[Norwegian]

Antidepressants

How big is the effect? What are the side effects? How is suicide risk affected?


Chapter 7 in Brinkmann S, Petersen A (eds.). Diagnoses: perspectives, criticism and discussion. Aarhus: The authors and Klim; 2015 translated from Danish:
(Kapitel 7 i Brinkmann S, Petersen A (red.). Diagnoser: perspektiver, kritik og diskussion. Aarhus: Forfatterne og Klim; 2015): http://www.deadlymedicines.dk/overdiagnostik-og-overbehandling-i-psykiatrien/

OVERDIAGNOSTIC AND OVERTREATMENT IN PSYCHIATRY translated from Danish: (OVERDIAGNOSTIK OG OVERBEHANDLING I PSYKIATRIEN:) http://www.deadlymedicines.dk/wp-content/uploads/2015/09/Diagnoser_kap-7.pdf

Page 168:
Do antidepressants have any effect on depression?
In round numbers, the randomized trials show that around 50%
of patients get better on an antidepressant and 40% on a placebo.
The effect in the 40% is often called a placebo effect, but it is
does not. Many of the patients would have gotten better, even if you didn't
had given them any treatment at all, as most depressions
goes away on its own after a few weeks. When both doctors and patients “have
experience for" that the treatment works, we must therefore say that we cannot
use that "experience" for something, since we don't know how it would be
gone without treatment.
The difference of 10% means that only one patient benefits
of treatment when treating ten patients. The real effect is
however, much less, if it exists at all. The experiments have
namely not been properly blinded. Antidepressant drugs have significant
side effects, and many patients and their doctors therefore want to know about it
blinded drug contains active substance or placebo. A systematic
review of 21 trials in a number of different diseases that had
both a blinded and an unblinded observer, found that the treatment effect
was overestimated by 36% on average (measured as odds ratio),
when the unblinded observer assessed the effect (Hróbjartsson et al.
2012). Most trials had used subjective effect measures, and the effect
of antidepressants is also assessed on very subjective scales (e.g. the Hamilton scale).
If we assume that the blinding is broken for all the patients
in the trials with antidepressants, and adjusts for the overestimation of the effect,
the loss of blinding causes, we find that antidepressants do not have
no effect (odds ratio 1.02) (Gøtzsche 2015a).
The blinding is probably not broken for all the patients, but you only have to
misclassify 5% of patients as to whether they have had an effect or
not until the apparent effect of antidepressants disappears (since 50%
with effect on active substance becomes 45%, and 40% on placebo also becomes 45%)
Page 177:
Brain damage
The situation is that the medication keeps the patients stuck in the patient role
and changes their personality (Gøtzsche 2015a; Healy 2004; Kessing
et al. 2005; Whitaker 2013), so they don't learn to deal with life's challenges.
Unfortunately, the opinion of leading psychiatrists is exactly the opposite.
They say it is important to take antipsychotics and antidepressants because
untreated schizophrenia (Lægemiddelindustriforeningen 2013) and depression
(Videbech & Dalsgaard 2014) can cause brain damage. I consider this
for being an equally unpleasant example of abuse of power, misinformation
and persuasion as the rock of the chemical imbalance.



Drag Info Madinamerica.com: Antidepressants as a treatment for depression https://www.madinamerica.com/drug-info-antidepressants/



Irving Kirsch et al. 2002: The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration. “The proportion of the drug response duplicated by placebo was significantly greater with observed cases (OC) data than with last observation carried forward (LOCF) data. If drug and placebo effects are additive, the pharmacological effects of antidepressants are clinically negligible.”



Jeffrey R. Vittengl 2017: Poorer Long-Term Outcomes among Persons with Major Depressive Disorder Treated with Medication. “The presence of major depressive disorder (MDD) and receipt of mental health treatment predicted greater depressive symptoms 9 years later”. The FDA’s “Major Depressive Disorder: Developing Drugs for Treatment Guidance for Industry” states the following: “Antidepressants in established classes (e.g., SSRIs, SNRIs) typically need studies of 6 to 8 weeks duration to demonstrate efficacy.”



Hengartner M.P · Angst J.· Rössler W.2018: Antidepressant Use Prospectively Relates to a Poorer Long-Term Outcome of Depression: Results from a Prospective Community Cohort Study over 30 Years. https://www.karger.com/Article/Abstract/488802



Hengartner et al. 2019: ‘Newer-generation antidepressants and suicide risk in randomized controlled trials: A re-analysis of the FDA database
New study: antidepressants significantly raise the risk of suicide in the treatment of depression for adults:
“Earlier analysis of this data did not reveal the increased risk because the method used was incorrect.
Previously, calculations were based on ‘person exposure years’ (PEY) rather than the number of patients receiving treatment...
Suicide attempts and suicides combined was about 2.5 times higher”.
“Our findings thus conflict with the work by Khan et al. [5], who based their effect estimates on PEY rather than the number of patients.
When hazards are not constant over time, PEY is inappropriate [10] and may obscure a true adverse drug effect”



Hengartner et al. 2019: Reply to the Letter to the Editor: “Newer-Generation Antidepressants and Suicide Risk: Thoughts on Hengartner and Plöderl’s Re-Analysis”: To demonstrate that misreported suicides can substantially bias the results, we show in Table 1 that the suicide risk accord-ing to a Bayesian random-effects meta-analysis (the method rec-ommended by Ren et al. [6]) of the uncorrected data table was OR = 2.49, 0.82–45.32 (note the discrepancy to Hayes et al. [1]).



Ny studie sår fornyet tvil om medisiner mot depresjon

Forskningen på antidepressiva har så store metodeproblemer at vi ikke kan stole på resultatene, ifølge en ny analyse. Anerkjent professor er uenig.
Systematisk skjevhet, utvalg av positive resultater, mangelfull rapportering av bivirkninger. Det er noen av problemene i studiene av medisiner mot depresjon.
Metodeproblemene er så store at vi ikke vet om medisinene virker.
https://forskning.no/angst-depresjon-medisiner/ny-studie-sar-fornyet-tvil-om-medisiner-mot-depresjon/1359079



How common and severe are six withdrawal effects from, and addiction to, antidepressants? The experiences of a large international sample of patients
Author JohnRead https://doi.org/10.1016/j.addbeh.2019.106157

Over half (55%) of people who had tried to come off or reduce antidepressants report some degree of difficulty coming off, with 27% ticking ‘very difficult’
•61% report ‘withdrawal effects’, with 44% of these describing the effects as ‘severe’
•40% report ‘addiction’, with 39% of these describing their addiction as ‘severe’
•‘Anxiety/panic’ (66%) and ‘Irritability (62%) are particularly common.
•Less than 1% had been told anything about withdrawal effects or dependence.
https://www.sciencedirect.com/science/article/abs/pii/S0306460319309001?via%3Dihub



Forskere konkluderer: «Lykkepiller» virker ikke mot depresjon
Stor gjennomgang av forskning tyder på at SSRI-medisiner mot depresjon gjør mer skade enn nytte. Men hvorfor opplever da noen at de hjelper? Marie Barse JOURNALIST, VIDENSKAB.DK PUBLISERT Lørdag 18. februar 2017 – 04:00
https://forskning.no/depresjon/forskere-konkluderer-lykkepiller-virker-ikke-mot-depresjon/364440



James Davies et al. 2019: Clinical guidelines on antidepressant withdrawal urgently need updating
Letters Antidepressant withdrawal
Clinical guidelines on antidepressant withdrawal urgently need updating
BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l2238 (Published 20 May 2019)
Cite this as: BMJ 2019;365:l2238
https://www.bmj.com/content/365/bmj.l2238utm_source=twitter&utm_medium=hootsuite&utm_term=&utm_content=&utm_campaign=editors



Susan McPherson et al. 2019: Long-term outcomes of trials in the National Institute for Health and Care Excellence depression guideline:
“The forthcoming National Institute for Health and Care Excellence depression guideline reviews short-term outcomes for long-term depression. We present effect sizes for long-term outcomes in trials that report these data. Psychological therapies become more effective, whereas antidepressants become less effective over the long term.”
https://www.researchgate.net/publication/335693982_Long-term_outcomes_of_trials_in_the_National_Institute_for_Health_and_Care_Excellence_depression_guideline



Campaigning forces Royal College of Psychiatrists to change its position on antidepressant withdrawal by CEP Admin on 30/05/2019

http://cepuk.org/2019/05/30/royal-college-psychiatrists-call-update-nice-antidepressant-guidelines-following-cep-campaign/

Ny studie sår fornyet tvil om medisiner mot depresjon.
Forskningen på antidepressiva har så store metodeproblemer at vi ikke kan stole på resultatene, ifølge en ny analyse. Anerkjent professor er uenig.
Marie Barse JOURNALIST, VIDENSKAB.DK PUBLISERT Fredag 19. juli 2019 – 04:30
https://forskning.no/angst-depresjon-medisiner/ny-studie-sar-fornyet-tvil-om-medisiner-mot-depresjon/1359079



Anti-depressants CAN ruin lives: Major U-turn as psychiatrists say millions of patients MUST be warned over severe side effects. By BEN SPENCER MEDICAL CORRESPONDENT FOR THE DAILY MAIL PUBLISHED: 22:00 BST, 29 May 2019

-For years side effects of withdrawing from antidepressants were branded 'mild'

-But the Royal College of Psychiatrists has now changed its position to 'severe'

-UK prescribes more antidepressants than any other Western country

https://www.dailymail.co.uk/news/article-7084025/Royal-College-Pyschiatrists-warn-doctors-anti-depressants-dangerous-effects.html



Keller et al. 2001 «Study 329» (Wikipedia) der en re-analysis av rådata korrigerte den opprinnelige konklusjonen.
In conclusion, the findings of this (original) study provide evidence of the efficacy and safety of Paxil in the treatment of adolescent depression.
The reanalyses concluded that "[t]he efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome," and that there were "clinically significant increases in ... suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group."



Maß, R,. Backhaus, K., Lohrer, K., Szelies, M., & Unkelbach, B. K. (2023). No benefit of antidepressants in inpatient treatment of depression. A longitudinal, quasi experimental field study. Psychopharmacology. https://doi.org/10.1007/s00213-023-06417-4



Winfried Rief, John M. Kelley, Yvonne Nestoriuc, (2023). Placebo and nocebo effects in depression: Implications for treatment and clinical trial designs. “ Although antidepressants show statistically greater efficacy compared to placebos, the effect sizes are small, and the specific effect of these drugs provides only a small clinical benefit to patients.Placebo responses in double-blind trials are about 80% as large as the response to antidepressants.” https://doi.org/10.1093/med/9780197645444.003.0016






Jahanna Moncrieff et al. 2022: The serotonin theory of depression: a systematic umbrella review of the evidence
The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.https://www.nature.com/articles/s41380-022-01661-0

Inner Compass Initiative. Strømmet direkte 1. sep. 2022: Moving Beyond Myth: A Postmortem Analysis of Chemical Imbalances and Antidepressants Efficacy. https://www.youtube.com/watch?v=5pGkjBnrPe8