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1.
Int Clin Psychopharmacol ; 35(1): 49-58, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31453901

RESUMO

Evidence supports increasing antipsychotic use in bipolar disorder, especially second-generation antipsychotics. However, data regarding first-generation antipsychotic contemporary use are limited. We studied 380 Northern Italian bipolar disorder inter-episode patients, grouped according to current antipsychotic use, stratified by bipolar subtype (BDI vs. BDII). Furthermore, we compared first-generation antipsychotic users vs. non-users. In our sample (n = 357), 81.8% were taking antipsychotics (74% second-generation antipsychotics, 24.1% first-generation antipsychotics), with antipsychotic use in BDI significantly more prevalent than in BDII (85.2% vs. 72.0%). Overall, antipsychotic users vs. non-users had higher rates of hypo/manic last episode, lifetime psychiatric hospitalization, psychosis, and current psychotropic use, but lower rates of anxiety disorder main comorbidity and current antidepressant use. First-generation antipsychotic use rates (30.3% in BDI vs. 6.5% in BDII) were associated with more frequently being unpartnered, having elevated first/last episodes, higher lifetime hospitalization, involuntary commitment, psychosis, and psychosocial rehabilitation rates, and more current psychotropic use, but lower Global Assessment Functioning scores and less current antidepressant use. Bipolar disorder patients had robust antipsychotic (second-generation antipsychotic > first-generation antipsychotic) use, consistently with previous reports. FGAs were still prescribed for a substantial group of patients, likely suffering from severe bipolar disorder. Prescriptions need to be monitored to assess their appropriateness and adherence to evidence-based recommendations.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Antidepressivos/uso terapêutico , Antipsicóticos/classificação , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/classificação , Transtorno Bipolar/epidemiologia , Comorbidade , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Feminino , Humanos , Itália , Masculino , Índice de Gravidade de Doença
2.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(4): 324-335, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1011506

RESUMO

Objective: To present the essential guidelines for pharmacological management of patients with psychomotor agitation in Brazil. Methods: This is a systematic review of articles retrieved from the MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and SciELO databases published from 1997 to 2017. Other relevant articles in the literature were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools. Results: Of 5,362 articles retrieved, 1,731 abstracts were selected for further reading. The final sample included 74 articles that met all inclusion criteria. The evidence shows that pharmacologic treatment is indicated only after non-pharmacologic approaches have failed. The cause of the agitation, side effects of the medications, and contraindications must guide the medication choice. The oral route should be preferred for drug administration; IV administration must be avoided. All subjects must be monitored before and after medication administration. Conclusion: If non-pharmacological strategies fail, medications are needed to control agitation and violent behavior. Once medicated, the patient should be monitored until a tranquil state is possible without excessive sedation. Systematic review registry number: CRD42017054440.


Assuntos
Humanos , Agitação Psicomotora/tratamento farmacológico , Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Guias de Prática Clínica como Assunto , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/diagnóstico , Antipsicóticos/classificação , Benzodiazepinas/classificação , Brasil , Gerenciamento Clínico
3.
Lancet Psychiatry ; 6(9): 753-765, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31320283

RESUMO

BACKGROUND: Antipsychotic drugs might cause acutely occurring, serious side-effects and thus contribute to the increased physical morbidity and mortality observed in patients with severe mental health disorders. We examined this hypothesis by doing a meta-analysis of International Conference on Harmonisation-Good Clinical Practice-defined serious adverse events occurring in placebo-controlled trials of antipsychotics. METHODS: For this systematic review and meta-analysis, we included randomised controlled trials (RCTs) comparing second-generation antipsychotics with placebo. We searched MEDLINE, Embase, Cochrane CENTRAL, BIOSIS, PsycINFO, PubMed, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for trials published in any language from database inception up until Jan 27, 2017. Trials were included without limitations in population (diagnostic category, age, sex, ethnicity), dosing regimen, blinding status, duration, or publication year. Only psychological studies lasting less than 1 day and trials done in mainland China were excluded. We contacted pharmaceutical companies, drug regulatory authorities, and study investigators for additional data. The primary outcome was the number of patients with at least one somatic serious adverse event. We estimated minimum and maximum numbers of patients with the outcome in each study group and synthesised the results with odds ratios (ORs) in a common-effects meta-analysis. This study is registered with PROSPERO, number CRD42016033930. FINDINGS: We identified 597 RCTs, comprising 108 664 participants, that met the inclusion criteria. 314 trials (67 642 participants) with details on individual serious adverse events available constituted the main dataset for meta-analysis. 88% of these were 13 weeks (approximately 3 months) or shorter in duration (median 6 weeks, IQR 4-9). At least one somatic serious adverse event occurred in 698 (1·63%) to 862 (2·02%) of 42 600 patients on antipsychotics, and in 343 (1·37%) to 419 (1·67%) of 25 042 patients on placebo. The odds ratios (ORs) were 1·24 (95% CI 1·08-1·42) and 1·24 (1·10-1·41) based on the minimum and maximum estimate, respectively. In predefined subgroup analyses we found evidence suggesting a larger effect in older patients (>65 years; OR 1·56, 95% CI 1·22-1·98; 1·58, 1·25-1·99) as compared with adults (18-65 years; 1·09, 0·91-1·29; 1·10, 0·95-1·28); likewise in children or adolescents (<18 years) although the evidence was more uncertain (1·49, 0·81-2·75; 1·54, 0·85-2·77). Of 597 included RCTs, 30 (5%), 358 (60%), and 209 (35%) were rated at high, moderate, or low risk of bias, respectively. τ2 was zero for both analyses of the primary outcome (minimum estimate, maximum estimate). A Bayesian sensitivity analysis using external information on heterogeneity gave similar results. INTERPRETATION: We found evidence that antipsychotics cause short-term somatic serious adverse events on top of somatic serious adverse events occurring independent of treatment. This effect appears to be mainly driven by results in older patients. Hence, clinicians should be aware that antipsychotics are potentially toxic, particularly when treating patients sharing risk factors with the older population. FUNDING: German Ministry of Education and Research.


Assuntos
Antipsicóticos/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Placebos/efeitos adversos , Distúrbios Somatossensoriais/induzido quimicamente , Adolescente , Adulto , Idoso , Antipsicóticos/classificação , Antipsicóticos/uso terapêutico , China/epidemiologia , Humanos , Incidência , Transtornos Mentais/mortalidade , Pessoa de Meia-Idade , Placebos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Distúrbios Somatossensoriais/epidemiologia , Distúrbios Somatossensoriais/mortalidade , Adulto Jovem
4.
J Clin Psychiatry ; 80(4)2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31163104

RESUMO

OBJECTIVE: To evaluate stroke risk among users of typical antipsychotics compared to users of atypical antipsychotics in a non-elderly and non-demented US population. METHODS: New users of antipsychotics aged 18-64 years without dementia were identified via electronic health care data from 13 health plans participating in the Sentinel System from January 2001 to September 2015. The risk of hospitalized stroke events, identified via ICD-9-CM diagnostic criteria, was compared between typical and atypical antipsychotic users using 1:1 matching on propensity score. Adjusted hazard ratios (HRs) and 95% CIs during the entire follow-up period and during 1- to 15-day and 16- to 90-day risk windows were estimated. The risk associated with haloperidol use was estimated separately. RESULTS: A total of 45,495 typical antipsychotic users were matched 1:1 to atypical antipsychotic users. While unmatched HRs suggest an increased stroke risk among typical antipsychotic users compared to atypical antipsychotic users, no increased risk was observed after matching during the entire follow-up period (HR = 0.87; 95% CI, 0.54-1.41), the 1- to 15-day risk window (HR = 1.16; 95% CI, 0.41-3.32), or the 16- to 90-day risk window (HR = 0.52; 95% CI, 0.20-1.36). The adjusted HR for haloperidol was 1.31 (95% CI, 0.54-3.21). CONCLUSION: These findings were not suggestive of an increased stroke risk in typical antipsychotic users compared to atypical antipsychotic users in a non-elderly and non-demented population.


Assuntos
Antipsicóticos , Acidente Vascular Cerebral , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/classificação , Antipsicóticos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Prevalência , Garantia da Qualidade dos Cuidados de Saúde/métodos , Medição de Risco/métodos , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
5.
Braz J Psychiatry ; 41(4): 324-335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843960

RESUMO

OBJECTIVE: To present the essential guidelines for pharmacological management of patients with psychomotor agitation in Brazil. METHODS: This is a systematic review of articles retrieved from the MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and SciELO databases published from 1997 to 2017. Other relevant articles in the literature were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools. RESULTS: Of 5,362 articles retrieved, 1,731 abstracts were selected for further reading. The final sample included 74 articles that met all inclusion criteria. The evidence shows that pharmacologic treatment is indicated only after non-pharmacologic approaches have failed. The cause of the agitation, side effects of the medications, and contraindications must guide the medication choice. The oral route should be preferred for drug administration; IV administration must be avoided. All subjects must be monitored before and after medication administration. CONCLUSION: If non-pharmacological strategies fail, medications are needed to control agitation and violent behavior. Once medicated, the patient should be monitored until a tranquil state is possible without excessive sedation. SYSTEMATIC REVIEW REGISTRY NUMBER: CRD42017054440.


Assuntos
Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Guias de Prática Clínica como Assunto , Agitação Psicomotora/tratamento farmacológico , Antipsicóticos/classificação , Benzodiazepinas/classificação , Brasil , Gerenciamento Clínico , Humanos , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/diagnóstico
6.
Curr Opin Psychiatry ; 32(3): 179-184, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30720484

RESUMO

PURPOSE OF REVIEW: To provide an update on the frequency of antipsychotic-induced tardive dyskinesia and its management in patients with schizophrenia spectrum disorders in studies published since the last systematic review in 2008. RECENT FINDINGS: Recent data about antipsychotic-induced tardive dyskinesia in patients with schizophrenia underscore the superiority of newer generation antipsychotics (21%) over first-generation antipsychotics (30%) with respect to prevalence and incidence rates. Regarding recently tested management strategies, the new vesicular monoamine transporter 2 inhibitors valbenazine and deutetrabenazine have been found to be effective and may be considered as first-line pharmacotherapy for tardive dyskinesia. Owing to quality issues of randomized controlled trials and/or small sample sizes, limited and conflicting evidence remains for most treatment strategies. SUMMARY: The reviewed literature reveals lower prevalence rates of antipsychotic-induced tardive dyskinesia in patients treated with newer generation compared with first-generation antipsychotics. The evidence of vesicular monoamine transporter 2 inhibitors as a first-line therapy for tardive dyskinesia is well supported by several controlled clinical trials.


Assuntos
Antipsicóticos/efeitos adversos , Conduta do Tratamento Medicamentoso , Discinesia Tardia , Antipsicóticos/classificação , Antipsicóticos/uso terapêutico , Humanos , Prevalência , Discinesia Tardia/induzido quimicamente , Discinesia Tardia/epidemiologia , Discinesia Tardia/terapia
7.
Pharmacopsychiatry ; 52(4): 175-179, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29791934

RESUMO

INTRODUCTION: While the current nomenclature of psychotropic drugs is disease-based, their approved indications do not always match their classifications. METHODS: Information on approved indications of "second-generation antipsychotics" and "newer antidepressants" that are available in the United States (US), the United Kingdom (UK), France, Germany, and Japan were extracted from their packet inserts. RESULTS: A significant proportion of "atypical antipsychotics" were approved for psychiatric conditions other than psychotic disorders (i. e., bipolar disorder, major depressive disorder, and autistic disorder) as follows: 76.9% in the US, 66.7% in the UK, 66.7% in France, 60.0% in Germany, and 44.4% in Japan. Likewise, more than half of "newer antidepressants" had approved indications for psychiatric conditions other than depression (e. g., panic disorder, obsessive compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder): 56.3% in the US, 69.2% in the UK, 69.2% in France, 50.0% in Germany, and 62.5% in Japan. CONCLUSIONS: Our results raise concerns regarding generic terminologies of "antipsychotics" and "antidepressants" since the conventional indication-based nomenclature does not fit well with the official indication.


Assuntos
Antidepressivos/classificação , Antipsicóticos/classificação , Transtornos Mentais/classificação , Transtornos Mentais/tratamento farmacológico , Terminologia como Assunto , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Aprovação de Drogas , Humanos , Uso Off-Label
8.
BMC Psychiatry ; 18(1): 399, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587176

RESUMO

BACKGROUND: Bipolar and other psychiatric disorders are associated with considerably increased risk of suicidal behaviour, which may include self-poisoning with medication used to treat the disorder. Therefore, choice of medication for treatment should include consideration of toxicity, especially for patients at risk. The aim of this study was to estimate the relative toxicity of specific drugs within two drug categories, antipsychotics and mood stabilizers, using large-scale databases to provide evidence that could assist clinicians in making decisions about prescribing, especially for patients at risk of suicidal behaviour. METHOD: Two indices were used to assess relative toxicity of mood stabilisers and antipsychotics: case fatality (the ratio between rates of fatal and non-fatal self-poisoning) and fatal toxicity (the ratio between rates of fatal self-poisoning and prescription). Mood stabilisers assessed included lithium [reference], sodium valproate, carbamazepine, and lamotrigine, while antipsychotics included chlorpromazine [reference], clozapine, olanzapine, quetiapine and risperidone. Fatal self-poisoning (suicide) data were provided by the Office for National Statistics (ONS), non-fatal self-poisoning data by the Multicentre Study of Self-harm in England, and information on prescriptions by the Clinical Practice Research Datalink. The primary analysis focussed on deaths due to a single drug. Cases where the drug of interest was listed as the likely primary toxic agent in multiple drug overdoses were also analysed. The study period was 2005-2012. RESULTS: There appeared to be little difference in toxicity between the mood stabilisers, except that based on case fatality where multiple drug poisonings were considered, carbamazepine was over twice as likely to result in death relative to lithium (OR 2.37 95% CI 1.16-4.85). Of the antipsychotics, clozapine was approximately18 times more likely to result in death when taken in overdose than chlorpromazine (single drug case fatality: OR 18.53 95% CI 8.69-39.52). Otherwise, only risperidone differed from chlorpromazine, being less toxic (OR 0.06 95% CI 0.01-0.47). CONCLUSIONS: There was little difference in toxicity of the individual mood stabilisers. Clozapine was far more toxic than the other antipsychotics. The findings are relevant to prescribing policy, especially for patients at particular risk of suicidal behaviour.


Assuntos
Antipsicóticos , Overdose de Drogas , Conduta do Tratamento Medicamentoso , Transtornos Mentais , Risco Ajustado/métodos , Comportamento Autodestrutivo , Suicídio , Tranquilizantes , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/classificação , Overdose de Drogas/etiologia , Overdose de Drogas/prevenção & controle , Overdose de Drogas/psicologia , Inglaterra , Feminino , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/psicologia , Padrões de Prática Médica , Comportamento Autodestrutivo/prevenção & controle , Comportamento Autodestrutivo/psicologia , Suicídio/prevenção & controle , Suicídio/psicologia , Suicídio/estatística & dados numéricos , Tranquilizantes/administração & dosagem , Tranquilizantes/efeitos adversos , Tranquilizantes/classificação
9.
J Psychiatr Pract ; 24(6): 416-419, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30395549

RESUMO

Several companies offer pharmacogenetic testing for psychiatry on the basis of the claim that the outcome of drug selection is better when guided by such testing than when such testing is not used. This column examines the results of the GeneSight Psychotropic Test which groups various antidepressants and antipsychotics into 3 bins: green ("use as directed"), yellow ("use with caution"), and red ("use with increased caution and more frequent monitoring"). The authors examined how frequently the same drugs appeared in these different bins in 19 patients. They found that of the 22 antidepressants evaluated, 2 were virtually always (>90%) in the green bin: desvenlafaxine and levomilnacipran; and 8 were almost never (≤10.5%) in the green bin: citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, paroxetine, and sertraline. Of the 16 antipsychotics evaluated, they found that 4 were virtually always (>90%) in the green bin: asenapine, lurasidone, paliperidone, and ziprasidone; and 2 were almost never (≤10.5%) in the green bin: chlorpromazine and thioridazine. What was common among those drugs almost always in the green bin versus those almost never in the green bin were newer versus older marketed drugs and those not dependent versus dependent on oxidative metabolism for their clearance. The authors concluded that the results of this pharmacogenetic testing could be predicted on the basis of knowledge of the pharmacology of the drugs, particularly whether their clearance was dependent on oxidative drug metabolism.


Assuntos
Antidepressivos/classificação , Antidepressivos/farmacologia , Antipsicóticos/classificação , Antipsicóticos/farmacologia , Testes Farmacogenômicos , Humanos
10.
Can Fam Physician ; 64(9): 660-662, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30209096

RESUMO

Question A 10-year-old male patient presented to my clinic with irritability associated with autism spectrum disorder, and previous therapeutic efforts had not been successful. Treatment with quetiapine has considerably reduced irritability and improved his quality of life; however, the patient's mother has stated that her child's clothes are no longer fitting because his waist size has increased substantially, and that he has gained 5 kg since treatment initiation 8 weeks ago. Should second-generation antipsychotic (SGA) treatment be stopped or continued, and how can these side effects be best mitigated in a family practice setting?Answer Use of SGAs in pediatric patients has increased in recent years, which has brought to light a number of worrisome metabolic side effects that occur in children. Owing to the efficacy of treatment, SGAs must often be continued despite side effects. Even if the drug has been prescribed elsewhere, family physicians should closely monitor these patients following the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children guidelines. When starting an SGA, patients and their families should be educated on the importance of healthy eating and physical activity to preemptively mitigate potential side effects. Recent studies have also shown adjunctive metformin to have a potential role in reducing weight gain.


Assuntos
Antipsicóticos/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Doenças Metabólicas/induzido quimicamente , Antipsicóticos/classificação , Criança , Monitoramento de Medicamentos/métodos , Fidelidade a Diretrizes , Humanos , Doenças Metabólicas/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde
11.
Eur Psychiatry ; 52: 85-94, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29734130

RESUMO

BACKGROUND: The Antipsychotic Long-acTing injection in schizOphrenia (ALTO) study was a non-interventional study across several European countries examining prescription of long-acting injectable (LAI) antipsychotics to identify sociodemographic and clinical characteristics of patients receiving and physicians prescribing LAIs. ALTO was also the first large-scale study in Europe to report on the use of both first- or second-generation antipsychotic (FGA- or SGA-) LAIs. METHODS: Patients with schizophrenia receiving a FGA- or SGA-LAI were enrolled between June 2013 and July 2014 and categorized as incident or prevalent users. Assessments included measures of disease severity, functioning, insight, well-being, attitudes towards antipsychotics, and quality of life. RESULTS: For the 572 patients, disease severity was generally mild-to-moderate and the majority were unemployed and/or socially withdrawn. 331/572 were prevalent LAI antipsychotic users; of whom 209 were prescribed FGA-LAI. Paliperidone was the most commonly prescribed SGA-LAI (56% of incident users, 21% of prevalent users). 337/572 (58.9%) were considered at risk of non-adherence. Prevalent LAI users had a tendency towards better insight levels (PANSS G12 item). Incident FGA-LAI users had more severe disease, poorer global functioning, lower quality of life, higher rates of non-adherence, and were more likely to have physician-reported lack of insight. CONCLUSIONS: These results indicate a lower pattern of FGA-LAI usage, reserved by prescribers for seemingly more difficult-to-treat patients and those least likely to adhere to oral medication.


Assuntos
Antipsicóticos/uso terapêutico , Qualidade de Vida/psicologia , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/classificação , Preparações de Ação Retardada/uso terapêutico , Europa (Continente) , Feminino , Humanos , Injeções Intramusculares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico
13.
Curr Opin Psychiatry ; 31(3): 169-175, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29517519

RESUMO

PURPOSE OF REVIEW: To examine the recent literature regarding sudden death in patients with schizophrenia and synthesize salient conclusions based on this evidence. RECENT FINDINGS: Sudden cardiac death (SCD) is the largest subset of sudden unexpected death (SUD), with up to 40% of SUD from cardiovascular causes. SCD has been associated with exposure to both first and second-generation antipsychotics. Clozapine [odds ratio (OR) 3.67, 95% confidence interval (CI) 1.94-6.94] confers the highest risk of SCD followed by risperidone (OR 3.04, 95% CI 2.39-3.86) then olanzapine (OR 2.04, 95% CI 1.52-2.74). SCD not associated with antipsychotic use has been correlated to several modifiable and nonmodifiable risk factors - obesity, smoking, dyslipidemia, diabetes, hypertension, age, sex, and history of cardiovascular disease. Other subsets of SUD include hematological and pulmonary causes, including agranulocytosis leading to sepsis, deep vein thrombosis leading to pulmonary embolisms, and aspiration pneumonia leading to sepsis. SUMMARY: There is a huge paucity in genetic and pharmacogenetic data focused on SUD in schizophrenia. Future studies should emphasize the genetic aspects as well as clarify the underlying molecular mechanisms of these pathways. Additionally, early detection of those patients at high risk for SUD and discovery of preventive measures should also be emphasized.


Assuntos
Antipsicóticos , Morte Súbita Cardíaca , Esquizofrenia , Antipsicóticos/classificação , Antipsicóticos/farmacologia , Comorbidade , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Humanos , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Esquizofrenia/mortalidade
14.
Lancet Psychiatry ; 5(4): 327-338, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29503163

RESUMO

BACKGROUND: Antipsychotic drugs improve schizophrenia symptoms and reduce the frequency of relapse, but treatment response is highly variable. Little is known about the genetic factors associated with treatment response. We did a genome-wide association study of antipsychotic treatment response in patients with schizophrenia. METHODS: The discovery cohort comprised patients with schizophrenia from 32 psychiatric hospitals in China that are part of the Chinese Antipsychotics Pharmacogenomics Consortium. Patients who met inclusion criteria were randomly assigned (1:1:1:1:1:1) to six groups (olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, and haloperidol or perphenazine; those assigned to haloperidol or perphenazine were subsequently assigned [1:1] to one or the other) for 6 weeks. Antipsychotic response was quantified with percentage change on the Positive and Negative Syndrome Scale. Single-nucleotide polymorphisms (SNPs) were tested for their association with treatment response. Linkage-disequilibrium-independent SNPs that exhibited potential associations (ie, p<1 × 10-5) were tested in a validation cohort comprising patients from the Chinese Antipsychotics Pharmacogenetics Consortium from five collaborative hospitals, who were treated with olanzapine, risperidone, or aripiprazole for 8 weeks. FINDINGS: The discovery cohort contained 2413 patients and the validation cohort 1379 patients. In the discovery cohort, we identified three novel SNPs (rs72790443 in MEGF10 [p=1·37 × 10-8], rs1471786 in SLC1A1 [p=1·77 × 10-8], and rs9291547 in PCDH7 [p=4·48 × 10-8]) that were associated with antipsychotic treatment response at a genome-wide significance level. These associations were confirmed in the validation cohort (p<0·05). In the combined sample of the discovery and validation cohorts, we identified five novel loci showing genome-wide significant associations with general antipsychotic treatment response (rs72790443 in MEGF10 [p=1·40 × 10-9], rs1471786 in SLC1A1 [p=2·33 × 10-9], rs9291547 in PCDH7 [p=3·24 × 10-9], rs12711680 in CNTNAP5 [p=2·12 × 10-8], and rs6444970 in TNIK [p=4·85 × 10-8]). In antipsychotic-specific groups, after the combination of results from both samples, the rs2239063 SNP in CACNA1C was associated with treatment response to olanzapine (p=1·10 × 10-8), rs16921385 in SLC1A1 was associated with treatment response to risperidone (p=4·40 × 10-8), and rs17022006 in CNTN4 was associated with treatment response to aripiprazole (p=2·58 × 10-8). INTERPRETATION: We have identified genes related to synaptic function, neurotransmitter receptors, and schizophrenia risk that are associated with response to antipsychotics. These findings improve understanding of the mechanisms underlying treatment responses, and the identified biomarkers could eventually guide choice of antipsychotic in patients with schizophrenia. FUNDING: National Key Technology R&D Program of China, National Natural Science Foundation of China.


Assuntos
Antipsicóticos/uso terapêutico , Farmacogenética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Adulto , Antipsicóticos/classificação , Caderinas/genética , Moléculas de Adesão Celular Neuronais/genética , China , Contactinas/genética , Transportador 3 de Aminoácido Excitatório/genética , Feminino , Estudo de Associação Genômica Ampla , Quinases do Centro Germinativo , Humanos , Modelos Logísticos , Masculino , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Resultado do Tratamento
15.
Curr Opin Psychiatry ; 31(3): 200-212, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29528898

RESUMO

PURPOSE OF REVIEW: This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. RECENT FINDINGS: Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications. SUMMARY: The findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.


Assuntos
Antipsicóticos , Farmacogenética , Esquizofrenia , Antipsicóticos/efeitos adversos , Antipsicóticos/classificação , Antipsicóticos/farmacocinética , Resistência a Medicamentos/genética , Humanos , Farmacogenética/métodos , Farmacogenética/tendências , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Discinesia Tardia/induzido quimicamente , Discinesia Tardia/genética , Discinesia Tardia/prevenção & controle , Resultado do Tratamento
16.
J Clin Psychiatry ; 79(2)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29469245

RESUMO

OBJECTIVE: A recent moderately long-term study found an antipsychotic to be more effective than an antidepressant as the next-step treatment of unresponsive major depressive disorder (MDD). It is thus timely to examine recent trends in the pharmacoepidemiology of antipsychotic treatment of MDD. METHODS: Data from the 2006-2015 National Ambulatory Medical Care Survey, nationally representative samples of office-based outpatient visits in adults with MDD (ICD-9-CM codes 296.20-296.26 and 296.30-296.36) (n = 4,044 unweighted), were used to estimate rates of antipsychotic prescribing over these 10 years. Multivariable logistic regression analysis identified demographic and clinical factors independently associated with antipsychotic use in MDD. RESULTS: Antipsychotic prescribing for MDD increased from 18.5% in 2006-2007 to 24.9% in 2008-2009 and then declined to 18.9% in 2014-2015. Visits with adults 75 years or older showed the greatest decline from 27.0% in 2006-2007 to 10.7% in 2014-2015 (OR for overall trend = 0.73; 95% CI, 0.56-0.95). The most commonly prescribed antipsychotic agents were aripiprazole, olanzapine, quetiapine, and risperidone. Antipsychotic prescription was associated with being black or Hispanic, having Medicare among adults under 65 years or Medicaid as a primary source of payment, and receiving mental health counseling, 3 or more concomitant medications, and diagnosis of cannabis use disorder (P < .01). CONCLUSIONS: Antipsychotics, prescribed for about one-fifth of adults with MDD, increased and then declined from 2006 to 2015, reflecting, first, FDA approval and then concern about adverse effects in the elderly. Future research should track evolving trends following the publication of evidence of greater long-term effectiveness of antipsychotic than antidepressant next-step therapy in adults with MDD.


Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/classificação , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/etnologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/psicologia , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Estados Unidos/epidemiologia
17.
Schizophr Res ; 193: 107-113, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28629889

RESUMO

The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients.


Assuntos
Antipsicóticos/uso terapêutico , Revisão de Uso de Medicamentos/estatística & dados numéricos , Medicamentos Genéricos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/classificação , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Risperidona/uso terapêutico , Esquizofrenia/epidemiologia , Estatísticas não Paramétricas , Sulpirida/uso terapêutico , Taiwan/epidemiologia , Resultado do Tratamento
18.
Schizophr Res ; 193: 23-28, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28735640

RESUMO

BACKGROUND: The concept of dose equivalence of depot medication is important for many scientific and clinical purposes. METHODS: A systematic literature search on four second-generation antipsychotics available as long-acting injectable drugs and haloperidol was conducted. We used the minimum effective dose method which is based on randomized fixed dose studies where the smallest dose which was significantly more efficacious than placebo in the primary outcome was declared as minimum effective dose. We calculated equivalent doses from acute phase studies but we also reported the minimum effective doses found in relapse prevention studies. RESULTS: The acute phase minimum effective doses/olanzapine equivalents were: aripiprazole lauroxil 441mg (300mg aripiprazole)/4wks/0.71; aripiprazole 400mg/4weeks/0.95 (aripiprazole maintena); paliperidone palmitate 25mg/4weeks/0,06; risperidone 25mg/2weeks/0,12; RBP-7000 90mg/4weeks/0,21; olanzapine 210mg/2weeks/1. CONCLUSIONS: The minimum effective dose method is an operationalized and evidence-based approach for determining antipsychotic dose equivalence which can also be applied to long-acting injectable formulations. Doses may not have been chosen low enough to find the truly minimum effective dose. Comparisons with other methods will be necessary to come to ultimate conclusions.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/farmacocinética , Esquizofrenia/tratamento farmacológico , Antipsicóticos/classificação , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Humanos , Equivalência Terapêutica
19.
Int J Neuropsychopharmacol ; 21(4): 355-360, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29106549

RESUMO

Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Materials and Methods: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145, and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate. Results: In cell cultures, the measured Kb confirmed high affinity of loxapine for the D2; intermediate affinity for the D1, D4, D5, 5-HT2C receptorsl and a lack of affinity toward D3, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D2 and 5-HT2A receptors. Conclusion: This preclinical study reveals that loxapine receptorial spectrum is close to an "atypical" profile (D2/5HT2A ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification.


Assuntos
Antipsicóticos/farmacocinética , Loxapina/farmacocinética , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Animais , Antipsicóticos/classificação , Células CHO , Cricetulus , Células HEK293 , Humanos , Loxapina/classificação , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
20.
Encephale ; 44(6S): S34-S38, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30935485

RESUMO

Despite the lack of progress in the curative treatment of mental illness, especially schizophrenia, the accumulation of neuroscience data over the past decade suggests the re-conceptualization of schizophrenia. With the advent of new biomarkers and cognitive tools, new neuroscience technologies such as functional dynamic connectivity and the identification of subtle clinical features; it is now possible to detect early stages at risk or prodromes of a first psychotic episode. Current concepts reconceptualizes schizophrenia as a neurodevelopmental disorder at early onset, with polygenic risk and only symptomatic treatment for positive symptoms at this time. The use of such technologies in the future suggests new diagnostic and therapeutic options. Next steps include new pharmacological perspectives and potential contributions of new technologies such as quantitative system pharmacology brain computational modeling approach.


Assuntos
Antipsicóticos , Intervenção Médica Precoce/métodos , Farmacologia Clínica/métodos , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idade de Início , Antipsicóticos/classificação , Antipsicóticos/uso terapêutico , Encéfalo , Criança , Pré-Escolar , Continuidade da Assistência ao Paciente , Diagnóstico Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Integração de Sistemas , Adulto Jovem
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