Valproic acid induced oxidative brain injury in rats: Protective effect of edaravone

Back to table of contents Previous article Next article DepartmentsFull AccessThe Effectiveness of High-Dosage Amisulpride Combined With Moderate-Dosage Sodium Valproate Treatment for an Overweight Patient With Psychotic Bipolar DisorderYi-Cheng Hou, M.Sc., and Chien-Han Lai, M.D.Yi-Cheng HouSearch for more papers by this author, M.Sc., and Chien-Han LaiSearch for more papers by this author, M.D.Published Online:1 Apr 2014https://doi.org/10.1176/appi.neuropsych.13040091AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Several atypical antipsychotics were approved for the treatment of bipolar affective disorder.1 However, the data of amisulpiride in this field is still limited. I want to share a case of psychotic bipolar disorder with successful control of symptoms under the combined treatment of high-dosage amisulpiride and moderate-dosage sodium valproate.Case ReportMiss Y is an overweight case of psychotic bipolar disorder with unstable symptom control under several atypical antipsychotics, such as olanzapine, risperidone, quetiapine, or aripiprazole in recent 2–3 years. She also received several mood stabilizers, such as lithium or sodium valproate, but with undesirable body weight gain side effects. The bipolar symptoms (mostly mania) and psychotic symptoms (delusion of reference) still did not respond to the above medications [Young Mania Rating Scales (YMRS) scores: 36; Brief Psychiatric Rating Scale-18 (BPRS-18) scores: 38]. The medications were abruptly switched to amisulpiride 800 mg/day with sodium valproate 1000 mg/day to avoid previous body weight gain side effects under high dose of sodium valproate [body mass index (BMI): 31.21]. Her symptoms improved with residual delusion of reference and irritability after 3 weeks of the above-mentioned therapy (YMRS scores: 15; BPRS-18 scores: 20). She requested for more amisulpiride to control residual symptoms; the dose of amislpiride was increased to 1000 mg/day with significant improvement since the use of amisulpiride and sodium valproate for 6 weeks (YMRS scores: 9; BPRS scores: 12). No intolerable side effects were mentioned under high-dosage amisulpiride combined with moderate-dosage sodium valproate (BMI: 29.98). There was no relapse of symptoms under this regimen at the next 3-month follow-up.DiscussionThe role of atypical antipsychotics in manic phase is discussed and compared with typical antipsychotics in recent years.1,2 Even though there is some controversy about the intolerable side effects and the efficacy of atypical antipsychotics,2 the lower relapse rate of mania during maintenance therapy of atypical antipsychotics is still an advantage for bipolar disorder treatment.1 Yatham mentioned that atypical antipsychotics, such as olanzapine, quetiapine, ziprasidone, aripiprazole, and risperidone, can be an alternative to or combined with the mood stabilizers.3,4 However, among the atypical antipsychotics, there is no well-controlled study of amisulpiride for bipolar disorder. In this case, the effectiveness of 1000 mg/day amisulpiride in the control of psychotic and manic symptoms has been shown with combination of 1000 mg/day sodium benzoate. The dopamine-related pathophysiology of bipolar disorder are dopamine D2 and D3 receptors.5,6 As we know, amisulpiride is a compound with actions over dopamine D2 and D3 receptors,7 the treatment effect might be associated with dopamine mechanisms. Amisulpiride has a favorable profile for metabolic syndrome or body weight gain side effects, which is an unfavorable consequence of previous antipsychotics in this patient. To my knowledge, this is the first case report about high-dosage amisulpiride combined with medium-dosage sodium valproate for bipolar disorder. It can be an option for our patients while facing such dilemma of treatment.Department of Nutrition, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation New Taipei City, Taiwan, ROCDepartment of Psychiatry, Cheng Hsin General Hospital, Taipei City, Taiwan, ROCSend correspondence to Dr. Lai; e-mail: [email protected]comThe authors report no financial relationships with commercial interests.References1 Derry S, Moore RA: Atypical antipsychotics in bipolar disorder: systematic review of randomised trials. BMC Psychiatry 2007; 7:40Crossref, Medline, Google Scholar2 Gentile S: Atypical antipsychotics for the treatment of bipolar disorder: more shadows than lights. CNS Drugs 2007; 21:367–387Crossref, Medline, Google Scholar3 Yatham LN: Acute and maintenance treatment of bipolar mania: the role of atypical antipsychotics. Bipolar Disord 2003; 5(Suppl 2):7–19Crossref, Medline, Google Scholar4 Yatham LN: Atypical antipsychotics for bipolar disorder. Psychiatr Clin North Am 2005; 28:325–347Crossref, Medline, Google Scholar5 Massat I, Souery D, Del-Favero J, et al.: Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders. Am J Med Genet 2002; 114:177–185Crossref, Medline, Google Scholar6 Chiaroni P, Azorin JM, Dassa D, et al.: Possible involvement of the dopamine D3 receptor locus in subtypes of bipolar affective disorder. Psychiatr Genet 2000; 10:43–49Crossref, Medline, Google Scholar7 Chivers JK, Gommeren W, Leysen JE, et al.: Comparison of the in-vitro receptor selectivity of substituted benzamide drugs for brain neurotransmitter receptors. J Pharm Pharmacol 1988; 40:415–421Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 26Issue 2 Spring 2014Pages E34-E35 Metrics PDF download History Published online 1 April 2014 Published in print 1 April 2014

Treatments for late-life bipolar disorder

Treatment Costs Related to Bipolar Disorder and Comorbid Conditions Among Medicaid Patients With Bipolar Disorder

Despite a marked increase in treatment for bipolar disorder among youths, little is known about their pattern of service use. This article describes mental health service use in the year before and after a new clinical diagnosis of bipolar disorder. Claims were reviewed between April 1, 2004, and March 31, 2005, for 1,274,726 privately insured youths (17 years and younger) who were eligible for services at least one year before and after a service claim; 2,907 youths had new diagnosis of bipolar disorder during this period. Diagnoses of other mental disorders and prescriptions filled for psychotropic drugs were assessed in the year before and after the initial diagnosis of bipolar disorder. The one-year rate of a new diagnosis of bipolar disorder was .23%. During the year before the new diagnosis of bipolar disorder, youths were commonly diagnosed as having depressive disorder (46.5%) or disruptive behavior disorder (36.7%) and had often filled a prescription for an antidepressant (48.5%), stimulant (33.0%), mood stabilizer (31.8%), or antipsychotic (29.1%). Most youths with a new diagnosis of bipolar disorder had only one (28.8%) or two to four (28.7%) insurance claims for bipolar disorder in the year starting with the index diagnosis. The proportion starting mood stabilizers after the index diagnosis was highest for youths with five or more insurance claims for bipolar disorder (42.1%), intermediate for those with two to four claims (24.2%), and lowest for those with one claim (13.8%). Most youths with a new diagnosis of bipolar disorder had recently received treatment for depressive or disruptive behavior disorders, and many had no claims listing a diagnosis of bipolar disorder after the initial diagnosis. The service pattern suggests that a diagnosis of bipolar disorder is often given tentatively to youths treated for mental disorders with overlapping symptom profiles and is subsequently reconsidered.

The anticonvulsant valproic acid and the atypical antipsychotics olanzapine and quetiapine provide synergistic mood-stabilising, antidepressant and antipsychotic activities in the treatment of bipolar and schizoaffective disorders. Existing literature shows that pharmacokinetic and pharmacodynamics drug-drug interactions (DDIs) possibly occur with the use of such a combination. Clinical reports of a possible interaction between the drugs leading to an increased risk of adverse drug reactions have also emerged. The main objective of this paper is to review the incidence of DDIs between the anticonvulsant and the antipsychotics, to postulate the possible mechanisms of the interaction and to establish whether certain target populations are at an increased susceptibility to such interactions. The usefulness of therapeutic drug monitoring (TDM) of the antipsychotics to monitor for an interaction was also assessed. A systematic database search was carried out using the search engine provided by PubMed using the following key words: olanzapine, quetiapine, valproic acid, pharmacokinetic drug-drug interaction, bipolar disorder, therapeutic drug monitoring. Evidence of a possible clinically relevant DDI between valproic acid and both antipsychotics has been uncovered. A possible mechanism for the interactions has been postulated, and the importance of TDM has been discussed. Further research is required to determine whether DDIs occur with the concurrent use of valproic acid and olanzapine or quetiapine, and to investigate the potential of TDM as a clinical tool in improving pharmacotherapy and preventing toxicity.

Synaptic, intracellular, and neuroprotective mechanisms of anticonvulsants: are they relevant for the treatment and course of bipolar disorders?

Several mood stabilizers, such as lithium, valproic acid and carbamazepine are widely used for the prevention and treatment of bipolar disorders. However, there is number of patients unresponsive to either monotherapy or combination treatment. This proportion may be even higher in patients with mixed episodes or rapid cycling. Conventional antipsychotics have been used over four decades to treat bipolar disorders, especially those with psychotic features. It has been reported that they may induce or exacerbate major depressive episodes, while high incidence of extrapyramidal side effects has also been noted. Furthermore, literature review suggests that their long-term use may be related to poor functioning. Atypical antipsychotics characterized by a much-improved tolerability and safety profile can be used as an adjunctive therapy for psychotic bipolar patients or as alternatives for the treatment of bipolar patients with mania who have not responded to lithium or other mood stabilizers. It has been demonstrated that olanzapine monotherapy is efficacious in the treatment of acute mania. Certain atypical antipsychotics may possess antidepressant effects as addon therapy in patients with mood disorders. The existing literature suggests their long-term use in low doses as adjunctive treatments of mood stabilizing agents in severe refractory patients. The issue of efficacy and tolerability of atypical antipsychotics alone or in combination with mood stabilizers in bipolar disorders is critical, challenging and warrants further exploration in the context of larger controlled studies. from International Society on Brain and Behaviour: 1st International Congress on Brain and Behaviour Hyatt Regency Hotel, Thessaloniki, Greece, 20–23 November, 2003

Lithium during pregnancy.

Bipolar disorder is a clinically important condition in the geriatric psychiatric population, with reported prevalences ranging from 4 to 19 percent (1,2). However, study of bipolar disorder among elderly patients has been limited. A search of MED LINE for the 20-year period from 1977 to 1997 revealed that the most recent comprehensive review that summarized approaches to pharma cotherapy for elderly patients with bipolar disorder was done by Young (3) in 1997. The review indicated that minimal research had been conducted on the clinical efficacy of the various mood stabilizers among elderly patients compared with younger patients. In a five-year retrospective analysis of an adult hospital population irrespective of age (the mean age was about 43 years), Frye and associates (4) compared the efficacy of the three mood stabilizers—valp roic acid, carbamazepine, and lithium—and the combination of them in treatment of patients with classic and dysphoric mania. Length of stay in the hospital was used as the major outcome measure. Some patients who were treated with valproic acid received a highload dosage of 20 mg per kilogram of body weight. The analysis by Frye and associates indicated that when used alone, valproic acid had significantly better efficacy than either lithium or carbamazepine in helping patients achieve hospital discharge. Most studies of geriatric populations have examined only lithium treatment for patients with acute mania (5), despite the findings by Pur year and Kunik (6) that valproic acid is well tolerated by elderly patients. With the Food and Drug Administration’s 1995 approval of valproic acid for use in treatment of bipolar disorder, the need to study its clinical efficacy among elderly patients was apparent. Our study examined the comparative efficacy of selected mood stabilizers among elderly patients. Our hypothesis was that valproic acid would be superior to other agents. Methods The study focused on an inpatient geriatric population with bipolar disorder and was modeled after the study by Frye and associates (4). We did a retrospective chart review at a university-affiliated county hospital in New York State. The charts of psychiatric patients age 60 or older with a discharge diagnosis of bipolar disorder were reviewed for the four-year period from 1993 to 1996. Of 122 charts identified for the study, 72 satisfied all inclusion and exclusion criteria for analysis. Patients were included if they met DSM-IV criteria for bipolar disorder at admission and were maintained on mood stabilizer monotherapy with lithium, carbamazepine, or valproic acid during hospitalization. If patients had more than one course of mono therapy while hospitalized, the monotherapy that resulted in discharge was used in the analysis of length of treatment. Patients were excluded if their hospital stay was lengthened because of medical illness, if they were not placed on a mood stabilizer, or if they were treated with more than one mood stabilizer simultaneously. Data gathered from the 72 charts included demographic information such as age, gender, family history of psychiatric illness, number of years with the diagnosis of bipolar disorder, and number of previous psychiatric hospitalizations. Assessment and treatment data included mood stabilizer used, blood levels of the medication at discharge, length of treatment with the mood stabilizer in days, and Global Assessment of Functioning (GAF) score at admission and discharge.

Although lithium has been the most commonly used maintenance treatment in bipolar disorder for several decades, valproate is being used increasingly - especially in the United States of America. There is a need to clarify whether the increasingly prominent prophylactic role of valproate in bipolar disorder is justified. To review the effectiveness of valproate, relative to placebo, other mood stabilisers and antipsychotics, in the prevention and/or attenuation of acute episodes of bipolar disorder. The effectiveness of valproate was considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. The CCDAN group search strategy was used. The following databases were searched: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Controlled Clinical Trials Register (CCCTR), EMBASE, MEDLINE, LILACS, PsycLIT and Psyndex. Reference lists of relevant papers and major textbooks of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. Randomised controlled trials which compared valproate with placebo, alternative mood stabilisers (including lithium and carbamazepine) or neuroleptics, where the stated intent of intervention was the maintenance treatment of bipolar disorder. Participants were males and females of all ages with a diagnosis of bipolar disorder however diagnosed, approximating to ICD 10 Code F31 and DSM IV 296, but including patients diagnosed as ICD-9 manic depressive psychosis and DSM-III and DSM-IIIR bipolar disorder. Data were extracted from the original reports individually by two reviewers. The main outcomes to be assessed were: 1. The effectiveness of valproate treatment in preventing or attenuating further episodes of bipolar disorder, including its effectiveness in rapid cycling disorder. 2. The acceptability of valproate treatment to patients. 3. The prevalence of side-effects. 4. Mortality on valproate treatment. Outcomes concerning relapse/recurrence were analysed excluding data from discontinuation studies, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of valproate treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were analysed using Review Manager version 4.1. One trial of 12 months duration with 372 participants was identified comparing lithium, divalproex and placebo. It had several methodological limitations. The primary analysis of time to occurrence of mood episode described in the main trial report found no reliable difference between the treatments, although there was a trend for divalproex to be more effective than lithium. In the analysis in this review, patients taking divalproex who left the study because of the occurrence of an mood episode were significantly less in number than those on placebo (RRR 37%; RR 0.63; 95% CI 0.44 to 0.90). There was no significant difference in the numbers of patients in receipt of divalproex compared with those in receipt of lithium who left the study because they suffered any mood episode. (RRR 22%; RR 0.78; 95% C.I. 0.52 to 1.17). There was insufficient information to allow sub-group analyses of rapid-cycling disorder. The divalproex group had significantly more patients suffering tremor (RRI 223%; RR 3.23; 95% C.I. 1.85 to 5.62), weight gain (RRI 187%; RR 2.87; 95% C.I. 1.34 to 6.17) and alopecia (RRI 143%; RR 2.43; 95% C.I. 1.05 to 5.65) than the placebo group. In comparison with the lithium, divalproex was associated with more frequent sedation (RRI 58%; RR 1.58; 95% C.I. 1.08 to 2.32) and infection (RRI 107%; RR 2.07; 95% C.I. 1.16 to 3.68), but less suffered thirst (RRR 62%; RR 0.38; 95% C.I. 0.18 to 0.81) and polyuria (RRR 57%; RR 0.43; 95% C.I. 0.22 to 0.82). In view of the equivocal findings of this review, conclusions about the efficacy and acceptability of valproate compared to placebo and lithium cannot be made with any degree of confidence. With current evidence, patients and clinicians would probably wish to use lithium before valproate for maintenance treatment. At present, the observed shift of prescribing practice to valproate is not based on reliable evidence of efficacy

Bipolar disorder is a chronic and severe affective disorder which has a significant impact on patient functioning and well-being, and on total medical costs. Divalproex sodium (Depakote®) has been shown to be effective in treating acute mania and for the long-term treatment of bipolar disorder. Few health-related quality of life or pharmacoeconomic studies have been completed comparing divalproex sodium with other mood stabilizers. Clinical trials have demonstrated that the response to divalproex sodium therapy is associated with improvements in health-related quality of life outcomes and reduced disability days. No statistically significant differences on health-related quality of life outcomes have been observed between divalproex sodium, lithium or olanzapine (Zyprexa®) treatment in bipolar disorder. Effective mood stabilizer therapy results in improvements in patient functioning and well-being, but there is little evidence differentiating the effects of divalproex sodium on these outcomes compared with other mood stabilizer treatments. The current pharmacoeconomic studies suggest that divalproex sodium is associated with lower total and inpatient medical costs compared with lithium. A small, recent clinical trial has also demonstrated that total outpatient costs are lower for divalproex sodium compared with olanzapine. Additional cost-effectiveness studies are required to examine the impact of divalproex sodium versus other mood stabilizers in the treatment of bipolar disorder.

Treatment of Comorbid Bipolar Disorder and Epilepsy With Valproate

Moringa oleifera (M. oleifera) is a popular medicinal plant that has become a wide research area in recent years due to its detected biological effects and its bioactive compounds. Valproic acid (VPA) is a medication used in the treatment of epilepsy and bipolar disorder and high doses or prolonged use of VPA can result in oxidative stress in cells. Since M. oleifera has high biological activities and contains many bioactive compounds, it is necessary to understand whether it plays a role in reducing oxidative damage, especially that caused VPA. The relationship between VPA and tongue tissue needs to be investigated, since VPA has negative effects on oral health and it is known that tongue tissue plays an important role in the continuity of oral health. In the present study, 3.0-3.5month-old female Sprague Dawley rats (160-250g) were divided into four groups (Control, Moringa, VPA, VPA + M), and VPA was administered via gavage. The aim was to understand the protective/preventive effects of ethanolic M. oleifera leaves extract against oxidative stress through biochemical parameters. Additionally, molecular docking studies were conducted on niazicin-A, niazimin-A, and niazimin-B found in M. oleifera leaves based on in vivo results. The results indicate that M. oleifera extract treats oxidative damage to the tongue tissue, and niazimin-A and niazimin-B particularly show high binding affinities to myeloperoxidase (MPO) and lactate dehydrogenase (LDH) enzymes. Further studies may suggest that the use of M. oleifera leaves extract with VPA could prevent potential negative effects on tongue tissue.

Tiagabine, an anticonvulsant, has been reported to have efficacy in prophylactic treatment of bipolar disorder in case reports and in case series. To review the efficacy and acceptability of tiagabine, relative to placebo, and other agents in the prevention and/or attenuation of episodes of bipolar affective disorder. The efficacy and acceptability of tiagabine were considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of affective disorder were examined.Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. Specialist journals and conference proceedings were handsearched. Randomised controlled trials which compare tiagabine with placebo, alternative mood stabilisers or antipsychotics, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder, were sought. Bipolar patients, male and female, of all ages were to be included. Data were to be extracted from the original reports if they met our inclusion criteria. The main outcomes to be assessed were:(1) The efficacy of tiagabine treatment in preventing or attenuating further episodes of bipolar affective disorder, including its efficacy in rapid cycling disorder.(2) The acceptability of tiagabine treatment to patients.(3) The prevalence of side effects.(4) Mortality, if any, on tiagabine treatment.Outcomes concerning relapse or recurrence were to be analysed excluding data from studies using discontinuation protocols, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of tiagabine treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were to be analysed using Review Manager version 4.2.8. No randomised controlled trials of tiagabine in the maintenance treatment of bipolar disorder were found. There is an insufficient methodologically rigorous evidence base to provide guidance on the use of tiagabine in the maintenance treatment of bipolar disorder. There is a need for randomised controlled trials examining the therapeutic potential of this agent in bipolar disorder, after the nature of reported episodes of syncope or seizure in tiagabine-treated bipolar patients has been established.

A number of recent studies have questioned whether, despite modern treatment, the natural course of bipolar illness today still involves multiple relapses and impaired psychosocial functioning. This prospective follow-up study examined longitudinal outcome in a large group of inpatients with affective disorders. Fifty-one bipolar manic patients and 49 unipolar depressed patients were interviewed three times: 1) during hospitalization, 2) approximately 2 years after discharge, and 3) approximately 4.5 years after discharge. Subjects were treated under routine conditions and assessed for global adjustment, rehospitalization, and work and social functioning. Only 41% of the bipolar group had a good overall outcome by the time of the 4.5-year follow-up. The bipolar patients had more severe work impairment than the unipolar group. More than one-half of the bipolar patients were rehospitalized at least once during the 4.5-year follow-up period. Outcome for both diagnostic groups improved significantly over time. Many contemporary bipolar patients demonstrate gradual improvement in the first several years after hospitalization. However, a subgroup approaching 60% still experience poor posthospital adjustment in one or more areas of functioning.