scholarly journals Levetiracetam as an Adjunctive Treatment for Mania: A Double-Blind, Randomized, Placebo-Controlled Trial

2022 ◽  
pp. 1-12
Author(s):  
Amir Keshavarzi ◽  
Aziz Sharifi ◽  
Leila Jahangard ◽  
Alireza Soltanian ◽  
Annette Beatrix Brühl ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Performance ◽  
Effect Size ◽  
Rating Scale ◽  
Medium Effect ◽  
Large Effect Size ◽  
Placebo Condition ◽  
Double Blind ◽  
Subjective Sleep ◽  
Over Time

<b><i>Background:</i></b> Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania. <b><i>Methods:</i></b> A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants’ acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants’ cognitive performance was assessed at baseline and at day 24 at the end of the study. <b><i>Results:</i></b> Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition. <b><i>Conclusions:</i></b> Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance.

scholarly journals Transdiagnostic comparison of visual working memory capacity in bipolar disorder and schizophrenia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Catherine V. Barnes-Scheufler ◽  
Caroline Passow ◽  
Lara Rösler ◽  
Jutta S. Mayer ◽  
Viola Oertel ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Working Memory ◽  
Visual Working Memory ◽  
Effect Size ◽  
Working Memory Capacity ◽  
Memory Capacity ◽  
Medium Effect ◽  
Full Spectrum ◽  
Small Effect Size ◽  
The Difference

Abstract Background Impaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. Methods 62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler’s K. Results Working memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. Conclusions These findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.

scholarly journals Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maximilian Pilhatsch ◽  
Thomas J Stamm ◽  
Petra Stahl ◽  
Ute Lewitzka ◽  
Anne Berghöfer ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Phenotypic Expression ◽  
Anxiety Symptoms ◽  
Controlled Study ◽  
Double Blind ◽  
Comorbid Anxiety ◽  
Depressed Patients ◽  
Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

scholarly journals Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: A meta-analysis

2002 ◽  
Vol 180 (5) ◽  
pp. 396-404 ◽  
Author(s):  
David Smith ◽  
Carrie Dempster ◽  
Julie Glanville ◽  
Nick Freemantle ◽  
Ian Anderson
Keyword(s):  
Systematic Review ◽  
Effect Size ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Remission Rate ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Randomised Trials ◽  
Double Blind

BackgroundIn individual studies and limited meta-analyses venlafaxine has been reported to be more effective than comparator antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs).AimsTo perform a systematic review of all such studies.MethodWe conducted a systematic review of double-blind, randomised trials comparing venlafaxine with alternative antidepressants in the treatment of depression. The primary outcome was the difference in final depression rating scale value, expressed as a standardised effect size. Secondary outcomes were response rate, remission rate and tolerability.ResultsA total of 32 randomised trials were included. Venlafaxine was more effective than other antidepressants (standardised effect size was −0.14, 95% Cl −0.07 to −0.22). A similar significant advantage was found against SSRIs (20 studies) but nottricyclic antidepressants (7 studies).ConclusionsVenlafaxine has greater efficacy than SSRIs although there is uncertainty in comparison with other antidepressants. Further studies are required to determine the clinical importance of this finding.

scholarly journals Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder

2006 ◽  
Vol 51 (4) ◽  
pp. 234-242 ◽  
Author(s):  
Sidney H Kennedy ◽  
Kari A Fulton ◽  
R Michael Bagby ◽  
Andrea L Greene ◽  
Nicole L Cohen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sexual Function ◽  
Rating Scale ◽  
Primary Objective ◽  
Major Depressive ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive ◽  
Over Time

Objective: The primary objective was to evaluate sexual function (SF) separately in men and women with major depressive disorder (MDD) before and during treatment with bupropion sustained release (SR) or paroxetine. The secondary objectives involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time. Method: There were 141 patients (68 women and 73 men) who met DSM-IV criteria for a current major depressive episode. They were randomly assigned to receive bupropion SR (150 to 300 mg daily) or paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. Results: Prior to treatment, women reported significantly lower SF on both the Sex FX and IRSD-F scales, compared with men. During treatment, there were no significant drug differences on measures of SF over time for women; however, men who were treated with paroxetine reported a worsening of SF, whereas bupropion SR did not significantly alter SF. Both bupropion SR and paroxetine produced clinically and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission. There was a statistically significant correlation between the 2 measures of SF at all visits. There was also a significant inverse relation between depression and SF in women, but not in men, irrespective of drug. Conclusion: According to the Sex FX scale, a significant difference in antidepressant-related sexual dysfunction was detected in men, but not women, during treatment with bupropion SR or paroxetine.

Platelet-Rich Plasma Versus Corticosteroid Injections in the Management of Elbow Epicondylitis and Plantar Fasciitis: An Updated Systematic Review and Meta-analysis

2019 ◽  
Vol 48 (10) ◽  
pp. 2572-2585 ◽  
Author(s):  
Kai Huang ◽  
Grey Giddins ◽  
Li-dong Wu
Keyword(s):  
Systematic Review ◽  
Clinical Efficacy ◽  
Effect Size ◽  
Plantar Fasciitis ◽  
Platelet Rich Plasma ◽  
Meta Analysis ◽  
Medium Effect ◽  
Large Effect Size ◽  
Short Term

Background: Platelet-rich plasma (PRP), as a promising alternative to traditional corticosteroid (CS), is now increasingly used in the treatment of elbow epicondylitis (EE) and plantar fasciitis (PF). To date, however, the synthesis of information on the clinical efficacy of PRP versus CS is limited with divergent conclusions. Purpose: To compare the clinical efficacy of PRP and CS injections in reducing pain and improving function in EE and PF. Study Design: Systematic review and meta-analysis. Methods: Online databases were searched from inception to October 2018 for prospective studies evaluating PRP versus CS injections for EE or PF. Independent reviewers undertook searches, screening, and risk-of-bias appraisals. The primary outcomes of interest were pain and function in both the short term (1-3 months) and the long term (≥6 months). Results: Twenty trials with 1268 participants were included. For EE, PRP provides a statistically and clinically meaningful long-term improvement in pain, with a very large effect size of −1.3 (95% CI, −1.9 to −0.7) when compared with CS, but the evidence level was low. For EE, there was moderate evidence that CS provides a statistically meaningful improvement in pain in the short term, with a medium effect size of 0.56 (95% CI, 0.08-1.03) as compared with PRP; this improvement might not be clinically significant. For PF, there was low evidence that PRP provides a statistically and clinically meaningful long-term improvement in function (American Orthopedic Foot & Ankle Society score), with a very large effect size of 1.94 (95% CI, 0.61-3.28). There were no significant differences between the groups in improvement in function in EE and pain and short-term function in PF, but the quality of the evidence was low. Conclusion: The use of PRP yields statistically and clinically better improvement in long-term pain than does CS in the treatment of EE. The use of PRP yields statistically and clinically better long-term functional improvement than that of CS in the treatment of PF.

An Open-Label Trial of Aripiprazole Monotherapy in Children and Adolescents with Bipolar Disorder

CNS Spectrums ◽  
2007 ◽  
Vol 12 (9) ◽  
pp. 683-689 ◽  
Author(s):  
Joseph Biederman ◽  
Eric Mick ◽  
Thomas Spencer ◽  
Robert Doyle ◽  
Gagan Joshi ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Vital Signs ◽  
Pediatric Bipolar Disorder ◽  
Open Label ◽  
Young Mania ◽  
Double Blind ◽  
Scale Scores ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale

ABSTRACTIntroduction: Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder.Methods: This was an 8-week, open-label, prospective study of aripiprazole 9.4±4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale, Clinical Global Impressions-Improvement scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis.Results: Fifteen of the 19 bipolar youth (79%) completed the study. Aripiprazole treatment was associated with clinically and statistically significant improvement in mean Young Mania Rating Scale scores (−18.0±6.9, P<.0001). With the important exception of two cases of extrapyramidal symptoms that precipitated dropout, aripiprazole was well tolerated with no statistically significant increase in body weight (1.8±1.7 kg, P=.2).Conclusion: Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder. Future placebo-controlled, double blind studies are warranted.

scholarly journals A Dietary Mobile App for Patients Undergoing Hemodialysis: Prospective Pilot Study to Improve Dietary Intakes

10.2196/17817 ◽  
2020 ◽  
Vol 22 (7) ◽  
pp. e17817
Author(s):  
Cosette Fakih El Khoury ◽  
Rik Crutzen ◽  
Jos M G A Schols ◽  
Ruud J G Halfens ◽  
Mirey Karavetian
Keyword(s):  
Health Care ◽  
Pilot Study ◽  
Effect Size ◽  
Mobile App ◽  
Dietary Guidelines ◽  
Medium Effect ◽  
Dietary Intakes ◽  
Large Effect Size ◽  
Prospective Pilot Study ◽  
Medium Effect Size

Background Mobile technology has an impact on the health care sector, also within dietetics. Mobile health (mHealth) apps may be used for dietary assessment and self-monitoring, allowing for real-time reporting of food intakes. Changing eating behaviors is quite challenging, and patients undergoing hemodialysis, particularly, struggle to meet the target intakes set by dietary guidelines. Usage of mobile apps that are developed in a person-centered approach and in line with recommendations may support both patients and health care practitioners. Objective This study is a pilot that aims at estimating the potential efficacy of a dietary intervention using a theory-based, person-centered smartphone app. Results will be used to improve both the app and a planned large-scale trial intended to assess app efficacy thoroughly. Methods A prospective pilot study was performed at the hemodialysis unit of Al Qassimi Hospital (The Emirate of Sharjah). All patients that fulfilled the study inclusion criteria were considered eligible to be enrolled in the pilot study. Upon successful installation of the app, users met with a dietitian once a week. Outcomes were measured at baseline (T0) and 2 weeks post app usage (T1). This pilot is reported as per guidelines for nonrandomized pilot and feasibility studies and in line with the CONSORT 2010 checklist for reporting pilot or feasibility trials. Results A total of 23 patients completed the pilot intervention. Mean energy intakes increased from 24.4 kcal/kg/day (SD 8.0) to 29.1 kcal/kg/day (SD 7.8) with a medium effect size (d=0.6, 95% CI 0.0-1.2). Mean protein intakes increased from 0.9 g/kg/day (SD 0.3) to 1.3 g/kg/day (SD 0.5) with a large effect size (d=1.0, 95% CI 0.4-1.6); mean intake of high biological value (%HBV) proteins also increased from 58.6% (SD 10.1) to 70.1% (SD 10.7) with a large effect size (d=1.1, 95% CI 0.5-1.7). Dietary intakes of minerals did not change, apart from sodium which decreased from a mean intake of 2218.8 mg/day (SD 631.6) to 1895.3 mg/day (SD 581.0) with a medium effect size (d=0.5, 95% CI 0.1-1.1). Mean serum phosphorus, potassium, and albumin levels did not change relevantly. Mean serum iron increased from 7.9 mg/dL (SD 2.8) to 11.5 mg/dL (SD 7.9) postintervention with a medium effect size (d=0.6, 95% CI 0.0-1.2). Conclusions This pilot study showed that the KELA.AE app has the potential to improve dietary intakes. Processes related to procedure, resources, tools, and app improvement for a future trial were assessed. A more extended intervention using a randomized controlled trial is required to estimate parameters concerning app efficacy accurately.

scholarly journals Transdiagnostic Comparison of Visual Working Memory Capacity in Bipolar Disorder and Schizophrenia

2020 ◽  
Author(s):  
Catherine Barnes-Scheufler ◽  
Caroline Passow ◽  
Lara Rösler ◽  
Jutta Mayer ◽  
Viola Oertel ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Working Memory ◽  
Visual Working Memory ◽  
Effect Size ◽  
Working Memory Capacity ◽  
Memory Capacity ◽  
Medium Effect ◽  
Full Spectrum ◽  
Small Effect Size ◽  
The Difference

Abstract BackgroundImpaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. Methods62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler’s K. ResultsWorking memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. ConclusionsThese findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.

scholarly journals 108 Lurasidone in Children and Adolescents With Bipolar Depression Presenting With Mixed Features

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 70-70
Author(s):  
Cynthia Siu ◽  
Andrei Pikalov ◽  
Michael Tocco ◽  
Antony Loebel
Keyword(s):  
Children And Adolescents ◽  
Effect Size ◽  
Repeated Measures ◽  
Mixed Model ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Depression Score ◽  
Double Blind ◽  
Increased Risk ◽  
Mixed Features

AbstractObjectiveTo evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed features.MethodsPatients 10 to 17 years of age, inclusive, with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with once-daily, flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed features (subthreshold hypomanic symptoms) was defined as a YMRS score > 5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome), and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures (MMRM) analysis.ResultsAt baseline, mixed features were present in 54.2% of patients (lurasidone, n=97/173; placebo, n=89/170). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in CDRS-R scores at week 6 in the mixed features group (-21.5 vs -15.9; P<0.01; effect size, 0.45), and in the group without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Likewise, lurasidone was associated with greater effect size (vs placebo) for reductions inCGI-BP-S scores at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features(lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%).ConclusionsIn this post-hoc analysis, lurasidone was found to be efficacious for treating child and adolescent patients with bipolar depression presenting with mixed features(assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.Funding AcknowledgementsSunovion Pharmaceuticals Inc.

scholarly journals Methylene blue treatment for residual symptoms of bipolar disorder: Randomised crossover study

2017 ◽  
Vol 210 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Martin Alda ◽  
Margaret McKinnon ◽  
Ryan Blagdon ◽  
Julie Garnham ◽  
Susan MacLellan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Methylene Blue ◽  
Crossover Study ◽  
Rating Scale ◽  
Neuroprotective Effects ◽  
Double Blind ◽  
Residual Symptoms ◽  
Symptoms Of Depression ◽  
Hamilton Rating Scale ◽  
Active Dose

BackgroundResidual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects.AimsWe conducted a double-blind crossover study of a low dose (15 mg, ‘placebo’) and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine.MethodThirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning.ResultsThe active dose of methylene blue significantly improved symptoms of depression both on the Montgomery–Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects.ConclusionsMethylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder.

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