Adjunctive tianeptine treatment for bipolar disorder: A 24-week randomized, placebo-controlled, maintenance trial.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of tianeptine as an adjunctive maintenance treatment for bipolar depression. METHODS: This is a multicenter double-blind randomized placebo-controlled maintenance trial of adjunctive tianeptine 37.5 mg/day. Participants ( n=161) had a Montgomery-Asberg Depression Rating Scale ⩾12 at entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine ( n=69) were randomized to adjunctive tianeptine ( n=36) or placebo ( n=33) in addition to usual treatment. Kaplan-Meier estimates and the Mantel-Cox log-rank test were used to evaluate differences in time to intervention for a mood episode between the tianeptine and placebo groups. We also assessed overall functioning, biological rhythms, quality of life, rates of manic switch and serum brain-derived neurotrophic factor levels. RESULTS: There were no differences between adjunctive tianeptine or placebo regarding time to intervention or depression scores in the 24-week double-blind controlled phase. Patients in the tianeptine group showed better performance in the letter-number sequencing subtest from the Wechsler Adult Intelligence Scale at the endpoint ( p=0.014). Tianeptine was well tolerated and not associated with higher risk for manic switch compared to placebo. CONCLUSION: Tianeptine was not more effective than placebo in the maintenance treatment of bipolar depression. There is preliminary evidence suggesting a pro-cognitive effect of tianeptine in working memory compared to placebo.

Neuroprogression and illness trajectories in bipolar disorder.

INTRODUCTION: The longitudinal course of bipolar disorder is highly variable, and a subset of patients seems to present a progressive course associated with brain changes and functional impairment. Areas covered: We discuss the theory of neuroprogression in bipolar disorder. This concept considers the systemic stress response that occurs within mood episodes and late-stage deficits in functioning and cognition as well as neuroanatomic changes. We also discuss treatment refractoriness that may take place in some cases of bipolar disorder. We searched PubMed for articles published in any language up to June 4th, 2016. We found 315 abstracts and included 87 studies in our review. Expert commentary: We are of the opinion that the use of specific pharmacological strategies and functional remediation may be potentially useful in bipolar patients at late-stages. New analytic approaches using multimodal data hold the potential to help in identifying signatures of subgroups of patients who will develop a neuroprogressive course.

Cognition and functioning in bipolar depression

Objectives: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. Methods: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. Results: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001). Conclusion: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes.

Cognition and functioning in bipolar depression.

OBJECTIVES: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. METHODS: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. RESULTS: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001). CONCLUSION: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes.

Cognitive impairment in school-aged children with early trauma.

Exposure to traumatic events during childhood is often associated with the development of psychiatric disorders, cognitive impairment, and poor functioning in adulthood. However, few studies have examined cognitive function, including executive function, memory, and attention, in school-aged children with early trauma compared with age- and sex-matched controls. We recruited 30 medication-naive children between 5 and 12 years of age with a history of early severe trauma from a foster care home, along with 30 age- and sex-matched controls. Psychiatric diagnoses were based on Kiddie Schedule for Affective Disorders and Schizophrenia Epidemiologic Version (K-SADS-E) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and were confirmed with a clinical interview. The neuropsychologic battery was tailored to assess broad cognitive domains such as learning/working memory, executive function, attention, verbal/premorbid intellectual functioning, and impulsivity. There was a higher prevalence of subsyndromal symptoms in children with a history of childhood trauma, although they rarely met all of the diagnostic criteria for a disorder. Moreover, lower estimated intellectual functioning scores were associated with subsyndromal symptoms in children with a history of trauma, and they performed more poorly on the Digits Span Test of the Wechsler Intelligence Scale for Children-III Edition, suggesting attention impairment. There is a high prevalence of subsyndromal symptoms in school-aged children with trauma and an attention impairment, which may contribute to a cumulative deficit early in cognitive development. These findings further support the need for early interventions that can prevent cognitive impairment when childhood trauma occurs.

Childhood trauma, impulsivity, and executive functioning in crack cocaine users.

BACKGROUND: The use of crack cocaine is a major public health concern in Brazil and internationally. Recent data suggest that childhood trauma is associated with worse outcomes among cocaine users. This study had the objective of evaluating the relationship of childhood trauma with executive functioning and impulsivity in outpatients with crack cocaine use disorders. METHODS: This is a cross-sectional study of 84 consecutive outpatients with a primary crack cocaine use disorder who sought treatment in Porto Alegre, Brazil. Childhood trauma was evaluated with the Childhood Trauma Questionnaire; executive functioning, with the Wisconsin Card Sorting Test; and impulsivity, with the Barratt Impulsivity Scale. RESULTS: Childhood trauma was strongly associated with executive dysfunction and impulsivity, even when controlled for possible confounders. CONCLUSIONS: Childhood trauma may be associated with executive dysfunction and impulsivity in crack cocaine users. The full impact of trauma needs to be further investigated in longitudinal studies.

Correlates and impact of obsessive-compulsive comorbidity in bipolar disorder.

BACKGROUND: Anxiety morbidity in general is frequent and harmful in bipolar disorder. Little is known, however, whether obsessive-compulsive comorbidity entails particular effects. This report aims to evaluate the prevalence and impact of obsessive-compulsive disorder (OCD) comorbidity in a relatively large clinical sample of bipolar disorder, with other lifetime anxiety comorbidities used as a more rigorous control group. METHODS: A cross-sectional study in a consecutive clinical sample, with anxiety comorbidity derived from the intake Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was conducted. Anxiety was assessed with the Hamilton Anxiety Rating Scale. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to assess (hypo)manic and depressive symptoms. The domains of the WHOQOL BREF were used to evaluate quality of life. RESULTS: Lifetime prevalence of OCD comorbidity was 12.4%. No cases of OCD were detected during mania. Compared with subjects with no anxiety comorbidity, those with lifetime OCD were more likely to have a history of suicide attempts, rapid cycling, and alcohol dependence. Patients with OCD had a lower score on all domains of the WHOQOL. Compared with those with other lifetime anxiety disorders, those with OCD had more anxiety, which mediated a lower WHOQOL social domain. CONCLUSIONS: Bipolar disorder patients with obsessive-compulsive comorbidity have a number of indicators of an overall more severe illness. The presence of more anxiety symptoms and a lower social quality of life may be more specific features of the bipolar-OCD comorbidity.

Functional impact of biological rhythm disturbance in bipolar disorder.

Bipolar disorder (BD) is characterized by frequent recurrence, incomplete recovery, cognitive dysfunction and poor functioning. Impairment lingers in the interepisodic period and mechanisms leading to this dysfunctional state are not fully comprehended. To our knowledge the association of biological rhythm dysfunction with functioning in BD has not been assessed directly. The objective of this study was to measure and quantify the impact of rhythm dysfunction on interepisodic functioning in BD. We also tested the association between executive functioning and sleep and rhythm problems. Eighty-one outpatients with BD and 79 matched control subjects were consecutively recruited. Functional impairment was assessed with the Functioning Assessment Short Test (FAST) and biological rhythms with the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). A subsample had their executive functioning assessed with the Wisconsin Card Sorting Test (WCST). Patients and control subjects were well matched. Functioning and rhythm scores were correlated in patients and control subjects. The BRIAN score was the strongest predictor of functioning in the regression model. Biological rhythms partially mediated the impairment associated with bipolar disorder. The rhythm score was also associated with executive functioning. Biological rhythm dysfunction was a potent predictor of functioning in interepisodic patients with bipolar disorder; it may also mediate much of the disorder-induced disability. These results further the notion that biological rhythms may be interesting targets for diverse interventions aiming to improve functioning and prevent relapse in interepisodic bipolar disorder.