[_98fj]

Just a couple of unordered facts here, because discussions about this topic tend to get very confused:

1. Serotonin is a very basic, very old transmitter found in all bilateral animals. Humans have two sites of serotonin-production, one in the body, one in the brain. 90% of serotonin resides in the body.

2. Serotonin in general regulates "activity". It affects hunger, gut-movement, sleep, cell-growth, mood, body-temperature, blood-pressure and many other things. Any drugs changing serotonin-levels also affect these areas, that is why there are so many adverse effects.

3. SSRIs help exactly one group of people: those who have too low levels of serotonin. When their serotonin is boosted, circuits in the brain like the connection between thoughts and emotions start to work properly, hence they get more in touch with themselves.

4. People who have too little serotonin can show the exact same symptoms like people whose serotonin levels way too high (!!). Prescribing SSRIs to those people will worsen their state and may even lead to life-threatening conditions.

5. The level of serotonin can be tested properly by exactly one method: laboratory blood/urine sampling, which costs a couple hundred dollars, but is available. These doctors generally also know about amino-acid therapy, which consists of nutritional supplements which help the body in manufacture the missing transmitter. This can lower the need for medication, but needs proper testing first.

6. People can have proper serotonin levels and still be sad/angry/depressed. The question still is which brain-circuit is malfunctioning. If the problem is the connection between emotions and thought, serotonin helps. If the malfunctioning circuitry concerns attention regulation [0], like with people who have a genetic disposition towards ADHD, then dopamine helps.

7. People can have all their neurotransmitters adjusted to proper levels and still not be perfectly well. We are talking about signalling inside mutable structures here. Changes in signalling affect the structure, changing the structure affects the signalling.

Fixing neurotransmitters makes someone able to use all of his brain. He still has to use it properly though, to get better.

[0] https://en.wikipedia.org/wiki/Frontostriatal_circuit

[khed]

I am a practicing physician with 2 years of graduate level course work in neuroscience.

Point 3 and 4 are wrong. There is no evidence that SSRIs work by fixing a chemical imbalance.

There are multiple metananlyses in top tier journals that indicate that SSRIs have an irrelevant clinical effect. SSRIs are almost all placebo with the downside of causing serious side effects. The small effect that isn't due to placebo is probably not clinically relevant.

The only cogent defense of SSRIs I have read is http://slatestarcodex.com/2014/07/07/ssris-much-more-than-yo.... The author is a practicing psychiatrist. The main disagreement he has with the large metaanalyses is that even though the effect size is small it's better than nothing.

[_98fj]

I know these things from a friend who is a doctor and works with these neurotransmitter tests since about 10 years.

I asked her how accurate these tests were and she said that, while you can't read everything off a sheet, there are patients, where she can already guess the result of the tests from the bodily symptoms the patient is describing (energy level at which times of the day, feeling of hunger, insomnia etc.).

Quite often serotonin is low and once it has been boosted (verified by an additional test a couple of month later) the patient is feeling a lot better.

Which, like I said, doesn't imply that that's all there is to mental well-being.

These tests also measure stress hormones, which usually are out of bounds as well.

> There is no evidence that SSRIs work by fixing a chemical imbalance.

I don't even know how one would define "chemical imbalance" in such a complex system as the human body.

All I know is that there are average ranges for transmitters and the more somebody's results are inside these ranges, the better he typically feels.

[khed]

There is no evidence for the chemical imbalance hypothesis. Your friend anecdotal evidence is contradicted by a large body of emprical research. For a good overview of the evidence on SSRIs on depression I would recommend the article "antidepressants and the placebo effect". https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/?report...

[kqr]

Balls I went deep on this one. Almost makes me want to subscribe to BJPsych or something. So interesting!

[mfukar]

I think you should both stop here.

[Broken_Hippo]

I don't. This sort of discussion from people in the field and what their friends see is helpful because it can change how other laypeople see the issue. Furthermore, I like seeing these sorts of discussions because I feel they make me more intelligent through gaining a different perspective.

[mfukar]

I'm sorry - no text on Hacker News will convince me the person typing it is an expert in anything. Especially when they present inaccuracies and opinions as facts.

[Balgair]

No way! Having MDs or MD like people on HN is a joy! We talk about the inanities of compsci jargon all the time on this site. Hearing the debates in Bio and the Medical field on here is a rare joy!

[kvb]

I like the way Scott Alexander frames the effect size. This is from the conclusion the blog post you link:

  An important point I want to start the conclusion section
  with: no matter what else you believe, antidepressants are 
  not literally ineffective. Even the most critical study – 
  Kirsch 2008 – finds antidepressants to outperform placebo 
  with p < .0001 significance. An equally important point: 
  everyone except those two Scandinavian guys with the long 
  names agree that, if you count the placebo effect, 
  antidepressants are extremely impressive. The difference 
  between a person who gets an antidepressant and a person 
  who gets no treatment at all is like night and day. The 
  debate takes place within the bounds set by those two 
  statements. Antidepressants give a very modest benefit 
  over placebo. Whether this benefit is so modest as to not 
  be worth talking about depends on what level of benefits 
  you consider so modest as to not be worth talking about. 
  If you are as depressed as the average person who 
  participates in studies of antidepressants, you can expect 
  an antidepressant to have an over-placebo-benefit with an 
  effect size of 0.3 to 0.5. That's the equivalent of a diet 
  pill that gives you an average weight loss of 9 to 14 
  pounds, or a growth hormone that makes you grow on average 
  0.8 to 1.4 inches.

Note that this is the over-placebo benefit, and placebos already have a large benefit in most depression studies.

[ada1981]

Some good info here, however just want to point out that feeling sad / angry is not te result of a brain circuit malfunctioning.

All of our emotions are useful signals and it's often our learned responses to those emotions that are the problem.

[_98fj]

I agree, that was bad wording on my side.