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.

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. Tukey's 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.

Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients.

BackgroundThe neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels.MethodsWe conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder.ResultsThrough a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges’ g = −0.57, P = 0.010) and depressive (Hedges’ g = −0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one.ConclusionsIn summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0529-7) contains supplementary material, which is available to authorized users.

Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.

Clinical implications of predominant polarity and the polarity index in bipolar disorder: a naturalistic study.Objective: Predominant polarity (PP) is an important variable in maintenance treatment of bipolar disorder (BD). This study aimed at determining the role of polarity index (PI), a metric indicating antimanic versus antidepressive prophylactic potential of drugs, in clinical decision-making. Method: Two hundred and fifty-seven of 604 (43%) of patients with BD-I or II fulfilled criteria for manic (MPP) or depressive PP (DPP). The PI, representing the ratio of number needed to treat (NNT) for depression prevention to NNT for mania prevention, was calculated for patients' current treatment. MPP and DPP groups were compared regarding sociodemographic, clinical and therapeutic characteristics. Results: One hundred and forty-three patients (55.6%) fulfilled criteria for DPP and 114 (44.4%) for MPP. Total PI, Antipsychotics' PI, and mood stabilizers PI were higher, indicating a stronger antimanic action, in MPP. MPP presented higher prevalence of BD-I, male gender, younger age, age at onset and at first hospitalization, more hospitalizations, primary substance misuse, and psychotic symptoms. DP correlated with BD-II, depressive onset, primary life events, melancholia, and suicide attempts. Conclusion:The results confirm the usefulness of the PI. In this large sample, clinical differences among these groups justify differential treatment approach. The PI appears to be a useful operationalization of what clinicians do for maintenance therapy in BD.

Objective: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. Methods: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). Results: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI] = 0.65 to 1.86) for functional outcome and −0.72 (95% CI = −1.27 to −0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. Conclusion: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.

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