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The International Journal of... Jul 2015Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD.
METHODS
Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model.
RESULTS
Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05-0.27; I(2) = 46%) and delayed recall (SMD 0.24; 95% CI 0.15-0.34; I(2) = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes.
CONCLUSIONS
Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall.
Topics: Antidepressive Agents; Cognition; Cognition Disorders; Depressive Disorder, Major; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26209859
DOI: 10.1093/ijnp/pyv082 -
Drug Safety 2002Panax ginseng C. A. Meyer is a perennial herb native to Korea and China and has been used as an herbal remedy in eastern Asia for thousands of years. Modern therapeutic... (Review)
Review
Panax ginseng C. A. Meyer is a perennial herb native to Korea and China and has been used as an herbal remedy in eastern Asia for thousands of years. Modern therapeutic claims refer to vitality, immune function, cancer, cardiovascular diseases, improvement of cognitive and physical performance and sexual function. A recent systematic review of randomised controlled trials found that the efficacy of ginseng root extract could not be established beyond doubt for any of these indications. In order to obtain a balanced assessment of the therapeutic value of P. ginseng it is also necessary to consider the safety profile. In view of the extremely widespread use of P. ginseng it seems important to ask whether this herbal medicine involves health risks for the consumer. This review was conducted as a systematic attempt to document and evaluate all the available safety data on P. ginseng root extracts. Systematic searches were performed in five electronic databases and the reference lists of all papers located were checked for further relevant publications. All articles containing original data on adverse events and drug interactions with P. ginseng were included. Information was also requested from 12 manufacturers of ginseng preparations, the spontaneous reporting schemes of the WHO and national drug safety bodies. No language restrictions were imposed. Data from clinical trials suggest that the incidence of adverse events with ginseng monopreparations is similar to that with placebo. The most commonly experienced adverse events are headache, sleep and gastrointestinal disorders. The possibility of more serious adverse events is indicated in isolated case reports and data from spontaneous reporting schemes; however, causality is often difficult to determine from the evidence provided. Combination products containing ginseng as one of several constituents have been associated with serious adverse events and even fatalities. Interpretation of these cases is difficult as ingredients other than P. ginseng may have caused the problems. Possible drug interactions have been reported between P. ginseng and warfarin, phenelzine and alcohol. Collectively, these data suggest that P. ginseng monopreparations are rarely associated with adverse events or drug interactions. The ones that are documented are usually mild and transient. Combined preparations are more often associated with such events but causal attribution is usually not possible.
Topics: Clinical Trials as Topic; Databases, Bibliographic; Drug Interactions; Female; Herb-Drug Interactions; Humans; Male; Panax
PubMed: 12020172
DOI: 10.2165/00002018-200225050-00003 -
Neuropsychiatric Disease and Treatment 2012This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal...
This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2-delta ligands), but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment.
PubMed: 22665997
DOI: 10.2147/NDT.S23317 -
The Cochrane Database of Systematic... Jun 2010Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly targeting affective or impulsive symptom clusters.
OBJECTIVES
To assess the effects of drug treatment in BPD patients.
SEARCH STRATEGY
We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field.
SELECTION CRITERIA
Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects.
DATA COLLECTION AND ANALYSIS
Two authors selected trials, assessed quality and extracted data, independently.
MAIN RESULTS
Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants.The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed.Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition.Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes.
AUTHORS' CONCLUSIONS
The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).
Topics: Antidepressive Agents; Antipsychotic Agents; Borderline Personality Disorder; Fatty Acids, Omega-3; Humans; Randomized Controlled Trials as Topic
PubMed: 20556762
DOI: 10.1002/14651858.CD005653.pub2 -
Journal of Clinical Psychopharmacology Oct 2010This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and... (Comparative Study)
Comparative Study Meta-Analysis Review
This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The outcome measures included mean change in Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates of response and remission. Overall, 19 publications were included. Medications included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole, phenelzine, and divalproex. The most trials were identified for quetiapine (5) and lamotrigine (6). Not all medications were associated with symptomatic improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with lamotrigine, paroxetine, aripiprazole, and lithium not being different from placebo. Highest reductions in MADRS scores versus placebo were reported for the olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], -9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, -4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to -3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All medications except paroxetine, lithium, aripiprazole, and phenelzine significantly improved the ratio of probabilities of response (overall rate, 1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo. Variability in efficacy exists between treatments of bipolar depression. Quetiapine and the olanzapine-fluoxetine combination showed the greatest symptomatic improvement. Efficacy considerations will need to be balanced against safety and tolerability of the individual agents.
Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Triazines
PubMed: 20814319
DOI: 10.1097/JCP.0b013e3181f15849 -
European Child & Adolescent Psychiatry Jun 2016Despite limited evidence, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are used to reduce symptoms of selective mutism (SM)... (Review)
Review
Despite limited evidence, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are used to reduce symptoms of selective mutism (SM) in children unresponsive to psychosocial interventions. We review existing evidence for the efficacy of these medications, limitations of the literature, and resulting treatment considerations. Bibliographic searches were conducted in Medline, Embase, PsycInfo, Web of Science and Cochrane up to June 2015. Two reviewers independently sought studies of children with SM as primary psychiatric diagnosis, which reported response to medication treatment. Abstracts were limited to those reporting original data. Two reviewers independently assessed the ten papers reporting on >2 subjects regarding study design, key results, and limitations. Heterogeneity of designs mandated a descriptive summary. Symptomatic improvement was found for 66/79 children treated with SSRIs and 4/4 children treated with phenelzine. Only 3/10 studies had unmedicated comparison groups and only two were double-blinded. This review may be affected by publication bias, missed studies, and variability of outcome measures in included studies. Although there is some evidence for symptomatic improvement in SM with medication, especially SSRIs, it is limited by small numbers, lack of comparative trials, lack of consistent measures, and lack of consistent reporting on tolerability. The clinician must weigh this paucity of evidence against the highly debilitating nature of SM, and its adverse effects on the development of those children whose progress with psychosocial interventions is limited or very slow. Studies of optimal dosage and timing of medications in relation to psychosocial treatments are also needed.
Topics: Child; Humans; Monoamine Oxidase Inhibitors; Mutism; Selective Serotonin Reuptake Inhibitors
PubMed: 26560144
DOI: 10.1007/s00787-015-0794-1 -
Clinical Practice and Epidemiology in... Sep 2006A number of studies have suggested a link between the patient's psyche and the course of inflammatory bowel disease (IBD). Although pharmacotherapy with antidepressants...
BACKGROUND
A number of studies have suggested a link between the patient's psyche and the course of inflammatory bowel disease (IBD). Although pharmacotherapy with antidepressants has not been widely explored, some investigators have proposed that treating psychological co-morbidities with antidepressants may help to control disease activity. To date a systematic analysis of the available studies assessing the efficacy of antidepressants for the control of somatic symptoms in IBD patients has not been performed.
METHODS
We searched electronic databases, without any language restriction. All relevant papers issued after 1990 were examined.
RESULTS
12 relevant publications were identified. All of them referred to non-randomised studies. Antidepressants reported in these publications included paroxetine, bupropion, amitriptyline, phenelzine, and mirtazapine. In 10 articles, paroxetine, bupropion, and phenelzine were suggested to be effective for treating both psychological and somatic symptoms in patients suffering from IBD. Amitriptyline was found ineffective for treating somatic symptoms of IBD. Mirtazapine was not recommended for IBD patients.
CONCLUSION
Although most of reviewed papers suggest a beneficial effect of treatment with antidepressants in patients with IBD, due to the lack of reliable data, it is impossible to judge the efficacy of antidepressants in IBD. Properly designed trials are justified and needed based upon the available uncontrolled data.
PubMed: 16984660
DOI: 10.1186/1745-0179-2-24 -
The American Journal of Psychiatry Jul 2011The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older). (Comparative Study)
Comparative Study Review
OBJECTIVE
The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older).
METHOD
The authors conducted an electronic database search and reviewed the 14 articles that fit predetermined criteria. Refractory depression was defined as failure to respond to at least one course of treatment for depression during the current illness episode. The authors rated the validity of studies using a standard checklist and calculated the pooled proportion of response to any treatment reported by at least three studies.
RESULTS
All the studies that met inclusion criteria investigated pharmacological treatment. Most were open-label studies, and the authors found no double-blind randomized placebo-controlled trials. The overall response rate for all active treatments investigated was 52% (95% CI=42-62; N=381). Only lithium augmentation was assessed in more than two trials, and the response rate was 42% (95% CI=21-65; N=57). Only two studies included comparison groups receiving no additional treatment, and none of the participants in these groups responded. In single randomized studies, extended-release venlafaxine was more efficacious than paroxetine, lithium augmentation more than phenelzine, and selegiline more than placebo.
CONCLUSIONS
Half of the participants responded to pharmacological treatments, indicating the importance of managing treatment-refractory depression actively in older people. The only treatment for which there was replicated evidence was lithium augmentation. Double-blind randomized controlled trials for management of treatment-refractory depression in older people, encompassing pharmacological and nonpharmacological therapies and populations that reflect the levels of physical and cognitive impairment present in the general older population with depression, are needed.
Topics: Adult; Age Factors; Aged; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder, Major; Drug Resistance; Drug Therapy, Combination; Evidence-Based Medicine; Female; Humans; Lithium Compounds; Male; Meta-Analysis as Topic; Middle Aged; Polypharmacy; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 21454919
DOI: 10.1176/appi.ajp.2011.10081165 -
Journal of Affective Disorders Mar 2021Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants.
METHODS
In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo).
RESULTS
Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments.
LIMITATIONS
The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants.
CONCLUSIONS
The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.
Topics: Antidepressive Agents; Depressive Disorder; Humans; Monoamine Oxidase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33601690
DOI: 10.1016/j.jad.2021.01.021 -
The Cochrane Database of Systematic... 2001Bulimia Nervosa (BN) represents an important public health problem and is related to serious morbidity and even mortality. This review attempted to systematically... (Review)
Review
BACKGROUND
Bulimia Nervosa (BN) represents an important public health problem and is related to serious morbidity and even mortality. This review attempted to systematically evaluate the use of antidepressant medications compared with placebo for the treatment of bulimia nervosa.
OBJECTIVES
The primary objective of this review was to determine whether using antidepressant medications was clinically effective for the treatment of bulimia nervosa. The secondary objectives were: (i) to examine whether there was a differential effect for the various classes/types of antidepressants with regard to effectiveness and tolerability (ii) to test the hypothesis that the effect of antidepressants on bulimic symptoms was independent of its effect on depressive symptoms
SEARCH STRATEGY
(1) electronic searches of MEDLINE (1966 to December 2000), EMBASE (1980-December 2000), PsycLIT (to December 2000), LILACS & SCISEARCH (to 1997) (2) the Cochrane Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register - ongoing (3) inspection of the references of all identified trials (4) contact with the pharmaceutical companies and the principal investigator of each included trial (5) inspection of the International Journal of Eating Disorders - ongoing
INCLUSION CRITERIA
every randomized, placebo-controlled trial in which antidepressant medications were compared to placebo to reduce the symptoms of bulimia nervosa in patients of any age or gender. Quality criteria: reports were considered adequate if they were classified as A or B according to the Cochrane Manual. The Jadad scale, with a cut off of 2 points, was applied to check the validity of the above referred criterion but was not used as an inclusion criterion.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two reviewers for each included trial. Dichotomous data were evaluated by the relative risk with 95% confidence intervals (CI) around this measure, based on the random effects model; continuous data were evaluated by the standardised mean difference with the 95% CI. NNT was calculated using the inverse of the absolute risk reduction.
MAIN RESULTS
Currently the review includes 16 trials comparing antidepressants with placebo: 6 trials with TCAs (imipramine, desipramine and amitryptiline), 3 with SSRIs (fluoxetine), 4 with MAOIs (phenelzine, isocarboxazid and brofaromine) and 3 with other classes of drugs (mianserine, trazodone and bupropion). Similar results were obtained in terms of efficacy for these different groups of drugs. The pooled RR for remission of binge episodes was 0.88 (95% CI 0.83-0.93; p<0,001) favoring drugs. The NNT for a mean treatment duration of 8 weeks, taking the non-remission rate in the placebo controls of 92% as a measure of the baseline risk was 9 (95% CI 6 - 16). The RR for clinical improvement, defined as a reduction of 50% or more in binge episodes was 0.63 (95% CI 0.55-0.74) and the NNT for a mean treatment duration of 9 weeks was 4 (95% CI 3 - 6), with a non-improvement rate of 67% in the placebo group. Patients treated with antidepressants were more likely to interrupt prematurely the treatment due to adverse events. Patients treated with TCAs dropped-out due to any cause more frequently that patients treated with placebo. The opposite was found for those treated with fluoxetine, suggesting it may be a more acceptable treatment. Independence between antidepressant and antibulimic effects could not be evaluated due to incomplete published data.
REVIEWER'S CONCLUSIONS
The use of a single antidepressant agent was clinically effective for the treatment of bulimia nervosa when compared to placebo, with an overall greater remission rate but a higher rate of dropouts. No differential effect regarding efficacy and tolerability among the various classes of antidepressants could be demonstrated.
Topics: Antidepressive Agents; Bulimia; Humans; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 11687198
DOI: 10.1002/14651858.CD003391