-
Frontiers in Pharmacology 2020To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults.
OBJECTIVE
To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults.
METHODS
Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the baseline in the total number of full panic attacks, Clinical Global Impression-Severity of Illness (CGI-S) score, and the proportion of participants with zero full panic attacks and with a 50% or greater reduction in the number of full panic attacks. The tolerability outcomes included withdrawal rate and the incidence of adverse events (AEs).
RESULTS
13RCTs were included. The pooled analyses showed patients who received paroxetine experienced greater improvements in the number of full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; ≥50% reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70, 95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05) than placebo. There was no evident difference in the total withdrawal rate (OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29, 95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was lower than the placebo group. Meanwhile, the incidence of any treatment-emergent adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine group was higher in comparison with the placebo.
CONCLUSIONS
Paroxetine is an effective and well-tolerated short-term treatment for adults with panic disorder.
PubMed: 32296330
DOI: 10.3389/fphar.2020.00275 -
European Neuropsychopharmacology : the... Jul 2020One problem areas of animal models and tests for neuropsychiatric disorders is unclear reproducibility, including both internal and external validity. One way to examine... (Meta-Analysis)
Meta-Analysis
Similarities and dissimilarities in the effects of benzodiazepines and specific serotonin reuptake inhibitors (SSRIs) in the defensive marble burying test: A systematic review and meta-analysis.
One problem areas of animal models and tests for neuropsychiatric disorders is unclear reproducibility, including both internal and external validity. One way to examine external validity is with systematic reviews and meta-analyses, a standard practice in clinical research that is relatively neglected in preclinical research. Considering the need to evaluate the validity and reproducibility of frequently used animal models, this study presents a meta-analysis of the effects of prototypic benzodiazepines and specific serotonin reuptake inhibitors (SSRIs) in the mouse defensive marble burying test (MBT). These drug groups were selected because although they differ in their biological targets as well as in their clinical use, they are both commonly used for the treatment of anxiety disorders. A PubMed literature search was performed to identify studies that examined the effects of benzodiazepines (diazepam, alprazolam, chlordiazepoxide, clonazepam) or SSRIs (fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine) in the MBT in mice. For benzodiazepines, 73 experiments were included. Benzodiazepines effect size was 2.04 and Q statistics was 1959 with a significant correlation between dose and effect size (r = 0.31, p = 0.007). For SSRIs we identified 47 experiments. Effect size of SSRIs was 2.24 and Q statistics was 493.38. No correlation was found between dose and effect size (r = 0.23, p = 0.12). The current results support the external validity of the defensive marble burying test as a screening test for anxiolytic effects. However, these results indicate that significant attention should be given to the administration schedules of benzodiazepines and SSRIs.
Topics: Animals; Anxiety; Benzodiazepines; Disease Models, Animal; Drug Administration Schedule; Mice; Motor Activity; Selective Serotonin Reuptake Inhibitors
PubMed: 32456852
DOI: 10.1016/j.euroneuro.2020.04.007 -
The Australasian Journal of Dermatology Feb 2022Anecdotal evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) cause cutaneous adverse...
Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor associated cutaneous adverse drug reactions: A systematic review of case reports and case series.
Anecdotal evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) cause cutaneous adverse drug reactions (CADRs). However, there is limited information on the factors associated with these occurrences. In this study, we aimed to describe the demographic, clinical and pharmacological characteristics associated with CADRs encountered by patients administered SSRIs and/or SNRIs for psychiatric diagnoses and to compare the differences in these factors between severe and non-severe CADRs. A protocol was developed a priori (PROSPERO: CRD42020204830) in line with the PRISMA guidelines. We searched PubMed/Medline, PsycINFO and SCOPUS from inception to October 2020 to identify case reports and/or case series of SSRI and SNRI associated CADRs. Additional cases were obtained from the retrieved articles' bibliography. A total of 141 articles were included in the study, documenting 173 CADRs. Females accounted for 128 (74.0%) of the analysed CADRs. The median age of the cases was 42 IQR (27; 53) with no statistically significant differences in age between males and females (P = 0.542). A total of 157 (90.8%) of the reported CADRs were associated with SSRIs, particularly fluoxetine 68 (39.5%), sertraline 30 (17.4%) and paroxetine 25 (14.5%). Non-severe CADRs and severe CADRs accounted for 23 (13.4%) and 149 (86.6%) reports respectively. No statistically significant differences were observed for gender (P = 0.616), age at onset (P = 0.493) and time to onset (P = 0.105) between non-severe CADRs and SCARs. In conclusion, CADRs following SSRIs and SNRIs disproportionately affect females in the reproductive age group compared to males and are mostly associated with SSRIs.
Topics: Drug Eruptions; Humans; Serotonin and Noradrenaline Reuptake Inhibitors; Sex Distribution
PubMed: 34958129
DOI: 10.1111/ajd.13780 -
Clinical Breast Cancer Apr 2022Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with... (Review)
Review
Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with concurrent use. It remains unclear however whether this interaction is clinically important. A systematic review of studies comparing endocrine therapy (including tamoxifen and aromatase inhibitors) alone or concurrent with antidepressants in breast cancer patients was performed. The literature search sought studies within MEDLINE, EMBASE, and the Cochrane Collaboration Library published from database inception until December 1, 2020. Outcomes of interest included recurrence, breast cancer-specific survival, overall mortality, quality of life, and treatment compliance. Studies were assessed with the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle Ottawa tool for case-control and cohort studies. From 695 citations, we included 15 studies (2 randomized controlled trials [255 patients], 10 retrospective cohort studies [75,678 patients], and 3 case-control studies [18,836 patients]). While between-study clinical and methodologic differences (including analysis of confounding variables) precluded formal meta-analysis, findings from included studies did not find consistent evidence that concurrent use of antidepressants (including paroxetine) with tamoxifen therapy has negative impacts on the outcomes of interest. In this systematic review, despite data from nearly 100,000 patients, concurrent use of tamoxifen and antidepressants showed no consistent negative effect on clinical outcomes. Given the recognized harm to patients of changing either endocrine therapy or antidepressants to avoid concurrent use, current evidence-based guidelines should be updated accordingly. More rigorously designed pharmacoepidemiologic studies are needed.
Topics: Antidepressive Agents; Breast Neoplasms; Female; Humans; Practice Guidelines as Topic; Quality of Life; Retrospective Studies; Tamoxifen
PubMed: 34740542
DOI: 10.1016/j.clbc.2021.10.003 -
Therapeutic Drug Monitoring Apr 2020The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among...
BACKGROUND
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among high-risk substance users. Various phenethylamines and NPS are also highly used in populations with mental disorders, depression, or attention deficit hyperactivity disorder (ADHD). Moreover, NPS use is highly prevalent among men and women with risky sexual behavior. Considering these specific populations and their frequent concurrent use of drugs, such as antidepressants, ADHD medication, and antiretrovirals, reports on potential interactions between these drugs, and phenethylamines 4-FA and 2C-B, were reviewed.
METHODS
The authors performed a systematic literature review on 4-FA and 2C-B interactions with antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, bupropion, venlafaxine, phenelzine, moclobemide, and tranylcypromine), ADHD medications (atomoxetine, dexamphetamine, methylphenidate, and modafinil), and antiretrovirals.
RESULTS
Limited literature exists on the pharmacokinetics and drug-drug interactions of 2C-B and 4-FA. Only one case report indicated a possible interaction between 4-FA and ADHD medication. Although pharmacokinetic interactions between 4-FA and prescription drugs remain speculative, their pharmacodynamic points toward interactions between 4-FA and ADHD medication and antidepressants. The pharmacokinetic and pharmacodynamic profile of 2C-B also points toward such interactions, between 2C-B and prescription drugs such as antidepressants and ADHD medication.
CONCLUSIONS
A drug-drug (phenethylamine-prescription drug) interaction potential is anticipated, mainly involving monoamine oxidases for 2C-B and 4-FA, with monoamine transporters being more specific to 4-FA.
Topics: Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Depressive Disorder; Dimethoxyphenylethylamine; Drug Interactions; Humans; Phenethylamines; Prescription Drugs
PubMed: 32022784
DOI: 10.1097/FTD.0000000000000725 -
Medicina (Kaunas, Lithuania) Aug 2019Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold... (Meta-Analysis)
Meta-Analysis
Efficacy of Low-Dose Paroxetine for the Treatment of Hot Flushes in Surgical and Physiological Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Trials.
Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) -7.97 [-10.51, -5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, -0.40 awakenings/night [-1.38, 0.58 CI]). Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.
Topics: Female; Hot Flashes; Humans; Ovariectomy; Paroxetine; Postmenopause; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders
PubMed: 31480427
DOI: 10.3390/medicina55090554 -
Neuropsychiatric Disease and Treatment 2022There is variation in the safety profile of antidepressants. Rates of adverse events along with the costs of treating them can be an important factor influencing the...
PURPOSE
There is variation in the safety profile of antidepressants. Rates of adverse events along with the costs of treating them can be an important factor influencing the choice of depression treatment. This study sought to estimate the comparative safety of commonly prescribed antidepressants, and how the costs of treating these varied across European countries.
METHODS
A systematic literature review was conducted (in Medline, Embase, PsycINFO and CENTRAL) to identify placebo-controlled trials reporting rates of at least one type of sexual dysfunction, weight change, insomnia, anxiety, and anhedonia. Eight antidepressants were considered: duloxetine, escitalopram, fluoxetine, paroxetine, sertraline, trazodone, venlafaxine, and vortioxetine. This evidence was synthesised via Bayesian random effects network meta-analyses to provide comparative estimates of safety. A systematic search identified country-specific costs of managing depression and adverse events of antidepressants. Evidence on costs and safety was combined in an economic model to provide country-specific costs for Bulgaria, the Czech Republic, Greece, Hungary, Italy, Romania, Slovakia, Portugal, and Poland.
RESULTS
Trazodone had the lowest rates of both insomnia (odds ratio 0.66, 95% credible interval 0.31 to 1.38) and anxiety (0.13, <0.01 to 1.80). All antidepressants were associated with increased rates of sexual dysfunction relative to placebo. Weight change was largest for fluoxetine (kg change -1.01, -1.40 to -0.60) and sertraline (-1.00, -1.36 to -0.65), although heterogeneity was extreme for this outcome. No evidence was identified for anhedonia. Total costs were lowest for trazodone in all nine of the countries evaluated. This was primarily due to reduced rates of treatment discontinuation.
CONCLUSION
Trazodone generally had the best safety profile of the antidepressants evaluated. This led to healthcare costs being lowest for trazodone in all nine European countries, emphasising the importance of considering rates of adverse events when choosing a pharmacological treatment to treat symptoms of depression.
PubMed: 35698594
DOI: 10.2147/NDT.S356414 -
In utero exposure to antidepressant medication and neonatal and child outcomes: a systematic review.Acta Psychiatrica Scandinavica Jan 2020The aim of this study is to systematically review published studies, reporting outcomes to offspring following in utero exposure to antidepressant medications, which...
OBJECTIVE
The aim of this study is to systematically review published studies, reporting outcomes to offspring following in utero exposure to antidepressant medications, which used an untreated depressed comparison group.
METHODS
OVID, Scopus, EBSCO Collections, the Cochrane Library and Web of Science databases were searched for relevant publications published between January 1950 and May 2018 and a total of 188 potentially eligible studies were identified.
RESULTS
Following review, 16 primary studies were eligible for inclusion. Antidepressant exposure was associated with an increased risk of lower gestational age, preterm birth, but not low birthweight or being small for gestational age compared to untreated depression. There is some evidence that congenital defects are associated with antidepressant use, particularly between cardiac defects and paroxetine use. There is conflicting evidence regarding neurodevelopment in offspring, with some reports of increased incidence of autistic spectrum disorders and depression, but also reports of no problems when measuring emotional symptoms, peer problems, conduct problems and hyperactivity-inattention scores.
CONCLUSION
When compared with an untreated depressed group, antidepressant exposure was associated with adverse outcomes at birth, while there is insufficient data to determine whether the association between antidepressants and congenital defects or developmental disorders is a true association. However, although we compared treated vs. untreated depression there still may be residual confounding as an untreated depressed group is likely to have less severe depression.
Topics: Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Conduct Disorder; Congenital Abnormalities; Depressive Disorder; Female; Gestational Age; Heart Defects, Congenital; Humans; Infant, Newborn; Neurodevelopmental Disorders; Paroxetine; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 31648376
DOI: 10.1111/acps.13120 -
Journal of Clinical Neuroscience :... Oct 2020The type and quantities of antidepressants are increasing, but the efficacy and safety of first-line and emerging drugs vary between studies. In this article, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The type and quantities of antidepressants are increasing, but the efficacy and safety of first-line and emerging drugs vary between studies. In this article, we estimated the efficacy and safety of first-line and emerging antidepressants (anti-inflammatory drugs and ketamine).
METHOD
ystematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the depression, depressive symptoms, antidepressants, fluoxetine (Prozac), paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, duloxetine, NSAIDs, anti-cytokine drugs or pioglitazone published before May 1st, 2019. Information on study characteristics, depression or depressive symptoms, antidepressants and the descriptive statistics (including efficacy and safety of antidepressants) was extracted independently by 2 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. The response and remission of antidepressants were used as clinical evaluation indicators, and the evaluation criteria were clinical depression scales. OR value of antidepressants as assessed by meta-analysis.
RESULTS
The literature search retrieved 5529 potentially relevant articles of which 49 studies were finally included. We compared the efficacy of antidepressants (seven first-line antidepressants (fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, duloxetine), there kinds of anti-inflammatory drugs(NASIDs, cytokine-inhibitor, pioglitazone) and ketamine) by comparing the OR values.
CONCLUSION
The three drugs with the highest OR value in response were NASID (OR = 3.62(1.58, 8.32)), venlafaxin (OR = 3.50(1.83, 6.70)) and ketamine (OR = 3.28(1.89, 5.68)), while the highest OR value in remission were NASID (OR = 3.17(1.60, 6.29)), ketamine (OR = 2.99(1.58, 5.67)) and venlafaxin (OR = 2.55(1.72, 3.78)). Through reading the literature, we found 69 SNPs associated with depression. Major depression was a debilitating disorder that could ultimately lead to enormous societal and economical challenge [1]. The number of person which affected by depression was up to 16% of the population worldwide. More than 300 million individuals were estimated to suffer depression these days [1,2]. Therefore, it is apparent that safety and effective treatments for depression are necessary. In the 1930 s, the first drug for schizophrenia was discovered. This finding was a landmark for the emerging of biological psychiatry. In the 1950 s, pharmacologists had stumbled upon the antidepressant effect of imipramine. Since then, every 30 years, the use of antidepressants had made a pulsatile leap. Selective serotonin reuptake inhibitors (SSRIs) are the most widely-prescribed psychiatric drugs for the treatment of depression. However, the efficacy was variable and incomplete: 60%-70% of the patients do not experience remission, while 30%-40% do not show a significant response [3,4]. Nevertheless, SSRIs, SNRIs (selective serotonin-norepinephrine reuptake inhibitors, which can block norepinephrine at the same time) and NaSSAs (norepinephrine and selective serotonin receptor agonist), constituted the first-line clinical drugs. Nearly 30 years after the outbreak of SSRIs, antidepressants have ushered in a new chapter. It has been found that anti-inflammatory drugs could also have the small and moderate antidepressant effect and it's widely discussed [5]. More than 40 anti-inflammatory drugs have been certificated to have antidepressant effects in preclinical and clinical studies [6]. The antidepressant that has been approved for use recently is ketamine. There is no comprehensive comparison of the efficacy of all these drugs. In this review, we tried to estimate the efficacy and safety of first-line antidepressants, anti-inflammatory drugs and ketamine. On the other hand, with the development of GWAS, SNPs related to depression have been reported, and the corresponding mechanisms have been elaborated, respectively. However, patients with these SNPs have not been treated with individualized drugs according to the mechanisms. We hope to push this process forward through the summary of this article.
METHODS
Search Strategy and Study Eligibility.
Topics: Antidepressive Agents; Depression; Humans
PubMed: 33099342
DOI: 10.1016/j.jocn.2020.08.013 -
The World Journal of Biological... Nov 2021To address the extreme suicide risk period following a suicidal crisis, we aimed to assess the current evidence for specific healthcare system-based interventions on...
OBJECTIVES
To address the extreme suicide risk period following a suicidal crisis, we aimed to assess the current evidence for specific healthcare system-based interventions on suicide-related outcomes within one-week or one-month in individuals with current suicidal ideation (SI) or a recent suicide attempt (SA).
METHODS
We performed a database (Medline, Academic Search Complete, PsycARTICLES, the Cochrane library, PubMed) and manual reference search for randomised controlled trials, published between March 2000 and March 2020. Antisuicidal efficacy was defined as SI, SA, or a closely related concept. Quality was assessed with the Cochrane Risk of Bias 2 tool for randomised trials.
RESULTS
Out of 34 trials, five reported ketamine or esketamine superiority over placebo in reducing SI in depressed subjects within one week, while five studies had negative findings. Single trials reported positive results for one-month antisuicidal efficacy of buprenorphine, paroxetine, a crisis response plan, and assertive case management. Most trials were underpowered and had moderate-to-high risk of bias.
CONCLUSIONS
Preliminary mixed evidence suggests the possible utility of several pharmacological (ketamine, esketamine paroxetine, and buprenorphine) and non-pharmacological (a crisis response plan, and assertive case management) interventions. Only the immediate efficacy of ketamine was supported by multiple studies, and replication is needed.
Topics: Humans; Suicidal Ideation; Suicide, Attempted
PubMed: 33783294
DOI: 10.1080/15622975.2021.1907712