Isabella Pacchiarotti

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: A long-term, follow-up study

OBJECTIVE To identify clinical and neurocognitive predictors of long-term functional outcome in patients with bipolar disorder METHODS A total of 32 subjects who met criteria for bipolar I or II disorder were recruited from the Barcelona Bipolar Disorder Program and were assessed clinically and neuropsychologically at baseline. After an average 4-year follow-up, they were interviewed with the Functioning Assessment Short Test (FAST) to assess functional outcome. Multivariate analyses were applied to identify clinical and neurocognitive predictors of functional outcome. RESULTS The main regression model for predictors of overall psychosocial functioning identified subclinical depressive symptoms (beta=0.516, t=3.51, p=0.002), and free delayed recall in a verbal memory task (beta=-0.314, t=-2.144, p=0.041), accounting for 36% of the variance. Specific predictors of occupational functioning were, again, subthreshold depression (beta=0.435, t=2.8, p=0.009) and a measure of executive function, digits backwards (beta=-0.347, t=-2.23, p=0.034). This model explained around 28% of the variance (corrected R(2)=0.28; F=6.38, gl=2, p=0.004). CONCLUSIONS Subdepressive symptomatology together with neurocognitive impairments related to verbal memory and executive functions are predictor variables of long-term functional outcome in bipolar disorder.

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Melancholia agitata and mixed depression

Objective:  The diagnostic entity of major depressive episode includes both simple and agitated or mixed depression. Mixed depression is characterized by a full depressive episode with several symptoms of excitatory nature. Mixed depressions worsen if treated with antidepressants.

Gender differences in a cohort study of 604 bipolar patients: The role of predominant polarity

BACKGROUND Some clinical differences between gender regarding the course and outcome of bipolar disorders have already been described and some others remain still controversial. AIMS To explore gender differences regarding clinical and socio-demographic characteristics amongst bipolar patients with particular attention to predominant polarity and depressive symptoms. METHOD Data were collected from DSM-IV type I and II bipolar patients (n=604), resulting from the systematic follow-up of the Bipolar Disorders Program, Hospital Clinic of Barcelona, over an average follow-up of 10 years. Socio-demographic and clinical variables were collected in order to detect gender-related differences. RESULTS Bipolar women are more likely than men to show a predominance of depressive polarity as well as a depressive onset whilst men would be more likely to suffer from comorbid substance use disorders. Women significantly have a higher lifetime prevalence of psychotic depression and a higher prevalence of axis II comorbid disorders. Bipolar women are also more likely to have a family history of suicide and a lifetime history of attempted suicide. Suicide attempts are more often violent amongst bipolar men. In a backward logistic regression model, two variables were responsible for most gender-related clinical differences: type of predominant polarity - more likely to be depressive amongst women - (B=-0.794, p=0.027, Exp(B)=0.452; CI= 0.223-0.915), alcohol abuse (B=-1.095, p=0.000, Exp(B)=2990; CI= 1.817-4.919) and cocaine abuse (B=0.784, p=0.033, Exp(B)=2.189; CI= 1.066-4.496) - more prevalent amongst men. CONCLUSION The main characteristic featuring bipolar women is depression, both at illness onset and as a predominant polarity all along the illness course. This may have important diagnostic and therapeutic implications.

Suicidal Risk Factors in Bipolar I and II Disorder Patients

BACKGROUND Suicidal risks may be similar in bipolar I and II disorders, but predictive risk factors are not well established for each disorder type or across cultures. METHOD Accordingly, we compared selected demographic and clinical factors for long-term association with nonlethal suicidal acts or ideation in 290 DSM-IV bipolar I (n = 204) and II (n = 86) disorder patients followed for a mean of 9.3 years at the University of Barcelona, using preliminary bivariate comparisons followed by multivariate logistic regression modeling. RESULTS Rates of suicidal ideation (41.5%) and acts (19.7%) were similarly prevalent with bipolar I and II disorders and somewhat more common among women. Factors significantly and independently associated with suicidal acts were determined by multivariate modeling and ranked in order of their strength of association: suicidal ideation, more mixed episodes, Axis II comorbidity, female sex, more antidepressant trials, rapid cycling, predominant lifetime depression, having been hospitalized, older onset, and longer delay of diagnosis. Suicidal ideation was associated with suicidal acts, more antidepressant trials, predominant depressions, more mixed-episodes/year, depressive first-lifetime episodes, electroconvulsive therapy use, delay of bipolar disorder diagnosis, unemployment, melancholic features, Axis II disorders, rapid cycling, and more depressions per year. Risk factors selectively associated with suicidal risk, overall, included more mixed-states per year and melancholic features, whereas hospitalization, unemployment, and predominantly depressive recurrences were more characteristic of diagnostic subtypes. CONCLUSIONS Suicidal risk-factors found to be independent of bipolar disorder diagnostic subtype included mixed-states, melancholic depressive features, and more antidepressant trials.

Suicide in a large population of former psychiatric inpatients

Aims:  The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric inpatients receiving retrospective and prospective DSM‐IV diagnoses.

Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients.

Valentí M, Pacchiarotti I, Rosa AR, Bonnín CM, Popovic D, Nivoli AMA, Murru A, Grande Í, Colom F, Vieta E. Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients.
Bipolar Disord 2011: 13: 145–154.

Predominant polarity and temperament in bipolar and unipolar affective disorders

INTRODUCTION Recently, the concept of predominant polarity (two-thirds of episodes belonging to a single pole of the illness) has been introduced to further characterise subtypes of bipolar disorders. This concept has been proven to have diagnostic and therapeutic implications, but little is known on the underlying psychopathology and temperaments. With this study, we aimed to further validate the concept and explore its relationships with temperament. METHODS This study enrolled 143 patients with bipolar or unipolar disorder. We analysed predominant polarity in the sample of bipolar I patients (N=124), focussing on those who showed a clear predominance for one or the other polarity, and distinguishing manic/hypomanic (MP) from depressive polarity (DP), and a unipolar major depression (UP) group (N=19),. We also assessed temperament by means of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). RESULTS Over 55% of the bipolar I sample fulfilled predominant polarity criteria, with two-thirds of those meeting criteria for MP and one third for DP. MP and DP were similar in scoring higher than UP on the hyperthymic/cyclothymic scales of the TEMPS-A; the UP group scored higher on the anxious/depressive scales. DISCUSSION Our results show that both bipolar I MP and DP subgroups are temperamentally similar and different from UP. Depression in DP bipolar I patients should be viewed as the overlap of depression on a hyperthymic/cyclothymic temperament. These findings confirm the value of the predominant polarity concept as well as the importance of temperaments to separate bipolar from unipolar disorders.

Has number of previous episodes any effect on response to group psychoeducation in bipolar patients? A 5‐year follow‐up post hoc analysis

Colom F, Reinares M, Pacchiarotti I, Popovic D, Mazzarini L, Martínez-Arán A, Torrent C, Rosa A, Palomino-Otiniano R, Franco C, Bonnin CM, Vieta E. Has number of previous episodes any effect on response to group psychoeducation in bipolar patients? A 5-year follow-up post hoc analysis. Objective: One of the main utilities of staging in bipolar disorder is enhancing the formulation of pharmacological and non-pharmacological treatment strategies. Hence, it is essential to ascertain whether the number of previous episodes influences treatment response. Hereby, we present a 5-year post hoc study on the efficacy of group psychoeducation for bipolar disorders according to the number of previous episodes. Methods: For this subanalysis, we have compared the 5-year outcome of 120 euthymic psychoeducated versus non-psychoeducated bipolar patients according to the number of previous episodes at study entry. Results: Patients with more than seven episodes at study entry did not show any significant improvement with psychoeducation according to time to recurrence. Patients with more than 14 episodes did not benefit from psychoeducation in terms of a reduction of time spent ill. Patients with 7 or 8 episodes showed a benefit in terms of fewer days spent in hypomania, depression, mixed episodes or any episodes but not mania, while patients with 9–14 episodes showed a benefit in terms of fewer days spent in hypomania and depression but not in mixed states or mania. Only patients who presented up to 6 episodes showed reduction in time spent in any episode polarity. Conclusion: The number of previous episodes clearly worsens response to psychoeducation, perhaps in a more subtle way than that observed with other psychological therapies. Psychoeducation should be delivered as soon as possible in the illness course, supporting the idea of early intervention.