-
Journal of Psychopharmacology (Oxford,... Oct 2021There is extensive evidence that antidepressant drugs restore normal brain function by repairing damage to ventral hippocampus (vHPC) and medial prefrontal cortex...
BACKGROUND
There is extensive evidence that antidepressant drugs restore normal brain function by repairing damage to ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). While the damage is more extensive in hippocampus, the evidence of treatments, such as deep brain stimulation, suggests that functional changes in prefrontal cortex may be more critical. We hypothesized that antidepressant non-response may result from an insufficiency of transmission from vHPC to mPFC.
METHOD
Antidepressant non-responsive Wistar Kyoto (WKY) rats were subjected to chronic mild stress (CMS), then treated with chronic daily administration of the antidepressant drug venlafaxine (VEN) and/or repeated weekly optogenetic stimulation (OGS) of afferents to mPFC originating from vHPC or dorsal HPC (dHPC).
RESULTS
As in many previous studies, CMS decreased sucrose intake, open-arm entries on the elevated plus maze (EPM), and novel object recognition (NOR). Neither VEN nor vHPC-mPFC OGS alone was effective in reversing the effects of CMS, but the combination of chronic VEN and repeated OGS restored normal behaviour on all three measures. dHPC-mPFC OGS restored normal behaviour in the EPM and NOR test irrespective of concomitant VEN treatment, and had no effect on sucrose intake.
CONCLUSIONS
The synergism between VEN and vHPC-mPFC OGS supports the hypothesis that the antidepressant non-responsiveness of WKY rats results from a failure of antidepressant treatment fully to restore transmission in the vHPC-mPFC pathway.
Topics: Animals; Antidepressive Agents; Depression; Disease Models, Animal; Hippocampus; Male; Maze Learning; Optogenetics; Prefrontal Cortex; Rats; Rats, Inbred WKY; Stress, Psychological; Venlafaxine Hydrochloride
PubMed: 34617804
DOI: 10.1177/02698811211048281 -
PeerJ 2024Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn)...
Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.
Topics: Male; Animals; Rats; Rats, Wistar; Venlafaxine Hydrochloride; Corticosterone; Synbiotics; Cognition
PubMed: 38435986
DOI: 10.7717/peerj.17033 -
Evidence-based Mental Health Nov 2022Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.
BACKGROUND
Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.
OBJECTIVES
To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments.
DESIGN AND SETTING
Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018.
PARTICIPANTS
24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine.
MAIN OUTCOME MEASURES
Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates.
RESULTS
Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose.
CONCLUSIONS
There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm.
CLINICAL IMPLICATIONS
Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.
Topics: Humans; Mirtazapine; Cohort Studies; Venlafaxine Hydrochloride; Depression; Amitriptyline; Electronic Health Records; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Suicide; United Kingdom
PubMed: 35246454
DOI: 10.1136/ebmental-2021-300355 -
Toxins Sep 2020Paclitaxel, a primary chemotherapeutic agent used to treat numerous solid malignancies, is commonly associated with debilitating peripheral neuropathy. However, a...
Paclitaxel, a primary chemotherapeutic agent used to treat numerous solid malignancies, is commonly associated with debilitating peripheral neuropathy. However, a satisfactory gold-standard monotherapy for this neuropathic pain is not currently available. A combination strategy of two or more medications with different properties may achieve more beneficial effects than monotherapy. Thus, we investigated the analgesic efficacies and spinal mechanisms of the combination strategy, including bee venom acupuncture (BVA) and venlafaxine (VLX) against paclitaxel-induced allodynia in mice. Four intraperitoneal infusions of paclitaxel on alternating days (2 mg/kg/day) induced cold and mechanical allodynia for at least 1 week as assessed using acetone and the von Frey hair test, respectively. Co-treatment of BVA (1.0 mg/kg, s.c., ST36) with VLX (40 mg/kg, i.p.) at the medium dose produced a longer-lasting and additive effect than each monotherapy at the highest dose (BVA, 2.5 mg/kg; VLX, 60 mg/kg). Spinal pre-administration of idazoxan (α-adrenergic receptor antagonist, 10 μg), methysergide (mixed 5-HT/5-HT receptor antagonist, 10 μg), or MDL-72222 (5-HT receptor antagonist, 10 μg) abolished this analgesia. These results suggest that the combination therapy with BVA and VLX produces long-lasting and additive analgesic effects on paclitaxel-induced allodynia, via the spinal noradrenergic and serotonergic mechanism, providing a promising clinical strategy.
Topics: Acupuncture Therapy; Analgesics; Animals; Bee Venoms; Combined Modality Therapy; Disease Models, Animal; Hyperalgesia; Male; Mice, Inbred C57BL; Paclitaxel; Pain Threshold; Serotonin and Noradrenaline Reuptake Inhibitors; Spinal Cord; Venlafaxine Hydrochloride
PubMed: 32998357
DOI: 10.3390/toxins12100620 -
Basic & Clinical Pharmacology &... Apr 2022Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae, are high likely...
Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae, are high likely co-administered in China. ZJP could significantly inhibit VEN pharmacokinetics in vitro and in rats through suppression of CYP2D6 activity. To date, however, no clinical study has demonstrated the clinical relevance. Here, the VEN pharmacokinetics at a single dose of VEN with or without co-administration of ZJP was compared. ZJP had a weak herb-drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means of C and AUC of VEN increased by 36.7% and 34.6%, respectively, and the corresponding 90% confidence intervals (CIs) of geometric mean ratios (GMRs) exceed outside bioequivalent range of 0.80-1.25. However, the corresponding 90% CIs of GMRs of these parameters for ODV were within the range. Since ODV exposure (AUC), approximately 3.4-fold higher than that of VEN, hardly changed, the systemic exposure of VEN active moiety (VEN + ODV) with ZJP increased slightly (≤8.5%) compared with that of VEN alone. In addition, the incidence of VEN-related side effects, especially gastrointestinal relevance, was significantly reduced with ZJP. Therefore, rational concomitant use of VEN and ZJP might have low risk of HDI and be promising in clinical practice.
Topics: Animals; Antidepressive Agents; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Rats; Venlafaxine Hydrochloride
PubMed: 35132786
DOI: 10.1111/bcpt.13713 -
Molecules (Basel, Switzerland) Jun 2020Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish...
Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to produce the main metabolites from citalopram, metoprolol, sertraline, and venlafaxine. Metabolism in fish S9 fractions was compared to that in sheep. The metabolism of citalopram was further studied in fish. Our results suggest a large difference in the rate of metabolites formation between fish and sheep. Fish hepatic S9 fractions do not show an ability to form metabolites from venlafaxine, which was also the case for sheep. Citalopram, metoprolol, and sertraline were metabolized by both fish and sheep S9. Citalopram showed concentration-dependent -desmethylcitalopram formation with V = 1781 pmol/min/mg and K = 29.7 μM. The presence of ellipticine, a specific CYP1A inhibitor, in the incubations reduced the formation of -desmethylcitalopram by 30-100% depending on the applied concentration. These findings suggest that CYP1A is the major enzyme contributing to the formation of -desmethylcitalopram. In summary, the results from the present in vitro study suggest that common carp can form the major metabolites of citalopram, metoprolol, and sertraline.
Topics: Animals; Carps; Citalopram; Cytochrome P-450 CYP1A1; Female; In Vitro Techniques; Male; Metoprolol; Microsomes, Liver; Pharmaceutical Preparations; Sertraline; Sheep; Venlafaxine Hydrochloride
PubMed: 32531944
DOI: 10.3390/molecules25112690 -
Revista Brasileira de Ginecologia E... Sep 2022To evaluate the effect of neuromodulatory drugs on the intensity of chronic pelvic pain (CPP) in women.
OBJECTIVE
To evaluate the effect of neuromodulatory drugs on the intensity of chronic pelvic pain (CPP) in women.
DATA SOURCES
Searches were carried out in the PubMed, Cochrane Central, Embase, Lilacs, OpenGrey, and Clinical Trials databases.
SELECTION OF STUDIES
The searches were carried out by two of the authors, not delimiting publication date or original language. The following descriptors were used: OR , associated with MESH/ENTREE/DeCS: , , , , , , , , , , , , , , , , and , with the Boolean operator . Case reports and systematic reviews were excluded.
DATA COLLECTION
The following data were extracted: author, year of publication, setting, type of study, sample size, intervention details, follow-up time, and results.
DATA SYNTHESIS
A total of 218 articles were found, with 79 being excluded because they were repeated, leaving 139 articles for analysis: 90 were excluded in the analysis of the titles, 37 after reading the abstract, and 4 after reading the articles in full, and 1 could not be found, therefore, leaving 7 articles that were included in the review.
CONCLUSION
Most of the studies analyzed have shown pain improvement with the help of neuromodulators for chronic pain. However, no improvement was found in the study with the highest statistical power. There is still not enough evidence that neuromodulatory drugs reduce the intensity of pain in women with CPP.
Topics: Amitriptyline; Anticonvulsants; Antidepressive Agents; Antidepressive Agents, Tricyclic; Chronic Pain; Citalopram; Duloxetine Hydrochloride; Female; Gabapentin; Humans; Imipramine; Norepinephrine; Nortriptyline; Pelvic Pain; Pregabalin; Serotonin; Sertraline; Venlafaxine Hydrochloride
PubMed: 36044916
DOI: 10.1055/s-0042-1755459 -
Journal of Psychiatric Research Nov 2020Psychomotor Retardation is a key symptom of Major Depressive Disorder. According to the literature its presence may affect the prognosis of treatment. Aim of the present... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Psychomotor Retardation is a key symptom of Major Depressive Disorder. According to the literature its presence may affect the prognosis of treatment. Aim of the present study is to investigate the prognostic role of Psychomotor Retardation in patients with unipolar Psychotic Depression who are under antidepressant treatment.
METHODS
The Salpetriere Retardation Rating Scale was administered at baseline and after 6 weeks to 122 patients with unipolar Psychotic Depression who were randomly allocated to treatment with imipramine, venlafaxine or venlafaxine plus quetiapine. We studied the effects of Psychomotor Retardation on both depression and psychosis related outcome measures.
RESULTS
73% of the patients had Psychomotor Retardation at baseline against 35% after six weeks of treatment. The presence of Psychomotor Retardation predicted lower depression remission rates in addition to a higher persistence of delusions. After six weeks of treatment, venlafaxine was associated with higher levels of Psychomotor Retardation compared to imipramine and venlafaxine plus quetiapine.
CONCLUSIONS
Our data confirm that Psychomotor Retardation is a severity marker of unipolar Psychotic Depression. It is highly prevalent and predicts lower effectivity of antidepressant psychopharmacological treatment.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Prognosis; Psychotic Disorders; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 32877825
DOI: 10.1016/j.jpsychires.2020.07.020 -
Scientific Reports Oct 2022Recently, drug-controlled release nanotechnology has gained special attention in biomedicine. This work focuses on developing novel electrospun polymeric nanofibers...
Recently, drug-controlled release nanotechnology has gained special attention in biomedicine. This work focuses on developing novel electrospun polymeric nanofibers (NFs) for buccal delivery of VEN to avoid the hepatic metabolism and enzymatic degradation in the GIT and develop an effective control of drug release. The optimized NFs were obtained by blending polylactic acid (PLA), and poly (ɛ-caprolactone) (PCL) fixed at a ratio of 1:1. It was characterized for morphology, drug-loading, FTIR, XRD, DSC, and in vitro drug release. Ex vivo permeability of the blend NFs was assessed using chicken pouch mucosa compared to VEN suspension, followed by histopathological examination. Further, the cytotoxic effect in three different cell lines using WST-1 assay. SEM morphologies refer to defect-free uniform NFs of PLA, PCL, and PLA/PCL mats. These fibers had a diameter ranging from 200 to 500 nm. The physico-thermal characterization of NFs depicted that the drug was successfully loaded and in an amorphous state in the PLA/PCL NFs. In vitro release of NFs substantiated a bi-phasic profile with an initial burst release of about 30% in the initial 0.5 h and a prolonged cumulative release pattern that reached 80% over 96 h following a non-Fickian diffusion mechanism. Ex vivo permeation emphasizes the major enhancement of the sustained drug release and the noticeable decrease in the permeability of the drug from NFs. Cytotoxicity data found that IC of VEN alone was 217.55 μg/mL, then VEN-NFs recorded an IC value of 250.62 μg/mL, and plain NFs showed the lowest toxicity and IC 440.48 μg/mL in oral epithelial cells (OEC). Histopathology and cell toxicity studies demonstrated the preserved mucosal architecture and the preclinical safety. The developed PLA/PCL NFs can be promising drug carriers to introduce a step-change in improved psychiatric treatment healthcare.
Topics: Nanofibers; Polymers; Venlafaxine Hydrochloride; Delayed-Action Preparations; Polyesters
PubMed: 36302929
DOI: 10.1038/s41598-022-22878-7 -
Journal of Psychopharmacology (Oxford,... Oct 2020Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with... (Clinical Trial)
Clinical Trial
BACKGROUND
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects.
METHODS
Adults ⩾60 years of age in a current major depressive episode were treated in a protocolized manner with venlafaxine XR; 429 participants were treated for 8-16 weeks with a daily dose up to 300 mg to achieve remission from depression. Cardiac measures included sitting and standing BP and heart rate.
RESULTS
Of participants who were normotensive at baseline, 6.5% were found to have elevated BP during the study (1.9% <225 mg/day; 9.8% ⩾225 mg/day). There was no significant change in mean BP in the overall sample, or in the subgroup treated with doses ⩾225 mg/day. Additionally, 20.1% of the participants who did not have orthostatic hypotension at baseline were found to have orthostatic hypotension (16.8% <225 mg/day; 22.4% ⩾225 mg/day). Participants with new-onset orthostatic hypotension were significantly more likely to fall than the other participants.
CONCLUSION
A large proportion of older adults treated with venlafaxine experience orthostatic hypotension, putting them at risk for falls. A smaller proportion experience elevated BP. Older patients prescribed venlafaxine, particularly at high doses, should be advised and counseled about these adverse effects.
Topics: Accidental Falls; Aged; Aged, 80 and over; Blood Pressure; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Hypertension; Hypotension, Orthostatic; Male; Middle Aged; Prospective Studies; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 32842836
DOI: 10.1177/0269881120944154