment endpoint. Significant improvements from baseline to endpoint were seen in the mood symptom domains of anxiety/depression (10.4±4.1 vs 8.7±3.9) and uncontrolled hostility/excitement (7.6±3.6 vs 6.9±3.8). Mean Global Assessment of Function (GAF) score improved significantly from 59.4±15.6 at baseline to 66.4±17.7 (p < 0.001) at endpoint. Of 87 patients hospitalized at baseline, 67% were discharged at endpoint. Both quality of life (SF-36) and satisfaction with treatment were improved significantly at endpoint. Total ESRS scores fell progressively throughout the study, and the reduction was already statistically significant (p < 0.001) at 4 weeks. Small but statistically significant (p < 0.001) mean shifts of 1.8% were seen in body weight and Body Mass Index (BMI). Patients with schizoaffective disorder derived several benefits from a change to risperidone long-acting injectable, including reductions in psychiatric symptoms (particularly the mood symptom domains) and a reduction in the severity of drug-induced neurological movement disorders.


2020 ◽  
Vol 11 (1) ◽  
pp. 6-13
Author(s):  
Zh. B. Bibekova ◽  
E. A. Strel’cov ◽  
A. S. Makarchuk

This literature review addresses the effectiveness and safety of long-acting antipsychotic therapy for schizophrenia. The results of randomized trials of recent years are described in detail. The efficacy of taking drugs at the following key research points was examined: the general clinical impression of the severity of the condition (CGI-S), the general clinical impression of the change in state during treatment (CGI-I), and the positive and negative syndrome scale (PANSS). A systematic literature search was conducted using the Scopus, Web of Science, MedLine, elibrary, and other databases.


2022 ◽  
pp. 026988112110558
Author(s):  
Gurpreet Rekhi ◽  
Jenny Tay ◽  
Jimmy Lee

Background: Both drug-induced Parkinsonism (DIP) and tardive dyskinesia (TD) have been shown to be associated with lower health-related quality of life (HRQOL) in schizophrenia, but few studies have examined their relative impact. Aims: This study aimed to examine and compare the association of DIP and TD with HRQOL in schizophrenia. Methods: In total, 903 patients with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). EuroQoL five-dimensional (EQ-5D-5L) utility scores were derived from PANSS scores via a previously validated algorithm and used as a measure of HRQOL. Results: In total, 160 (17.7%) participants had only DIP, 119 (13.2%) had only TD, and 123 (13.6%) had both DIP and TD. HRQOL was lowest for participants with both DIP and TD, followed by only DIP group, only TD group, and highest in the group with neither condition. HRQOL scores differed significantly between the four groups, F(3, 892) = 13.724, p < 0.001, [Formula: see text] = 0.044). HRQOL of participants having only DIP or both DIP and TD was significantly lower than those having neither condition. There was no significant interaction between the presence of DIP and TD on the association with HRQOL. Conclusions: DIP was the main antipsychotic-induced movement disorder associated with a poorer HRQOL in patients with schizophrenia. Therefore, clinicians should focus on prevention, detection, and effective management of DIP to optimize HRQOL in patients with schizophrenia.


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