Manic Episodes In Patients Research Articles

Does Decreased Vitamin D Level Trigger Bipolar Manic Attacks?

Bipolar disorder is a chronic psychiatric disorder with depression and manic episodes. It is one of the leading causes of disease-related disability worldwide. Despite the presence of various alternative drug options for bipolar disorder, some patients do not adequately benefit from the treatment. Therefore, possible underlying mechanisms need to be clarified. Recently, studies on the relationship between bipolar disorder and vitamin D (Vit D) have attracted attention. Although many studies have found an association between depression and Vit D deficiency, little is known about the relationship between manic episodes and Vit D. The aim of this study was to compare Vit D and related metabolites of bipolar manic episodes prior to treatment, bipolar remission after treatment, and healthy control groups. This case-control study consisted of 34 bipolar manic episode patients and 34 healthy controls. Disease activity was evaluated with the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). Firstly, serum 25-hydroxy vitamin D (25-OHD), calcium (Ca) and phosphorus (P) levels of patients in the bipolar manic episode were measured and compared with healthy control. Secondly, serum 25-OHD, Ca and P levels in the euthymic periods of the same patients were measured and compared with healthy control. Bipolar manic episode Vit D levels were lower when compared to healthy controls; while there was no difference in terms of Ca and P levels. There was no significant difference between the bipolar euthymic period patients and the healthy control group in terms of 25-OHD, Ca and P levels. Our results demonstrated low serum Vit D concentrations in the acute manic episode of bipolar disorder. Decreased Vit D level may play a role in the onset of the manic episode, or malnutrition and insufficient sunlight during the manic episode may have caused Vit D deficiency. Future studies are needed to exclude potential confounding factors and to compare all mood episodes.

Neutrophil-Lymphocyte Ratio, Monocyte-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Manic Episode Patients with Bipolar Disorder

Objective: Inflammation is one of several etiopathological mechanisms contributing to bipolar disorder. Neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are relatively cheap hematological parameters recommended to measure the level of inflammation. In this study, the NLR, MLR, and PLR values of the same patients during manic and euthymic periods were compared to a healthy control group. Methods: This retrospective study was conducted on inpatients with bipolar disorder manic episodes at the University Faculty of Medicine psychiatry clinic. Ninety-nine patients with manic episodes of bipolar disorder and age and gender-matched 101 volunteers without prior psychiatric illness were included in the study. Neutrophil, lymphocyte, monocyte, and platelet counts during the disease period were recorded, and NLR, MLR, and PLR values were calculated from these values. Similar hematological parameters of the same patients in the euthymic period after discharge were compared. Results: Patients with manic episodes were shown to have significantly higher neutrophil, platelet, NLR, MLR, and PLR levels than the control group (p<0.001). Monocyte count was significantly lower in manic episode patients compared to controls (p<0.001). Neutrophil and monocyte counts were significantly lower during the euthymic period compared to the control group, while NLR, MLR, and PLR levels were higher (p<0.001). Conclusions: The fact that NLR, MLR, and PLR are higher in BD patients compared to the healthy control group in both manic and euthymic periods indicates that they can be used as trait biomarkers.

First-episode mania after COVID-19: A case series in Iran.

Increasing reports of manic episodes in patients during acute infection with COVID-19 have been documented since the pandemic began, including individuals without a previous personal or family history of bipolar disorder. As infections and autoimmunity have putative roles in bipolar disorder, we aimed to document the clinical presentations, associated stressors, family aggregation patterns, and brain imaging and electroencephalographic correlates with a series of patients with episodes of mania that emerged shortly after COVID-19 infections. We obtained all relevant clinical information from 12 patients whose first manic episode started within a month of COVID-19 infection and were treated at Rasool-e-Akram hospital and Iran psychiatric hospital, two tertiary medical centers in Tehran, Iran, in 2021. Patients had a mean age of 44. The interval between the onset of symptoms of COVID and mania ranged between 0 and 28 days (mean: 16.25, median: 14 days); it was observed to be shorter in patients with a family history of mood disorders but not in those receiving corticosteroids. Alongside a descriptive overview of our sample, we provide detailed narrative descriptions of two of the cases for illustrative purposes and discuss our observations in the context of other cases reported elsewhere and the state-of-the-art regarding infectious diseases, COVID-19, and bipolar disorder as reported in previous literature. Our case series documents observational and naturalistic evidence from a dozen of cases of mania in the context of acute COVID-19, which, while limited, calls for analytical research of the phenomenon, and points at a family history of bipolar disorder and the use of corticosteroids as factors for particular focus.

Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration

AimNeurofilament light chain protein (NEFL), is defined as a structural protein which exists particularly in axones of neurons and is released to the cerum in consequence of neuroaxonal damage. The aim of this study is to investigate the peripheral cerumNEFLlevels of children and adolescents with early onset schizophrenia and bipolar disorder. MethodIn this study, we evaluated serum levels of NEFL in children and adolescents (13–17 years) with schizophrenia, bipolar disorder and healthy control group. The study is conducted with 35 schizophrenia, 38 bipolar disorder manic episode patients and 40 healthy controls. ResultsThe median age of the patient and control groups was 16 (IQR- Interquartile Range: 2). There was no statistical difference in median age (p = 0.52) and gender distribution(p = 0.53) between groups. NEFL levels of the patients with schizophrenia were significantly higher than the controls. NEFL levels of the patients with bipolar disorder were significantly higher than the controls. Serum levels of NEFL of the schizophrenia were higher than the bipolar disorder; however, the difference was not statistically significant. ConclusionIn conclusion, serum NEFL level, as a confidential marker of neural damage, is increased in the children and adolescents with bipolar disorder and schizophrenia. This result may indicatea degenerative period in neurons of children and adolescents with schizophrenia or bipolar disorder and may play a role in the pathophisiology of these disorders. This result shows that there is neuronal damage in both diseases, but neuronal damage may be more in schizophrenia.

Effect of Hypertension on Blood Lithium Level and its Concentration to Dose Ratio in Manic Episode Patients

Effect of Hypertension on Blood Lithium Level and its Concentration to Dose Ratio in Manic Episode Patients

Comparative, Single-Dose, 2-Way Cross-Over Bioavailability Study of Two Olanzapine 10 Mg Tablet Formulations in Healthy Volunteers Under Fasting Conditions.

Objectives: Olanzapine is an atypical antipsychotic that is approved across Europe, the USA, and in many other countries for oral treatment of schizophrenia and acute manic episodes in patients with bipolar disorder as well as for maintenance therapy to prevent recurrence in responders. The objective of the present study was to compare the pharmacokinetics of two 10 mg tablet formulations of Olanzapine following a single oral dose in healthy volunteers under fasting conditions, as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. Methods: This study was a randomized, open-label, two-treatment, two-period, two-sequences, single-dose, cross-over design with a washout period of 14 days. Both the test and the reference products were administered as 10 mg tablets with 240 mL of water after an overnight fast in each study period. A total of twenty blood samples were collected before dosing and within 144 hours after drug administration. Adverse events were monitored, recorded, and evaluated by investigators throughout the study. Results: Of the 24 healthy adult male subjects enrolled, all of them completed both study periods. The geometric mean ratio 90% confidence intervals (CI) for fasting Cmax, AUC0-t, and AUC0-infinity were 94.83-113.71%, 95.04-105.69% and 95.94-107.00%, respectively. The 90% CI for the ratios of the three primary pharmacokinetic parameters (using log-transformed data) were within the range of 80-125%, meeting the regulatory criteria for bioequivalence. Conclusions: The generic Olanzapine was bioequivalent to the reference formulation. It was well tolerated and provides an acceptable alternative to the reference drug.

Effect of Probiotic Supplements on Oxidative Stress Biomarkers in First-Episode Bipolar Disorder Patients: A Randomized, Placebo-Controlled Trial.

Background: Currently no study has examined the effects of probiotic administration on the symptoms of anxiety, depression, and mania, as well as their correlations with the biomarkers of oxidative stress in patients with bipolar disorder (BPD). The aim of this study is to determine the effects of probiotic supplementation on plasma oxidative stress-related biomarkers and different domains of clinical symptom in patients suffering from BPD. Methods: Eighty first-episode drug-naive patients with BPD were recruited. The subjects were randomized to receive psychotropic drugs supplementing with either probiotic or placebo and scheduled to evaluate with follow-ups for clinical symptom improvements and changes in the oxidative stress biomarkers. The Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Young Mania Rating Scale were used to assess the clinical symptomatology. The panel of plasma oxidative stress biomarkers were determined by ultra-performance liquid chromatography–mass spectrometry (UPLC–MS/MS) at baseline and for 3 months of follow-up, i.e., at post-treatment month 1, 2, and 3. Results: After 3 months of intervention, decreased levels of plasma lysophosphatidylcholines (LPCs) were found in both placebo and probiotic groups. However, six other oxidative stress biomarkers (i.e., creatine, inosine, hypoxanthine, choline, uric acid, allantoic acid) increased in BPD patients after the two types of therapies. In addition, a positive correlation between changes of LPC (18:0) and YMRS scale was found in BPD patients and this association only existed in the probiotic group. Additionally, the mania symptom greatly alleviated (pretreatment–posttreatment, odds ratio = 0.09, 95%CI = 0.01, 0.64, p= 0.016) in patients who received probiotic supplements as compared with the placebo group. Conclusion: The changes in plasma biomarkers of oxidative stress in patients with BPD have a potential to be trait-like markers, and serve as prognostic indexes for bipolar patients. Daily intakes of probiotics have advantageous effects on BPD patients with certain clinical symptoms, especially manic symptoms. The treatment may be a promising adjunctive therapeutic strategy for BPD patients in manic episode.

Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in patients with affective disorders

ObjectiveThere is substantial evidence to support that the alterations in the immune-inflammation system play a crucial role in the pathogenic mechanism of affective disorders. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) have been recently investigated as simple, rapid, and inexpensive inflammation markers. The purpose of the research is to use large-scale clinical data to study the difference of the inflammation ratios in first-episode MDD, recurrent MDD, BD depressive episodes and manic episode. MethodsA cross-sectional design was applied to retrospectively analyse the data that were extracted from electronic health records. A total of 16,174 Chinese affective disorder patients were enrolled in this study, and 6681 healthy subjects served as controls. The differences in the NLR, MLR, PLR and whole blood count data among different groups were compared, and the contributing factors for the occurrence of MDD and BD were analysed. ResultsFirst-episode and recurrent MDD patients exhibited significantly elevated NLRs and MLRs compared to healthy controls. Compared with the MDD patients, the BD patients showed higher NLRs and MLRs and lower PLRs. Further analysis showed that the BD manic episode patients had significantly elevated NLRs and MLRs compared to patients with BD depressive episodes or MDD. MLR was a risk factor for the occurrence of MDD and that the NLR and MLR were risk factors for the occurrence of BD. ConclusionsOur study highlights the role of systemic inflammation in the pathophysiology of MDD and BD, particularly during manic BD episodes.

Speechreading as a secondary diagnostic tool in bipolar disorder

Speech perception used to be seen as a solely an auditory phenomenon until the discovery of the “McGurk Effect” and in recent decades it has come to be understood as a multimodal, specifically, an auditory-visual process. Behavioural studies have shown that the magnitude of auditory-visual integration shows differences across ages and languages. A new question regarding the integration of auditory and visual speech information pertains to the case of mental disorders – a domain in which a significant paucity of data exits. The available studies (e.g., schizophrenic patients) generally point out to lessened levels of integration on both behavioural and cortical levels in respective clinical populations. A recent study with bipolar disordered individuals has shown that while those in manic and depressive episodes give similar behavioural responses to McGurk stimuli revealing an integration of auditory and visual speech information similar to the control group. However, in a visual-only condition (i.e., lipreading), compared to the control group and manic episode patients, those in the depressive episode show very impoverished levels of lipreading. We hypothesize that, during depressive episode of bipolar patients, abnormal lipreading is associated with impaired occipito-temporal connections in the dominant hemisphere, which are compensated by early activation of anterior cingulate gyrus and IFG, either through dominant or non-dominant hemisphere pathways. This can relay the signal in reverse fashion to the multimodal procession areas like posterior superior temporal sulcus, hence allowing audiovisual integration. This finding calls for cortical imaging studies to unearth the physiological processes involved in both lipreading and auditory-visual speech processing in the bipolar disordered individuals. A full understanding of these processes will provide practitioners with secondary diagnostic tools and knowledge regarding this disorder.

P.0076 Evaluation of the staging after the first manic episode in patients with bipolar disorder

P.0076 Evaluation of the staging after the first manic episode in patients with bipolar disorder

Secondary Mania induced by TNF-α inhibitors: A systematic review.

A growing number of studies support a bidirectional relationship between inflammation and bipolar disorders. Tumor necrosis factor‐α (TNF‐α) inhibitors have recently attracted interest as potential therapeutic compounds for treating depressive symptoms, but the risk for triggering mood switches in patients with or without bipolar disorders remains controversial. Thus, we conducted a systematic review to study the anti‐TNF‐α medication‐induced manic or hypomanic episodes. PubMed, Scopus, Medline, and Embase databases were screened for a comprehensive literature search from inception until November 2020, using The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Out of the initial 75 references, the screening resulted in the inclusion of four case reports (each describing one patient) and a cohort study (in which 40 patients out of 7600–0.53% – experienced elated mood episodes after infliximab administration). Of these 44 patients, 97.7% experienced a manic episode and 2.3% hypomania. 93.2% of patients had no history of psychiatric disorder or psychotropic treatment. Only 6.8% had a history of psychiatric disorders with the affective spectrum (4.6% dysthymia and 2.3% bipolar disorder). The time of onset of manic or hypomanic symptoms varied across TNF‐α inhibitors with an early onset for Infliximab and a later onset for Adalimumab and Etanercept. These findings suggest that medications targeting the TNF‐α pathway may trigger a manic episode in patients with or without affective disorders. However, prospective studies are needed to evaluate the relative risk of such side effects and identify the population susceptible to secondary mania.

Pontine hemorrhage as beginning of bipolar disorder or organic mania. A case report

IntroductionPublished evidence describes the appearance of manic episodes in patients who suffer localized brain lesions with no prior psychiatric history.ObjectivesA case report is presented alongside a review of the relevant literature regarding the relationship between Bipolar disorder and strokes.MethodsWe present the case of a 54-year-old man who, after suffering a pontine hemorrhage, developed a depressive mood for which he was treated with Sertraline 50 mg. The following month the patient developed hypomanic mood, disinhibition, insomnia and megalomaniac ideation. He was treated with Risperidone 2 mg and the antidepressant was withdrawn. The symptomology disappeared shortly after but a few months later he developed a major depressive disorder (inhibition, ideas of ruin and guilt, low mood, decreased intake and daily activities…). He was treated again with antidepressants (Citalopram 30mg) and lithium was introduced in the absence of a total response.ResultsMania secondary to brain lesions has been observed in multiple studies, where an association is made mainly with lesions at the frontal, temporal, subcortical limbic brain areas and in lesions causing hypofunctionality on the right side. Most of the cases described occurred in male patients with no prior psychiatric record and with associated vascular risk.ConclusionsIt is important to carry out an exhaustive medical history to be able to identify the cases of secondary mania so as not to ignore the underlying neurological condition in the approach.DisclosureNo significant relationships.

Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte and Monocyte-to-Lymphocyte Ratio in Bipolar Disorder.

Background: Several inflammatory hypotheses have been suggested to explain the etiopathogenesis of bipolar disorder (BD) and its different phases. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios have been proposed as potential peripheral biomarkers of mood episodes. Methods: We recruited 294 patients affected by BD, of which 143 were experiencing a (hypo)manic episode and 151 were in a depressive phase. A blood sample was drawn to perform a complete blood count. NLR, PLR, and MLR were subsequently calculated. A t-test was performed to evaluate differences in blood cell counts between depressed and (hypo)manic patients and a regression model was then computed. Results: Mean values of neutrophils, platelets, mean platelet volume, NLR, PLR, and MLR were significantly higher in (hypo)manic than depressed individuals. Logistic regression showed that PLR may represent an independent predictor of (hypo)mania. Conclusions: Altered inflammatory indexes, particularly PLR, may explain the onset and recurrence of (hypo)manic episodes in patients with BD. As inflammatory ratios represent economical and accessible markers of inflammation, further studies should be implemented to better elucidate their role as peripheral biomarkers of BD mood episodes.

Effects of Lithium Combined with Second-Generation Antipsychotics for the Treatment of Manic Episodes in Patients with Bipolar Disorder: A Naturalistic Study in China.

ObjectiveTo explore the therapeutic effects of lithium combined with second-generation antipsychotics (SGAs) of quetiapine, clozapine, olanzapine, and risperidone for the treatment of manic episodes in patients with bipolar disorder (BD) to guide the selection of medications.MethodsWe examined the case data of patients with BD who experienced manic episodes and were hospitalized in a Class 3A Psychiatric Hospital in Anhui Province from January 2015 to October 2019. The enrolled patients were rated using the Bech–Rafaelsen Mania Rating Scale (BRMS) before and after treatment, and relevant adverse effects were monitored.ResultsAnalysis of the collected case data of 182 patients showed significant differences in the BRMS scores on admission and at discharge of patients treated with lithium combined with each SGA. The chi-square test showed no obvious difference in the final therapeutic effects of lithium combined with each of the four SGAs (χ2 = 7.365, P = 0.146). However, there were differences in the incidence of adverse effects (χ2 = 10.604, P = 0.014) and remission rate after 2 weeks of treatment (χ2 = 10.174, P = 0.017). Logistic regression analysis revealed that the incidence of adverse effects was related to the length of stay in hospital and clozapine treatment. The remission rate after 2 weeks was associated with the length of stay in hospital, clozapine treatment, and age of onset.ConclusionLithium combined with SGAs (quetiapine, clozapine, olanzapine, and risperidone) effectively improves the manic symptoms of patients with BD who experience manic episodes. Lithium combined with quetiapine for the treatment of bipolar manic episode has advantages with respect to the speed of effective and incidence of adverse effects.

Psychiatric Adverse Events Associated With Infliximab: A Cohort Study From the French Nationwide Discharge Abstract Database.

IntroductionInfliximab (IFX) was the first anti-tumor necrosis factor (TNFα) antibody to be used in the treatment of severe chronic inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis. A number of serious adverse drug reactions are known to be associated with IFX use; they include infections, malignancies, and injection site reactions. Although a few case reports have described potential psychiatric adverse events (including suicide attempts and manic episodes), the latter are barely mentioned in IFX’s summary of product characteristics. The objective of the present retrospective study was to detect potential psychiatric adverse events associated with IFX treatment by analyzing a national discharge abstract database.Materials and MethodsWe performed an historical cohort study by analyzing data from the French national hospital discharge abstract database (PMSI) between 2008 and 2014. All patients admitted with one of the five diseases treated with IFX were included.ResultsOf the 325,319 patients included in the study, 7,600 had been treated with IFX. The proportion of hospital admissions for one or more psychiatric events was higher among IFX-exposed patients (750 out of 7,600; 9.87%) than among non-exposed patients (17,456 out of 317,719; 5.49%). After taking account of potential confounders in the cohort as a whole, a semi-parametric Cox regression analysis gave an overall hazard ratio (HR) [95% confidence interval] (CI) of 4.5 [3.95; 5.13] for a hospital admission with a psychiatric adverse event during treatment with IFX. The HR (95%CI) for a depressive disorder was 4.97 (7.35; 6.68). Even higher risks were observed for certain pairs of adverse events and underlying pathologies: psychotic disorders in patients treated for ulcerative colitis (HR = 5.43 [2.01; 14.6]), manic episodes in patients treated for severe psoriasis (HR = 12.6 [4.65; 34.2]), and suicide attempts in patients treated for rheumatoid arthritis (HR = 4.45 [1.11; 17.9]).DiscussionThe present retrospective, observational study confirmed that IFX treatment is associated with an elevated risk of psychiatric adverse events. Depending on the disease treated, physicians should be aware of these potential adverse events.

Efficacy of melatonin as an adjunct in the treatment of acute mania: a double-blind and placebo-controlled trial

This is a double-blind, placebo-controlled, parallel-grouped clinical trial, which was designed to investigate the potential effects of melatonin add-on treatment with lithium and risperidone on acute manic episodes in patients with bipolar disorder (BD). A total of 54 patients were included and randomly assigned into two groups of melatonin and placebo. The trial group received 3 mg/day risperidone, 900 mg/day lithium, and 6 mg/day melatonin. The placebo group received the same dose of risperidone and lithium plus placebo. The participants were evaluated at four sessions, consisting of baseline, weeks 1, 4, and 6. The manic symptoms and overall clinical improvement of the patients were assessed using the Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Improvement (CGI-I), respectively. Two trial groups were matched based on all baseline characteristics. The patients in two trial groups had comparable serum lithium levels at weeks 1, 4, and 6. Our results from the general linear model repeated measures analysis showed a significant effect for time × treatment interaction on YMRS scores (P = 0.021 and F-value = 3.7). Furthermore, outcomes of the CGI-I rating scale demonstrated that patients in the melatonin group had better clinical improvements compared to the placebo group (P = 0.018). Our results provided preliminary evidence supporting melatonin as an effective adjunctive treatment leading to significant improvements in manic symptoms and overall clinical status in acute episodes of mania.

Cognitive flexibility and problem-solving in patients with bipolar disorder

Introduction: This study focuses on the cognitive impairment in patients with bipolar disorder and also the distribution of cognitive flexibility and problem-solving by degree of education, chronicity, and episode of patient is in at the time of evaluation.Methods: This was a cross sectional descriptive study with purposive sampling method. The population was the Harmony in Diversity Group in Surabaya, Indonesia. Twenty-two patients agreed to be subjects and each of them finished the Wisconsin Card Sorting Test (WCST) to measure cognitive flexibility and the Tower of London (TOL) to measure problem-solving. Results: The WCST score are below normal for 90.9% of the patients. Higher cognitive flexibility is found in patients with bachelor’s degree and euthymic patients, while lower cognitive flexibility is found in patients in depression episode, manic episode, and mixed episode. No patients could finish the TOL within the minimum required steps. Better problem-solving is found in patients in manic episode and euthymic patients while lower problem-solving is found in mixed episode and depressive episode.Conclusion: The cognitive flexibility and problem-solving in patients with bipolar disorder are lower than the normal cut off. The type of episode and chronicity are contributing factors. Euthymic patients tend to have better cognitive flexibility and manic patients tend to have better problem-solving ability.

SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR AMONG MANIC AND EUTHYMIC PATIENTS WITH BIPOLAR DISORDER TYPE I .

Background: Bipolar disorders (BD) have been accompanied with disturbances in neuroplasticity. Brain-de‌rived neurotrophic factor (BDNF) plays important role in neuroplasticity. It plays a vital role in the neurobiology of such disorders.Objectives: This study aimed to check BDNF serum levels in euthymic BD type I patients and correlate them with the clinical manifestations.Methods: Forty-eight Egyptian individuals were included in this study. They were arranged in three groups: The first one ‘G-A’ included twelve patients diagnosed with bipolar I disorder in manic episode; while the second ‘G-B’ consisted of twelve patients diagnosed with bipolar I disorder in full remission, and the third group ‘G-C’ consisted of 24 healthy persons as control subjects. The cases were diagnosed according to DSM-5 and psychometric analysis. The BDNF levels were assessed using the technique of quantitative sandwich enzyme immunoassay.Results: There was no statistical significant difference between the studied groups as regard demographic characteristics. Serum BDNF levels were lower in bipolar I patients in manic episode compared with those in euthymic state and also control subjects.Conclusion: patients with manic episode of bipolar I disorder have lower serum BDNF levels compared with those with euthymic state and control group.

Effect of Rivastigmine (Acetyl Cholinesterase Inhibitor) versus Placebo on Manic Episodes in Patients with Bipolar Disorders: Results from a Double Blind, Randomized, Placebo-Controlled Clinical Trial

Background: To treat patients with bipolar disorders (BPD) during the acute phase, the standard procedure is to administer lithium or sodium valproate. To further optimize treatment, acetylcholinesterase inhibitors such as donepezil and galantamine have gained increased interest, though with conflicting results. In the present randomized, double-blind, placebo-controlled clinical trial, we investigated whether, and to what extent, adjuvant rivastigmine might improve symptoms of mania in patients with BPD during the acute manic phase. Methods: A total of 70 patients with BPD in an acute state of mania (mean age 33.8 years; 24% females) took part in this study. After a thorough clinical interview, standard treatment consisted of 20mg/kg/day of sodium valproate; next, patients were randomly assigned either to the adjuvant rivastigmine or to the placebo condition. The study duration was 24 days. The dose of rivastigmine was 1.5 mg for the first 7 days and 3 mg from day 8 to day 24. Experts blind to the patients’ study condition rated patients’ mania scores, symptom severity, and symptom improvements at baseline (except symptom improvements) and 4, 8, 12, and 24 days after the beginning of this study. Results: Symptoms of mania improved over time, but more so in the adjuvant rivastigmine compared to the placebo condition. Greater improvements were observed from day 8 on. Conclusions: The pattern of results from the present randomized, placebo-controlled, double-blind study suggests that adjuvant rivastigmine, a cholinesterase inhibitor, improved symptoms of mania among a larger sample of inpatients with BPD and in the acute manic state. However, the improvements were modest, and the results should be replicated and above all balanced against side effects.

Clinical Characteristics and Psychotropic Drug Prescription Patterns of Bipolar Disorder Patients with a History of Suicidal Attempts: Findings from the REAP-BD, Korea.

Our study aimed to analyze the clinical characteristics and psychotropic prescription patterns of a history of suicide attempts in South Koreans with bipolar disorder (BD), by using only Korean data from the Research on Asian Psychotropic Prescription Pattern for Bipolar disorder. The patterns of clinical characteristics and psychotropic drug use were compared among 53 patients with a history of suicide attempts and 297 without this history; the potential effects of confounding variables were adjusted with binary logistic analyses for discrete variables and analyses of covariance for continuous variables. After adjusting the effects of age, sex, duration of illness, and enrollment as an outpatient, patients with a history of suicide attempts were characterized by a significantly more prevalent depressive episode, lower prevalent remission state, lower levels of hemoglobin, and more use of antidepressants, anxiolytics, and hypnotics compared to those without lifetime suicide attempt. The inability to plan goal-directed behavior may be an intervening factor in the relationship between suicide attempts and depression in BD. Relatively low hemoglobin levels can be associated with manic episodes in patients with a history of suicide attempts and the use of antidepressants, anxiolytics, or hypnotics can be associated with suicide attempts in BD patients.