Guanglei Xun

Treatment-resistant depression (TRD) is a major challenge in clinical psychiatry, characterized by insufficient response to at least two different classes of antidepressants. Despite advances in treatment, many TRD patients continue to experience significant symptoms and reduced quality of life. The study aims to provide an exploratory assessment of toludesvenlafaxine hydrochloride sustained-release tablets for efficacy and safety in TRD. We conducted an open-label, single-arm, exploratory 8-week study in adults with TRD (n = 31) receiving Toludesvenlafaxine. The primary endpoint was the change in the Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline to week 8. Secondary endpoints included changes in anxiety, quality of life, and functional status, as well as the assessment of safety. Within-group improvements were observed in MADRS scores at weeks 2, 4, and 8 compared with baseline (P < 0.0001), with an average reduction of -13.0 ± 9.6 at week 8. The MADRS response rate (≥ 50% reduction) was 22.6% at week 4 and 45.2% at week 8, while the remission rate (MADRS ≤ 12) was 9.7% at week 4 and 29.0% at week 8. Secondary outcomes, including the Hamilton Anxiety Rating Scale (HAMA), the Sheehan Disability Scale (SDS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), showed significant improvements from baseline. Toludesvenlafaxine was well-tolerated, with a low incidence of adverse events, none of which were severe. These findings suggest that Toludesvenlafaxine may be associated with improvements in both depressive and anxiety symptoms, as well as quality of life, in patients with TRD. This study provides evidence supporting the use of Toludesvenlafaxine as an effective treatment option for TRD and emphasizes the need for further research to confirm its long-term efficacy and safety. The study strictly adhered to the TREND guidelines, Chinese clinical trial Registry, ChiCTR2400080665, 2024-02-04. RXL-SAT-06.

Objective: Agitation represents a serious and prevalent symptomatology within acute schizophrenia. This study aims to conduct a nuanced comparison of the efficacy and safety profiles of intramuscular (IM) ziprasidone versus IM haloperidol in the management of agitation among patients with acute schizophrenia. Methods: This investigation was structured as a randomized, 3-day study, utilizing flexible dosing strategies. It included 69 patients diagnosed with schizophrenia, who were randomly allocated to receive either IM ziprasidone (n = 35, 20 to 40 mg/day) or IM haloperidol (n = 34, 5 to 10 mg/day). The primary endpoints included comparative analyses of the change in Positive and Negative Syndrome Scale (PANSS) total scores and Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores from baseline to study completion across the two groups. Results: At baseline, there were no significant differences between the IM ziprasidone and haloperidol groups. Both treatments led to significant reductions in PANSS-EC total scores (haloperidol, p = 0.001; ziprasidone, p = 0.001) and PANSS total scores (haloperidol, p = 0.001; ziprasidone, p = 0.001) from baseline to study endpoint. Nevertheless, no significant difference was observed between the two groups in terms of changes in PANSS-EC scores (p = 0.312) and PANSS total scores (p = 0.159) from baseline to endpoint. The haloperidol group exhibited a higher incidence of adverse events compared with the ziprasidone group, reaching statistical significance (p = 0.027). Conclusions: Our findings indicate that both medications are equally effective in controlling agitation symptoms. However, ziprasidone exhibited superior characteristics in safety and tolerability, particularly in reducing the incidence of extrapyramidal symptoms. Clinical Trial Registration: The study was registered at https://www.chictr.org.cn/showproj.html?proj=246996, registration number: ChiCTR2500100002, date of registration: 1 April 2025.

Purpose: Previous studies suggest that homocysteine (Hcy) may be involved in the pathogenesis of bipolar disorder (BD) and major depressive disorder (MDD) by influencing glutamatergic transmission, inflammation, and other mechanisms. There are no established biomarkers to distinguish BD from MDD. This study aims to compare Hcy levels between BD and MDD. Patients and Methods: We collected medical records of patients aged 14– 75 admitted to the hospital from January 1 to July 1, 2022 with a discharge diagnosis of MDD or BD, including all examinations of patients at admission (acute phase) and discharge (non-acute phase). We measured Hcy levels in healthy controls (HC). Results: The analysis included 104 patients with MDD, 103 patients with BD, and 80 HC. Hcy levels were higher in the MDD and BD group than in the HC group and higher in the BD group than in the MDD group, both in the acute and non-acute phases (all P < 0.05). There was no significant difference in Hcy levels between the psychotropic medication users and non-users in the BD or MDD group (all P > 0.05). Multivariate logistic regression analysis only for the MDD and BD group indicated that the likelihood of BD diagnosis was significantly associated with Hcy levels (in the acute phase: OR = 1.052, P = 0.016; in the non-acute phase: OR = 1.101, P < 0.001) after controlling for gender, age, and metabolic indicators. Conclusion: Our study suggests that Hcy levels were elevated in MDD and BD patients and were higher in BD patients than in MDD patients, which provides evidence for a possible relationship between one-carbon metabolism and the pathogenesis of BD. Besides, Hcy may be one of the potential biomarkers to distinguish BD from MDD.

At present, no well-established biomarkers were ever found to distinguish unipolar depression and bipolar disorder (BD). This study aimed to provide a clearer comparison of UA levels between BD and major depressive disorder. Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences in UA levels of BD-M (bipolar mania/hypomania) were higher than BD-D (bipolar depression) subgroups, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. The comparison of number of participants with hyperuricemia among groups confirmed the above results. There were no significant differences in UA levels of between drug-use and drug-free/naïve subgroups. UA could distinguish BD and UD significantly both in acute and remission stage. The study suggests patients with BD had a higher level of UA than UD, especially in mania episode. UA may be a potential biomarker to distinguish BD from UD.

Much evidence shows that some Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)-defined unipolar depression (UD) with bipolarity manifests bipolar diathesis. Little is known about the cognitive profiles of patients with depression with bipolarity (DWB). The study aimed to investigate the differences in cognitive profiles among patients with bipolar depression (BD), major depressive disorder (namely, UD), and DWB. Drug-naïve patients with BD, UD, and DWB and healthy controls (HC) were recruited (30 cases in each group). Cognitive function was evaluated by THINC-it (THINC-intelligent tool), Wisconsin Card Sorting Test (WCST), and continuous performance test (CPT). For THINC-it, no significant differences of the Z-scores in both objective and subjective factors were found between the DWB group and BD group, but the Z-scores in the BD group were significantly lower than those in the UD group. For WCST, significant differences were found between the BD group and DWB group in the number of responses, categories completed, trails to completed first category, perseverative responses, and perseverative errors. All the indices of WCST in the DWB group were significantly worse than those in the UD group except for trails to completed first category and total number of response correct. For CPT, only scores of leakage responses and false responses in the four-digit number in the BD group and DWB group were significantly higher than those in the UD group; no significant difference was found between the BD group and DWB group. The results indicated that patients with DWB might perform differently from those with UD but similarly to those with BD with cognition impairment.

Background: At present, no well-established biomarkers were ever found to distinguish unipolar depression (UD) and bipolar disorder (BD). This study aimed to provide a clearer comparison of UA levels between BD and major depressive disorder. Methods: Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. Results: UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences in UA levels of BD-M (bipolar mania/hypomania) were higher than BD-D (bipolar depression) subgroups, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. The comparison of number of participants with hyperuricemia among groups confirmed the above results. There were no significant differences in UA levels of between drug-use and drug-free/naïve subgroups. Conclusion: The study suggests patients with BD had a higher level of UA than UD, especially in mania episode.

Rationale: Piribedil is an orally active dopamine agonist that has been widely used for Parkinson disease (PD), with its partial D2/D3 agonistic functions and alpha2-adrenoreceptor antagonistic effects, piribedil has been proved to be efficacious in the relief of motor symptoms in PD, while it can also lead to impulse control disorders such as pathological gambling due to its dopamine agonistic effects. Patient concerns: A 28-year-old Chinese female patient with Parkinson disease and a history of taking piribedil finally developed pathological gambling and depressive episode. Diagnoses: After a careful clinical observation and evaluation, the patient met the criteria of severe depressive episode and pathological gambling due to antiparkinson therapy. Interventions: We discontinued piribedil and picked bupropion, a dopamine reuptake inhibitor, to alleviate the depressive symptom. Benzhexol and selegiline were also added for the control of motor fluctuations. Outcomes: After 3 weeks’ treatment, the patient's depressive mood was significantly alleviated and her recurring PD symptoms were also relieved. She was no more addicted to network gambling, and there was no recurrence during the 1-year follow-up. Lessons: Piribedil-induced problem gambling and impulse control disorders are side effects needed to be evaluated when commencing a patient on piribedil. This case further emphasizes the importance of monitoring and controlling Parkinson symptoms after drug reduction or withdrawal. Anticipation of this risk strengthens the significance of detailed medical history-taking and targeted clinical management.

Background: At present, no well-established biomarkers were ever found to distinguish unipolar disorder (UD) and bipolar disorder (BD). This study aimed to explore whether uric acid (UA) could be a biomarker to distinguish UD and BD. Methods: Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. Results: UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences of UA levels between BD-M and BD-D subgroups were not significant, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. Only in UD group, UA levels of drug-use subgroup were higher than drug-naïve/free subgroup, but differences disappeared when analyzed stratified by sex; whether in drug-use or drug-naïve/free subgroup, differences of UA levels between BD-M and BD-D groups were not significant.Conclusion: The study suggests UA levels may be a biomarker of BD to distinguish from UD.