44 replies to this topic

[stephen_b]

This site makes arguments that the low serotonin explanation theory of depression is flawed. Part of the argument presented there is that if low serotonin were the cause, the increase in serotonin following antidepressant administration should immediately relieve depression, which is not the case.

It also cites a French drug tianeptine that increases serotonin reuptake and which is claimed to be as effective as prozac, which does the opposite. (I think that claim is that prozac, after a few weeks, has the effect of reducing the amount of serotonin in the synapses, which not coincidentally is the same time it starts affecting depression.

Any thoughts on whether this idea has merit?

Stephen

[edward]

Definitely has merit as far as I am concerned, my own depression was never fully relieved until my dopamine and norepinephrine systems were boosted, first by Welbutrin, now by low dose deprenyl and modafinil.

Also remember the first antidepressant was a MAOI which affected serotonin, norepinephrine and dopamine, and all the subsequent antidepressants up until Prozac in the 90s were Norepinephrine focused, all had some effect on Serotonin but that was not the focus.

I also think depression is much more complex then we realize. Note also there are many neurotransmitter substances that remain a mystery to us. Note also the brain to a large part still remains a mystery. We are still in the dark ages of neuroscience.

[FunkOdyssey]

Depression is definitely complex and there is no single theory that can adequately explain it for everyone, considering there are so many different causes. Just to name a few, hypothyroidism, hypogonadism, chronic infection, heavy metal toxicity, etc, etc, etc. What is most shocking is that anyone ever accepted serotonin imbalance as a universal theory for depression.

Edited by FunkOdyssey, 19 June 2008 - 04:25 PM.

[VictorBjoerk]

What is the exact reason that starvation creates depression?

[sUper GeNius]

There is some good evidence that SSRI's promote the growth of a small group of neurons in the brain, a group that is diminished/killed by chronic stress. In support of this hypothesis, it is known that the time required for neurons to grow and reach maturation is about the same amount of time that it takes for a person on an SSRI to realize beneficial effects.

[ortcloud]

I think that boosting serotonin via ssri is just a convenient way for the pharma companies to get the most efficacy and least side effects for the general population regardless of the reason of the depression in the first place, which the drug co's couldnt care less about. Maybe we are assuming that they are insinuating that depression is a serotonin deficiency.

[mentatpsi]

is it just me or is a symptom basis for disease incomplete and rather simplistic? My basis is exactly the same as Funk's; it seems rather foolish to even have a disorder called depression with a generic cause. It's an easy marketing move; generic cause equals generic solution. I'm just waiting for the day of truly advanced medicine.

[sUper GeNius]

is it just me or is a symptom basis for disease incomplete and rather simplistic? My basis is exactly the same as Funk's; it seems rather foolish to even have a disorder called depression with a generic cause. It's an easy marketing move; generic cause equals generic solution. I'm just waiting for the day of truly advanced medicine.

Generic cause? There are different types of depression, and several treatments available. SSRI's are simply one type. These drugs are tested against animal models, like in mice. One is the helplessness response, where mice stop swimming under stressful conditions.

[mentatpsi]

is it just me or is a symptom basis for disease incomplete and rather simplistic? My basis is exactly the same as Funk's; it seems rather foolish to even have a disorder called depression with a generic cause. It's an easy marketing move; generic cause equals generic solution. I'm just waiting for the day of truly advanced medicine.

Generic cause? There are different types of depression, and several treatments available. SSRI's are simply one type. These drugs are tested against animal models, like in mice. One is the helplessness response, where mice stop swimming under stressful conditions.

SSRI's are used quite a bit more prescribed than other depression drugs[1], I'm bothered by the perception that there is one type and a tendency to use that one type.

What i was getting at was that depression could be a side effect of various other conditions, I'm just saying i'd prefer a better diagnostic system involving analyzing the brain, rather than a behavioral diagnostic system for disorders. It seems archaic to observe a person's behaviors and base medication on that, it's quite a flawed system. Especially when a psychiatrist is hasty to make a decision or is biased towards a particular medication.

[1]

"Nearly 150 million U.S. prescriptions were dispensed in 2004 for SSRIs and similar antidepressants called SNRIs, according to IMS Health, a Fairfield, Conn., drug data and consulting company – more than for any other drug except codeine..."
August 13, 2007, David Kupelian, WorldNetDaily, "Why so many Americans today are 'mentally ill'";

http://www.worldnetd...RTICLE_ID=57143

"Since the introduction of Prozac in 1987-and this was the first of the second-generation psychiatric drugs said to be so better than the first-the number of so-called disabled mentally ill in the United States has been increasing at the rate of 150,000 people per year, or 410 people newly disabled by "mental illness" every day."


Peter Stastny / Peter Lehmann (Eds.) - Alternatives Beyond Psychiatry

more articles on: http://ssri-research.com/statistics

[FunkOdyssey]

SSRI's are used quite a bit more prescribed than other depression drugs[1], I'm bothered by the perception that there is one type and a tendency to use that one type.

What i was getting at was that depression could be a side effect of various other conditions, I'm just saying i'd prefer a better diagnostic system involving analyzing the brain, rather than a behavioral diagnostic system for disorders. It seems archaic to observe a person's behaviors and base medication on that, it's quite a flawed system. Especially when a psychiatrist is hasty to make a decision or is biased towards a particular medication.

Definitely agree -- depression is often a behavioral manifestation of physical problems that a psychiatrist is unqualified / unable to diagnose, so with an SSRI you're throwing a side effect ridden band-aid on a deeper issue. This is confirmed IMHO by the poor efficacy of all antidepressant treatments which barely outperform the placebo in most trials.

In the cases where depression is caused by chronic stress alone (bad family situation, kids at school picking on you every day, etc) then an SSRI makes more sense (although tianeptine would be better IMO).

Edited by FunkOdyssey, 23 June 2008 - 04:22 PM.

[mentatpsi]

[...]
Definitely agree -- depression is often a behavioral manifestation of physical problems that a psychiatrist is unqualified / unable to diagnose, so with an SSRI you're throwing a side effect ridden band-aid on a deeper issue. This is confirmed IMHO by the poor efficacy of all antidepressant treatments which barely outperform the placebo in most trials.

In the cases where depression is caused by chronic stress alone (bad family situation, kids at school picking on you every day, etc) then an SSRI makes more sense (although tianeptine would be better IMO).

I agree completely .

My opinion on the chronic stress through the examples given is that Cognitive Behavioral Therapy would be a wiser choice of therapy rather then going directly to medications. I believe the tendency to deal with adaptation problems with medication first is one of the issues of current practices. For the most part it could just be an issue of the cognitions underlying the perspective of the problems. Behavior is such a superficial level of analysis, so many interpretations could be had by just observing an individual. As such, real analysis at this level takes time, something that isn't demonstrated in current practices. Only given the right tools might the time decrease and efficiency increase.

Still i have to admit Tianeptine looks pretty interesting .

Edited by mysticpsi, 23 June 2008 - 07:20 PM.

[eternaltraveler]

I'm bothered by the perception that there is one type and a tendency to use that one type.

SSRIs are tried first in america because they have a much better side effect profile than other anti depressant drugs commonly used. TCAs and MAOIs have higher efficacy, but their side effects are terrible. Something like Bupropion is somewhere in the middle.

It would be malpractice to jump immediately to MAOIs before trying SSRIs.

Best for depression is ECT. It scares people but is the best option when someone is so depressed that they have a high likelyhood of killing themselves (it works immediately).

[mentatpsi]

I'm bothered by the perception that there is one type and a tendency to use that one type.

SSRIs are tried first in america because they have a much better side effect profile than other anti depressant drugs commonly used. TCAs and MAOIs have higher efficacy, but their side effects are terrible. Something like Bupropion is somewhere in the middle.

hmm, well that does make sense. How is it in other countries? Would be interesting to know how different cultures influence pharmacy...

Best for depression is ECT. It scares people but is the best option when someone is so depressed that they have a high likelyhood of killing themselves (it works immediately).

i've always wondered how that works

[london710]

interesting:
http://en.wikipedia.org/wiki/Ketamine

The National Institute of Health News reports that a study of 18 patients has found that ketamine significantly improved treatment-resistant major depression within hours of injection.[24] The improvement lasted up to one week after the single dose.[25] The patients in the study were previously treatment resistant, having tried an average of six other treatments that failed. NIMH director Dr. Thomas Insel said in the paper:

"To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose. These were very treatment-resistant patients."

The researchers apparently attribute the effect to ketamine being an NMDA receptor antagonist.[26] Those findings of Zarate et al corroborate earlier findings by Berman et al.[27] However Zarate et al do raise some concerns about their results due to a possible lack of blinding, because of the inebriating effects of low dose ketamine infusion, and it is recommended that future studies include an active placebo.

The findings by Zarate et al. are confirmed by Liebrenz et al, who substantially helped a 55-year-old male subject with a treatment-resistant major depression and a co-occurring alcohol and benzodiazepine dependence by giving an intravenous infusion of 0.5 mg/kg ketamine over a period of 50 minutes and Goforth et al who helped a patient with severe, recurrent major depressive disorder that demonstrated marked improvement within 8 hours of receiving a preoperative dose of ketamine and one treatment of electroconvulsive therapy with bitemporal electrode placement.[28]<[29]

However, a new study in mice by Zarate et al. shows that blocking the NMDA receptor is an intermediate step. According to this study, blocking NMDA increases the activity of another receptor, AMPA, and this boost in AMPA activity is crucial for ketamine’s rapid antidepressant actions. NMDA and AMPA are receptors for the neurotransmitter glutamate. The glutamate system has been implicated in depression recently. This is a departure from previous thinking, which had focused on serotonin and norepinephrine. The glutamate system may represent a new avenue for treatment and research.[30]

[ajnast4r]

to play devils advocate here, st johns wort absolutely 100% changed my life in and of itself. while i've never tried a pharmaceutical SSRI, st johns wort's main method of action is serotonin reuptake inhibition (although it appears to be a lot more complex than JUST that, effecting dopamine and glutamate systems as well). it completely eliminated my depressive episodes.

Edited by ajnast4r, 24 June 2008 - 12:02 AM.

[mentatpsi]

to play devils advocate here, st johns wort absolutely 100% changed my life in and of itself. while i've never tried a pharmaceutical SSRI, st johns wort's main method of action is serotonin reuptake inhibition (although it appears to be a lot more complex than JUST that, effecting dopamine and glutamate systems as well). it completely eliminated my depressive episodes.

to be stereotypical, that's because it's natural. lol jk . I was really just critiquing the method, and for the most part just being idealistic. It's a market, and until these technologies become cheaper and therefore more readily available i can only hope. I sometimes worry that a tendency for one type of medication could easily be a monopoly forming. Monopolies hinder progress by various methods, but elrond makes a good point it could just be the lower risk profile of SSRIs. Still, there are various advancements in medicines to be had (smart drugs), and i'm waiting for it .

Congratz on finding something that works .

[cyborgdreamer]

In the cases where depression is caused by chronic stress alone (bad family situation, kids at school picking on you every day, etc) then an SSRI makes more sense (although tianeptine would be better IMO).

Depending on the person, I would think it would be better to help them get out of a bad situation than medicate them so that they'll tolerate it.

[sUper GeNius]

In the cases where depression is caused by chronic stress alone (bad family situation, kids at school picking on you every day, etc) then an SSRI makes more sense (although tianeptine would be better IMO).

Depending on the person, I would think it would be better to help them get out of a bad situation than medicate them so that they'll tolerate it.

Sometimes the damage done to the brain by the chronic stress is permanent. In addition, SSRI's are used for traumatic stress disorder as well. i.e I'm not in downtown Baghdad anymore, but I'm still sick.

[FunkOdyssey]

In the cases where depression is caused by chronic stress alone (bad family situation, kids at school picking on you every day, etc) then an SSRI makes more sense (although tianeptine would be better IMO).

Depending on the person, I would think it would be better to help them get out of a bad situation than medicate them so that they'll tolerate it.

Of course, but that will not always be possible, especially from the perspective of the health-care provider (limited ability to influence those circumstances). In that case, the best you can do may be an SSRI, since telling patients to order tianeptine from an Indian pharmacy is generally frowned on. This example is one of the few where an SSRI may be genuinely helpful to prevent or reverse negative changes like hippocampal atrophy that are induced by chronic stress.

Edited by FunkOdyssey, 24 June 2008 - 01:29 PM.

[ajnast4r]

its a real shame that the first & foundational consideration for a drug is its ability to bring profit... we have an entire medical community who have passed up treating patients with phytopharmacueticals like the WS5572 st johns wort extract that have been shown NUMEROUS times to be as or MORE effective than any tricyclic or ssri its been put up against, with much less incident of side effect. its so disgusting to me just how much of a hand pharmaceutical companies have in what we consider valid medicine/practice today.

http://www.ncbi.nlm....Pubmed_RVDocSum

The clinical efficacy of some standardized St. John's Wort extracts (SWEs) such as WS(®) 5570, WS(®) 5572 or LI 160 in the treatment of mild, moderate and severe major depression has been demonstrated in 38 controlled clinical trials and two recent meta-analyses.Sixteen post-marketing surveillance studies with such preparations, based on a total of 34,804 patients, recorded an incidence of adverse events (AEs) among patients between 0% and 6%. Of these studies, the four large-scale surveillance studies with a total of 14,245 patients recorded a rate of AEs ranging from 0.1% to 2.4% and a drop-out rate due to AEs of 0.1-0.9%. This is at least ten-fold lower than that recorded with synthetic antidepressants. AEs associated with SWE treatment were mild and transient in nearly all cases. As with synthetic antidepressants, pharmacokinetic interactions may occur occasionally as a result of activity changes of drug-metabolising and drug-transporting proteins, especially CYP 3A4 and P-gp. Risks to the patient are not caused by SWE but by drugs with a narrow therapeutic range. Consequently, SWE preparations should not be taken concurrently with other antidepressants, with coumarin-type anticoagulants, the immunosuppressants cyclosporine and tacrolimus, protease and reverse transcriptase inhibitors used in anti-HIV treatment or with certain antineoplastic agents. However, such cases are extremely rare and, with medical supervision, easily avoided. In conclusion, the safety of SWE must be considered more favourable than that of synthetic antidepressants.

PMID: 16428030 [PubMed - indexed for MEDLINE

*:

ws5572 = perika
li160 = kira

Edited by ajnast4r, 24 June 2008 - 02:20 PM.

[mike250]

and I was always under the impression that St John's wort was just a weak version of SSRIs

[ajnast4r]

and I was always under the impression that St John's wort was just a weak version of SSRIs

st johns wort's method of action is VERY complex... and the science proves its a MUCH better starting place than any synthetics for people with mild-moderate depression, but somehow i doubt you will ever see many mainstream doctors make that recommendation.

im also a big believer that st johns wort is having permanent effects on the brain... i, and a lot of other users, have been able to cut my dose by 2/3 after a year of use and maintain the same positive benefits. a good portion of people come off it totally, and having had their depression totally relieved.

CNS Drugs. 2003;17(8):539-62.

Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.

Edited by ajnast4r, 24 June 2008 - 03:12 PM.

[mentatpsi]

I'm a bit biased against most SSRIs, i find them to produce zombie like emotional states rather than actually raising moods, plus the other side effects are rather bothersome. If the individual is capable of regulating the emotions himself with the right training i'd say that would be a wiser approach.

That's an interesting find though ajnast4r. I am also bothered by big pharma but i don't really see a solution to it since this is essentially the way things go - destroy competition. The only real solution is to become knowledgeable.

london710's find is also interesting...

[Irradiance]

Having tried tianeptine for several weeks, I am of the opinion that it does absolutely nothing. Most likely the positive benefits are placebo. I'm very sensitive the slight changes in my neurochemistry, and I never noticed even the slightest inkling of any effect whatsoever. My girlfriend felt similarly, although she's not as sensitive as I am. Conversely, SSRIs and the like have a rather profound effect, whether or not it's the right one or desirable.

[ajnast4r]

I'm a bit biased against most SSRIs, i find them to produce zombie like emotional states rather than actually raising moods, plus the other side effects are rather bothersome.

i had the same effect from 5-htp, emotionally flattening. i became very blah & apathetic after about a week of 100mg daily. whereas st johns wort was the exact opposite; increased the vividness of positive emotion, and decreased the sharpness of negative emotion... among other things (decreased introversion, increased optimism, increased motivation, increase in overall positive mood & wellbeing, complete cessation of depressive episodes)

as ive mentioned before, my depression was not inherent or situational... i believe it was caused by mdma abuse, so my extreme results with sjw may be due to that. although a good friend of mine who has never abused drug recently started on sjw, and noticed the same effects within a few days.

[mike250]

I'm a bit biased against most SSRIs, i find them to produce zombie like emotional states rather than actually raising moods, plus the other side effects are rather bothersome.

i had the same effect from 5-htp, emotionally flattening. i became very blah & apathetic after about a week of 100mg daily. whereas st johns wort was the exact opposite; increased the vividness of positive emotion, and decreased the sharpness of negative emotion... among other things (decreased introversion, increased optimism, increased motivation, increase in overall positive mood & wellbeing, complete cessation of depressive episodes)

as ive mentioned before, my depression was not inherent or situational... i believe it was caused by mdma abuse, so my extreme results with sjw may be due to that. although a good friend of mine who has never abused drug recently started on sjw, and noticed the same effects within a few days.

it also seems that not every St John's wort extract is equivalent. Most of the stuff sold OTC is of shady quality.

[quarter]

I'm a bit biased against most SSRIs, i find them to produce zombie like emotional states rather than actually raising moods, plus the other side effects are rather bothersome.

i had the same effect from 5-htp, emotionally flattening. i became very blah & apathetic after about a week of 100mg daily. whereas st johns wort was the exact opposite; increased the vividness of positive emotion, and decreased the sharpness of negative emotion... among other things (decreased introversion, increased optimism, increased motivation, increase in overall positive mood & wellbeing, complete cessation of depressive episodes)

as ive mentioned before, my depression was not inherent or situational... i believe it was caused by mdma abuse, so my extreme results with sjw may be due to that. although a good friend of mine who has never abused drug recently started on sjw, and noticed the same effects within a few days.

Do you recommend a particular brand of SJW? Dosage?

Anybody else have experiences with SJW? I like the sound of ajnast4r's experience with it. I'm stressed about finances and work and finding its making me overly negative.

[mike250]

I'm a bit biased against most SSRIs, i find them to produce zombie like emotional states rather than actually raising moods, plus the other side effects are rather bothersome.

i had the same effect from 5-htp, emotionally flattening. i became very blah & apathetic after about a week of 100mg daily. whereas st johns wort was the exact opposite; increased the vividness of positive emotion, and decreased the sharpness of negative emotion... among other things (decreased introversion, increased optimism, increased motivation, increase in overall positive mood & wellbeing, complete cessation of depressive episodes)

as ive mentioned before, my depression was not inherent or situational... i believe it was caused by mdma abuse, so my extreme results with sjw may be due to that. although a good friend of mine who has never abused drug recently started on sjw, and noticed the same effects within a few days.

Do you recommend a particular brand of SJW? Dosage?

Anybody else have experiences with SJW? I like the sound of ajnast4r's experience with it. I'm stressed about finances and work and finding its making me overly negative.

http://www.iherb.com...px?c=1&pid=4561
http://www.iherb.com...px?c=1&pid=3410

[quarter]

http://www.iherb.com...px?c=1&pid=4561
http://www.iherb.com...px?c=1&pid=3410

Thanks and I should have read the whole thread.

[graatch]

ajnast4r, so, just to make it totally clear, SJW did NOT have the typical SSRI sides of:

- emotional blunting
- apathy
- impotence
- poor focus

?

If so, I might have to try it out. These side effects make the "classic" SSRI a no-go for me.