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Pharmaceuticals
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Optimized or Precise Pharmacological Treatment of Bipolar Disorder
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Optimized or Precise Pharmacological Treatment of Bipolar Disorder

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 February 2025 | Viewed by 16136

Special Issue Editor

Prof. Dr. Shaohua Hu

E-Mail Website
Guest Editor
School of Medicine, Zhejiang University, Hangzhou 310058, China
Interests: neurobiology and neruoimmune mechanisms of bipolar disorder; molecular genetics of sexual orientation

Special Issue Information

Dear Colleagues,

Bipolar disorder (BD) is known to be associated with persistently high rates of morbidity and mortality. Consequently, it is the leading cause of disability around the world. However, the pathophysiology of mood disorders remains poorly understood and effective clinical management requires further development.

In this Special Issue, we seek to highlight (i) novel psychotropic drug-treatment targets for BD and (ii) how they are linked to the search for novel therapeutics for BD. The mechanisms, efficacy, and safety of these treatment strategies need to be verified in future studies.

We welcome original research articles, review articles, as well as clinical trials that focus on—but are not limited to—the following areas:

  • The clinical efficacy and safety of probiotics and prebiotics for emotional symptoms or cognitive impairment of BD;
  • The potential novel biomarkers of the BD phenotype of linking to immune and inflammatory;
  • Exploring the efficacy and safety of novel compounds for BD;
  • Establishing a predictive model of clinical efficacy for BD and outcomes based on big-data analysis.
  • Clinical translation of cutting-edge basic research.

Prof. Dr. Shaohua Hu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (5 papers)

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Research

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12 pages, 1330 KiB  
Article
Efficacy of Quetiapine Monotherapy and Combination Therapy for Patients with Bipolar Depression with Mixed Features: A Randomized Controlled Pilot Study
by Zheng Wang, Danhua Zhang, Yanli Du, Yin Wang, Tingting Huang, Chee H. Ng, Huimin Huang, Yanmeng Pan, Jianbo Lai and Shaohua Hu
Pharmaceuticals 2023, 16(2), 287; https://doi.org/10.3390/ph16020287 - 14 Feb 2023
Cited by 4 | Viewed by 4908
Abstract
Effective pharmacotherapy of bipolar depression with mixed features defined by DSM-5 remains unclear in clinical treatment guidelines. Quetiapine (QTP) and valproate have potential treatment utility but are often inadequate as monotherapy. Meanwhile, the efficacy of combination therapies of QTP plus valproate or lithium [...] Read more.
Effective pharmacotherapy of bipolar depression with mixed features defined by DSM-5 remains unclear in clinical treatment guidelines. Quetiapine (QTP) and valproate have potential treatment utility but are often inadequate as monotherapy. Meanwhile, the efficacy of combination therapies of QTP plus valproate or lithium have yet to be verified. Hence, we conducted a randomized controlled pilot study to evaluate the efficacy of QTP monotherapy in patients with bipolar depression with mixed features defined by DSM-5 and compared the combination therapy of QTP plus valproate (QTP + V) versus QTP plus lithium (QTP + L) for those patients who responded insufficiently to QTP monotherapy. Data was analyzed according to the intent-to-treat population. Generalized linear mixed model was performed by using “nlme” package in R software. A total 56 patients were enrolled, among which, 35 patients responded to QTP alone, and 11 and 10 patients were randomly assigned to QTP + V and QTP + L group, respectively. Nearly 60% enrolled patients responded to QTP monotherapy at the first two weeks treatment. No statistically significant difference in efficacy between QTP + V and QTP + L was observed. In conclusion, QTP monotherapy appeared to be efficacious in patients with bipolar depression with mixed features, and for those who responded insufficiently to QTP, combining with either valproate or lithium appeared to have positive effects. Full article
(This article belongs to the Special Issue Optimized or Precise Pharmacological Treatment of Bipolar Disorder)
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12 pages, 805 KiB  
Article
Lurasidone versus Quetiapine for Cognitive Impairments in Young Patients with Bipolar Depression: A Randomized, Controlled Study
by Xiangyuan Diao, Dan Luo, Dandan Wang, Jianbo Lai, Qunxiao Li, Peifen Zhang, Huimin Huang, Lingling Wu, Shaojia Lu and Shaohua Hu
Pharmaceuticals 2022, 15(11), 1403; https://doi.org/10.3390/ph15111403 - 14 Nov 2022
Cited by 6 | Viewed by 3625
Abstract
The clinical efficacy of lurasidone and quetiapine, two commonly prescribed atypical antipsychotics for bipolar depression, has been inadequately studied in young patients. In this randomized and controlled study, we aimed to compare the effects of these two drugs on cognitive function, emotional status, [...] Read more.
The clinical efficacy of lurasidone and quetiapine, two commonly prescribed atypical antipsychotics for bipolar depression, has been inadequately studied in young patients. In this randomized and controlled study, we aimed to compare the effects of these two drugs on cognitive function, emotional status, and metabolic profiles in children and adolescents with bipolar depression. We recruited young participants (aged 10–17 years old) with a DSM-5 diagnosis of bipolar disorder during a depressive episode, who were then randomly assigned to two groups and treated with flexible doses of lurasidone (60 to 120 mg/day) or quetiapine (300 to 600 mg/day) for consecutive 8 weeks, respectively. All the participants were clinically evaluated on cognitive function using the THINC-it instrument at baseline and week 8, and emotional status was assessed at baseline and the end of week 2, 4, and 8. Additionally, the changes in weight and serum metabolic profiles (triglyceride, cholesterol, and fasting blood glucose) during the trial were also analyzed. In results, a total of 71 patients were randomly assigned to the lurasidone group (n = 35) or the quetiapine group (n = 36), of which 31 patients completed the whole treatment course. After an 8-week follow-up, participants in the lurasidone group showed better performance in the Symbol Check Reaction and Accuracy Tests, when compared to those in the quetiapine group. No inter-group difference was observed in the depression scores, response rate, or remission rate throughout the trial. In addition, there was no significant difference in serum metabolic profiles between the lurasidone group and the quetiapine group, including triglyceride level, cholesterol level, and fasting blood glucose level. However, the quetiapine group presented a more apparent change in body weight than the lurasidone group. In conclusion, the present study provided preliminary evidence that quetiapine and lurasidone had an equivalent anti-depressive effect, and lurasidone appeared to be superior to quetiapine in improving the cognitive function of young patients with bipolar depression. Full article
(This article belongs to the Special Issue Optimized or Precise Pharmacological Treatment of Bipolar Disorder)
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17 pages, 3391 KiB  
Article
Effects of Dexamethasone and Pentoxifylline on Mania-like and Depression-like Behaviors in Rats
by Ahmad Nassar and Abed N. Azab
Pharmaceuticals 2022, 15(9), 1063; https://doi.org/10.3390/ph15091063 - 26 Aug 2022
Cited by 4 | Viewed by 2471
Abstract
Several studies support the notion that inflammation plays a role in the pathophysiology and treatment approaches of psychiatric illnesses, particularly mood disorders. Congruently, classic anti-inflammatory drugs were found efficacious in randomized clinical trials of patients with mood disorders. Moreover, accumulating data indicate that [...] Read more.
Several studies support the notion that inflammation plays a role in the pathophysiology and treatment approaches of psychiatric illnesses, particularly mood disorders. Congruently, classic anti-inflammatory drugs were found efficacious in randomized clinical trials of patients with mood disorders. Moreover, accumulating data indicate that psychotropic drugs exhibit some anti-inflammatory effects. This study was undertaken to examine the efficacy of dexamethasone (a potent corticosteroid) and pentoxifylline (a methylxanthine drug with proven anti-tumor necrosis factor-α inhibitory activity) in behavioral models in rats, which were treated intraperitoneally with either dexamethasone or pentoxifylline for two weeks and then subjected to a battery of behavioral tests. Treatment with pentoxifylline, but not dexamethasone, was associated with antidepressant-like and anti-manic-like effects. The beneficial behavioral effects of pentoxifylline were accompanied by a prominent reduction in pro-inflammatory mediator levels in the brain. For the first time, the current work proves the efficacy of pentoxifylline against both mania-like and depressive-like behaviors. These results suggest that pentoxifylline may be a promising therapeutic intervention for patients with mood disorders. Taking into account the excellent tolerability profile of pentoxifylline in humans, it is warranted to conduct randomized clinical trials to investigate its therapeutic efficacy in patients with psychiatric disorders. Full article
(This article belongs to the Special Issue Optimized or Precise Pharmacological Treatment of Bipolar Disorder)
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33 pages, 5727 KiB  
Article
Activating SIRT-1 Signalling with the Mitochondrial-CoQ10 Activator Solanesol Improves Neurobehavioral and Neurochemical Defects in Ouabain-Induced Experimental Model of Bipolar Disorder
by Bidisha Rajkhowa, Sidharth Mehan, Pranshul Sethi, Aradhana Prajapati, Manisha Suri, Sumit Kumar, Sonalika Bhalla, Acharan S. Narula, Abdulrahman Alshammari, Metab Alharbi, Nora Alkahtani, Saeed Alghamdi and Reni Kalfin
Pharmaceuticals 2022, 15(8), 959; https://doi.org/10.3390/ph15080959 - 2 Aug 2022
Cited by 17 | Viewed by 3105
Abstract
Bipolar disorder (BD) is a chronic mental illness characterized by mood fluctuations that range from depressive lows to manic highs. Several studies have linked the downregulation of SIRT-1 (silent mating type information regulation-2 homologs) signaling to the onset of BD and other neurological [...] Read more.
Bipolar disorder (BD) is a chronic mental illness characterized by mood fluctuations that range from depressive lows to manic highs. Several studies have linked the downregulation of SIRT-1 (silent mating type information regulation-2 homologs) signaling to the onset of BD and other neurological dysfunctions. This research aimed to look into the neuroprotective potential of Solanesol (SNL) in rats given ICV-Ouabain injections, focusing on its effect on SIRT-1 signaling activation in the brain. Ouabain, found in hypothalamic and medullary neurons, is an endogenous inhibitor of brain Na+/K+ ATPase. The inhibition of brain Na+/K+ ATPase by Ouabain may also result in changes in neurotransmission within the central nervous system. SNL is a Solanaceae family active phytoconstituent produced from the plant Nicotiana tabacum. SNL is used as a precursor for the production of CoQ10 (Coenzyme Q10), a powerful antioxidant and neuroprotective compound. In the current study, lithium (Li), an important mood stabilizer drug, was used as a control. This study looked at the neuroprotective potential of SNL at dosages of 40 and 80 mg/kg in ICV-OUA injections that caused BD-like neurobehavioral and neurochemical defects in Wistar rats. Wistar rats were placed into eight groups (n = 6) and administered 1 mM/0.5 µL ICV-OUA injections for three days. Neurochemical assessments were done in rat brain homogenates, CSF, and blood plasma samples at the end of the experiment protocol schedule. Long-term SNL and lithium administration have been shown to decrease the number of rearing and crossings and reduce time spent in the center, locomotor activities, and immobility time. Solansesol treatment gradually raises the amount of Na+/K+ ATPase, limiting the severity of behavioural symptoms. These findings also revealed that SNL increases the levels of SIRT-1 in CSF, blood plasma, and brain homogenate samples. Moreover, in rat brain homogenates and blood plasma samples, SNL modulates apoptotic markers such as Caspase-3, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic). Mitochondrial-ETC complex enzymes, including complex-I, II, IV, V, and CoQ10, were also restored following long-term SNL treatment. Furthermore, SNL lowered inflammatory cytokines (TNF-α, IL-1β) levels while restoring neurotransmitter levels (serotonin, dopamine, glutamate, and acetylcholine) and decreasing oxidative stress markers. Histological examinations also validated Solanesol’s protective effect. As a result, our findings suggest that SNL, as a SIRT-1 signalling activator, may be a promising therapeutic approach for BD-like neurological dysfunctions. Full article
(This article belongs to the Special Issue Optimized or Precise Pharmacological Treatment of Bipolar Disorder)
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Review

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10 pages, 247 KiB  
Review
Cariprazine in Bipolar Disorder and Substance Use: A Dual Approach to Treatment?
by Simone Pardossi, Alessandro Cuomo, Despoina Koukouna, Mario Pinzi and Andrea Fagiolini
Pharmaceuticals 2024, 17(11), 1464; https://doi.org/10.3390/ph17111464 - 31 Oct 2024
Viewed by 604
Abstract
Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, [...] Read more.
Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, suicide, and poor clinical outcomes. Current treatment strategies, including lithium and valproate, show limited efficacy in treating both BD and SUD. Psychotherapeutic approaches such as cognitive behavioral therapy (CBT) offer benefits but lack a specific focus on substances such as cannabis and cocaine. Since there is still debate on how to treat this comorbidity, there is a need to find new therapeutic options; this mini-review examines the pharmacological properties of cariprazine and its emerging role in the treatment of comorbid BD and SUD. Cariprazine, an atypical antipsychotic with partial agonism at dopamine D2 and D3 receptors, has shown promise in treating both mood symptoms and cognitive dysfunction in BD. Its unique affinity for D3 receptors, which are involved in motivation and reward processing, may offer advantages in reducing drug craving. Clinical trials indicate that cariprazine effectively treats manic, depressive, and mixed episodes in BD with a favorable side effect profile, particularly at lower doses. Preliminary results suggest its potential to reduce craving and substance use in individuals with co-occurring BD and SUD. Therefore, cariprazine, with its unique pharmacodynamic mechanism, could be further studied for the treatment of BD in comorbidity with SUD. However, evidence on the role of cariprazine in the treatment of SUDs remains limited, based primarily on case reports and animal studies. Further research, including large-scale clinical trials, is needed to determine its full efficacy in this dual diagnosis. Full article
(This article belongs to the Special Issue Optimized or Precise Pharmacological Treatment of Bipolar Disorder)
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