Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study.

OBJECTIVE: Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. METHODS: The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. RESULTS: Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. CONCLUSIONS: In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.

Real-World Evidence of Antipsychotic Monotherapy Versus Polypharmacy in the Treatment of Schizophrenia Spectrum Disorders.

PURPOSE/BACKGROUND: It is still not well known whether antipsychotic monotherapy versus polypharmacy differs in terms of efficacy in the emergency department (ED) utilization, presentation with agitation/aggression, and rehospitalization in schizophrenia spectrum disorders (SSD) patients. This study aimed to determine the effectiveness of antipsychotic monotherapy and polypharmacy for these outcomes in the real world. METHODS/PROCEDURES: The study was conducted with electronic health records of 669 SSD patients admitted to the ED. Patients were evaluated in 4 groups according to antipsychotic use at the first admission to ED: antipsychotic noncompliance for more than 90 days, antipsychotic noncompliance for 15 to 90 days, antipsychotic monotherapy, and polypharmacy. All patients followed up for at least 1 year after index admission. The primary outcomes determined an association between antipsychotic monotherapy versus polypharmacy and all-cause psychiatric hospitalization between the groups after index admission in the SSD. FINDINGS/RESULTS: The groups, including patients with antipsychotic noncompliance, had higher ED visits, more hospitalizations, and more admissions with agitation/aggression compared with antipsychotic monotherapy or polypharmacy. However, no differences were found between monotherapy and polypharmacy groups regarding these outcomes. In addition, there was no difference in the risk of hospitalization in monotherapy antipsychotic users compared with polypharmacy users. Patients discharged with monotherapy or polypharmacy also had similar rehospitalization rates at follow-up. IMPLICATIONS/CONCLUSIONS: There is no positive evidence that recommending polypharmacy over antipsychotic monotherapy is superior with regard to the resulting frequency of ED visits, ED admissions with agitation/aggression, hospitalization, and rehospitalization. In this context, antipsychotic monotherapy may be preferred over polypharmacy in patients who are not resistant to treatment.

Facial emotion recognition is associated with executive functions and depression scores, but not staging of dementia, in mild-to-moderate Alzheimer's disease.

BACKGROUND: Although deficits in facial emotion recognition (FER) significantly affect interpersonal communication and social functioning, there is no consensus on how FER affects Alzheimer's disease (AD). In this study, we aimed to investigate the clinical and neuropsychological factors affecting the possible deficits in the FER abilities of patients with AD. METHODS: This cross-sectional study included 37 patients with mild [clinical dementia rating (CDR) scale score = 1] or moderate (CDR = 2) AD, in whom vascular dementia and depression were excluded, and 24 cognitively normal (CDR = 0) subjects. FER ability was determined using the facial emotion identification test (FEIT) and facial emotion discrimination test (FEDT). All participants underwent mini-mental state examination (MMSE), frontal assessment battery (FAB), and geriatric depression scale (GDS). The neuropsychiatric inventory-clinician rating scale (NPI-C), Katz index of independence in activities of daily living, and Lawton instrumental activities of daily living were also administered to patients with AD. RESULTS: The FEIT and FEDT total scores showed that patients with mild and moderate AD had significant FER deficits compared to healthy controls. However, no significant difference was observed between patients with mild and moderate AD in the FEIT and FEDT total scores. FEIT and FEDT scores were not correlated with the MMSE and NPI-C total and subscales scores in patients with AD. Linear regression indicated that FEIT and FEDT total scores were significantly related to age and FAB scores. The GDS score negatively moderated the relationship between FAB and FEDT. CONCLUSIONS: This study demonstrated a decreased FER ability in patients with AD. The critical point in FER deficits is the presence of dementia, not the dementia stage, in AD. It has been determined that executive functions and depression (even at a subsyndromal level), which have limited knowledge, are associated with FER abilities.

Successful treatment of severe alcohol withdrawal delirium with very high-dose diazepam (260-480 mg) administration.

INTRODUCTION: Alcohol withdrawal delirium, commonly known as "delirium tremens (DT)", is the most severe clinical condition of alcohol withdrawal syndrome (AWS). Symptoms of DT include changes in consciousness and cognitive and perceptual impairments that fluctuate during the day. Treatment includes general support, such as helping the patient to re-orientate, close monitoring of vital signs and adequate hydration, and symptomatic treatment for agitation, autonomic instability, and hallucinations. In symptomatic treatment of DT, benzodiazepines are most commonly preferred due to their GABA-ergic effects. Diazepam, a benzodiazepine, has a faster onset of action than other benzodiazepines when administered intravenously (iv) and effectively controls symptoms. Although low doses of diazepam usually relieve DT symptoms, very high doses may be required in some patients. This case series discusses patients receiving high doses of diazepam to relieve DT symptoms. CASE REPORT: Four male patients aged from 43 to 57 years who regularly consumed alcohol with a daily average of 20-100 standard drinks and developed DT afterwards and were followed up in the intensive care unit are presented. In these patients, the symptoms of DT were relieved, and somnolence was achieved with the administration of very high-dose IV diazepam (260-480 mg/day), contrary to routine treatment doses. All patients were successfully treated and discharged without any morbidity. CONCLUSION: Severe AWS can potentially result in death otherwise managed quickly and adequately. Diazepam is a suitable agent for severe AWS or DT treatment. Clinicians should keep in mind that high-dose diazepam treatment may be required in the treatment of DT that develops after a long-term and high amount of alcohol consumption. Publications reporting the need for very high doses of diazepam in DT are limited and usually published long ago; in this context, our findings are significant. The evidence is often based on case reports and uncontrolled studies, so controlled trials are needed to determine optimal treatment doses in severe DT.

Thiol-disulphide Homeostasis in Patients with Schizophrenia: The Potential Biomarkers of Oxidative Stress in Acute Exacerbation of Schizophrenia.

Objective: : Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. Methods: : Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global Impression-Severity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. Results: : After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. Conclusion: : These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.

Neutrophil/high-density lipoprotein cholesterol (HDL), monocyte/HDL and platelet/HDL ratios are increased in acute mania as markers of inflammation, even after controlling for confounding factors.

OBJECTIVE: Recent studies show that inflammation is related to the pathogenesis of acute mania of bipolar disorder. Neutrophil/high-density lipoprotein (HDL) ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR) and platelet/HDL ratio (PHR) have recently been investigated as novel markers of inflammation. In addition, the atherogenic index of plasma (AIP) and atherogenic coefficient (AC) are the leading atherogenic indices. The study aimed to investigate these inflammation and atherogenic index markers in acute mania of bipolar disorder. Another aim was to determine whether there is a relationship between these markers and disease severity and psychotic symptoms. METHODS: A total of 109 BD-M and 101 (HC) were enrolled in the study. The differences in NHR, LHR, MHR, PHR, AIP and AC and their association with illness severity and psychotic symptoms were analyzed after adjusting for age, sex, total cholesterol level, body-mass index and smoking status. Then, a receiver operating characteristic (ROC) curve and linear discriminant analysis (LDA) were used to analyze these parameters' diagnostic potential. Moreover, the Young Mania Rating Scale (YMRS) and Clinical Global Impression Scale for use in bipolar illness-Severity subscale (CGI-BP-S) were used to assess the severity of clinical symptoms. RESULTS: We found higher levels of NHR, MHR, PHR and AIP, but not LHR and AC, after adjusting confounding factors in patients with BD-M compared to HCs. In logistic regression analysis, higher levels of MHR and NHR were associated with BD-M. MHR, NHR and PHR were predictors for differentiating the BD-M group from the HC group. However, the severity of the illness or the psychotic feature of the manic episode did not significantly affect the parameters. In the ROC curve analysis of BD-M, the indicators with an area under the curve (AUC) higher than 0.6 were the MHR, NHR, PHR and LHR. CONCLUSIONS: These results provide information about the role of inflammation in the pathophysiology of BD-M. Even after controlling for confounding factors, MHR, NHR, PHR and AIP are potential biomarkers for BD-M. Moreover, the increase in AIP may explain the co-morbidity between BD and cardiovascular diseases. However, the severity of the illness or the psychotic feature of the manic episode did not significantly affect the levels of inflammation ratios used in our study. Due to the low cost and widespread use of lipid metabolism and related inflammation rates, it may be beneficial to know the MHR, NHR, PHR and AIP levels in BD-M patients.

Thiol-disulphide homeostasis, ischemia-modified albumin, complete blood count-derived inflammatory markers and C-reactive protein from acute mania to early remission in bipolar disorder.

OBJECTIVES: There is much recent evidence that inflammation contributes to the pathophysiology of acute mania in bipolar disorder (BD). However, no study was evaluated in which the change in thiol-disulphide homeostasis, ischemia-modified albumin (IMA), complete blood count-derived inflammatory markers (CBC-IMs) and C-reactive protein (CRP) levels in bipolar patients was followed-up from acute mania to early remission. METHODS: Seventy-seven bipolar patients in acute mania and ninety-one HC were enrolled. We measured levels of thiol-disulphide parameters, IMA, and CBC-IMs such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red-cell-distribution-width (RDW)-to-platelet ratio (RPR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI), CRP and platelet-to-albumin ratio (PAR), after adjusting for age, gender, body-mass index (BMI) and smoking status, during acute mania to subsequent early remission. The results were compared with HC. RESULTS: The levels or ratios of all thiol-disulphide parameters except for disulphide, IMA and CRP of bipolar patients in both acute mania and early remission were significantly different from HC, after adjusting for confounders. The NLR, SII, CRP and PAR values of bipolar patients were significantly higher in only acute mania compared to HC. Significant changes in thiol-disulphide parameters and IMA levels were not found in early remission after acute mania. LIMITATIONS: Short follow-up period and lack of drug-naive patients. CONCLUSIONS: Our results suggest that thiol-disulphide parameters, IMA level and SIRI value might be a trait biomarkers of inflammation in BD. In addition, NLR, SII and PAR values and CRP level might be a state biomarker of inflammation in bipolar patients in a manic phase.

Investigating the jumping to conclusion bias in bipolar disorder.

INTRODUCTION: Hemsley and Garety described the "jumping to conclusions bias" in which patients with delusions may reach unreasonable results with insufficient information. In this study patients with bipolar disorder and healthy volunteers were compared in terms of jumping to conclusions bias using the beads in the jar task. METHODS: 37 patients with DSM-5 diagnosis of bipolar disorder and 30 healthy controls were tested with the Beads Task (BT), Tower of London Test (ToL) and Barrat Impulsiveness Scale (BIS). RESULTS: In the BT, the mean score of DtD (draws to decision) and JTC (jumping to conclusions) scores were not statistically different between the two groups. In the ToL test, the duration of the total execution and the total time were significantly longer in the bipolar group than the control group. BIS scores were significantly higher in the bipolar group. YMRS (Young Mania Rating Scale) scores were not correlated with BT. CONCLUSIONS: This study is the first clinical study to assess the jumping to conclusions bias in patients with bipolar disorder. No JTC bias was detected in bipolar disorder. Further studies may assess JTC in larger samples to determine the effects of clinical state changes, psychotic symptoms, medication and impulsivity.