A recent in vitro study reported that the photoinitiator 2-isopropylthioxanthone (2-ITX) is an endocrine-disrupting compound (EDC). However, it is not clear whether other photoinitiators such as 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) produce endocrine-disrupting effects. The purpose of this study was thus to assess the association between estrogenic activity and exposure to photoinitiators. For estimation of the proliferative effect of the photoinitiators, the E-screen assay was used. Six photoinitiators, 2,2-dimethoxy-2-phenylacetophenone (2,2-DMPAP), 2-ethylhexyl 4-(dimethylamino)benzoate (2-EHDAB), 1-HCHPK, 2-ITX, methyl-2-benzoylbenzoate (MBB), and MTMP, significantly increased number of MCF-7 cells, an estrogen-sensitive human breast cancer cell line. In addition, pretreatment with estrogen receptor (ER) antagonists such as clomiphene, tamoxifen, or fulvestrant, significantly reversed the proliferative effect of each photoinitiator. Data demonstrated that the six photoinitiators produced endocrine-disrupting effects and that these photoinitiators interacted with ER as agonists. Evidence indicates that the six photoinitiators demonstrated estrogenic activity via ER as agonists.

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Aim Whether patients with adult bipolar disorder (BD) who have been clinically stabilized with lithium or lamotrigine should continue this medication is not established fully. This systematic review and meta‐analysis evaluated the efficacy and safety of lithium and lamotrigine for maintenance treatment in clinically stable patients with adult BD. Methods This meta‐analysis included only double‐blind, randomized, placebo‐controlled trials with an enrichment design that selected patients who responded acutely to lithium or lamotrigine. Reports prior to November 15, 2018, were retrieved from the PubMed/Cochrane Library/Embase. The primary outcome was the relapse rate due to any mood episode at the study endpoint. Other outcomes were relapse rates due to a manic/hypomanic/mixed episode or depression at the study endpoint, discontinuation rate, death, and death by suicide. Risk ratios (RRs) (95% confidence intervals) were calculated. When the random‐effects model showed significant differences between groups, the number‐needed‐to‐treat (NNT) was estimated. Results The search retrieved two studies regarding lithium (N = 218) and four evaluating lamotrigine (N = 706). Both drugs were superior to placebo for reducing the relapse rate due to any mood episode [lithium: RR = 0.52 (0.41‐0.66), P < 0.00001, I2 = 0%, NNT = 2.3 (1.6‐4.2); lamotrigine: RR = 0.81 (0.70‐0.93), P = 0.004, I2 = 0%, NNT = 8.3 (5.0‐25.0)] and all‐cause discontinuation. There were no significant differences in other outcomes between lithium or lamotrigine and the placebo groups. Conclusion Both drugs showed benefit for preventing relapse in clinically stable patients with adult BD. However, the number of studies and patients in this analysis was small.

Rationale: It was recently demonstrated that the priming stimulation effect (PSE) in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this novel experimental model have not been fully clarified.Objective: To elucidate the involvement of dopamine uptake inhibition in motivated behavior and the difference in experimental characteristics between closely related experimental models, we investigated the effects of the dopamine uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test (FST), and on conditioned place preference (CPP). In addition, the role of dopamine receptor signaling in the runway model was evaluated using dopamine receptor agonists and antagonists.Results: GBR12909 dose-dependently increased running speed on the runway and GBR12909 did not produce significant place conditioning behavior.

In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous injection solution. Importantly, 1-HCHPK and MTMP have been demonstrated to be cytotoxic to normal human peripheral blood (PB) mononuclear cells (MNC). Cell death (apoptosis) pathways can be classified into two modes, caspase-dependent and -independent pathways. However, it is unclear whether methyl 2-benzoylbenzoate (MBB) induces the caspase-dependent and/or -independent pathway in normal human PBMNC. In the present in vitro study, we examined the levels of MBB in a solution from an intravenous fluid bag and the cytotoxicity of MBB towards normal human PBMNC via the caspase-8-, caspase-9-, or apoptosis-inducing factor (AIF)-mediated apoptosis pathways. We found that extracts from the injection solution had been contaminated with approximately 80 μM of the photoinitiator MBB. In addition, MBB induced apoptosis in the high concentration range in normal human PBMNC in vitro. Moreover, we found that MBB-induced apoptosis occurs via the caspase-9 pathway, but not the AIF pathway. In conclusion, we suggest that MBB has cytotoxic effects on normal human PBMNC in vitro, which are mediated via the caspase-dependent pathway.

Objectives: A systematic review and meta-analysis of double-blind, randomized placebo-controlled trials were conducted to examine how soon an increase in recurrence risk could be observed among bipolar I disorder (BDI) patients who were clinically stable with the combination therapy of mood stabilizers with second-generation antipsychotics (SGA+MS) treatment following second-generation antipsychotics discontinuation (i.e., MS alone) compared with SGA+MS maintenance.Methods: Embase, PubMed, and CENTRAL databases were used for systematic literature searches until May/22/2020. The primary outcome was the recurrence rate of any mood episode at 6 months. The secondary outcomes were the recurrence rates of manic/hypomanic/mixed and depressive episodes and all-cause discontinuation at 6 months. The recurrence rates at 1, 2, 3, 9, and 12 months were also investigated. Results:Eight studies (mean study duration = 58.25 ± 33.63 weeks) were identified (SGA+MS group [n = 1,456: 3 aripiprazole+MS studies, 1 lurasidone+MS study, 1 olanzapine+MS study, 2 quetiapine+MS studies, 1 ziprasidone+MS study] and placebo+MS group [n = 1,476]). Pooled SGA+MS exhibited lower recurrence rates of any mood episode, manic/hypomanic/mixed episodes, and depressive episodes as well as reduced all-cause discontinuation at every observational point. The risk ratios (95% confidence interval) of the recurrence rate at 6 months were 0.51 (0.39-0.86) for any mood episode, 0.42 (0.30-0.59) for manic/hypomanic/mixed episodes, and 0.39 (0.28-0.54) for depressive episodes. The RR for all-cause discontinuation was 0.67

Duloxetine is a serotonin/noradrenaline reuptake inhibitor that is used as an antidepressant. However, it is known to cause constipation as a side effect. Magnesium compounds, such as magnesium oxide and magnesium hydroxide aqueous solution, are often combined with duloxetine to ameliorate the constipation caused by duloxetine. However, there is concern that these magnesium compounds might alter the effects of duloxetine via physicochemical interactions. In this study, we attempted to clarify the interactions that take place between duloxetine and magnesium oxide using in vivo and in vitro experiments. We evaluated the influence of magnesium oxide on in vitro duloxetine concentrations using HPLC. In addition, we examined the in vivo antidepressant-like effects and serum concentrations of duloxetine in rats. In the in vitro experiment, the duloxetine concentration was significantly decreased by co-treatment with magnesium oxide. In the in vivo experiment, the antidepressant-like effects of duloxetine were not affected by the combined oral administration of magnesium oxide and a duloxetine formulation although the serum duloxetine level was significantly decreased. However, the antidepressant-like effects of a duloxetine reagent were significantly attenuated by the co-administration of magnesium oxide. These results suggest that duloxetine and magnesium oxide directly interact and that such interactions affect the absorption and antidepressant-like effects of duloxetine.