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Pharmacological Research Dec 2022Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in... (Review)
Review
Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.
Topics: Adult; Humans; Fibromyalgia; Antidepressive Agents; Fatigue; Musculoskeletal Pain; Employment
PubMed: 36336218
DOI: 10.1016/j.phrs.2022.106547 -
The Cochrane Database of Systematic... Aug 2015Neuropathic pain, which is caused by nerve damage, is increasing in prevalence worldwide. This may reflect improved diagnosis, or it may be due to increased incidence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuropathic pain, which is caused by nerve damage, is increasing in prevalence worldwide. This may reflect improved diagnosis, or it may be due to increased incidence of diabetes-associated neuropathy, linked to increasing levels of obesity. Other types of neuropathic pain include post-herpetic neuralgia, trigeminal neuralgia, and neuralgia caused by chemotherapy. Antidepressant drugs are sometimes used to treat neuropathic pain; however, their analgesic efficacy is unclear. A previous Cochrane review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining chronic neuropathic pain in the first instance. Venlafaxine is a reasonably well-tolerated antidepressant and is a serotonin reuptake inhibitor and weak noradrenaline reuptake inhibitor. Although not licensed for the treatment of chronic or neuropathic pain in most countries, it is sometimes used for this indication.
OBJECTIVES
To assess the analgesic efficacy of, and the adverse effects associated with the clinical use of, venlafaxine for chronic neuropathic pain in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library, and MEDLINE and EMBASE via Ovid up to 14 August 2014. We reviewed the bibliographies of any randomised trials identified and review articles, contacted authors of one excluded study and searched www.clinicaltrials.gov to identify additional published or unpublished data. We also searched the meta-Register of controlled trials (mRCT) (www.controlled-trials.com/mrct) and the WHO International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/) for ongoing trials but did not find any relevant trials.
SELECTION CRITERIA
We included randomised, double-blind studies of at least two weeks' duration comparing venlafaxine with either placebo or another active treatment in chronic neuropathic pain in adults. All participants were aged 18 years or over and all included studies had at least 10 participants per treatment arm. We only included studies with full journal publication.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data using a standard form and assessed study quality. We intend to analyse data in three tiers of evidence as described by Hearn 2014, but did not find any first-tier evidence (ie evidence meeting current best standards, with minimal risk of bias) or second-tier evidence, that was considered at some risk of bias but with adequate participant numbers (at least 200 in the comparison). Third-tier evidence is that arising from studies with small numbers of participants; studies of short duration, studies that are likely to be of limited clinical utility due to other limitations, including selection bias and attrition bias; or a combination of these.
MAIN RESULTS
We found six randomised, double-blind trials of at least two weeks' duration eligible for inclusion. These trials included 460 participants with neuropathic pain, with most participants having painful diabetic neuropathy. Four studies were of cross-over design and two were parallel trials. Only one trial was both parallel design and placebo-controlled. Mean age of participants ranged from 48 to 59 years. In three studies (Forssell 2004, Jia 2006 and Tasmuth 2002), only mean data were reported. Comparators included placebo, imipramine, and carbamazepine and duration of treatment ranged from two to eight weeks. The risk of bias was considerable overall in the review, especially due to the small size of most studies and due to attrition bias. Four of the six studies reported some positive benefit for venlafaxine. In the largest study by Rowbotham, 2004, 56% of participants receiving venlafaxine 150 to 225 mg achieved at least a 50% reduction in pain intensity versus 34% of participants in the placebo group and the number needed to treat for an additional beneficial outcome was 4.5. However, this study was subject to significant selection bias. Known adverse effects of venlafaxine, including somnolence, dizziness, and mild gastrointestinal problems, were reported in all studies but were not particularly problematic and, overall, adverse effects were equally prominent in placebo or other active comparator groups.
AUTHORS' CONCLUSIONS
We found little compelling evidence to support the use of venlafaxine in neuropathic pain. While there was some third-tier evidence of benefit, this arose from studies that had methodological limitations and considerable risk of bias. Placebo effects were notably strong in several studies. Given that effective drug treatments for neuropathic pain are in current use, there is no evidence to revise prescribing guidelines to promote the use of venlafaxine in neuropathic pain. Although venlafaxine was generally reasonably well tolerated, there was some evidence that it can precipitate fatigue, somnolence, nausea, and dizziness in a minority of people.
Topics: Adult; Analgesics, Non-Narcotic; Antidepressive Agents, Second-Generation; Carbamazepine; Humans; Imipramine; Middle Aged; Neuralgia; Off-Label Use; Patient Dropouts; Randomized Controlled Trials as Topic; Venlafaxine Hydrochloride
PubMed: 26298465
DOI: 10.1002/14651858.CD011091.pub2 -
The Lancet. Psychiatry Jul 2024Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
METHODS
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
FINDINGS
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
INTERPRETATION
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
FUNDING
None.
Topics: Humans; Antidepressive Agents; Incidence; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 38851198
DOI: 10.1016/S2215-0366(24)00133-0 -
Frontiers in Psychiatry 2022Consistent evidence suggests residual depressive symptomology are the strongest predictors of depression relapse following cognitive-behavioral therapy (CBT) and...
A Systematic Review and Individual Patient Data Network Analysis of the Residual Symptom Structure Following Cognitive-Behavioral Therapy and Escitalopram, Mirtazapine and Venlafaxine for Depression.
OBJECTIVE
Consistent evidence suggests residual depressive symptomology are the strongest predictors of depression relapse following cognitive-behavioral therapy (CBT) and antidepressant medications (ADM's). Psychometric network models help detecting and understanding central symptoms that remain post-treatment, along with their complex co-occurrences. However, individual psychometric network studies show inconsistent findings. This systematic review and IPD network analysis aimed to estimate and compare the symptom network structures of residual depressive symptoms following CBT, ADM's, and their combination.
METHODS
PsycINFO, PsycArticles, and PubMed were systematically searched through October 2020 for studies that have assessed individuals with major depression at post-treatment receiving either CBT and/or ADM's (venlafaxine, escitalopram, mirtazapine). IPD was requested from eligible samples to estimate and compare residual symptom psychometric network models post-CBT and post-ADM's.
RESULTS
In total, 25 from 663 eligible samples, including 1,389 patients qualified for the IPD. Depressed mood and anhedonia were consistently central residual symptoms post-CBT and post-ADM's. For CBT, fatigue-related and anxiety symptoms were also central post-treatment. A significant difference in network structure across treatments (CBT vs. ADM) was observed for samples measuring depression severity using the MADRS. Specifically, stronger symptom occurrences were present amongst post-CBT (vs. ADM's) and amongst post-ADM's (vs. CBT). No significant difference in global strength was observed across treatments.
CONCLUSIONS
Core major depression symptoms remain central across treatments, strategies to target these symptoms should be considered. Anxiety and fatigue related complaints also remain central post-CBT. Efforts must be made amongst researchers, institutions, and journals to permit sharing of IPD. A protocol was prospectively registered on PROSPERO (CRD42020141663; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=141663).
PubMed: 35178002
DOI: 10.3389/fpsyt.2022.746678 -
Acta Psychiatrica Scandinavica Jun 2018Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and venlafaxine, and at analysing a potential influence of the investigated drugs on the placebo response.
METHOD
We conducted a comprehensive systematic review and meta-analysis of placebo-controlled, double-blind RCTs, which examined the efficacy of duloxetine and venlafaxine in the acute treatment of major depressive disorder.
RESULTS
We included 71 studies (29 duloxetine trials and 43 venlafaxine trials; one study provided data for the duloxetine and the venlafaxine data set). The placebo effect sizes, defined as pre-postscore change divided by baseline standard deviation, differed significantly between venlafaxine and duloxetine studies (-2.51 vs. -2.09; test for subgroup differences P = 0.028; high heterogeneity). The analysis of effect modifiers and the metaregression analyses confirmed the drug, next to baseline depression severity and publication status, as the most influential independent predictor.
CONCLUSION
Our analyses show a significant difference in the placebo response between venlafaxine and duloxetine trials and suggest that the investigated drug has an influence on the placebo response that is not related to baseline severity, changes over the years or other variables we included.
Topics: Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Placebo Effect; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 29603140
DOI: 10.1111/acps.12881 -
Neuropsychopharmacology Reports Mar 2024To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.
METHODS
Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.
CONCLUSIONS
Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
Topics: Humans; Aged; Depressive Disorder, Major; Japan; Antidepressive Agents; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 38318955
DOI: 10.1002/npr2.12422 -
Psychopharmacology May 2016Current psychotropic medications have been shown to modulate immune activation. However, the effects of individual psychotropic agents on the immune system and how these... (Review)
Review
RATIONALE
Current psychotropic medications have been shown to modulate immune activation. However, the effects of individual psychotropic agents on the immune system and how these might contribute to their efficacy remain largely unclear.
OBJECTIVE
This paper aims to review previous literature on the effects of antidepressants and antipsychotics on the immune system, with a systematic review of in vitro findings, and discuss the relevance of these effects for the response to treatment and future drug development.
RESULTS
Inflammatory markers have been associated with fluctuations in clinical status and with treatment response both in depression and psychosis. The in vitro literature on antidepressants shows that some antidepressants, such as clomipramine and fluoxetine, more consistently decrease pro-inflammatory cytokines (interleukin (IL)-6, interferon (IFN)-γ, tumour necrosis factor (TNF)-α), whilst others (mirtazapine and venlafaxine) tend to increase their levels. However, any overall conclusion is challenged by several inconsistent findings, which appear partly dependent on different methodological approaches used. The in vitro studies on antipsychotics are even less clear-cut showing pro- and anti-inflammatory activity for the same antipsychotic agent (haloperidol, clozapine, risperidone) across different studies. We also noted inconsistencies between in vivo and in vitro literature, which could partly be attributed to the interaction in vivo with various biological systems or lifestyle factors that can modulate the immune system.
CONCLUSIONS
Inflammatory markers seem to hold potential for developing more individualised treatment strategies in the future. In this context, further research disentangling the differential immunomodulatory effects of different drugs could be used for tailoring treatment to specific individuals, according to their immune endophenotypes.
Topics: Animals; Anti-Inflammatory Agents; Humans; Immunologic Factors; Inflammation; Inflammation Mediators; Psychiatry; Psychotropic Drugs
PubMed: 26268146
DOI: 10.1007/s00213-015-4044-5 -
Breastfeeding Medicine : the Official... 2019The aim of this study was to determine the quality of lactation studies investigating antidepressants in breast milk according to the Food and Drug Administration (FDA)...
The aim of this study was to determine the quality of lactation studies investigating antidepressants in breast milk according to the Food and Drug Administration (FDA) draft guidelines and the article by Begg et al., 2002, published in the official journal of the International Lactation Consultant Association (ILCA). We used PubMed and LactMed for the literature search. Furthermore, cross references were searched for additional studies. A total number of 60 articles were included for review. For selective serotonin reuptake inhibitors and venlafaxine, only two studies correctly assessed the absolute infant dose and milk to plasma ratio; one sertraline and one fluoxetine study. Of all tricyclic antidepressants, one study for amitriptyline and one for nortriptyline assessed these endpoints correctly. We found a lack of information on breast milk sampling methods in many studies. Concentrations needed for the calculations were based on single measurements instead of at least five measurements during one dose interval, and the relative infant dose was not normalized by maternal weight, or an average maternal weight of 70 kg was used as a standard. We conclude that the quality of the current literature on this topic does not meet the standards of the FDA. Studies of higher quality are needed to determine the extent of drug transfer to breast milk for antidepressants, so an adequate recommendation about use of these drugs during lactation can be given.
Topics: Antidepressive Agents; Biomedical Research; Breast Feeding; Female; Humans; Lactation; Milk, Human; Research Design
PubMed: 31013435
DOI: 10.1089/bfm.2019.0021 -
Progress in Neuro-psychopharmacology &... Apr 2021Data regarding the ability of antidepressants to enter fetal, newborn and infant fluids have become gradually available, but mechanisms of antidepressant transfer remain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Data regarding the ability of antidepressants to enter fetal, newborn and infant fluids have become gradually available, but mechanisms of antidepressant transfer remain poorly understood. Here we calculated penetration ratios in an array of matrices from combined samples of pregnant/breastfeeding women taking antidepressants.
METHOD
We performed a systematic literature search of PubMed and EMBASE to identify studies with concentrations of antidepressants from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal plasma concentration. When data from multiple studies were available, we calculated combined penetration ratios, weighting the study mean by study size.
RESULTS
Eighty-five eligible studies were identified. For amniotic fluid, the highest penetration ratios were estimated for venlafaxine (mean 2.77, range 0.43-4.70 for the active moiety) and citalopram (mean 2.03, range 0.35-6.97), while the lowest ratios were for fluvoxamine (mean 0.10) and fluoxetine (mean 0.11, range 0.02-0.20 for the active moiety). For umbilical cord plasma, nortriptyline had the highest ratio (mean 2.97, range 0.25-26.43) followed by bupropion (mean 1.14, range 0.3-5.08). For breast milk, the highest ratios were observed for venlafaxine (mean 2.59, range 0.85-4.85), mianserin (mean 2.22, range 0.80-3.64) and escitalopram (mean 2.19, range 1.68-3.00).
CONCLUSION
We observed considerable variability across antidepressants regarding their ability to enter fetal, newborn and infant fluids. Measuring antidepressant concentrations in a maternal blood sample can provide a reliable estimate of fetal/infant exposure, although further evidence for concentration-dependent effects is required.
Topics: Amniotic Fluid; Antidepressive Agents; Breast Feeding; Female; Fetal Blood; Humans; Infant; Milk, Human; Pregnancy; Pregnancy Complications
PubMed: 33358964
DOI: 10.1016/j.pnpbp.2020.110228 -
Basic & Clinical Pharmacology &... Jan 2016Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective... (Review)
Review
Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective Serotonin reuptake inhibitors, SSRIs, a vast amount of data are available. For the newer antidepressant group of serotonin and noradrenaline reuptake inhibitors, SNRIs, significantly less data are available. Following the PRISMA guideline for systematic reviews, we performed a systematic search on the risk of major congenital malformations after first trimester in utero exposure to venlafaxine or duloxetine. We identified eight cohort studies reporting on the outcome upon in utero exposure to venlafaxine or duloxetine during the first trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107 major malformations, resulting in a relative risk estimate and 95% confidence interval of 1.12 (0.92-1.35). The corresponding data for duloxetine were 668 infants and 16 major malformations, resulting in a relative risk estimate and 95% confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to venlafaxine is not associated with an increased risk of major congenital malformations. The amount of data for duloxetine are significantly smaller but does not suggest a clinically important increased risk.
Topics: Abnormalities, Drug-Induced; Cohort Studies; Depressive Disorder, Major; Duloxetine Hydrochloride; Female; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 26435496
DOI: 10.1111/bcpt.12497