The evidence suggests that use of the term ‘antidepressant’ quickly caught on. By 1959 the term was being used routinely in over 100 papers. Where the meaning of the term was spelled out it was in vague terms suggesting some action on a disease process, reminiscent of the language of Kuhn. Thus antidepressant drugs were referred to as having a ‘worthwhile effect upon depressive illness’ or having ‘value’ or ‘benefits’ in the treatment of depression without any explication of what this effect might consist of.
In 1961, leading American psychiatrist Frank Ayd confidently used the term antidepressant, explaining that antidepressant drugs ‘control or eradicate target symptoms such as depressed mood, psychomotor retardation, loss of interest’. Many papers repeated the assertion that imipramine’s effects were strongest in endogenous depression. Often there was no reference to Kuhn’s paper or to anything else, suggesting that the association between the benefits of imipramine and endogenous type depression was regarded as established beyond doubt.
However one early study already contradicted this proposed association and it has not been confirmed in subsequent overviews.
As early as 1959 the idea that the new drugs for depression were disease-specific treatments was strongly and explicitly endorsed by prominent psychiatrists. At a major conference on depression held in Cambridge, England in 1959 Professor
Erik Jacobsen expressed the belief that
The monoamine oxidase inhibitor antidepressants seem, in theory, to be closer to the ideal psychotropic drugs, with strong and clear-cut effects on pathological states and almost no effect on normals.
Jacobsen suggested that the effects of the MAOI antidepressants such as iproniazid were clearly distinguishable from effects of stimulant drugs. Like Kline and colleagues, he assumed that their effects in depression were due to monoamine oxidase inhibition, but did not explain how they could be differentiated from stimulants which were also known to act in this way. At the same conference Pierre Deniker and his colleague declared that
The action of imipramine, and to a lesser extent iproniazid, is not merely sedative and symptomatic, like that of the neuroleptics, but is curative.
They proposed that it was possible to dispense with ECT for all but the most severe cases, and that it was in ‘protracted involutional melancholia that imipramine gives results really superior to those of ECT’. In contrast to Jacobsen, who was eager to detach antidepressants from stimulants, Deniker and Lamperiere (1964) made the remarkable assertion that imipramine as well as iproniazid ‘behave as stimulants, and thus resemble amphetamine, even though their action is more complex’. They suggested that imipramine induced insomnia, for example, and that it could be differentiated electrophysiologically from chlorpro-mazine.
These statements are difficult to understand given that imipramine was already clearly described as having sedative properties and being closely related to chlorpromazine. Therefore, Deniker and Lamperiere’s observations are still coloured by the idea that an antidepressant drug must induce a chemical stimulant effect. However they also demonstrate the desire for a coherent and single disease-based account of the action of drugs being used for depression.
At another psychopharmacology conference held in the United States in 1962, it was suggested that antidepressants ‘strike almost specifically at the governing mechanisms of affectivity which are disturbed in manic depressive psychosis’. Their specificity of action was again contrasted with stimulants:
The earliest reports of the use of antidepressant medication seemed to indicate that the purpose of the medication was simply some special kind of stimulation which was useful in relieving lethargy and withdrawal. It was soon evident, however to good clinical observers, that the action of antidepressant substances was much more specific.
A similar sentiment was expressed in a later British textbook of psychopharmacology: ‘Antidepressant drugs, like imipramine and the monoamine oxidase inhibitors differ from euphoriant drugs such as amphetamine in that they appear to act specifically against depressive symptoms’.
The ascendancy of the disease-centred model of antidepressant drugs is apparent in textbooks and formularies from the 1960s. As early as 1960 textbooks referred to iproniazid and imipramine as ‘antidepressants’ and explicitly distinguished them from stimulants. The British National Formulary classification first included a category of ‘antidepressants’ in 1963 (British Medical Association and Pharmaceutical Society of Great Britain 1963), noting that ‘the treatment and prognosis of mental depression has been considerably enhanced by the use of antidepressant drugs’. The old category of ‘stimulants’ was abandoned in this edition and amphetamines and other stimulants were included in the category of antidepressants along with imipramine and ‘monoamine oxidase inhibitors’ such as iproniazid.
However some researchers challenged the view that antidepressants were disease-specific drugs. In 1964, a psychiatrist called E.H. Hare and his colleagues published a report of a controlled trial comparing ‘Drinamyl’ a widely used preparation containing barbiturates and amphetamine, with imipramine. They found no difference between the two treatments and concluded ‘that imipramine has no specific antidepressive action’. Hare and colleagues also suggested that ‘in so far as antidepressive drugs are effective in the treatment of depressive illness, this is in virtue of a sedative action’ and recommended that they should be compared with other ‘purely sedative’ drugs.
In 1964, prominent American psychopharmacologists John Overall, Leo Hollister and colleagues set out to examine the ‘specificity of drug classes’ by comparing the effects of imipramine and an ‘antipsychotic’ drug thior-idazine. They pointed out how imipramine and chlorpromazine ‘share many pharmacodynamic effects, differing mainly in potency’. The study found no difference between imipramine and thioridazine in depressed patients. The authors concluded that they could not confirm ‘the specificity of action ordinarily attributed to antipsychotic and antidepressant drugs’. However these were already dissenting voices in a psychiatric climate that had overwhelmingly adopted the notion of the ‘antidepressant’ as a specific treatment for depression. Further expressions of scepticism were occasionally published subsequently but provoked little discussion.
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