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The Cochrane Database of Systematic... Dec 2019Although antidepressants are often a first-line treatment for adults with moderate to severe depression, many people do not respond adequately to medication, and are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although antidepressants are often a first-line treatment for adults with moderate to severe depression, many people do not respond adequately to medication, and are said to have treatment-resistant depression (TRD). Little evidence exists to inform the most appropriate 'next step' treatment for these people.
OBJECTIVES
To assess the effectiveness of standard pharmacological treatments for adults with TRD.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (March 2016), CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science (31 December 2018), the World Health Organization trials portal and ClinicalTrials.gov for unpublished and ongoing studies, and screened bibliographies of included studies and relevant systematic reviews without date or language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with participants aged 18 to 74 years with unipolar depression (based on criteria from DSM-IV-TR or earlier versions, International Classification of Diseases (ICD)-10, Feighner criteria or Research Diagnostic Criteria) who had not responded to a minimum of four weeks of antidepressant treatment at a recommended dose. Interventions were: (1) increasing the dose of antidepressant monotherapy; (2) switching to a different antidepressant monotherapy; (3) augmenting treatment with another antidepressant; (4) augmenting treatment with a non-antidepressant. All were compared with continuing antidepressant monotherapy. We excluded studies of non-standard pharmacological treatments (e.g. sex hormones, vitamins, herbal medicines and food supplements).
DATA COLLECTION AND ANALYSIS
Two reviewers used standard Cochrane methods to extract data, assess risk of bias, and resolve disagreements. We analysed continuous outcomes with mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (CI). For dichotomous outcomes, we calculated a relative risk (RR) and 95% CI. Where sufficient data existed, we conducted meta-analyses using random-effects models.
MAIN RESULTS
We included 10 RCTs (2731 participants). Nine were conducted in outpatient settings and one in both in- and outpatients. Mean age of participants ranged from 42 - 50.2 years, and most were female. One study investigated switching to, or augmenting current antidepressant treatment with, another antidepressant (mianserin). Another augmented current antidepressant treatment with the antidepressant mirtazapine. Eight studies augmented current antidepressant treatment with a non-antidepressant (either an anxiolytic (buspirone) or an antipsychotic (cariprazine; olanzapine; quetiapine (3 studies); or ziprasidone (2 studies)). We judged most studies to be at a low or unclear risk of bias. Only one of the included studies was not industry-sponsored. There was no evidence of a difference in depression severity when current treatment was switched to mianserin (MD on Hamilton Rating Scale for Depression (HAM-D) = -1.8, 95% CI -5.22 to 1.62, low-quality evidence)) compared with continuing on antidepressant monotherapy. Nor was there evidence of a difference in numbers dropping out of treatment (RR 2.08, 95% CI 0.94 to 4.59, low-quality evidence; dropouts 38% in the mianserin switch group; 18% in the control). Augmenting current antidepressant treatment with mianserin was associated with an improvement in depression symptoms severity scores from baseline (MD on HAM-D -4.8, 95% CI -8.18 to -1.42; moderate-quality evidence). There was no evidence of a difference in numbers dropping out (RR 1.02, 95% CI 0.38 to 2.72; low-quality evidence; 19% dropouts in the mianserin-augmented group; 38% in the control). When current antidepressant treatment was augmented with mirtazapine, there was little difference in depressive symptoms (MD on Beck Depression Inventory (BDI-II) -1.7, 95% CI -4.03 to 0.63; high-quality evidence) and no evidence of a difference in dropout numbers (RR 0.50, 95% CI 0.15 to 1.62; dropouts 2% in mirtazapine-augmented group; 3% in the control). Augmentation with buspirone provided no evidence of a benefit in terms of a reduction in depressive symptoms (MD on Montgomery and Asberg Depression Rating Scale (MADRS) -0.30, 95% CI -9.48 to 8.88; low-quality evidence) or numbers of drop-outs (RR 0.60, 95% CI 0.23 to 1.53; low-quality evidence; dropouts 11% in buspirone-augmented group; 19% in the control). Severity of depressive symptoms reduced when current treatment was augmented with cariprazine (MD on MADRS -1.50, 95% CI -2.74 to -0.25; high-quality evidence), olanzapine (MD on HAM-D -7.9, 95% CI -16.76 to 0.96; low-quality evidence; MD on MADRS -12.4, 95% CI -22.44 to -2.36; low-quality evidence), quetiapine (SMD -0.32, 95% CI -0.46 to -0.18; I2 = 6%, high-quality evidence), or ziprasidone (MD on HAM-D -2.73, 95% CI -4.53 to -0.93; I2 = 0, moderate-quality evidence) compared with continuing on antidepressant monotherapy. However, a greater number of participants dropped out when antidepressant monotherapy was augmented with an antipsychotic (cariprazine RR 1.68, 95% CI 1.16 to 2.41; quetiapine RR 1.57, 95% CI: 1.14 to 2.17; ziprasidone RR 1.60, 95% CI 1.01 to 2.55) compared with antidepressant monotherapy, although estimates for olanzapine augmentation were imprecise (RR 0.33, 95% CI 0.04 to 2.69). Dropout rates ranged from 10% to 39% in the groups augmented with an antipsychotic, and from 12% to 23% in the comparison groups. The most common reasons for dropping out were side effects or adverse events. We also summarised data about response and remission rates (based on changes in depressive symptoms) for included studies, along with data on social adjustment and social functioning, quality of life, economic outcomes and adverse events.
AUTHORS' CONCLUSIONS
A small body of evidence shows that augmenting current antidepressant therapy with mianserin or with an antipsychotic (cariprazine, olanzapine, quetiapine or ziprasidone) improves depressive symptoms over the short-term (8 to 12 weeks). However, this evidence is mostly of low or moderate quality due to imprecision of the estimates of effects. Improvements with antipsychotics need to be balanced against the increased likelihood of dropping out of treatment or experiencing an adverse event. Augmentation of current antidepressant therapy with a second antidepressant, mirtazapine, does not produce a clinically important benefit in reduction of depressive symptoms (high-quality evidence). The evidence regarding the effects of augmenting current antidepressant therapy with buspirone or switching current antidepressant treatment to mianserin is currently insufficient. Further trials are needed to increase the certainty of these findings and to examine long-term effects of treatment, as well as the effectiveness of other pharmacological treatment strategies.
Topics: Humans; Antidepressive Agents; Antipsychotic Agents; Depression; Drug Resistance; Drug Therapy, Combination; Mianserin; Patient Dropouts; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31846068
DOI: 10.1002/14651858.CD010557.pub2 -
Sleep & Breathing = Schlaf & Atmung Jun 2020To establish the efficacy of oral antidepressants compared to placebo in improving obstructive sleep apnea (OSA) as measured on a polysomnography study. Secondary... (Meta-Analysis)
Meta-Analysis
PURPOSE
To establish the efficacy of oral antidepressants compared to placebo in improving obstructive sleep apnea (OSA) as measured on a polysomnography study. Secondary outcomes included self-reported sleepiness.
METHODS
Authors identified prospective randomized placebo-controlled studies from MEDLINE through PubMed, Web of Science, the Cochrane Library and EMBASE up to February 2019 in English language. Antidepressants included tricyclic antidepressants (TCA), tetracyclic antidepressants (TeCA), selective serotonin reuptake inhibitors (SSRI), and serotonin receptor modulators (SRM). Studies were assessed for inclusion and exclusion criteria, as well as risk of bias based on the Cochrane handbook.
RESULTS
The initial search yielded 254 unduplicated references ultimately reduced to 8 relevant studies, in which 198 OSA participants were included. Patients with an average baseline AHI of 26.7 events/hour taking 15-45mg mirtazapine had a statistically significant reduction in apnea-hypopnea index compared to placebo by -10.5 events/hour (p<0.001), apnea index by -3.6 events/hour (p=0.001) and hypopnea index by -5.9 events/hour (p=0.037). In one study, patients taking 100mg trazodone 1 night improved significantly in AHI compared to placebo group (p<0.001). Arousal index, sleepiness, and sleep efficiency were not statistically significantly reduced with any antidepressant medication compared to placebo (p>0.05).
CONCLUSIONS
Of the five antidepressant medications studied, only mirtazapine and trazadone showed a statistically significant reduction in AHI in the treated groups but not in sleepiness scale nor an increase in sleep efficiency. In this review, the total sample sizes were small, adverse side effects of some of the antidepressant medications were clinically significant, overall risk of bias of the studies was high or unclear, and overall quality of the evidence was low. Based on the evidence available at this time, we cannot recommend the antidepressants studied in the treatment of OSA.
Topics: Antidepressive Agents; Humans; Placebos; Prospective Studies; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 31720982
DOI: 10.1007/s11325-019-01954-9 -
Psychiatry Research Nov 2019Depression has brought huge disease burden to the world. This systematic review aimed to compare the efficacy and safety of pharmacological and non-pharmacological...
Depression has brought huge disease burden to the world. This systematic review aimed to compare the efficacy and safety of pharmacological and non-pharmacological treatments for major depressive disorder (MDD). We searched electronic databases with time range from 1990.1.1 to 2018.9.5. Randomized controlled trials (RCTs) including adult patients with MDD were eligible for inclusion. We conducted network meta-analyses using multivariate meta-analyses models under the frequency framework. Primary outcomes were efficacy (response rate) and safety (overall risk of adverse events). We estimated summary odds ratios (ORs) based on group-level data. 20,937 citations were identified, 91 trials comprising 10,991 participants were included in efficacy study, and 32 trials comprising 5245 participants were included in safety study. In terms of efficacy, all treatments studied (acupuncture, mirtazapine, herbal medicine, venlafaxine, physical exercise, cognitive-behavioral therapy (CBT), bupropion, fluoxetine, and vortioxetine) except for probiotics were significantly more effective than placebo. In terms of safety, bupropion, fluoxetine, venlafaxine, and vortioxetine were significantly less safe than placebo. Herbal medicine and mirtazapine had no significant difference in overall risk of adverse events compared with placebo. Acupuncture, CBT, physical exercise and probiotics were lack of eligible safety data.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Bupropion; Cognitive Behavioral Therapy; Depressive Disorder, Major; Fluoxetine; Humans; Mirtazapine; Network Meta-Analysis; Treatment Outcome; Venlafaxine Hydrochloride; Vortioxetine
PubMed: 31627074
DOI: 10.1016/j.psychres.2019.112595 -
Maturitas Nov 2019Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this...
Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.
Topics: Antidepressive Agents; Cognitive Behavioral Therapy; Continuous Positive Airway Pressure; Depression; Exercise; Female; Hormone Replacement Therapy; Humans; Menopause; Mirtazapine; Quality of Life; Restless Legs Syndrome; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sleep; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 31547910
DOI: 10.1016/j.maturitas.2019.08.006 -
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 -
Journal of the American Geriatrics... Aug 2019To assess adverse effects of pharmacologic antidepressants for treatment of major depressive disorder (MDD) in adults 65 years of age or older. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess adverse effects of pharmacologic antidepressants for treatment of major depressive disorder (MDD) in adults 65 years of age or older.
DESIGN
Systematic review and meta-analysis.
SETTING
Specialist or generalist outpatient setting, rehabilitation facility, and nursing facilities.
PARTICIPANTS
Persons 65 years and older with MDD.
INTERVENTION
Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, or vortioxetine compared with another antidepressant, placebo, or nonpharmacologic therapy.
MEASUREMENTS
Adverse events, arrhythmias, cognitive impairment, falls, fractures, hospitalization, mortality, QTc prolongation, serious adverse events, and withdrawals due to adverse events.
RESULTS
Nineteen randomized controlled trials and two observational studies were included. Most studies evaluated treatment of the acute phase (<12 wk) of MDD of moderate severity. SSRIs led to a statistically similar frequency of overall adverse events vs placebo (moderate strength of evidence [SOE]), but SNRIs caused more overall adverse events vs placebo (high SOE) during the acute treatment phase. Both SSRIs and SNRIs led to more study withdrawals due to adverse events vs placebo (SSRIs low SOE; SNRIs moderate SOE). Duloxetine led to a more falls vs placebo (moderate SOE) during 24 weeks of acute and continuation treatment of MDD.
CONCLUSION
In patients 65 years of age or older with MDD, treatment of the acute phase of MDD with SNRIs, but not SSRIs, was associated with a statistically greater number of overall adverse events vs placebo. SSRIs and SNRIs led to a greater number of study withdrawals due to adverse events vs placebo. Duloxetine increased the risk of falls that as an outcome was underreported in the literature. Few studies examined head-to-head comparisons, most trials were not powered to evaluate adverse events, and results of observational studies may be confounded. Comparative long-term studies reporting specific adverse events are needed to inform clinical decision making regarding choice of antidepressants in this population. J Am Geriatr Soc 67:1571-1581, 2019.
Topics: Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder, Major; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Observational Studies as Topic; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 31140587
DOI: 10.1111/jgs.15966 -
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 -
Journal of Perianesthesia Nursing :... Aug 2019Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via... (Meta-Analysis)
Meta-Analysis
PURPOSE
Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via 5HT3 receptor antagonism.
DESIGN
Systematic review and meta-analysis.
METHODS
We identified seven randomized controlled trials by systematically searching electronic databases that compare the efficacy of mirtazapine versus placebo or ondansetron in reducing PONV.
FINDINGS
Mirtazapine reduced PONV overall versus placebo in three studies (risk ratio [RR] = 0.44; 95% confidence interval [CI] 0.32 to 0.62) both on conventional meta-analysis and trial sequential analysis. One study comparing mirtazapine with ondansetron found similar rates of PONV (RR = 0.96; 95% CI 0.48 to 1.94). Mirtazapine reduced preoperative anxiety versus placebo or ondansetron (standardized mean difference -1.4; 95% CI -2.56 to -0.23) but increased sedation (RR = 22.47; 95% CI 5.61 to 89.93). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality of evidence was moderate to low.
CONCLUSIONS
This meta-analysis suggests that mirtazapine reduces PONV overall versus placebo. We found evidence of reduction in preoperative anxiety, although mirtazapine increased the risk of sedation.
Topics: Antiemetics; Humans; Mirtazapine; Postoperative Nausea and Vomiting
PubMed: 30879907
DOI: 10.1016/j.jopan.2018.11.006