RESUMEN
A 22-year-old woman, known to have a BMI of 12 kg/m2 and a personality disorder, developed urinary retention on a normal dose of quetiapine. She had earlier tolerated a dose of 800 mg quetiapine without complications. The daily dose was 600 mg in combination with oxazepam and zolpidem. Reduction had no effect. The patient intervened with intermittent urinary catheterization the next 19 months. Normal urinary function returned three days after the last dose of quetiapine 25 mg. This case report shows that patients with a low BMI may be more receptive of the anticholinergic effects of quetiapine.
Asunto(s)
Antipsicóticos , Fumarato de Quetiapina , Retención Urinaria , Humanos , Fumarato de Quetiapina/efectos adversos , Retención Urinaria/inducido químicamente , Femenino , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Adulto Joven , Dibenzotiazepinas/efectos adversos , Dibenzotiazepinas/administración & dosificaciónRESUMEN
PURPOSE: The "early intervention" paradigm in psychiatry holds significant promise for preventing psychosis. Recent evidence showed that individuals at clinical high risk for psychosis (CHR-P) with antipsychotic (AP) prescription at baseline have higher psychosis transition rates compared with those without AP, although the underlying cause remains unclear. In this article, we reviewed international guidelines on early intervention in CHR-P people, paying specific attention to clinical recommendations on AP treatment. Then, we comment on these suggestions in the light of recent empirical evidence examining AP prescription in CHR-P populations within "real-world" clinical settings. METHODS: This search was conducted on PubMed/MEDLINE, PsycINFO, EMBASE, and Google, looking for both "Guidelines AND CHR-P OR UHR OR Early Psychosis." RESULTS: International guidelines generally recommend not using AP as first-line treatment, but only when psychosocial interventions have failed. CHR-P people with AP drug showed high prevalence rates and had more severe clinical picture at entry. Is this a "warning signal" for potentially higher psychosis transition risk? Is it a direct AP iatrogenic effect? Is it possible to detect specific CHR-P subgroup that may benefit from AP? These are the questions that this article seeks to explore. CONCLUSIONS: The current framework for identifying CHR-P subjects has defined psychometric criteria mainly based on positive symptoms. In our opinion, this is reductive, especially for evaluating therapeutic outcomes and prognosis. A more comprehensive assessment considering quality of life, psychiatric comorbidity, persistent negative symptoms, subjective experience of CHR-P psychopathology, and social/personal recovery is thus needed.
Asunto(s)
Antipsicóticos , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/tratamiento farmacológico , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Antipsicóticos/administración & dosificación , Guías de Práctica Clínica como Asunto , Intervención Médica Temprana , Síntomas ProdrómicosRESUMEN
There is little evidence for psychopharmacotherapy in pica. A few studies reported some benefit from the use of SSRIs, atypical antipsychotics and methylphenidate. That said, evidence to deploy these agents remains, at large, flimsy. Here, despite scarcity, we review available literature and draw some generalities that can inform decision-making on clinical grounds.
Asunto(s)
Antipsicóticos , Pica , Humanos , Pica/tratamiento farmacológico , Antipsicóticos/administración & dosificación , Antipsicóticos/farmacología , Metilfenidato/administración & dosificación , Metilfenidato/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificaciónRESUMEN
Introduction: Second-Generation Antipsychotics (SGAs) are widely used for treating psychiatric disorders due to their favorable side effect profile compared to First-Generation Antipsychotics (FGAs). However, SGAs are associated with significant metabolic side effects. This study aims to explore the sociodemographic and health differences between individuals using SGAs and those not using them. Methods: A comparative cross-sectional study was conducted with 148 participants, including 102 SGA users and 46 non-users. Data were collected from patients and medical records, encompassing sociodemographic factors and health variables including diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, waist circumference, fasting blood glucose, cholesterol, triglycerides, HDL, LDL, and BMI. Statistical analyses included chi-square and Fisher's exact tests to compare the two groups. Results: SGA users had higher rates of overweight and obesity compared to non-users (p = 0.000), with 30.4% overweight and 29.4% obese among SGA users versus 21.7% overweight and 4.3% obese among non-users. A higher prevalence of cardiovascular disease was observed in SGA users (11.8% vs. 2.2%, p = 0.076). Although not statistically significant, trends indicated higher rates of diabetes mellitus and hyperlipidemia in non-users (30.4% vs. 18.6%, p = 0.110 and 7% vs. 0%, p = 0.083, respectively). Conclusion: This study highlights significant differences in BMI and cardiovascular disease prevalence between SGA users and non-users, reinforcing the need for comprehensive metabolic monitoring in patients treated with SGAs. The findings underscore the importance of considering sociodemographic factors in managing the health risks associated with SGA use. Further research with larger sample sizes and longitudinal designs is warranted to better understand these associations and develop targeted interventions.
Asunto(s)
Antipsicóticos , Síndrome Metabólico , Humanos , Estudios Transversales , Masculino , Femenino , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Arabia Saudita/epidemiología , Síndrome Metabólico/epidemiología , Síndrome Metabólico/inducido químicamente , Persona de Mediana Edad , Adulto , Trastornos Mentales/epidemiología , Trastornos Mentales/tratamiento farmacológico , Prevalencia , Obesidad/epidemiología , Obesidad/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Sobrepeso/epidemiología , Sobrepeso/inducido químicamenteRESUMEN
We discuss a case with off-label sublingual administration of atropine for clozapine-induced sialorrhea (CIS) after failure of two commonly used agents to manage CIS. Atropine had a demonstrable efficacy, as measured by means of sialometry conducted before and after its administration. The salivary rate, initially measured at 0.60 g/min one hour before atropine administration, reduced to 0.23 g/min two hours after administration. Sublingual administration of atropine was found to be an efficacious option for this patient, but safety issues particularly tachycardia and pragmatics such as risk of inadvertent overdose led to its discontinuation after the initial dose. Developing micro-dosing devices for sublingual atropine could enhance administration precision, reduce side effects, and provide a cost-effective solution. The case report also underscores the need to employ sialometry for the objective assessment of treatment outcomes in future research trials for hypersalivation.
Asunto(s)
Antipsicóticos , Atropina , Trastorno Bipolar , Clozapina , Sialorrea , Humanos , Sialorrea/inducido químicamente , Sialorrea/tratamiento farmacológico , Administración Sublingual , Clozapina/administración & dosificación , Clozapina/efectos adversos , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Atropina/administración & dosificación , Trastorno Bipolar/tratamiento farmacológico , Masculino , Adulto , Uso Fuera de lo IndicadoRESUMEN
INTRODUCTION: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study. METHODS: The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations. CONCLUSION: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations. PATIENT OR PUBLIC CONTRIBUTION: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.
Asunto(s)
Antipsicóticos , Aripiprazol , Trastorno Bipolar , Análisis Costo-Beneficio , Investigación Cualitativa , Fumarato de Quetiapina , Humanos , Trastorno Bipolar/tratamiento farmacológico , Aripiprazol/uso terapéutico , Fumarato de Quetiapina/uso terapéutico , Antipsicóticos/uso terapéutico , Antipsicóticos/economía , Antipsicóticos/administración & dosificación , Antidepresivos/uso terapéutico , Antidepresivos/economía , Entrevistas como Asunto , Quimioterapia Combinada , Femenino , Masculino , AdultoRESUMEN
This report presents challenging psychopharmacotherapy management of a psychotic disorder in a patient with a delicate pharmacogenetic profile and drug-drug interactions. A 31-year old woman diagnosed with schizophrenia in 2017 was referred by her psychiatrist to a clinical pharmacologist for interpretation of a pharmacogenetic test and advice regarding optimal psychopharmacotherapy. In spite of adherence to aripiprazole, olanzapine, risperidone, and levomepromazine, and rational anxiolytic therapy, she still experienced anxiety, anhedonia, loss of appetite, sleeping problems, and auditory hallucinations with commands to harm herself. Due to a lack of alternative therapeutic steps, low aripiprazole serum concentrations, and a lack of explanation for pharmacotherapy unresponsiveness, pharmacogenetic testing was performed. The patient was defined as CYP2D6 *1/*1, CYP1A2 *1F/*1F, CYP3A4 *1/*1B, CYP3A5 *1/*3, and having increased activity of the enzymes UGT1A4 and UGT2B7, intermediate activity of ABCB1 transporter, and low activity of COMT. Carbamazepine was discontinued, aripiprazole was increased to a maximum of 30 mg/day orally with long-acting injection (400 mg monthly), and olanzapine was increased to a daily dose of 35 mg orally. These changes led to an optimal therapeutic drug concentration and improved clinical status. At the last follow-up, the patient was without severe auditory hallucinations, became more engaged in daily life, had more interaction with others, had found a job, and even had started an emotional relationship. In psychiatry, pharmacogenetic testing is an important tool for guiding pharmacological therapy, particularly in patients with an unsatisfactory clinical response and a lack of alternative therapeutic steps for pharmacotherapy unresponsiveness.
Asunto(s)
Antipsicóticos , Interacciones Farmacológicas , Humanos , Adulto , Femenino , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/genética , Aripiprazol/administración & dosificación , Aripiprazol/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Citocromo P-450 CYP1A2/genética , Pruebas de Farmacogenómica , Farmacogenética , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP2D6/genéticaRESUMEN
BACKGROUND: Antipsychotic medications are effective treatments for schizophrenia (SZ) and bipolar I disorder (BD-I), but when presented with different treatment options, there are tradeoffs that individuals make between clinical improvement and adverse effects. As new options become available, understanding the attributes of antipsychotic medications that are valued and the tradeoffs that individuals consider when choosing among them is important. METHODS: A discrete-choice experiment (DCE) was administered online to elicit preferences across 5 attributes of oral antipsychotics: treatment efficacy (i.e., improvement in symptom severity), weight gain over 6 months, sexual dysfunction, sedation, and akathisia. Eligible respondents were aged 18-64 years with a self-reported clinician diagnosis of SZ or BD-I. RESULTS: In total, 144 respondents with SZ and 152 with BD-I completed the DCE. Of those with SZ, 50% identified themselves as female and 69.4% as White, with a mean (SD) age of 41.0 (10.1) years. Of those with BD-I, most identified themselves as female (69.7%) and as White (77.6%), with a mean (SD) age of 40.0 (10.7) years. In both cohorts, respondents preferred oral antipsychotics with better efficacy, less weight gain, no sexual dysfunction or akathisia, and lower risk of sedation. Treatment efficacy was the most important attribute, with a conditional relative importance (CRI) of 31.4% for respondents with SZ and 31.0% for those with BD-I. Weight gain (CRI = 21.3% and 23.1%, respectively) and sexual dysfunction (CRI = 23.4% and 19.2%, respectively) were adverse effects in this study that respondents most wanted to avoid. Respondents with SZ were willing to accept 9.8 lb of weight gain or > 25% risk of sedation for symptom improvement; those with BD-I were willing to accept 8.5 lb of weight gain or a > 25% risk of sedation. CONCLUSIONS: In this DCE, treatment efficacy was the most important attribute of oral antipsychotic medications among respondents with SZ and BD-I. Weight gain and sexual dysfunction were the adverse effects respondents most wanted to avoid; however, both cohorts were willing to accept some weight gain or sedation to obtain better efficacy. These results highlight features that patients value in antipsychotic medications and how they balance benefits and risks when choosing among treatments.
Asunto(s)
Antipsicóticos , Trastorno Bipolar , Prioridad del Paciente , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/administración & dosificación , Femenino , Adulto , Masculino , Esquizofrenia/tratamiento farmacológico , Persona de Mediana Edad , Trastorno Bipolar/tratamiento farmacológico , Administración Oral , Aumento de Peso/efectos de los fármacos , Adulto Joven , Conducta de Elección , Adolescente , Resultado del TratamientoRESUMEN
BACKGROUND: Smoking enhances plasma clozapine clearance, but the magnitude of the effect across the dose and age ranges is unclear. METHODS: We audited clozapine dose and predose plasma clozapine and N -desmethylclozapine (norclozapine) concentrations by sex and smoking habit in samples submitted for clozapine TDM, 1996-2017. RESULTS: There were 105,316/60,792 and 34,288/31,309 samples from male/female smokers/nonsmokers, respectively. There were distinct dose-median plasma concentration trajectories for male/female smokers/nonsmokers across the range <50 to >850 mg d -1 . For both sexes, the percentage difference in median plasma clozapine in nonsmokers versus smokers averaged 50% but was greatest for men (76%) and women (59%) in the 151 to 250 mg d -1 dose band. In men, the percentage difference declined steadily to 34% at doses of ≥850 mg d -1 . In women, the difference after falling initially remained relatively constant at 40% to 54%. The pattern in median plasma clozapine/norclozapine ratio by plasma clozapine concentration and dose groups was independent of sex and smoking habit, but increased with plasma clozapine concentration (higher ratio at higher concentrations) and also changed with dose. Median plasma clozapine concentration and median clozapine dose by sex and smoking habit were similar up to age 60 years. Proportional weight gain was similar over time in smokers and nonsmokers of either sex. IMPLICATIONS: These data explain the variations in the effect size of starting or stopping smoking on plasma clozapine concentration at constant dose reported in different studies. Changes in smoking habit in patients prescribed clozapine require prompt dose adjustment.
Asunto(s)
Antipsicóticos , Fumar Cigarrillos , Clozapina , Relación Dosis-Respuesta a Droga , Humanos , Clozapina/análogos & derivados , Clozapina/sangre , Clozapina/administración & dosificación , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antipsicóticos/sangre , Antipsicóticos/administración & dosificación , Factores Sexuales , Fumar Cigarrillos/sangre , Adulto Joven , Anciano , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/sangreAsunto(s)
Antipsicóticos , Clozapina , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Humanos , Clozapina/efectos adversos , Clozapina/administración & dosificación , Neutropenia/inducido químicamente , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Masculino , Persona de Mediana Edad , FemeninoRESUMEN
BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization. METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models. RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable. CONCLUSION: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.
Asunto(s)
Antipsicóticos , COVID-19 , Clozapina , Cumplimiento de la Medicación , Aceptación de la Atención de Salud , Trastornos Psicóticos , Humanos , Masculino , Femenino , COVID-19/epidemiología , Clozapina/uso terapéutico , Clozapina/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/epidemiología , Manitoba/epidemiología , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Aceptación de la Atención de Salud/estadística & datos numéricos , Preparaciones de Acción Retardada , Hospitalización/estadística & datos numéricos , Anciano , Adulto JovenRESUMEN
Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Ketamina , Corteza Prefrontal , Risperidona , Esquizofrenia , Caracteres Sexuales , Animales , Ketamina/farmacología , Ketamina/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inducido químicamente , Esquizofrenia/fisiopatología , Masculino , Femenino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Risperidona/farmacología , Risperidona/administración & dosificación , Ratas , Antipsicóticos/farmacología , Antipsicóticos/administración & dosificación , Reconocimiento en Psicología/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Ratas Wistar , Conducta Animal/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Actividad Motora/efectos de los fármacosRESUMEN
To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint. Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation. SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.
Asunto(s)
Antipsicóticos , Preparaciones de Acción Retardada , Metaanálisis en Red , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Adulto , Ensayos Clínicos Controlados Aleatorios como Asunto , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
BACKGROUND: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone. METHOD: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment. RESULTS: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05). CONCLUSIONS: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.
Asunto(s)
Antipsicóticos , Resistencia a la Insulina , Olanzapina , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/sangre , Masculino , Femenino , Olanzapina/uso terapéutico , Olanzapina/efectos adversos , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Tiazoles/uso terapéutico , Tiazoles/efectos adversos , Tiazoles/administración & dosificación , Piperazinas/uso terapéutico , Piperazinas/efectos adversos , Piperazinas/administración & dosificación , Benzodiazepinas/uso terapéutico , Benzodiazepinas/efectos adversosRESUMEN
An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0â¯mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3â¯mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.
Asunto(s)
Antipsicóticos , Apomorfina , Agonistas de Dopamina , Actividad Motora , Quinpirol , Ratas Long-Evans , Risperidona , Animales , Apomorfina/farmacología , Apomorfina/administración & dosificación , Risperidona/farmacología , Risperidona/administración & dosificación , Quinpirol/farmacología , Ratas , Agonistas de Dopamina/farmacología , Agonistas de Dopamina/administración & dosificación , Femenino , Masculino , Actividad Motora/efectos de los fármacos , Antipsicóticos/farmacología , Antipsicóticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/efectos de los fármacos , Animales Recién Nacidos , Factores de Edad , Factores SexualesRESUMEN
Intranasal (IN) delivery offers potential to deliver antipsychotic drugs with improved efficacy to the brain. However, the solubilization of such drugs and the frequency of required re-application both represent challenges to its practical implementation in treating various mental illnesses including schizophrenia. Herein, we report a sprayable nanoparticle network hydrogel (NNH) consisting of hydrophobically-modified starch nanoparticles (SNPs) and mucoadhesive chitosan oligosaccharide lactate (COL) that can gel in situ within the nasal cavity and release ultra-small penetrative SNPs over time. Hydrophobization of the SNPs enables enhanced uptake and prolonged release of poorly water soluble drugs such as olanzapine from the NNH depot through mucous and ultimately into the brain via the nose-to-brain (N2B) pathway. The hydrogel shows high in vitro cytocompatibility in mouse striatal neuron and human primary nasal cell lines and in vivo efficacy in an amphetamine-induced pre-clinical rat schizophrenia model, with IN-delivered NNH hydrogels maintaining successful attenuation of locomotor activity for up to 4 h while all other tested treatments (drug-only IN or conventional intraperitoneal delivery) failed to attenuate at any time point past 0.5 h. As such, in situ-gelling NNHs represent a safe excipient for the IN delivery of hydrophobic drugs directly to the brain using customized SNPs that exhibit high penetration and drug complexing properties to maximize effective drug delivery.
Asunto(s)
Administración Intranasal , Hidrogeles , Nanopartículas , Olanzapina , Almidón , Animales , Hidrogeles/química , Nanopartículas/química , Almidón/química , Olanzapina/química , Olanzapina/administración & dosificación , Olanzapina/farmacología , Ratas , Ratones , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Esquizofrenia/tratamiento farmacológico , Portadores de Fármacos/química , Masculino , Antipsicóticos/química , Antipsicóticos/farmacología , Antipsicóticos/administración & dosificación , Encefalopatías/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Quitosano/química , Línea Celular , Encéfalo/metabolismo , Encéfalo/efectos de los fármacosRESUMEN
Antipsychotic polypharmacy is commonly used in clinical settings, with a growing trend in using long-acting injections to mitigate many side effects of polypharmacy. A previous study demonstrated that long-acting aripiprazole once-monthly (AOM) injection increased treatment adherence, restored functionality, and improved symptoms. However, there is insufficient evidence to demonstrate the therapeutic effects of AOM in polypharmacy practice. This observational study aimed to investigate the real-world clinical benefits and effectiveness of AOM by assessing changes in drug dosage, the number of drugs, clinical functioning, psychotic symptoms, and the duration of drug efficacy. Study participants were recruited from eight study sites, with the baseline visit marking the initiation of drug treatment. Clinical and demographic data were collected from medical records at screening, baseline, and months 1, 3, 6, 9, and 12. Over 12 months, we analyzed changes in drug dosage, the number of drugs, and scores of the Positive and Negative Syndrome Scale-6 (PANSS-6), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity (CGIS). Data from 139 participants were analyzed. Total 12-month antipsychotic doses calculated in chlorpromazine equivalents (CPE) were reduced by 32.6%. A comparison of total monthly antipsychotic doses in CPE between the first and last months showed a 24.6% reduction in the dose. Additionally, the quantity of benzodiazepine tablets/capsules, total benzodiazepine doses calculated in lorazepam equivalents, and quantity of tablets/capsules of mood stabilizers, anticholinergics, and beta blockers were significantly reduced. GAF scores increased by 14.1% over 12 months, and PANSS-6 total scores reduced by 17.3% over 12 months, with significant differences observed from month 1 and baseline, respectively. The scores steadily improved until month 9 compared to those of the previous months, continuing to improve through month 12. The CGI-S score reduced by 14.3% over 12 months, showing a significant decrease from month 1 and a steady improvement until month 6, maintaining this improvement until month 12. In conclusion, this study demonstrated the early effectiveness of AOM in treating Korean patients with schizophrenia on polypharmacy. AOM improved function and clinical symptoms in patients with schizophrenia from treatment onset and caused a decrease in the quantity and dosage of drugs taken by the patients.
Asunto(s)
Antipsicóticos , Aripiprazol , Polifarmacia , Esquizofrenia , Humanos , Aripiprazol/administración & dosificación , Aripiprazol/uso terapéutico , Masculino , Femenino , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Preparaciones de Acción Retardada , Resultado del TratamientoRESUMEN
BACKGROUND: Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia (SCZ), but SGAs may differ in the severity of side effects. Long-term studies are lacking, and previous observational studies have limitations, such as failure to account for confounding factors and short follow-up durations. AIMS: To compare the long-term anthropometric and metabolic side effects of seven SGAs in a Chinese population, using a within-subject approach to reduce the risk of confounding. METHOD: We collected longitudinal data of SGA prescriptions, concomitant medications, fasting blood glucose (BG), lipid profiles, and BMI in a cohort of 767 patients with SCZ, with follow-up lasting up to 18.7 years (median â¼6.2 years). A total of 192,152 prescription records were retrieved, with 27,723 metabolic measures analysed. Linear mixed models were used to estimate the effects of SGA on BG, lipid profiles and BMI. Besides studying the effects of SGA medications (as binary predictors), we also investigated the effects of SGA dosage on metabolic profiles. RESULTS: Considering SGA medications as binary predictors, clozapine and olanzapine were associated with the most substantial worsening of lipid profiles and BMI. A significant increase in BG was observed with clozapine only. Amisulpride, paliperidone and quetiapine were associated with worsened lipid profiles and increased BMI. Conversely, aripiprazole was associated with significant improvement in lipid profiles but a small increase in BMI. When SGA dosage was considered, the model showed consistent results overall. At the minimum effective dose, clozapine was associated with the most severe metabolic side effects, followed by olanzapine. Risperidone and aripiprazole showed the least metabolic side effects, with aripiprazole being significantly associated with lower lipids. CONCLUSIONS: This study clarified the long-term and dose-dependent effects of different SGAs on anthropometric and metabolic parameters in Chinese SCZ patients. Our findings may inform clinicians and SCZ patients of SGA choices.
Asunto(s)
Antipsicóticos , Olanzapina , Esquizofrenia , Humanos , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Femenino , Masculino , Adulto , China , Olanzapina/efectos adversos , Olanzapina/administración & dosificación , Persona de Mediana Edad , Índice de Masa Corporal , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios Longitudinales , Clozapina/efectos adversos , Clozapina/administración & dosificación , Fumarato de Quetiapina/efectos adversos , Fumarato de Quetiapina/administración & dosificación , Risperidona/efectos adversos , Risperidona/administración & dosificación , Estudios de Seguimiento , Adulto Joven , Relación Dosis-Respuesta a Droga , Aripiprazol/administración & dosificación , Aripiprazol/efectos adversos , Aripiprazol/farmacología , Lípidos/sangre , Pueblos del Este de AsiaRESUMEN
Increasing attention is being afforded to understanding the bidirectional relationship that exists between oral drugs and the gut microbiota. Often overlooked, however, is the impact that pharmaceutical excipients exert on the gut microbiota. Subsequently, in this study, we contrasted the pharmacokinetic performance and gut microbiota interactions between two commonly employed formulations for poorly soluble compounds, namely 1) an amorphous solid dispersion (ASD) stabilised by poly(vinyl pyrrolidone) K-30, and 2) a lipid nanoemulsion (LNE) comprised of medium chain glycerides and lecithin. The poorly soluble antipsychotic, lurasidone, was formulated with ASD and LNE due to its rate-limiting dissolution, poor oral bioavailability, and significant food effect. Both the ASD and LNE were shown to facilitate lurasidone supersaturation within in vitro dissolution studies simulating the gastrointestinal environment. This translated into profound improvements in oral pharmacokinetics in rats, with the ASD and LNE exerting comparable â¼ 2.5-fold improvements in lurasidone bioavailability, compared to the pure drug. The oral formulations imparted contrasting effects on the gut microbiota, with the LNE depleting the richness and abundance of the microbial ecosystem, as evidenced through reductions in alpha diversity (Chao1 index) and operational taxonomical units (OTUs). In contrast, the ASD exerted a 'gut neutral' effect, whereby a mild enrichment of alpha diversity and OTUs was observed. Importantly, this suggests that ASDs are effective solubility-enhancing formulations that can be used without comprising the integrity of the gut microbiota - an integral consideration in the treatment of mental health disorders, such as schizophrenia, due to the role of the gut microbiota in regulating mood and cognition.