
Yale scientists explain how ketamine vanquishes depression within hours - 001sky
http://news.yale.edu/2012/10/04/yale-scientists-explain-how-ketamine-vanquishes-depression-within-hours
======
chunkyslink
I used to take quite a few drugs recreationally and I can quite honestly say
that Ketamine gave me 'God like' experiences unlike anything else I have ever
experienced. Repeatedly (and reproducibly) I could 'see' everything in the
universe from the smallest particle to the planets and solar system in one go.
I could comprehend nature, science and space and observe everything working as
a system, from a point way above it all (it is dissociative after all). It
made me euphoric and happy and when coming down from the experience I could
(and still can) remember that feeling and how powerful it was / is. Of course
to an observer I was basically asleep in a chair.

This news doesn't surprise me at all.

~~~
alwaysinshade
I had a somewhat different experience. I thought that I had stopped breathing
and that my heart had ceased (in actual fact my body was numb - I couldn't
feel a pulse) so I stood in front of a mirror completely naked for the next 20
minutes staring at my chest. Thankfully reason stepped in and I managed to
compute that if my pulse or breathing had ceased, I'd be in a heap on the
floor rather than obsessing in front of a mirror. Suddenly I felt calm and
proceeded to throw out some cool graphics in Photoshop and made an excellent
puff pastry quiche. Again, without clothes.

My lesson was that drugs should be experimented with in the company of a
friend or partner.

~~~
ktizo
Sounds like quite a risky quiche. Did it come with extra crunchy bits?

~~~
001sky
<http://en.wikipedia.org/wiki/K-hole>

------
DanBC
Hacker News has a few readers who self-experiment with a variety of
substances.

I'm not trying to stop them, but there are reports of Ketamine abuse being
damaging to the bladder. Some people have had their bladders removed.

(<http://www.bbc.co.uk/news/health-17411492>)

(<http://www.bbc.co.uk/news/uk-17344089>)

I have no idea on the dosing needed for harmful effects - is several large
doses enough? Would very many small doses be harmful?

Some people taking anti-depressants do so for a long time. Most are
recommended to take them for at least two years to prevent relapse, but some
medications (especially venlafaxine) can be hard to come off. (I've been told
that I'll probably be taking venlafaxine for the rest of my life.)

So, this news is exciting because better understanding of mental health
problems is really important, and better treatments would be fantastic. But
please be careful when self-experimenting with possible nootropics.

~~~
tryitnow
"But please be careful when self-experimenting with possible nootropics."

I would also add "please be careful when following the advice of a physician."

In fact, I think it may be best to just say "Please be careful."

~~~
DanBC
eh, that's probably truer that most people like to think about.

------
001sky
Orignal is <http://www.sciencemag.org/content/338/6103/68> (paywall)

_________________

 _Abstract

Basic and clinical studies demonstrate that depression is associated with
reduced size of brain regions that regulate mood and cognition, including the
prefrontal cortex and the hippocampus, and decreased neuronal synapses in
these areas. Antidepressants can block or reverse these neuronal deficits,
although typical antidepressants have limited efficacy and delayed response
times of weeks to months. A notable recent discovery shows that ketamine, a
N-methyl-d-aspartate receptor antagonist, produces rapid (within hours)
antidepressant responses in patients who are resistant to typical
antidepressants. Basic studies show that ketamine rapidly induces
synaptogenesis and reverses the synaptic deficits caused by chronic stress.
These findings highlight the central importance of homeostatic control of mood
circuit connections and form the basis of a synaptogenic hypothesis of
depression and treatment response._

~~~
shrivats
For greater context, note that this is a Review article (that is to say, not
an article describing new research, but rather an article synthesizing many
recently published results and hypothesizing a theory that could unite them).
It's part of a special issue that _Science_ is doing this week that focuses on
depression. See <http://www.sciencemag.org/content/338/6103/67.full> (not pay-
walled) for a discussion of the various depression-centric papers that are in
this issue.

~~~
samstave
With great context comes great information!

------
tokenadult
From the press release submitted here: "In large doses, ketamine can cause
short-term symptoms of psychosis and is abused as the party drug 'Special K.'"
This is a general problem with drugs for mood disorders--the human mood
regulatory system is very complicated, and it is possible for patients to
engage in behavior that is dangerous to self and to others when they have low
mood (are in a depressive episode) or when they have high mood (are in a manic
episode). That's why a careful physician always asks about a patient's
personal history when beginning treatment of someone seeking treatment for
depression, to avoid starting out with treatments likely to trigger mania.
Some human beings only get depressed, and never manic, but some can go awry in
either direction.

I heard a National Public Radio story with interviews of researchers on the
same issue as the press release submitted here while on a drive this
afternoon. What most excites researchers about the ketamine studies is not a
prospect of using ketamine itself as a frequent first-line drug for treating
depression, but rather as a model for understanding brain function better and
eventually developing new drugs that are even longer-lasting for treating
depression and even less likely to trigger mania. Human mood disorders are
very diverse--there are probably hundreds of rare genetic variants that
increase the risk of mood system disruption under varying kinds of
environmental stress--so there surely will not be just one drug that will
successfully treat all patients, but rather a gradually growing toolkit of
better and better drugs to treat more and more patients with less risk and
fewer side-effects.

AFTER EDIT: User shrivats just kindly pointed, in a subcomment, to the overall
summary of the Science special issue on depression, in which the ketamine
research and related research is discussed. A paragraph describing another
article in that issue is especially helpful for HN participants: "However, not
all is bleak. There are individuals who overcome difficult situations and show
astonishing resilience in the face of adverse circumstances and other forms of
acute or chronic traumatic stress. Studying them might provide us with clues
about what can go right. Southwick and Charney (p. 79) provide an overview of
current ideas about why some people are more protected against stress and
depression than others and how this knowledge may help us develop better
treatments and successful prevention strategies." Several HN participants
regularly write about strategies of building resilience to face the stress
that many hackers face. Further research on that issue will also be part of
the package in future improved treatments for mood disorders.

~~~
im3w1l
It would be nice if we could device a diminishing returns pill. I am not
really sure how that would work, but maybe use a metabolical pathway as rate
limiter?

------
starpilot
> In their research, Duman and others show that in a series of steps ketamine
> triggers release of neurotransmitter glutamate, which in turn stimulates
> growth of synapses. Research at Yale has shown that damage of these synaptic
> connections caused by chronic stress is rapidly reversed by a single dose of
> ketamine.

There's burgeoning evidence that depression is tied to a lack of neurogenesis
(creation of new brain cells), which may also be tied to serotonin levels.
Some believe that the reason SSRIs take weeks to have antidepressive effects,
even though serotonin levels are restored almost immediately, is that it takes
a while for that to stimulate new brain cells. It's far from certain though
that serotonin has anything to do with depression or neurogenesis. The
atypical antidepressant tianeptine (currently unapproved in the US, but widely
used in western europe) apparently reduces serotonin levels while boosting
neurogenesis, the study of which is summarized well by Stanford neuroscientist
Robert Sapolsky [1]:

> … tianeptine prevented many of these stress-induced changes. These included
> the spectroscopic alterations, the inhibition of cell proliferation, and a
> significant increase in hippocampal volume (as compared with stress +
> vehicle animals). Of significance (see below), tianeptine did not prevent
> the stress-induced rise in cortisol levels.

The restoration of hippocampal volume is important because it's been shown
that low hippocampal volumes correlate with emotional abuse in adolescents [2]
(also by Yale researchers). This was breathtaking for me - bad parenting
literally causes brain damage.

Special K and tianeptine aren't the only efforts at curing depression through
neurogenesis. Neuralstem [3] is testing a drug in humans to treat major
depressive disorder by restoring hippocampal volume, with a controlled study
to complete early next year. That is the only new drug I'm aware of.
Regardless, the serotonin model of depression, the one which produced Prozac
etc. isn't the last word, and it's looking more likely that a dearth of new
synapses may be the culprit in clinical depression.

[1] <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/>

[2]
[http://www.medpagetoday.com/Pediatrics/DomesticViolence/3002...](http://www.medpagetoday.com/Pediatrics/DomesticViolence/30029)

[3] <http://www.neuralstem.com/pharmaceuticals-for-depression>

~~~
robbiep
On the point of neurogenesis this is also the theorised mechanism of
Electroconvulsive therapy for Treatment-resistant depression - it's been
interesting watching the evidence for the mechanisms of the 2 different
treatments slowly grow

~~~
tryitnow
Cool.

For those of you who would like a reference supporting this claim, check out
the following: <http://www.ncbi.nlm.nih.gov/pubmed/10051225>.

I often share stuff I read on HN with friends and it's useful to have evidence
beyond "some dude on HN said so."

~~~
robbiep
thanks, I was too lazy to look it up.

------
kevinalexbrown
Here's my shot at "the most revealing job interview question" (not looking for
a job, I do neuroscience in a separate area):

The review explains why the rapid action of ketamine excites so many
researchers:

 _The discovery that ketamine rapidly increases the number and function of
synaptic connections has focused attention on synaptogenesis as a fundamental
process for the treatment of depressive symptoms and also suggests that
disruption of synaptogenesis and loss of connections underlies the
pathophysiology of depression._

This excites researchers not because ketamine itself would be used to combat
depression, but because depression is still extremely symptomatically defined,
making it difficult to design treatments for. That's roughly how it's
diagnosed in the diagnostic manual used by most psychiatrists: check off a
list of symptoms, if you have enough, you're depressed. It's like going to the
doctor and explaining that your stomach hurts and they say "well, looks like
you have abdominal pain, here's some Advil." Treating the symptoms would be
great if only there were a happiness dial in the brain. Indeed, the effect of
most anti-depressants is often demonstrated prior to a mechanistic
understanding of _why_ they make many patients feel better.

Recently there has been substantial evidence of "synaptogenesis" - the
formation of new potential connections between neurons - from multiple
treatments, including ketamine. So now we have this new picture emerging:
depressed patients tend to have atrophied and "less-connected" neurons in some
brain areas, and some drugs can reverse it, in particular ketamine can reverse
it quite rapidly, and it works in rodents as well as humans.

That makes it very amenable to study. The way this often works in the lab is
the following. Take some rodents, subject them to unpredictable stress to get
them depressed, then give some ketamine. It makes them better. Euthanize the
rodents, slice the brains, and note that the non-ketamine ones have less
dendritic spines in certain areas ("potential input points to a neuron"), but
remarkably, the ketamine ones have more in those areas.

The most important step comes next, where you try to find out what ketamine is
actually doing, since, again, there's no happiness dial in the brain. Create
strains of "knock-out" rodents, where you block the production of certain
chemicals or proteins you think ketamine might affect by altering their
genetic composition. This step is crucial, because it allows you to find out
_which_ effect of ketamine is providing the benefit, because there are many.
You can do this both by observing both behavior (does the ketamine not improve
mood in the genetically altered rodents?) and in physiology (does the ketamine
still increase synaptogenesis in the altered rodents?).

In the end you can kind of work out a map of sorts: ketamine does X things to
the brain and Y in X are the ones that are important, sometimes in certain
combinations. Then you can start creating intelligent drugs that pinpoint
those important processes, to avoid the unfortunate side effects of drugs like
ketamine. Moreover, you now have a better _physiological_ understanding of
depression, instead of just a symptomatic one.

To put it in machine-learning language, it's like going from ideal observer
analysis like mutual information, to an actual parametric model where you
understand the distributions themselves.

~~~
chmike
There are many assumptions in the article and in your comment. We have two
data we will for now assume are facts: 1\. depressed people feel better after
taking ketamine 2\. katamine taking is correlated with synapse generation

You manage to infer, as well as the author of the OP, that depression
decreases the number of synapses or eventually induce a sort fatigue in
synapses because of stress. That depression is not only correlated but also
induced by synapse depletion, that increasing the number of synapse is what
makes depressed people feel better, that depression (the symptom) has one
cause, here stress inducing synapse fatigue or depletion, etc.

It takes just common sense thinking to understand that most of this reasoning
is just crap. Suggesting to put that in a machine learning language is is even
more depressing.

~~~
SeanDav
Who are you? What is the area of your expertise that makes you think you are
qualified to make this comment? What are your sources?

~~~
lutusp
I suggest that you resist posting this kind of inquiry in a scientific
discussion. In science, only evidence counts, not authority or expertise. In
science, the quality of evidence is all that matters, not its source.

In religion and politics, people are judged based on their origins and their
"authority". Not in science.

The OP should have posted sources or links, but apart from that, his remark
needs to be evaluated on its merits, not _his_ merits.

"Science is the organized skepticism in the reliability of expert opinion." —
Richard Feynman

~~~
ryanmolden
The way in which you formulate responses tends to go a long way in determining
the reaction you will get. Disagreeing with people is fine and good,
disparaging them for lacking common sense or being foolish is generally not
helpful and shows either a high level of immaturity or a profound lack of
understanding of effective human communication.

Here is a quick rewrite of the snarkiest bit of the post that I think is not
only drastically more civil but just as effective:

"I fear the reasoning here is incorrect as it conflates correlation with
causation. Being too hasty in using this conclusion with machine learning
would be a mistake."

I know there is a segment here that doesn't believe tone/communication style
should matter, that it is, or should be, entirely about the underlying
verisimilitude of their statements; unfortunately, that is not how 99% of
human beings actually operate. So while you are free to rail against reality
it will make you drastically less effective than you might otherwise be.

~~~
lutusp
> Disagreeing with people is fine and good, disparaging them for lacking
> common sense or being foolish

Okay, but first, locate and circle the words you have just assigned to me in
my original post. What? Can't find those words? Know the expression "straw
man"?

~~~
ryanmolden
My response was really meant to be addressed to chmike, I put it as a response
to your post only because you claimed, like so many others here do, that all
that matters are facts not "authority" (which you do call out) or
"tone/style", which you don't specifically call out but is also a classic
theme in these kind of discussions. Your response does fall squarely under the
umbrella of my original advice though, I am not sure if the irony was intended
or not. Your accusation of use of a straw man seems to also imply you view
this as a debate instead of a discussion, which is sad but not uncommon.

~~~
lutusp
> only because you claimed, like so many others here do, that all that matters
> are facts not "authority"

I ... never ... said .. any ... such ... thing.

Circle the words on the screen in front of you, where I ever uttered these
words, anywhere, on God's green Earth.

You need to start reading what people say, not what your overactive
imagination believes they said.

> ... seems to also imply you view this as a debate instead of a discussion
> ...

When someone invents a position to conveniently argue against, of course it's
a debate -- a debate between fantasy and reality.

Notice how I have in each and every case replied directly to your words, which
I quote in full. Notice how you don't have time to check in with reality
before ascending your soapbox.

~~~
vidarh
> I ... never ... said .. any ... such ... thing.

Can you then perhaps elaborate how else we should take this quote from you:

> I suggest that you resist posting this kind of inquiry in a scientific
> discussion. In science, only evidence counts, not authority or expertise. In
> science, the quality of evidence is all that matters, not its source.

As well as this in your reply to me:

> The bottom line in science, and in any scientific discussion, is that
> authority and expertise are never important. The greatest amount of
> scientific eminence is trumped by the smallest amount of scientific
> evidence.

Of course you might argue that this is not a "scientific discussion", but that
would make both of these messages meaningless or intentionally obtuse in the
context they were posted.

------
siganakis
Also of interest is the observation that Ketamine (and PCP) are associated
with NMDA Antagonist Neurotoxicity (Olney's Lesions), a form of brain damage.

Not really something you should want to self medicate with at this point until
more research is done.

<http://www.dextroverse.org/txt/olney.txt>

<http://en.wikipedia.org/wiki/Olneys_lesions>

~~~
civilian
I originally majored in biochemistry, so this stuff is a nerdy enjoyment.

The levels of ketamine required to form Olney's Lesions are 40mg/kg (given
olney.txt), whereas the typical dose to reach a k-hole (the highest
recreational level) is 1mg/kg.
<http://www.erowid.org/chemicals/ketamine/ketamine_dose.shtml> Also:
<http://en.wikipedia.org/wiki/Olneys_lesions#Controversy>

In addition, the dosage levels of recreational ketamine are lower than the
anesthetic dosages of ketamine. Repeated use of ketamine would probably still
cause problems though, though the problems would be more along the lines of
general drug dependency and not being able to think straight.

 _> Not really something you should want to self medicate with at this point
until more research is done._

I dunno. Depression can be really dangerous & costly too-- both from suicide
and just generally not being happy in life.

~~~
dtf
Ketamine has been known to be "psychologically dependent" with heavy use - I
guess the real world might seem a bit dull for some after all the crazy things
that happen in the K-hole. But very heavy users can also experience extreme
bladder damage, as their tolerance and dosage rise.

It's fascinating to see these demonised recreational drugs being researched
finally for their beneficial side-effects, sometimes in very small doses.
Another one that comes to mind is the reported use of sub-psychoactive doses
of LSD to combat the horror of cluster headaches.

~~~
civilian
My buddy suffers from cluster headaches and he self-retreated with low doses
of LSD. But he was talking to his doctor in the last year, and he learned that
there are ergotamine-based cluster headache medications. LSD also comes from
that chemical, so he jumped on the opportunity.

He's been cluster-headache free since January, and he's really happy that he
doesn't have to rely on the black market for medication.

------
espeed
_In their research, Duman and others show that in a series of steps ketamine
triggers release of neurotransmitter glutamate, which in turn stimulates
growth of synapses._

MSG is monosodium glutamate, and there is research to show MSG is toxic --
it's the glutamate that's bad for you, not the sodium. Flooding your body with
excess glutamate throws off the brain's delicate balance of this
neurotransmitter and leads to excitotoxicity
(<http://en.wikipedia.org/wiki/Excitotoxicity>).

The blood-brain barrier protects you from some of it, but the blood-brain
barrier is not fully formed in babies, and this is why MSG not allowed in baby
food. However, the blood brain barrier can be weakened by any number of
reasons in adults, such as when you have a fever.

Why would ketamine's release of glutamate be different and good for you in
this case?

~~~
D3
Because it's a potent NMDA antagonist which blocks glutamate induced
excitotoxicity.

Also see:
[http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potent...](http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potential_for_treatment_of_excitotoxicity)

------
fluxon
Yale scientists excitedly, repeatedly explain to anyone in the quad how
ketamine vanquishes depression within hours, in, you know, a million million
ways (yale.edu)

I've read too many Onion headlines to ever read headlines like this again.

------
pella
Ketamine & autism

"Drug Reverses Abnormal Brain Function in Rett Syndrome Mice"

[http://www.sciencedaily.com/releases/2012/10/121003132418.ht...](http://www.sciencedaily.com/releases/2012/10/121003132418.htm)

 _"ScienceDaily (Oct. 3, 2012) — A promising study out October 3 in the
Journal of Neuroscience showed that in a mouse model of Rett syndrome,
researchers were able to reverse abnormalities in brain activity and improve
neurological function by treating the animals with an FDA-approved anesthesia
drug, ketamine. Rett syndrome is among the most severe autism-related
disorders, affecting about one in 10,000 female births per year, with no
effective treatments available."_

------
lutusp
> _Yale scientists explain how ketamine vanquishes depression within hours_

Translation: "Yale scientists speculate about how ketamine vanquishes
depression within hours" And until there's a strictly designed study with a
control group, we'll be no closer to a definitive answer. But considering the
drug and its role and target, a control group would be unethical.

~~~
lifeisstillgood
Err why is a non lethal, not particularly damaging drug going to be an
unethical drug trial?

~~~
lutusp
> Err why is a non lethal, not particularly damaging drug going to be an
> unethical drug trial?

Antidepression drugs, indeed all psychoactive drugs, are always a potential
ethics issue. Consider the brouhaha that erupted when it was discovered that
some antidepression drugs caused people to commit suicide or have suicidal
thoughts:

[http://www.medicinenet.com/script/main/art.asp?articlekey=31...](http://www.medicinenet.com/script/main/art.asp?articlekey=31649)

A quote: "The FDA has warned that children and adults taking antidepressants
can become suicidal in the first weeks of therapy and that physicians should
watch patients closely when first giving the drugs or changing dosages. The
FDA is asking drug manufacturers to place explicit warnings about the drugs'
side effects, including the risk of suicide, on their labels."

Any human-administered drug is a potential ethical issue, from vitamins
upward. Imagine a study in which an experimental group is given a daily
vitamin, and a control group is given a placebo but told they're receiving a
vitamin. Several years go by and the relative health of the study participants
is closely monitored.

Can you not see the ethical issue here? Can you not imagine the lawsuits that
would result from the parents of those in the control group who perhaps didn't
thrive as expected, or for some completely imaginary consequence having
nothing to do with the vitamin study, but sufficient to sue for civil damages?

And finally, depression drugs are hardly "non lethal, not particularly
damaging". They are a source of great controversy and have been the focus of a
number of conflicts over the years.

~~~
screwt
That's why it's normal these days, for clinical studies, for the control group
to receive current best available treatment, rather than a placebo.

After all, what you're generally trying to find out is whether the new
treatment is better than what you already have - just being better than a
placebo isn't very informative.

If you're interested in this sort of thing, I strongly recommend reading Ben
Goldacre's work[1].

[1] Start at badscience.net.

~~~
lutusp
> That's why it's normal these days, for clinical studies, for the control
> group to receive current best available treatment, rather than a placebo.

That's one of the reasons such studies are so unreliable -- they depend on a
comparison of two or more drugs that may operate in different ways, rather
than comparing a drug to the absence of a drug.

The result is predictable -- unbiased meta-analyses show that antidepressants
don't work:

[http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...](http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050045)

This is not to say that wouldn't have been the outcome anyway, regardless of
the methods used, only that testing two drugs at once introduces confounding
factors.

------
anigbrowl
Interesting news, but the potential for abuse is worrisome. Recreational
ketamine produces dissociative states similar to heavy drunkenness in the
short term, and frequent repeat use is known to damage a part of the brain
called Broca's region through cellular overheating, seriously impacting speech
formation.

~~~
Homunculiheaded
When looking at pharmaceutical drugs that also have a recreation use I think
the number one thing to be concerned with is how addictive they are. From what
I can find there really isn't any evidence to support the claim that ketamine
is very addictive.

Also depression is in and of itself dangerous. Even avoiding the entire topic
of suicide, depression can lead to a variety of self destructive behaviors and
poor decisions. Additionally plenty of people suffering from depression will
naturally 'self medicate' with drugs that don't actually address the
underlying neurological issues that ketamine might, and certainly can cause
physical harm.

I think it's somewhat odd that in the 21st century we still aren't comfortable
seeing physical and mental illness on the same level. People committing
suicide die of an illness in no different a way than people dying of cancer.
Yet there is very little in the way of public support of combating suicide the
way there is for cancer. There is little debate that opiates (dramatically
more risk for abuse) should be used to treat physical pain, and yet people get
very nervous about the potential for misuse in a much less risky drug which
could provide similar relief to mental anguish.

~~~
Teapot
Combating depressions and suicides. In many cases there's also outside causes
that begins downward spirals.

People often suggests therapy and/or pills that changes _you_. But they rare
suggests exploring external causes, and external solutions.

For example, it may be better to drug bullies rather than victims...

~~~
ippisl
Some social critics say psychology/psychiatry's rise is in part because it let
other people and institutions do victim blaming, and not invest in treating
societal problems.

It also fits well with neo-liberal thought:"little concern for externalities",
"rational consumer" and this kind of bullshit.

------
victorbstan
In the article, near the end, they suggest that scientists are looking into
alternatives that work like Ketamine, but so far none work as fast as K.

"Efforts to develop drugs that replicate the effects of ketamine have produced
some promising results, but they do not act as quickly as ketamine.
Researchers are investigating alternatives they hope can duplicate the
efficacy and rapid response of ketamine."

So my question is, why not just administer K?

~~~
Jtsummers
Side effects from abuse, and the short term (7-10 day) duration of the effect.
If they can isolate the effective properties and recreate them, it's possible
to find a drug or drugs that can solve those two problems. Also, it's unlikely
that (due to it's potential for abuse) ketamine prescriptions will be handed
out anytime soon. So patients can go in for weekly treatment, or researchers
can find something more palatable to the current political climate.

------
scotty79
Was the antidepressant effects of ketamine observed at normal anesthetic
dosages (1-2mg/kg)?

~~~
sneak
The antidepressant effects are found at even half of that.

------
soup10
Recreational drugs temporarily make people happier? No way... I'm glad the
fine minds at Yale are studying such important, ground breaking stuff. I can't
wait until this research leads to new antidepressants that turn more people
into zombies.

~~~
navs
I'd rather be a zombie than continue on as I do today

~~~
OldSchool
That statement implies that you're currently not medicated and also depressed.
If that's the case, you really should meet with a psychiatrist; there's no
reason to suffer.

The hyper-rational type of people here are more likely to believe in the
absoluteness of their own perception of reality and therefore are less likely
to seek treatment. If you're a hold-out and apparently in need, truly you'd be
surprised how much medically-manipulated brain chemistry can improve your
quality of life. A person's emotional world is highly plastic but successfully
changing it requires the precise knowledge and quality control that is
provided by a doctor and medicine.

~~~
gruseom
_you'd be surprised how much medically-manipulated brain chemistry can improve
your quality of life_

Except in severe depression, antidepressants have no clinical advantage over
placebos:

[http://www.thedailybeast.com/newsweek/2010/01/28/the-
depress...](http://www.thedailybeast.com/newsweek/2010/01/28/the-depressing-
news-about-antidepressants.html)

According to Kirsch, antidepressant trials were also compromised by side-
effect leakage: the drugs had side effects while the placebos did not, so
patients knew when they were not taking a placebo. That's the equivalent of
putting your finger on the scale. As far as I know, there has been no attempt
to measure that distorting effect (Kirsch only mentions it), nor any clinical
trials of antidepressants conducted on a level playing field, where the
placebo had similar side effects to the drug. But I haven't searched, and if
such studies exist, I'd welcome correction.

~~~
derleth
> Except in severe depression, antidepressants have no clinical advantage over
> placebos:

ECT can have a much better effect in these cases.

[http://www.mayoclinic.com/health/electroconvulsive-
therapy/M...](http://www.mayoclinic.com/health/electroconvulsive-
therapy/MY00129)

[http://www.cbsnews.com/8301-504763_162-57400793-10391704/ele...](http://www.cbsnews.com/8301-504763_162-57400793-10391704/electroconvulsive-
therapy-effectively-treats-severe-depression-how/)

And, it turns out, antidepressants can help ECT:

[http://www.sciencedaily.com/releases/2009/07/090706161300.ht...](http://www.sciencedaily.com/releases/2009/07/090706161300.htm)

But keep in mind that ECT is only for _crisis-level severe_ depression:

> ECT uses an electrical stimulus to the brain to induce seizures. It is
> prescribed for patients with crisis-level severe depression – who are
> catatonic (people who are so slowed down that they stop moving, talking and
> eating) or suicidal – or for patients with major depression who have not
> responded to medication.

