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World Psychiatry : Official Journal of... Jun 2024Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative...
Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.
Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.
PubMed: 38727044
DOI: 10.1002/wps.21205 -
Behavioural Brain Research Jun 2024Chronic unpredictable mild stress (CUMS) method has been introduced as a rodent model of depression. On the other hand, olanzapine, as an antipsychotic, can induce...
The effect of olanzapine on spatial memory impairment, depressive-like behavior, pain perception, and BDNF and synaptophysin expression following childhood chronic unpredictable mild stress in adult male and female rats.
Chronic unpredictable mild stress (CUMS) method has been introduced as a rodent model of depression. On the other hand, olanzapine, as an antipsychotic, can induce antidepressant and antipsychotic effects. Also, olanzapine may improve cognitive functions. Both CUMS and olanzapine can also affect the expression level of brain-derived neurotrophic factor (BDNF) and synaptophysin, the molecular factors involved in synaptic function, and learning and memory. In this study, we investigated the effect of olanzapine on locomotor activity (using open field test), pain threshold (using hot plate), depressive-like behavior (using forced swim test), spatial learning and memory (using Morris water maze), and BDNF and synaptophysin hippocampal expression (using real-time PCR) in both male and female CUMS rats. CUMS was performed for three consecutive weeks. Olanzapine was also injected intraperitoneally at the dose of 5 mg/kg. Our data showed that olanzapine can reverse the effects of CUMS on behavioral functions and BDNF and synaptophysin expression levels in the hippocampus of both males and females. It was also shown that olanzapine effects on spatial memory, pain perception, and BDNF and synaptophysin level were stronger in females than males. In conclusion, we suggested that the therapeutic effects of olanzapine in CUMS rats may be closely related to the function of BDNF and synaptophysin. Also, the therapeutic effects of olanzapine may be stronger in females. Therefore, and for the first time, we showed that there may be a sex difference in the effects of olanzapine on behavioral and molecular changes following CUMS.
Topics: Animals; Female; Male; Rats; Antipsychotic Agents; Behavior, Animal; Brain-Derived Neurotrophic Factor; Depression; Disease Models, Animal; Hippocampus; Memory Disorders; Olanzapine; Pain Perception; Spatial Memory; Stress, Psychological; Synaptophysin; Rats, Wistar
PubMed: 38718877
DOI: 10.1016/j.bbr.2024.115039 -
CNS Drugs Jul 2024Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability.
METHODS
This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters.
RESULTS
There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reported weight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or other laboratory indicators were found.
CONCLUSIONS
While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia.
Topics: Humans; Antipsychotic Agents; Male; Female; Schizophrenia; Adult; Double-Blind Method; Sex Characteristics; Middle Aged; Treatment Outcome; Psychiatric Status Rating Scales; Young Adult; Medication Adherence; Sex Factors
PubMed: 38713452
DOI: 10.1007/s40263-024-01089-w -
Cureus Apr 2024Drug-induced lung injury (DILI) occurs when exposure to a drug leads to inflammation and, eventually, fibrosis of the lung interstitium. While DILI is a rare side effect...
Drug-induced lung injury (DILI) occurs when exposure to a drug leads to inflammation and, eventually, fibrosis of the lung interstitium. While DILI is a rare side effect of antipsychotic medication, once it manifests, it requires detailed investigation and prompt treatment. Diagnosing DILI can be challenging at times due to its similarity to conditions such as infectious diseases or interstitial pneumonia induced by other causes. We hereby report a fatal case of suspected DILI associated with olanzapine. A 61-year-old female with a history of delusional disorder was admitted to our hospital due to worsened psychiatric symptoms. Ten milligrams of olanzapine had been initiated a week prior to admission by a psychiatrist at the local clinic to control these symptoms. After admission, although the patient claimed no respiratory symptoms, she developed a slight fever and deterioration of chest radiologic findings. Bronchoalveolar lavage revealed a progressively bloody return of fluid, suggesting pulmonary alveolar hemorrhage. Since no respiratory disorders have been noted, and considering the exclusion of other potential diagnoses, DILI was strongly suspected. Although olanzapine was promptly discontinued, the patient's condition rapidly deteriorated. Despite high-dose steroid therapy, the patient's response to treatment was inadequate, and she finally succumbed to the illness. This case highlights that olanzapine may induce lung injury similar to other psychiatric drugs. Furthermore, early diagnosis and treatment are essential for patients with psychiatric disorders who may sometimes present with fewer symptoms.
PubMed: 38707165
DOI: 10.7759/cureus.57571 -
Journal of Hazardous Materials Jul 2024The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments....
The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 μg/L) and RIS (0.03 and 3 μg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.
Topics: Animals; Carps; Gastrointestinal Microbiome; Antipsychotic Agents; Behavior, Animal; Risperidone; Water Pollutants, Chemical; Olanzapine; Brain-Gut Axis; Swimming; Social Behavior
PubMed: 38701724
DOI: 10.1016/j.jhazmat.2024.134444 -
Medicine May 2024This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of intraoperative dexmedetomidine on postoperative delirium and pro-inflammatory cytokine levels in elderly patients undergoing thoracolumbar compression fracture surgery: A prospective, randomized, placebo-controlled clinical trial.
BACKGROUND
This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients undergoing thoracolumbar compression fracture surgery.
METHODS
In this randomized, double-blind, placebo-controlled trial conducted from October 2022 to January 2023 at Anting Hospital in Shanghai, 218 elderly patients were randomized into DEX (n = 110) and normal saline (NS, n = 108) groups. The DEX group received 0.5 µg/kg/h DEX, and delirium incidence was assessed using the Confusion Assessment Method (CAM) on days 1 to 3 post-surgery. Levels of interleukins IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured pre-operation (T0) and on postoperative days 1 (T1) and 3 (T3). Preoperative (T0) and postoperative day 1 (T1) cerebrospinal fluid (CSF) samples were treated with varying concentrations of olanzapine or DEX to observe their regulatory effects on the expression of Phospho-ERK1/2 and Phospho-JNK.
RESULTS
Dexmedetomidine significantly lowered the incidence of POD to 18.2%, compared to 30.6% in the NS group (P = .033). While all patients showed an initial increase in cytokine levels after surgery, by T3, IL-6 and TNF-α levels notably decreased in the DEX group, with no significant change in IL-1β levels across groups. The adverse events rate was similar between groups, demonstrating the safety of DEX in this population. In postoperative CSF samples, treatment with 0.5 mM DEX significantly downregulated Phospho-JNK and upregulated Phospho-ERK1/2 expression, demonstrating a dose-dependent modulation of inflammatory responses.
CONCLUSION
Dexmedetomidine is effective in reducing early POD in elderly patients post-thoracolumbar compression fracture surgery. It also decreases IL-6 and TNF-α levels, indicating its potential in managing postoperative inflammatory responses. Treatment with 0.5 mM DEX significantly modulated Phospho-ERK1/2 and Phospho-JNK expressions in postoperative CSF samples, indicating a dose-dependent effect on reducing inflammation. This study contributes to understanding DEX's role in improving postoperative outcomes in elderly patients.
Topics: Humans; Dexmedetomidine; Female; Male; Double-Blind Method; Aged; Cytokines; Fractures, Compression; Thoracic Vertebrae; Prospective Studies; Postoperative Complications; Lumbar Vertebrae; Spinal Fractures; Delirium; Intraoperative Care; Middle Aged
PubMed: 38701286
DOI: 10.1097/MD.0000000000037931 -
Indian Journal of Psychological Medicine May 2024
PubMed: 38699762
DOI: 10.1177/02537176231222566 -
The Lancet. Oncology May 2024
Topics: Humans; Olanzapine; Nausea; Vomiting; Antiemetics; Antineoplastic Agents; Benzodiazepines
PubMed: 38697160
DOI: 10.1016/S1470-2045(24)00195-5 -
The Lancet. Oncology May 2024
Topics: Humans; Antiemetics; Antineoplastic Agents; Benzodiazepines; Nausea; Olanzapine; Treatment Outcome; Vomiting
PubMed: 38697159
DOI: 10.1016/S1470-2045(24)00092-5 -
The Lancet. Oncology May 2024
Topics: Humans; Antiemetics; Antineoplastic Agents; Benzodiazepines; Nausea; Olanzapine; Treatment Outcome; Vomiting
PubMed: 38697158
DOI: 10.1016/S1470-2045(24)00129-3