In a similar sense, psychiatry began in nineteen fifty-three, between the reports about chlorpromazine in France and the validation of John Cade’s discovery of the antimanic effect of lithium in nineteen fifty-four. This was not too late for Professor Owens or for me; we ourselves were too late to witness the actual introduction of antipsychotics, but we have spent our professional lives in an era dominated by developments in neuroscience and therapeutics. We have lived through the elucidation of the mechanisms of action of antipsychotics, and of dopamine as a neurotransmitter.

Reference OwensOwens (2012a,Reference Owensb, this issue) regrets the loss of the concept of ataraxy, and that little attention has been given to understanding its neural basis. However, this affective ‘detachment’, or ‘indifference’, which was unique and distinct from sedation, may be what is now described as the effect of antipsychotics to reduce ‘incentive salience’, a vital aspect of emotion dependent on dopamine function (Reference Berridge and RobinsonBerridge 1998).

The distinction between classes of ‘typical’ and ‘atypical’ antipsychotics is unfashionable, but the words are embedded in our language and we need to share a meaning. This was addressed by Reference KerwinKerwin (1994): ‘clinical atypicality would be defined by the low propensity to produce extrapyramidal side-effects and tardive dyskinesia relative to typical drugs like haloperidol and chlorpromazine’. This definition avoids the old/new dichotomy, allowing some older drugs to be included, but preserves the usefulness of the class distinction.

It is useful to note that Owens has recanted his earlier teaching that anticholinergic drugs should be used only if (or when) extrapyramidal side-effects occur, but now recommends their routine use for starting anyone on haloperidol. In countries where patients are treated exclusively with older antipsychotics, it appears that ‘Parkinsonism is as prominent a risk as ever’ only with the older typical antipsychotics. This is also the conclusion of independent meta-analyses (Reference Leucht and DavisLeucht 2011).

Although the atypicals share no other quality than this, they do show individual differences in efficacy as well as side-effects. The statement that ‘Most clinicians would now accept the American view that in terms of efficacy (and, post-CATIE, effectiveness too) all antipsychotics are comparable’ (Reference OwensOwens 2012a) contrasts with experience with clozapine and meta-analyses of the newer drugs, which shows small but real superiority in efficacy for some new drugs over older ones (Reference CooksonCookson 2008a; Reference Leucht and DavisLeucht 2011).

The differences are more striking when the treatment of mania is analysed. A multi-treatment meta-analysis (Reference Cipriani, Barbui and SalantiCipriani 2011) confirms the impression from individual randomised controlled trials (Reference CooksonCookson 2008b) that no atypical antipsychotic is superior in efficacy to haloperidol in mania and some are distinctly inferior.

The history of the discovery of chlorpromazine is informative (and often asked about in the Royal College of Psychiatrists’ Membership examination, the MRCPsych). Most accounts give credit to the pharmaceutical industry (Paul Charpentier, the chemist who synthesised it, and Simone Courvoisier, the pharmacologist who named the drug Largactil^© for its diversity of pharmacological and potential clinical actions) and to the clinicians (Henri Laborit, a surgeon with particular interest in anaesthesia, and the psychiatrists Professor Jean Delay and Dr Pierre Deniker). We should remember, as the professional historian Edward Reference ShorterShorter (1997: p. 250) put it:

Owens and I have seen the efforts of the pharmaceutical industry to improve the quality of anti-psychotics available to our patients and to extend the indications for these drugs. Given his concerns about neurological side-effects it is surprising that Owens gives industry little credit for developing the newer drugs. Indeed, the widespread distrust of the motives and products of the industry bodes ill for the future of psychiatry (Reference KendallKendall 2011). New drugs are staggeringly expensive to develop, and no organisation apart from the pharmaceutical industry will fund them. It is tempting to convey our disappointment in the pharmaceutical industry in the way of a jilted lover, who suddenly realises that the beloved was interested not just in their higher aspirations but in their money and says they will never trust a suitor again.

We shall certainly need better psychotropic drugs, including antipsychotics. Unless we appreciate the advances that have been made in drug treatments, we shall feel, like Philip Larkin: