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Journal of Clinical PsychopharmacologySince insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific.
METHODS
This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks).
RESULTS
EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome.
CONCLUSIONS
Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.
Topics: Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Psychotic Disorders; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 37930199
DOI: 10.1097/JCP.0000000000001756 -
Neuropharmacology Feb 2024The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake...
The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake inhibitor (SNRIs) in modulating vulvar pain led to the hypothesis that PV might involve central mechanisms. Here, we investigate whether vulvar pain is associated with gene-expression changes in mood, stress and pain systems, including amygdala (Amg), medial prefrontal cortex (mPFC), and periaqueductal gray matter (PAG). Additionally, we examined the analgesic and anxiolytic effects of venlafaxine. We found that the development of chronic vulvar pain in an animal model of PV is associated by overexpression of genes related to neuronal-activity and neuroinflammation in the Amg, mPFC, and PAG. Additionally, changes in the expression of GABA and serotonin synthesis, and reuptake were noted in the Amg and mPFC. Unsurprisingly, anxiety-like behavior and emotional-disorder were observed in rats with chronic vulvar pain. Nevertheless, treatment with venlafaxine (37.5 mg/kg) for one month significantly improves the vulvar hypersensitivity, as well as reduces the anxiety level. More critically, the long-term gene expression adaptation in serotonin receptor and synthesis, GABA synthesis, neuroplasticity, and neuroinflammation in the Amg, mPFC, and PAG, were modulated by venlafaxine in rats with vulvar pain. Our findings suggest that vulvar hypersensitivity induced by inflammation might associated with gene expression changes in brain areas that are involved in mood, stress and pain regulation. These changes probably play a role in central sensitization, and anxiety. Strikingly, enhancing the activity of serotonin and noradrenaline via venlafaxine treatment in rats with vulvar pain induces analgesic and anxiolytic effects.
Topics: Humans; Female; Rats; Animals; Venlafaxine Hydrochloride; Vulvodynia; Anti-Anxiety Agents; Serotonin; Neuroinflammatory Diseases; Selective Serotonin Reuptake Inhibitors; Norepinephrine; Chronic Pain; gamma-Aminobutyric Acid; Analgesics
PubMed: 37984764
DOI: 10.1016/j.neuropharm.2023.109788 -
Clinical Neurology and Neurosurgery Jun 2024Migraine, as a primary headache disorder, stands as one of the primary causes of disability worldwide. Consequently, prophylactic treatments are highly recommended for...
OBJECTIVE
Migraine, as a primary headache disorder, stands as one of the primary causes of disability worldwide. Consequently, prophylactic treatments are highly recommended for individuals experiencing recurrent migraine episodes. Our study aimed to compare the efficacy and safety profiles of venlafaxine and nortriptyline in the prophylactic management of migraine.
METHODS
In this single-center, randomized, double-blind clinical trial, 210 migraine patients were allocated into two groups in a 1:1 ratio. One group received venlafaxine (37.5 mg, orally twice daily), while the other group administered nortriptyline (25 mg, orally once daily). A neurologist documented (1) headache intensity using the Visual Analog Scale (VAS) and 6-point Behavioral Rating Scale (BRS-6), (2) headache frequency (per month), and (3) headache duration (in hours) of participants on days 0, 45, and 90 of the intervention.
RESULTS
Following the 90-day intervention, a significant decrease was observed in VAS, BRS-6, frequency, and duration of headaches within both groups (all with p-values <0.001). No difference in VAS, BRS-6, or headache durations was observed between the two groups after 45 and 90 days of treatment (all p-values > 0.05). Although the headache frequency exhibited no difference between the groups after 45 days (p-value = 0.097), a significantly lower frequency in the venlafaxine group was observed at day 90 of the intervention (p-value = 0.011). The reductions in attack parameters in the 0-45- and 0-90-day intervals did not meet statistical significance between the two groups (p-values > 0.05). 77.0 % of the participants in the venlafaxine group and 79.2 % in the nortriptyline group experienced a minimum of 50 % improvement in all attack parameters. Venlafaxine demonstrated a statistically significant lower incidence of adverse reactions in comparison to nortriptyline (p-value = 0.005). A total of 33 adverse drug reactions were documented in the venlafaxine group and 53 in the nortriptyline group, with insomnia observed in the former and xerostomia in the latter as the most prevalent side effects.
CONCLUSIONS
Venlafaxine and nortriptyline demonstrate clinically significant and comparable therapeutic efficacy for migraine patients in reducing the intensity, frequency, and duration of headache attacks. Venlafaxine may be preferred to nortriptyline in the context of migraine preventive treatment under comparable conditions due to its lower incidence of adverse effects.
PubMed: 38901375
DOI: 10.1016/j.clineuro.2024.108400 -
Frontiers in Pharmacology 2023We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers,...
We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers, antiseizure medications, and antidepressants such as tricyclics and serotonin-noradrenaline reuptake inhibitors. PubMed, Web of Science, Embase, and Cochrane Center for Clinical Trials were systematically searched for relevant randomized clinical trials (RCTs) from March 2023 to May 2023. Studies on the efficacy and tolerability of prophylactic treatments for VM were included. Efficacy was measured using the average vertigo frequency per month and dizziness handicap inventory (DHI) improvement after 3-6 months of treatment. Tolerability was measured by the number of patients reporting at least one adverse event (AE). Network meta-analyses were performed according to a Bayesian framework and a random-effects model based on odds ratios or mean differences (MDs) and 95% confidence intervals (CIs). A sequence of ranking probability was calculated according to the surface under the cumulative ranking (SUCRA) curve. This network meta-analysis was previously registered with PROSPERO (CRD42023422258). Five RCTs comprising 334 patients were analyzed by synthesizing the published evidence. Considering the examined prophylactic therapies, there is significant evidence that valproate acid (VPA) is superior to placebo or abortive treatment alone (MD = -4.12, 95% CI = -8.09, -0.15) in reducing the frequency of vertigo. Flunarizine (MD = 20.00, 95% CI = 10.90, 29.10), valproate acid (MD = 18.88, 95% CI = 10.42, 27.34), and venlafaxine (MD = 11.48, 95% CI = 9.84, 13.12) were significantly more effective than placebo or abortive treatment in reducing DHI. VPA most strongly reduced the frequency of vertigo according to SUCRA, but it ranked third-to-last in tolerability. Flunarizine ranked best in DHI improvement but worst in tolerability. Metoprolol ranked worst for efficacy but best for tolerability. VPA and flunarizine reduced the frequency of vertigo and improved DHI, but they had unfavorable tolerability. The effects of metoprolol on vertigo require further study. Given the low certainty and limited sample, additional head-to-head RCTs are warranted to further confirm efficacy. https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42023422258.
PubMed: 38186654
DOI: 10.3389/fphar.2023.1332973 -
Psychopharmacology Bulletin Aug 2023A growing body of evidence has recently suggested that taking venlafaxine during pregnancy may be linked to increased risk of certain congenital defects. The study aimed...
OBJECTIVES
A growing body of evidence has recently suggested that taking venlafaxine during pregnancy may be linked to increased risk of certain congenital defects. The study aimed to address the effects of venlafaxine use during pregnancy on the development of the brain in mice.
EXPERIMENTAL DESIGN
Fourteen female BALB/c mice were randomly divided into two equally-sized groups: venlafaxine-treated and control. After mating, pregnant mice of venlafaxine-treated group were orally received the venlafaxine 35 mg/kg/day throughout pregnancy, while pregnant control mice did not receive any treatment. All pups were killed on postnatal day 21 and brain images were quantified using ImageJ software. The mRNA expression levels of SHANK3, TUBB5 and DDC of genes in pups' brain tissue samples were evaluated using quantitative real-time PCR method.
PRINCIPAL OBSERVATIONS
The mean brain size of pups was significantly smaller in the venlafaxine-treated group than in the control group. Results showed that the mRNA expression levels of SHANK3 and TUBB5 was significantly downregulated in venlafaxine-treated mice compared to control group. Expression of DDC gene didn't showed significant differences between two groups.
CONCLUSIONS
These results provide evidence that use of venlafaxine during pregnancy may affect the brain development in mice and altered the expression of SHANK3 and TUBB5 genes in brain tissue.
Topics: Animals; Female; Mice; Pregnancy; Aromatic-L-Amino-Acid Decarboxylases; Brain; Nerve Tissue Proteins; RNA, Messenger; Venlafaxine Hydrochloride
PubMed: 37601086
DOI: No ID Found -
Environmental Toxicology and Chemistry Jul 2024Wastewater treatment plant (WWTP) effluent often releases pharmaceuticals like venlafaxine (a serotonin-norephinephrine reuptake inhibitor antidepressant) to freshwater...
Wastewater treatment plant (WWTP) effluent often releases pharmaceuticals like venlafaxine (a serotonin-norephinephrine reuptake inhibitor antidepressant) to freshwater ecosystems at levels causing adverse metabolic effects on fish. Changes to fish metabolism can be regulated by epigenetic mechanisms like microRNA (small RNA molecules that regulate mRNA translation), including regulating mitochondrial mRNAs. Nuclear-encoded microRNAs regulate mitochondrial gene expression in mammals, and have predicted effects in fish. We aimed to identify whether venlafaxine exposure changed mitochondrial respiration and resulted in differentially abundant mitochondrial microRNA (mitomiRs) in zebrafish brains. In vitro exposure of brain homogenate to below environmentally relevant concentrations of venlafaxine (<1 µg/L) caused a decrease in mitochondrial respiration, although this was not driven by changes to mitochondrial Complex I or II function. To identify whether these effects occur in vivo, zebrafish were exposed to 1 µg/L venlafaxine for 0, 1, 6, 12, 24, and 96 h. In vivo, venlafaxine exposure had no significant effects on brain mitochondrial respiration; however, select mitomiRs (dre-miR-301a-5p, dre-miR-301b-3p, and dre-miR-301c-3p) were also measured, because they were bioinformatically predicted to regulate mitochondrial cytochrome c oxidase subunit I (COI) abundance. These mitomiRs were differentially regulated based on venlafaxine exposure (with miR-301c-3p abundance differing during the day and miR-301b-3p being lower in exposed fish at night), and with respect to sex and time sampled. Overall, the results demonstrated that in vitro venlafaxine exposure to zebrafish brain caused a decrease in mitochondrial respiration, but these effects were not seen after acute in vivo exposure. Results may have differed because in vivo exposure allows for fish to mitigate effects through mechanisms that could include mitomiR regulation, and because fish were only acutely exposed. Environ Toxicol Chem 2024;43:1569-1582. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Animals; Zebrafish; Venlafaxine Hydrochloride; Mitochondria; Brain; MicroRNAs; Water Pollutants, Chemical; Cell Respiration
PubMed: 38695684
DOI: 10.1002/etc.5884 -
International Journal of Molecular... May 2024Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to...
Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group ( < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine ( < 0.05 central zone; ≤ 0.05 periphery zone) and SMe1EC2M3 ( < 0.05 central zone; < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST ( < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group ( < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group ( < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD.
Topics: Animals; Rats; Male; Disease Models, Animal; Antidepressive Agents; Venlafaxine Hydrochloride; Depression; Behavior, Animal; Depressive Disorder, Treatment-Resistant; Rats, Inbred WKY; Stress, Psychological; Anxiety; Indoles; Anhedonia
PubMed: 38791304
DOI: 10.3390/ijms25105265 -
Expert Opinion on Pharmacotherapy 2023Mental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants... (Review)
Review
Moving from serotonin to serotonin-norepinephrine enhancement with increasing venlafaxine dose: clinical implications and strategies for a successful outcome in major depressive disorder.
INTRODUCTION
Mental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants are widely accepted as first-line pharmacological treatment for major depressive disorder (MDD), patient response to such treatment is variable, with more than half failing to achieve complete remission, and residual symptoms are frequently present.
AREAS COVERED
Here, the pharmacodynamics of venlafaxine XR are reviewed in relation to its role as both a selective serotonin reuptake inhibitor (SSRI) and a serotonin-norepinephrine-reuptake inhibitor (SNRI), and we look at how these pharmacodynamic properties can be harnessed to guide clinical practice, asking the question 'is it possible to develop a symptom-cluster-based approach to the treatment of MDD with comorbid anxiety utilizing venlafaxine XR?.' Additionally, three illustrative clinical cases provide practical examples of the utility of venlafaxine-XR in real-world clinical practice. The place of venlafaxine XR in managing fatigue/low energy, a frequent residual symptom in MDD, is explored using pooled data from clinical trials of venlafaxine XR.
EXPERT OPINION
Venlafaxine XR should be considered as a first-line treatment for MDD with or without comorbid anxiety, and there are clear pharmacodynamic signals supporting a symptom cluster-based treatment paradigm for venlafaxine XR.
Topics: Humans; Venlafaxine Hydrochloride; Depressive Disorder, Major; Serotonin; Norepinephrine; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Cyclohexanols; Treatment Outcome; Delayed-Action Preparations
PubMed: 37501324
DOI: 10.1080/14656566.2023.2242264 -
Annals of Internal Medicine Mar 2024The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of...
The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.
DESCRIPTION
The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against.
METHODS
Subject experts from both departments developed 12 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Recommendations were made after consensus was reached; they were based on quality and strength of evidence and informed by other factors, including feasibility and patient perspectives. Once the draft was peer reviewed by an external group of experts and their inputs were incorporated, the final document was completed.
RECOMMENDATIONS
The revised CPG includes 34 recommendations in the following 5 topic areas: assessment and diagnosis, prevention, treatment, treatment of nightmares, and treatment of posttraumatic stress disorder (PTSD) with co-occurring conditions. Six recommendations on PTSD treatment were rated as strong. The CPG recommends use of specific manualized psychotherapies over pharmacotherapy; prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy; paroxetine, sertraline, or venlafaxine; and secure video teleconferencing to deliver recommended psychotherapy when that therapy has been validated for use with video teleconferencing or when other options are unavailable. The CPG also recommends against use of benzodiazepines, cannabis, or cannabis-derived products. Providers are encouraged to use this guideline to support evidence-based, patient-centered care and shared decision making to optimize individuals' health outcomes and quality of life.
Topics: Humans; United States; Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic, Acute; Veterans; Quality of Life; Psychotherapy; United States Department of Veterans Affairs
PubMed: 38408360
DOI: 10.7326/M23-2757 -
Journal of Integrative Neuroscience Jul 2023Stress can lead to emotional and mental symptoms such as anxiety, sadness, panic attacks, and depression. Malic acid was chosen due to malic acid has the ability to...
BACKGROUND
Stress can lead to emotional and mental symptoms such as anxiety, sadness, panic attacks, and depression. Malic acid was chosen due to malic acid has the ability to improve antioxidant activity and improves liver damage. This study evaluates malic acid anti-depressant activity in the hypothalamus of stressed rats.
METHODS
Thirty-six male albino rats were divided into 2 equal groups; Normal and chronic mild stress (CMS) rats. Normal rats were divided into 3 equal groups; control, malic acid, and venlafaxine drug groups: normal rats were administered orally with 1 mL of saline solution, 250 mg/kg of malic acid, and 20 mg/kg of venlafaxine drug, respectively. CMS rats were divided into 3 equal groups; CMS, CMS + malic acid, and CMS + venlafaxine drug: CMS rats were administered orally with 1 mL of saline solution, 250 mg/kg of malic acid, and 20 mg/kg of venlafaxine drug, respectively. All the above-mentioned treatments were administered once a day by oral gavage for 6 weeks.
RESULTS
The obtained results revealed that the animal behavioral tests such as forced swimming test, tail suspension test, sucrose preference test, and open-field test (center square entries test, center square duration test, and distance travelled test), norepinephrine, dopamine, serotonin, γ-aminobutyric acid, nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity, oxidative index, conjugated dienes, catalase, glutathione peroxidase, superoxide dismutase, malondialdehyde, interleukin-6, tumor necrosis factor-α, interleukin-10, interleukin-1β, sodium/potassium-ATPase activity, and histamine-N-methyl transferase () and tyrosine hydroxylase () enzymes in the hypothalamus of stressed rats, were returned to approaching the normal state in the stressed group after treating with malic acid for 6 weeks.
CONCLUSIONS
Malic acid ameliorated stressed-related symptoms and it inhibited superoxide anion and neuro-inflammation in the hypothalamus of stressed rats.
Topics: Rats; Male; Animals; Venlafaxine Hydrochloride; Saline Solution; Depression; Hypothalamus; Stress, Psychological; Oxidative Stress
PubMed: 37519180
DOI: 10.31083/j.jin2204098