Antidepressants-related weight gain masks a bigger picture.
Gafoor and colleagues must be commended for concerns about adverse effects of antidepressants and adding evidence about weight gain.(1) Indeed, as a general rule, the drug safety issue is too frequently overlooked. It is even a desperate need with antidepressants as: a) selective publications, sponsorship biases and,(2) ghost-writing have been the norm (eg. GSK cynically named its program for paroxetine “CASSPER” after the friendly ghost CASPER; b) antidepressants effect size is small, around 0.30, while psychotherapies are at least as effective, even for severe depression and also in the real life setting, on the long term without adverse effects.(3)
However, the main finding about drug safety may not be about weight gain. Fig 4 provided the percentage of prescriptions with International Nonproprietary Names: Citalopram and escitalopram represented 25%, duloxetine 2%; venlafaxine 6%.(1) Accordingly, one third of prescriptions concerned drugs which offer no clinical benefit vs older ones but only harms: a) deadly torsade de pointe due to QT prolongation with citalopram or escitalopram (4) or with venlafaxine to a lesser extend; b) life-threatening serious effect such as liver injury or skin reactions including Stevens-Johnson Syndrome with duloxetine.(5,6)
The BMJ group has been publishing two dozens of articles about the “Choosing Wisely“ campaign since 2015.(7) This campaign seems putting the cart before the horse. First of all, regulatory agencies should clean their Augean stable and balance their accelerated approval processes with accelerated withdrawals of drugs with adverse effects that are disproportionate to their benefits or drugs superseded by others with a better harm-benefit balance.(8) Indeed, one third of doctors are unable to choose according to the motto: first do not harm.
Last, have the authors tested a potential interference in the recruitment (from 2004 to 2014) and/or in findings due to the Improving Access to Psychological Therapies launched in 2008. This self-referral service, mainly cognitive-behavioural treatment approaches for people with depressive diagnoses, has been such a a success that it is a beacon for Quebec and Belgium which recently implemented it. In contrast, France flies in the face of the evidence and good country sense: its costly and mandatory healthcare scheme unwisely chooses to reimburse homeopathy, not psychotherapies.
1 Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ 2018;361:k1951
2 Maund E, Tendal B, Hróbjartsson A et al. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of clinical study reports, trial registries, and publications. BMJ 2014;348:g3510.
3 Wiles NJ, Thomas L, Turner N et al. Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial. Lancet Psychiatry 2016;3:137-44.
4 Castro VM, Clements CC, Murphy SN. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013;346:f288.
5 Wernicke J, Pangallo B, Wang F et al. Hepatic effects of duloxetine-I: non-clinical and clinical trial data. Curr Drug Saf 2008;3:132-42.
7 Colla CH, Sequist TD, Rosenthal MB, Schpero WL, Gottlieb DJ, Morden NE. Use of non-indicated cardiac testing in low-risk patients: Choosing Wisely. BMJ Qual Saf 2015;24:149-53.
8 Braillon A, Menkes DB. Balancing accelerated approval for drugs with accelerated withdrawal. JAMA Intern Med 2016;176:566-7.
Rapid Response:
Antidepressants-related weight gain masks a bigger picture.
Gafoor and colleagues must be commended for concerns about adverse effects of antidepressants and adding evidence about weight gain.(1) Indeed, as a general rule, the drug safety issue is too frequently overlooked. It is even a desperate need with antidepressants as: a) selective publications, sponsorship biases and,(2) ghost-writing have been the norm (eg. GSK cynically named its program for paroxetine “CASSPER” after the friendly ghost CASPER; b) antidepressants effect size is small, around 0.30, while psychotherapies are at least as effective, even for severe depression and also in the real life setting, on the long term without adverse effects.(3)
However, the main finding about drug safety may not be about weight gain. Fig 4 provided the percentage of prescriptions with International Nonproprietary Names: Citalopram and escitalopram represented 25%, duloxetine 2%; venlafaxine 6%.(1) Accordingly, one third of prescriptions concerned drugs which offer no clinical benefit vs older ones but only harms: a) deadly torsade de pointe due to QT prolongation with citalopram or escitalopram (4) or with venlafaxine to a lesser extend; b) life-threatening serious effect such as liver injury or skin reactions including Stevens-Johnson Syndrome with duloxetine.(5,6)
The BMJ group has been publishing two dozens of articles about the “Choosing Wisely“ campaign since 2015.(7) This campaign seems putting the cart before the horse. First of all, regulatory agencies should clean their Augean stable and balance their accelerated approval processes with accelerated withdrawals of drugs with adverse effects that are disproportionate to their benefits or drugs superseded by others with a better harm-benefit balance.(8) Indeed, one third of doctors are unable to choose according to the motto: first do not harm.
Last, have the authors tested a potential interference in the recruitment (from 2004 to 2014) and/or in findings due to the Improving Access to Psychological Therapies launched in 2008. This self-referral service, mainly cognitive-behavioural treatment approaches for people with depressive diagnoses, has been such a a success that it is a beacon for Quebec and Belgium which recently implemented it. In contrast, France flies in the face of the evidence and good country sense: its costly and mandatory healthcare scheme unwisely chooses to reimburse homeopathy, not psychotherapies.
1 Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ 2018;361:k1951
2 Maund E, Tendal B, Hróbjartsson A et al. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of clinical study reports, trial registries, and publications. BMJ 2014;348:g3510.
3 Wiles NJ, Thomas L, Turner N et al. Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial. Lancet Psychiatry 2016;3:137-44.
4 Castro VM, Clements CC, Murphy SN. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013;346:f288.
5 Wernicke J, Pangallo B, Wang F et al. Hepatic effects of duloxetine-I: non-clinical and clinical trial data. Curr Drug Saf 2008;3:132-42.
6 http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm255064.htm
7 Colla CH, Sequist TD, Rosenthal MB, Schpero WL, Gottlieb DJ, Morden NE. Use of non-indicated cardiac testing in low-risk patients: Choosing Wisely. BMJ Qual Saf 2015;24:149-53.
8 Braillon A, Menkes DB. Balancing accelerated approval for drugs with accelerated withdrawal. JAMA Intern Med 2016;176:566-7.
Competing interests: No competing interests