The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats.

BACKGROUND: Vortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration. METHODS: The experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue. RESULTS: Interestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/ß-glucosaminidase (ß-NAG), ß-Galactosidase (ß-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group. CONCLUSION: Thus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Serotonin is a common thread linking different classes of antidepressants.

Depression pathology remains elusive. The monoamine hypothesis has placed much focus on serotonin, but due to the variable clinical efficacy of monoamine reuptake inhibitors, the community is looking for alternative therapies such as ketamine (neurogenesis theory of antidepressant action). There is evidence that different classes of antidepressants may affect serotonin levels; a notion we test here. We measure hippocampal serotonin in mice with voltammetry and study the effects of acute challenges of escitalopram, fluoxetine, reboxetine, and ketamine. We find that pseudo-equivalent doses of these drugs similarly raise ambient serotonin levels, despite their differing pharmacodynamics because of differences in Uptake 1 and 2, rapid SERT trafficking, and modulation of serotonin by histamine. These antidepressants have different pharmacodynamics but have strikingly similar effects on extracellular serotonin. Our findings suggest that serotonin is a common thread that links clinically effective antidepressants, synergizing different theories of depression (synaptic plasticity, neurogenesis, and the monoamine hypothesis).

Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson's Disease: An Updated Review.

Depression represents one of the most common non-motor disorders in Parkinson's disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind-body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.

Attention Bias Modification Treatment Versus a Selective Serotonin Reuptake Inhibitor Or Waiting List Control for Social Anxiety Disorder: A Randomized Clinical Trial.

OBJECTIVE: Social anxiety disorder is common and impairing. The efficacy of pharmacotherapy is moderate, highlighting the need for alternative therapies. This study compared the efficacy of gaze-contingent music reward therapy (GC-MRT), an eye-tracking-based attention bias modification treatment, with a selective serotonin reuptake inhibitor (SSRI) treatment or a waiting list control condition in reducing social anxiety disorder symptoms. Superior clinical effects of similar magnitude were expected for the active treatments relative to the control condition. METHODS: Participants were 105 treatment-seeking adults with social anxiety disorder, randomly allocated to 12 weeks of GC-MRT, SSRI, or waiting list control. Mean changes in clinician-rated and self-reported social anxiety symptoms from baseline to mid- and posttreatment assessments were compared between groups using generalized estimating equations. Changes in attentional dwell time on threat were also examined. RESULTS: Analysis indicated a significant differential reduction in symptoms between groups. Patients in the GC-MRT and SSRI groups had lower social anxiety scores at the mid- and posttreatment assessments compared with patients in the waiting list group. The efficacy of the active treatments did not differ. Only patients in the GC-MRT group showed reduction in dwell time on threat from baseline to posttreatment assessment. CONCLUSIONS: Eye-tracking-based attention bias modification is an acceptable and effective treatment option for social anxiety disorder.

The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials.

BACKGROUND: Depression is the most common mental disorder, affecting about 3.8% of the population worldwide. Clinical symptoms of depression include sadness, anxiety and frequent mood swings, among others. Selective serotonin reuptake inhibitors (SSRIs), psychotherapy and behavioral therapy are commonly used for the treatment of this condition. Since SSRIs are associated with various side effects, extract of St. John's wort (SJW) has been suggested as an effective alternative. However, there are conflicting studies regarding its efficacy. Many studies have reported positive outcomes with low adverse effects, while others did not find it to be a suitable alternative. OBJECTIVES: To analyze the available studies using SJW for depression therapy and to thoroughly evaluate its effectiveness compared to SSRIs and placebo. MATERIAL AND METHODS: Relevant articles for our meta-analysis were found using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases. Studies were included as per the predefined Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria. A demographic summary of the patients treated with either SJW, placebo or SSRIs was collected and Hamilton Depression Rating Scale (HAMD) scores were extracted. Risks of bias analysis, diagnostic odds ratio (OR), risk ratio (RR), and sensitivity calculation were evaluated using Revman software, and the publication bias was assessed using MedCalc software. RESULTS: Fourteen clinical trials with a total of 2270 depression patients were included in accordance with the inclusion criteria. All analyzed papers were published between 2000 and 2022. For patients treated with either SSRIs or SJW, a pooled OR of 2.44 with a 95% confidence interval (95% CI) of 1.33-4.45 was obtained. The data were heterogeneous, with a tau2 value of 0.54, χ2 value of 31.05, degrees of freedom (df) value of 7, I2 value of 77%, and an overall Z-value of 2.90 with p = 0.004. CONCLUSION: Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.

Selective serotonin reuptake inhibitors in the treatment of depression, anxiety, and post-traumatic stress disorder in substance use disorders: a Bayesian meta-analysis.

PURPOSE: Examine SSRIs' efficacy in treating depression, anxiety, PTSD, and substance use in individuals with addiction. METHODS: From their inception until August 6, 2021, we searched Google Scholar, PubMed, Scopus, OVID MEDLINE, and Academic Search Complete. We included randomized controlled trials (RCTs) and omitted open-label studies. Bayesian analysis was performed. Bayes factor (BF) established efficacy and tau (τ) statistical heterogeneity. The RoB2 method assessed potential biases. Subgroup analysis was carried out to determine SSRI performance. Treatment duration, SSRI dosage, and attrition rate were all examined in meta-regression. RESULTS: We investigated 64 RCTs with 6128 participants. SSRIs reduced depressive symptoms in opioid, alcohol, cocaine, cannabis, and nicotine use disorders (d = 0.353, BF > 99); social anxiety symptoms in alcohol use disorder (d = 0.875, BF > 99); and generalized anxiety symptoms in opioid, alcohol, cocaine, marijuana, and nicotine use disorders (d = 0.346, BF = 4.236). Evidence for PTSD was inconclusive. SSRIs facilitated abstinence for opioid, alcohol, cocaine, cannabis, and nicotine use (d = 0.325, BF > 99); reduced craving for alcohol, cocaine, and nicotine use (d = 0.533, BF = 24.129); and reduced alcohol use (d = 0.452, BF > 99) and cocaine use (d = 0.255, BF = 3.87). Fluoxetine showed the highest antidepressant effect. There was no effect of attrition rate, SSRI dosage, or treatment length on SSRI's efficacy. CONCLUSIONS: Results support the use of SSRIs to treat substance use, depression, and anxiety in individuals with addiction. PROTOCOL REGISTRATION: PROSPERO registration number: CRD42020164944.

An up-to-date overview of the pharmacotherapeutic options for premature ejaculation.

INTRODUCTION: Premature ejaculation (PE) is a sexual dysfunction of unknown etiology affecting a substantial number of males and deteriorating sexual health and quality of life of the patient and his partner. Treatment still remains challenging; however, pharmacotherapy is considered the mainstay of therapy with behavioral and psychosexual interventions being particularly important as adjudicate procedures, within the context of a holistic approach. AREAS COVERED: The authors review the literature on the available medications for PE, both officially registered and non-registered. Currently, only dapoxetine and an anesthetic spray containing lidocaine and prilocaine (Fortacin™) are officially approved, with the rest being used off-label. Herein, updated data regarding the efficacy and safety of the pharmaceutical agents are presented. EXPERT OPINION: On-demand dapoxetine is reportedly efficacious and safe in treating lifelong PE and is the first medication to be approved for this purpose. Fortacin has also shown considerable efficacy and may be reliably used on-demand. Phosphodiesterase type 5 inhibitors (PDE5Is) have been found to be effective in the treatment of PE and are therefore recommended either as monotherapy or combined with other therapies (i.e. dapoxetine). Adverse events of any therapy should be taken under consideration. Physicians should encourage patients to discuss their needs and expectations and grade any improvement of their condition with treatment.

Selective Serotonin Reuptake Inhibitors and Nutraceutical Combination in Major Depression Disorder: A Case-Control Study.

Introduction: Major depressive disorder (MDD) is a primary cause of disability in adults, affecting daily functioning and decreasing quality of life. The focus on the role of nutraceuticals as adjunctive treatments to improve antidepressant response is paying growing interest. The study aims to compare the antidepressants response in the utilization of selective serotonin reuptake inhibitors (SSRIs) versus a combination of SSRIs and nutraceutical supplements based on S-Adenosyl methionine (SAMe), N-acetylcysteine (NAC) and folate in terms of efficacy and tolerability. Methods: A case-control study was carried out between March 2018 and September 2019. Cases and controls were evaluated through the following scales: Hospital Anxiety Depression Scale (HADS); Clinical Global Impression (CGI); Patient Global Impression of Improvement (PGI-I); Antidepressant Adverse Events checklist (AES). Results: A significant difference between the two groups of patients emerged at T1 in the HADS-A (p = 0.004) score and in the CGI score (p = 0.01), due to a major improvement in patients with a nutraceutical co-prescription. At T3 a significant statistical difference emerged, showing a greater improvement at HADS-D in the case group (p = 0.006), confirmed by a higher remission rate in patients taking a nutraceutical co-prescription. No differences in terms of adverse events emerged. Conclusion: This study shows promising data about the role of nutraceuticals as adjunctive treatment in major depressive disorder to improve SSRIs efficacy, with good tolerability. More data are needed to confirm these results, particularly about the role of nutraceuticals to decrease the latency of SSRIs response.

Analysis of the clinical efficacy of acupuncture combined with selective serotonin reuptake inhibitors (SSRIs) in the treatment depression / 药学实践杂志

Objective To explore the clinical efficacy of acupuncture combined with SSRIs in the treatment of patients with depression. Methods A total of 83 patients with depression admitted to our hospital between January 2019 and January 2020 were selected as the research objects. Patients in the control group were treated with SSRIs, and the combined treatment (observation) group was treated with acupuncture on the basis of the control group. The clinical efficacy, anxiety (HAMD) and depression scale (HAMD) of patients in the two groups were compared. Results After treatment, the clinical efficacy of depression patients in the observation group was significantly higher than that in the control group (P<0.05). HAMA and HAMD scores showed statistical difference between the two groups. HAMA and HAMD scores of patients in the observation group were lower than those in the control group (P<0.05). Conclusion Acupuncture combined with SSRIs in the treatment of depression can significantly improve the patient's condition, reduce the patient's anxiety and depression, and has a positive significance for the treatment of the patients.

Peripheral neuropathic pain.

Neuropathic pain (NP) can have either central nervous system causes or ones from the peripheral nervous system. This article will focus on the epidemiology, classifications, pathology, non-invasive treatments and invasive treatments as a general review of NP involving the peripheral nervous system. NP has characteristic symptomatology such as burning and electrical sensations. It occurs in up to 10% of the general population. Its frequency can be attributed to its occurrence in neck and back pain, diabetes and patients receiving chemotherapy. There are a wide range of pharmacologic options to control this type of pain and when such measures fail, numerous interventional methods can be employed such as nerve blocks and implanted stimulators. NP has a cost to the patient and society in terms of emotional consequences, quality of life, lost wages and the cost of assistance from the medical system and thus deserves serious consideration for prevention, treatment and control.

Response to SSRI intervention and amygdala activity during self-referential processing in major depressive disorder.

There are conflicting reports on the impact of antidepressants on neural reactions for positive information. We thus hypothesized that there would be clinically important individual differences in neural reactivity to positive information during SSRI therapy. We further predicted that only those who responded to SSRIs would show increased amygdala reactivity to positive information following treatment to a level similar to that seen in healthy participants. Depressed individuals (n = 17) underwent fMRI during performance of a task involving rating the self-relevance of emotionally positive and negative cue words before and after receiving 12 weeks of SSRI therapy. At post-treatment, SSRI responders (n = 11) had increased amygdala activity in response to positive stimuli, and decreased activity in response to negative stimuli, compared to non-responders (n = 6). Results suggest that normalizing amygdala responses to salient information is a correlate of SSRI efficacy. Second line interventions that modulate amygdala activity, such as fMRI neurofeedback, may be beneficial in those who do not respond to SSRI medications.

Current and Future Therapies for Psoriasis with a Focus on Serotonergic Drugs.

Psoriasis is a chronic immune-mediated skin disease, with a pathogenesis resulting from a combination of genetic and environmental factors. The pathogenesis of psoriasis is driven by the interaction between innate and adaptive immune cells and keratinocytes, in a complex process mediated by cytokines and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis, and infiltration of white cells in the skin, which cause the characteristic psoriasis plaques. Several studies have suggested that the neurotransmitter serotonin, a key mediator between the skin and the neuroendocrine system, also plays an important role in the pathogenesis of psoriasis. Psoriasis often needs long-term treatment, which can be a burden. Thus, the choice of the treatment is crucial to increase the patients' adherence and quality of life. This review addresses the currently available systemic and topical treatments for psoriasis, used by themselves or combined with phototherapy. It particularly focuses on the importance of advanced drug delivery systems as a way to increase the drug penetration and retention in the skin, while also enhancing its solubility and stability. Finally, we discuss the role of the serotonin system in psoriasis, and summarize what is known about the effects of antidepressants, in particular specific serotonin reuptake inhibitors, on the physical symptoms of this disease.

Can acupuncture combined with SSRIs improve clinical symptoms and quality of life in patients with depression? Secondary outcomes of a pragmatic randomized controlled trial.

OBJECTIVES: To explore the effects of acupuncture (manual acupuncture or electroacupuncture) combined with SSRIs for moderate to severe depression improving major clinical symptoms and life quality of the patients on secondary outcomes. DESIGN: Pragmatic, parallel, randomized controlled trial. SETTING: 6 hospitals in China. INTERVENTIONS: 6 weeks of manual acupuncture (MA)+selective serotonin reuptake inhibitors (SSRIs), electroacupuncture (EA)+SSRIs, and SSRIs alone. MAIN OUTCOME MEASURES: The primary outcome was response rate of 17-item Hamilton Depression Scale (HAMD-17) total score at 6th week. The secondary outcomes reported in this analysis were HAMD-17 factor scores at 1st, 2nd, 4th, 6th, 10th week and WHO Quality of Life-BREF (WHOQOL-BREF) scores at 6th week. RESULTS: 477 patients were randomly assigned into MA + SSRIs (n = 161), EA + SSRIs (n = 160), or SSRIs alone (n = 156) groups. For HAMD-17 (at 6th week), the MA + SSRIs group was significantly better than the SSRIs alone group in retardation factor (p = 0.008), while the EA+SSRIs group was significantly better than the SSRIs alone group in anxiety/somatization factor (p<0.001) and sleep disturbance factor (p = 0.002). For WHOQOL-BREF (at 6th week), the EA + SSRIs group, compared with the SSRIs alone group, produced a more significant improvement in the overall quality of life, general health, physical health, and psychological health (p<0.05). While, the MA + SSRIs group, compared to the SSRIs alone group, showed significant advantage only in psychological health (p = 0.023). CONCLUSIONS: Either MA or EA combined SSRIs treatment could improve symptoms and quality of life for patients with moderate to severe depression. The main limitation of this trial was not using a sham control therefore the placebo effect could not be excluded.

Effects of SSRIs on peripheral inflammatory cytokines in patients with Generalized Anxiety Disorder.

BACKGROUND: Extensive research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, inflammation has been implicated in the pathogenesis of depression and anxiety. The immunomodulating effects of antidepressants on depression have been reported, however, there is no evidence of the similar effects of antidepressants on anxiety. The aim of the study was to investigate the effects of selective serotonin reuptake inhibitors (SSRIs) on peripheral inflammatory cytokines in patients with first episode generalized anxiety disorder (GAD). METHODS: A prospective cohort design was employed: 42 patients with first episode GAD were treated with either escitalopram or sertraline for 12 weeks. Anxiety was measured by the Generalized Anxiety Disorder Scale and the State Trait Anxiety Inventory, serum pro-inflammatory cytokine levels were measured by the enzyme-linked immunosorbent assay (ELISA), and CRP determined by an immunoturbidimetric method before and after SSRIs treatment RESULTS: Baseline levels of anxiety and pro-inflammatory cytokines including IL-1α, IL-6, IL-8, IL-12, IFN-γ, and CRP were significantly reduced after treatment of SSRIs (p < 0.05 in all cases). In addition, the change of anxiety measures co-vary with the change of peripheral cytokine levels (p < 0.05 in all cases). The regression model revealed that log transformed baseline levels of CRP and IL-6 predicted treatment response (p < 0.05 in both cases). CONCLUSIONS: This study is the first to investigate the effects of SSRIs on pro-inflammatory cytokines in patients with first episode GAD. The findings indicate moderate acute anti-inflammatory effects of SSRIs in GAD, and suggest that these anti-inflammatory effects may underlie anxiolytic effects of SSRIs. The study also indicates that serum levels of CRP and IL-6 may predict treatment response. However, data from randomized controlled trials is warranted to confirm these findings.

Manual or electroacupuncture as an add-on therapy to SSRIs for depression: A randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants, however, only around 60% of patients could benefit from them. Acupuncture is supported by insufficient evidence to help with symptom relieving and SSRIs tolerance. This pragmatic randomized controlled trial compared SSRIs alone versus SSRIs together with manual acupuncture (MA) or electroacupuncture (EA) in moderate to severe depressed patients. Patients were randomly allocated to receive MA + SSRIs (161), EA + SSRIs (160), or SSRIs alone (156) for six weeks, and then followed up for another four weeks. The primary outcome was response rate of the 17-item Hamilton Depression Scale (HAMD-17) at 6th week. The secondary outcomes were HAMD-17 (remission rate, early onset rate, total score), Self-Rating Depression Scale (SDS: total score), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS: total and domain scores), number of patients with adjusted dosage of SSRIs and adverse events (AEs). Both MA + SSRIs and EA + SSRIs were significantly better than SSRIs at 6th week on HAMD-17 response rate (RR = 1.21, 95% CI 1.04, 1.42, P = 0.013; RR = 1.27, 95% CI 1.09, 1.48, P = 0.0014), HAMD-17 early onset rate (P < 0.0001), HAMD-17 and SDS total scores (P < 0.05), CGI (P < 0.01), SERS total score (P < 0.01), number of patients with increased dosage of SSRIs (P < 0.01). For HAMD-17 remission rate, EA + SSRIs was significantly higher than SSRIs (P = 0.0083), while MA + SSRIs showed no significant difference at 6th week (P = 0.092). No unintended acupuncture-related severe AE was observed. This study identified that both MA and EA showed beneficial effects in addition to SSRIs alone in patients with moderate to severe depression, and were well tolerated. Clinical trials registration: ChiCTR-TRC-08000297.

Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb inhibitory action of serotonin on food intake.

The neurotransmitter serotonin (5-HT) acts as an important regulator of the critical neurodevelopmental processes and thus alterations in 5-HT signaling early promotes permanent structural and functional changes in brain. The selective serotonin reuptake inhibitors (SSRIs), as fluoxetine and citalopram, blocking serotonin transporter (SERT) at the presynaptic neuron, which regulates extracellular 5-HT levels. Evidence suggests that the exposure to SSRIs in the neurodevelopmental period may alters 5-HT signaling sensitivity on food intake control. The aim of the present study was to evaluate the effects of neonatal exposure to fluoxetine on molecular and cellular components of the serotonergic system and food intake control in young animals. Methods: The animals were divided according to experimental manipulation, Fluoxetine Group (FG): male pups received application of fluoxetine (10 mg/kg, 10 µL/g) and Saline Group (SG): male pups received saline application (0.9% NaCl, 10 µL/g), both throughout lactation (PND1-PND21). They evaluated body weight, food intake, SERT gene and protein expression, serotonin content in the hypothalamus. The neonatal exposure to fluoxetine promoted reduction in body weight, disturb the serotonin hypophagic response, and increase the serotonin and SERT hypothalamic in young animals. We conclude that the changes of components of the serotonergic system by neonatal exposure to fluoxetine may be responsible for disturb the inhibitory action of serotonin on food intake.

Body composition, biochemical, behavioral and molecular alterations in overfed rats after chronic exposure to SSRI.

Serotonin (5-HT) plays a regulatory role in coordinating the neural circuits regulating energy balance, with differences in both 5-HT availability at the synapse and the activity of 5-HT receptors mediating anorectic (via POMC/CART activation) and orexigenic (via NPY/AgRP activation) responses. In conditions of overweight and obesity the control of energy balance is clearly deregulated, and serotonergic modulation appears to make a significant contribution to weight gain. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) that increases 5-HT availability in the synaptic cleft may thus have potential effects on energy balance. Our aim was to use an overfeeding model to investigate the effects of chronic FLX treatment on energy balance-related parameters regulated by hypothalamic neuropeptides. Nursing male Wistar rats were assigned to normofed (9 pups/dam) or overfed (3 pups/dam) groups beginning at 3 days of age and continuing until 21 days of age, when commercial chow and water were made available ad libitum until experimental treatments were begun. From 39 through 59 days of age groups were divided according to pharmacological treatment: 1) NV group, normofed + vehicle solution (NaCl 0.9%, 10 ml/kg b.w.), 2) NF group, normofed + FLX (10 mg/kg b.w., in vehicle solution, 10 ml/kg b.w.) 3), OV, overfed + vehicle solution and 4) OF, overfed + FLX. At 60 days of age, body weight, white and brown adipose tissue content, and food intake were determined, and serum biochemical parameters and hypothalamic neuropeptide gene expression were measured. Results showed that FLX induced reductions in several murinometric indices, improvement of adipose profile, hypophagic behavior, reduction in serum parameters, and positive modulation of hypophagia-related genes. These data suggest that the beneficial effects of FLX-treatment on overfeeding-induced physical and behavioral effects in rats was due to hypothalamic alterations that led to improvement in energy balance in animals with a compromised metabolism.

Dextromethorphan/quinidine for the treatment of pseudobulbar affect.

OBJECTIVE: To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA). DATA SOURCES: A literature search of MEDLINE/PubMed (January 1966-June 2013) was conducted using search terms pseudobulbar affect, pathological laughing and/or crying, emotional lability, dextromethorphan, and quinidine. STUDY SELECTION AND DATA EXTRACTION: English language clinical trials and case reports evaluating the safety and efficacy of DM/Q in PBA were included for review. Bibliographies of all relevant articles were reviewed for additional citations. DATA SYNTHESIS: PBA, a poorly understood disorder, is characterized by involuntary crying and/or laughing. In the past, antidepressants and antiepileptics have been used off-label with mixed results. Four clinical trials have evaluated the use of DM/Q for the treatment of PBA. Although the therapeutic outcomes with DM/Q have been positive, interpretation of the published evidence is limited by small sample size and short treatment duration. CONCLUSIONS: Based on the data available, DM/Q may be a viable, short-term treatment alternative for PBA. Long-term safety and efficacy data are lacking.