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Charles L. Bowden - One of the best experts on this subject based on the ideXlab platform.

  • ziprasidone plus a Mood Stabilizer in subjects with bipolar i disorder a 6 month randomized placebo controlled double blind trial
    The Journal of Clinical Psychiatry, 2010
    Co-Authors: Charles L. Bowden, Eduard Vieta, Kathleen S Ice, Jeffrey H Schwartz, Paul P Wang, Mark Versavel
    Abstract:

    Objective To evaluate the efficacy and safety of ziprasidone adjunctive to a Mood Stabilizer for the maintenance treatment of bipolar mania. Method Subjects with DSM-IV bipolar I disorder with a Mania Rating Scale score > or = 14 were enrolled. Subjects achieving > or = 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or valproate (period 1) were randomly assigned in the 6-month, double-blind maintenance period (period 2) to ziprasidone plus Mood Stabilizer or placebo plus Mood Stabilizer. The primary and key secondary end points were the time to intervention for a Mood episode and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (log-rank test). The study was conducted from December 2005 to May 2008. Results A total of 127 and 113 subjects were randomly assigned to ziprasidone and placebo, respectively. Intervention for a Mood episode was required in 19.7% and 32.4% of ziprasidone and placebo subjects, respectively. The time to intervention for a Mood episode was significantly longer for ziprasidone than placebo (P = .0104). The median time to intervention for a Mood episode among those requiring such an intervention (n = 61) was 43.0 days for ziprasidone versus 26.5 days for placebo. The time to discontinuation for any reason was significantly longer for ziprasidone (P = .0047). Adjunctive ziprasidone treatment was well tolerated. Among treatment-emergent adverse events occurring in > or = 5% of subjects in either treatment group during period 2, only tremor occurred more frequently in the ziprasidone versus placebo group (6.3% vs 3.6%). Conclusions Ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a Mood Stabilizer for long-term maintenance treatment of bipolar mania. Trial registration clinicaltrials.gov Identifier: NCT00280566.

  • p01 206 a 6 month randomized placebo controlled double blind trial of ziprasidone plus a Mood Stabilizer in subjects with bipolar i disorder
    European Psychiatry, 2009
    Co-Authors: Eduard Vieta, Charles L. Bowden, Kathleen S Ice, Jeffrey H Schwartz, O Gurtovaya, Paul P Wang
    Abstract:

    Background The objective of this study was to evaluate the efficacy and safety of ziprasidone adjunctive to a Mood Stabilizer for the maintenance treatment of bipolar mania. Methods Male and female subjects with bipolar I disorder with MRS 3 14 were enrolled. Subjects achieving ≥ 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or divalproex were randomized into the 6-month double-blind maintenance period, to ziprasidone + Mood Stabilizer or placebo + Mood Stabilizer. The primary and key secondary end points were the time to intervention for a Mood episode, and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (Log-rank test). Results 127 and 112 subjects were randomized to and treated in the ziprasidone and placebo groups, respectively. The time to intervention for a Mood episode was significantly different, favoring ziprasidone (p = 0.0104). 19.7% and 32.4% of ziprasidone and placebo subjects, respectively, required intervention for a Mood episode. Time to discontinuation for any reason was significantly different (p = 0.0047), favoring ziprasidone. Among treatment-emergent adverse events occurring in the double-blind period, the only event occurring more frequently in the ziprasidone group than in the placebo group (≥ 5%) was tremor (6.3% vs 3.6%, respectively). Conclusions These results demonstrate that ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a Mood Stabilizer for long-term maintenance treatment of bipolar mania.

  • Risperidone in combination with Mood Stabilizers: a 10-week continuation phase study in bipolar I disorder.
    The Journal of clinical psychiatry, 2004
    Co-Authors: Charles L. Bowden, Joyce E. Myers, Fred Grossman, Yang Xie
    Abstract:

    BACKGROUND: Combination therapy (risperidone and a Mood Stabilizer) for patients with a history of bipolar disorder (DSM-IV) and hospitalized for treatment of a manic episode was assessed in a 13-week study. METHOD: Subjects received flexible doses of a Mood Stabilizer (lithium or divalproex) plus placebo, risperidone, or haloperidol in a 3-week double-blind study. They could then enter a 10-week open-label study during which they received risperidone combined with a Mood Stabilizer. RESULTS: Of the 156 patients enrolled in the 3-week study, 85 entered the 10-week open-label extension, of whom 48 completed 10 weeks of treatment. The mean +/- SE doses of risperidone were 3.8 +/- 0.3 mg/day during the 3-week study and 3.1 +/- 0.2 mg/day during the 10-week study. At double-blind endpoint, mean reductions in Young Mania Rating Scale (YMRS) scores were significantly greater in patients receiving risperidone plus Mood Stabilizer than in those receiving placebo plus Mood Stabilizer (-14.3 vs. -8.2, p

  • risperidone in combination with Mood Stabilizers a 10 week continuation phase study in bipolar i disorder
    The Journal of Clinical Psychiatry, 2004
    Co-Authors: Charles L. Bowden, Joyce E. Myers, Fred Grossman, Yang Xie
    Abstract:

    BACKGROUND: Combination therapy (risperidone and a Mood Stabilizer) for patients with a history of bipolar disorder (DSM-IV) and hospitalized for treatment of a manic episode was assessed in a 13-week study. METHOD: Subjects received flexible doses of a Mood Stabilizer (lithium or divalproex) plus placebo, risperidone, or haloperidol in a 3-week double-blind study. They could then enter a 10-week open-label study during which they received risperidone combined with a Mood Stabilizer. RESULTS: Of the 156 patients enrolled in the 3-week study, 85 entered the 10-week open-label extension, of whom 48 completed 10 weeks of treatment. The mean +/- SE doses of risperidone were 3.8 +/- 0.3 mg/day during the 3-week study and 3.1 +/- 0.2 mg/day during the 10-week study. At double-blind endpoint, mean reductions in Young Mania Rating Scale (YMRS) scores were significantly greater in patients receiving risperidone plus Mood Stabilizer than in those receiving placebo plus Mood Stabilizer (-14.3 vs. -8.2, p <.001). Further significant (p <.001) reductions were seen during the 10 weeks of treatment with risperidone plus Mood Stabilizer. Symptom remission (YMRS score Mood Stabilizer was efficacious and well tolerated in the continuation treatment of patients initially hospitalized for the management of an acute manic episode.

  • combination of a Mood Stabilizer with risperidone or haloperidol for treatment of acute mania a double blind placebo controlled comparison of efficacy and safety
    American Journal of Psychiatry, 2002
    Co-Authors: Gary S Sachs, Fred Grossman, Nassir S Ghaemi, A Okamoto, Charles L. Bowden
    Abstract:

    OBJECTIVE: The study assessed the efficacy and safety of risperidone as an adjunctive agent to Mood Stabilizers in the treatment of acute mania. METHOD: This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a Mood Stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures. RESULTS: The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with...

Raymond W Lam - One of the best experts on this subject based on the ideXlab platform.

  • pet study of the effects of valproate on dopamine d2 receptors in neuroleptic and Mood Stabilizer naive patients with nonpsychotic mania
    American Journal of Psychiatry, 2002
    Co-Authors: Lakshmi N. Yatham, Peter F Liddle, Raymond W Lam, Ishin Shiah, Carol J Lane, Jon A Stoessl, Vesna Sossi, Thomas J Ruth
    Abstract:

    OBJECTIVE: A previous study reported a higher than normal density of dopamine D2 receptors in psychotic mania but not in nonpsychotic mania. The purpose of this study was to further examine D2 receptor density in a larger sample of nonpsychotic manic patients by using positron emission tomography (PET) and [11C]raclopride. METHOD: Thirteen neuroleptic- and Mood- Stabilizer-naive patients with DSM-IV mania without psychotic features and 14 healthy comparison subjects underwent [11C]raclopride PET scans. Of the 13 patients, 10 were treated with divalproex sodium monotherapy. PET scans were repeated 2–6 weeks after commencement of divalproex sodium. D2 receptor binding potential was calculated by using a ratio method with the cerebellum as the reference region. RESULTS: The [11C]raclopride D2 binding potential was not significantly different in manic patients than in the comparison subjects in the striatum. Treatment with divalproex sodium had no significant effect on the [11C]raclopride D2 binding potential...

  • pet study of 18f 6 fluoro l dopa uptake in neuroleptic and Mood Stabilizer naive first episode nonpsychotic mania effects of treatment with divalproex sodium
    American Journal of Psychiatry, 2002
    Co-Authors: Lakshmi N. Yatham, Peter F Liddle, Raymond W Lam, Ishin Shiah, Jon A Stoessl, Vesna Sossi, Elton T C Ngan, Gayle Scarrow, Miguel Imperial, Thomas J Ruth
    Abstract:

    OBJECTIVE: Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and Mood-Stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring [18F]6-fluoro-l-dopa ([18F]DOPA) uptake in the striatum with positron emission tomography (PET). METHOD: Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [18F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2–6 weeks after beginning treatment with divalproex sodium monotherapy. [18F]DOPA uptake rate constants (Ki values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function. RESULTS: No significant differences in [18F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After tr...

  • pet study of 18f 6 fluoro l dopa uptake in neuroleptic and Mood Stabilizer naive first episode nonpsychotic mania effects of treatment with divalproex sodium
    International Conference on Bipolar Disorder, 2002
    Co-Authors: Lakshmi N. Yatham, Peter F Liddle, Raymond W Lam, Ishin Shiah, Jon A Stoessl, Vesna Sossi, Elton T C Ngan, Gayle Scarrow, Miguel Imperial, Thomas J Ruth
    Abstract:

    Objective: Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and Mood-Stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring [ 18 F]6-fluoro-L-dopa ([ 18 F]DOPA) uptake in the striatum with positron emission tomography (PET). Method: Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [ 18 F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6 weeks after beginning treatment with divalproex sodium monotherapy. [ 18 F]DOPA uptake rate constants (K i values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function. Results: No significant differences in [ 18 F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, [ 18 F]DOPA rate constants were significantly reduced in the patients and were lower in the patients than in the comparison subjects. Conclusions: Although presynaptic dopamine function as reflected by [ 18 F]DOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.

  • Comparative efficacy of typical and atypical antipsychotics as add-on therapy to Mood Stabilizers in the treatment of acute mania.
    The Journal of clinical psychiatry, 2001
    Co-Authors: Debra S. Miller, Lakshmi N. Yatham, Raymond W Lam
    Abstract:

    BACKGROUND Typical antipsychotics are commonly used in combination with Mood Stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to Mood Stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to Mood Stabilizers in a clinically relevant, naturalistic setting. METHOD This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) Mood Stabilizer and typical antipsychotic, (2) Mood Stabilizer and atypical antipsychotic, and (3) combination: Mood Stabilizer plus a typical antipsychotic, then switched to Mood Stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to Mood Stabilizers for the treatment of patients with mania.

Demaw Chuang - One of the best experts on this subject based on the ideXlab platform.

  • the Mood Stabilizer lithium potentiates the antidepressant like effects and ameliorates oxidative stress induced by acute ketamine in a mouse model of stress
    The International Journal of Neuropsychopharmacology, 2015
    Co-Authors: Chitso Chiu, Lisa Scheuing, Guangping Liu, Hsiaomei Liao, Gabriel R Linares, Dora Lin, Demaw Chuang
    Abstract:

    Background: Evidence suggests that mammalian target of rapamycin activation mediates ketamine’s rapid but transient antidepressant effects and that glycogen synthase kinase-3β inhibits this pathway. However, ketamine has associated psychotomimetic effects and a high risk of abuse. The Mood Stabilizer lithium is a glycogen synthase kinase-3 inhibitor with strong antisuicidal properties. Here, we used a mouse stress model to investigate whether adjunct lithium treatment would potentiate ketamine’s antidepressant-like effects. Methods: Mice received chronic restraint stress and long-term pre- or postketamine lithium treatment in drinking water. The effects of lithium on ketamine-induced antidepressant-like effects, activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways, oxidative stress, and dendritic spine density in the brain of mice were investigated. Results: Subtherapeutic (600mg/L) lithium-pretreated mice exhibited an antidepressant-like response to an ineffective ketamine (2.5mg/kg, intraperitoneally) challenge in the forced swim test. Both the antidepressant-like effects and restoration of dendritic spine density in the medial prefrontal cortex of stressed mice induced by a single ketamine (50mg/kg) injection were sustained by postketamine treatment with 1200mg/L of lithium for at least 2 weeks. These benefits of lithium treatments were associated with activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways in the prefrontal cortex. Acute ketamine (50mg/kg) injection also significantly increased lipid peroxidation, catalase activity, and oxidized glutathione levels in stressed mice. Notably, these oxidative stress markers were completely abolished by pretreatment with 1200mg/L of lithium. Conclusions: Our results suggest a novel therapeutic strategy and justify the use of lithium in patients who benefit from ketamine.

  • Mood Stabilizer regulated mirnas in neuropsychiatric and neurodegenerative diseases identifying associations and functions
    American Journal of Translational Research, 2013
    Co-Authors: Joshua G Hunsberger, Emily Bame Fessler, Fairouz L Chibane, Yan Leng, Dragan Maric, Abdel G Elkahloun, Demaw Chuang
    Abstract:

    Identifying mechanisms to enhance neuroprotection holds tremendous promise in developing new treatments for neuropsychiatric and neurodegenerative diseases. We sought to determine the potential role for microRNAs (miRNAs) in neuroprotection following neuronal death. A neuronal culture system of rat cerebellar granule cells was used to examine miRNA expression changes following glutamate-induced excitotoxicity and neuroprotective treatments. Combination treatment with the Mood Stabilizers lithium and valproic acid provided near-complete protection from glutamate excitotoxicity. Numerous miRNAs were detected by microarrays to be regulated by the combined lithium and valproic acid treatment, and the following candidates were confirmed using real-time PCR: miR-34a, miR-147b, miR-182, miR-222, miR-495, and miR-690. We then verified the apoptotic actions of miR-34a mimic in a human neuroblastoma cell line (SH-SY5Y) under basal conditions and following endoplasmic reticulum stress. To gain insight into the function of these Mood Stabilizer-regulated miRNAs, we performed two separate analyses: a candidate approach using Ingenuity Pathway Analysis that was restricted to only our PCR-verified miRNAs, and a global approach using DIANA-mirPath that included all significantly regulated miRNAs. It was observed that the pathways associated with Mood Stabilizer-regulated miRNAs in our study (global approach) are strongly associated with pathways implicated in neuropsychiatric diseases such as schizophrenia. We also observed an overlap in the Mood Stabilizer-regulated miRNAs identified from our study along with dysregulated miRNAs in both neuropsychiatric and neurodegenerative disorders. We anticipate that these associations and overlaps implicate critical pathways and miRNAs in disease mechanisms for novel therapeutic treatments that may hold potential for many neurological diseases.

  • neuroprotective and neurotrophic actions of the Mood Stabilizer lithium can it be used to treat neurodegenerative diseases
    Critical Reviews in Neurobiology, 2004
    Co-Authors: Demaw Chuang
    Abstract:

    The Mood stabilizing drug lithium has emerged as a robust neuroprotective agent in preventing apoptosis of neurons. Long-term treatment with lithium effectively protects primary cultures of rat brain neurons from glutamate-induced, NMDA receptor-mediated excitotoxicity. This neuroprotection is accompanied by an inhibition of NMDA-receptor-mediated calcium influx, upregulation of anti-apoptotic Bcl-2, downregulation of pro-apoptotic p53 and Bax, and activation of cell survival factors. Lithium treatment antagonizes glutamate-induced activation of c-Jun-N-terminal kinase (JNK), p38 kinase, and AP-1 binding, which has a major role in cytotoxicity, and suppresses glutamate-induced loss of phosphorylated cAMP responsive element binding protein (CREB). Lithium also induces the expression of brain-derived neurotrophic factor (BDNF) and subsequent activation TrkB, the receptor for BDNF, in cortical neurons. The activation of BDNF/TrkB signaling is essential for the neuroprotective effects of this drug. In addition, lithium stimulates the proliferation of neuroblasts in primary cultures of CNS neurons. Lithium also shows neuroprotective effects in rodent models of diseases. In a rat model of stroke, post-insult treatment with lithium or valproate, another Mood Stabilizer, at therapeutic doses markedly reduces brain infarction and neurological deficits. This neuroprotection is associated with suppression of caspase-3 activation and induction of chaperone proteins such as heat shock protein 70. In a rat model of Huntington's disease (HD) in which an excitotoxin is unilaterally infused into the striatum, both long- and short-term pretreatment with lithium reduces DNA damage, caspase-3 activation, and loss of striatal neurons. This neuroprotection is associated with upregulation of Bcl-2. Lithium also induces cell proliferation near the injury site with a concomitant loss of proliferating cells in the subventricular zone. Some of these proliferating cells display neuronal or astroglial phenotypes. These results corroborate our findings obtained in primary neuronal cultures. The neuroprotective and neurotrophic actions of lithium have profound clinical implications. In addition to its present use in bipolar patients, lithium could be used to treat acute brain injuries such as stroke and chronic progressive neurodegenerative diseases.

  • valproic acid a Mood Stabilizer and anticonvulsant protects rat cerebral cortical neurons from spontaneous cell death a role of histone deacetylase inhibition
    FEBS Letters, 2003
    Co-Authors: Mira Jeong, Ryota Hashimoto, Vladimir V Senatorov, Koichiro Fujimaki, Ming Ren, Min Soo Lee, Demaw Chuang
    Abstract:

    We studied the neuroprotective effects of valproic acid (VPA), a primary Mood Stabilizer and anticonvulsant, in cultured rat cerebral cortical neurons (CCNs). CCNs underwent spontaneous cell death when their age increased in culture. As shown by mitochondrial activity and calcein-AM assays, treatment of CCNs with VPA starting from day 9 in vitro markedly increased viability and prolonged the life span of the cultures. The neuroprotective action of VPA was time-dependent and occurred at therapeutic levels with a maximal effect at about 0.5 mM. LiCl (1 mM) also protected CCNs from aging-induced, spontaneous cell death but less effectively. VPA-induced neuroprotection in aging CCN cultures was associated with a robust increase in histone H3 acetylation levels and the protective effect was mimicked by treatment with a histone deacetylase inhibitor, trichostatin A, but not by VPA analogs which are inactive in blocking histone deacetylase. Our results suggest a role of histone deacetylase inhibition in mediating the neuroprotective action of VPA.

Joseph R Calabrese - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety of quetiapine xr as monotherapy or adjunctive therapy to a Mood Stabilizer in acute bipolar depression with generalized anxiety disorder and other comorbidities a randomized placebo controlled trial
    The Journal of Clinical Psychiatry, 2014
    Co-Authors: Keming Gao, David E Kemp, Stephen J Ganocy, Philip K Chan, Mary Beth Serrano, Carla Conroy, Ming Ren, Jun Chen, Elizabeth Karberg, Joseph R Calabrese
    Abstract:

    OBJECTIVE To study the efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a Mood Stabilizer in acute bipolar I or II depression with comorbid generalized anxiety disorder (GAD) and other comorbidities. METHOD The study was conducted from January 2007 to November 2011. The Mini-International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV bipolar disorder, GAD, and other Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. The Hamilton Depression Rating Scale-17 items (HDRS-17) was used as a primary outcome to evaluate the difference between the 2 groups using the change from baseline to end of study. Last observation carried forward and mixed-effects modeling for repeated measures were used to analyze the primary and secondary outcome measures. RESULTS Of the 120 patients screened, 100 patients were randomized to receive quetiapine-XR (n = 50) or placebo (n = 50). Twenty-six patients in the quetiapine-XR and 18 in the placebo group completed the study. The mean quetiapine-XR dose was 276 ± 50 mg/d (50-300 mg/d). There was no significant difference between the 2 groups in the change from baseline to end of study in HDRS-17 total score with an effect size of 0.19 favoring quetiapine-XR. There were also no significant differences between the 2 groups in secondary efficacy and safety outcome measures. CONCLUSIONS Quetiapine-XR was not significantly superior to placebo in bipolar I or II depression with GAD and other comorbidities, suggesting that data from relatively "pure" bipolar patients may not be generalizable to a highly comorbid population. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00671853.

  • acute efficacy of divalproex sodium versus placebo in Mood Stabilizer naive bipolar i or ii depression a double blind randomized placebo controlled trial
    The Journal of Clinical Psychiatry, 2011
    Co-Authors: David J Muzina, Keming Gao, David E Kemp, Sammy Khalife, Stephen J Ganocy, Philip K Chan, Mary Beth Serrano, Carla Conroy, Joseph R Calabrese
    Abstract:

    OBJECTIVE To conduct an exploratory evaluation of the acute efficacy of extended-release divalproex sodium compared to placebo in patients with bipolar I or II depression. METHOD Outpatients aged 18-70 years with Mood Stabilizer-naive bipolar I or II disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 6 weeks of divalproex sodium monotherapy or placebo. The primary outcome measure was mean change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Secondary outcomes included rates of response and remission, changes in the Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores, and changes in anxiety symptoms as measured by the Hamilton Anxiety Rating Scale. The study was conducted between 2003 and 2007. RESULTS Fifty-four subjects with bipolar I (n = 20) or bipolar II (n = 34) disorder were randomly assigned to divalproex or placebo; 67% (36 of 54) met DSM-IV criteria for rapid cycling. Divalproex treatment produced statistically significant improvement in MADRS scores compared with placebo from week 3 onward. The proportions of patients meeting response criteria were 38.5% (10 of 26) in the divalproex group versus 10.7% (3 of 28) for the placebo group (P = .017). The proportions of patients meeting remission criteria were 23.1% (6 of 26) for divalproex versus 10.7% (3 of 28) for placebo (P = .208). Subgroup analysis revealed no separation between divalproex and placebo for those with bipolar II diagnoses. Nausea, increased appetite, diarrhea, dry mouth, and cramps were the most common side effects. CONCLUSIONS These data suggest that divalproex sodium is efficacious and reasonably well tolerated in the acute treatment of Mood Stabilizer-naive patients with bipolar depression, particularly for those with rapid-cycling type I presentations, and that confirmatory large-scale studies are indicated. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00194116.

  • efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy
    Archives of General Psychiatry, 2002
    Co-Authors: Carlos A. Zarate, Mauricio Tohen, Charles L. Bowden, Joseph R Calabrese, Gary S Sachs, K Roy N Chengappa, Trisha Suppes, David J Kupfer, Robert W Baker
    Abstract:

    Background A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes. Methods The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing Mood-Stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + Mood-Stabilizer) or monotherapy (placebo + Mood-Stabilizer). Results Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (−13.11 vs −9.10; P = .003). Clinical response rates (≥50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P P DSM-IV mixed episode; HAMD-21 score of ≥20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy ( P Conclusion Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.

Mauricio Tohen - One of the best experts on this subject based on the ideXlab platform.

  • What makes a drug a primary Mood Stabilizer
    Molecular Psychiatry, 2002
    Co-Authors: Paul E Keck, Susan L Mcelroy, Neil M. Richtand, Mauricio Tohen
    Abstract:

    The term 'Mood Stabilizer' has been applied to a number of medications for the treatment of patients with bipolar disorder. The operational definition of the properties of a Mood-stabilizing medication has varied according to the properties of specific medications and the clinical characteristics of the illness. Randomized controlled trials of agents accepted or proposed as Mood Stabilizers are reviewed to marshall the available evidence in support of this claim. In addition, potential pharmacological mechanisms underlying Mood-stabilizing effects of established compounds are reviewed.

  • efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy
    Archives of General Psychiatry, 2002
    Co-Authors: Carlos A. Zarate, Mauricio Tohen, Charles L. Bowden, Joseph R Calabrese, Gary S Sachs, K Roy N Chengappa, Trisha Suppes, David J Kupfer, Robert W Baker
    Abstract:

    Background A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes. Methods The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing Mood-Stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + Mood-Stabilizer) or monotherapy (placebo + Mood-Stabilizer). Results Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (−13.11 vs −9.10; P = .003). Clinical response rates (≥50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P P DSM-IV mixed episode; HAMD-21 score of ≥20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy ( P Conclusion Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.

  • Is clozapine a Mood Stabilizer
    The Journal of clinical psychiatry, 1995
    Co-Authors: Carlos A. Zarate, Mauricio Tohen, Michael D. Banov, M. K. Weiss, Jonathan O. Cole
    Abstract:

    Background Clozapine has been increasingly shown to be effective in the acute and maintenance treatment of bipolar disorders. For this reason, we studied whether clozapine alone is effective as a Mood Stabilizer in patients with refractory bipolar disorders. Method Subjects were part of a long-term follow-up study cohort of 193 patients with refractory Mood disorders who were treated with clozapine at McLean Hospital prior to July 1, 1992. Patients included in this study were those older than 16 years with bipolar disorder (manic or mixed) and schizoaffective disorder, bipolar type, discharged taking clozapine alone (N = 17). Hospital records on all patients were reviewed by trained raters blind to "best-estimate" diagnoses. Response to clozapine was determined by the Clinical Global Impressions-Improvement (CGI-I) scale. Patients were contacted at least 6 months after clozapine initiation for semistructured follow-up interviews by raters blind to diagnosis and baseline information. Results Seventeen subjects were contacted 16.1 +/- 5.6 months after clozapine initiation. Most of the 17 patients had previously failed trials of lithium, valproate, carbamazepine, neuroleptics, combinations of these, and electroconvulsive therapy; or had tardive dyskinesia. Of these patients, 65% (11/17) continued to be on clozapine therapy alone at follow-up and had no subsequent rehospitalization or affective episode. At follow-up, there was a significant decrease in the rehospitalization rate (p = .025) than before starting clozapine and a significant improvement in CGI-I scores (p = .02). Conclusion Clozapine monotherapy is an effective Mood Stabilizer, reducing both the number of affective episodes and rehospitalizations in patients with severe refractory bipolar illness.