Motivation in pharmcotherapy research and clozapine (a ramble)

Clozapine was an astounding success when it was released on the market,
so much so that after the manufacturers withdrew it was brought back
because it was so prized for it's ability to treat. This ability may not
be as potent as the early studies suggest but there's little doubt in
most medical professionals minds that there is no better cure for
schizophrenia. That's because they come from a biomedical perspective
and the biomedical perspective is well supported by research, though the
research may be fundamentally flawed if the measures aren't correct and
PANSS, a commonly used measure, is designed to be pharmacotherapy sensitive.

Anyway, clozapine is a really dangerous drug and I'm sure that even
though it's become licensed for more things the medical profession would
prefer an alternative with the same capability to improve people's state
of being based on the psychiatric, psychopathological measures of
schizophrenia
.
The problem is for treatment resistant schizophrenia there is no other
alternative apart from even more risky treatments. Abilify (aripralozone
or whatever) is the first of a new and more targeted type of
antipsychotic. I don't know a lot about how its neutobiological action
differs from second generation antispsychotics but I know it has fewer
side effects. I think this is a result of the targeted nature of it's
neurobiological effect but this is a guess.

Clozapine is very much different in that paradigm of targeted
pharmacological action on the neurotransmitters that are suggested to be
responsible for the negative outcomes in severe mental, illnesses. It
works on a broad spectrum of dopamine receptors and also on the 5HT
serotonin receptor (if I remember right). It also affects a number of
other body functions to cause the numerous side effects, the most
notable of which is the depletion of certain cells that make up the
immune system. It was this illness - clozapine-induced agranulocytosis -
that caused it to be withdrawn/

What I can't believe is in the interim there hasn't been a better
solution for treatment resistant schizophrenia. In the UK and US (and I
can guess this is true in other parts of the world that have well-funded
mental healthcare systems) it is the treatment of choice after two
trials of other antipsychotics. It is also becoming licensed for use
outside the treatment of psychosis.

Perhaps the reason is there are few people who need to take the drug. In
the UK it's between 6000-7000 people who take clozapine. It's a small
number but there's a high number of premature deaths unrelated to
suicide. This fact came out in the media last year and was part of how
I got involved in this long process of learning about clozpaine.

Is that enough for psychiatrists and pharmaceutical companies to
research into an alternative for treatment resistant schizophrenia that
will kill fewer patients in the short and long term.

Here's the thing. The pharmaceutical companies would want a safe version
of clozapine. It would dominate the market. Aside from the risk to life
clozapine is supposedly the best treatment for the 'cardinal symptoms'
of schizophrenia, the attempted suicide rate and works when other
antipsychotics at standard doses don't. I question the actual effect,
i.e. is it really just an amazing chemical straight jacket that calms a
patient to remove they untoward behaviours in the same way a
straitjacket treats madness or low THC cannabis is an antipsychotic.

So what is the cause of the lack of alternative and the lack of a search
for the alternative to clozapine? Is it just that psychiatrists, in the
institutional depression of a 'disease' they can't treat, turn to
treatments for emotional and behavioural disorders that kill patients
quickly and slowly.