Re: Drugs and Despair

From: Anders Sandberg (
Date: Fri May 19 2000 - 07:16:45 MDT

Eirikur Hallgrimsson <> writes:

> The antidepressant discussion has yanked me out of my normal lurk mode.
> Antidepressants are very interesting in Extropian terms--basically
> they are a primitive form of self-modification, and all the issues
> about modifying oneself show up in one way or another in the
> antidepressant arena, starting with the fact that many, if not most,
> people are threatened by those of us who want to modify ourselves,
> and want to be able to control or restrict this. And just try to
> tell a psychiatrist that *you* are in control of your treatment.

Exactly. It is also something that can be done here and now, and leads
to a lot of interesting and uncomfortable (for some) political
questions. I think it is a good idea as a transhumanist to read up on
the area even if you don't use any psychopharmacology yourself, in
order to familiarise oneself with the issues, some prevalent memes and
strategies, so that when the real bombshells start to appear we are
ready to do some serious debating.

> The stimulant analogy connects for me to the "Prozac poop-out effect"
> that many people experience at around seven years on SSRIs.
> Seemingly SSRIs are hard for the body's homeostatic mechanisms to
> work around. Maybe it even takes seven years. Which would make a
> heck of a lot of sense because the speculated mechanism whereby you
> develop a tolerance for SSRIs is that you actually prune connections,
> losing synapses to get the data rates (where?) back to where they
> want to be. Scary stuff. There just aren't any long term studies.

Well, there are some studies like Benmansour S, Cecchi M, Morilak DA,
Gerhardt GA, Javors MA, Gould GG, Frazer A Effects of chronic
antidepressant treatments on serotonin transporter function, density,
and mRNA level. J Neurosci 1999 Dec 1;19(23):10494-501 (SSRIs
decreased the amount of serotonin transporter in chronically treated
rats, but not the serotonin levels in the hippocampus). But long-term
human data is of course only possible to get after a long time.

I have not seen any papers about synaptic loss with SSRIs though.

> Exactly how bad do the drug companies want to prove that you lose
> synapses? I was pretty worried about being expected to be a good
> sheep and take high doses of SSRIs as permanent maintenance for life.

The drug companies might dislike it, but you can make a scientific
career out of discovering such an effect. There is a thriving
scientific cottage industry of analysing side effects, just check

> I think that you can push the brain around with strong drugs, but
> they aren't the answer for life, partly because of tolerance
> development, but also because there's no learning in a drug, and
> depression appears to be a learned thing, which has serious
> biochemical effects on you, but those effects aren't the cause.

Depression may be multifactorial, and some forms due to a serotonin
weakness and some other forms due to bad learning. Cognitive therapy
seems to do well with depression just because it helps the patients to
learn to cope with the everyday problems that might otherwise trigger
a new depressive episode; the drugs are however often necessary to get
the patient into a state where therapy might be helpful.

The interesting question is what happens if/when we get smart drugs
that actually do have learning effects.

> My theory is that the brain chemistry changes are how the evolved
> depression mechanism gets its results. My thinking is that
> depression is a mechanism designed to allow an individual to survive
> and possibly get a chance to reproduce, given serious low-status, low
> pecking-order in our ancestral tribal environment. Some of us fall
> into the depressed mode more easily, but everyone has the potential
> to get there if pushed hard enough and long enough.

Since sexual responsiveness in depression is usually strongly
decreased, I don't think it helps reproduction at all. I'm sceptical
about arguments for an evolutionary "meaning" of depression; it
doesn't have to be a feature, just a weakness that ordinarily doesn't
matter much.

> My experience is that "attack" dosages of 2 to 3X the max spec'd
> dosage of SSRIs can significantly impact acute despair in 4 to 8
> hours, but I'm not a doctor and that's playing with fire. This
> personal experience of mine has never been confirmed in another
> person, so I could very well be off base here. I'd really like to
> see research on this, though, because it would be nice to have a
> powerful tool to pull people back from the brink.

I don't know much about it (being more of a memory person than a
psychopharmacology person), but one possibility is a serotonin peak
due to near total reuptake blockade, combined with a very likely
strong placebo effect.

> St. John's Wort, an herb available as capsules at most any health
> food store, has significant SSRI effects. For some reason, that
> fact doesn't seem to get into press much.

Yes, it is often touted as "natural" and hence, in the opinion of
many, "safe". Besides, it is not really that selective either. I guess
that the low dosages most people take just make the side effects less

> Oh, one parting note about SSRI's (or any effective antidepressant,
> actually) and suicide or violence. Take someone who is essentially
> completely disabled by depression. Stimulate the heck out of some of
> their neural pathways with a drug. They aren't collapsed on the
> couch anymore. They actually could carry out suicide plans that were
> probably beyond them in the totally depressed state. The same goes
> for taking action against someone else. I've not read anything about
> this, but I have spoken to several clinicians who regard this as a
> significant risk of SSRIs, and give it as a reason why they always
> start patients with low doses.

This is overall a problem in treating depression using any
means. Suicides tend to occur when they are making progress, rather
than in the descending or deepest depression. Very sad.

I think one of the first things I will do when I get the chance to
redesign my brain is to fix the monoaminergic systems - they are far
too important and pervasive to be allowed to run without good
supervision and optimisation. Evolution has just optimised them to
work well enough on average in the entire population, not well enough
in me as an individual.

Demand accountability of the catecholamines!

Anders Sandberg                                      Towards Ascension!                  
GCS/M/S/O d++ -p+ c++++ !l u+ e++ m++ s+/+ n--- h+/* f+ g+ w++ t+ r+ !y

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