Long-term effectiveness and safety of endoxifen in the treatment of bipolar mania: a case report

Bipolar disorder (BD) displays abnormalities in protein kinase C (PKC) signaling, and evidence suggests that inhibiting PKC may help treat mania. Endoxifen a potent inhibitor of the PKC signaling pathway, is effective in controlling acute bipolar mania, at doses of 8 mg OD, for a period of 3-weeks. Here we present the case of a patient with severe mania, increased alcohol consumption administered endoxifen 8 mg BID for a period of 3-months, to achieve a better response. High-dose, long-term treatment with endoxifen was efficacious in controlling manic symptoms, with no adverse effects. Additionally, the patient didn’t consume alcohol during the course of treatment. This case showed the long-term effectiveness and safety of high-dose endoxifen to control mania in a patient with BD.

The Evolution of Social Media and the Impact on Modern Therapeutic Relationships

Combining the most popular social networking sites (SNS), Facebook, Twitter, Instagram, Linkedin, and Pinterest, the number of social networking users has exceeded two billion ( Jain, 2013 ). The average American spends on average 37 min to 2 h and 16 min on SNS each day, which surpasses any other internet activity, including email ( Adler, 2014 ; Batastini & Vitacco, 2020 ; Kemp, 2019 ). The high number of users and the amount of time people spend social networking has given rise to an increased interest of research on social medical and mental health. For example, several studies have shown that extended social media use increases depression ( Coyne et al., 2020 ; Veretilo & Billick, 2012 ), symptoms of bipolar mania, narcissism, and histrionic personality disorder in adults 18–35 ( Rosen et al., 2013 ) and decreases self-esteem among adolescents ( Coyne et al., 2020 ; Shapiro & Margolin, 2014 ).

Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

Differences in single positive formal thought disorder symptoms between closely matched acute patients with schizophrenia and mania

Formal thought disorders (FTD) are a hallmark diagnostic feature of schizophrenia (SZ) and (bipolar) mania (MA). FTD can be separated into positive (pFTD) and negative dimensions. It is unclear whether there are differences in pFTD on a single symptom level between acutely ill patients with SZ and MA, which cannot be attributed to cognitive impairment. We compared single pFTD symptoms in two groups of acutely ill patients with ICD-10 bipolar mania and schizophrenia, closely matched for age, sex, pFTD TALD score, verbal IQ and neuropsychological test performance (executive function, verbal fluency, attention, and working memory). SZ patients had higher severity of the TALD symptoms “perseverations” and “poverty of content of speech” than those with MA (Mann–Whitney U, significant, Bonferroni corrected). Speech in acute SZ patients differs from MA in that it conveys little information and adheres to previously mentioned ideas and topics. Matching for confounding variables, such as IQ and cognition, is important when comparing patients with different diagnoses.

Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State

Introduction: Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA).Materials and Methods: Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables.Results: Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further post-hoc t-tests showed a gradient descent of activity—depression > HC > mania—in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores.Conclusions: Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top–down regulation in task-independent networks.