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British Journal of Clinical Pharmacology Dec 2018Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI)...
AIM
Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI.
METHOD
Pubmed, Web of Science, Cochrane Library and Embase were searched for studies reporting on the effect of the DDI among adults published until April 2018. Data on pharmacokinetics, pharmacodynamics and clinical outcomes from experimental, observational and case report studies were retrieved. The protocol of this study was registered in PROSPERO (CRD42018093087).
RESULTS
We found nine eligible articles that consisted of four experimental and two observational studies as well as three case reports. Experimental studies reported that paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients. Case reports concerned bradycardia and atrioventricular block due to the DDI. Results from observational studies were conflicting. A cohort study indicated that the DDI was significantly associated with the incidence of early discontinuation of metoprolol as an indicator of the emergence of metoprolol-related side effects. In a case-control study, the DDI was not significantly associated with bradycardia.
CONCLUSION
Despite the contradictory conclusions from the current literature, the majority of studies suggest that the DDI can lead to adverse clinical consequences. Since alternative antidepressants and beta-blockers with comparable efficacy are available, such DDIs can be avoided. Nonetheless, if prescribing the combination is unavoidable, a dose adjustment or close monitoring of the metoprolol-related side effects is necessary.
Topics: Cytochrome P-450 CYP2D6; Drug Interactions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Metoprolol; Middle Aged; Paroxetine
PubMed: 30248178
DOI: 10.1111/bcp.13741 -
The Cochrane Database of Systematic... Dec 2018Studies report that up to 80% of individuals with chronic obstructive pulmonary disease (COPD) may struggle with symptoms of depression. However, this major comorbidity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies report that up to 80% of individuals with chronic obstructive pulmonary disease (COPD) may struggle with symptoms of depression. However, this major comorbidity in COPD is rarely managed effectively. A number of recent studies indicate that left untreated, COPD-related depression is associated with worse quality of life, worse compliance with COPD treatment plan, increased exacerbations, hospital admissions, and healthcare costs when compared to individuals with COPD without depression. Regrettably, COPD practice guidelines do not provide conclusive treatment recommendations for the use of antidepressants in patients with COPD, and base their guidelines on findings from trials in the general population. This may be problematic, as there is an elevated risk of respiratory issues associated with antidepressant treatment and COPD. Evaluating effectiveness and safety of pharmacological interventions specifically for patients with COPD and depression was therefore paramount.
OBJECTIVES
To assess the effectiveness and safety of pharmacological interventions for the treatment of depression in patients with COPD.
SEARCH METHODS
The last search was performed on 26 November 2018. We initially searched the following databases via the Specialised Trials Registers of the Cochrane Airways and Common Mental Disorders Groups (to June 2016): MEDLINE, Embase, PsycINFO, CINAHL, AMED, and the Cochrane Library trials register (CENTRAL). Searches from June 2016 to November 2018 were performed directly on Ovid MEDLINE, Embase, PsycINFO and the Cochrane Library (Issue 11, 2018). We searched ClinicalTrials.gov, the ISRCTN registry, and the World Health Organization International Clinical Trials Registry Platform to 26 November 2018. We searched the grey literature databases to identify studies not indexed in major databases and the reference lists of studies initially identified for full-text screening.
SELECTION CRITERIA
All published and unpublished randomised controlled trials (RCTs) comparing the efficacy of pharmacological interventions with no intervention, placebo or co-intervention in adults with diagnosed COPD and depression were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed articles identified by the search for eligibility. Our primary outcomes were change in depressive symptoms and adverse events. The secondary outcomes were: change in quality of life, change in dyspnoea, change in forced expiratory volume in one second (FEV), change in exercise tolerance, change in hospital utilisation (length of stay and readmission rates), and cost-effectiveness. For continuous outcomes, we calculated the pooled mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI) as appropriate. For dichotomous outcomes, we calculated the pooled odds ratio (OR) and corresponding 95% CI using a random-effects model. We assessed the quality of evidence using the GRADE framework.
MAIN RESULTS
Of the 1125 records screened for eligibility, four RCTs (N = 201 participants), and one on-going study, met the inclusion criteria. Two classes of antidepressants were investigated in two separate comparisons with placebo: a tricyclic antidepressant (TCA) and selective serotonin reuptake inhibitors (SSRIs).TCA versus placeboOnly one RCT (N = 30 participants) provided results for this comparison.Primary outcomesThe TCA (nortriptyline) reduced depressive symptoms post-treatment compared to placebo (MD -10.20, 95% CI -16.75 to -3.65; P = 0.007; very low-quality evidence), as measured by the Hamilton Depression Rating Scale (HAM-D). Three participants withdrew from the trial due to adverse events related to the tested antidepressant (dry mouth, sedation, orthostatic hypotension).Secondary outcomesThe overall results post-treatment indicated that nortriptyline was not effective in improving the quality of life of individuals with COPD, as measured by the Sickness Impact Profile (MD -2.80, 95% CI -11.02 to 5.42; P = 0.50; very low-quality evidence).The results for the change in dyspnoea for the domains examined (e.g. dyspnoea scores for 'most day-to-day activities') post-treatment showed no improvement in the intervention group (MD 9.80, 95% CI -6.20 to 25.80; P = 0.23; very low-quality evidence).No data were reported for change in FEV, change in exercise tolerance, change in hospital utilisation, or cost-effectiveness. The TCA study provided short-term results, with the last follow-up data collection at 12 weeks.The quality of the evidence for all the outcomes evaluated was very low due to a small sample size, imprecision, attrition, and selection and reporting bias.SSRIs versus placeboThree RCTs (N = 171 participants) provided results for this comparison.Primary outcomesThe pooled results for two studies showed no difference for the change in depressive symptoms post-intervention (SMD 0.75, 95% CI -1.14 to 2.64; 148 participants; 2 studies; P = 0.44; very low-quality evidence). High heterogeneity was observed (I² = 95%), limiting the reliability of these findings.While it was not possible to meta-analyse the total adverse events rates across the studies, it was possible to combine the results for two medication-specific adverse effects: nausea and dizziness. There were no significant post-treatment group differences for nausea (OR 2.32, 95% CI 0.66 to 8.12; 171 participants; 3 studies; P = 0.19; very low-quality evidence) or dizziness (OR 0.61, 95% CI 0.09 to 4.06; 143 participants; 2 studies; P = 0.61; very low-quality evidence).Secondary outcomesThe pooled analysis of two trials reporting data for the change in quality of life did not show improvement post-treatment in the intervention group compared to placebo (SMD 1.17, 95% CI -0.80 to 3.15; 148 participants; 2 studies; P = 0.25; very low-quality evidence).There was no difference between groups in change in FEV post-treatment (MD 0.01, 95% CI -0.03 to 0.05; 148 participants; 2 studies; P = 0.60; low-quality evidence). However, two trials reported improvement in exercise tolerance in the SSRI group versus the placebo group (MD 13.88, 95% CI 11.73 to 16.03; 148 participants; 2 studies; P < 0.001; very low-quality evidence).The trials included in this comparison did not report data related to the change in dyspnoea, hospital utilisation rates, or cost-effectiveness.
AUTHORS' CONCLUSIONS
There is insufficient evidence to make definitive statements about the efficacy or safety of antidepressants for treating COPD-related depression. New RCTs are needed; with better methodological quality and more accurate reporting of the methods used. Moreover, longer-term follow-up data collection is needed, including outcomes such as adverse events, hospital utilisation and cost-effectiveness.
Topics: Antidepressive Agents, Tricyclic; Depression; Dizziness; Dyspnea; Exercise Tolerance; Forced Expiratory Volume; Humans; Nausea; Nortriptyline; Paroxetine; Placebos; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 30566235
DOI: 10.1002/14651858.CD012346.pub2 -
Current Neuropharmacology 2020The aims of this study were to systematically review the efficacy, acceptability, and tolerability of repetitive transcranial magnetic stimulation (rTMS) combined with...
OBJECTIVES
The aims of this study were to systematically review the efficacy, acceptability, and tolerability of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants in the treatment of the first major depressive disorder (MDD) episode.
MATERIALS AND METHODS
The primary efficacious outcome was the pooled mean-endpoint scores of the Hamilton Depression Rating Scale (HAMD). Rates of response, remission rate, overall discontinuation and discontinuation due to adverse events were also evaluated. Search in the Scopus, PubMed, CINAHL, and Cochrane Controlled Trials Register databases for interesting outcomes was carried out in March 2018.
RESULTS
A total of 108 randomized patients of two randomized controlled trials were included in this study. The pooled mean- endpoint scores of the HAMD in one, two, and four weeks for rTMS plus antidepressants (citalopram or paroxetine) were greater than that of sham plus the antidepressants. The pooled rates of overall discontinuation and discontinuation rates due to adverse events were not different between the two groups.
CONCLUSION
According to a piece of limited evidence, the high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) could accelerate the antidepressant effect of SSRIs in young patients with a first-episode major depressive disorder. However, the acceptability and tolerability of HF-rTMS in the treatment of such patients are no better than an antidepressant alone. However, further well-defined and large sample-size studies of HF-rTMS combined with an antidepressant in MDD should be carried out to warrant these results.
Topics: Adult; Antidepressive Agents; Bias; Clinical Trials as Topic; Combined Modality Therapy; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 32091338
DOI: 10.2174/1570159X18666200221113134 -
PloS One 2020RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its...
Exploring the utility of RDoC in differentiating effectiveness amongst antidepressants: A systematic review using proposed psychometrics as the unit of analysis for the Negative Valence Systems domain.
BACKGROUND
RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its clinical utility remains controversial.
AIM
To explore RDoC's potential clinical utility by examining antidepressant effectiveness through Negative Valence Systems (NVS) domain constructs.
METHOD
A systematic review was conducted on Web of Science, MEDLINE, EMBASE and PsycINFO for antidepressant trials that included psychometric instruments assessed by Watson, Stanton & Clark (2017) to represent NVS constructs of Acute Threat, Potential Threat and Loss.
RESULTS
221 citations were identified; 13 were included in qualitative synthesis, none for quantitative analysis. All suffered from significant bias risks. 9 antidepressants were investigated, most within 1 construct, and most were found to be effective. Paroxetine, citalopram and fluvoxamine were found to be effective for Acute Threat, fluoxetine, desvenlafaxine and sertraline for Potential Threat, and sertraline, fluvoxamine, fluoxetine and desvenlafaxine effective for Loss. Nefazodone was found to be ineffective for acute fear.
CONCLUSION
Preliminary evidence supports RDoC NVS constructs' clinical utility in assessing antidepressant effectiveness, but lack of discriminant validity between Potential Threat and Loss supports their recombination into a single Distress construct. Finding of effectiveness within "normal" construct levels support the utility of a dimensional approach. Testable hypotheses were generated that can further test RDoC's clinical utility.
Topics: Algorithms; Antidepressive Agents; Citalopram; Clinical Trials as Topic; Depressive Disorder; Desvenlafaxine Succinate; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Psychometrics; Sertraline; Treatment Outcome
PubMed: 33326436
DOI: 10.1371/journal.pone.0243057 -
Medicine Feb 2020To compare the therapeutic effect of 6 SSRIs among the Chinese senile depression patients. And drug-induced nausea leads to low compliance in elderly depression patients... (Meta-Analysis)
Meta-Analysis
Comparative risk of Selective Serotonin Reuptake Inhibitors (SSRIs)-induced nausea among Chinese senile depression patients: A network meta-analysis of randomized-controlled trials.
OBJECTIVES
To compare the therapeutic effect of 6 SSRIs among the Chinese senile depression patients. And drug-induced nausea leads to low compliance in elderly depression patients in China, it is urgent to assess the safety of 6 SSRIs with respect to induced-nausea among the Chinese senile depression patients.
METHOD
In the present study, a network of meta-analysis was conducted to assess the efficacy of 6 SSRIs among the Chinese senile depression patients, in addition, the safety of 6 SSRIs with respect to induced-nausea among the Chinese senile depression patients was also evaluated. PubMed, Embase databases, WanFang, CNKI, ChongqingWeiPu were searched for the related articles. The primary outcome of this study were the number of effective cases of SSRIs and the number of cases of nausea caused by SSRIs in Chinese elderly depressed patients. Odds ratios (ORs) and corresponding 95% confidence intervals(95%CIs) were calculated within pairwise and network meta-analysis.
RESULTS
Twenty eight trials were identified, including 2246 patients, the network meta-analysis indicated that Escitalopram was associated with a lower risk of nausea compared Paroxetine (odds ratios 0.49, 95%CI = 0.34-0.69) when they were used in Chinese elderly depressed patients. Escitalopram also exhibited distinct advantages compared other SSRIs.In terms of drug efficacy, Escitalopram was significantly superior to Paroxetine (OR = 2.26, 95%CI = 1.55-3.37).
CONCLUSION
The rank of SSRIs with respect to induced-nausea was: Combination of EP > Fluoxetine > Paroxetine > Citalopram > Sertraline > Fluvoxamine > Escitalopram, respectively.
Topics: Aged; Aged, 80 and over; China; Depression; Depressive Disorder; Female; Humans; Male; Medication Adherence; Middle Aged; Nausea; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 32049832
DOI: 10.1097/MD.0000000000019133