scholarly journals Associations of CYP2D6, ABCB1 2677G>T/A and 3435C>T with effectiveness and safety of pharmacotherapy for acute psychotic episodes in adolescents over 28 days

Author(s):  
D. V. Ivaschenko ◽  
N. I. Buromskaya ◽  
P. V. Shimanov ◽  
R. V. Deitsch ◽  
M. I. Nastovich ◽  
...  

Introduction. Pharmacokinetic genetic factors are prognostically relevant when prescribing antipsychotics to adult patients. Currently, there is a dearth of research on adolescents with an acute psychotic episode. Aim. To identify possible associations of CYP2D6, CYP3A4/5 and ABCB1 gene polymorphic variants with the efficacy and safety of pharmacotherapy in adolescents with an acute psychotic episode within 28 days. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD- 10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs776746), CYP2D6*4, *9, *10 (rs3892097, rs4986774, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) by real-time PCR. Results. Carriers of ABCB1 2677G>T/A significantly less frequently demonstrated response to pharmacotherapy according to PANSS scale on day 14 compared to GG homozygotes (64.6 % vs. 94.7 %; p=0.014). Carriers of the ABCB1 3435C>T differed by a higher total UKU SERS score on day 14 compared to CC genotype carriers (9.21±5.95 vs. 5.1±4.48; p=0.037). Patients with «intermediate» CYP2D6 metabolism were more likely to have reduced sleep duration (13.6 % vs. 0 %; p=0.031). ABCB1 2677G>T/A (51 % vs. 15.8 %; p=0.012) and 3435C>T (46.6 % vs. 10 %; p=0.039) were more frequently associated with dry mouth. ABCB1 3435C>T carriers were also more likely to have orthostatic vertigo (34.5 % vs. 0 %; p=0.028). Conclusion. Carriage of the ABCB1 3435C>T was associated with greater efficacy of pharmacotherapy for acute psychotic episode in adolescents after 28 days, but also increases the risk of adverse reactions in the first 2 weeks of treatment. The ABCB1 2677G>T/A was associated with an increased risk of adverse reactions as well as less reduction of psychotic symptoms on day 14 of pharmacotherapy.

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Dmitriy V. Ivashchenko ◽  
Sofi Z. Khoang ◽  
Bakhu V. Makhmudova ◽  
Nina I. Buromskaya ◽  
Pavel V. Shimanov ◽  
...  

AbstractObjectivesPrediction of the antipsychotic’s effectiveness is a relevant topic in the field of personalized medicine.MethodsThe research design of this study is a prospective observation with posthoc analysis of associations of genetic polymorphisms with safety parameters and effectiveness of antipsychotic therapy. We observed 53 adolescents with an acute psychotic episode which were prescribed antipsychotics for 14 days. We evaluated the effectiveness of antipsychotics with the Positive and Negative Symptoms Scale and the safety with the UKU Side Effects Rating Scale, Simpson-Angus Scale, and Barnes Akathisia rating scale. We genotyped CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7767746), CYP2D6*4, *9, *10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), DRD2 (rs1800497), DRD4 (rs1800955), HTR2A (rs6313) by the real-time polymerase chain reaction method.ResultsWe found significantly more frequent “increased dream activity” between CYP2D6 intermediate metabolizers and normal metabolizers (54 vs. 22%; p=0.043). The «increased duration of sleep» was more often observed in homozygotes TT of ABCB1 2677G>T/A (50 vs. 15.8%, p=0.006) and TT of 3435C>T (41.7 vs. 8.2%, p=0.007).ConclusionsWe found that CYP2D6 and ABCB1 polymorphisms were associated with the safety of antipsychotics in adolescents with an acute psychotic episode.


2000 ◽  
Vol 177 (6) ◽  
pp. 516-521 ◽  
Author(s):  
Max Birchwood ◽  
Zaffer Iqbal ◽  
Paul Chadwick ◽  
Peter Trower

BackgroundDepression in schizophrenia is a rather neglected field of study, perhaps because of its confused nosological status. Three course patterns of depression in schizophrenia, including post-psychotic depression (PPD), are proposed.AimsWe chart the ontogeny of depression and psychotic symptoms from the acute psychotic episode over a 12-month period and test the validity of the proposed course patterns.MethodOne hundred and five patients with ICD–10 schizophrenia were followed up on five occasions over 12 months following the acute episode, taking measures of depression, positive symptoms, negative symptoms, neuroleptic exposure and side-effects.ResultsDepression accompanied acute psychosis in 70% of cases and remitted in line with the psychosis; 36% developed PPD without a concomitant increase in psychotic symptoms.ConclusionsThe results provided support for the validity of two of the three course patterns of depression in schizophrenia, including PPD. Post-psychotic depression occurs de novo without concomitant change in positive or negative symptoms.


Author(s):  
D. V. Ivaschenko ◽  
L. V. Fedina ◽  
N. I. Buromskaya ◽  
P. V. Shimanov ◽  
R. V. Deitsch ◽  
...  

Introduction. Antipsychotics are the main drugs for treatment of schizophrenia spectrum disorders. Pharmacodynamic genetic factors are being actively studied to improve the accuracy of antipsychotic selection based on pharmacogenetic testing. Purpose of this study: to establish associations of genetic polymorphisms of the DRD2, DRD3, DRD4, HTR2A, COMT, ZNF804A, and ANKS1B genes with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode during a 28-day follow-up. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD-10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms DRD2 rs1800497 (C>T), DRD3 rs6280 (C>T), DRD3 rs324026 (C>T), DRD4 rs1800955 (C>T), HTR2A rs6313 (T>C), COMT rs4680 (Val158Met, G>A), ZNF804A rs1344706 (A>C), ANKS1B rs7968606 (C>T) by real-time PCR. Results. DRD2 rs1800497 T allele carriers had a stronger reduction in the PANSS subscore «Productive Symptomatics» on day 14 (Me=-7.0 [-9.0;-5.0] vs Me=-7.0 [-8.0;-2.0]; p=0.018) and day 28 of follow-up (Me=-11.0 [-9.0;-5.5] vs Me=-8.0 [-8.0;-2.0]; p=0.019). Also, greater improvement on the CGAS scale on day 14 of follow-up was seen in TC+CC HTR2A rs6313 carriers (Me=2.0 [1.0;3.0] vs. Me=2.0 [1.0;2.0]; p=0.029). DRD3 rs324026 homozygous carriers (TT) had a significantly lower SAS score (Me=0.5 [0.0; 1.0] vs. Me=1.0 [0.0; 5.0]; p=0.016) and UKU subscore «Neurological Disorders» on 28 days of antipsychotic therapy (Me=0.0 [0.0; 0.0] vs. Me=1.0 [0.0; 3.8]; p=0.005). DRD3 rs324026 TT carriers also had lower severity of akathisia according to the BARS scale. Carriers of the T DRD4 rs1800955 allele had a higher SAS scale score on day 28 of therapy compared with CC homozygotes (Me=1.0 [0.0;4.0] vs Me=0.0 [0.0;1.0]; p=0.036). Conclusion. The DRD2 rs1800497 was a predictor of better reduction of productive symptoms; HTR2A rs6313 demonstrated a similar association. The DRD2 rs1800497 polymorphic variant was a predictor of better reduction of productive symptomatology; HTR2A rs6313 demonstrated a similar association. DRD3 rs324026 and HTR2A rs6313 were associated with a lower frequency of neurological adverse reactions and akathisia. In contrast, carriers of the DRD4 rs1800955 were more prone to adverse reactions on pharmacotherapy.


1986 ◽  
Vol 1 (2) ◽  
pp. 108-122 ◽  
Author(s):  
Nancy C. Andreasen ◽  
William M. Grove

SummaryMost investigators concur that schizophrenia is probably a heterogeneous group of disorders that share the common features of psychotic symptoms, partial response to neuroleptics, and a relatively poor outcome. The subdivision of schizophrenia into two subtypes, positive versus negative, has achieved wide acceptance throughout the world during recent years. This distinction has heuristic and theoretical appeal because it unites phenomenology, pathophysiology, and etiology into a single comprehensive hypothesis.In spite of its wide appeal, the distinction has a number of problems. These include the failure to distinguish between symptom syndromes and diseases; failure to deal with the mixed patient; failure to take longitudinal course into account; and failure to address conceptually and methodologically the distinction between positive and negative symptoms.This paper focuses primarily on the conceptual basis for two instruments designed to measure positive and negative symptoms, the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), originally described in 1982. Since their description, these scales have been used in a variety of other centers. These scales are based on the hypothesis that negative symptoms represent a deficit or diminution in normal psychological functions wliile positive symptoms represent an excess or distortion of normal functions. Reliability data are now available from Italy, Spain, and Japan which suggest that these scales can be used reliably in cultural settings outside the United States. The results of these studies are summarized in this paper. In addition, a replication study involving a new sample of 117 schizophrenics collected at the University of Iowa is described. In this second study of the SANS and SAPS, internal consistency is found to be quite high in the SANS. Thus negative symptoms appear to be more internally correlated with one another than are positive symptoms. The implications of this result are discussed. A principal components analysis is used to explore the relationship between positive and negative symptoms. While the study reported in 1982 suggested that positive and negative symptoms are negatively correlated, in the present study they appear to be uncorrelated. Overall, the results suggest that the SANS and SAPS are useful comprehensive instruments for the evaluation of positive and negative symptoms. The relationship between these symptoms and external validators such as cognitive functioning or CT scan abnormalities will be reported in a subsequent investigation.


2001 ◽  
Vol 178 (6) ◽  
pp. 518-523 ◽  
Author(s):  
Attila Sipos ◽  
Glynn Harrison ◽  
David Gunnell ◽  
Shazad Amin ◽  
Swaran P. Singh

BackgroundLittle is known about predictors of hospitalisation in patients with first-episode psychosis.AimsTo identify the pattern and predictors of hospitalisation of patients with a first psychotic episode making their first contact with specialist services.MethodThree-year follow-up of a cohort of 166 patients with a first episode of psychosis making contact with psychiatric services in Nottingham between June 1992 and May 1994.ResultsEighty-eight (53.0%) patients were admitted within 1 week of presentation; 32 (19.3%) were never admitted during the 3 years of follow-up. Manic symptoms at presentation were associated with an increased risk of rapid admission and an increased overall risk of admission; negative symptoms and a longer duration of untreated illness had an increased risk of late admission.ConclusionsCommunity-oriented psychiatric services might only delay, rather than prevent, admission of patients with predominantly negative symptoms and a longer duration of untreated illness. First-episode studies based upon first admissions are likely to be subject to selection biases, which may limit their representativeness.


2001 ◽  
Vol 178 (5) ◽  
pp. 433-440 ◽  
Author(s):  
John Milton ◽  
Shazad Amin ◽  
Swaran P. Singh ◽  
Glynn Harrison ◽  
Peter Jones ◽  
...  

BackgroundRecent research has reported increased risk of aggressive incidents by individuals with psychotic illness.AimsTo examine acts of aggression in first-episode psychosis.MethodSubjects with a first-episode psychosis were ascertained from a defined catchment area (Nottingham, UK) and reassessed at 3 years (n=166) using clinical interview, informants, health care and forensic records.ResultsOf the subjects, 9.6% demonstrated at least one act of serious aggression (defined as weapon use, sexual assault or victim injury) during at least one psychotic episode and 23.5% demonstrated lesser acts of aggression (defined as all other acts of aggression). For all aggressive subjects (33.1%), unemployment (OR=3.6, 95%CI 1.6–8.0), comorbid substance misuse (OR=3.1, CI 1.1–8.8) and symptoms of overactivity at service contact (OR=6.9, CI 2.7–17.8) had independent effects on risk of aggression.ConclusionsWe confirmed some previously reported demographic and clinical associations with aggression in first-episode psychosis but no relationship with specific psychotic symptoms or diagnostic groups was observed.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S218-S218
Author(s):  
David Kim ◽  
Ric Procyshyn ◽  
Lik Hang Lee ◽  
William Panenka ◽  
Olga Leonova ◽  
...  

Abstract Background There is considerable evidence supporting the association between extrapyramidal symptoms (EPS) and psychotic symptoms in patients with schizophrenia (SCZ). However, it is not well understood whether such an association exists in individuals without SCZ and how the association differs from those with SCZ. Our aim was to examine the associations of EPS with psychotic symptoms and compare them between SCZ and non-SCZ individuals. Methods We used data from a 10-year community-based study of homeless or precariously housed persons from Vancouver, Canada. Diagnosis of SCZ was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Severity of psychotic symptoms was rated using the Positive and Negative Syndrome Scale (PANSS). Severity of parkinsonism, dyskinesia, and dystonia was rated using the Extrapyramidal Symptom Rating Scale (ESRS), and akathisia using the Barnes Akathisia Rating Scale (BARS). Presence of EPS was defined as having at least moderate severity on the ESRS (i.e., ≥4 out of 8) or BARS (i.e., ≥3 out of 5) Clinical Global Impression-Severity (CGI-S) scale. Absence of EPS was defined as scoring ≤2 on the ESRS or ≤1 on the BARS CGI-S scale. Two-way analysis of covariance was performed using SCZ and EPS as independent variables and PANSS five factors (i.e., positive symptoms, negative symptoms, disorganization, excitement, and depression) as dependent variables, controlling for age, antipsychotic users, and cocaine- or methamphetamine-dependent individuals. Multiple linear regression analysis was performed for both SCZ and non-SCZ groups, controlling for the same confounding variables, to examine 1) associations of the severity of EPS subtypes with PANSS factors and 2) whether the presence of multiple EPS subtypes would be associated with increased SCZ symptoms relative to the presence of a single subtype. Results A total of 223 participants were included in this study (mean age: 44.1 ± 12.0 years; 76.1% male). Eighty-four participants met the diagnosis of SCZ, of whom 39 met our criteria for having EPS and 32 for not having EPS. The remaining 139 participants were not diagnosed with SCZ, of whom 50 had EPS and 72 did not. None of the participants had clinically significant dystonia. Overall, significant main effects of EPS were found for total symptoms (F1,182 = 24.4, p < 0.001), negative symptoms (F1,182 = 16.3, p < 0.001), disorganization (F1,181 = 16.6, p < 0.001), and excitement (F1,182 = 15.8, p < 0.001), but not positive symptoms or depression. The presence of EPS was associated with greater total symptoms and disorganization in both SCZ and non-SCZ groups. Significant interaction effects between SCZ and EPS were found for negative symptoms (F1,182 = 6.0, p = 0.015) and excitement (F1,182 = 3.9, p = 0.050), where the presence of EPS was associated with greater negative symptoms and excitement in SCZ participants, but not in non-SCZ participants. Consistent in both SCZ and non-SCZ groups, there were significant positive associations of the severity of 1) parkinsonism with negative symptoms, 2) dyskinesia with disorganization and total symptoms, and 3) akathisia with excitement. The presence of multiple EPS subtypes, relative to a single subtype, was not associated with significant increases in any SCZ symptoms, except a significant increase in excitement in non-SCZ participants. Discussion The presence of EPS is clearly associated with greater symptoms of SCZ, even in individuals without SCZ. People with SCZ may experience greater negative symptoms and excitement as a result of EPS than those without SCZ. Subtypes of EPS are distinctively associated with factors of SCZ symptoms. Future studies should elucidate the mechanisms underlying these associations.


1998 ◽  
Vol 13 (2) ◽  
pp. 104-106 ◽  
Author(s):  
M Moldavsky ◽  
D Stein ◽  
R Benatov ◽  
P Sirota ◽  
A Elizur ◽  
...  

SummaryThree adolescent and two adult patients suffering from chronic excited psychoses (either schizophrenia or schizoaffective disorder) resistant to traditional neuroleptics and clozapine were treated with combined clozapine-lithium. Improvement was assessed with the Positive and Negative Symptoms Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impressions, administered before and during combined clozapine-lithium treatment. All patients demonstrated a significant improvement with this combination. There was no occurrence of agranulocytosis, neuroleptic malignant syndrome or other clinically significant adverse effects.


1995 ◽  
Vol 166 (2) ◽  
pp. 236-240 ◽  
Author(s):  
Toshinori Kitamura ◽  
Yuji Okazaki ◽  
Akira Fujinawa ◽  
Masahiro Yoshino ◽  
Yomishi Kasahara

BackgroundThe literature on the statistical analysis of symptoms of psychoses was limited to positive and negative symptoms in schizophrenia. The present study explored the relationship between positive and negative symptoms as well as affective symptoms in a wider category of psychotic disorders.MethodThe symptoms of 584 psychiatric patients, consecutively admitted to any of the 95 mental hospitals in Japan, were studied. They manifested at least one of the following: (a) delusions, (b) hallucinations, (c) formal thought disorder, (d) catatonic symptoms, or (e) negative (defect) symptoms.ResultsFactor analysis yielded five factors interpretable as (a) manic symptoms, (b) depressive symptoms, (c) negative (defect) symptoms and formal thought disorders, (d) positive (psychotic) symptoms, and (e) catatonic symptoms.ConclusionThese results suggest that although major symptoms seen among psychotic patients can be categorised into positive, negative, manic, and depressive groups, corresponding to current knowledge of phenomenology, catatonic symptoms constitute a discrete syndrome, while formal thought disorders merge into the negative syndrome.


2011 ◽  
Vol 1 (6) ◽  
pp. 189-196 ◽  
Author(s):  
Zeynep Kotan ◽  
Berrin Ertepe ◽  
Cengiz Akkaya ◽  
Emre Sarandol ◽  
Güven Ozkaya ◽  
...  

Background: Amisulpride is a second-generation antipsychotic which has been proved to be effective in the control of both positive and negative symptoms of schizophrenia. In this study we aimed to determine metabolic, endocrinologic and cardiac effects of amisulpride commonly used in our clinical practice. Methods: A total of 18 patients (11 males, 7 females) diagnosed with schizophrenia received amisulpride at the dosage of 800 mg/day and were followed up for 24 weeks. Positive and negative psychotic symptoms, extrapyramidal and sexual side effects, metabolic, endocrinologic and cardiac parameters were evaluated at regular intervals. Results: Significant improvement in both positive and negative symptoms was observed in patients starting from the second week of treatment. Prolactin levels increased significantly both in men and women starting from the measurement on day 4. Prolactin elevation was significantly higher in women than in men. Increase in total cholesterol level became significant at week 24. No other significant difference was observed between weeks 1 and 24 regarding the other parameters. Conclusions: The clinical data from the present study supports the fact that amisulpride is an effective and safe antipsychotic drug, but elevates prolactin levels in both sexes.


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