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JAMA Feb 2023Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years.... (Review)
Review
IMPORTANCE
Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]).
OBSERVATIONS
Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene.
CONCLUSIONS AND RELEVANCE
During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.
Topics: Female; Humans; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Hot Flashes; Medroxyprogesterone Acetate; Menopause; Neoplasms; Paroxetine; Venlafaxine Hydrochloride; Venous Thromboembolism; Sweating; Female Urogenital Diseases; Autonomic Nervous System Diseases
PubMed: 36749328
DOI: 10.1001/jama.2022.24140 -
The Lancet. Psychiatry Jul 2019Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.
METHODS
We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4-12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.
FINDINGS
28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.
INTERPRETATION
For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.
FUNDING
Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.
Topics: Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Mirtazapine; Randomized Controlled Trials as Topic; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 31178367
DOI: 10.1016/S2215-0366(19)30217-2 -
Pharmacogenomics Jul 2019Antidepressant response could be from 42 to 50% genetically determined. Venlafaxine (VEN) was the sixth most-prescribed antidepressant in the USA in 2017. Therefore, we... (Review)
Review
Antidepressant response could be from 42 to 50% genetically determined. Venlafaxine (VEN) was the sixth most-prescribed antidepressant in the USA in 2017. Therefore, we reviewed studies which focused on the pharmacogenetics of VEN and found that there is a lack of guidelines for pharmacogenetic testing for VEN. Within investigated genetic polymorphisms, few of them can be indicated as potential predictors of VEN efficacy and tolerance. However, additional pharmacogenetic studies of VEN should be performed to reproduce already obtained results or explain contradictory ones. The individualization of pharmacotherapy is a key issue in providing patients with the highest possible quality of treatment, therefore pharmacogenetic studies should be one of the components of therapy optimization.
Topics: Antidepressive Agents; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Genotype; Humans; Pharmacogenetics; Polymorphism, Genetic; Venlafaxine Hydrochloride
PubMed: 31368838
DOI: 10.2217/pgs-2019-0031 -
Psychotherapy and Psychosomatics 2018Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim... (Review)
Review
BACKGROUND
Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation.
METHODS
PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included.
RESULTS
Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.
CONCLUSIONS
Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.
Topics: Adrenergic Uptake Inhibitors; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Humans; Mood Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride
PubMed: 30016772
DOI: 10.1159/000491524 -
The British Journal of Psychiatry : the... Mar 2020There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological...
There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological interventions. Fluoxetine, paroxetine, sertraline and venlafaxine are the best-evidenced drugs, with lower-level evidence for other medications. It is important that prescribing for PTSD is evidence-based.
Topics: Evidence-Based Medicine; Fluoxetine; Humans; Paroxetine; Sertraline; Stress Disorders, Post-Traumatic; Venlafaxine Hydrochloride
PubMed: 32345407
DOI: 10.1192/bjp.2020.40 -
CMAJ : Canadian Medical Association... Apr 2021
Topics: Administration, Intravenous; Animals; Antidepressive Agents, Second-Generation; Drug Overdose; Glucose; Humans; Hypoglycemia; Venlafaxine Hydrochloride
PubMed: 33875464
DOI: 10.1503/cmaj.78409 -
The Journal of Laryngology and Otology Sep 2023Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a systematic review and meta-analysis to determine the effectiveness of available prophylactic medication.
METHOD
literature search was performed using PubMed, Ovid and Embase databases. Qualitative and quantitative analysis were performed as well as risk of bias analysis. Meta-analysis for the mean differences for pre- and post-treatment impact based on Dizziness Handicap Inventory and Vertigo Symptom Scale were performed. Proportionate transformation meta-analysis for the successful event rate based on complete symptoms control was explored.
RESULTS
Thirteen publications were identified: 3 were randomised, controlled trials and 10 were non-randomised, controlled trials. Propranolol and venlafaxine improved the Vertigo Symptom Scale score by -13.31 points and -4.16 points, respectively, and the Dizziness Handicap Inventory score by -32.24 and -21.24, respectively. Only propranolol achieved statistically significant impact with 60 per cent of patients achieving complete symptom control.
CONCLUSION
Propranolol should be offered as the first-line treatment for vestibular migraine followed by venlafaxine. Amitriptyline, flunarizine and cinnarizine showed a trend for symptom improvement, but this was not statistically significant.
Topics: Humans; Dizziness; Propranolol; Venlafaxine Hydrochloride; Vertigo; Migraine Disorders
PubMed: 36200521
DOI: 10.1017/S0022215122001979 -
Expert Opinion on Pharmacotherapy Jun 2017Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly... (Review)
Review
Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.
Topics: Adult; Benzhydryl Compounds; Cataplexy; Drug Therapy, Combination; Humans; Modafinil; Narcolepsy; Neuropeptides; Off-Label Use; Orexins; Piperidines; Quality of Life; Sleep; Sodium Oxybate; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 28443381
DOI: 10.1080/14656566.2017.1323877 -
American Family Physician Mar 2023Posttraumatic stress disorder (PTSD) is common, with a lifetime prevalence of approximately 6%. PTSD may develop at least one month after a traumatic event involving the...
Posttraumatic stress disorder (PTSD) is common, with a lifetime prevalence of approximately 6%. PTSD may develop at least one month after a traumatic event involving the threat of death or harm to physical integrity, although earlier symptoms may represent an acute stress disorder. Symptoms typically involve trauma-related intrusive thoughts, avoidant behaviors, negative alterations of cognition or mood, and changes in arousal and reactivity. Assessing for past trauma in patients with anxiety or other psychiatric illnesses may aid in diagnosing and treating PTSD. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., text revision provides diagnostic criteria, and the PTSD Checklist for DSM-5 uses these diagnostic criteria to help physicians diagnose PTSD and determine severity. First-line treatment of PTSD involves psychotherapy, such as trauma-focused cognitive behavior therapy. Pharmacotherapy is useful for patients who have residual symptoms after psychotherapy or are unable or unwilling to access psychotherapy. Selective serotonin reuptake inhibitors (i.e., fluoxetine, paroxetine, and sertraline) and the serotonin-norepinephrine reuptake inhibitor venlafaxine effectively treat primary PTSD symptoms. The addition of other pharmacotherapy, such as atypical antipsychotics or topiramate, may be helpful for residual symptoms. Patients with PTSD often have sleep disturbance related to hyperarousal or nightmares. Prazosin is effective for the treatment of PTSD-related sleep disturbance. Clinicians should consider testing patients with PTSD for obstructive sleep apnea because many patients with PTSD-related sleep disturbance have this condition. Psychiatric comorbidities, particularly mood disorders and substance use, are common in PTSD and are best treated concurrently.
Topics: Humans; Stress Disorders, Post-Traumatic; Selective Serotonin Reuptake Inhibitors; Sertraline; Fluoxetine; Venlafaxine Hydrochloride
PubMed: 36920821
DOI: No ID Found -
Psychological Medicine Jul 2023Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been... (Review)
Review
BACKGROUND
Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD.
METHOD
We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts.
RESULT
After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents.
CONCLUSION
This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.
Topics: Humans; Venlafaxine Hydrochloride; Citalopram; Paroxetine; Fluoxetine; Bupropion; Sertraline; Antidepressive Agents
PubMed: 35346413
DOI: 10.1017/S0033291722000678