Which patients with bipolar depression receive antidepressant augmentation? Results from an observational multicenter study.

BACKGROUND: To identify demographic and clinical characteristics of bipolar depressed patients who require antidepressant (AD) augmentation, and to evaluate the short- and long-term effectiveness and safety of this therapeutic strategy. METHODS: One hundred twenty-two bipolar depressed patients were consecutively recruited, 71.7% of them received mood stabilizers (MS)/second-generation antipsychotics (SGA) with AD-augmentation and 28.3% did not. Patients were evaluated at baseline, and after 12 weeks and 15 months of treatment. RESULTS: The AD-augmentation was significantly higher in patients with bipolar II compared with bipolar I diagnosis. Patients with MS/SGA + AD had often a seasonal pattern, depressive polarity onset, depressive index episode with anxious features, a low number of previous psychotic and (hypo)manic episodes and of switch. They had a low irritable premorbid temperament, a low risk of suicide attempts, and a low number of manic symptoms at baseline. After 12 weeks of treatment, 82% of patients receiving ADs improved, 58% responded and 51% remitted, 3.8% had suicidal thoughts or projects, 6.1% had (hypo)manic switch, and 4.1% needed hospitalization. During the following 12 months, 92% of them remitted from index episode, 25.5% did not relapse, and 11% needed hospitalization. Although at the start advantaged, patients with AD-augmentation, compared with those without AD-augmentation, did not significantly differ on any outcome as well on adverse events in the short- and long-term treatment. CONCLUSION: Our findings indicate that ADs, combined with MS and/or SGA, are short and long term effective and safe in a specific subgroup for bipolar depressed patients.

Is short-term antidepressant treatment effective and safe in bipolar depression? Results from an observational multicenter study.

OBJECTIVES: To investigate the short-term effectiveness and the short-term and long-term safety of acute antidepressant (AD) treatment of bipolar depression in a naturalistic setting. METHODS: Patients with bipolar (n = 86) or unipolar (n = 111) depression were consecutively recruited and treated with AD (combined with mood stabilizer [MS] and/or second-generation antipsychotics in bipolar depression). Exclusion criteria were mixed depression, high mood instability, previous predominantly mixed depression (both bipolar and unipolar depression), rapid cycling course and previous switch AD-emerging (bipolar depression). RESULTS: After 12 weeks of treatment, no difference was found in remission, response and improvement rates between bipolar and unipolar depression. Concerning short-term safety, switching and suicidality did not differ significantly between the two groups, and no suicide attempt was observed. Concerning long-term safety, patients with bipolar depression had a significant reduction of depressive and total recurrences during the year of follow-up, compared to the year before entering the study, without significant changes in (hypo)mania and mixed depression recurrences, and suicide rates. CONCLUSIONS: Acute AD treatment of bipolar depression is effective in the short-term and safe in the short- and long-term, when administered in combination with MSs and/or second-generation antipsychotics, with a low risk of switch, mixed depression and cycle acceleration.

QT and QTc in Male Patients with Psychotic Disorders Treated with Atypical Neuroleptics.

OBJECTIVE: We explored the potential association between antipsychotics and QT/QTc duration changes in hospitalized male patients with psychotic disorders. METHODS: The chart review was conducted on 184 male patients hospitalized between 2013 and 2015 at the Psychiatric Clinic of Pisa, Italy. Patients who were treated with one atypical antipsychotic at the time of the ECG recording were 109/184 (59.2%). QT/QTc were compared considering the atypical antipsychotic received. RESULTS: 96.3% (n = 105/109) of the sample showed QTc values ≤ 430 ms; 4 patients (3.7%) had QTc values between 430 and 450 msec (2 with paliperidone, 1 with risperidone, and 1 with olanzapine). The mean QT duration of the overall sample was 368.0 ± 28.0 and the mean QTc 400.1 ± 17.8. QTc values did not reveal statistically significant differences. QT values were significantly different (chi-square = 17.3; df = 5; p = .004). Statistically significant differences between aripiprazole and paliperidone (349.0 ± 28.3 versus 390.5 ± 29.8; p = .002) and between clozapine and paliperidone (361.1 ± 22.43 versus 390.5 ± 29.8; p = .033) were found. CONCLUSIONS: Aripiprazole was the least interfering neuroleptic with QT/QTc. Paliperidone was the atypical neuroleptic with the most relevant difference with aripiprazole, but only on QT.

Plasma amyloid-ß levels in drug-resistant bipolar depressed patients receiving electroconvulsive therapy.

AIMS: Alterations of plasma amyloid-ß (Aß) peptides have been related to a high risk for cognitive impairment and dementia. The present study aimed to measure plasma Aß peptides (Aß40, Aß42) and the Aß40/Aß42 ratio in a sample of drug-resistant bipolar depressed patients, as well as to explore the possible correlation between biological parameters and clinical changes along an electroconvulsive therapy (ECT) course. METHODS: Aß40 and Aß42 were measured by means of an ELISA assay in 25 drug-resistant bipolar depressed patients before (T0) and 1 week after (T1) the end of ECT. The patients were clinically evaluated by means of the Hamilton Rating Scale for Depression, 21-item (HRSD-21), the Mini-Mental State Examination, and the Clinical Global Impressions-Severity of Illness Scale. RESULTS: Plasma Aß levels and the Aß40/Aß42 ratio were similar at T0 and T1. The Aß40/Aß42 ratio correlated positively with the HRSD total score at both T0 and T1. At T0, a negative correlation was found between the Aß40/Aß42 ratio and the improvement of depressive and cognitive symptoms. Moreover, remitters (n = 9; HRSD ≤10) showed a significantly lower Aß40/Aß42 ratio at T0 than nonremitters. CONCLUSION: The present data suggest that a low Aß40/Aß42 ratio might characterize a subgroup of depressed patients who respond to ECT, while higher values of this parameter seem to be typical of more severe cases of patients with cognitive impairment.

Effect of comorbidity on coronary reperfusion strategy and long-term mortality after acute myocardial infarction.

BACKGROUND: Chronic comorbidity is a prognostic determinant in ST-segment elevation myocardial infarction (STEMI). This study was aimed at determining to what extent this effect is independent or derives from adoption of different therapeutic strategies. METHODS: Seven hundred forty patients with STEMI hospitalized within 12 hours of symptom onset were enrolled in a population-based registry, in a health district comprising 1 teaching hospital with and 5 district hospitals without percutaneous coronary intervention (PCI) facilities. Three categories of increasing chronic comorbidity score (CS-1, n = 259; CS-2, n = 235; CS-3, n = 246) were identified from age-adjusted associations of comorbidities with 1-year survival. RESULTS: Higher CS was associated with lower direct admission or transferal rates to hospital with PCI. Coronary reperfusion therapy (PCI in 91.5% of 470 cases) was adopted less frequently (P < .001) in CS-3 (41.9%) than CS-2 (69.4%) or CS-1 (78.8%). Compared with conservative therapy (n = 270), reperfusion therapy reduced 1-year mortality in the whole series not significantly (P = .816) in CS-1 but significantly in CS-2 (P = .012) and CS-3 (P = .001). This trend persisted after adjusting for age, Killip class, and acute myocardial infarction location (hazard ratio [HR] = 0.63 [95% CI 0.14-2.80], HR = 0.62 [95% CI 0.31-1.25], and HR = 0.47 [95% CI 0.26-0.86] in CS-1, CS-2, and CS-3, respectively). By hypothesizing an extension of coronary reperfusion therapy utilization rate in CS-2 and CS-3 to that in CS-1, from 21 (crude analysis) to 20 (adjusted analysis) deaths were classified as potentially avoidable. CONCLUSION: Increased mortality in patients with chronic comorbidity and STEMI derives, at least in part, from underutilization of coronary reperfusion therapy, and might be reduced with a more aggressive therapeutic approach.

Age and comorbidity in acute myocardial infarction: a report from the AMI-Florence Italian registry.

A total of 930 cases of ST-segment elevation myocardial infarction were prospectively recorded in the Florence health district. Factors influencing survival or those associated with use of revascularization (percutaneous coronary intervention, 91%) were identified through multivariate analyses (Cox and logistic regression, respectively). The independent protective effect of coronary reperfusion therapy (CRT) was evident at 36 months (39% reduction in the risk of death). After adjusting for all multivariate predictors, CRT use was 63% less likely at age 85 years and older than at under 65 years (p<0.001). Since beyond advancing age, comorbidity appeared to be associated with a reduced chance of CRT, three chronic comorbidity score categories were calculated using information on past medical history. Increased 1-year mortality in patients with higher comorbidity score categories derives, at least in part, from underutilization of CRT. Results confirm that although they might potentially benefit from CRT during ST-segment elevation myocardial infarction, older and frail patients are excluded from CRT, even when eligible.

Decreased plasma levels of brain-derived neurotrophic factor (BDNF) during mixed episodes of bipolar disorder.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and neuroplasticity. Decreased blood levels of BDNF have been found during acute manic and depressive states. BDNF has been proposed as a biomarker in illness phases of mood disorders. No information is available regarding BDNF levels during the mixed states of bipolar disorder (BD). The aim of this study was to evaluate BDNF levels during mixed episodes of BD patients and compare them with those of healthy subjects and depressed patients. METHODS: Plasma BDNF levels were measured by an ELISA assay in 18 patients with major depressive episode (MDE), 19 patients with mixed episode (ME) and 15 healthy subjects (HS). RESULTS: BDNF levels were significantly higher in HS, as compared with patients׳ samples (HS vs. MDE patients: p<001; HS vs. ME patients: p=.022). No significant differences were found between BDNF levels of ME and MDE patients. The severity of illness as assessed by CGI-S was significantly higher in ME than in MDE patients (p=.01). LIMITATIONS: The small sample size may have weakened the power of statistical analyses. All patients received mood-stabilizing and antidepressant treatments which have been reported to influence peripheral BDNF levels. CONCLUSIONS: Our results are consistent with previous studies showing reduced BDNF during both manic and depressive episodes. This finding supports the role of BDNF as a state-marker of mood episodes, and may represent a contribution to a unitary approach model between unipolar and BDs, as well as to the manic-depressive spectrum model.

Food addiction spectrum: a theoretical model from normality to eating and overeating disorders.

The authors comment on the recently proposed food addiction spectrum that represents a theoretical model to understand the continuum between several conditions ranging from normality to pathological states, including eating disorders and obesity, as well as why some individuals show a peculiar attachment to food that can become an addiction. Further, they review the possible neurobiological underpinnings of these conditions that include dopaminergic neurotransmission and circuits that have long been implicated in drug addiction. The aim of this article is also that at stimulating a debate regarding the possible model of a food (or eating) addiction spectrum that may be helpful towards the search of novel therapeutic approaches to different pathological states related to disturbed feeding or overeating.