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Expert Opinion on Pharmacotherapy 2023Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more... (Review)
Review
INTRODUCTION
Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more hospitalizations are all factors that are related to dysthymia. Given the significant prevalence of dysthymia (including persistent depressive disorder) worldwide, its comorbidity with several mental disorders, and the detrimental effects of these comorbidities, it is important to conduct a systematic review to compare the effects of pharmacological acute and maintenance treatments for dysthymia with placebo and standard care in the last 10 years, based on the publication of DSM5.
AREAS COVERED
This systematic review was performed according to PRISMA guidelines. Databases, including PubMed and Cochrane Central Register of Controlled Trials, were searched to assess the effects of pharmacological acute and maintenance treatments for dysthymia in comparison with placebo and treatment as usual.
EXPERT OPINION
Our review shows that SSRIs and SNRIs present efficacy for dysthymia treatment, and L-Acetylcarnitine should be investigated further for this condition in elderly patients. The comparison of antidepressant medication versus placebo showed coherent results based on three studies favoring pharmacotherapy as an effective treatment for participants with dysthymia. However, the scarcity of research on continuation and maintenance therapy in people with dysthymia highlights the need for more primary research.
Topics: Aged; Humans; Antidepressive Agents; Comorbidity; Depressive Disorder; Dysthymic Disorder; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 37787056
DOI: 10.1080/14656566.2023.2265809 -
The Australian and New Zealand Journal... Jul 2022Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in diagnostic criteria and in the overall study design. The aim of this study was to systematically review and, where appropriate, meta-analyse estimates related to the pairwise comorbidity between mood disorders and substance-related disorders, after sorting these estimates by various study designs.
METHODS
We searched PubMed (MEDLINE), Embase, CINAHL and Web of Science for publications between 1980 and 2017 regardless of geographical location and language. We meta-analysed estimates from original articles in 4 broadly defined mood and 35 substance-related disorders.
RESULTS
After multiple eligibility steps, we included 120 studies for quantitative analysis. In general, regardless of variations in diagnosis type, temporal order or use of adjustments, there was substantial comorbidity between mood and substance-related disorders. We found a sixfold elevated risk between broadly defined mood disorder and drug dependence (odds ratio = 5.7) and fivefold risk between depression and cannabis dependence (odds ratio = 4.9) while the highest pooled estimate, based on period prevalence risk, was found between broadly defined dysthymic disorder and drug dependence (odds ratio = 11.3). Based on 56 separate meta-analyses, all pooled odds ratios were above 1, and 46 were significantly greater than 1 (i.e. the 95% confidence intervals did not include 1).
CONCLUSION
This review found robust and consistent evidence of an increased risk of comorbidity between many combinations of mood and substance-related disorders. We also identified a number of under-researched mood and substance-related disorders, suitable for future scrutiny. This review reinforces the need for clinicians to remain vigilant in order to promptly identify and treat these common types of comorbidity.
Topics: Comorbidity; Humans; Mood Disorders; Odds Ratio; Prevalence; Substance-Related Disorders
PubMed: 34708662
DOI: 10.1177/00048674211054740 -
Acta Psychiatrica Scandinavica Jun 2023Quality of Life (QoL) is an important outcome in mental disorders. We investigated whether antidepressant pharmacotherapy improved QoL vs. placebo among patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quality of Life (QoL) is an important outcome in mental disorders. We investigated whether antidepressant pharmacotherapy improved QoL vs. placebo among patients with MDD.
METHODS
Systematic literature search in CENTRAL, Medline, PubMed Central, and PsycINFO of double-blind, placebo-controlled RCTs. Screening, inclusion, extraction, and risk of bias assessment were conducted independently by two reviewers. We calculated summary standardized mean differences (SMD) with 95%-CIs. We followed Cochrane Collaboration's Handbook of Systematic Reviews and Meta-Analyses and PRISMA guidelines (protocol registration at OSF).
RESULTS
We selected 46 RCTs out of 1807 titles and abstracts screened, including 16.171 patients, 9131 on antidepressants and 7040 on placebo, a mean age of 50.9 years, with 64.8% women. Antidepressant drug treatment resulted in a SMD in QoL of 0.22 ([95%-CI: 0.18; 0.26] I 39%) vs. placebo. SMDs differed by indication: 0.38 ([0.29; 0.46] I 0%) in maintenance studies, 0.21 ([0.17; 0.25] I 11%) in acute treatment studies, and 0.11 ([-0.05; 0.26], I 51%) in studies focussing on patients with a physical condition and major depression. There was no indication of subtstantial small study effects, but 36 RCTs had a high or uncertain risk of bias, particularly maintenance trials. QoL and antidepressive effect sizes were associated (Spearman's rho 0.73, p < 0.001).
CONCLUSIONS
Antidepressants' effects on QoL are small in primary MDD, and doubtful in secondary major depression and maintenance trials. The strong correlation of QoL and antidepressive effects indicates that the current practice of measuring QoL may not provide sufficient additional insights into the well-being of patients.
Topics: Humans; Female; Middle Aged; Male; Depressive Disorder, Major; Quality of Life; Antidepressive Agents; Dysthymic Disorder; Randomized Controlled Trials as Topic
PubMed: 36905396
DOI: 10.1111/acps.13541 -
The Cochrane Database of Systematic... Mar 2023Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap... (Review)
Review
BACKGROUND
Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have a negative impact in terms of quality of life, compliance with anticancer treatment, suicide risk and possibly the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results.
OBJECTIVES
To evaluate the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage).
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was November 2022.
SELECTION CRITERIA
We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was 1. efficacy as a continuous outcome. Our secondary outcomes were 2. efficacy as a dichotomous outcome, 3. Social adjustment, 4. health-related quality of life and 5. dropouts. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified 14 studies (1364 participants), 10 of which contributed to the meta-analysis for the primary outcome. Six of these compared antidepressants and placebo, three compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update, we included four additional studies, three of which contributed data for the primary outcome. For acute-phase treatment response (six to 12 weeks), antidepressants may reduce depressive symptoms when compared with placebo, even though the evidence is very uncertain. This was true when depressive symptoms were measured as a continuous outcome (standardised mean difference (SMD) -0.52, 95% confidence interval (CI) -0.92 to -0.12; 7 studies, 511 participants; very low-certainty evidence) and when measured as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.74, 95% CI 0.57 to 0.96; 5 studies, 662 participants; very low-certainty evidence). No studies reported data on follow-up response (more than 12 weeks). In head-to-head comparisons, we retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs) and for mirtazapine versus TCAs. There was no difference between the various classes of antidepressants (continuous outcome: SSRI versus TCA: SMD -0.08, 95% CI -0.34 to 0.18; 3 studies, 237 participants; very low-certainty evidence; mirtazapine versus TCA: SMD -4.80, 95% CI -9.70 to 0.10; 1 study, 25 participants). There was a potential beneficial effect of antidepressants versus placebo for the secondary efficacy outcomes (continuous outcome, response at one to four weeks; very low-certainty evidence). There were no differences for these outcomes when comparing two different classes of antidepressants, even though the evidence was very uncertain. In terms of dropouts due to any cause, we found no difference between antidepressants compared with placebo (RR 0.85, 95% CI 0.52 to 1.38; 9 studies, 889 participants; very low-certainty evidence), and between SSRIs and TCAs (RR 0.83, 95% CI 0.53 to 1.22; 3 studies, 237 participants). We downgraded the certainty of the evidence because of the heterogeneous quality of the studies, imprecision arising from small sample sizes and wide CIs, and inconsistency due to statistical or clinical heterogeneity.
AUTHORS' CONCLUSIONS
Despite the impact of depression on people with cancer, the available studies were few and of low quality. This review found a potential beneficial effect of antidepressants against placebo in depressed participants with cancer. However, the certainty of evidence is very low and, on the basis of these results, it is difficult to draw clear implications for practice. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which drug to prescribe may be based on the data on antidepressant efficacy in the general population of people with major depression, also taking into account that data on people with other serious medical conditions suggest a positive safety profile for the SSRIs. Furthermore, this update shows that the usage of the newly US Food and Drug Administration-approved antidepressant esketamine in its intravenous formulation might represent a potential treatment for this specific population of people, since it can be used both as an anaesthetic and an antidepressant. However, data are too inconclusive and further studies are needed. We conclude that to better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.
Topics: Adult; Humans; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depression; Depressive Disorder, Major; Mirtazapine; Neoplasms; Selective Serotonin Reuptake Inhibitors
PubMed: 36999619
DOI: 10.1002/14651858.CD011006.pub4 -
Depression and Anxiety Jan 2019There is still uncertainty if and to what extent chronic depression (CD) presents with specific features especially in contrast to the nonchronic course of major... (Comparative Study)
Comparative Study
BACKGROUND
There is still uncertainty if and to what extent chronic depression (CD) presents with specific features especially in contrast to the nonchronic course of major depressive disorder (non-CD). This systematic review aims to summarize the existing literature regarding sociodemographic factors, psychopathology, and course of disease in patients with CD in comparison to patients with non-CD.
METHODS
A structured database search (MEDLINE, PsycINFO, Web of Science, CENTRAL) was performed. All studies comparing CD with non-CD patients were included. Twenty-eight studies, including cohort studies, cross-sectional studies, and observational studies, were identified in which both subgroups were diagnosed according to DSM-IV or DSM-5, respectively. Primary outcome were group comparisons focused on sociodemographic factors, childhood adversity, onset of the disorder, comorbidities, severity and course of the depressive symptoms, and specific psychopathology.
RESULTS
Patients with CD had an earlier onset of depressive symptoms, higher rates of psychiatric comorbidities, and a complicated treatment course (e.g., higher rates of suicidality) compared to non-CD. We also found some evidence for specific features in the psychopathology of CD patients (submissive and hostile interpersonal styles) in contrast to non-CD patients. Results were inconsistent with regard to childhood maltreatment. No differences were found regarding the severity of depressive symptoms and most sociodemographic factors.
CONCLUSION
Despite some inconsistencies, the results of this review verified important differences between CD and non-CD. However, future research is needed to characterize especially the specific psychopathology of CD in comparison to non-CD patients to develop more tailored treatment strategies.
Topics: Cohort Studies; Comorbidity; Cross-Sectional Studies; Depression; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Humans
PubMed: 30300454
DOI: 10.1002/da.22835 -
Depression and Anxiety Aug 2014We aimed to synthesize the available evidence on the relative efficacy and acceptability of specific treatments for persistent depressive disorder. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aimed to synthesize the available evidence on the relative efficacy and acceptability of specific treatments for persistent depressive disorder.
METHODS
We searched several databases up to January 2013 and included randomized controlled trials that compared acute pharmacological, psychotherapeutic, and combined interventions with each other or placebo. The outcome measures were the proportion of patients who responded to (efficacy) or dropped out from (acceptability) the allocated treatment. Data synthesis was performed with network meta-analysis.
RESULTS
A network of 45 trials that tested 28 drugs included data from 5,806 and 5,348 patients concerning efficacy and acceptability, respectively. A second network of 15 trials that tested five psychotherapeutic and five combined interventions included data from 2,657 and 2,719 patients concerning efficacy and acceptability, respectively. Among sufficiently tested treatments, fluoxetine (odds ratio (OR) 2.94), paroxetine (3.79), sertraline (4.47), moclobemide (6.98), imipramine (4.53), ritanserin (2.35), amisulpride (5.63), and acetyl-l-carnitine (5.67) were significantly more effective than placebo. Pairwise comparisons showed advantages of moclobemide (2.38) and amisulpride (1.92) over fluoxetine. Sertraline (0.57) and amisulpride (0.53) showed a lower dropout rate than imipramine. Interpersonal psychotherapy with medication outperformed medication alone in chronic major depression but not in dysthymia. Evidence on cognitive behavioral analysis system of psychotherapy plus medication was partly inconclusive. Interpersonal psychotherapy was less effective than medication (0.48) and cognitive behavioral analysis system of psychotherapy (0.45). Several other treatments were tested in single studies.
CONCLUSIONS
Several evidence-based acute pharmacological, psychotherapeutic, and combined treatments for persistent depressive disorder are available with significant differences between them.
Topics: Depressive Disorder, Treatment-Resistant; Humans; Patient Compliance; Treatment Outcome
PubMed: 24448972
DOI: 10.1002/da.22236 -
Molecular Psychiatry Jun 2023Comorbid mental disorders in subjects at clinical high risk for psychosis (CHR-P) may impact preventive care. We conducted a PRISMA/MOOSE-compliant systematic... (Meta-Analysis)
Meta-Analysis
Comorbid mental disorders in subjects at clinical high risk for psychosis (CHR-P) may impact preventive care. We conducted a PRISMA/MOOSE-compliant systematic meta-analysis, searching PubMed/PsycInfo up to June 21st, 2021 for observational studies/randomized controlled trials reporting on comorbid DSM/ICD-mental disorders in CHR-P subjects ( protocol ). The primary and secondary outcomes were baseline and follow-up prevalence of comorbid mental disorders. We also explored the association of comorbid mental disorders compared with CHR-P versus psychotic/non-psychotic control groups, their impact on baseline functioning and transition to psychosis. We conducted random-effects meta-analyses, meta-regression, and assessed heterogeneity/publication bias/quality (Newcastle Ottawa Scale, NOS). We included 312 studies (largest meta-analyzed sample = 7834, any anxiety disorder, mean age = 19.98 (3.40), females = 43.88%, overall NOS > 6 in 77.6% of studies). The prevalence was 0.78 (95% CI = 0.73-0.82, k = 29) for any comorbid non-psychotic mental disorder, 0.60 (95% CI = 0.36-0.84, k = 3) for anxiety/mood disorders, 0.44 (95% CI = 0.39-0.49, k = 48) for any mood disorders, 0.38 (95% CI = 0.33-0.42, k = 50) for any depressive disorder/episode, 0.34 (95% CI = 0.30-0.38, k = 69) for any anxiety disorder, 0.30 (95% CI 0.25-0.35, k = 35) for major depressive disorders, 0.29 (95% CI, 0.08-0.51, k = 3) for any trauma-related disorder, 0.23 (95% CI = 0.17-0.28, k = 24) for any personality disorder, and <0.23 in other mental disorders (I > 50% in 71.01% estimates). The prevalence of any comorbid mental disorder decreased over time (0.51, 95% CI = 0.25-0.77 over 96 months), except any substance use which increased (0.19, 95% CI = 0.00-0.39, k = 2, >96 months). Compared with controls, the CHR-P status was associated with a higher prevalence of anxiety, schizotypal personality, panic, and alcohol use disorders (OR from 2.90 to 1.54 versus without psychosis), a higher prevalence of anxiety/mood disorders (OR = 9.30 to 2.02) and lower prevalence of any substance use disorder (OR = 0.41, versus psychosis). Higher baseline prevalence of alcohol use disorder/schizotypal personality disorder was negatively associated with baseline functioning (beta from -0.40 to -0.15), while dysthymic disorder/generalized anxiety disorder with higher functioning (beta 0.59 to 1.49). Higher baseline prevalence of any mood disorder/generalized anxiety disorder/agoraphobia (beta from -2.39 to -0.27) was negatively associated with transition to psychosis. In conclusion, over three-quarters of CHR-P subjects have comorbid mental disorders, which modulate baseline functionig and transition to psychosis. Transdiagnostic mental health assessment should be warranted in subjects at CHR-P.
Topics: Female; Humans; Young Adult; Agoraphobia; Alcoholism; Depressive Disorder, Major; Prevalence; Psychotic Disorders; Male; Adolescent
PubMed: 37296309
DOI: 10.1038/s41380-023-02029-8 -
Open Access Rheumatology : Research and... 2019Patients with rheumatoid arthritis (RA) are prone to depression due to several factors related to their RA, including chronic and persistent pain, functional disability,... (Review)
Review
Patients with rheumatoid arthritis (RA) are prone to depression due to several factors related to their RA, including chronic and persistent pain, functional disability, economic constraints, and the side effects of RA medication. Previous Iranian studies showed conflicting and inconclusive findings regarding the prevalence of depression among RA patients. Therefore, this systematic review and meta-analysis was conducted to estimate the true prevalence of depression in Iranian patients with RA. Search for eligible articles was performed using the keywords of depression, depressive disorder, dysthymic disorder, major depressive disorder, RA, and Iran, and their possible combinations in the following databases: Scientific Information Database, MagIran, Web of Science/ISI, PubMed, and Scopus. The search was restricted to articles published in Persian and English languages. The meta-analysis was performed using the random effects model, and the data were analyzed using the STATA software version 12. Overall, six articles were selected; the overall prevalence of depression among the Iranian patients with RA was 65.58% (95% CI: 56.53%-74.62%). There were no significant relationships between the prevalence of depression and articles' methodological quality and year of publication, participants' age, sample size, and duration of disease. More than half of RA patients suffer from depression. The overlap between the physical symptoms of RA and depression in this group of patients makes it difficult to correctly diagnose depression; therefore, initiative and efforts are required to improve the identification of early depression symptoms in RA patients in order to effectively manage their depression.
PubMed: 30863193
DOI: 10.2147/OARRR.S191459 -
The Cochrane Database of Systematic... Apr 2018Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results.
OBJECTIVES
To assess the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage).
SEARCH METHODS
We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 6), MEDLINE Ovid (1946 to June week 4 2017), Embase Ovid (1980 to 2017 week 27) and PsycINFO Ovid (1987 to July week 4 2017). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials.
SELECTION CRITERIA
We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis).
DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into Review Manager 5 using a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We retrieved a total of 10 studies (885 participants), seven of which contributed to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update we included one additional unpublished study. These new data contributed to the secondary analysis, while the results of the primary analysis remained unchanged.For acute-phase treatment response (6 to 12 weeks), we found no difference between antidepressants as a class and placebo on symptoms of depression measured both as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants; very low certainty evidence) and as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants; very low certainty evidence). No trials reported data on follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, showing no difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants; very low certainty evidence). No clear evidence of a beneficial effect of antidepressants versus either placebo or other antidepressants emerged from our analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low certainty evidence). In terms of dropouts due to any cause, we found no difference between antidepressants as a class compared with placebo (RR 0.85, 95% CI 0.52 to 1.38, seven RCTs, 479 participants; very low certainty evidence), and between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the certainty (quality) of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity.
AUTHORS' CONCLUSIONS
Despite the impact of depression on people with cancer, the available studies were very few and of low quality. This review found very low certainty evidence for the effects of these drugs compared with placebo. On the basis of these results, clear implications for practice cannot be deduced. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent to prescribe may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. To better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.
Topics: Adjustment Disorders; Adult; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depression; Depressive Disorder; Depressive Disorder, Major; Dysthymic Disorder; Humans; Neoplasms; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 29683474
DOI: 10.1002/14651858.CD011006.pub3 -
The Cochrane Database of Systematic... Jun 2015Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy and tolerability of antidepressants in this population group are few and often report conflicting results.
OBJECTIVES
To assess the effects and acceptability of antidepressants for treating depressive symptoms in adults (18 years or older) with cancer (any site and stage).
SEARCH METHODS
We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 3), MEDLINE Ovid (1946 to April week 3, 2014), EMBASE Ovid (1980 to 2014 week 17) and PsycINFO Ovid (1987 to April week 4, 2014). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials.
SELECTION CRITERIA
We included RCTs allocating adults (18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis) comparing antidepressants versus placebo, or antidepressants versus other antidepressants.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into RevMan 5 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We retrieved a total of nine studies (861 participants), with seven studies contributing to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants and one-three armed study compared two antidepressants and a placebo arm. For the acute phase treatment response (6 to 12 weeks), we found very low quality evidence for the effect of antidepressants as a class on symptoms of depression compared with placebo when measured as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants) or as a proportion of people who had depression (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants). No trials reported data on the follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, providing very low quality evidence for the difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants). No clear evidence of an effect of antidepressants versus either placebo or other antidepressants emerged from the analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low quality evidence). We found very low quality evidence for the effect of antidepressants as a class in terms of dropouts due to any cause compared with placebo (RR 0.87, 95% CI 0.49 to 1.53, six RCTs, 455 participants), as well as between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the quality of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity.
AUTHORS' CONCLUSIONS
Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.
Topics: Adjustment Disorders; Adult; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depression; Depressive Disorder; Depressive Disorder, Major; Dysthymic Disorder; Humans; Neoplasms; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 26029972
DOI: 10.1002/14651858.CD011006.pub2