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British Journal of Clinical Pharmacology Apr 2016The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into... (Meta-Analysis)
Meta-Analysis Review
AIMS
The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category.
METHOD
A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.
RESULTS
Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.
CONCLUSIONS
Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.
Topics: Abnormalities, Drug-Induced; Female; Heart Defects, Congenital; Humans; Maternal Exposure; Paroxetine; Pregnancy; Pregnancy Trimester, First; Risk Assessment; Selective Serotonin Reuptake Inhibitors
PubMed: 26613360
DOI: 10.1111/bcp.12849 -
International Clinical... May 2008A systematic review and meta-analysis were conducted to evaluate the comparative efficacy and tolerability of second-generation antidepressants in social anxiety... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis were conducted to evaluate the comparative efficacy and tolerability of second-generation antidepressants in social anxiety disorder. Studies were identified by searching MEDLINE, Embase, The Cochrane Library, PsychLit, and the International Pharmaceutical Abstracts from January 1980 through October 2006. Comparative evidence was summarized and indirect comparisons were made using network meta-analysis. Only three head-to-head trials were identified; comparative trials found only minimal differences in efficacy between escitalopram and paroxetine, and no statistically significant differences in efficacy between extended-release venlafaxine and paroxetine. Pooled evidence from 15 placebo-controlled trials suggests that escitalopram [relative benefit (RB) 1.3; 95% confidence interval (CI) 1.2-1.5], paroxetine (RB 1.9; 95% CI 1.5-2.3), sertraline (RB 1.8; 95% CI 1.5-2.2), and venlafaxine (RB 1.7; 95% CI 1.5-1.9) all produce significantly more responders than placebo; evidence favored fluvoxamine over placebo but was not significant (RB 1.5; 95% CI 0.9-2.4). Network meta-analysis did not reveal differences in efficacy among drugs. Overall, a fair amount of evidence supports the efficacy of escitalopram, fluvoxamine, paroxetine, sertraline, and venlafaxine in social anxiety disorder. The drugs do not differ in efficacy, although their adverse event profiles do.
Topics: Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Disability Evaluation; Evidence-Based Medicine; Humans; Phobic Disorders; Recovery of Function; Severity of Illness Index; Treatment Outcome
PubMed: 18408531
DOI: 10.1097/YIC.0b013e3282f4224a -
Sexual Health Apr 2016Eutectic Mixture of Local Anaesthetics (EMLA) is recommended for use off-label as a treatment for premature ejaculation (PE). Other topical anaesthetics are available,... (Meta-Analysis)
Meta-Analysis Review
Eutectic Mixture of Local Anaesthetics (EMLA) is recommended for use off-label as a treatment for premature ejaculation (PE). Other topical anaesthetics are available, some of which have been evaluated against oral treatments. The purpose of this systematic review was to evaluate the evidence from randomised controlled trials (RCTs) for topical anaesthetics in the management of PE. Bibliographic databases including MEDLINE were searched to August 2014. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. IELT and other outcomes were pooled across RCTs in a meta-analysis. Between-trial heterogeneity was assessed. Nine RCTs were included. Seven were of unclear methodological quality. Pooled evidence (two RCTs, 43 participants) suggests that EMLA is significantly more effective than placebo at increasing IELT (P<0.00001). Individual RCT evidence also suggests that Topical Eutectic-like Mixture for Premature Ejaculation (TEMPE) spray and lidocaine gel are both significantly more effective than placebo (P=0.003; P<0.00001); and lidocaine gel is significantly more effective than sildenafil or paroxetine (P=0.01; P=0.0001). TEMPE spray is associated with significantly more adverse events than placebo (P=0.003). More systemic adverse events are reported with tramadol, sildenafil and paroxetine than with lidocaine gel. Diverse methods of assessing sexual satisfaction and ejaculatory control with topical anaesthetics are reported and evidence is conflicting. Topical anaesthetics appear more effective than placebo, paroxetine and sildenafil at increasing IELT in men with PE. However, the methodological quality of the existing RCT evidence base is uncertain.
Topics: Anesthetics, Local; Humans; Male; Premature Ejaculation; Randomized Controlled Trials as Topic
PubMed: 26599522
DOI: 10.1071/SH15042 -
Iranian Journal of Medical Sciences May 2022Hot flashes (HF) are a common symptom during the menopausal transition. It is therefore important to identify effective drugs that can alleviate HF. This study aimed to... (Review)
Review
The Efficacy and Safety of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors in the Treatment of Menopausal Hot Flashes: A Systematic Review of Clinical Trials.
BACKGROUND
Hot flashes (HF) are a common symptom during the menopausal transition. It is therefore important to identify effective drugs that can alleviate HF. This study aimed to systematically review published clinical trials on the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of HF in healthy menopausal women.
METHODS
In this systematic review, articles published during 2003-2019 in PubMed, MEDLINE, Web of Science, Scopus, Science Direct, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials, and Google Scholar as well as Iranian databases such as SID, and Magiran were searched. The quality of the selected articles was assessed using the Jadad score calculation.
RESULTS
Thirty-six articles on randomized controlled trials were included in this study, out of which 27 articles had acceptable, and nine had weak methodological quality. Findings on SSRIs class of drugs indicated that escitalopram, paroxetine, and fluoxetine have higher efficacy and safety in the treatment of menopausal HF than other drugs. Studies on the effectiveness of sertraline, citalopram, and fluvoxamine are limited in number or show inconsistent results. Therefore, further high-quality studies are required to confirm their effectiveness in alleviating HF. Within the SNRIs class, venlafaxine and desvenlafaxine showed significant efficacy in the treatment of menopausal HF. However, studies on the effectiveness of duloxetine are also limited, which requires further research.
CONCLUSION
Most studies have indicated the efficacy and safety of some antidepressants, such as SSRIs and SNRIs, in decreasing the frequency and severity of HF. These drugs are therefore recommended for the treatment of menopausal HF.
Topics: Female; Hot Flashes; Humans; Iran; Menopause; Norepinephrine; Randomized Controlled Trials as Topic; Serotonin; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 35634530
DOI: 10.30476/ijms.2020.87687.1817 -
The Cochrane Database of Systematic... May 2017Approximately 20% of stroke patients experience clinically significant levels of anxiety at some point after stroke. Physicians can treat these patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 20% of stroke patients experience clinically significant levels of anxiety at some point after stroke. Physicians can treat these patients with antidepressants or other anxiety-reducing drugs, or both, or they can provide psychological therapy. This review looks at available evidence for these interventions. This is an update of the review first published in October 2011.
OBJECTIVES
The primary objective was to assess the effectiveness of pharmaceutical, psychological, complementary, or alternative therapeutic interventions in treating stroke patients with anxiety disorders or symptoms. The secondary objective was to identify whether any of these interventions for anxiety had an effect on quality of life, disability, depression, social participation, caregiver burden, or risk of death.
SEARCH METHODS
We searched the trials register of the Cochrane Stroke Group (January 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2017, Issue 1: searched January 2017); MEDLINE (1966 to January 2017) in Ovid; Embase (1980 to January 2017) in Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1937 to January 2017) in EBSCO; and PsycINFO (1800 to January 2017) in Ovid. We conducted backward citation searches of reviews identified through database searches and forward citation searches of included studies. We contacted researchers known to be involved in related trials, and we searched clinical trials registers for ongoing studies.
SELECTION CRITERIA
We included randomised trials including participants with a diagnosis of both stroke and anxiety for which treatment was intended to reduce anxiety. Two review authors independently screened and selected titles and abstracts for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias. We performed a narrative review. We planned to do a meta-analysis but were unable to do so as included studies were not sufficiently comparable.
MAIN RESULTS
We included three trials (four interventions) involving 196 participants with stroke and co-morbid anxiety. One trial (described as a 'pilot study') randomised 21 community-dwelling stroke survivors to four-week use of a relaxation CD or to wait list control. This trial assessed anxiety using the Hospital Anxiety and Depression Scale and reported a reduction in anxiety at three months among participants who had used the relaxation CD (mean (standard deviation (SD) 6.9 (± 4.9) and 11.0 (± 3.9)), Cohen's d = 0.926, P value = 0.001; 19 participants analysed).The second trial randomised 81 participants with co-morbid anxiety and depression to paroxetine, paroxetine plus psychotherapy, or standard care. Mean levels of anxiety severity scores based on the Hamilton Anxiety Scale (HAM-A) at follow-up were 5.4 (SD ± 1.7), 3.8 (SD ± 1.8), and 12.8 (SD ± 1.9), respectively (P value < 0.01).The third trial randomised 94 stroke patients, also with co-morbid anxiety and depression, to receive buspirone hydrochloride or standard care. At follow-up, the mean levels of anxiety based on the HAM-A were 6.5 (SD ± 3.1) and 12.6 (SD ± 3.4) in the two groups, respectively, which represents a significant difference (P value < 0.01). Half of the participants receiving paroxetine experienced adverse events that included nausea, vomiting, or dizziness; however, only 14% of those receiving buspirone experienced nausea or palpitations. Trial authors provided no information about the duration of symptoms associated with adverse events. The trial of relaxation therapy reported no adverse events.The quality of the evidence was very low. Each study included a small number of participants, particularly the study of relaxation therapy. Studies of pharmacological agents presented details too limited to allow judgement of selection, performance, and detection bias and lack of placebo treatment in control groups. Although the study of relaxation therapy had allocated participants to treatment using an adequate method of randomisation, study recruitment methods might have introduced bias, and drop-outs in the intervention group may have influenced results.
AUTHORS' CONCLUSIONS
Evidence is insufficient to guide the treatment of anxiety after stroke. Further well-conducted randomised controlled trials (using placebo or attention controls) are required to assess pharmacological agents and psychological therapies.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Buspirone; Depression; Humans; Middle Aged; Paroxetine; Pilot Projects; Psychotherapy; Randomized Controlled Trials as Topic; Relaxation Therapy; Stroke
PubMed: 28535332
DOI: 10.1002/14651858.CD008860.pub3 -
Progress in Neuro-psychopharmacology &... Jul 2022Sleep quality disturbances are a common occurrence in post-traumatic stress disorder (PTSD) and may remain after evidence-based treatment for PTSD has been implemented.... (Meta-Analysis)
Meta-Analysis Review
Efficacy, acceptability, and tolerability of antidepressants for sleep quality disturbances in post-traumatic stress disorder: A systematic review and network meta-analysis.
Sleep quality disturbances are a common occurrence in post-traumatic stress disorder (PTSD) and may remain after evidence-based treatment for PTSD has been implemented. If left untreated, sleep disturbance can perpetuate or aggravate the disorder. A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) was conducted comparing efficacy, acceptability, and tolerability among antidepressants for sleep quality improvement in PTSD, using Cochane's RoB2.0 and GRADE approach for NMA. The Cochrane Library, LILACS, PsycINFO, PTSDpubs, and PubMed Central databases were searched from inception to November 29, 2020, leading to the retrieval of 3733 reports. After the selection process, seven RCTs were included in the review (N = 600). We found low certainty of evidence (LCE) that sertraline may improve sleep quality (measured by PSQI) in adult patients with PTSD (MD -0.48, 95% CrI -0.63 to -0.32). Sertraline was as well accepted (RR 1.12, 95% CrI -0.83 to 1.52, very low certainty [VLCE]) and as well tolerated as placebo (RR 0.58, 95% CrI 0.28 to 1.14, LCE). Mirtazapine (MD -3.35, 95% CrI -9.06 to 2.39, LCE), paroxetine (MD -3.13, 95% CrI -7.47 to 1.26, VLCE), nefazodone (MD -0.25, 95% CrI -5.95 to 5.38, VLCE), and bupropion (MD -2.28, 95% CrI -4.75 to 0.21, VLCE) were similar to placebo for improving sleep quality. These antidepressants resulted in little or no benefit for sleep in PTSD. Although the NMA suggested that sertraline may improve sleep in PTSD compared to placebo, due to the low certainty, these estimates are not robust enough to guide clinical decisions.
Topics: Adult; Antidepressive Agents; Humans; Network Meta-Analysis; Sertraline; Sleep Quality; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 35395322
DOI: 10.1016/j.pnpbp.2022.110557 -
The Cochrane Database of Systematic... Sep 2012This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms.
OBJECTIVES
To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit is due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states.
SEARCH METHODS
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; PsycINFO; CINAHL; Web of Science; BIOSIS; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 5 January 2012.
SELECTION CRITERIA
Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus.
DATA COLLECTION AND ANALYSIS
Two authors critically appraised the retrieved studies and extracted data independently. Where necessary we contacted study authors for further information.
MAIN RESULTS
Six trials involving 610 patients were included. Trial quality was generally low. Four of the trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. One study investigated trazodone, an atypical antidepressant, versus placebo. Only the trial using the SSRI drug reached the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop-out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the trials assessing tricyclic antidepressants suggested that there was a slight improvement in tinnitus but these effects may have been attributable to methodological bias. The trial that investigated the SSRI drug found no overall improvement in any of the validated outcome measures that were used in the study although there was possible benefit for a subgroup that received higher doses of the drug. This observation merits further investigation. In the trial investigating trazodone, the results showed an improvement in tinnitus intensity and in quality of life after treatment, but in neither case reached statistical significance. Reports of side effects including sedation, sexual dysfunction and dry mouth were common.
AUTHORS' CONCLUSIONS
There is as yet insufficient evidence to say that antidepressant drug therapy improves tinnitus.
Topics: Amitriptyline; Antidepressive Agents; Depression; Humans; Nortriptyline; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Tinnitus; Trazodone; Trimipramine
PubMed: 22972065
DOI: 10.1002/14651858.CD003853.pub3 -
The Cochrane Database of Systematic... Jul 2012Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode. Systematic reviews have already highlighted some differences in efficacy between second-generation antidepressants. Citalopram, one of the first selective serotonin reuptake inhibitors (SSRI) introduced in the market, is one of these antidepressant drugs that clinicians use for routine depression care.
OBJECTIVES
To assess the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with tricyclics, heterocyclics, other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression.
SEARCH METHODS
We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012. No language restriction was applied. We contacted pharmaceutical companies and experts in this field for supplemental data.
SELECTION CRITERIA
Randomised controlled trials allocating patients with major depression to citalopram versus any other antidepressants.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), patient acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
MAIN RESULTS
Thirty-seven trials compared citalopram with other antidepressants (such as tricyclics, heterocyclics, SSRIs and other antidepressants, either conventional ones, such as mirtazapine, venlafaxine and reboxetine, or non-conventional, like hypericum). Citalopram was shown to be significantly less effective than escitalopram in achieving acute response (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.08 to 2.02), but more effective than paroxetine (OR 0.65, 95% CI 0.44 to 0.96) and reboxetine (OR 0.63, 95% CI 0.43 to 0.91). Significantly fewer patients allocated to citalopram withdrew from trials due to adverse events compared with patients allocated to tricyclics (OR 0.54, 95% CI 0.38 to 0.78) and fewer patients allocated to citalopram reported at least one side effect than reboxetine or venlafaxine (OR 0.64, 95% CI 0.42 to 0.97 and OR 0.46, 95% CI 0.24 to 0.88, respectively).
AUTHORS' CONCLUSIONS
Some statistically significant differences between citalopram and other antidepressants for the acute phase treatment of major depression were found in terms of efficacy, tolerability and acceptability. Citalopram was more efficacious than paroxetine and reboxetine and more acceptable than tricyclics, reboxetine and venlafaxine, however, it seemed to be less efficacious than escitalopram. As with most systematic reviews in psychopharmacology, the potential for overestimation of treatment effect due to sponsorship bias and publication bias should be borne in mind when interpreting review findings. Economic analyses were not reported in the included studies, however, cost effectiveness information is needed in the field of antidepressant trials.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram; Cyclohexanols; Depression; Humans; Morpholines; Paroxetine; Reboxetine; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 22786497
DOI: 10.1002/14651858.CD006534.pub2 -
The Cochrane Database of Systematic... May 2014Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions.Imipramine is a tricyclic antidepressant that is occasionally used to treat neuropathic pain.
OBJECTIVES
To assess the analgesic efficacy of imipramine for chronic neuropathic pain in adults, and to assess the associated adverse events.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE on 18 November 2013, as well as the reference lists of retrieved papers and other reviews. We also used our own handsearched database for older studies, and two clinical trials databases.
SELECTION CRITERIA
We included randomised, double-blind studies of at least two weeks' duration comparing imipramine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 and over. We included only articles with full journal publication and extended trial abstracts and summaries.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier from data involving small numbers of participants which was considered very likely to be biased or used outcomes of limited clinical utility, or both.
MAIN RESULTS
Five studies treated 168 participants with painful diabetic neuropathy or polyneuropathy. The mean age in individual studies was between 47 and 56 years. Four studies used a cross-over, and one a parallel group design; 126 participants were randomised to receive imipramine 25 mg to 350 mg daily (most took 100 mg to 150 mg daily). Comparators were placebo (an active placebo in one study), paroxetine, mianserin, venlafaxine, and amitriptyline, and treatment was given for 2 to 12 weeks. All studies had one or more sources of potential major bias.No study provided first or second tier evidence for any outcome. No data were available on the proportion of people with at least 50% or 30% reduction in pain or equivalent, and data were available from only one study for our other primary outcome of Patient Global Impression of Change, reported as patient evaluation of pain relief of complete or good. No pooling of data was possible, but third tier evidence in individual studies indicated some improvement in pain relief with imipramine compared with placebo, although this is was very low quality evidence, derived mainly from group mean data and completer analyses, in small, short duration studies where major bias is possible.Four studies reported some information about adverse events, but reporting was inconsistent and fragmented, and the quality of evidence was very low. Participants taking imipramine generally experienced more adverse events, notably dry mouth, and a higher rate of withdrawal due to adverse events, than did participants taking placebo.
AUTHORS' CONCLUSIONS
This review found little evidence to support the use of imipramine to treat neuropathic pain. There was very low quality evidence of benefit but this came from studies that were methodologically flawed and potentially subject to major bias. Effective medicines with much greater supportive evidence are available.
Topics: Adult; Analgesics; Antidepressive Agents, Tricyclic; Diabetic Neuropathies; Humans; Imipramine; Middle Aged; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 24838845
DOI: 10.1002/14651858.CD010769.pub2 -
BMJ Medicine 2022To assess and clarify the relations between selective serotonin reuptake inhibitor (SSRI) dose efficacy, acceptability (early treatment discontinuation (dropouts)), and...
OBJECTIVE
To assess and clarify the relations between selective serotonin reuptake inhibitor (SSRI) dose efficacy, acceptability (early treatment discontinuation (dropouts)), and tolerability (reported adverse drug effects), and critically evaluate methods previously used to examine SSRI dose-response effects for the treatment of depression in adults.
DESIGN
Systematic review of reviews and meta-narrative synthesis.
DATA SOURCES
Embase, Medline, PsycINFO, Scopus, and the Cochrane Collaboration library, from 1975 to December 2021. Reference lists of national depression treatment guidelines were systemically searched by hand.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Reviews assessing SSRI monotherapy dose-response effects for the treatment of depression in adults (age ≥18 years) reporting efficacy, acceptability, or tolerability. Reviews meeting inclusion criteria had a high degree of heterogeneity, due to methodological diversity; therefore, a meta-narrative synthesis approach was applied. Standard daily doses were defined as 20 mg citalopram, fluoxetine, paroxetine; 50 mg sertraline; and 10 mg escitalopram. Risk of bias was assessed using the Risk of Bias in Systematic Reviews tool, in line with Cochrane recommendations.
RESULTS
The search identified 9138 records; 387 full text reports were assessed for eligibility, 42 of which matched the inclusion criteria. The majority, 83% (n=35), of reviews included data for studies with a duration of ≤12 weeks (ie, the acute phase of depression treatment). Of 39 reviews assessing efficacy, the majority (n=26) indicated that individual SSRIs and SSRI class demonstrated flat dose-response effects; standard doses were optimal for efficacy. Acceptability or tolerability were assessed in 28 reviews. Higher than standard daily doses were associated with higher dropout rates and a greater incidence of adverse drug effects (eg, nausea, sexual dysfunction, fatigue, anxiety). Despite a range of methods being reported, there was an overall consensus regarding SSRI dose related efficacy, dropouts, and adverse drug effects.
CONCLUSION
Standard daily doses of SSRIs for the treatment of depression in adults provide a favourable balance between efficacy, acceptability, and tolerability. Patients are encouraged to talk to their prescriber or community pharmacist if they experience adverse effects or have any concerns about their drug treatments.
PubMed: 36936596
DOI: 10.1136/bmjmed-2021-000017