Search

OBJECTIVES: The aim of this study was to investigate the clinical factors associated with the development of rapid cycling, as well as to elucidate the role of antidepressants. METHODS: The present study (NCT01503489) is a prospective, naturalistic cohort study conducted in a sample of 289 patients diagnosed with bipolar disorder followed and treated for up to 14 years. The patients were divided into two groups on the basis of the development of a rapid cycling course (n = 48) or no development of such a course (n = 241), and compared regarding sociodemographic, clinical, and outcome variables. RESULTS: Among the 289 patients, 48 (16.6%) developed a rapid cycling course during the follow-up. Several differences were found between the two groups, but after performing Cox regression analysis, only atypical depressive symptoms (p = 0.001), age at onset (p = 0.015), and number of suicide attempts (p = 0.030) persisted as significantly associated with the development of a rapid cycling course. CONCLUSIONS: The development of rapid cycling during the course of bipolar disorder is associated with a tendency to chronicity, with a poorer outcome, and with atypical depressive symptomatology. Our study also suggests that the development of rapid cycling is associated with a higher use of antidepressants. Language: en

A marked disparity between functional recovery and symptomatic improvement has been demonstrated in bipolar disorder. However, most of the previous studies have been conducted in the United States, and there is little prospective research from Europe on this topic. The main objective of the present six-month follow-up study was to assess functioning in a sample of Spanish bipolar disorder patients following an acute episode or subsyndromal state. Additionally, we also evaluated the sensitivity to change of the Functioning Assessment Short Test (FAST).A total of 97 bipolar disorder patients with syndromal (n = 59) or subsyndromal (n = 38) symptoms were evaluated using the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale. The FAST was the primary measure to assess multiple areas of psychosocial functioning. Functioning was evaluated at four different time periods: baseline, 21 days, three months, and six months.A significant improvement in global functioning was found in the whole sample over the six-month period, as indicated by a reduction of FAST total score (mean ± standard deviation) from 39.97 ± 15.10 to 30.65 ± 16.93 (F = 36.104, p = 0.0001). This was also evident in all areas of functioning studied. However, only 26.4% of remitted patients (n = 42) achieved functional recovery, while 79.6% of the total sample (N = 97) experienced clinical remission of acute symptoms.Although many patients presented syndromal recovery, only a minority of them achieved favorable functioning in multiple areas, even after specialized mental health care. Furthermore, the FAST scale was sensitive to detect minimal changes in functioning in both short (21 days) and long (6 months) periods, which may be relevant to the use of this scale in clinical trials.

Over one half of bipolar patients have been reported to be more prone to either depressive or manic relapses. This study aimed to define profiles of drugs used for maintenance treatment of bipolar disorder (BD) by the means of Polarity Index. Polarity Index is a new metric indicating the relative antimanic versus antidepressive preventive efficacy of drugs. Polarity Index was retrieved by calculating Number Needed to Treat (NNT) for prevention of depression and NNT for prevention of mania ratio, as emerging from the results of randomized placebo-controlled trials. Included trials were randomized and double blind, with a minimal duration of 24 weeks, assessing effectiveness of a mood stabilizer or antipsychotic drug alone or in combination with a mood stabilizing agent versus a placebo comparator in BD maintenance treatment. Polarity Index value above 1.0 indicates a relative greater antimanic prophylactic efficacy, number below 1.0 a relative greater antidepressive efficacy. The polarity index for the drugs used in maintenance therapy for bipolar disorder was 12.09 for risperidone, 4.38 for aripiprazole, 3.91 for ziprasidone, 2.98 for olanzapine, 1.39 for lithium, 1.14 for quetiapine, and 0.40 for lamotrigine. Polarity index of valproate and oxcarbazepine may not be reliable due to the failure of their maintenance trials. The polarity index provides a measure of how much antidepressant versus antimanic a drug is in bipolar disorder prophylaxis, and may guide the choice of maintenance therapy in bipolar patients.

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.

The aim of this study was to elucidate the factors associated with the occurrence of mixed episodes, characterized by the presence of concomitant symptoms of both affective poles, during the course of illness in bipolar I disorder patients treated with an antidepressant, as well as the role of antidepressants in the course and outcome of the disorder.We enrolled a sample of 144 patients followed for up to 20 years in the referral Barcelona Bipolar Disorder Program and compared subjects who had experienced at least one mixed episode during the follow-up (n=60) with subjects who had never experienced a mixed episode (n=84) regarding clinical variables.Nearly 40% of bipolar I disorder patients treated with antidepressants experienced at least one mixed episode during the course of their illness; no gender differences were found between two groups. Several differences regarding clinical variables were found between the two groups, but after performing logistic regression analysis, only suicide attempts (p0.001), the use of serotonin norepinephrine reuptake inhibitors (p=0.041), switch rates (p=0.010), and years spent ill (p=0.022) were significantly associated with the occurrence of at least one mixed episode during follow-up.The occurrence of mixed episodes is associated with a tendency to chronicity, with a poorer outcome, a higher number of depressive episodes, and greater use of antidepressants, especially serotonin norepinephrine reuptake inhibitors.

BackgroundThere is evidence that bipolar disorder (BD) is associated with significant neurocognitive deficits and this occurs in individuals with BD type I (BD I) and with BD type II (BD II). Only a few studies have focused on cognitive impairment in BD II. The aim of this study was to describe the pattern of cognitive impairment in patients with BD II, in order to identify specific cognitive deficits that distinguish BD II from BD I patients as well as from healthy subjects.MethodWe performed a systematic review of the literature of neuropsychological studies of BD II published between 1980 and July 2009. Fourteen articles fulfilled the inclusion criteria and were included in this review.ResultsMain cognitive deficits found in BD II include working memory and some measures of executive functions (inhibitory control) and approximately half of the studies also detected verbal memory impairment.ConclusionsThere are subtle differences between the two subtypes regarding cognition. This may suggest neurobiological differences between the two subgroups which will be helpful in order to determine cognitive endophenotypes in BD subtypes.

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.

Due to the episodic and chronic nature of bipolar disorder (BD), maintenance therapy represents a critical part of treatment; however, there is a paucity of studies comparing effectiveness of available long-term treatments.The aim of this study is to determine and compare the efficacy of pharmacological treatments for maintenance treatment of BD by means of the number needed to treat (NNT).The efficacy of drugs used for maintenance treatment of BD, as emerging from the results of randomized controlled trials, was assessed using the size effect measure of NNT. PubMed searches were conducted on English-language articles published until May 2010 using the search terms "bipolar disorder," "mania," "mixed episode," or "bipolar depression," cross-referenced with trial characteristic search phrases and generic names of medications. The search was supplemented by manually reviewing reference lists from identified publications.In 15 studies, aripiprazole, olanzapine, quetiapine, risperidone long-acting injection, lithium, lamotrigine, and divalproex proved effectiveness in terms of NNTs (≥ 10% advantage over placebo) for prevention of relapse into any mood episode. Quetiapine, lithium, risperidone long-acting injection, aripiprazole, and olanzapine are effective in manic recurrence prevention. Lamotrigine, quetiapine, and lithium present significant NNTs for prevention of depressive relapses.All of the pharmacological agents assessed were effective in the prevention of any kind of mood episode; however, different efficacy profiles were found for prevention of manic and/or depressive relapses. The comparison of NNT values of the available agents may represent a useful tool in clinical settings, in order to facilitate implementation of long-term pharmacological interventions in patients with BD.

Background The temperament evaluation of the Memphis, Pisa, Paris and San Diego questionnaire (TEMPS), in its rater-wise and its self-evaluation forms, has been designed to evaluate temperamental characteristics in clinical and non-clinical populations. The validation process is currently in progress in various countries. In order to improve this validation process we have extended the area of correlations of its self-evaluation form (TEMPS-A[P]) to MMPI, and to a special RS that allows assessment of the emotional-affective state following a stressful situation. Methods In 693 candidates applying to become cadets in the Italian Air Force we have assessed the correlation between the TEMPS-A[P] and the MMPI validity and clinical scales, and administered an emotional-affective state questionnaire (EAS-RS) after they had gone through the stressful challenge of taking an academy entrance examination. Results As regards MMPI validity scales, TEMPS-A[P] depressive candidates tend to report their symptoms sincerely. Hyperthymic candidates tend to give false answers so that others will see them in a good light. Cyclothymic and irritable candidates tend to exaggerate symptoms. As regards the MMPI clinical scales, a low level of linkage between affective temperaments and abnormal personality traits was found. As regards EAS-RS: hyperthymic temperament on one hand, and cyclothymic and depressive temperaments on the other, are characterized by counter-polar emotional states following the test; these are desirable in the first case and undesirable in the other two . Conclusions The convergent and discriminant validity of TEMPS-A[P] was confirmed. From a personalistic point of view, temperaments seem to belong to the realm of normality rather than to that of pathology, in line with their putative adaptive role.

It is commonly assumed that people who are addicted to certain substances would abuse any substance. This position has never been supported by validly collected and analyzed research data. In this study, the authors examine the use of street methadone by heroin addicts seeking their first agonist opioid treatment in a clinical setting. Fifty-four heroin addicts who resorted to street methadone use were compared by socio-demographic, current clinical, and disease-related variables to 251 peers who do not use street methadone. Heroin addicts who resort to street methadone use are more likely to be females and to have a higher degree of education, are less likely to engage in polyabuse (use of more than three substances), are less severely ill, have been addicted for a shorter period of time, and have been seeking treatment sooner in the course of their disease. Also, they suffer from a wider range of psychopathological distress symptoms. In Italy, resorting to street methadone does not seem to be a surrogate form of heroin addiction, but rather represents means of harm reduction, with treatment seeking occurring shortly after its initiation. This should be accounted for when deciding on take-home policies and issues of potential methadone diversion.

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.

a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Molecular Psychiatry 11, 252– 260. [3] Malloy-Diniz L.F., Neves F.S., Costa Abrantes S.S., Fuentes D., Correa H., 2009. Suicide behavior and neuropsychological assessment of type I bipolar patients. Journal of Affective Disorders 112, 231–236.