Andrea Murru

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.

New treatment guidelines for acute bipolar mania: A critical review

A number of treatment guidelines for bipolar disorder have been published and updated in the last few years. They are aimed at providing a synthesis of the best available scientific knowledge, and their application to every-day work should be helpful to clinicians. The aim of this report is to critically review recent guidelines focusing on the treatment of manic/hypomanic and mixed episodes. Guidelines are quite heterogeneous in methodology and conclusions, but they all agree that the treatment of manic/hypomanic and mixed episodes should generally be initiated with a medication such as lithium (Li), valproate (VPA) or atypical antipsychotics (AAP), including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone as monotherapy. All guidelines agree on stopping ongoing antidepressant medication during mania. Combination therapy including Li or VPA with an AAP is suggested usually as second-line choice, sometimes as first-choice treatment for severe mania. Carbamazepine is mostly suggested as second line and not recommended in combination. Other antiepileptic drugs are not recommended for the treatment of mania, although lamotrigine may be maintained if it was prescribed previously for the prevention of depressive episodes. Main sources of discrepancies among guidelines include benefit-risk ratio issues (how much priority is given to efficacy over safety and tolerability), starting with combination versus monotherapy, and how to deal with treatments which are more experience-based than evidence-based (i.e.: electroconvulsive therapy).

Validation of the Italian version of the "Mood Disorder Questionnaire" for the screening of bipolar disorders

The study measured the accuracy of the Italian version of the Mood Disorder Questionnaire (MDQ) as a screening instrument for bipolar disorders in a psychiatric setting.Methods154 consecutive subjects attending the Division of Psychiatry of the University of Cagliari (Italy), were screened for bipolar disorders using the Italian translation of the MDQ, and diagnostically interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) by physicians.ResultsOn the basis of the SCID: 51 (33.1%) received a diagnosis of bipolar or schizoaffective bipolar type disorders, 63 (40.9%) were diagnosed as having at least one psychiatric disorder in Axis I (other than bipolar or schizoaffective bipolar type disorders), whilst 40 (25.9%) were unaffected by any type of psychiatric disorder. MDQ showed a good accuracy for bipolar or schizoaffective bipolar type disorders: the cut-off 4 had sensitivity 0.90 and specificity 0.58; the cut-off 5 had sensitivity 0.84 and specificity 0.70; and the cut-off 6 had sensitivity 0.76 and specificity 0.86. The accuracy for bipolar II disorders was sufficient but not excellent: the cut-off 4 had sensitivity 0.80 and specificity 0.45; the cut-off 5 had sensitivity 0.70 and specificity 0.55; and the cut-off 6 had sensitivity 0.55 and specificity 0.65.ConclusionOur results seem to indicate a good accuracy of MDQ, and confirm the results of recent surveys conducted in the USA. Moreover the instrument needs to be validated in other settings (e.g. in general practice).

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.

The accuracy of the Italian version of the Hypomania Checklist (HCL-32) for the screening of bipolar disorders and comparison with the Mood Disorder Questionnaire (MDQ) in a clinical sample

BackgroundThe study measured the accuracy of the Italian version of the Hypomania Checklist (HCL-32) for self-assessment as a screening instrument for bipolar disorder (BPD) in a psychiatric setting and compared results with a previous study, carried out in a comparable sample and in the same setting, using the Mood Disorder Questionnaire (MDQ).Methods123 consecutive subjects attending a psychiatric division were screened for BPD using the Italian translation of the HCL-32, and diagnostically interviewed with the SCID by physicians. The sample of the previous study using the MDQ consisted of 154 subjects.ResultsOn the basis of the SCID: 26 received a diagnosis of bipolar/schizoaffective disorder, 57 were diagnosed as having at least another psychiatric disorder in Axis-I, whilst 40 were unaffected by any type of psychiatric disorder. Comparing the bipolar with all other patients the HCL-32 showed a good accuracy: cut-off 8: sensitivity 0.92-specificity 0.48; cut-off 10: sensitivity 0.88-specificity 0.54; cut-off 12: sensitivity 0.85-specificity 0.61. The accuracy for BPD-II (10) remains good: cut-off 8: sensitivity 0.90-specificity 0.42; cut-off 10: sensitivity 0.80-specificity 0.47; cut-off 12: sensitivity 0.80-specificity 0.54. The comparison with the MDQ performance shows that both screening tools may show good results, but HCL-32 seems to be more sensitive in detecting BPD-II.ConclusionOur results seem to indicate good accuracy of HCL-32 as a screening instrument for BPD in a psychiatric setting, with a low rate of false negatives, and a fairly good degree of identification of BPD-II.

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.

Mood instability and functional recovery in bipolar disorders.

The aim of this study was to identify psychopathological factors associated with long‐term functional outcome in euthymic bipolar disorder patients and to test new measures of mood instability and symptoms intensity.

Risk factors for antidepressant-related switch to mania.

OBJECTIVE Treatment of bipolar depression with antidepressants is strongly debated on the basis of the methodologically poor and insufficient data supporting their use and the widely held belief that antidepressants can induce new episodes of abnormal mood elevation or accelerate the rate of cycling. The present study aimed at identifying clinical risk factors for switch into hypomania, mania, or mixed states, within 8 weeks after introduction of an antidepressant or after increasing its dosage, in a prospective, longitudinal design. METHOD 221 consecutive DSM-IV-TR depressed bipolar I and II disorder patients were treated with antidepressants, which were added to previously prescribed mood stabilizers and/or atypical antipsychotics. No patient was on antidepressant monotherapy. The patients were enrolled from October 2005 through January 2010. The primary outcome was the assessment of switch to mania or hypomania within 8 weeks after the introduction or dose increase of an antidepressant. Both groups were compared with analysis of variance and χ² procedures. RESULTS Treatment-emergent affective switch was detected in 54 patients (24.4%) (switch group) while 167 patients (75.6%) (nonswitch group) did not experience a treatment-related switch. The main clinical differences significantly associated with the occurrence of an antidepressant-related switch, after performing logistic regression analysis, were higher rate of previous switches (P < .001) in the switch versus the nonswitch group, lower rate of responses to antidepressants (P < .001) in the switch versus the nonswitch group, and earlier age at onset (P = .026) in the switch versus the nonswitch group. DISCUSSION Bipolar patients with an earlier age at onset and an illness course characterized by lower rate of response to antidepressants and higher rate of switches into mania or hypomania were found to be the ones with higher switch risk. Nevertheless, a greater number of previous antidepressant exposures was not associated with the occurrence of an antidepressant-associated switch. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01503489.

Lithium: Still a Cornerstone in the Long-Term Treatment in Bipolar Disorder?

Background: Scientific literature considers lithium a key treatment for the acute and long-term management of bipolar disorder (BD). Despite its worldwide clinical use, the effectiveness of lithium has been questioned. The aim of this work is to critically review the available data on randomized controlled trials (RCTs) concerning long-term lithium treatment. Methods: A systematic search for long-term treatment RCTs with at least 6 months of follow-up was performed. Six RCTs enrolling 1,561 bipolar I and II patients of adult and pediatric age, randomizing 534 to lithium, were identified. All studies are controlled trials sponsored by industry, investigating new treatments for BD, with lithium as an active comparator, and therefore not specifically designed to study lithium efficacy or safety. Results: Results from earliest studies suggest a high effectiveness of lithium against both mania and depression, while more recent studies highlight lithium as more effective than placebo in mania and hypomania, without significant evidence in depression. Lithium does not achieve significant differences in efficacy when compared with divalproex; it seems less effective than lamotrigine in preventing depression and less effective than olanzapine in manic and mixed episodes. Conclusions: Despite a number of methodological issues (enriched designs, unbalanced samples, potential inclusion of lithium nonresponders in some studies), lithium appears to have a clear antimanic prophylactic activity and some efficacy in the prevention of depression. Lithium should still have a major role in the long-term treatment of BD.

Differential outcome of bipolar patients receiving antidepressant monotherapy versus combination with an antimanic drug

INTRODUCTION Despite antidepressants are widely used in treating bipolar depression, there is much debate about their utility and their potential dangers, involving mood switches and suicidality. Our hypothesis was that the pattern of initial antidepressant prescription, i.e., alone (AM) or in combination with stabilizers (AC) might impact the long-term outcome of patients with bipolar disorder (BP). We aimed to test this hypothesis and to identify outcome measures that could be predicted by initial AM or AC treatment in patients with BP. METHODS We included 95 patients with DSM-IV BP from a pool of 138 patients following a BP program. Patients were rated for initial AM vs. AC treatment when they were first seen in primary care and subdivided into two groups accordingly. Differences in their clinical course were sought investigating course both retrospectively and prospectively (mean follow-up 10 years). Primary outcome measures comprised suicidality and switch rate. RESULTS There were significantly more patients who switched in the AM group than in the AC group. The number of suicide attempts was higher in the AM group. Significance was retained after performing logistic regression. LIMITATIONS Sample size was small and severe BP patients might be overrepresented in this sample. DISCUSSION Initial AM treatment of patients subsequently diagnosed as BP may entrain a course characterized by higher proneness to switch and suicidal behaviour. Accurate initial diagnosis of bipolar depression should prompt combined treatment with antimanic drugs.