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Der Nervenarzt Jun 2024In addition to trauma-focussed psychotherapy, pharmacological treatment is often unavoidable, especially in patients with severe posttraumatic stress disorder (PTSD). As... (Review)
Review
In addition to trauma-focussed psychotherapy, pharmacological treatment is often unavoidable, especially in patients with severe posttraumatic stress disorder (PTSD). As long as comorbid disorders do not dictate the pharmacotherapy approach, sertraline and paroxetine, along with other off-label prescribable substances approved in Germany, can be used for the treatment of PTSD. Venlafaxine, in particular, has shown good effectiveness in studies, whereas risperidone has shown lower effectiveness in augmentation. Overall, only a small to medium effect size is to be expected for all substances. Psychopharmacotherapy plays an important role in addressing sleep disorders, which are highly prevalent in PTSD. Treatment of trauma-related nightmares can be attempted with doxazosin or clonidine. In contrast, there are limited empirical data available for sleep disorders associated with PTSD, but the pharmacological treatment of insomnia can provide some guidance.
PubMed: 38916664
DOI: 10.1007/s00115-024-01684-8 -
Fortschritte Der Neurologie-Psychiatrie Jun 2024There are only few publications on long-term treatments for major depressive disorder (MDD) lasting 5 years or longer. Most clinical controlled trials lasted no longer...
BACKGROUND
There are only few publications on long-term treatments for major depressive disorder (MDD) lasting 5 years or longer. Most clinical controlled trials lasted no longer than 2 years and some recent studies suggested an advantage of cognitive behavioral therapy (CBT) over antidepressants in relapse prevention of MDD.
METHODS
Exclusively outpatient "real world" treatment of severe melancholia, prospectively documented over 10 years with different serial treatment strategies, discontinuation phenomena and complications.
METHODS
Compared to CBT, agomelatine, mirtazapine, bupropion and high-dose milnacipran, high-dose venlafaxine (extended-release form, XR) was effective, even sustainably. Asymptomatic premature ventricular contractions (PVCs) were found at the beginning of the treatment of the MDD, which initially led to the discontinuation of high-dose venlafaxine (300 mg daily). Even the various treatment strategies mentioned above were unable to compensate for or prevent the subsequent severe deterioration in MDD (2 rebounds, 1 recurrence). Only the renewed use of high-dose venlafaxine was successful. PVC no longer occurred and the treatment was also well tolerated over the years, with venlafaxine serum levels at times exceeding 5 times the recommended upper therapeutic reference level (known bupropion-venlafaxine interaction, otherwise 2.5 to 3-fold increase with high-dose venlafaxine alone). During dose reduction or after gradual discontinuation of high-dose venlafaxine, rather mild withdrawal symptoms occurred, but as described above, also two severe rebounds and one severe recurrence happened.
DISCUSSION
This long-term observation supports critical reflections on the discontinuation of successful long-term treatment with antidepressants in severe MDD, even if it should be under "the protection" of CBT. The PVC seemed to be more related to the duration of the severe major depressive episode than to the venlafaxine treatment itself. A particular prospective observation of this longitudinal case study is that relapses (in the sense of rebounds) during or after previous venlafaxine tapering seemed to herald the recurrence after complete recovery. Remarkably, neither relapses nor recurrence could be prevented by CBT.
CONCLUSION
In this case, high-dose venlafaxine has a particular relapse-preventive (and "recurrence-preventive") effect with good long-term tolerability.
PubMed: 38901434
DOI: 10.1055/a-2332-6107 -
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 -
Expert Opinion on Pharmacotherapy Jun 2024Adrenergic neurotransmitter reuptake inhibitors are gaining attention in treatment for attention-deficit hyperactivity disorder (ADHD). Due to their effects on...
INTRODUCTION
Adrenergic neurotransmitter reuptake inhibitors are gaining attention in treatment for attention-deficit hyperactivity disorder (ADHD). Due to their effects on norepinephrine, dopamine, and serotonin neurotransmission, they benefit both ADHD and comorbid disorders and have some other advantages including longer duration of action and fewer adverse effects compared to stimulants. There is continued interest in these agents with novel mechanisms of action in treatment of ADHD.
AREAS COVERED
The authors conducted a PubMed literature search using the following key words: 'ADHD' AND 'adrenergic reuptake inhibitors' OR 'nonstimulants' OR 'atomoxetine' OR 'Viloxazine' OR 'Dasotraline' OR 'Centanafadine' OR 'PDC-1421' OR 'Reboxetine' OR 'Edivoxetine' OR 'Bupropion' OR 'Venlafaxine' OR 'Duloxetine.' They reviewed FDA fact sheets of available medications for safety/tolerability studies and reviewed published clinical studies of these medications for treatment of ADHD.
EXPERT OPINION
Adrenergic neurotransmitter reuptake inhibitors fit the diverse needs of children and adolescents with ADHD with 1) poor tolerability to stimulants (e.g. due to growth suppression, insomnia, rebound irritability, co-morbid depression, anxiety and tic disorders, substance abuse or diversion concerns), 2) cardiac risks, and/or 3) need for extended duration of action. Their differences in receptor affinities and modulating effects support the unique benefits of individual agents.
PubMed: 38900676
DOI: 10.1080/14656566.2024.2369197 -
Frontiers in Psychiatry 2024Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut...
BACKGROUND
Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZ-treated mice are largely unclear.
METHODS
Male C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage from the third week onward during CPZ treatment.
RESULTS
CPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in β-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of and in CPZ-treated mice.
CONCLUSION
The anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice.
PubMed: 38899045
DOI: 10.3389/fpsyt.2024.1347867 -
Pharmacogenomics May 2024We herein inferred the genetic diversity of CYP450 isoenzymes to predict the percentage of patients who need dose adjustment in drugs used in psychiatry. Data of 784...
We herein inferred the genetic diversity of CYP450 isoenzymes to predict the percentage of patients who need dose adjustment in drugs used in psychiatry. Data of 784 Greek patients receiving psychiatric care who were genotyped for CYP2D6, CYP2C19, CYP1A2, CYP3A5 and CYP2C9 isoenzymes were inferred to gene-drug pairs according to the US FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group annotations and published literature. Atypical metabolism was found for 36.8% of patients in CYP2D6, 49.2% in CYP2C19, 45% in CYP1A2, 16.7% in CYP3A5 and 41.8% in CYP2C9. Dosage adjustment need was estimated for 10.2% of venlafaxine, 10.0% of paroxetine, 6.4% of sertraline, 30.8% of citalopram, 52.1% of escitalopram, 18.2% of fluvoxamine, 54.1% of tricyclic antidepressants, 16.7% of zuclopenthixol, 10.6% of haloperidol and 13.3% of risperidone treated patients. Clinical psychiatric pharmacogenomic implementation holds promise to improve drug effectiveness and safety.
PubMed: 38884939
DOI: 10.1080/14622416.2024.2346072 -
Water Research Jun 2024Wastewater treatment plants (WWTPs) are essential for maintaining a good water quality of surface waters. However, WWTPs are also associated with water quality...
Wastewater treatment plants (WWTPs) are essential for maintaining a good water quality of surface waters. However, WWTPs are also associated with water quality deterioration and hydro-morphological alteration. Riverine communities respond to these stressors with changes in their community structure, abundance and diversity. In this study, we used a dataset of 94 monitoring sites across North Rhine-Westphalia, Germany to investigate the influence of WWTPs on the water quality and hydro-morphological quality in river sections downstream of WWTP effluents. More specifically, we analyzed the effects of the percentage of WWTP effluents (in relation to median base flow) on four stressor groups (physico-chemistry, micropollutants, hydrological and morphological alteration) using Linear Mixed Models (LMM). Furthermore, we assessed the impact of a selection of twelve ecologically relevant stressor variables reflecting water quality deterioration and hydro-morphological alteration on reference fish communities using Canonical Correspondence Analysis (CCA). The percentage of WWTP effluents was correlated with water quality, especially with toxic units of a wide range of pharmaceuticals including diclofenac, venlafaxine and sulfamethoxazole (R² up to 0.54) as well as specific pesticides (e.g., terbutryn: R² = 0.33). The correlation of percent WWTP effluents with hydro-morphological alteration was weaker and most pronounced for the frequency of high flow (R² = 0.24) and flow variability (R² = 0.19). About 40 % of the variance in the fish community structure were explained by 12 stressor variables in the CCA models. Water quality and hydrological, but not morphological stressors showed strong albeit highly variable effects on individual fish species. The results indicate that water quality degradation and hydrological alteration are important factors determining the ecological status of fish communities. In this context, WWTP effluents can impose relevant point sources of pollution that affect water quality but also cause alterations of the hydrological regime. Further management measures addressing both stressor groups are needed to improve the ecological status.
PubMed: 38880012
DOI: 10.1016/j.watres.2024.121914 -
Journal of Pineal Research Aug 2024The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at...
The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at high concentrations in the aquatic environment. Concerns have been raised related to the health of aquatic organisms in response to this nontargeted pharmaceutical exposure. For instance, we previously demonstrated that exposure to venlafaxine perturbs neurodevelopment, leading to behavioural alterations in zebrafish (Danio rerio). We also observed disruption in serotonin expression in the pineal and raphe, regions critical in regulating circadian rhythms, leading us to hypothesize that zygotic exposure to venlafaxine disrupts the circadian locomotor rhythm in larval zebrafish. To test this, we microinjected zebrafish embryos with venlafaxine (1 or 10 ng) and recorded the locomotor activity in 5-day-old larvae over a 24-h period. Venlafaxine deposition reduced larval locomotor activity during the light phase, but not during the dark phase of the diurnal cycle. The melatonin levels were higher in the dark compared to during the light photoperiod and this was not affected by embryonic venlafaxine deposition. Venlafaxine exposure also did not affect the transcript abundance of clock genes, including clock1a, bmal2, cry1a and per2, which showed a clear day/night rhythmicity. A notable finding was that exposure to luzindole, a melatonin receptor antagonist, decreased the locomotor activity in the control group in light, whereas the activity was higher in larvae raised from the venlafaxine-deposited embryos. Overall, zygotic exposure to venlafaxine disrupts the locomotor activity of larval zebrafish fish during the day, demonstrating the capacity of antidepressants to disrupt the circadian rhythms in behaviour. Our results suggest that disruption in melatonin signalling may be playing a role in the venlafaxine impact on circadian behaviour, but further investigation is required to elucidate the possible mechanisms in larval zebrafish.
Topics: Animals; Zebrafish; Venlafaxine Hydrochloride; Larva; Locomotion; Circadian Rhythm; Zebrafish Proteins; Zygote; Motor Activity; Melatonin
PubMed: 38874070
DOI: 10.1111/jpi.12984 -
Nature and Science of Sleep 2024This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).
PURPOSE
This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).
METHODS
Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Fatigue Severity Scale (FSS), polysomnography, multiple sleep latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate.
RESULTS
Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time ( =0.007), decreased sleep efficiency ( =0.002), shortening of sleep onset latency ( <0.001), elevated wake after sleep onset ( =0.002), increased N1% ( =0.006), and reduced N2%, N3%, and REM% ( =0.007, <0.001, =0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity ( <0.001), and increased brain fatigue ( =0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue ( <0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue ( =0.013, =0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (=0.012, =0.030).
CONCLUSION
NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.
PubMed: 38873239
DOI: 10.2147/NSS.S452665