Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Background.The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.Method.Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.Results.Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.Conclusions.Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

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Psychotic versus non-psychotic bipolar disorder: Socio-demographic and clinical profiles in an Italian nationwide study

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867418823268 ◽

2019 ◽

Vol 53 (8) ◽

pp. 772-781 ◽

Cited By ~ 5

Author(s):

Alfredo Carlo Altamura ◽

Massimiliano Buoli ◽

Bruno Mario Cesana ◽

Andrea Fagiolini ◽

Andrea de Bartolomeis ◽

...

Keyword(s):

Bipolar Disorder ◽

Confidence Interval ◽

Clinical Features ◽

Odds Ratio ◽

Age At Onset ◽

Psychotic Symptoms ◽

Bipolar Type ◽

Bipolar Patients ◽

Depressive Episodes ◽

First Diagnosis

Objective: Psychotic versus non-psychotic patients with bipolar disorder have been traditionally associated with different unfavorable clinical features. In this study on bipolar Italian patients, we aimed to compare clinical and demographic differences between psychotic and non-psychotic individuals, exploring clinical factors that may favor early diagnosis and personalized treatment. Methods: A total of 1671 patients (males: n = 712 and females: n = 959; bipolar type 1: n = 1038 and bipolar type 2: n = 633) from different psychiatric departments were compared according to the lifetime presence of psychotic symptoms in terms of socio-demographic and clinical variables. Chi-square tests for qualitative variables and Student’s t-tests for quantitative variables were performed for group comparison, and a multivariable logistic regression was performed, considering the lifetime psychotic symptoms as dependent variables and socio-demographic/clinical characteristics as independent variables. Results: Psychotic versus non-psychotic bipolar subjects resulted to: be more frequently unemployed ( p < 0.01) and never married/partnered ( p < 0.01); have an earlier age at onset ( p < 0.01); more frequently receive a first diagnosis different from a mood disorder ( p < 0.01); have a shorter duration of untreated illness ( p < 0.01); have a more frequently hypomanic/manic prevalent polarity ( p < 0.01) and a prevalent manic–depressive type of cycling ( p < 0.01); present a lower lifetime number of depressive episodes ( p < 0.01), but have more manic episodes ( p < 0.01); and less insight ( p < 0.01) and more hospitalizations in the last year ( p < 0.01). Multivariable regression analysis showed that psychotic versus non-psychotic bipolar patients received more frequently a first diagnosis different from bipolar disorder (odds ratio = 0.64, 95% confidence interval = [0.46, 0.90], p = 0.02) or major depressive disorder (odds ratio = 0.66, 95% confidence interval = [0.48, 0.91], p = 0.02), had more frequently a prevalent manic polarity (odds ratio = 1.84, 95% confidence interval = [1.14, 2.98], p < 0.01) and had a higher number of lifetime manic episodes (more than six) (odds ratio = 8.79, 95% confidence interval = [5.93, 13.05], p < 0.01). Conclusion: Lifetime psychotic symptoms in bipolar disorder are associated with unfavorable socio-demographic and clinical features as well as with a more frequent initial misdiagnosis.

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Bipolar depression: trial-based insights to guide patient care

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2008.10.2/dekemp ◽

2008 ◽

Vol 10 (2) ◽

pp. 181-192 ◽

Cited By ~ 1

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Unmet Need ◽

Mood Stabilizers ◽

Number Needed To Treat ◽

Clinical Approach ◽

Clinical Trial Results ◽

Major Depressive Episodes ◽

Depressive Episodes ◽

Illness Phase

For the majority of patients with bipolar disorder, major depressive episodes represent the most debilitating and difficult-to-treat illness dimension. Patients spend significantly more time depressed than manic or hypomanic, and attempt suicide more frequently during this illness phase, yet the availability of treatments remains limited. The discovery of more effective therapeutics for managing depressive episodes is arguably the greatest unmet need in bipolar disorder. This article provides an evidence-based summary of pharmacological treatments for the acute and longitudinal management of bipolar depression. Clinical trial results are reviewed for a diverse array of compounds, inclusive of traditional mood stabilizers (eg, lithium and divalproex), atypical antipsychotics, unimodal antidepressants, and modafinil. Where applicable, differences in efficacy across compounds are examined through discussion of number needed to treat and effect size determinations. A pragmatic clinical approach is presented for management of the depressed phase of bipolar disorder.

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Rethinking the Treatment Paradigm for Bipolar Depression: The Importance of Long-Term Management

CNS Spectrums ◽

10.1017/s1092852900004351 ◽

2004 ◽

Vol 9 (S9) ◽

pp. 11-18 ◽

Cited By ~ 4

Author(s):

Claudia F. Baldassano ◽

Christos A. Ballas ◽

John P. O'Reardon

Keyword(s):

Bipolar Disorder ◽

Maintenance Therapy ◽

Bipolar Depression ◽

Open Label ◽

Randomized Controlled Studies ◽

Treatment Paradigm ◽

Bipolar Patients ◽

Depressive Episodes ◽

Term Management

ABSTRACT:The need for long-term management of bipolar disorder is evident. Bipolar patients spend more time depressed than manic; however, few agents used for maintenance therapy of bipolar disorder have demonstrated good efficacy in delaying relapse into depression. This article provides a comprehensive review of open-label and randomized, controlled studies examining prophylactic efficacy in bipolar disorder, especially bipolar depression. Lithium, considered the gold standard for bipolar disorder maintenance therapy may be more effective in delaying manic relapse than in delaying depressive relapse. Evidence for the efficacy of divalproex and carbamazepine in delaying depressive relapse is yet to be fully elucidated. Lamotrigine has demonstrated efficacy in delaying time to depressive relapse. Unpublished studies show ohnzapine's efficacy in preventing manic recurrence, while its efficacy in preventing depressive recunence is yet to be proven. As patients with bipohr disorder are prone to experiencing depressive episodes, more attention needs to be focused on preventing depressive relapse. To date, three agents—lithium, lamotrigine, and olanzapine—have been shown to have prophylactic benefits in treating this highly recunent disorder.

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

International Journal of Bipolar Disorders ◽

10.1186/s40345-019-0155-y ◽

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

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Quality of life in bipolar disorders compared to schizophrenia

European Psychiatry ◽

10.1016/s0924-9338(11)71941-1 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 231-231

Author(s):

L. Zouari ◽

I. Abida ◽

M. Walha ◽

J. Masmoudi ◽

J. Ben Thabet ◽

...

Keyword(s):

Quality Of Life ◽

Bipolar Disorder ◽

Short Form ◽

Age At Onset ◽

Bipolar Disorders ◽

Subscale Score ◽

Sf 36 ◽

Schizophrenic Patients ◽

Bipolar Patients

IntroductionThe classic opinion of a favorable prognosis of bipolar disorders, compared to schizophrenia, is refuted by modern conceptions.ObjectivesThe aim of this study was to assess the quality of life (QOL) in bipolar patients compared to schizophrenic patients’, and to identify clinical and sociodemographic variables statistically associated to a poor QOL in bipolar disorder patients.MethodsOne hundred and twenty outpatients, 50 with bipolar disorder and 70 with schizophrenia, according to DSM-IV-TR criteria, were included in the study. The QOL has been assessed, in all patients, using the «36 item Short-Form Health Survey» (SF-36).ResultsThirty-six percent of the bipolar patients had a poor QOL, versus 37% among the schizophrenic patients. The bipolar patients had the score of the standardized vitality subscale significantly lower than schizophrenic patients’ (p = 0.036); the latter had the standardized general health subscale score significantly lower (p = 0.03). There were no other statistically significant differences. The multivariate analyses showed three variables significantly correlated to a poor QOL in bipolar patients: age at the time of the study ≥ 40 years (p = 0.01), professional irregularity or inactivity (p = 0.005), age at onset ≥ 25 years (p = 0.004).ConclusionOur survey of the QOL in bipolar patients showed that it did not differ globally from the schizophrenic patients’, with the SF-36 scale. Results reported in the literature are not in agreement. Further longitudinal studies on several months, with other assessments, would permit to verify the validity of our results.

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Early and Late Onset Bipolar Disorders in Older Adults

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2179 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S211-S211

Author(s):

N. Smaoui ◽

L. Zouari ◽

N. Charfi ◽

M. Maâlej-Bouali ◽

N. Zouari ◽

...

Keyword(s):

Older Adults ◽

Bipolar Disorder ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Age At Onset ◽

Bipolar Disorders ◽

Medical Diagnoses ◽

The Mean ◽

Bipolar Patients

IntroductionAge of onset of illness may be useful in explaining the heterogeneity among older bipolar patients.ObjectiveTo examine the relationship of age of onset with clinical, demographic and behavioral variables, in older patients with bipolar disorder.MethodsThis was a cross-sectional, descriptive and analytical study, including 24 patients suffering from bipolar disorders, aged 65 years or more and followed-up in outpatient psychiatry unit at Hedi Chaker university hospital in Sfax in Tunisia. We used a standardized questionnaire including socio-demographic, behavioral and clinical data. Age of onset was split at age 40 years into early-onset (< 40 years; n = 12) and late-onset (≥ 40 years; n = 12) groups.ResultsThe mean age for the entire sample was 68.95 years. The mean age of onset was 39.95 years. The majority (60%) of patients were diagnosed with bipolar I. Few meaningful differences emerged between early-onset and late-onset groups, except that tobacco use was significantly higher in the late-onset group (66.6% vs. 16.6%; P = 0.027). No significant differences between the early-onset and late-onset groups were seen on demographic variables, family history and number of medical diagnoses or presence of psychotic features.ConclusionOur study found few meaningful behavioral differences between early versus late age at onset in older adults with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Cognitive impact in bipolar disorder

Archives of Depression and Anxiety ◽

10.17352/2455-5460.000042 ◽

2019 ◽

pp. 052-058

Author(s):

Bourin Michel

Keyword(s):

Bipolar Disorder ◽

Verbal Memory ◽

Visual Memory ◽

Age Of Onset ◽

Cognitive Difficulties ◽

Speed Of Information Processing ◽

History Of ◽

Bipolar Patients ◽

Disability Severity ◽

Depressive Episodes

It appears that bipolar patients suffer from cognitive difficulties whereas they are in period of thymic stability. These intercritical cognitive difficulties are fairly stable and their severity is correlated with the functional outcome of patients. Nevertheless, the profile of cognitive impairment varies significantly from study to study quantitatively and qualitatively. According to the studies, the authors find difficulties in terms of learning, verbal memory, visual memory, working memory, sustained attention, speed of information processing, functions executive. On the other hand, deficits of general intelligence, motor functions, selective attention, and language are not usually found. One of the reasons for the heterogeneity of results is the difficulty of exploring cognition in bipolar disorder. Many factors must be taken into account, such as the presence of residual mood symptoms, the longitudinal history of the disorder (age of onset, number of episodes due, among others, the neurotoxic impact of depressive episodes and deleterious cognitive effects). (length of hospitalization), level of disability severity, comorbidities (particularly addictive).

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Impulsivity predicts illness severity in long-term course of bipolar disorder: A prospective approach

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867418783062 ◽

2018 ◽

Vol 52 (9) ◽

pp. 876-886 ◽

Cited By ~ 2

Author(s):

Jonas Rote ◽

Alice-Mai-Ly Dingelstadt ◽

Annette Aigner ◽

Michael Bauer ◽

Jana Fiebig ◽

...

Keyword(s):

Bipolar Disorder ◽

Linear Regression Analysis ◽

Age At Onset ◽

Illness Severity ◽

Observation Time ◽

Barratt Impulsiveness Scale ◽

Trait Impulsivity ◽

Morbidity Index ◽

Bipolar Patients ◽

The Impact

Background: Bipolar disorder is a common, severe and chronic mental illness. Despite this, predictors of illness severity remain poorly understood. Impulsivity is reported to be associated with bipolar disorder and aggravating comorbidities. This study therefore sought to examine the predictive value of impulsivity for determining illness severity in euthymic bipolar disorder patients. Methods: Baseline trait impulsivity of 120 bipolar euthymic patients (81 bipolar disorder I [68%], 80 female [67%]) and 51 healthy controls was assessed using Barratt Impulsiveness Scale 11. The impact of impulsivity on illness severity (measured with morbidity index) was prospectively tested in 97 patients with sufficient follow-up data (average observation time: 54.4 weeks), using linear regression analysis. Results: Barratt Impulsiveness Scale 11 total (β = 0.01; p < 0.01) and in particular Barratt Impulsiveness Scale 11 attentional subscale scores (β = 0.04; p < 0.001) predicted illness severity in bipolar disorder, while controlling for other clinical variables. Only age at onset persisted as an additional, but less influential predictor. Barratt Impulsiveness Scale 11 total scores and Barratt Impulsiveness Scale 11 attentional subscale scores were significantly higher in euthymic patients compared to controls. This was not observed for the motor or non-planning subscale scores. Limitations: The average year-long observation time might not be long enough to account for the chronic course of bipolar disorder. Conclusion: Trait impulsivity and particularly attentional impulsivity in euthymic bipolar patients can be strong predictors of illness severity in bipolar disorder. Future studies should explore impulsivity as a risk assessment for morbidity and as a therapeutic target in bipolar disorder patients.

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Repetitive transcranial magnetic stimulation in the treatment of bipolar disorder

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125320973790 ◽

2020 ◽

Vol 10 ◽

pp. 204512532097379

Author(s):

Danielle Hett ◽

Steven Marwaha

Keyword(s):

Bipolar Disorder ◽

Transcranial Magnetic Stimulation ◽

Side Effects ◽

Magnetic Stimulation ◽

Sleep Problems ◽

Bipolar Depression ◽

Repetitive Transcranial Magnetic Stimulation ◽

Controlled Trial ◽

Total N ◽

Depressive Episodes

Bipolar disorder (BD) is a debilitating mood disorder marked by manic, hypomanic and/or mixed or depressive episodes. It affects approximately 1–2% of the population and is linked to high rates of suicide, functional impairment and poorer quality of life. Presently, treatment options for BD are limited. There is a strong evidence base for pharmacological (e.g., lithium) and psychological (e.g., psychoeducation) treatments; however, both of these pose challenges for treatment outcomes (e.g., non-response, side-effects, limited access). Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, is a recommended treatment for unipolar depression, but it is unclear whether rTMS is an effective, safe and well tolerated treatment in people with BD. This article reviews the extant literature on the use of rTMS to treat BD across different mood states. We found 34 studies in total ( N = 611 patients), with most assessing bipolar depression ( n = 26), versus bipolar mania ( n = 5), mixed state bipolar ( n = 2) or those not in a current affective episode ( n = 1). Across all studies, there appears to be a detectable signal of efficacy for rTMS treatment, as most studies report that rTMS treatment reduced bipolar symptoms. Importantly, within the randomised controlled trial (RCT) study designs, most reported that rTMS was not superior to sham in the treatment of bipolar depression. However, these RCTs are based on small samples ( NBD ⩽ 52). Reported side effects of rTMS in BD include headache, dizziness and sleep problems. Ten studies ( N = 14 patients) reported cases of affective switching; however, no clear pattern of potential risk factors for affective switching emerged. Future adequately powered, sham-controlled trials are needed to establish the ideal rTMS treatment parameters to help better determine the efficacy of rTMS for the treatment of BD.

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