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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 -
Psychiatry Research Nov 2019Dissociative Disorder (DD) is a large group of disorders that shares common psychopathology. Psychopharmacological agents have sparse evidence in the treatment of DD in...
BACKGROUND
Dissociative Disorder (DD) is a large group of disorders that shares common psychopathology. Psychopharmacological agents have sparse evidence in the treatment of DD in general. Multiple pharmacotherapy options have been used without conclusive evidence.
METHODS
We conducted a systematic review of data in English language from 1967 to 2019 the protocol of which was registered under PROSPERO (Study ID CRD42019127235). Using PRISMA guidelines, 5 RCTs reporting data on 214 participants providing data on response to pharmacotherapy in dissociative disorder were included.
RESULTS
The treatment response rate of pharmacotherapy group as measured in reduction in dissociative symptoms was 68.42% (n = 65/95), significantly higher than that of 39.49% (n = 47/119) in the control group. And, the pooled RR was 1.59 (95% CI, 0.76-3.30; P = 0.21). The overall effect estimates are favourable to pharmacotherapy group over placebo.
CONCLUSION
It would be apt to conclude that Paroxetine and Naloxone are the only pharmacological agents studied through RCTs and found to have modest evidence for controlling depersonalization symptoms and dissociative symptoms that are comorbid with PTSD and BPD. Results of this meta-analysis should be interpreted with caution in view of high heterogeneity and scanty literature on RCTs on various subtypes of DD.
Topics: Dissociative Disorders; Female; Humans; Male; Naloxone; Paroxetine; Psychotropic Drugs; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31470213
DOI: 10.1016/j.psychres.2019.112529 -
Therapeutic Drug Monitoring Feb 2020Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to...
PURPOSE
Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to identify potential pharmacokinetic and pharmacodynamic interactions between new psychoactive substances of the cathinone class and specific prescription drugs.
METHODS
The authors performed a systematic literature review on interactions between synthetic cathinones (mephedrone, methylone, methylenedioxypyrovalerone, and alpha-pyrrolidinopentiophenone) and antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine), attention deficit hyperactivity disorder (ADHD) medications (atomoxetine, dexamphetamine, methylphenidate, modafinil) or HIV medications.
RESULTS
Although no pharmacokinetic interactions have been reported in previous literatures, such interactions are likely to occur. Metabolic pathways of cathinones, antidepressants, and ADHD medications have been shown to overlap, including metabolism via cytochrome P450 enzymes and their inhibition. Consistent with this finding, interactions of bupropion (a cathinone) with antidepressants and ADHD medications have been found to increase their serum concentrations and half-lives. Additionally, limited pharmacodynamic interactions have been reported. However, as cathinones, antidepressants, and ADHD medications have been reported to increase the extracellular monoamine concentration by affecting reuptake transporters, interactions among these compounds are likely. Presumably, even higher monoamine concentrations could be observed when cathinones are combined with prescription drugs with a similar mode of action, as has been reported in animals exposed to duloxetine and bupropion. HIV medications have a different mode of action; thus, they have been reported to be less likely to have pharmacodynamic interactions with cathinones.
CONCLUSIONS
Clinicians should be aware of possible interactions between synthetic cathinones and prescription drugs, which may increase the risk of drug toxicity or reduce the therapeutic efficacy of the drugs. Qualitative drug screening for cathinones using mass spectrometry methods may aid the early detection of these agents.
Topics: Alkaloids; Anti-HIV Agents; Central Nervous System Stimulants; Cytochrome P-450 Enzyme System; Drug Interactions; Half-Life; Humans; Models, Biological; Selective Serotonin Reuptake Inhibitors
PubMed: 31425490
DOI: 10.1097/FTD.0000000000000682 -
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 -
Annals of Clinical Psychiatry :... Nov 2019Anxiety in late-life is a frequently encountered condition. The aim of this review is to systematically examine the efficacy and tolerability of antidepressants for...
BACKGROUND
Anxiety in late-life is a frequently encountered condition. The aim of this review is to systematically examine the efficacy and tolerability of antidepressants for treating anxiety disorders among older adults.
METHODS
Electronic searches of The Cochrane Central Register of Controlled Trials and the standard bibliographic databases PubMed, MEDLINE, EMBASE, and PsycINFO were performed in August 2018 and updated in October 2018 for randomized controlled trials (RCTs) evaluating antidepressants for late-life anxiety. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine.
RESULTS
Data from 12 papers describing 10 RCTs of antidepressants for late-life anxiety are included in this review. There were 2 studies each of sertraline, escitalopram, and duloxetine, and 1 study each of citalopram, paroxetine, venlafaxine, and imipramine. Across all trials, antidepressants were associated with a significant reduction in anxiety symptoms at the end of the study period. Limitations of the trials include a preponderance of generalized anxiety disorder and relatively less data on other anxiety disorders, and limited data on long-term use of antidepressants for anxiety.
CONCLUSIONS
Antidepressants are beneficial for treating anxiety disorders in late life and are generally well tolerated.
Topics: Aged; Antidepressive Agents; Anxiety Disorders; Citalopram; Duloxetine Hydrochloride; Humans; Late Onset Disorders; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 31369663
DOI: No ID Found -
The Lancet. Psychiatry Jul 2019Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.
METHODS
We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4-12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.
FINDINGS
28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.
INTERPRETATION
For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.
FUNDING
Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.
Topics: Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Mirtazapine; Randomized Controlled Trials as Topic; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 31178367
DOI: 10.1016/S2215-0366(19)30217-2 -
Psychosomatic Medicine Sep 2019Individual studies have reported conflicting effects of selective serotonin reuptake inhibitors (SSRIs) on glycemia. We systematically reviewed the effects of SSRIs on... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Individual studies have reported conflicting effects of selective serotonin reuptake inhibitors (SSRIs) on glycemia. We systematically reviewed the effects of SSRIs on glycemia and whether metabolic and psychological factors moderated these effects.
METHODS
We systematically searched for placebo-controlled randomized controlled trials investigating the effect of SSRIs on glycemia (fasting blood glucose or HbA1c) as a primary or secondary outcome. Random effects meta-analysis was conducted to compute an overall treatment effect. Meta-regression tested whether depression, type 2 diabetes, insulin resistance, treatment duration, and weight loss moderated treatment effects.
RESULTS
Sixteen randomized controlled trials (n = 835) were included and glycemia was usually a secondary outcome. Overall, SSRIs improved glycemia versus placebo (pooled effect size (ES) = -0.34, 95% confidence interval (CI) = -0.48 to -0.21; p < .001, I = 0%). Individually, fluoxetine (ES = -0.29, 95% CI = -0.54 to -0.05; p = .018) and escitalopram/citalopram (ES = -0.33, 95% CI = -0.59 to -0.07; p = .012) outperformed placebo, but paroxetine (ES = -0.19, 95% CI = -0.58 to 0.19; p = .33) did not. Results were similar in populations selected for depression as those not. Across studies, baseline insulin resistance (p = .46), treatment duration (p = .47), diabetes status (p = .41), and weight loss (p = .93) did not moderate changes. Heterogeneity for all analyses was nonsignificant.
CONCLUSIONS
SSRIs seem to have an association with improvement in glycemia, which is not moderated by depression status, diabetes status, or change in weight across studies. Future powered trials with longer treatment duration are needed to confirm these findings.
REGISTRATION
PROSPERO ID: CRD4201809239.
Topics: Blood Glucose; Comorbidity; Depressive Disorder; Glucose Metabolism Disorders; Glycated Hemoglobin; Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 31136376
DOI: 10.1097/PSY.0000000000000707 -
Journal of Affective Disorders Jul 2019Antidepressants are frequently prescribed and are the first-line pharmacological treatments for psychiatric disorders in children and adolescents. Although...
OBJECTIVE
Antidepressants are frequently prescribed and are the first-line pharmacological treatments for psychiatric disorders in children and adolescents. Although antidepressants are generally effective and well-tolerated by children, between 31% to 48% will not respond and up to 25% will experience an adverse drug reaction. Evidence from adult populations suggests pharmacogenetic information can assist with identifying individuals at greatest risk for poor response or adverse drug reactions but the evidence base in pediatric populations is less clear.
METHOD
We systematically identified, reviewed, and critically evaluated the antidepressant pharmacogenetics literature among children and adolescents using standardized tools and consensus criteria.
RESULTS
We identified 24 studies, most of which were of fair to moderate quality. Collectively, the studies identified 25 significant gene-antidepressant associations involving 10 genes (ABCB1, BDNF, CYP2C19, CYP2D6, FKBP5, GNB3, HTR1B, HTR2A, SLC6A4, TPH2) and nine antidepressants (amitriptyline, citalopram, escitalopram, fluoxetine, fluvoxamine, nortriptyline, paroxetine, sertraline, and venlafaxine). None of the identified associations have been independently replicated in children.
LIMITATIONS
Included studies were heterogenous in terms of study design, genes and drugs assessed, and outcomes measured.
CONCLUSION
The antidepressant pharmacogenetics knowledge base in pediatric populations is still emerging, but results to date echo many of the gene-antidepressant associations identified in adult populations. Given ubiquitous prescribing of antidepressants in the care of children and adolescents with psychiatric disorders, further research on identifying new and confirming current gene-antidepressant associations are warranted.
Topics: Adolescent; Amitriptyline; Antidepressive Agents; Child; Citalopram; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Female; Fluoxetine; Fluvoxamine; Humans; Male; Mental Disorders; Nortriptyline; Paroxetine; Pharmacogenetics; Serotonin Plasma Membrane Transport Proteins; Sertraline; Tryptophan Hydroxylase; Venlafaxine Hydrochloride; Young Adult
PubMed: 31112844
DOI: 10.1016/j.jad.2019.05.025 -
Sleep Medicine Reviews Aug 2019Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy...
Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy of pharmacotherapy in adults with OSA and delineate the underlying mechanisms. Seven databases were systematically screened for randomised controlled trials (RCTs) from their inception to September 2018. According to a pre-registered study protocol (PROSPERO-ID-CRD42018086446) network meta-analysis was performed to obtain intervention effects on the apnoea-hypopnoea-index (AHI) based on data extracted from published reports. We identified 58 RCTs (n = 1710 patients) investigating 44 different drugs or drug-combinations. Interventions were classified into seven pathomechanism-groups and summarized narratively. A meta-analysis of 17 trials for seven drugs (acetazolamide, donepezil, mirtazapine, ondansetron, paroxetine, protriptyline, theophylline) indicated a small effect for acetazolamide (mean difference in AHI -9.6/h [-17.7; -1.4]; p = 0.02). In the network meta-analysis (I = 50%) nine drugs (tramazoline, liraglutide, spironolactone/furosemide, acetazolamide, dronabinol, zonisamide, phentermine, spironolactone, and ondansetron/fluoxetine) significantly lowered the AHI compared to placebo. Although some trials indicate favorable outcomes, these results are only valid for distinctive OSA-phenotypes or were not clinically significant. The effect sizes were small, the majority of trials were not adequately powered. There is currently insufficient evidence to recommend any pharmacotherapy for OSA and no phase-III trials are available.
Topics: Adult; Drug Therapy; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive
PubMed: 31075665
DOI: 10.1016/j.smrv.2019.04.009 -
The Cochrane Database of Systematic... Mar 2019Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.Panic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action.
OBJECTIVES
To assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data.
SELECTION CRITERIA
All double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability.
MAIN RESULTS
We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence).
AUTHORS' CONCLUSIONS
Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.
Topics: Adult; Aged; Agoraphobia; Benzodiazepines; Buspirone; Humans; Imipramine; Middle Aged; Numbers Needed To Treat; Panic Disorder; Paroxetine; Patient Dropouts; Placebos; Propranolol; Randomized Controlled Trials as Topic; Remission Induction; Young Adult
PubMed: 30921478
DOI: 10.1002/14651858.CD010677.pub2