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Medicine May 2021Psychotropic drugs are frequently used for functional dyspepsia (FD); however, the efficacy of these drugs for treating FD remains controversial. We aimed to... (Comparative Study)
Comparative Study Meta-Analysis
Psychotropic drugs are frequently used for functional dyspepsia (FD); however, the efficacy of these drugs for treating FD remains controversial. We aimed to comprehensively compare the relative efficacies of different psychotropic drugs for FD in adults.To conduct this study, we searched the PubMed, Embase, and Cochrane Library databases on March 10, 2019, and conducted a frequentist network meta-analysis on the search results. The primary outcome was treatment efficacy estimated by the proportion of patients who achieved a certain percentage decrease in symptoms or who dropped below the threshold of the global FD symptom scores. The secondary outcome was acceptability, defined as all-cause discontinuation. Odds ratios (ORs) were reported with 95% confidence intervals (CIs).We deemed 10 trials to be eligible for analysis, and these trials included 970 participants and 10 psychotropic drugs. Flupentixol + melitracen (F + M) (OR, 10.00; 95% CI, 1.59 to 62.73), tandospirone (3.24, 1.38 to 7.60), imipramine (2.21, 1.02 to 4.79), and amitriptyline (1.71, 1.06 to 3.09) were significantly superior to placebo. According to the surface under the cumulative ranking curve, the most effective treatment was F + M (89.0%), whereas the least effective was R137696 (13.6%). In terms of acceptability, escitalopram (0.32, 0.11 to 0.92) was ranked as the worst drug (12.6%), followed by imipramine and sertraline.The present network meta-analysis suggests that F + M, tandospirone, imipramine, and amitriptyline are more effective than placebo as treatment for FD. Our results indicate that among the ten psychotropic drugs included, F + M is likely to be the most effective drug for alleviating dyspepsia symptoms.
Topics: Dyspepsia; Humans; Psychotropic Drugs
PubMed: 34011118
DOI: 10.1097/MD.0000000000026046 -
Photodermatology, Photoimmunology &... Mar 2022Tricyclic antidepressants (TCAs) are still widely used and are available to purchase without prescription in some countries. Awareness of adverse cutaneous drug...
BACKGROUND/PURPOSE
Tricyclic antidepressants (TCAs) are still widely used and are available to purchase without prescription in some countries. Awareness of adverse cutaneous drug reactions is essential.
METHOD
We reported a case of photo-distributed hyperpigmentation due to imipramine and carried out a systematic search of the related articles using the search terms "tricyclic antidepressants" or "tricyclic antidepressive agents", and "hyperpigmentation" or "photosensitivity disorder". Fifty non-duplicate citations were identified of which 28 articles which were independently assessed in full. The review was registered in PROSPERO, CRD42018107338.
RESULTS
The remaining 25 articles met our inclusion criteria. Photo-distributed hyperpigmentation tricyclic antidepressant-induced photosensitivity reactions (TIPs) was the most common presentation. In 21 cases, this presented as an asymptomatic discolouration of exposed sites. Imipramine (81%), amitriptyline (9.5%), desipramine hydrochloride (4.8%) and mirtazapine (4.8%) were reported to be the culprit drugs. Nineteen were female with a mean age at presentation of 55 years. Mean duration from commencing the culprit drug until the development of discolouration was 10.4 years. Mean daily dose was 222.7 mg for imipramine. Histology was characteristic with golden-brown or brownish granules deposited in dermis. Staining for Masson-Fontana and MEL-5 was positive in all cases. Phototesting had not been done in cases prior to ours (negative 3 months after discontinuation of imipramine). Three further reports of suspected TIP presented with non-specific and eczematous eruption. The two presentations were reported along with systemic problems (thrombocytopenia and hepatic injury).
CONCLUSIONS
This systematic review highlights the characteristic features of exposed site hyperpigmentation of TCA-induced photosensitivity occurring after prolonged drug exposure in many cases.
Topics: Antidepressive Agents, Tricyclic; Female; Humans; Hyperpigmentation; Imipramine; Photosensitivity Disorders; Skin
PubMed: 34358364
DOI: 10.1111/phpp.12724 -
Asian Spine Journal Dec 2019Antidepressant drugs can be advantageous in treating psychiatric and non-psychiatric illnesses, including spinal disorders. However, spine surgeons remain unfamiliar...
Antidepressant drugs can be advantageous in treating psychiatric and non-psychiatric illnesses, including spinal disorders. However, spine surgeons remain unfamiliar with the advantages and disadvantages of the use of antidepressant drugs as a part of the medical management of diseases of the spine. Our review article describes a systematic method using the PubMed/Medline database with a specific set of keywords to identify such benefits and drawbacks based on 17 original relevant articles published between January 2000 and February 2018; this provides the community of spine surgeons with available cumulative evidence contained within two tables illustrating both observational (10 studies; three cross-sectional, three case-control, and four cohort studies) and interventional (seven randomized clinical trials) studies. While tricyclic antidepressants (e.g., amitriptyline) and duloxetine can be effective in the treatment of neuropathic pain caused by root compression, venlafaxine may be more appropriate for patients with spinal cord injury presenting with depression and/or nociceptive pain. Despite the potential associated consequences of a prolonged hospital stay, higher cost, and controversial reports regarding the lowering of bone mineral density in the elderly, antidepressants may improve patient satisfaction and quality of life following surgery, and reduce postoperative pain and risk of delirium. The preoperative treatment of preexisting psychiatric diseases, such as anxiety and depression, can improve outcomes for patients with spinal cord injury-related disabilities; however, a preoperative platelet function assay is advocated prior to major spine surgical procedures to protect against significant intraoperative blood loss, as serotonergic antidepressants (e.g., selective serotonin reuptake inhibitors) and bupropion can increase the likelihood of bleeding intraoperatively due to drug-induced platelet dysfunction. This comprehensive review of this evolving topic can assist spine surgeons in better understanding the benefits and risks of antidepressant drugs to optimize outcomes and avoid potential hazards in a spine surgical setting.
PubMed: 31422644
DOI: 10.31616/asj.2018.0237 -
Journal of Affective Disorders Apr 2020The efficacy ranking of antidepressants for post-stroke depression (PSD) has not been assessed thoroughly yet due to the lack of network meta-analyses with sufficiently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy ranking of antidepressants for post-stroke depression (PSD) has not been assessed thoroughly yet due to the lack of network meta-analyses with sufficiently large sample size.
METHODS
Seven databases including PubMed, Embase, CENTRAL, CBM, CNKI, WanFang and VIP were systematically searched for eligible randomized controlled trials (RCTs) regarding nine antidepressants (citalopram, escitalopram, venlafaxine, paroxetine, duloxetine, amitriptyline, doxepin, sertraline and mirtazapine) treating PSD patients. Stata 15 software and R software were utilized for statistical analyses.
RESULTS
51 RCTs were included in this NMA. For the key efficacy outcomes, escitalopram, mirtazapine, sertraline, citalopram, venlafaxine and paroxetine were associated with larger reduction of the Hamilton Depression Scale (HAMD) total score compared with placebo at 2 weeks. Among the nine antidepressants, escitalopram ranked the best while amitriptyline was the least helpful. At 4 weeks, citalopram ranked higher than placebo and the other eight antidepressants. In contrast, amitriptyline and doxepin were associated with minimal reduction of HAMD score. At 8 weeks, changes in HAMD score were significantly greater in nine antidepressants groups compared to placebo group. Besides, mirtazapine ranked higher than citalopram and escitalopram. At endpoint, mirtazapine was related to the highest response rate, followed by venlafaxine and escitalopram, respectively.
LIMITATIONS
No restriction was imposed on doses of every antidepressant.
CONCLUSIONS
Escitalopram was associated with a quicker relief of depression, but mirtazapine was probably the best option when it comes to the efficacy of 8-week treatment duration. Amitriptyline and doxepin were nearly the worst choice regardless of the duration (2, 4 or 8 weeks).
Topics: Antidepressive Agents; China; Citalopram; Depression; Depressive Disorder, Major; Humans; Network Meta-Analysis; Selective Serotonin Reuptake Inhibitors; Stroke; Treatment Outcome
PubMed: 32056924
DOI: 10.1016/j.jad.2020.02.005 -
Frontiers in Neurology 2022To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network...
Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.
OBJECTIVE
To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis.
METHODS
A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs).
RESULTS
A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from -0.63 to -0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11.
CONCLUSION
BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy.
SYSTEMATIC REVIEW REGISTRATION
[https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].
PubMed: 35386408
DOI: 10.3389/fneur.2022.818522 -
Therapeutic Drug Monitoring Apr 2024Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
BACKGROUND
Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
METHODS
We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine. Four electronic databases were systematically searched.
RESULTS
We included 32 articles published 1996-2022. A strong relationship between serotonin transporter (SERT) occupancy and drug concentration is well established for selective serotonin reuptake inhibitors. Lower limits of recommended therapeutic reference ranges largely corroborate with the findings from positron emission tomography studies (80% SERT occupancy). Only a few novel studies have investigated alternative targets, that is, norepinephrine transporters (NETs), dopamine transporters (DATs), or monoamine oxidase A (MAO-A). For certain classes of drugs, positron emission tomography study data are inconclusive. Low DAT occupancy after bupropion treatment speculates its discussed mechanism of action. For MAO inhibitors, a correlation between drug concentration and MAO-A occupancy could not be established.
CONCLUSIONS
Neuroimaging studies are critical in TDM-guided therapy for certain antidepressants, whereas for bupropion and MAO inhibitors, the available evidence offers no further insight. Evidence for selective serotonin reuptake inhibitors is strong and justifies a titration toward suggested ranges. For SNRIs, duloxetine, and venlafaxine, NETs are sufficiently occupied, well above the SERT efficacy threshold. For these drugs, a titration toward higher concentrations (within the recommended range) should be considered in case of no response at lower concentrations.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Bupropion; Duloxetine Hydrochloride; Monoamine Oxidase Inhibitors; Antidepressive Agents; Positron-Emission Tomography; Monoamine Oxidase
PubMed: 38287888
DOI: 10.1097/FTD.0000000000001142 -
JAMA Neurology May 2021Mild traumatic brain injury (TBI) is experienced by 55.9 million people globally each year. The symptoms of mild TBI are diverse and sometimes long-lasting, requiring...
IMPORTANCE
Mild traumatic brain injury (TBI) is experienced by 55.9 million people globally each year. The symptoms of mild TBI are diverse and sometimes long-lasting, requiring frequent use of pharmacological interventions to mitigate them. A thorough understanding of the data supporting pharmacological interventions is important for decision-making among clinicians treating this common injury.
OBJECTIVE
To systematically review studies of pharmacological interventions and their associations with symptom burden reduction among patients with mild TBI and to use an evidence-based model to identify potential directions for future research that may aid in clinical decision-making.
EVIDENCE REVIEW
A systematic review was performed in PubMed, Scopus, and Web of Science. Search strings modified for the advanced search interfaces of each search engine were developed in consultation with a librarian and included combinations of search terms, such as brain concussion, post-concussion syndrome, mild traumatic brain injury, and pharmacological treatment. Articles published between January 1, 2000, and July 1, 2020, were analyzed. Studies were included if (1) they were clinical studies with discrete analyses of participants with mild TBI or complicated mild TBI, (2) they were assessments of a pharmacological intervention, (3) they included human participants, and (4) they were published in a peer-reviewed journal in the English language. Studies were excluded if the severity of TBI among participants could not be ascertained (ie, inadequate definition of mild TBI) and the inclusion criteria for the study required intracranial hemorrhage. A total of 23 studies examining 20 pharmacological interventions met the inclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias for Randomized Trials (for randomized clinical trials) and the Cochrane Risk of Bias in Non-Randomized Studies of Interventions (for all other studies). Data were analyzed from June to September 2020.
FINDINGS
A total of 1495 articles were identified; of those, 131 articles were excluded as duplicates. Titles and abstracts were screened for inclusion and exclusion criteria among the remaining 1364 articles, and 134 of those articles received a full-text review. After exclusions, 23 studies (11 randomized clinical trials, 7 prospective observational studies, 3 retrospective observational studies, and 2 case studies) examining 20 pharmacological interventions were identified for inclusion in the systematic review. Studies included 22 distinct participant populations comprising 8277 participants with mild TBI and 45 participants without TBI. Among 23 total studies, 8 studies specifically addressed the pediatric population, 9 studies had a low risk of bias, and 16 studies reported symptom burden reduction. Of the 20 pharmacological interventions examined in the studies, methylphenidate, sertraline hydrochloride, ondansetron, amitriptyline, and melatonin were the only medications included in multiple studies.
CONCLUSIONS AND RELEVANCE
This systematic review found a limited number of high-quality, clinically meaningful studies, particularly among children and individuals in the acute stage of injury; therefore, performing an evidence-based analysis that would inform clinical decision-making was not possible. Future studies are needed to focus on standardizing measures and increasing sample sizes (including large multicenter clinical trials) to generate a body of research that may provide additional options for the treatment of patients with mild TBI.
Topics: Brain Concussion; Brain Injuries, Traumatic; Child; Clinical Decision-Making; Humans; Post-Concussion Syndrome; Prospective Studies; Retrospective Studies
PubMed: 33464290
DOI: 10.1001/jamaneurol.2020.5079 -
CNS Spectrums Feb 2021More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal...
Comparative efficacy of pharmacological treatments on measures of self-rated functional outcomes using the Sheehan Disability Scale in patients with major depressive disorder: a systematic review and network meta-analysis.
OBJECTIVE
More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials.
METHODS
PubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities.
RESULTS
We included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low.
CONCLUSIONS
Our results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.
PubMed: 33583460
DOI: 10.1017/S1092852921000171 -
Chinese Medical Journal Jun 2024The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships...
BACKGROUND
The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD).
METHODS
We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships.
RESULTS
The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages.
CONCLUSIONS
Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit.
PubMed: 38902199
DOI: 10.1097/CM9.0000000000003138 -
Journal of Clinical Psychopharmacology 2019This review examined the current literature about the potential relationship between the use of antidepressants during pregnancy and neonatal seizures.
PURPOSE
This review examined the current literature about the potential relationship between the use of antidepressants during pregnancy and neonatal seizures.
METHODS
PubMed was searched for English language reports published between January 1, 1996, and October 31, 2018, by using combinations of the following key words: pregnancy, neonatal outcome, neonatal convulsion, neonatal seizure, SSRI, selective serotonin norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), antidepressants, sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, duloxetine, bupropion, amitriptyline, imipramine, and clomipramine.
FINDINGS
A total of 9 relevant studies that met the review criteria were examined. The prevalence rates of neonatal seizures in the antidepressant groups and control groups were 0.30% to 0.91% and 0.10% to 0.30%, respectively. The use of selective serotonin reuptake inhibitors was associated with up to 5-fold increase in the risk of neonatal seizures. Compared with the controls, higher risks were reported in newborns of pregnant women using any antidepressant or tricyclic antidepressants albeit in a limited number of studies. Exposure to antidepressants in the third trimester of pregnancy appeared to be associated more with neonatal seizures compared with earlier exposure.
IMPLICATONS
Although an increased risk of neonatal seizures in newborns antenatally exposed to antidepressants especially selective serotonin reuptake inhibitors may be suggested, the available studies have severe methodological limitations to enable any firm conclusion.
Topics: Antidepressive Agents; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Prevalence; Seizures
PubMed: 31425466
DOI: 10.1097/JCP.0000000000001093