Mental health policy and practice across Europe: an overview

Psychopharmaceuticals in Europe 147
alone (Healy 2001: 97). The drug was thought not to be a sedative like barbiturates
or chloral, but to act specifically on the symptoms of mental illness.
Nonetheless, up to the late 1960s, most psychiatrists thought of it as a general
‘tranquillizer’, and many thought that its main use was to make patients
more open to the kind of therapeutic rapport necessary for psychotherapy.
Indeed, many suggested that the effects of the drugs were not to remove the
symptoms, such as hallucinations, let alone to produce a cure for schizophrenia,
but to reduce the disturbance – thus, the patients might still hear the persecutory
voices but would be disinterested in them. But in the 1960s, large-scale
double-blind trials were adopted as the most convincing mode of proof in psychopharmacology,
and they seemed to demonstrate that neuroleptic drugs specifically
targeted the symptoms of schizophrenia. They also seemed to show
that the drugs produced a low level of adverse effects – a finding that was later
overturned with the gradual acceptance that the drugs were linked to an
irreversible dysfunction of movements known as tardive dyskinesia (Gelman
1999). The drugs now appeared to be more than mere ‘tranquillizers’ – they
seemed to target the specific symptoms of psychotic disorder.
Soon after the clinical effects of the drugs were accepted, attempts were made
to identify their mode of action. Experiments in rats seemed to show that chlorpromazine
and related drugs – often termed ‘neuroleptics’ – antagonized the
action of L-dopa and enhanced the accumulation of the metabolites of dopamine
and noradrenaline in the rat brain. On this basis, the researchers began to
argue that the neuroleptics in some way prevented, or blocked, dopamine, and
to some extent noradrenaline, from being taken up by the receptors after its
secretion into the synapse. By 1963, a fully formed ‘dopamine hypothesis’ was
articulated by Carlsson and Lindqvist for the specific mode of action of neuroleptic
drugs. By a simple reversal of the causal chain, it also seemed that we had
a dopamine hypothesis for schizophrenia itself – if antipsychotic drugs had
their effect by blocking the action of dopamine, then schizophrenia must be
linked to an excess of, or hypersensitivity to, dopamine. It seemed obvious that
there was a reciprocal relation between the mode of action of the drug and the
mode of causation of the condition. As more refined psychopharmacological
experimental techniques were developed, it became accepted that all the drugs
thought to be clinically effective as antipsychotics blockaded one particular
type of dopamine receptor – the so-called D 2 receptor – in one particular area of
the brain – the mesocortical regions. The problem was that the apparently firm
pharmacological evidence linking the clinical efficacy of a particular ‘antipsychotic’
to its affinity for postsynaptic D 2 receptors was not matched by firm
evidence that those diagnosed with schizophrenia had anything abnormal in
their dopamine system. Despite the unresolved disagreements about the status
and significance of evidence from patients, the dopamine hypothesis became
the fulcrum of the commercial development of drugs marketed as antipsychotics
throughout the 1960s and 1970s.
The argument about specificity of action of psychiatric drugs, and the belief
in the reciprocal relation between the mode of action of the drug and the
neurochemical basis of the condition, was also central to the development of
antidepressants. The first, imipramine (Tofranil) was also developed from antihistamines
during the early 1950s. There was little initial enthusiasm for this