Studies on psychiatric drugs

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#1
ADHD drugs
The following study is sometimes cited as evidence in favor of methylphenidate treatment

https://sci-hub.se/https://link.springer.com/article/10.2165/11589380-000000000-00000

However, the earlier advantage of having had continuous intake of medication for 14 months was no longer apparent at the 36-month follow-up.
They referenced this study:

ADHD-trial-36.png

https://depts.washington.edu/psychres/wordpress/wp-content/uploads/2017/11/100-Papers-in-Clinical-Psychiatry-Child-and-Adolescent-Psychiatry-3-year-follow-up-of-the-NIMH-MTA-Study..pdf

Other long term studies also show stimulants dont work in the case of ADHD

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815037/

Stimulants can still give a percieved benefit to people using them including individuals not diagnosed with ADHD

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813924/

Studies on how stimulant drugs affect academic performance for people with ADHD symptoms are mixed and overall inconclusive:

https://onlinelibrary.wiley.com/doi/10.1111/jcpt.13486?af=R
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264851/
https://link.springer.com/article/10.1007/s00787-018-1106-3

The following study did find that the group who took their medication as prescribed were less likely to abuse other substances but this was not a randomized controlled trial and can thus be discarded

https://www.sciencedaily.com/releases/2017/07/170712201249.htm

The study only looked at the first 2 years since starting on stimulant medication which is too short to draw any long term conclusion.

The Cochrane review found:

The quality of the evidence and hence the certainty or reliability of the evidence for the comparative studies is very low. The reliability of the evidence for the non-comparative studies is low due to weaknesses in study design. Accordingly, it is not possible to accurately estimate the risks of adverse events in children and adolescents prescribed methylphenidate.

Methyphenidiate might be associated with a number of serious adverse events. Methylphenidate produces a large number of other non-serious harmful effects in children and adolescents with ADHD. We suggest that clinicians and parents are alert to the importance of monitoring adverse events in a systematic, meticulous manner. If methylphenidate is to continue to have a place in ADHD treatment in the future, we need to identify subgroups of patients in whom the benefits of methylphenidate outweigh the harms. Just as we need to be able to identify who is likely to benefit from treatment, we also need to be able to identify those who are most at risk of experiencing adverse events. In order to do this, we need to undertake large-scale, high-quality RCTs along with other studies aimed at identifying those who respond and those who do not respond to treatment.
 

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#3
SSRI studies
SSRIs have an effect on sexual function, almost entirely negative: Decreased libido, increasing latency and amount of stimulation needed to reach orgasm, in some cases decreased genital sensitivity, anorgasmia. Some of these effects can persist after orgasm in a phenomenon known as post-SSRI sexual dysfunction (PSSD). Bala et al. (2018) reviewed the literature on PSSD. Haberfellner, Rittmannsberger (2004) reported spontaneous improvement in delay of orgasm caused by SSRIs after 6 months including complete remission of that effect in 31 % of users.

Moore et al. (2010) found that the SSRIs fluoxetine, paroxetine, sertraline, escitalpram, citalopram and duloxetine have a disproportionate number of case reports of being suspected of causing violent behavior. Note that this is a purely observational study and therefore it is subject to many confounders.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007725/

https://rxisk.org/post-ssri-sexual-dysfunction-pssd/

https://male-to-female.org/en/psychopharmacology
 

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#4
Extrapolating these results
There is no shortage of combinations of diagnosis and treatment, thus believers in the psychiatry cult can always tell themsleves "sure it doesn't work for these cases but i still got helped" (as if personal anecdotes would be evidence for anything). The negative long term results we have does however have bad implications for psychiatric drugs in general.

If the probability of a bad outcome of a psychiatric treatment is X than the probability for 2 of 2 trials being bad is X²

But the long term studies we have looked at here are in cases where short term results seemed to be positive, in many cases (such as with SSRIs) psychiatric drug struggle to beat placebo even in the short term.
 

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#5
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/

This shows Antidepressants effects vs placebo. It is a meta-analysis of meta-analysis so you cannot blindly trust the results (you can cherry-pick, etc) I looked through the methodologies of several blind to results before finding this methodology satisfactory, so I am not cherry picking based on outcome.

"This suggests that 89% of depressed patients are not receiving a clinically significant benefit from the antidepressants that are prescribed for them.

Yet this 11% figure may overestimate the number of people who benefit from antidepressants."

That's a pretty damming success rate, essentially an 8 in 9 chance being no better than sugar pills. But hey, that's better than nothing right? Well....

". Among the side effects of antidepressants are sexual dysfunction (which affects 70–80% of patients on SSRIs), long-term weight gain, insomnia, nausea, and diarrhea. Approximately 20% of people attempted to quit taking antidepressants show withdrawal symptoms. Antidepressants have been linked to increases in suicidal ideation among children and young adults. Older adults have increased risks of stroke and death from all causes. Pregnant women using antidepressants are at increased risk of miscarriage, and if they don’t miscarry, their offspring are more likely to be born with autism, birth malformations, persistent pulmonary hypertension, and newborn behavioral syndrome."

Now all of sudden we are looking at a 197 BILLION dollar industry that rarely has positive outcomes, but often has negative ones.

Compare to psychology https://link.springer.com/article/10.1007/s11482-019-09788-z (unfortunately the full study is behind a paywall but this is the abstract)

This shows much better outcomes, with a postive correlation accross 16k subjects. Also:

"Overall, we also found evidence of long-term effects of the interventions."
 

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#6
How trials are rigged
There are many ways in which psychiatric drugs trials are rigged in order to make the these drugs look less bad than they are.

0. People in the trial have often already started on the drug making them dependent on it, then the drug is abruptly withdrawn in the placebo group resulting in the placebo group getting severe withdrawal symptoms.
1. The time duration of the trial is set to be short (hiding long term negative outcomes).
2. Instead of measuring things that matters like quality of life subjective rating scales are used.
3. Drug trials are very rarily properly blinded. you can easily figure out if someone is on a placebo due to the severe side effects from the drugs.

Despite trying 0, 2 and 3 not a single long term Randomized controlled trial has demonstrated good outcome from a psychiatric drug for any mental disorder, they also need to limit the duration of the trials to successfully rig them. Often these trials are paid for by drug companies and they are not interested in paying for a trial that show their drug not to be effective.
 

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#7
Short term studies
Next we are going to look at proper short term studies to see if a real positive effect can be observed even short term

Stimulants: no (general population)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813924/

So while the users think they are being helped (able to focus better) in reality they would have ben better off getting a placebo.
 

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#8
Another fraudulent meta-analysis
Of course they hide this behind a paywall

1601456555072.png

https://sci-hub.se/https://doi.org/10.1111/jcpp.13305

A randomized discontinuation study included children with ASD and irritability that were responders to aripiprazole on irritability outcomes. In this study, a decrease in ABC hyper-activity over 6–9 months was found in children who were randomized to ongoing aripiprazole treatmentcompared to a switch to placebo (MD=5.20, 95%CI10.20,.20,I2=N/A; Findling et al., 2014).

No meaningful outcome was measured in any of the studies, they didn't ask the child in any of the studies, only authority figures and all studies were short term.
 

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#10
would you classify soy as a psychiatric drug ?
No absolutely not, with psychiatric drug i refer to drugs that target neurotransmitters (adderal, zyprexa, etc).

Hormones will also affect behaviour and this might actually be an effective way to affect human behaviour.
 

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#11
Bipolar I & lithium
Finding a good study on this turned out to be impossible.

m53t1.jpeg


https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.161.2.217

There are 4 obvious issue with the 1973 study

0. It didn't measure important outcomes like overall quality of life, mortality rate.

1. It only lasted 2 years

2. The treating physician knew whether or not the patient was on placebo.

3. The patients was already on lithium (and thus potentially dependent) when the study started.

https://sci-hub.se/https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490854

1609521129445.png


Patients returned to the hospital every four weeks to be evaluated, obtain study medication, and have their serum lithium monitored. Serum lithium determinations were obtained for both treatment groups. Inpatient streated with lithiumcarbonate, serum levels weret obemaintained between 0.5 and 1.4m Eq/liter.
One issue here is that they measured success by evaluating the patients based on some arbitrary rating scale subjecting the victims to forced treatments if they viewed them as too manic.

Its unclear if treating physician was the only one who knew who was given the drugs or of the ones determiniing who was going to be subjected to additional interventions also knew these things.

Did the Lithium actually help people to function well in the world outside the psych-ward? thats very unclear.

1609522146870.png
 

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#12
Antidepressants and quality of life
The following meta-analysis was used to find studies to analize

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663193/table/T1/?report=objectonly

Aberg-Wistedt et al, 2000 compared 2 different anti-depressants instead of comparing to placebo, it was a withdrawal trial, i was not able to get access to the full text using https://sci-hub.se or https://openaccessbutton.org/

Bellino et al, 2006 had poor sample size and high dropout rate, both groups were given

Ishak et al, 2013 was not a randomied controlled trial and i was not able to in any way get access to the full text.

Saveanu et al, 2015 compared anti-depressants against each other and the study only lasted 8 weeks.

I was able to get access to the full text https://sci-hub.se/10.1016/j.jpsychires.2014.12.018

Demyttenaere et al, 2008 was a randomized controlled trial with good sample size but it only lasted 8 weeks so it do not tell us much regarding the long-term outcomes.

I was able to get access to the full text https://sci-hub.se/10.1097/YIC.0b013e328303ac5f

This study will be analysed properly in the next post.
 

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#13
Study: Escitalopram marginally better than placebo (8 weeks of treatment)

1619599454274.png

This was on a 5-point scale and shows that both groups improved but without medication you didn't improve as fast.

https://sci-hub.se/10.1097/YIC.0b013e328303ac5f

It is worth noting that the placebo group wasn't a proper placebo group since it will be obvious whether or not you get the active ingredient due to side effects you get from SSRIs.

The study did measure "sexual drive" (which seems to get worse) but the study did not measure sexual function directly.

We would need a longer trial to better understand the long-term implications of using these drugs.
 

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#14
SSRI effective against BDD?
The placebo group did do worse in the following 16-week trial but that was based on assassment by the clinician which in most cases figured out whether or not the patient was in the placebo or active ingredient group. The trial did not try to find out whether or not the patient actually felt better overall when being given the SSRI, the trial is also too short to figure out whether or not the long-term outcomes would be good.

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/206211

The mean ± SD time to fluoxetine response (as assessed by a 30% decrease in BDD-YBOCS score) was 7.7 ± 3.5 (range, 2-12) weeks and to placebo was 5.3 ± 3.2 (range, 1-8) weeks (t29 = 1.97; P = .6). The mean ± SD fluoxetine dose at end point was 77.7 ± 8.0 (range, 40-80) mg/d; the fluoxetine equivalent in the placebo group was 76.0 ± 13.1 (range, 20-80) mg/d.

Of the 21 patients treated with open-label fluoxetine after placebo treatment during the double-blind phase (mean ± SD fluoxetine dose at end point, 61.1 ± 21.4 mg/d), 5 (24%) responded to the BDD-YBOCS. Scores decreased from a mean ± SD score of 29.3 ± 7.4 to 22.3 ± 7.2 (t20 = 5.14; P<.001). On the clinician-rated BDD-CGI, 9 (43%) responded, with7 (33%) much improved and 2 (10%) very much improved.

In 34 cases (69%), the clinician correctly judged whether the patient had received fluoxetine or placebo; this was the case for 25 (63%) patients. The clinician's judgment was incorrect in 6 (12%) cases and the patient's in 10 (25%). The clinician was unsure of group assignment in 9 (18%) of cases and the patient in 5 (13%).
 

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#16
What does Lithium-carbonate even do?
If you look at mainstream sites they will claim "we do not know how lithium works".

https://en.wikipedia.org/wiki/Lithium_carbonate

But websites and individuals critical of psychiatry often have explanations

Lithium is a neurotoxin. It inhibits the functioning of the nervous system so that people typically feel drowsy, lethargic and slowed up. These effects were observed in guinea pigs initially, and then in people with mania by the Australian doctor, John Cade, who first proposed that lithium might be a useful treatment for manic depression.

(1) Moncrieff J. The Myth of the Chemical Cure: a critique of psychiatric drug treatment. Basingstoke, Hampshire, UK: Palgrave Macmillan; 2008.
https://www.madinamerica.com/2015/06/reasons-not-to-believe-in-lithium/

The reference provided leads to some book that you cannot legally read without paying money, not a good source. They did not cite any proper study for this.

Relapse rates among patients taking lithium in randomised trials that have started with patients experiencing a manic episode (as the historical studies did) are uniformly higher too. In the comparison between lithium, Divalproex (Depakote) and placebo, for example, the lithium group relapsed at a rate of 31% a year (9). In the comparison between lithium, lamotrigine and placebo in people with mania it was 26% a year (10). Admittedly these figure include all relapses, and not just those severe enough to require hospitalisation. A large study conducted in the 1970s, however, found that rates of hospital admission for relapse were 21.5% per year in the lithium group.

Prien RF, Caffey EM, Jr., Klett CJ. Prophylactic efficacy of lithium carbonate in manic-depressive illness. Report of the Veterans Administration and National Institute of Mental Health collaborative study group. Arch Gen Psychiatry 1973 Mar;28(3):337-41
9: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/481596

Several ‘naturalistic’ studies have tracked the progress of people taking lithium and other treatments. The vast majority of these studies also show high relapse rates among those on lithium, even though most studies highly compliant populations and we know that people who are compliant with any treatment (including placebo) have better outcomes than those who are not. One study of patients who were known to be compliant with their lithium treatment for at least a year, for example, found a rate of relapse of 40% a year over a 6 year follow-up.
In this case they did reference a study, the study did show lithium treatment to be beneficial.

cambridge.org/core/journals/the-british-journal-of-psychiatry/article/longterm-clinical-effectiveness-of-lithium-maintenance-treatment-in-types-i-and-ii-bipolar-disorders/42CDDCBA8E5E5E8BB84B68E2BA201BB6
 
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