Mental health policy and practice across Europe: an overview

148 Mental health policy and practice
drug, partly because depression was not seen, at that time, as a major psychiatric
problem. Tofranil was launched in 1958, to some extent inspired by the success
of Thorazine and Largactil, and became established as the first ‘tricyclic’ antidepressant
in the 1960s – so-called because of its three-ringed chemical structure.
The antidepressant story is also a narrative culminating in the claim to
drug specificity – the claim that the drug acts at the neuronal site of the disorder.
In the early 1950s, an antitubercular drug called iproniazid was developed
from left-over V-2 rocket fuel which had been bought cheaply by Hoffman-La
Roche. But when it was used to treat tuberculosis it produced euphoria: newspapers
reported TB patients dancing in the corridors. Psychiatrists were soon
experimenting with its potential for the treatment of patients with mental disease.
Iproniazid was initially considered in the same category as other stimulants.
But in 1952 a series of papers were published arguing that it worked by
inhibiting the action of an enzyme called monoamine oxidase, thus slowing
down the depletion of these monoamines in the brain. And the substances then
identified as neurotransmitters in the brain were indeed monoamines – adrenaline,
norepinephrine, dopamine (the so-called catecholamines) and serotonin
(an indoleamine). Researchers began to suggest that depression and elation
themselves were correlated with the levels of these neurotransmitters, these
monoamines, in the brain. Initially, there seemed to be one very serious anomaly
– the tricyclic antidepressants such as imipramine did not inhibit monoamine
oxidase. However, this turned out to be a clue to a mechanism that would be
of major significance – that of reuptake. The tricyclics were shown to block
the mechanism by which neurones reabsorb and hence conserve the neurotransmitters
they secrete, leaving more of the active neurotransmitter present
in the synapse for longer. This mode of action has become crucial to the development
of the new family of selective serotonin reuptake inhibitors – SSRIs.
In 1960, there was resistance to the very idea that neurones in the brain
communicated chemically, and still more to the idea that the activity of neurotransmitters
could influence behaviour. Indeed, this whole way of thinking was
still controversial – this was the era of European antipsychiatry on the one hand,
and the psychoanalytic dominance of psychiatry in the United States on the
other. But, within two decades biological psychiatry had come to define the
common sense of psychiatric thought, and had established the pharmaceutical
companies as key players in understanding and treating mental health problems.
Pharmaceutical companies invested heavily in psychopharmacological
research, in the hope that it would lead to the development of new and profitable
drugs. There was only one major conceptual development over this period
– attention switched from the secretion of the neurotransmitters to the actions
of the receptors which ‘recognized’ certain amines and were activated when
they were released into the synapse. It was now argued that antidepressant
drugs worked because they too were ‘recognized’ by these receptors. When their
molecules ‘bound’ to receptor sites they might stimulate them, or they might
block their action: this became known as upregulation and downregulation of
receptors. In the new images, receptors and neurotransmitters were imagined as
locks and keys, the one working because it fit exactly into the other. The iconic
status of Prozac (fluoxetine hydrochloride) arose less from its efficacy than from
the belief that it was the first ‘smart drug’. A molecule was designed with a shape