When does Work mean Work in the case of Antidepressants
Dear Editor
For many people who have swallowed the chemical imbalance, low serotonin myth, works means corrects my serotonin system (1). The honest message to such patients is your serotonin system will be more abnormal after treatment than before (2).
This might be a risk worth taking if there was evidence that the drugs saved lives or prevented suicide attempts. They don’t. More people died on active treatment in antidepressant trials submitted to FDA than on placebo – even when all data during withdrawal and follow up periods were excluded. There is a doubling of suicidal events on these treatments than on placebo – again after the suicidal events in the withdrawal period were excluded (3).
These might be risks worth taking if there were evidence of a return to work or improvement in quality of life – there isn’t (4).
The data underpinning the works that Dr Kendrick and colleagues refer to is data showing company assays worked at getting their drugs to the market. These are not studies aimed at informing clinical practice. There is no access to the full datasets and the articles that inform meta-analyses and guidelines on these issues may be ghostwritten.
The working refers to a fall in Ham-D scores. It might be possible to infer working clinically if these clinician rated disease oriented data were supplemented with positive findings on patient rated disease oriented rating scale, along with clinician rated global impression scale data and patient rated global impression (Quality of Life) scale data. But there is no antidepressant with positive data across all four rating scale domains and the latest data suggests relative inefficacy on QoL data (5).
There are definitely times to take a risk on an antidepressant (6), but it is not clear to me that Dr Kendrick and colleagues have pointed to anything that might help inform shared decision making.
1. Kendrick A Collinson S BMJ 2022;378:o1993 Antidepressants and the serotonin hypothesis of depression.
2. Healy D (2015). Serotonin and Depression. The Marketing of a Myth. The BMJ 350: h1771 doi: 10.1136/bmj.h1771
3. Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 2009;339:b2880
4. Healy D (2000). The assessment of outcome in depression. Measures of social functioning. Reviews in Contemporary Pharmacotherapy 11, 295-301.
5. Almohammed OA, Alsalem AA, Almangour AA, Alotaibi LH, Al Yami MS, Lai L Antidepressants and health-related quality of life (HRQoL) for patients with depression: Analysis of the medical expenditure panel survey from the United States. PLoS ONE 2022; 17(4): e0265928. https://doi.org/10.1371/journal. pone.0265928
6. Healy D (1991). The marketing of 5HT: anxiety or depres¬sion. British J of Psychiatry, 158, 737 742.
Competing interests:
I reviewed and rejected several iterations of the Stone et al 2022 article cited in correspondence here.
Rapid Response:
When does Work mean Work in the case of Antidepressants
Dear Editor
For many people who have swallowed the chemical imbalance, low serotonin myth, works means corrects my serotonin system (1). The honest message to such patients is your serotonin system will be more abnormal after treatment than before (2).
This might be a risk worth taking if there was evidence that the drugs saved lives or prevented suicide attempts. They don’t. More people died on active treatment in antidepressant trials submitted to FDA than on placebo – even when all data during withdrawal and follow up periods were excluded. There is a doubling of suicidal events on these treatments than on placebo – again after the suicidal events in the withdrawal period were excluded (3).
These might be risks worth taking if there were evidence of a return to work or improvement in quality of life – there isn’t (4).
The data underpinning the works that Dr Kendrick and colleagues refer to is data showing company assays worked at getting their drugs to the market. These are not studies aimed at informing clinical practice. There is no access to the full datasets and the articles that inform meta-analyses and guidelines on these issues may be ghostwritten.
The working refers to a fall in Ham-D scores. It might be possible to infer working clinically if these clinician rated disease oriented data were supplemented with positive findings on patient rated disease oriented rating scale, along with clinician rated global impression scale data and patient rated global impression (Quality of Life) scale data. But there is no antidepressant with positive data across all four rating scale domains and the latest data suggests relative inefficacy on QoL data (5).
There are definitely times to take a risk on an antidepressant (6), but it is not clear to me that Dr Kendrick and colleagues have pointed to anything that might help inform shared decision making.
1. Kendrick A Collinson S BMJ 2022;378:o1993 Antidepressants and the serotonin hypothesis of depression.
2. Healy D (2015). Serotonin and Depression. The Marketing of a Myth. The BMJ 350: h1771 doi: 10.1136/bmj.h1771
3. Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 2009;339:b2880
4. Healy D (2000). The assessment of outcome in depression. Measures of social functioning. Reviews in Contemporary Pharmacotherapy 11, 295-301.
5. Almohammed OA, Alsalem AA, Almangour AA, Alotaibi LH, Al Yami MS, Lai L Antidepressants and health-related quality of life (HRQoL) for patients with depression: Analysis of the medical expenditure panel survey from the United States. PLoS ONE 2022; 17(4): e0265928. https://doi.org/10.1371/journal. pone.0265928
6. Healy D (1991). The marketing of 5HT: anxiety or depres¬sion. British J of Psychiatry, 158, 737 742.
Competing interests: I reviewed and rejected several iterations of the Stone et al 2022 article cited in correspondence here.