Acute Manic States Research Articles

Acute manic state with psychotic features in a teenager with autoimmune encephalitis: a case report

IntroductionAutoimmune disorders have become increasingly acknowledged as having a more causative role in encephalitis than previously assumed. Anti-N-methyl-d-aspartate receptor encephalitis seems to be the most prevalent disorder. Symptoms of the neuropsychiatric phase in children and adolescents include abnormal behavior, seizures, and neurologic symptoms. We present a report on a teenage girl with predominantly psychiatric symptoms, highlighting the need for awareness of the disease and multidisciplinary collaboration.Case presentationOur patient, a 17-year-old girl of Middle Eastern origin, had no earlier medical history, but a family history of autoimmune disease. One morning, she could not recognize her mother and soon developed increased energy and pressured speech. The condition worsened, with paranoid delusions. In the emergency unit, she ran around speaking incoherently. The condition was interpreted as a full-scale mania. After pediatric clearance, the patient was admitted to the Department of Child and Adolescent Psychiatry. Mood-stabilizing treatment was initiated with second-generation psychotics and lithium, but this brought no improvement. A multidisciplinary discussion was held with physicians from psychiatry and neurology. A lumbar puncture showed N-methyl-d-aspartate receptor antibodies, and autoimmune treatment was initiated. Computed tomography thorax/abdomen revealed a right-sided ovarian tumor. After salpingo-oophorectomy, our patient’s mental status gradually improved, as demonstrated by repeated testing. Seven months post discharge she was in a stable relationship and performing well in school.ConclusionThis case underlines the importance of collaboration between child and adolescent psychiatry and pediatrics, and gives pointers for timely diagnosis. Manic adolescents who do not respond to mood-stabilizing treatment should be subjected to further consultations and investigations. Psychiatrists and neurologists should develop an integrated approach to the management of brain disorders.

The Mania Pathway Protocol: An Application of Evidence-Based Interventions for the Treatment of Acute Mania on an Inpatient Psychiatric Unit.

Acute manic episodes are a psychiatric emergency related to violence and poor patient outcomes. Combination psychotropic therapy utilizing a mood stabilizer and an atypical antipsychotic has been shown to be more efficacious for treating acute mania compared to monotherapy with either mood stabilizers or antipsychotics alone. This quality improvement project implemented evidence-based interventions for treating acute mania. The mania pathway protocol was created as a comprehensive clinical guide for guiding mania treatment. The protocol was implemented on an inpatient psychiatric unit for patients with mania diagnoses including manic/mixed episodes of bipolar disorder or schizoaffective disorder. (1) to improve the treatment of mania by using evidence-based interventions for rapid mood stabilization and (2) to educate psychiatric providers on up-to-date interventions for treating acute manic states. Psychiatric providers were evaluated for knowledge enhancement through a pre-/post-educational session quiz. A retrospective chart review was used for data collection for patients treated with the mania pathway protocol. The retrospective chart review spanned 8 weeks post project implementation. Young Mania Rating Scale (YMRS) scores were analyzed to measure the effect on mania severity. The percentage decrease in mean Young Mania Rating Scale scores from admission to the fifth day of hospitalization was 61%. All psychiatric providers proved knowledge attainment by scoring 100% on the postintervention quiz. Rapid mood stabilization may be achieved by using a combination therapy-based mania protocol. Educational sessions can enhance psychiatric provider knowledge with regard to evidence-based treatments for mania.

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.

M22 - GENOME-WIDE METHYLOME AND TRANSCRIPTOME PROFILES OF MANIC EPISODE IN BIPOLAR DISORDER

Background Bipolar Disorder (BD) is a highly heritable psychiatric disorder. More than two thirds of BD patients have recurrent episodes throughout lifetime. To explore the underlying biological mechanisms of manic episode in BD, the current study adopted two experimental platforms to capture the episodic dynamic feature. We compared the differences of methylome and transcriptome between acute manic episode and remission, which were influenced by both inheritant genetic sequence and environmental stimuli. Methods We enrolled 12 BD patients with collected biological samples and clinical data at two time points, the acute manic state and remission in at least two-months follow-up for intra-individual comparisons. Young Mania Rating Scale (YMRS) score and Hamilton Depression Rating Scale (HAMD-21) were used to evaluate symptom severity. The manic state was defined as having YMRS score ≥21 and HAM-D ≤8; the remission was defined as having YMRS score Results The average reads number for RRBS and RNA-Seq were 38 and 30 millions, respectively. No significant global methylation changes were found across the whole-genome with adjustment of multiple testing, while 337 DMGs had nominal p-values Discussion With comprehensive genomic data obtained by high-throughput technologies at the genome-wide level, we identify potential biomarkers underlying BD manic state. The overlapping results of DEGs and DMGs are relevant to transcriptional regulation, such as PAX8 and FOXD2. Their functions are found to be related to mitochondrial dysfunction and brain development through transcriptional regulation. Further experimental studies are needed to validate these results. In conclusion, methylomic and transcriptomic biomarkers are identified for regulating BD manic episode, which could provide novel insights for the pathogenesis of manic illness, and facilitating to allocate better therapeutic targets for BD.

State-dependent alterations of lipid profiles in patients with bipolar disorder.

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p < 0.025). The lowest rate of dyslipidemia (hypertriglyceridemia or low high-density lipoprotein cholesterol) was observed in acute bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

TTe Sun, the Moon and the Mood: Seasonal Associations Between the Lunar Cycle and Acute Manic States.

Introduction The belief that specific stages of the lunar cycle are related to human biology or behaviour has been present in popular culture since antiquity. Based on folklore or on clinical experience, several studies investigating possible links between the lunar cycle and mental illness were performed, with controversial results. To date, according to our knowledge, no study has yet considered a possible variability of the relationship with the seasons. Objectives/Aims Our study aims to explore the relationship between the lunar cycle and acute manic states in bipolar patients, including a differentiation by seasons. Methods We designed an exploratory study, retrospectively analysing admissions of manic episodes over the period 2007/2013. Admission dates and dates of last symptomatic worsening were separated into seasons and then distributed into one of four quarters of the moon's synodic cycle. The last symptomatic worsening dates were obtained using information from admission notes, being considered whenever mentioned accurately and within no more than one week of admission. Results Concerning the Autumn/Winter (n=221), we found a statistically significant disparity in the distribution of cases by lunar quarters in the admission dates of manic episodes (p=0.038), especially in episodes with psychotic symptoms (n=196; p=0.018), and in the last symptomatic worsening of manic episodes (n=60; p Conclusions The lunar cycle appears to be strongly associated with acute manic states in bipolar patients, but the association seems determined by the season. Further studies are needed to corroborate or refute these results.

Management of Bipolar Disorder in Children and Adolescents

Treatment options for bipolar disorder have been primarily studied in adults. However, there is a growing body of research of these treatments in youths with bipolar disorder. Despite this there is still a huge gap in clinical trials performed on adults and children and as this manuscript will show, extrapolating results of adult studies doesn't necessarily translate to successful treatment in youths. Furthermore, although medication is the cornerstone of treatment in children and adolescents with bipolar disorder, psychosocial interventions are of paramount importance. The current manuscript will review the empirical evidence available for both pharmacological and psychosocial treatment strategies. In addition, evidence for the use of medications in different stages of bipolar disorder, including acute manic and mixed states and bipolar depression is addressed. The use of combination therapy, the treatment of pediatric bipolar disorder comorbid with other psychiatric conditions and the management of treatment resistant mania is also discussed.

Contrasting and convergent patterns of amygdala connectivity in mania and depression: A resting-state study

BackgroundwMania and depression in bipolar disorder (BP) manifest two extremes of aberrant emotional, physiologic and behavioral arousal states despite similarities in treatment response and neurocognitive deficits. We used resting-state functional magnetic resonance imaging (rsfMRI) to explore the common and unique abnormal functional connectivity underlying acute manic or depressed state in BP. Methods18 Patients with bipolar mania (BM), 10 patients with bipolar depression (BD) and 28 healthy controls underwent resting-state functional magnetic resonance imaging scanning. Left and right amygdala seed-to-voxel based functional connectivity were assessed and compared among the three groups. The relationships between aberrant functional connectivity and the severity of clinical symptoms, number of episodes, illness duration were investigated. ResultsCompared to healthy controls, both BM and BD groups showed reduced functional connectivity between bilateral amygdala and inferior frontal gyrus (orbital), striatum, right lingual gyrus and posterior cerebellar lobe. Furthermore right amygdala–hippocampal connectivity was decreased in BD but increased in BM. No significant correlations were found between strength of abnormal functional connectivity and clinical characteristic in BD or BM. LimitationsNo euthymic subjects were recruited, and the patients in current study were all on medication. ConclusionsThe presence of substantial overlap in the pattern of disturbed connectivity between amygdala and frontal, striatal, lingual and cerebellar regions suggests mood state-independent dysconnectivity. The contrasting pattern of functional connectivity between right amygdala and hippocampus in BD and BM provides a novel lead to the probable mechanistic differences in these two extremes of mood states.

Decreased plasma levels of brain-derived neurotrophic factor (BDNF) during mixed episodes of bipolar disorder

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and neuroplasticity. Decreased blood levels of BDNF have been found during acute manic and depressive states. BDNF has been proposed as a biomarker in illness phases of mood disorders. No information is available regarding BDNF levels during the mixed states of bipolar disorder (BD). The aim of this study was to evaluate BDNF levels during mixed episodes of BD patients and compare them with those of healthy subjects and depressed patients. MethodsPlasma BDNF levels were measured by an ELISA assay in 18 patients with major depressive episode (MDE), 19 patients with mixed episode (ME) and 15 healthy subjects (HS). ResultsBDNF levels were significantly higher in HS, as compared with patients׳ samples (HS vs. MDE patients: p<001; HS vs. ME patients: p=.022). No significant differences were found between BDNF levels of ME and MDE patients. The severity of illness as assessed by CGI-S was significantly higher in ME than in MDE patients (p=.01). LimitationsThe small sample size may have weakened the power of statistical analyses. All patients received mood-stabilizing and antidepressant treatments which have been reported to influence peripheral BDNF levels. ConclusionsOur results are consistent with previous studies showing reduced BDNF during both manic and depressive episodes. This finding supports the role of BDNF as a state-marker of mood episodes, and may represent a contribution to a unitary approach model between unipolar and BDs, as well as to the manic-depressive spectrum model.

Oral Loading of Sodium Valproate Compared to Intravenous Loading and Oral Maintenance in Acutely Manic Bipolar Patients

Background: In patients suffering from bipolar disorders (BPD), we explored to what extent oral loading of sodium valproate (SV) leads to more rapid symptom improvement compared to intravenous loading and oral maintenance administration. Methods: Ninety patients (mean age: 35.00 years) with BPD and currently in an acute manic state were randomly assigned to one of three study conditions: oral loading (20 mg/kg oral single-dose SV on the first day, then 10-15 mg/kg SV daily, divided dose), intravenous loading (20 mg/kg SV intravenous injection on the first day, then 10-15 mg/kg orally, divided dose), or oral maintenance administration (15-20 mg/kg SV daily from the beginning) over the first 7 days of treatment. SV plasma levels, side effects and symptoms were evaluated at baseline and on days 1, 3, and 7 after commencing treatment. Results: There were significant Time-by-Group interactions for symptom improvements, symptom severity, and SV plasma levels, with positive values in the oral and intravenous loading conditions, compared to the oral maintenance condition. Post hoc analyses showed that oral and intravenous conditions led to similar improvements. Conclusions: Both oral and intravenous loading of SV led to quicker and more efficient improvement and SV plasma levels as compared to an oral maintenance regimen.

Psychosocial and caring issues with a bipolar disorder senior inpatient during a manic episode

This case analysis focuses on a male elderly inpatient with bipolar disorder during an acute manic episode. During the case's 3-week hospitalization, we used a participant observation approach to provide individualized nursing care. Our nursing assessment focused on linking this case's manic symptoms and psychosocial issues. Based on a content analysis of our nursing process record and the five psychosocial issues of elderly bipolar disorder reported by Reiser et al (2008), five major themes were presented. These themes included indulging the memory of youth-hood (cohort beliefs); presenting his old but still strong physical function (physical health); making an attempt to learn and showing the ability (socio-cultural context); providing working expert service and ability (transition in role investments); and playing a positive role as a warm-heartedness senior person (intergenerational relationship). This case's manic symptoms and psychosocial issues showed that he wished to perform as a young man to compensate for his ageing physical state and psychological loss, which revealed he want to maintain his social value. In view of the nursing intervention for this case during the acute manic state, we needed to pay attention to preventing the patient from physical overexertion and falls. We further needed to remind him to drink sufficient water, eat food, and take adequate rest. When the acute symptoms were in remission, we tried to empathize with and understand his psychosocial issues and self-concept and to help him integrate his illness and life experience to accomplish the elderly development task.

Aripiprazole in the acute and maintenance phase of bipolar I disorder

Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second-generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents.

Review of the safety, efficacy, and side effect profile of asenapine in the treatment of bipolar 1 disorder

Objective:Asenapine is approved for acute manic and mixed states in bipolar disorder. The objective is to review the efficacy of asenapine in bipolar disorder, with a particular focus on acceptability and adherence to treatment.Methods:Five clinical trials were conducted in bipolar disorder manic or mixed states: two 3-week trials (n = 976) comparing asenapine to placebo, a 9-week extension (n = 504), and a 40-week extension (n = 107). One trial was conducted comparing asenapine to placebo (n = 326) as adjunctive therapy for subjects with an incomplete response to lithium or valproate. All trials were conducted in the USA and internationally.Results:Asenapine was found to be efficacious for manic and mixed states in bipolar disorder compared with placebo control, and compares equally well to olanzapine on efficacy measures after 3 weeks of treatment. Asenapine was not found to be efficacious for depression symptoms. Common asenapine side effects in the 40-week extension trial were sedation, insomnia, and dizziness, and 31% reported clinically significant weight gain, compared with 55% reporting clinically significant weight gain with olanzapine. Additionally, 18% had clinically significant changes in fasting blood glucose levels compared to 22% of those on olanzapine. In terms of patient acceptability, one concern may be sublingual administration requiring no liquids or food for 10 minutes after dosing and a twice-daily regimen. Suggestions about addressing barriers to adherence and acceptability are provided.Conclusion:Asenapine is a promising new medication in bipolar disorder. Asenapine in the long-term has a more favorable weight gain profile compared to olanzapine. No benefit was seen for depression symptoms, a major patient-reported concern. Some side effects do not remit after the short-term trials in at least 10% of patients.

Two Cases of Bipolar Disorder Successfully Stabilized for Five Years with a Low Dose of Risperidone and Lithium

Two patients with bipolar I disorder were successfully treated with a combination of risperidone and lithium in their acute manic states and maintenance periods. Although lithium monotherapy alone could not prevent relapse in these patients, the addition of a low dose of risperidone was well tolerated and effective for preventing recurrence over the long term. Plasma levels of HVA and MHPG were found to be elevated during the manic episodes and gradually decreased after the risperidone treatment. These results indicate that a low dose of risperidone to the lithium regimen was an effective and well tolerated means for treatment in the acute manic state and the later maintenance period in parallel with decreasing plasma levels of HVA and MHPG.

Les traitements adjuvants au cours de l’épisode maniaque

When treating patients with manic states, the physician has to deal with at least two main Issues. First, the therapeutic decision has to be rapid because of the unpredictability of its immediate course. This concerns often results in polypharmacy with adjunct treatments. However, the therapeutic choice has to be cautious since part of the treatment will be maintained for prophylaxis. According to recent guidelines, the use of monotherapy with mood stabilisers during acute manic states concerns only few patients with mostly hypomania to moderate mania. Up to date, antipsychotics and benzodiazepines are considered as adjunct treatment in mania with psychotic symptoms or hostility. However, survey studies show that antipsychotics are widely used as adjunct treatments to mood stabilisers, indeed beyond the indications held by the guidelines. Our objective was to describe the clinical situations justifying the addition of an adjunct treatment during acute mania and to clear up from published data, the advantages and the inconveniences of combining antipsychotics and/or benzodiazepines with a mood stabilisers in order to define differentiated indications. Mania associated with either agitation, sleep disturbances or psychotic symptoms requires most of the time to combine mood stabiliser and respectively, sedative and/or anxiolytic, hypnotic or anti-psychotic treatments. Patients suffering from mania associated with other disorders need specific treatment adjustment and combination related to their medical condition. Adjunctive conventional antipsychotic remains widely used in first intention treatment. The conventional antipsychotic is often prescribed alone in the first weeks prior to the association with a mood stabiliser. Nevertheless there are controversies in the literature about their efficiency and their delay of action with regard to other treatments. When the conventional antipsychotic is a part of their initial treatment, manic patients remain taking them when discharged from hospital and are still taking them after 6 Months in a great percentage of the cases. The adverse events with conventional antipsychotic are numerous and severe enough in bipolar patients to restrict their use in first intention mainly to psychotic mania. Moreover, there are evidences for higher sensitivity to adverse effects of the conventional antipsychotics in manic patients. When agitation in acute mania requires an adjunct to mood stabiliser, the conventional antipsychotic treatment could be use for over-excitation without catatonic features and with particular care with the risk of akathisia. Long term effects of conventional antipsychotics, especially on depressive recurrences, should argue to stop them as soon as possible. Since the safety of adjunctive new antipsychotics with mood stabilisers seems until now acceptable, its indication should be limited to acute psychotic manias. Adjunctive benzodiazepine, should be evaluated in the various types of mania with specific concerns with comorbidity frequently met in consultation-liaison psychiatry. Benzodiazepines plus mood stabilisers may be the treatment of choice for the manias in which anxious state, catatonic symptoms or sleeplessness.

Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania

Background: Deficits in sensorimotor gating as assessed by prepulse inhibition (PPI) and habituation of the human startle response have been noted in schizophrenia and other patients with known dysfunction in the brain substrates that regulate PPI. During acute mania, bipolar disorder (BD) and schizophrenia patients present with symptoms that are similar. To determine if these clinical similarities extend to neurophysiologic domains, PPI and startle habituation were assessed in BD patients with acute psychotic mania and compared with a sample of acutely psychotic schizophrenia patients and a normal comparison group. Methods: Fifteen BD patients, 16 schizophrenia patients, and 17 control subjects were assessed on PPI and startle habituation. Results: The BD patients had significantly lower PPI than did the control subjects in two of the three PPI conditions (60- and 120-msec interstimulus intervals) as well as less startle habituation. The BD patients did not statistically differ from the schizophrenia patients in PPI or habituation. Conclusions: These findings of sensorimotor gating deficits among bipolar disorder patients are consistent with other findings using different measures of information processing and suggest that the neurobiological substrates underlying sensorimotor gating may be dysregulated during acute manic and psychotic states.

The Psychotherapy of Mania

The manic or hypomanic patient paradoxically lives on the edge of loss and lowered self-esteem. This is due to present realities of the impact of the illness upon life and the prospect of cycling into depression and earlier developmental problems to which bipolar patients may be especially prone. Furthermore, manic behavior itself engages others in arguments and countertransference problems that may actually worsen the course of the illness. A psychotherapeutic approach taking these factors into account can have a favorable impact on the acute episode and the long-term course of the illness, provided the patient and psychiatrist are able to form a trusting relationship that survives any recurrences. Justification for these views derives from small series of patients and anecdotal impressions of experienced clinicians. Empirical research is needed on the efficacy of psychotherapy, independent of medication effects.

Effectiveness of lithium carbonate in the treatment of manic-depressive illness.

The author reports on the responses to lithium cabonate of 75 manic-depressive patients. Lithium carbonate was found to be highly effective in the acute manic state but without merit in the treatment of acute depression. Its efficacy was inversely related to age. Response to the drug varied in some patients; a positive response at one time was no guarantee for a similar response in subsequent trials. The possibility of different biochemical states underlying similar clinical states is discussed.