Effect of #Antidepressant Switching vs Augmentation on Remission Among Patients With Major #Depressive Disorder Unresponsive to Antidepressant Treatment
The VAST-D Randomized Clinical Trial
http://jamanetwork.com/journals/jama/article-abstract/2643308
Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase)
Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.
The VAST-D Randomized Clinical Trial
http://jamanetwork.com/journals/jama/article-abstract/2643308
Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase)
Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.
Jamanetwork
Effects of Antidepressant Switching vs Augmentation on Depression
This randomized clinical trial compares the effects on symptom remission of switching to bupropion, adding bupropion, or adding aripiprazole to baseline treatment among Veterans Affairs patients with antidepressant-resistant major depressive disorder.
Risk of relapse after #antidepressant discontinuation in #anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials
http://www.bmj.com/content/358/bmj.j3927
To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89).
Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).
Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients’ preferences
http://www.bmj.com/content/358/bmj.j3927
To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89).
Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).
Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients’ preferences
The BMJ
Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress…
Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of…
Association of #Antidepressant Medications With Incident Type 2 #Diabetes Among Medicaid-Insured Youths
https://jamanetwork.com/journals/jamapediatrics/article-abstract/2656620
Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment–emergent risk of type 2 diabetes among youths
Furthermore, for youths currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI, 1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for 3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose equivalents). By contrast, neither the duration nor the cumulative dose of other antidepressants was associated with an increased risk of type 2 diabetes. The risk of type 2 diabetes increased significantly with the average daily dose among youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52 for >15.0 vs ≤15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI use.
Conclusions and Relevance In a large cohort of youths insured by Medicaid, the use of SSRIs or SNRIs—the most commonly used antidepressant subclass—was associated with an increased risk of type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose
https://jamanetwork.com/journals/jamapediatrics/article-abstract/2656620
Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment–emergent risk of type 2 diabetes among youths
Furthermore, for youths currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI, 1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for 3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose equivalents). By contrast, neither the duration nor the cumulative dose of other antidepressants was associated with an increased risk of type 2 diabetes. The risk of type 2 diabetes increased significantly with the average daily dose among youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52 for >15.0 vs ≤15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI use.
Conclusions and Relevance In a large cohort of youths insured by Medicaid, the use of SSRIs or SNRIs—the most commonly used antidepressant subclass—was associated with an increased risk of type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose
Jamanetwork
Antidepressants and Incident Type 2 Diabetes Among Medicaid-Insured Youths
This cohort study uses Medicaid claims data to assess the association between antidepressant use and the risk of incident type 2 diabetes among youths by antidepressant subclass and duration of use, cumulative dose, and average daily dose.
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#Antidepressant utilisation and incidence of #weight gain during 10 years’ follow-up: population based cohort study
https://www.bmj.com/content/361/bmj.K1951
.. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P<0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations.
Conclusion Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated
#Antidepressant utilisation and incidence of #weight gain during 10 years’ follow-up: population based cohort study
https://www.bmj.com/content/361/bmj.K1951
.. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P<0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations.
Conclusion Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated
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acceptability of 21 #antidepressant drugs for the acute treatment of adults with major #depressive disorder: a systematic review and network meta-analysis
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext
In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
Interpretation
All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
acceptability of 21 #antidepressant drugs for the acute treatment of adults with major #depressive disorder: a systematic review and network meta-analysis
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext
In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
Interpretation
All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
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Association Between #Antidepressant Drug Use and Hip #Fracture in Older People Before and After Treatment Initiation
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2719274
Of the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.
Conclusions and Relevance The present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.
Association Between #Antidepressant Drug Use and Hip #Fracture in Older People Before and After Treatment Initiation
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2719274
Of the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.
Conclusions and Relevance The present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.
Jamanetwork
Association Between Antidepressant Drug Use and Hip Fracture in Older People
This population-based study examines the occurrence of hip fractures in elderly individuals before and after initiation of antidepressant medications.
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#Antidepressant use during pregnancy and the risk of gestational #diabetes mellitus: a nested case–control study
When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.
Conclusion The findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.
https://bmjopen.bmj.com/content/9/9/e025908
#Antidepressant use during pregnancy and the risk of gestational #diabetes mellitus: a nested case–control study
When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.
Conclusion The findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.
https://bmjopen.bmj.com/content/9/9/e025908
BMJ Open
Antidepressant use during pregnancy and the risk of gestational diabetes mellitus: a nested case–control study
Objectives The aim of this study was to determine the association between antidepressant (AD) classes, types and duration of use during pregnancy and the risk of gestational diabetes mellitus (GDM).
Design and setting A nested case–control study was conducted…
Design and setting A nested case–control study was conducted…