Massive Study Says SSRI Drugs Are BOTH Ineffective And Dangerous

haidut

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While the study is nothing new for the forum users here, what makes it important is that it is the largest study ever and includes reviewing all the available literature on the topic to date. The conclusion - not only are SSRI drugs ineffective but their risks far outweigh even the (mostly) theoretical benefits claimed by Big Pharma. Considering that apparently more 85% of people with depression spontaneously recover without any treatment, the case for SSRI use becomes completely untenable.

@aguilaroja

Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial... - PubMed - NCBI
"...CONCLUSIONS: SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects."

https://www.madinamerica.com/2017/10/rigorous-study-finds-antidepressants-worsen-long-term-outcomes/
"...Previous research has also found that antidepressants are no more effective than placebo for mild-to-moderate depression, and other studies have questioned whether such medications are effective even for severe depression. Concerns have also been raised about the health risks of taking antidepressants—such as a recent study which found that taking antidepressants increases one’s risk of death by 33% (see MIA report). In fact, studies have demonstrated that as many as 85% of people recover spontaneously from depression. In a recent example, researchers found that only 35% of people who experienced depression had a second episode within 15 years. That means that 65% of people who have a bout of depression are likely never to experience it again."
 

Frankdee20

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Taking these will lessen your brains chance at spontaneous recovery. They destroy brain resiliency, and create stages for dependency
 

Herbie

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From my own observations of spending time with people on ssris, the ones who are also taking lithium are the most stable.
 

haidut

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From my own observations of spending time with people on ssris, the ones who are also taking lithium are the most stable.

If they are taking lithium then there is no need for the SSRI. Lithium is a potent antidepressant by itself and to this day is the gold standard for treating both depression and mania (and bipolar by extension). The scare tactics about its kidney toxicity are overblown and nowhere near as serious as the suicide risk and increased all-cause mortality from SSRI. The only reason SSRI started getting co-prescribed with lithium was a massive lobbying/funding/ghostwriting campaign by the pharma industry so that SSRI can piggy back on lithium's success and acquire critical mass to be marketed on their own. So now, after a few decades of co-administration the waters are muddied enough to now claim that SSRI are beneficial on their own, but there is no evidence for that. It is much easier to make a study that shows a combination of two drugs is better than one of the drugs alone (especially when one of them is known to work) compared to showing benefit of each drug on their own against placebo. And since lithium was known to be effective, it was easy to fudge a few stats in studies to show SSRI are synergistic with lithium. This is a common and very pernicious tactic employed by Big Pharma as @aguilaroja mentioned several times.
 

Herbie

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If they are taking lithium then there is no need for the SSRI. Lithium is a potent antidepressant by itself and to this day is the gold standard for treating both depression and mania (and bipolar by extension). The scare tactics about its kidney toxicity are overblown and nowhere near as serious as the suicide risk and increased all-cause mortality from SSRI. The only reason SSRI started getting co-prescribed with lithium was a massive lobbying/funding/ghostwriting campaign by the pharma industry so that SSRI can piggy back on lithium's success and acquire critical mass to be marketed on their own. So now, after a few decades of co-administration the waters are muddied enough to now claim that SSRI are beneficial on their own, but there is no evidence for that. It is much easier to make a study that shows a combination of two drugs is better than one of the drugs alone (especially when one of them is known to work) compared to showing benefit of each drug on their own against placebo. And since lithium was known to be effective, it was easy to fudge a few stats in studies to show SSRI are synergistic with lithium. This is a common and very pernicious tactic employed by Big Pharma as @aguilaroja mentioned several times.

What a debarcle.

One I know was given both lithium and ssri from psychiatrists in the psych ward, I’ve seen a person in psychosis then put on lithium and completely changed them, amazing.

Another person I know told the psych how he wanted to feel and was prescribed ssri based on that, reminds me of a street dealer. The way they are sold into ssri’s gives them a placebo where they think they are functioning because of the drug but cannot see how stressed and disfuntional they are. I’ve found people find comfort in the diagnosis and drug taking.. “I’ve got this and I take this and I’m ok now, everyone else is taking something” - in denial, learned helplessness.
 

haidut

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What a debarcle.

One I know was given both lithium and ssri from psychiatrists in the psych ward, I’ve seen a person in psychosis then put on lithium and completely changed them, amazing.

Another person I know told the psych how he wanted to feel and was prescribed ssri based on that, reminds me of a street dealer. The way they are sold into ssri’s gives them a placebo where they think they are functioning because of the drug but cannot see how stressed and disfuntional they are. I’ve found people find comfort in the diagnosis and drug taking.. “I’ve got this and I take this and I’m ok now, everyone else is taking something” - in denial, learned helplessness.

In a state of low energy, certainty is very attractive because it helps legitimize dysfunction.
 

aguilaroja

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...The conclusion - not only are SSRI drugs ineffective but their risks far outweigh even the (mostly) theoretical benefits claimed...

Evidence for SSRI harm to bone metabolism is mounting. This is a placeholder. If time allows, I may do a longer, separate post:

Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone? - PubMed - NCBI
“Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants have also been associated with reduced bone mineral density and increased fracture risk. Therefore, SSRI exposure while breastfeeding may exacerbate lactational bone loss, compromising long-term bone health”

“Approximately 95% of peripheral serotonin is synthesized in the enterochromaffin cells of the gut in a non-lactating animal.. However, during lactation, the mammary gland contributes more significantly to circulating serotonin stores than the gut.… As such, the mammary gland coordinates serotonin homeostasis during lactation.”

“Intramammary SSRI administration to dairy cows accelerated mammary gland involution and repressed milk yield

“Mice treated with a high dose of fluoxetine (20 mg/kg) have less bone formation and whole-body BMD than control mice, although there was no effect in mice dosed with 5 mg/kg fluoxetine.… The length of exposure to fluoxetine also appears to have an effect. Short-term (three weeks) fluoxetine exposure increased bone mass by acting directly on the osteoclasts to prevent bone resorption, while longer use (six weeks) was associated with net bone loss via a decrease in bone formation…”

“Exposure to SSRI antidepressants during the peripartum period may exacerbate the mammary serotonin-PTHrP axis, resulting in persistent reductions in BMD and increasing the risk of osteoporosis and fracture.”

High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures: The MrOS Sweden Study. - PubMed - NCBI
“Serotonin was associated with hip fracture in linear analysis (hazard ratio
 = 1.27, 95% confidence interval [CI] 1.03-1.58) and to all fractures in a nonlinear manner,…”

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men. - PubMed - NCBI
“Among younger men (20-60 year; n = 557), adjusted mean CTx and PINP values were 12.4%…and 13.6%…lower among SSRI users compared to non-users, respectively….These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants…. SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.”
 

haidut

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Evidence for SSRI harm to bone metabolism is mounting. This is a placeholder. If time allows, I may do a longer, separate post:

Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone? - PubMed - NCBI
“Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants have also been associated with reduced bone mineral density and increased fracture risk. Therefore, SSRI exposure while breastfeeding may exacerbate lactational bone loss, compromising long-term bone health”

“Approximately 95% of peripheral serotonin is synthesized in the enterochromaffin cells of the gut in a non-lactating animal.. However, during lactation, the mammary gland contributes more significantly to circulating serotonin stores than the gut.… As such, the mammary gland coordinates serotonin homeostasis during lactation.”

“Intramammary SSRI administration to dairy cows accelerated mammary gland involution and repressed milk yield

“Mice treated with a high dose of fluoxetine (20 mg/kg) have less bone formation and whole-body BMD than control mice, although there was no effect in mice dosed with 5 mg/kg fluoxetine.… The length of exposure to fluoxetine also appears to have an effect. Short-term (three weeks) fluoxetine exposure increased bone mass by acting directly on the osteoclasts to prevent bone resorption, while longer use (six weeks) was associated with net bone loss via a decrease in bone formation…”

“Exposure to SSRI antidepressants during the peripartum period may exacerbate the mammary serotonin-PTHrP axis, resulting in persistent reductions in BMD and increasing the risk of osteoporosis and fracture.”

High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures: The MrOS Sweden Study. - PubMed - NCBI
“Serotonin was associated with hip fracture in linear analysis (hazard ratio
 = 1.27, 95% confidence interval [CI] 1.03-1.58) and to all fractures in a nonlinear manner,…”

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men. - PubMed - NCBI
“Among younger men (20-60 year; n = 557), adjusted mean CTx and PINP values were 12.4%…and 13.6%…lower among SSRI users compared to non-users, respectively….These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants…. SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.”



Considering serotonin is the most potent endogenous stimulant (more so than even CRH) of ACTH and thus cortisol release, the relationship between serotonin and osteoporosis/osteopenia should be quite obvious to the whitecoats. Peat wrote in one of his articles that anti-serotonin drugs are anabolic for the bones and the lowering of cortisol/estrogen and increase in gonadal steroidogenesis the 5-HT antagonists cause is probably one of the main beneficial mechanisms.
 

Wagner83

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Peat wrote in one of his articles that anti-serotonin drugs are anabolic for the bones and the lowering of cortisol/estrogen and increase in gonadal steroidogenesis the 5-HT antagonists cause is probably one of the main beneficial mechanisms.
What happens when one gets used to them and doesn't notice obvious effects or even negative effects? Are they still working in the same direction?
 

haidut

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What happens when one gets used to them and doesn't notice obvious effects or even negative effects? Are they still working in the same direction?

I would say yes, because they are maintaining the opposition to serotonin. Peat also said that many people notice a potent, initial effects to many supplements/chemicals that later on subsides. He said it can be addictive if the effects is always that strong, so it it is probably a good thing that things settle into a new normal that does not impress us much.
 

Frankdee20

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The only SSRI I know that has anti serotonin effects, specifically on receptor 2C, is Prozac
 

haidut

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The only SSRI I know that has anti serotonin effects, specifically on receptor 2C, is Prozac

Big Pharma is VERY sneaky. Some of of the newer SSRI are antagonists of several 5-HT receptors.
Vortioxetine - Wikipedia

So, they still get to claim serotonin is good for us since their new SSRI drug treats depression when in reality most of its effects are serotonin antagonism.
 

Frankdee20

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Big Pharma is VERY sneaky. Some of of the newer SSRI are antagonists of several 5-HT receptors.
Vortioxetine - Wikipedia

So, they still get to claim serotonin is good for us since their new SSRI drug treats depression when in reality most of its effects are serotonin antagonism.

At least the classification seems appropriate - Serotonin Modulators and Stimulators. Perhaps SSRI is no longer a sexy acronym. Looks like this one blocks 5ht3 the most, and activates 1A. I wonder if that’s on the pre or post synaptic side.
 

haidut

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At least the classification seems appropriate - Serotonin Modulators and Stimulators. Perhaps SSRI is no longer a sexy acronym. Looks like this one blocks 5ht3 the most, and activates 1A. I wonder if that’s on the pre or post synaptic side.

It is marketed as both, and since it is structurally derived from fluoxetine (even its name is a derivative) most people will think of it as an SSRI. That may even increase sales of older SSRI drugs by association, as newer drugs that are more successful due their serotonin antagonism become popular.
Vortioxetine: A Unique Antidepressant for Major Depressive Disorder
"...Vortioxetine received FDA approval for the treatment of major depressive disorder in 2013. The drug is an SSRI, but it also acts as a 5HT agonist, antagonist, and transport inhibitor.3"
 
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