Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model.

BACKGROUND/AIM: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment. MATERIALS AND METHODS: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms. RESULTS: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling. CONCLUSION: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.

[Effects of preoperative quetiapine on postoperative delirium and sleep quality in elderly orthopaedic patients].

Objective: To investigate the effects of preoperative quetiapine on postoperative delirium (POD) and sleep quality in elderly orthopedic patients. Methods: Prospectively, 111 elderly patients, American Society of Anesthesiologists (ASA) grade Ⅱ-Ⅲ, scheduled to undergo knee or hip surgery in the Affiliated Huangyan Hospital of Wenzhou Medical University under continuous spinal anesthesia from August 2021 to March 2023, were selected and randomly divided into two groups by random number table: control group (group C, 1 h preoperative placebo) and quetiapine group (group Q, 1 h preoperative quetiapine 12.5 mg). In group C, 54 cases were enrolled, including 25 males and 29 females, with an average age of (73.5±4.9) years. In group Q, 57 cases were enrolled, including 26 males and 31 females, with an average age of (74.8±5.0) years. The primary outcome measures were the incidence of POD evaluated by using confusion assessment method (CAM) at 24, 48, and 72 hours after surgery, and the secondary outcome measures included Pittsburgh sleep quality index (PSQI) scores at 24 and 48 hours after surgery and satisfaction of pain management within 24 hours after surgery. Results: The incidence of POD at 24, 48, and 72 h after surgery in group Q was 5.4% (3/57), 12.5% (7/57), 14.3% (8/57), respectively, while that in group C was 18.2% (10/54), 21.8% (12/54), 21.8% (12/54), respectively. The incidence of POD at 24 h after surgery in group Q was lower than that in group C (P=0.036). There was no significant difference in the incidence of POD at 48 and 72 h after surgery between two groups (all P>0.05). The PSQI score of patients in group Q at 24 and 48 h after surgery were (3.8±1.2) and (6.9±1.1) scores, respectively, which in group C were (10.5±2.8) and (7.3±1.3) scores, respectively. Compared with group C, the PSQI score of patients in group Q at 24 h after surgery was significantly higher (P<0.001), but there was no significant difference at 48 h after surgery (P=0.068). The satisfaction scores of pain management at 24 h after surgery in group Q was (91±7) scores, which was higher than that in group C of (81±6) scores (P<0.001). Conclusion: Oral intake of low-dose quetiapine 1 h preoperatively can reduce the incidence of POD, improve postoperative sleep quality and enhance postoperative satisfaction of pain management at 24 hours after surgery in elderly orthopedic patients undergoing knee or hip surgery.

Quetiapine effect on depressive-like behaviors, oxidative balance, and inflammation in serum of rats submitted to chronic stress.

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were as follows: to evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant, and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine (20 mg/kg), imipramine (30 mg/kg), and escitalopram (10 mg/kg). At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 (IL-6) levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.

Bupropion XL unapproved use in the prisons: Two cases focused on the bupropion pharmacology.

BACKGRUND: Bupropion (BUP) is a norepinephrine-dopamine reuptake inhibitor frequently used in prisons. Although its positive effects on depression treatment are often presented, there are many questions about its approved use in prisons and similar facilities. In this context, this article aims to present two case reports of BUP XL unapproved use and a review of the mechanism of action, formulations, and the clinical profile of BUP. METHODS: Two case reports. The patients' data for the case reports were obtained from their medical records. A PubMed search was conducted using the terms BUP, inmates, and efficacy to identify randomized and non-randomized controlled trials and case reports to evaluate the possible effects of BUP in prison settings. Only approved medications were included. RESULTS: The positive effects of BUP XL on major depressive disorder treatment are well-reported, but few reports are on the pharmacokinetics of BUP XL in prisons. The exact mechanism of its effect on the central nervous system is predominantly connected with its unique pharmacokinetics. CONCLUSIONS: This paper shows that BUP XL will continue to play an essential role in treating a major depressive disorder in adults in prisons and other related disorders, although a different treatment strategy should be preferred in patients with high addictive potential. Because of a similar mechanism of action, the most appropriate alternatives for BUP XL could be mirtazapine, agomelatine, aripiprazole, and quetiapine, although clinical trials are needed to confirm these alternatives.

Inflammatory markers at baseline correlate with subsequent clinical response to quetiapine in patients with bipolar disorder.

OBJECTIVES: Recent studies proposed the existence of a correlation between patients' inflammatory status and therapy response in bipolar disorder (BD). Here we investigated the correlation between levels of inflammatory markers and quetiapine (QUE) effects in BD patients. METHODS: In 15 hospitalised BD patients, we investigated changes in inflammatory markers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and cytokines after a 6-week treatment with QUE monotherapy. RESULTS: We found QUE treatment to significantly reduce CRP and IL-6 plasma levels. Moreover, we found higher CRP and IL-6 plasma levels at baseline correlated with better improvement of patients' clinical symptoms. CONCLUSION: The reported results, although preliminary, could be useful in clinical practice, providing not only markers for QUE response, but also allowing for identification of new targets and new therapies for the treatment of this condition.

Estudio de utilización de psicofármacos en usuarios de la policlínica del Hospital Vilardebó con diagnóstico de esquizofrenia (años 2006 y 2016) / Study of the use of psychotropic drugs in users of the Vilardebó Hospital polyclinic with a diagnosis of schizophrenia (2006 and 2016)

El tratamiento farmacológico de demostrada eficacia en la esquizofrenia es el antipsicótico. Sin embargo, en muchas ocasiones se requiere medicación concomitante que depende de comorbilidades y efectos adversos. Se realizó un estudio cuantitativo, longitudinal, retrospectivo, considerando el año 2006 y 2016, en una población de usuarios con esquizofrenia de la Policlínica del Hospital Vilardebó, analizando los tratamientos con psicofármacos. Se diferenciaron los tratamientos según monoterapia antipsicótica y polifarmacia con 2 antipsicóticos, y polifarmacia con más de 2 antipsicóticos, antidepresivos, estabilizantes del humor, benzodiacepinas y anticolinérgicos. La población inicial en 2006 fue de 621 pacientes y 398 pacientes continuaban en tratamiento en 2016. Mantuvieron el trata-miento con antipsicóticos 377 pacientes; 184 mantuvieron benzodiacepinas; 59 se mantuvieron con anticolinérgicos; 49, con estabilizantes del humor y 47, con antidepresivos. La monoterapia antipsicótica se presentó en torno al 50 % de la población estudiada. Se deberían revisar aquellas prácticas que se infieren a partir de este estudio, como el uso prolongado de anticolinérgicos, benzodiacepinas, y polifarmacia con más de 2 antipsicóticos, que está extendida en los usuarios con esquizofrenia. El tratamiento con clozapina fue el más estable y no parece aumentar la mortalidad en estos pacientes

Antipsychotics are the proved effective therapy for schizophrenia. However, on many occasions, associated drugs are required depending on comorbidities and side effects. A retrospective longitudinal quantitative study of drug prescription for 2006 and 2016 in patients with schizophrenia diagnosis was carried out in an outpatient clinic at Hospital Vilardebó. Treatments were classified as antipsychotic monotherapy, two antipsychotic drugs polypharmacy and polypharmacy with two antipsychotic drugs, antidepressants, mood stabilizers, benzodiazepines and anticholinergic drugs. Initial population in 2006 included 621 patients, 398 were still being treated in 2016. Antipsychotic drugs were still being received in 377 patients, benzodiazepines in 184, anticholinergic drugs in 59, mood stabilizers in 49, and anti-depressants in 47. Antipsychotic monotherapy was 50% of the population. Those practices that can be inferred from this study, with lengthy use of anticholinergic drugs, benzodiazepines, and the use of more than 2 antipsychotic drugs in patients with schizophrenia diagnosis should be revised. Clozapine therapy was the most stable and does not seem to increase mortality.

Antipsychotic use and risk of breast cancer in women with schizophrenia: a nationwide nested case-control study in Finland.

BACKGROUND: Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing antipsychotics contributes to increased odds of breast cancer. METHODS: We used Finnish nationwide registers of hospital treatment, prescription drug purchases, and cancer diagnoses to do a nested case-control study. Of women with schizophrenia, those with breast cancer (cases) were matched by age and duration of illness with five women without cancer (controls). Cases and controls were aged 18-85 years and exclusion criteria were any previous cancer diagnoses, receipt of organ transplant, mastectomy, or diagnosis of HIV. The main analysis was the association between cumulative exposure to prolactin-increasing drugs and breast cancer. The analyses were done with conditional logistic regression, by adjusting for comorbid conditions and concomitant medications. Ethnicity data were not available. FINDINGS: Of 30 785 women diagnosed with schizophrenia between 1972 and 2014, 1069 were diagnosed with breast cancer between Jan 1, 2000, and Dec 31, 2017. Compared with 5339 matched controls, 1-4 years cumulative exposure (adjusted odds ratio [OR] 0·95, 95% CI 0·73-1·25) or 5 or more years exposure (adjusted OR 1·19, 0·90-1·58) to prolactin-sparing antipsychotics (including clozapine, quetiapine, or aripiprazole) was not associated with an increased risk of breast cancer in comparison with minimal exposure (<1 year). When compared with less than 1 year of exposure to prolactin-increasing antipsychotics (all other antipsychotics), 1-4 years of exposure was not associated with an increased risk, but exposure for 5 or more years was associated with an increased risk (adjusted OR 1·56 [1·27-1·92], p<0·001). The risk for developing lobular adenocarcinoma associated with long-term use of prolactin-increasing antipsychotics (adjusted OR 2·36 [95% CI 1·46-3·82]) was higher than that of developing ductal adenocarcinoma (adjusted OR 1·42 [95% CI 1·12-1·80]). INTERPRETATION: Long-term exposure to prolactin-increasing, but not to prolactin-sparing, antipsychotics is significantly associated with increased odds of breast cancer. Monitoring prolactinemia and addressing hyperprolactinemia is paramount in women with schizophrenia being treated with prolactin-increasing antipsychotics. FUNDING: Finnish Ministry of Social Affairs and Health.

Successful diagnosis and treatment of pulmonary aspergillosis-related malignant catatonia using propofol and quetiapine: A case report.

INTRODUCTION: Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders. PATIENT CONCERNS: An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels. DIAGNOSES: At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement. INTERVENTIONS: Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely. OUTCOMES: The patient's MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital. CONCLUSION: This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment.

Psychosis in a primary hyperparathyroidism patient with mild hypercalcemia: A case report.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and an elevated level of serum parathyroid hormone (PTH). PHPT presents with a complex set of renal, skeletal, and neuropsychological symptoms. Parathyroidectomy (PTX) is a radical treatment that is recommended for all physically symptomatic patients with PHPT. However, psychiatric symptoms are not considered as an indication for surgery. There remains an important issue from the view of perioperative management of whether PTX should be performed with the presence of uncontrolled psychiatric symptoms or deferred until severe psychiatric symptoms have been controlled. We report a case of mild hypercalcemia that caused severe psychosis in PHPT, which improved dramatically following PTX and resulted in successful postoperative management. PATIENT CONCERN: Our patient was a 68-year-old Japanese woman. She was diagnosed with PHPT, which was triggered by mild hypercalcemia. She was due to receive an operation for osteoporosis and kidney stones. She had severe psychosis, despite medication. Blood examinations revealed mild hypercalcemia (10.4 mg/dL, 8.8-10.1 mg/dL) and elevated serum levels of intact PTH (184.0 pg/mL, 10-65 pg/mL). DIAGNOSIS: She was diagnosed with severe psychosis caused by mild hypercalcemia in PHPT. INTERVENTIONS: Although she was treated with 37.5 mg quetiapine and 2 mg risperidone daily, she was excessively sedated and rejected oral treatment. Therefore, we decided to perform the operation. OUTCOMES: Immediately following surgery, serum levels of calcium, and intact PTH were normalized. Her psychotic symptoms ceased completely 5 days after surgery. CONCLUSION: We emphasize that PHPT presents with various severe psychiatric symptoms, even in mild hypercalcemia. Psychiatric symptoms may be the only salient symptoms in PHPT, and thus clinicians should suspect PHPT in patients with psychiatric symptoms and mild hypercalcemia. Furthermore, PTX is recommended for PHPT-even in the presence of severe uncontrolled psychiatric symptoms, which carries risks for postoperative management-because psychiatric symptoms are expected to improve and good postoperative management is possible.

Potentially inappropriate prescriptions to Brazilian older people with Alzheimer disease: A cross-sectional study.

ABSTRACT: Older adults are the leading users of medications, where this can be associated with a high number of potentially inappropriate medications (PIMs) and of potentially inappropriate prescribing (PIP) and consequent harm to health. No Brazilian study evaluating potentially inappropriate prescribing in older patients with Alzheimer's disease (AD) was found. This study determined and analyzed the prevalence of PIP and PIM prescribed for older people with AD.A cross-sectional study was carried out at the Specialty Drugs Pharmacy in the city of Sorocaba, São Paulo State, Brazil. The MEDEX system provided the register in older people with AD and data were collected during interviews with patients and/or caregivers between June and September 2017. The PIMs were identified according to the 2019 Beers Criteria. The association between PIMs and independent variables was analyzed by Poisson regression.This study included 234 older patients with AD. The prevalence of PIP prescribed was 66.7% (n = 156). Of the 1073 medications prescribed, 30.5% (n = 327) were inappropriate with most affecting the central nervous system or cardiovascular, particularly quetiapine (12.8%) and acetylsalicylic acid (11.6%), respectively. Around 45.2% of the PIMs should be avoided in older people, especially sertraline (14.2%) and clonazepam (7.4%). After adjusted analysis, the PIMs were associated with the diagnosis of depression (P = 0.010) and the number of comorbidities (P = 0.005).There was a high number of PIMs among older people, a substantial number of which should have been avoided in this population. Health care professionals can apply these findings to improve safety in the use of medications for treating patients with AD.

Decreased cardiovascular death in schizophrenia patients treated with antipsychotics: A Korean national cohort study.

BACKGROUND: Patients with schizophrenia have a reduced life expectancy, but the association between antipsychotic usage and cause of death is uncertain. METHODS: The authors observed associations of antipsychotic usage with the mortality rate and cause of death in a population-based cohort of the Korean National Health Insurance Service database from 2003 to 2017. A total of 86,923 patients with schizophrenia were categorized by the total duration of antipsychotic prescription after schizophrenia diagnosis into treated (n = 77,139) and untreated (n = 9784) groups. The main outcome was all-cause mortality; causes of death included cardiovascular disease, pulmonary disease, diabetes, cancer, accident, suicide and homicide. RESULTS: The numbers of all-cause deaths and deaths from individual causes were significantly lower in the antipsychotic-treated group than in the untreated group (all cases, p < 10-4). When adjusted for covariates (age, sex, income, body mass index, alcohol consumption, hypertension, cancer and cerebral stroke), mortality rates due to ischemic heart disease (hazard ratio, HR, 0.38 [95% CI, 0.18-0.77]) and stroke (HR, 0.39 [95% CI, 0.19-0.80]) were significantly lower in the antipsychotic-treated group. Among 4 atypical antipsychotics (olanzapine, risperidone, aripiprazole and quetiapine), only aripiprazole was associated with a decreased mortality risk relative to olanzapine (HR, 0.55 [95% CI, 0.32-0.96]). CONCLUSIONS: Schizophrenia patients constantly prescribed antipsychotics had significantly lower rates of death from certain cardiovascular illnesses than untreated patients. Aripiprazole-treated schizophrenia was associated with a decreased risk of death compared with olanzapine-treated disease.

Why the Maternal Medication List Matters: Neonatal Toxicity From Combined Serotonergic Exposures.

Serotonergic medications are used for the prevention and treatment of depression during pregnancy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause poor neonatal adaptation, which has been attributed to withdrawal versus toxicity. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is often used as an adjunctive agent to selective serotonin reuptake inhibitors or SNRIs for refractory depression. Quetiapine, an atypical antipsychotic, may also be used in more complex cases. When combined with serotonergic drugs, bupropion and quetiapine are associated with increased risk of serotonin syndrome in adults. We describe a neonate exposed to venlafaxine (an SNRI), bupropion, and quetiapine in utero who presented nearly immediately after birth with encephalopathy and abnormal movements. The severity and rapidity of symptoms may be attributable to potentiation of venlafaxine's serotonergic effects by bupropion and quetiapine. Neonatal providers should be aware of maternal medications and prepare for possible adverse effects, particularly from common psychotropic exposures.

Haematologic malignancies associated with clozapine v. all other antipsychotic agents: a pharmacovigilance study in VigiBase®.

BACKGROUND: Clozapine is mainly used in patients with treatment-resistant schizophrenia and may lead to potentially severe haematologic adverse events, such as agranulocytosis. Whether clozapine might be associated with haematologic malignancies is unknown. We aimed to assess the association between haematologic malignancies and clozapine using Vigibase®, the WHO pharmacovigilance database. METHODS: We performed a disproportionality analysis to compute reporting odds-ratio adjusted for age, sex and concurrent reporting of antineoplastic/immunomodulating agents (aROR) for clozapine and structurally related drugs (loxapine, olanzapine and quetiapine) compared with other antipsychotic drugs. Cases were malignant lymphoma and leukaemia reports. Non-cases were all other reports including at least one antipsychotic report. RESULTS: Of the 140 226 clozapine-associated reports, 493 were malignant lymphoma cases, and 275 were leukaemia cases. Clozapine was significantly associated with malignant lymphoma (aROR 9.14, 95% CI 7.75-10.77) and leukaemia (aROR 3.54, 95% CI 2.97-4.22). Patients suffering from those haematologic malignancies were significantly younger in the clozapine treatment group than patients treated with other medicines (p < 0.001). The median time to onset (available for 212 cases) was 5.1 years (IQR 2.2-9.9) for malignant lymphoma and 2.5 years (IQR 0.6-7.4) for leukaemia. The aROR by quartile of dose of clozapine in patients with haematologic malignancies suggested a dose-dependent association. CONCLUSIONS: Clozapine was significantly associated with a pharmacovigilance signal of haematologic malignancies. The risk-benefit balance of clozapine should be carefully assessed in patients with risk factors of haematologic malignancies. Clozapine should be used at the lowest effective posology.

Quetiapine for delirium prophylaxis in high-risk critically ill patients.

BACKGROUND: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. METHODS: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. RESULTS: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). CONCLUSIONS: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Quetiapine treatment for cannabis use disorder.

BACKROUND: Pharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need. METHODS: In a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5-7 days), moderate use (2-4 days) and light use (0-1 days). RESULTS: At baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5-7.0; daily dollar value: median = $121.4; IQR: 73.8-206.3). The week-by-treatment interaction was marginally significant (χ2(2) = 5.56, P = .06). With each week, the odds of moderate compared to heavy use significantly increased in the quetiapine group (OR=1.17, P < .0001), but not significantly in the placebo group (OR=1.05, P = .16). The odds of light versus heavy use did not significantly differ over time (P = .12). Treatment was also associated with reduced cannabis withdrawal symptoms by 10.4% each week (95% CI: 8.9-11.8). No serious adverse events occurred during the study and no evidence of development of a movement disorder was detected. Adverse effects were not significantly different between the quetiapine and placebo treatment arms. CONCLUSIONS: The use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

Eficácia e segurança de Aripiprazol comparado a outros agentes potencializadores no tratamento de depressão refratária revisão rápida de evidências / Effectiveness and safety of Aripiprazole compared to other augmentative agents for treatment of resistant depression: rapid review of evidence

Tecnologia: Aripiprazol, antipsicóticos atípicos disponíveis no Sistema Único de Saúde, outras classes de potencializadores de tratamento depressivo. Indicação: Depressão refratária. Pergunta: Há diferenças de eficácia e segurança entre o Aripiprazol, Ziprasidona, Olanzapina, Quetiapina e Risperidona como agente potencializador do tratamento de depressão refratária? Há diferenças de eficácia e segurança entre as principais classes de drogas potencializadoras do tratamento de depressão refratária? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED, seguindo estratégias de buscas predefinidas. Foi feita a avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews version 2. Resultados: Foram selecionadas 3 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: Na potencialização do tratamento antidepressivo, o Aripiprazol, em dose padrão ou dose diária reduzida, não é superior à Quetiapina, Olanzapina/Fluoxetina ou Risperidona em desfechos de eficácia ou segurança para casos de depressão refratária com pelo menos uma falha terapêutica prévia. As diferentes classes de potencializadores de antidepressivos não diferem entre si nos desfechos de eficácia para casos de depressão refratária com duas ou mais falhas terapêuticas prévias. Ziprasidona e Quetiapina se mostraram mais eficazes que o placebo e seguros para promover remissão sintomática da depressão refratária

Technology: Aripiprazole, atypical antipsychotics available in the Brazilian Public Health System, other classes of augmentative antidepressant agent. Indication: Treatment-resistant depression (TRD). Question: Are there differences in efficacy and safety between Aripiprazole, Ziprasidone, Olanzapine, Quetiapine, and Risperidone as augmentative agent in the treatment of TRD? Are there differences in efficacy and safety between the main classes of augmentative drugs that enhance the treatment of TRD? Methods: A bibliographic survey was carried out in the PUBMED database, following predefined search strategies. The methodological quality of systematic reviews was assessed using the Assessing the Methodological Quality of Systematic Reviews version 2 tool. Results: 3 systematic reviews were selected that met the inclusion criteria. Conclusion: In potentiating antidepressant treatment, Aripiprazole, in standard dose or reduced daily dose, is not superior to Quetiapine, Olanzapine/fluoxetine or Risperidone in efficacy or safety outcomes for cases of TRD with at least one previous therapeutic failure. The different classes of antidepressant enhancers do not differ in efficacy outcomes for cases of TRD with two or more prior therapeutic failures. Ziprasidone and Quetiapine were more effective than placebo and safer for the outcome of symptomatic remission of TRD

Eficácia e segurança de Aripiprazol comparado aos antipsicóticos disponíveis no SUS para tratamento de Esquizofrenia em adultos: revisão rápida de evidências / Compared effectiveness and safety of Aripiprazol and antipsychotics available on Brazilian Public Health System for treatment of Schizophrenic adults: a rapid review of evidence

Tecnologia: Aripiprazol, antipsicóticos disponíveis no Sistema Único de Saúde (SUS). Indicação: Tratamento da esquizofrenia em adultos. Pergunta: O Aripiprazol é mais eficaz e seguro para promover controle sintomático, que os antipsicóticos disponíveis no SUS? Métodos: Levantamento bibliográfico foi realizado em bases de dados PUBMED, com estratégias estruturadas de busca, e a qualidade metodológica das revisões sistemáticas foi avaliada com a ferramenta AMSTAR II. Resultados: Foram identificados 109 resumos de revisões sistemáticas. Após leitura dos mesmos, foram selecionadas 2 revisões sistemáticas. Conclusão: Aripiprazol tem eficácia e segurança similar à Ziprasidona e Haloperidol, mas eficácia semelhante e maior segurança metabólica que a Quetiapina, Olanzapina, Clozapina e Risperidona. Ziprasidona apresenta vantagem sobre o Aripiprazol, pois tem menor risco de efeito colateral de mudanças na função sexual. Considerando que o perfil de eficácia e segurança do Aripiprazol é muito parecido com o dos outros antipsicóticos disponíveis no SUS, com mínimas diferenças, e seu custo de tratamento é inferior ao da Ziprasidona e Quetiapina, essa droga poderia estar disponível no SUS

Technology: Aripiprazole, antipsychotics available in the Brazilian Public Health System (BPHS). Indication: Treatment of schizophrenia in adults. Question: Is Aripiprazole more effective and safer to promote symptomatic control than antipsychotics available in BPHS? Methods: A bibliographic survey was carried out in PUBMED databases, with structured search strategies, and the methodological quality of systematic reviews was assessed using the AMSTAR II tool. Results: 109 abstracts of systematic reviews were identified. After reading them, 2 systematic reviews were selected. Conclusion: Aripiprazole has identical effectiveness and safety to Ziprasidone and Haloperidol, but similar efficacy and greater safety than Quetiapine, Olanzapine, Clozapine and Risperidone. Ziprasidone has an advantage over Aripiprazole as it has a lower risk of side effects of changes in sexual function. Since the Aripiprazole's effectiveness and safety profile is very similar to profile of others antipsychotics available in BPHS, with minimal differences, and it has cost lower than Ziprasidone and Quetiapine, this drug could be available in BPHS

Safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer: A large-scale multicenter prospective observational study in real-world palliative care settings.

OBJECTIVE: To clarify the safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer receiving palliative care. METHODS: This was a prospective observational study involving consecutive patients with advanced cancer and delirium receiving antipsychotics in inpatient hospices or psycho-oncology settings. Adjusted mean scores of the Delirium Rating Scale Revised-98 (DRS; range: 0-39) were calculated at baseline and Day 3 using generalized estimating equations. Adverse events over 7 days were evaluated. RESULTS: Data from 756 patients were analyzed (Mage = 72 ± 11 years, 62% male, 48% bedridden). The adjusted mean DRS score significantly decreased after antipsychotics administration (21.5 [95% confidence interval 19.5 to 23.4] to 20.8 [18.9 to 22.8], p = 0.03, effect size [ES] = 0.02). Significant improvement was associated with age of 75 or older (ES = 0.07), better performance status (0.32), longer estimated prognosis (0.25), psycho-oncological consultation settings (0.20), hyperactive (0.14) or mix-motor subtypes (0.24) of delirium, and quetiapine administration (0.19); significant deterioration was observed in patients with "days" prognosis (0.18). Extrapyramidal symptoms (9.8%) and somnolence (8.5%) were the most prevalent adverse events. CONCLUSIONS: The use of antipsychotics as part of comprehensive delirium management was safe and may provide some symptomatic benefits for patients with terminal illness and delirium. Along with adequate non-pharmacological interventions, judicious use of antipsychotics is still recommended.