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Annals of General Psychiatry 2017Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment... (Review)
Review
BACKGROUND
Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment outcomes. The aim of this study was to systematically review the evidence of the impact of smoking on new-generation antidepressants with an emphasis on the pharmacokinetic perspective.
METHODS
We present a systematic review of clinical trials comparing the serum levels of new-generation antidepressants in smokers and nonsmokers. Data were obtained from MEDLINE/PubMed, Embase, and other sources. Risk of bias was assessed for selection, performance, detection, attrition, and reporting of individual studies.
RESULTS
Twenty-one studies met inclusion criteria; seven involved fluvoxamine, two evaluated fluoxetine, sertraline, venlafaxine, duloxetine or mirtazapine, and escitalopram, citalopram, trazodone and bupropion were the subject of a single study. No trials were found involving other common antidepressants such as paroxetine or agomelatine. Serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone were significantly higher in nonsmokers compared with smokers.
CONCLUSIONS
There is evidence showing a reduction in the concentration of serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone in smoking patients as compared to nonsmokers. The evidence regarding other commonly used antidepressants is scarce. Nonetheless, smoking status should be considered when choosing an antidepressant treatment, given the risk of pharmacokinetic interactions.
PubMed: 28286537
DOI: 10.1186/s12991-017-0140-8 -
Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
METHODS
Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
RESULTS
High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
CONCLUSION
VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
Acta Neuropsychiatrica Aug 2020The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of these agents, the ranking of interventions, and the grading of results by quality of evidence.
METHODS
The Common Mental Disorder Controlled Trial Register and two trial registries were searched for randomised controlled trials (RCTs) comparing any pharmacological intervention or placebo in the treatment of SAD. We performed a standard pairwise meta-analysis using a random effects model and carried out a network meta-analysis (NMA) using the statistical package, R. Quality of evidence was also assessed.
RESULTS
We included 67 RCTs in the review and 21 to 45 interventions in the NMA. Paroxetine was most effective in the reduction of symptom severity as compared to placebo. Superior response to treatment was also observed for paroxetine, brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline. Higher dropout rates were found for fluvoxamine. Brofaromine, escitalopram, fluvoxamine, paroxetine, pregabalin, sertraline, and venlafaxine performed worse in comparison to placebo for the outcome of dropouts due to adverse events. Olanzapine yielded a relatively high rank for treatment efficacy and buspirone the worse rank for dropouts due to any cause.
CONCLUSION
The differences between drugs and placebo were small, apart from a significant reduction in symptom severity and response for paroxetine. We suggest paroxetine as a first-line treatment of SAD, with the consideration of future research on the drug olanzapine as well as brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline because we observed a response to treatment.
Topics: Adult; Anti-Anxiety Agents; Humans; Network Meta-Analysis; Phobia, Social; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32039743
DOI: 10.1017/neu.2020.6 -
Frontiers in Pharmacology 2022Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial....
Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial. There are also few comparisons of the efficacy among drugs used to treat CIPN. Therefore, this systematic review aimed to study the efficacy of drugs in treating CIPN using existing randomized controlled trials. Electronic databases were searched for randomized controlled trials (RCTs) involving any pharmaceutical intervention and/or combination therapy of treating CIPN. Seventeen RCTs investigating 16 drug categories, duloxetine, pregabalin, crocin, tetrodotoxin, venlafaxine, monosialotetrahexosyl ganglioside (GM1), lamotrigine, KA (ketamine and amitriptyline) cream, nortriptyline, amitriptyline, topical (bitter apple) oil, BAK (baclofen, amitriptyline hydrochloride, and ketamine) pluronic lecithin organogel, gabapentin, and acetyl l-carnitine (ALC), in the treatment of CIPN were retrieved. Many of the included RCTs consisted of small sample sizes and short follow-up periods. It was difficult to quantify due to the highly variable nature of outcome indicators. Duloxetine, venlafaxine, pregabalin, crocin, tetrodotoxin, and monosialotetrahexosyl ganglioside exhibited some beneficial effects in treating CIPN. Duloxetine, GM1, and crocin showed moderate benefits based on the evidence review, while lamotrigine, KA cream, nortriptyline, amitriptyline, and topical (bitter apple) oil were not beneficial. Further studies were necessary to confirm the efficacy of gabapentin in the treatment of CIPN because of the controversy of efficacy of gabapentin. Furthermore, BAK topicalcompound analgesic gel only had a tendency to improve the CIPN symptoms, but the difference was not statistically significant. ALC might result in worsening CIPN. Most studies were not of good quality because of small sample sizes. Therefore, standardized randomized controlled trials with large samples were needed to critically assess the effectiveness of these drugs in treating CIPN in the future.
PubMed: 36618919
DOI: 10.3389/fphar.2022.1080888 -
Pharmacological Reports : PR Apr 2016The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order... (Review)
Review
The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order for any generic drug to receive an approval of regulatory authorities, its bioequivalence with the corresponding reference product must be demonstrated. Moreover, generic drugs must meet the same quality standards as reference drugs. However, many psychiatrists express concerns about use of generic drugs. We carried out a systematic analysis of the relevant literature indexed in PubMed and Cochrane databases. The MeSH term "generic" was combined with terms describing antipsychotic and antidepressive drugs, including their pharmaceutical names and relevant mental disorders. All 26 articles including either clinical studies or case reports have been qualified for a detailed analysis. No cases describing switches between two generics were found. Therapeutic equivalence studies evaluating antipsychotics included clozapine, olanzapine, and risperidone. The clinical status was judged to have worsened in 15.7% patients treated with clozapine. The number of relapses before and after the switch was not significantly different in patients treated with olanzapine. Two case reports showed clinical state deterioration after switch to generic risperidone. The clinical outcome after conversion to a generic antidepressant was evaluated only in one retrospective study. That study analyzed the outcomes of treatment with citalopram and revealed mental state deterioration in 11.6% of patients. Only single reports describe cases of impaired efficacy or adverse events after the switch to a generic antidepressant, including fluoxetine, mirtazapine, and venlafaxine. No cases of suicidal attempt after the switch were reported. Although the overall number of described cases is rather modest, health professionals should be aware of possible changes in the therapeutic effectiveness after changing to a generic medicine.
Topics: Antidepressive Agents; Antipsychotic Agents; Clinical Studies as Topic; Drugs, Generic; Humans; Retrospective Studies; Therapeutic Equivalency
PubMed: 26922520
DOI: 10.1016/j.pharep.2015.08.017 -
Human Psychopharmacology Jan 2015The postnatal period represents a critical phase for mothers because of physiological hormonal changes, the increase of emotional reactions and a greater susceptibility... (Review)
Review
OBJECTIVE
The postnatal period represents a critical phase for mothers because of physiological hormonal changes, the increase of emotional reactions and a greater susceptibility for the onset/recrudescence of psychiatric disorders. Despite the evidence of an increasing utilization of antidepressant drugs during breastfeeding, there is still few reliable information on the neonatal safety of the selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors (SNRIs) [serotonin reuptake inhibitors (SRIs)] in nursing mothers. The aim of this study is to provide a systematic review on the neonatal safety profile of these drugs during breastfeeding, also assessing the limits of available tools.
METHODS
MEDLINE and PubMed databases were searched without any language restrictions by using the following set of keywords: ((SSRIs OR selective serotonin inhibitor reuptake OR SNRIs OR selective serotonin noradrenaline inhibitor reuptake) AND (breastfeeding OR lactation OR breast milk)). A separate search was also performed for each SSRIs (paroxetine, fluvoxamine, fluoxetine, sertraline, citalopram and escitalopram) and SNRIs (venlafaxine and duloxetine).
RESULTS
Sertraline and paroxetine show a better neonatal safety profile during breastfeeding as compared with other SRIs. Less data are available for fluvoxamine, escitalopram and duloxetine. Few studies followed up infants breastfeed for assessing the neurodevelopmental outcomes.
CONCLUSIONS
Literature review clearly indicates paroxetine and sertraline as the drugs that should be preferred as first line choice in nursing women who need an antidepressant treatment.
Topics: Antidepressive Agents; Breast Feeding; Databases, Bibliographic; Depression; Female; Humans; Infant; Infant, Newborn; Male; Selective Serotonin Reuptake Inhibitors
PubMed: 25572308
DOI: 10.1002/hup.2451 -
Psychopharmacology Bulletin May 2022Bipolar II disorder (BD-II) has limited evidence-based treatment guidelines. The aim of this systematic review and meta-analysis was to estimate the efficacy and safety... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Bipolar II disorder (BD-II) has limited evidence-based treatment guidelines. The aim of this systematic review and meta-analysis was to estimate the efficacy and safety of second-generation antidepressant (SGAD) monotherapy in acute BD-II depression.
METHODS
A literature search was conducted from the database inception through March 2021. Only randomized controlled trials (RCTs) were included. Outcome measures included: response rates, treatment-emergent affective switch (TEAS) rates, discontinuation due to side-effects, and all-cause discontinuation. Risk ratio (RR) was calculated using the Mantel-Haenszel random effects model.
RESULTS
3301 studies were screened, and 15 articles were selected for full-text review. Five studies met the inclusion criteria: Four double-blind RCTs (n = 533) and one open-label RCT (n = 83) were included. Two double-blind RCTs [n = 223, SGAD = 110 (venlafaxine = 65, sertraline = 45), lithium/control = 113] were included for meta-analysis. The response rate for SGAD monotherapy compared to lithium monotherapy were similar (RR = 1.44, 95% CI 0.78, 2.66). The TEAS rate for SGAD monotherapy was not significantly different from lithium monotherapy (p = 0.76). The discontinuation rate due to side-effects for SGAD monotherapy was significantly lower than lithium monotherapy with a RR = 0.32, 95% CI 0.11, 0.96, p = 0.04 but all-cause discontinuation rates were similar in both groups.
CONCLUSIONS
Limited data suggests short-term efficacy of venlafaxine and sertraline monotherapy in patients with acute BD-II depression with good side effect tolerability and without significantly increased switch rate. There is an urgent need for RCTs investigating the role of SGAD monotherapy in short and long-term among patients with BD-II.
Topics: Antidepressive Agents, Second-Generation; Bipolar Disorder; Depression; Humans; Lithium; Randomized Controlled Trials as Topic; Sertraline; Venlafaxine Hydrochloride
PubMed: 35721812
DOI: No ID Found -
Asian Journal of Psychiatry Jun 2021This systematic review aims to assess the efficacy and acceptability of the different types of antidepressants and benzodiazepines for the treatment of panic disorder... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aims to assess the efficacy and acceptability of the different types of antidepressants and benzodiazepines for the treatment of panic disorder (PD) in adult patients.
METHODS
PubMed, Web of Science, EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published between 1995 and 2020 on the use of antidepressants and benzodiazepines for the treatment of PD. A systematic review and network meta-analysis were performed.
RESULTS
42 RCTs were included in the network meta-analysis, with a comparison of 11 interventions.Escitalopram (odds ratios OR 1.52, 95 % credible interval CI 1.09-2.10), venlafaxine (OR 1.33, 95 % CI 1.16-1.51) and benzodiazepines (OR 1.50, 95 % CI 1.29-1.75) had greater efficacy and acceptability than the placebo. Imipramine(OR 1.43, 95 % CI 1.15-1.79) was also demonstrated to be efficacious and tolerated but the results were restricted to small sample size. Moreover, paroxetine, sertraline, fluoxetine, citalopram and clomipramine (OR 1.37, 1.36, 1.45, 1.33 and 1.36, respectively) were more efficacious, although the acceptability of paroxetine and sertraline were significantly less tolerated than benzodiazepines. Notably, the efficacy of reboxetine and fluvoxamine were merely as equal as that of the placebo.
OUTCOMES
This is the first systematic review of antidepressants and benzodiazepines for the treatment of PD to use a network analysis. Escitalopram and venlafaxine as well as benzodiazepines may be effective choices as treatments for PD with relatively good acceptability, which still needs to be confirmed byhigh-quality RCTs.
Topics: Adult; Antidepressive Agents; Benzodiazepines; Humans; Network Meta-Analysis; Panic Disorder; Paroxetine
PubMed: 33965693
DOI: 10.1016/j.ajp.2021.102664 -
The British Journal of Psychiatry : the... Feb 2015Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy.
AIMS
To determine the efficacy of all types of pharmacotherapy, as monotherapy, in reducing symptoms of PTSD, and to assess acceptability.
METHOD
A systematic review and meta-analysis of randomised controlled trials was undertaken; 51 studies were included.
RESULTS
Selective serotonin reuptake inhibitors were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.23, 95% CI -0.33 to -0.12). For individual pharmacological agents compared with placebo in two or more trials, we found small statistically significant evidence of efficacy for fluoxetine, paroxetine and venlafaxine.
CONCLUSIONS
Some drugs have a small positive impact on PTSD symptoms and are acceptable. Fluoxetine, paroxetine and venlafaxine may be considered as potential treatments for the disorder. For most drugs there is inadequate evidence regarding efficacy for PTSD, pointing to the need for more research in this area.
Topics: Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 25644881
DOI: 10.1192/bjp.bp.114.148551 -
The Cochrane Database of Systematic... Oct 2017Recognition is growing that social anxiety disorder (SAnD) is a chronic and disabling disorder, and data from early trials demonstrate that medication may be effective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recognition is growing that social anxiety disorder (SAnD) is a chronic and disabling disorder, and data from early trials demonstrate that medication may be effective in its treatment. This systematic review is an update of an earlier review of pharmacotherapy of SAnD.
OBJECTIVES
To assess the effects of pharmacotherapy for social anxiety disorder in adults and identify which factors (methodological or clinical) predict response to treatment.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR-Studies and CCMDCTR-References) to 17 August 2015. The CCMDCTR contains reports of relevant RCTs from MEDLINE (1950-), Embase (1974-), PsycINFO (1967-) and CENTRAL (all years). We scanned the reference lists of articles for additional studies. We updated the search in August 2017 and placed additional studies in Awaiting Classification, these will be incorporated in the next version of the review, as appropriate.
SELECTION CRITERIA
We restricted studies to randomised controlled trials (RCTs) of pharmacotherapy versus placebo in the treatment of SAnD in adults.
DATA COLLECTION AND ANALYSIS
Two authors (TW and JI) assessed trials for eligibility and inclusion for this review update. We extracted descriptive, methodological and outcome information from each trial, contacting investigators for missing information where necessary. We calculated summary statistics for continuous and dichotomous variables (if provided) and undertook subgroup and sensitivity analyses.
MAIN RESULTS
We included 66 RCTs in the review (> 24 weeks; 11,597 participants; age range 18 to 70 years) and 63 in the meta-analysis. For the primary outcome of treatment response, we found very low-quality evidence of treatment response for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (number of studies (k) = 24, risk ratio (RR) 1.65; 95% confidence interval (CI) 1.48 to 1.85, N = 4984). On this outcome there was also evidence of benefit for monoamine oxidase inhibitors (MAOIs) (k = 4, RR 2.36; 95% CI 1.48 to 3.75, N = 235), reversible inhibitors of monoamine oxidase A (RIMAs) (k = 8, RR 1.83; 95% CI 1.32 to 2.55, N = 1270), and the benzodiazepines (k = 2, RR 4.03; 95% CI 2.45 to 6.65, N = 132), although the evidence was low quality. We also found clinical response for the anticonvulsants with gamma-amino butyric acid (GABA) analogues (k = 3, RR 1.60; 95% CI 1.16 to 2.20, N = 532; moderate-quality evidence). The SSRIs were the only medication proving effective in reducing relapse based on moderate-quality evidence. We assessed tolerability of SSRIs and the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine on the basis of treatment withdrawal; this was higher for medication than placebo (SSRIs: k = 24, RR 2.59; 95% CI 1.97 to 3.39, N = 5131, low-quality evidence; venlafaxine: k = 4, RR 3.23; 95% CI 2.15 to 4.86, N = 1213, moderate-quality evidence), but there were low absolute rates of withdrawal for both these medications classes compared to placebo. We did not find evidence of a benefit for the rest of the medications compared to placebo.For the secondary outcome of SAnD symptom severity, there was benefit for the SSRIs, the SNRI venlafaxine, MAOIs, RIMAs, benzodiazepines, the antipsychotic olanzapine, and the noradrenergic and specific serotonergic antidepressant (NaSSA) atomoxetine in the reduction of SAnD symptoms, but most of the evidence was of very low quality. Treatment with SSRIs and RIMAs was also associated with a reduction in depression symptoms. The SSRIs were the only medication class that demonstrated evidence of reduction in disability across a number of domains.We observed a response to long-term treatment with medication for the SSRIs (low-quality evidence), for the MAOIs (very low-quality evidence) and for the RIMAs (moderate-quality evidence).
AUTHORS' CONCLUSIONS
We found evidence of treatment efficacy for the SSRIs, but it is based on very low- to moderate-quality evidence. Tolerability of SSRIs was lower than placebo, but absolute withdrawal rates were low.While a small number of trials did report treatment efficacy for benzodiazepines, anticonvulsants, MAOIs, and RIMAs, readers should consider this finding in the context of potential for abuse or unfavourable side effects.
Topics: Adult; Aged; Anticonvulsants; Chronic Disease; Humans; Middle Aged; Monoamine Oxidase Inhibitors; Phobia, Social; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 29048739
DOI: 10.1002/14651858.CD001206.pub3