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The Lancet. Psychiatry Mar 2024There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression.
METHODS
In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926.
FINDINGS
Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes.
INTERPRETATION
According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies.
FUNDING
None.
Topics: Male; Female; Humans; Middle Aged; Depressive Disorder, Major; Fluoxetine; Perphenazine; Network Meta-Analysis; Bipolar Disorder; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Depression; Antipsychotic Agents; Olanzapine
PubMed: 38360024
DOI: 10.1016/S2215-0366(24)00006-3 -
Nutrition Reviews Jan 2024Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an...
CONTEXT
Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions.
OBJECTIVE
A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD.
DATA SOURCES
Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022.
DATA EXACTION
Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305).
RESULTS
Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants.
CONCLUSION
Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42020222305.
PubMed: 38219239
DOI: 10.1093/nutrit/nuad171 -
Current Medicinal Chemistry 2018Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a...
BACKGROUND
Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients.
OBJECTIVE
The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD.
METHOD
We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS).
RESULTS
We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies).
CONCLUSION
Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).
Topics: Antipsychotic Agents; Cognitive Behavioral Therapy; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 29278206
DOI: 10.2174/0929867325666171222163645 -
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 -
Journal of Clinical PsychopharmacologyThis systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis.
PURPOSE
This systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis.
METHODS
A systematic search was conducted in PubMed, Elsevier, Science Direct, Embase, Springer Link, Wiley Online Library, CNKI, and Wanfang databases from the date of database inception to January 2023. Previously reported cases of venlafaxine-associated rhabdomyolysis were identified, and relevant data from these cases were collected for descriptive statistical analysis. Cases that met the inclusion criteria were evaluated to determine the correlation between adverse reactions and venlafaxine.
RESULTS
A total of 12 patients with venlafaxine-associated rhabdomyolysis were included. None of these patients had a history of muscle pain or discomfort. Of the 12 patients, 5 patients received venlafaxine at doses of ≤225 mg/d, whereas the remaining 7 patients received doses exceeding 225 mg/d. The main clinical symptoms included myalgia, muscle weakness, and renal injury. All 12 patients discontinued venlafaxine and received symptomatic care.
CONCLUSIONS
Venlafaxine, used either as a monotherapy or in combination with other drugs, may be associated with rhabdomyolysis. Creatine kinase levels may normalize or significantly decrease after discontinuation of venlafaxine and symptomatic treatment.
Topics: Rhabdomyolysis; Venlafaxine Hydrochloride; Humans; Male; Adult; Female; Middle Aged; Creatine Kinase; Myalgia
PubMed: 38506608
DOI: 10.1097/JCP.0000000000001838 -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
The Journal of Maternal-fetal &... Dec 2023Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk for gestational diabetes mellitus (GDM) is inconsistent. We perform a systematic review and meta-analysis to assess the GDM risk associated with antidepressant exposure during pregnancy.
METHODS
We systematically searched the PubMed and EMBASE databases until December 2021. We sought observational studies assessing the association between gestational antidepressant use and GDM.
RESULTS
Five observational studies were included in the analysis. Mothers exposed to antidepressants during pregnancy were at a significantly increased risk for GDM (relative risk [RR] 1.20, 95% confidence interval [CI] 1.11-1.30; < .001). However, after considering confounding by indication, we observed no significant effect of antidepressant use during pregnancy on the risk of GDM (RR 1.13, 95% CI 1-1.28; = .054; = 0%). Independent of clinical indication, subgroup analysis based on individual antidepressants suggested that the risk was increased by venlafaxine or amitriptyline use, but not by selective serotonin reuptake inhibitors.
CONCLUSIONS
The significant association between antidepressant exposure during pregnancy and GDM may be overestimated due to confounding by indication. However, the evidence remains insufficient, particularly for specific drug classes.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Amitriptyline
PubMed: 36599445
DOI: 10.1080/14767058.2022.2162817 -
Pain Medicine (Malden, Mass.) Oct 2017To investigate the efficacy of venlafaxine for neuropathic pain and review literature to determine if the medication provides adequate neuropathic pain relief. (Review)
Review
OBJECTIVE
To investigate the efficacy of venlafaxine for neuropathic pain and review literature to determine if the medication provides adequate neuropathic pain relief.
METHODS
Literature was reviewed on MEDLINE using various key words. These key words include: "venlafaxine and pain," "venlafaxine ER and pain," "venlafaxine XR and pain," "venlafaxine and neuropathic pain," "venlafaxine and neuropathy," "SSRI and neuropathic pain," "SSRI and neuropathy," "SNRI and neuropathic pain," "SNRI and neuropathy," "serotonin reuptake inhibitor and neuropathic pain," "serotonin reuptake inhibitor and neuropathy," "serotonin norepinephrine reuptake inhibitor and neuropathic pain" and "serotonin norepinephrine reuptake inhibitor and neuropathy." Using this guideline, 13 articles were reviewed.
RESULTS
A total of 13 studies reviewed, which are organized by date and diagnosis. It is evident that in the majority of studies, when compared with a placebo, there was a clinical significant reduction in neuropathic pain relief when using venlafaxine. Additionally, one study showed even more significant pain relief when using higher doses of venlafaxine (at least 150 mg). However, when compared with alternative neuropathic medications, venlafaxine for the most part did not perform any better in terms of efficacy.
CONCLUSION
In conclusion, venlafaxine is a safe and well-tolerated analgesic drug for the symptomatic treatment of neuropathic pain, and there is limited evidence that high-dose venlafaxine (150 mg/day) can be even more beneficial. While the present evidence is quite encouraging regarding venlafaxine's use for neuropathic pain, further research is needed to continue to expand on these findings, particularly when in consideration with other possible pharmacological agents.
Topics: Analgesics; Antidepressive Agents, Second-Generation; Humans; Neuralgia; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 27837032
DOI: 10.1093/pm/pnw261 -
Journal of Clinical Pharmacy and... Feb 2015Fibromyalgia is a painful disease affecting 1-2% of the United States population. Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Fibromyalgia is a painful disease affecting 1-2% of the United States population. Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and milnacipran, are well studied and frequently used for treating this disorder. However, efficacy data are limited for the SNRI venlafaxine despite its use in nearly a quarter of patients with fibromyalgia. Accordingly, we systematically reviewed the efficacy of venlafaxine for treatment of fibromyalgia.
METHODS
PubMed, Web of Science and the Cochrane Database were searched using the terms 'venlafaxine' and 'fibromyalgia'. Results were classified as primary studies or review articles based on abstract review. References of review articles were evaluated to ensure no primary studies evaluating venlafaxine were overlooked. All clinical studies that investigated venlafaxine for the treatment of fibromyalgia were included and graded on strength of evidence.
RESULTS AND DISCUSSION
Five studies met the inclusion criteria, including 4 open-label cohort studies and 1 randomized, controlled trial. Study durations ranged from 6 weeks to 6 months, and study sizes ranged from 11 to 102 participants. Four of the five published studies reported improvement in at least one outcome. Generally consistent improvements were observed in pain-related outcome measures, including the Fibromyalgia Impact Questionnaire (range, 26-29% reduction; n = 2 studies), Visual Analog Scale (range, 36-45% reduction; n = 2 studies), McGill Pain Questionnaire (48% reduction; n = 1 study) and Clinical Global Impression scale (51% had significant score change; n = 1 study). However, the few studies identified were limited by small sample size, inconsistent use of outcomes and methodological concerns.
WHAT IS NEW AND CONCLUSION
Studies assessing the efficacy of venlafaxine in the treatment of fibromyalgia to date have been limited by small sample size, inconsistent venlafaxine dosing, lack of placebo control and lack of blinding. In the context of these limitations, venlafaxine appears to be at least modestly effective in treating fibromyalgia. Larger randomized controlled trials are needed to further elucidate the full benefit of venlafaxine.
Topics: Cyclohexanols; Fibromyalgia; Humans; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 25294655
DOI: 10.1111/jcpt.12216 -
BMJ (Clinical Research Ed.) Jan 2016To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis.
MAIN OUTCOME MEASURES
Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.
DATA SOURCES
Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.
DATA EXTRACTION AND ANALYSIS
Two researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model).
RESULTS
We included 70 trials (64,381 pages of clinical study reports) with 18,526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly's website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.
CONCLUSIONS
Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.
Topics: Antidepressive Agents; Depressive Disorder; Double-Blind Method; Humans; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors; Suicidal Ideation; Suicide; Suicide Prevention
PubMed: 26819231
DOI: 10.1136/bmj.i65