Open-Label Adjunctive Topiramate in the Treatment of Unstable Bipolar Disorder

Objective: To assess open-label adjunctive topiramate in the treatment of outpatients with unstable bipolar disorder (BD). Method: Outpatients with DSM-IV–defined BD (I or II) exhibiting mood instability were enrolled in this 16-week, open-label, multicentre study. Topiramate was added to existing mood stabilizers and other psychotropic treatments. The primary effectiveness measure was the Clinical Global Impression of Severity (CGI-S) scale; other scales included the Young Mania Rating Scale (YMRS) and the Montgomery–Asberg Depression Rating Scale (MADRS). Safety assessments included monitoring adverse events, measuring tremor, monitoring vital signs and weight, and laboratory indices. We also evaluated patient satisfaction with treatment. Results: A total of 109 patients were enrolled. Intent-to-treat analysis showed significant improvement from baseline in the CGI-S, YMRS, and MADRS, starting at Week 2 ( P < 0.001), with further accrual of benefit between Week 2 and Week 16 ( P < 0.001). The mean modal dosage of topiramate during the stable dosing period was 180 mg daily. There was a mean 1.8 kg decrease in patient weight from topiramate initiation to Week 16 ( P < 0.001). Topiramate was well tolerated by most patients; 11% withdrew from the study owing to adverse events. We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment ( P < 0.005); no notable changes in vital signs were observed. At Week 16, 50% of the patients were “completely satisfied” with topiramate treatment. Conclusions: Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms, as well as reducing tremor and weight in outpatients with BD I or II.

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

CNS Spectrums ◽

10.1017/s1092852900021519 ◽

2007 ◽

Vol 12 (9) ◽

pp. 683-689 ◽

Cited By ~ 43

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.

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Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA study

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2009.00378.x ◽

2009 ◽

Vol 21 (3) ◽

pp. 125-132 ◽

Cited By ~ 3

Author(s):

Eric Constant ◽

Arlette Seghers ◽

Enio Ranalli ◽

Vincent Ryckmans ◽

Phillippe Snauwaert ◽

...

Keyword(s):

Adverse Events ◽

Adverse Drug Reactions ◽

Dose Escalation ◽

Rating Scale ◽

Vital Signs ◽

Severity Of Illness ◽

Manic Episode ◽

Drug Reactions ◽

Open Label ◽

Young Mania

Objective:The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode.Methods:In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400–800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21.Results:Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study.Conclusion:Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode.

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Does the efficacy of asenapine in bipolar disorder increase in the presence of comorbidity with a substance use disorder? A naturalistic study

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125316674698 ◽

2016 ◽

Vol 7 (2) ◽

pp. 67-77 ◽

Cited By ~ 8

Author(s):

Sergio De Filippis ◽

Ilaria Cuomo ◽

Georgios D. Kotzalidis ◽

Daniela Pucci ◽

Pietro Zingaretti ◽

...

Keyword(s):

Bipolar Disorder ◽

Substance Use ◽

Substance Use Disorder ◽

Repeated Measures ◽

Rating Scale ◽

Type I ◽

Open Label ◽

Young Mania ◽

Psychiatric Rating ◽

Psychiatric Rating Scale

Background: Asenapine is a second-generation antipsychotic approved in Europe for treating moderate-to-severe manic episodes in adults affected by type I bipolar disorder (BD-I). We aimed to compare its efficacy in psychiatric inpatients with BD-I, with or without substance use disorder (SUD). Methods: We administered flexible asenapine doses ranging from 5–20 mg/day to 119 voluntarily hospitalized patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) BD-I diagnosis, with or without SUD. Patients were assessed with clinician-rated questionnaires [i.e. Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Global Assessment of Functioning (GAF)]. Assessments were carried out at baseline (T0, prior to treatment), and 3 (T1), 7 (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF. Results: Patients improved on all scales ( p < 0.001) across all timepoints, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Patients without comorbid SUD showed greater reductions in BPRS scores at T2 and T3, greater reduction in YMRS scores at T3, and lower HARS scores at all timepoints. HDRS scores did not differ between the two groups at any timepoint. However, the reduction in HARS scores in the comorbid group was stronger than in the BD-I only group, albeit not significantly. Side effects were few and mild-to-moderate. Conclusions: The open-label design and the relatively short observation period may expose to both type I and type II statistical errors (false positive and false negatives). Asenapine showed effectiveness and safety in hospitalized BD-I patients. Its effect was stronger in patients without comorbid SUD.

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Combined treatment with reboxetine in depressed patients with no response to venlafaxine: a 6-week follow-up study

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2007.00187.x ◽

2007 ◽

Vol 19 (5) ◽

pp. 291-296 ◽

Cited By ~ 6

Author(s):

Cecilio Álamo ◽

Francisco López-Muñoz ◽

Gabriel Rubio ◽

Pilar García-García ◽

Antonio Pardo

Keyword(s):

Adverse Events ◽

Rating Scale ◽

Combined Treatment ◽

Open Label ◽

Serious Adverse Events ◽

Multicentric Study ◽

Intent To Treat ◽

Events Data ◽

Clinical Global Impression Improvement

Objective:The purpose of present study was to evaluate the efficacy of the addition of reboxetine in patients that had not previously responded, or had done so only partially, over 6 weeks of conventional pharmacological treatment with venlafaxine.Methods:This open-label, prospective and multicentric study included 40 outpatients diagnosed with major depressive disorder according to the DSM-IV criteria. Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression-Improvement (CGI-I). Safety was evaluated by recording spontaneously reported adverse events. Data were analysed on an intent-to-treat basis, using the last-observation-carried-forward method.Results:Mean HAMD reduction was 34.9% (P < 0.0001). The percentages of responders (≥50% reduction in HAMD) and patients considered as benefiting from complete remission (HAMD ≤ 10 points) at week 6 were 27.5 and 12.5%, respectively. By the end of the treatment, the score of CGI-I decreased 24.8% (P < 0.0001). Percentage of patient improving (CGI < 4 points) was 47.5%. The most common non-serious adverse events were constipation, nervousness, anxiety and insomnia.Conclusion:These findings suggest that the combined treatment of reboxetine and venlafaxine, in venlafaxine-resistant patients, may be an effective and well-tolerated strategy.

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Long-Term Safety and Effectiveness of Mixed Amphetamine Salts Extended Release in Adults With ADHD

CNS Spectrums ◽

10.1017/s1092852900002406 ◽

2005 ◽

Vol 10 (S20) ◽

pp. 16-25 ◽

Cited By ~ 41

Author(s):

Joseph Biederman ◽

Thomas J. Spencer ◽

Timothy E. Wilens ◽

Richard H. Weisler ◽

Stephanie C. Read ◽

...

Keyword(s):

Adverse Events ◽

Adult Adhd ◽

Extended Release ◽

Rating Scale ◽

Vital Signs ◽

Therapeutic Effects ◽

Open Label ◽

Dose Escalation Study ◽

Double Blind

AbstractObjective: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced–dose-escalation study of MAS XR in adults (≥ 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mgl day for 1 week, with subsequent titration up to 60 mgl day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-N). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2±13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity.Conclusion: Treatment with MAS XR 20–60 mgl day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.

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Efficacy and Tolerability of Long-Term, Open-Label, Mixed Amphetamine Salts Extended Release in Adolescents With ADHD

CNS Spectrums ◽

10.1017/s1092852900014103 ◽

2005 ◽

Vol 10 (S15) ◽

pp. 14-21 ◽

Cited By ~ 9

Author(s):

Thomas J. Spencer ◽

Joseph Biederman ◽

Timothy E. Wilens

Keyword(s):

Adverse Events ◽

Extended Release ◽

Rating Scale ◽

Controlled Trial ◽

Vital Signs ◽

Adhd Symptoms ◽

Open Label ◽

End Point ◽

Term Tolerability

AbstractObjectiveAssess long-term tolerability and efficacy of once-daily mixed amphetamine salts extended release (MAS XR) for attention-deficit/hyperactivity disorder (ADHD) in adolescents (13–17 years of age).MethodsEfficacy of MAS XR (10–60 mg/day) in 138 adolescents with ADHD was assessed in a 6-month, openlabel, extension study following participation in a 4-week, randomized, placebo-controlled trial of MAS XR. Efficacy was based on ADHD Rating Scale-IV (ADHD-RS-IV) scores and Clinical Global Impressions-Improvement (CGI-I) ratings at end point. Tolerability was based on reported adverse events, physical and laboratory examintions, vital signs, and electrocardiographic measures.FindingsPatients exhibited sustained improvement in ADHD symptoms in this 6-month, open-label study of MAS XR 10–60 mg/day. End point ADHD-RS-IV total score was significantly decreased from baseline (-7.9; P<.0001); similar decreases were seen for hyperactivity/impulsivity (-4.0; P<.0001) and indttentiveness (-3.8; P<.0001). Based on CGI-I ratings, 60.9% of patients were very much/much improved, 33.3% were unchanged, 5.8% were much worse, and 0% were very much worse. The most common adverse events related to MAS XR were anorexia (24.6%), weight loss (24.6%), headache (14.5%), and nervousness (13.0%).ConclusionLong-term MAS XR therapy is generally well tolerated and exerts sustained control of ADHD symptoms in otherwise healthy adolescents.

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Aripiprazole Augmentation to Mood Stabilizers for Obsessive-Compulsive Symptoms in Bipolar Disorder

Medicina ◽

10.3390/medicina57010009 ◽

2020 ◽

Vol 57 (1) ◽

pp. 9

Author(s):

Gabriele Di Salvo ◽

Giuseppe Maina ◽

Enrico Pessina ◽

Elena Teobaldi ◽

Francesca Barbaro ◽

...

Keyword(s):

Bipolar Disorder ◽

Adverse Events ◽

Prospective Observational Study ◽

Response Rate ◽

Clinical Symptoms ◽

Mood Stabilizers ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Promising Treatment ◽

The Mean

Background and objectives: Aripiprazole is a first-line agent in the treatment of bipolar disorder (BD) and available data demonstrates its efficacy on clinical symptoms in serotonin reuptake inhibitors-resistant obsessive-compulsive disorder (OCD) patients. Therefore, aripiprazole augmentation to mood stabilizers could represent a promising treatment in BD patients with comorbid OCD. The study examined the efficacy and safety of aripiprazole added to lithium or valproate for the treatment of obsessive-compulsive (OC) symptoms in euthymic BD patients with comorbid OCD. Materials and methods: This is a 12-week prospective observational study. The efficacy of aripiprazole on OC symptoms was assessed through the mean change of Yale–Brown Obsessive-Compulsive (YBOCS) total score. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Results: A total of 70 patients were included in the analyses. The withdrawal rate was 21.4%, mainly due to adverse events. Mean ± SD final aripiprazole dose was 15.2 ± 5.3 in the completer sample (N = 55). The Y-BOCS mean score decreased from 24.0 ± 4.1 at baseline to 17.1 ± 4.3 at 12 weeks. Treatment response rate (Y-BOCS reduction ≥ 35%) was 41.8%, while partial response rate (Y-BOCS reduction greater than 25% but less than 35% from baseline) accounted for the other 18.2% of patients. Overall, 91.4% of completers had at least 1 adverse effect (tremor, tension/inner unrest, reduced duration of sleep, akathisia). No significant differences emerged comparing aripiprazole efficacy and tolerability between patients treated with lithium or valproate. Conclusion: Our findings show that aripiprazole addition to lithium or valproate can reduce OC symptoms in real-world BD euthymic patients.

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Comparisons of Narrative Psychotherapy to Conventional CBT for the Psychotherapy of Psychosis and Bipolar Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1480 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s779-s779

Author(s):

L. Mehl-Madrona ◽

B. Mainguy

Keyword(s):

Bipolar Disorder ◽

Narrative Therapy ◽

Rating Scales ◽

Psychotic Disorders ◽

Rating Scale ◽

Therapy Group ◽

Well Being ◽

Outcome Data ◽

Symptom Scale ◽

Young Mania

IntroductionThere is ongoing debate about about both the value of psychotherapy in psychotic disorders and the best type of psychotherapy to use if necessary.MethodsWe conducted narrative psychotherapy with 18 adults, all diagnosed as having bipolar disorder with psychotic features and/or schizo-affective disorder. Outcome data consisted of the Positive and Negative Symptom Scale, the Clinical Global Impressions Scale, the Young Mania Rating Scale, the Hamilton Anxiety and Depression Scales, the My Medical Outcome Profile, Version 2(MYMOP2), and the Outcome Rating Scales of Duncan and Miller. We compare the outcomes of our patients to those of a matched comparison group receiving conventional psycho-education and cognitive behavioural therapy. Patients were seen for a minimum of 16 weeks over an average of 22 weeks. Average age was 31.5 years with a standard deviation of 8.1 years.ResultsThe narrative therapy group showed statistically significant reductions in all outcome measures compared to the conventional treatment group. They continued treatment significantly longer and had fewer re-hospitalizations. They were less distressed by voices.ConclusionsA narrative psychotherapy approach using dialogical theory and therapy ideas is a reasonable approach for the psychotherapy of psychosis. Review of psychotherapy notes showed that narrative approaches allowed the therapist to align with the patient as collaborator in considering the story presented and was therefore less productive of defensiveness and self-criticism than conventional approaches. The therapy included techniques for negotiating changes in illness narratives, identity narratives, and treatment narratives that were more conducive of well-being and recovery.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Recovery and its correlates among patients with bipolar disorder: A study from a tertiary care centre in North India

International Journal of Social Psychiatry ◽

10.1177/0020764016676214 ◽

2016 ◽

Vol 62 (8) ◽

pp. 726-736 ◽

Cited By ~ 5

Author(s):

Sandeep Grover ◽

Nandita Hazari ◽

Jitender Aneja ◽

Subho Chakrabarti ◽

Sunil Sharma ◽

...

Keyword(s):

Bipolar Disorder ◽

Mental Illness ◽

Depressive Symptoms ◽

Rating Scale ◽

Tertiary Care ◽

North India ◽

Personal Recovery ◽

Tertiary Care Centre ◽

Young Mania ◽

Level Of Functioning

Background and Aim: The goal of treatment in mental illness has evolved from a symptom-based approach to a personal recovery–based approach. The aim of this study was to evaluate the predictors of personal recovery among patients with bipolar disorder. Methodology: A total of 185 patients with bipolar disorder, currently in remission, were evaluated on Recovery Assessment Scale (RAS), Internalized Stigma of Mental Illness Scale (ISMIS), Brief Religious coping scale (RCOPE), Duke University Religiosity Index (DUREL), Religiousness Measures Scale, Hamilton depression rating scale (HDRS), Young Mania rating scale (YMRS) and Global Assessment of Functioning (GAF) scale. Results: The mean age of the sample was 40.5 (standard deviation (SD), 11.26) years. Majority of the participants were male, married, working, Hindu by religion and belonged to extended/joint families of urban background. In the regression analysis, RAS scores were predicted significantly by discrimination experience, stereotype endorsement and alienation domains of ISMIS, level of functioning as assessed by GAF, residual depressive symptoms as assessed by HDRS and occupational status. The level of variance explained for total RAS score and various RAS domains ranged from 36.2% to 46.9%. Conclusion: This study suggests that personal recovery among patients with bipolar disorder is affected by stigma, level of functioning, residual depressive symptoms and employment status of patients with bipolar disorder.

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Effect of Patiromer in Hyperkalemic Patients Taking and Not Taking RAAS Inhibitors

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248418788334 ◽

2018 ◽

Vol 23 (6) ◽

pp. 524-531 ◽

Cited By ~ 5

Author(s):

Robert A. Kloner ◽

Coleman Gross ◽

Jinwei Yuan ◽

Ansgar Conrad ◽

Pablo E. Pergola

Keyword(s):

Adverse Events ◽

Serum Potassium ◽

Common Adverse Event ◽

Open Label ◽

Serious Adverse Events ◽

End Point ◽

The Mean ◽

Baseline Characteristics ◽

Raas Inhibitors ◽

Post Hoc

Introduction: Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients with renal disease regardless of the use of renin–angiotensin–aldosterone system inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic patients similarly when given with or without food; unlike prior studies, patients were not required to be taking RAASi. We conducted post hoc analyses to provide the first report of patiromer in patients not taking RAASi. Methods: Hyperkalemic patients received patiromer, 8.4 g/d to start, adjusted to achieve and maintain serum potassium of 3.8 to 5.0 mEq/L. If taking RAASi, stable doses were required. The primary end point was the proportion of patients with serum potassium 3.8 to 5.0 mEq/L at week 3 or 4. This analysis presents data by patients taking or not taking RAASi. Results: Demographics and baseline characteristics were similar in patients taking (n = 67) and not taking RAASi (n = 45). Baseline mean (SD) serum potassium was 5.37 (0.37) mEq/L and 5.42 (0.43) mEq/L in patients taking and not taking RAASi, respectively. Mean (SD) daily patiromer doses were similar (10.7 [3.2] and 11.5 [4.0] g, respectively). The primary end point was achieved in 85% (95% confidence interval [CI]: 74-93) of patients taking RAASi and in 84% (95% CI: 71-94) of patients not taking RAASi. From baseline to week 4, the mean (SE) change in serum potassium was −0.67 (0.08) mEq/L in patients taking RAASi and −0.56 (0.10) mEq/L in patients not taking RAASi (both P < .0001 vs baseline, P = nonsignificant between groups). Adverse events were reported in 26 (39%) patients taking RAASi and 25 (54%) not taking RAASi; the most common adverse event was diarrhea (2% and 11%, respectively; no cases were severe). Five patients (2 taking RAASi) reported 6 serious adverse events; none considered related to patiromer. Conclusions: Patiromer was effective and generally well-tolerated for hyperkalemia treatment, whether or not patients were taking RAAS inhibitors.

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