Alex Last: BBC Witness History: The First Antipsychotic Drug

An interview of Thomas Ban

Barry Blackwell’s comments

        Tom Ban’s interview with BBC provides a brief account of chlorpromazine (Thorazine), “the first antipsychotic drug.” It was discovered in France by Deniker and Delay then manufactured and marketed worldwide by Rhone-Poulenc.

        Working with Heinz Lehmann in Canada Tom was among the first to observe the beneficial effects of this drug on about a dozen psychotic patients in early 1955. He notes the treatment was “palliative” not causal, “like penicillin,” and that while it helped decrease the asylum population there was a 50% increase in readmissions worldwide between 1955 and 1960.

        Responding to the interviewer’s questions, he notes that despite several new drugs in the category of antipsychotic compounds none is more effective and although their mechanism of action on dopamine receptors in the brain was identified, it failed to meet expectations this would “…lead to a new world of being able to identify and treat specific mental illnesses.” He attributes this to the DSM and ICD diagnostic systems in use today that “fail to resolve pharmacological homogeneity within categories.”

        Lucid and accurate, this account is restricted by the narrow band width of a pod-cast interview, leaving much unsaid about significant historical events between then and now.

        The reason chlorpromazine was not a panacea and that deinstitutionalization often led to re-admission between asylum and community, “the revolving door,” reflected features of both the clinical effects of the drug and the inadequacy of community support.

        The first clinical reports noted: “…agitation, aggressiveness and delusive conditions improved, contact with patients could be re-established, but deficiency symptoms did not change markedly” (Deniker 1970). The positive symptoms, hallucinations, delusions and lack of insight kept the patient hospitalized while the negative symptoms, cognitive and social deficiencies, were detrimental to life in community, although strong family support could ameliorate this.

        Failure to thrive in the community in America was despite significant governmental efforts to provide support. In 1963 Congress enacted the Community Mental Health Act with the intention that “…the cold mercy of custodial institutions would be supplanted by the open warmth of community concern and capability.” Over 17 years the government funded 789 Community Mental Health Centers (at a cost of billions of dollars) which opted instead to serve the “worried well” and treated less than 7% of former asylum patients; meanwhile 75% of the beds they once occupied were lost. Homelessness on urban streets became a problem.

        In the late decades of the 20^th century the number of antipsychotic drugs proliferated. These second generation (atypical) drugs were far more expensive and aggressively promoted by industry with unsupported claims of superior efficacy and fewer side effects. This misinformation was condoned by lack of face-to-face comparisons with older, less expensive first generation drugs in Phase 2 clinical studies. An exception might have been clozapine (Clozaril) which benefited some patients who had failed other antipsychotics but this drug had the serious, sometimes fatal, side effect of agranulocytosis for which FDA mandated monthly blood tests. I treated one such patient, a young male who did well for several years but relapsed when paranoid thoughts led to a conviction he was being experimented on; he refused blood tests, relapsed and remained psychotic.

        The presumption of superiority for the second generation drugs was ultimately proven false when the NIMH funded an effectiveness study (Stroup, McEvoy, Swartz et al. 2003) which compared the use, efficacy and side effects of four second generation drugs with perphenazine, a far cheaper first generation compound.

        Late in my career I began to write poetry using language able to  express the limits of what medication can accomplish in some patients - enough to blunt the ferocity of psychosis, insufficient for life in community.

Morning Coffee

This cafeteria is a collecting place,

A dingy museum of hope and cigarette butts.

But the man at the next table

Has made up his mind.

His hands on the table

Are cuddling a coffee cup;

His chest props up his chin

And his eyes are curtain-closed

As he dozes the day away

The sloping shoulders say

He is a veteran of living, waiting

With no victories to celebrate.

A few shrugged off memories

Warn him without words;

Yesterday was depression, tomorrow doubt.

Only today may be safe.

So he snoozes between sips

Between caffeine and Thorazine.

Living moment to moment,

Molecule to molecule.

If you knew enough it might be

He made the right choice

To stop and not go on,

To stay and not retreat.

Later, eyes open, he says hello.

But nobody notices or even nods.

Now he knows the comfort

Of not existing …

(Blackwell 2011)

References:

Blackwell B. Bits and Pieces of a Psychiatrist’s Life. Morning Coffee. Xlibris Corporation. 2011, pp. 406-7.

Deniker P. Introduction of Neuroleptic chemotherapy into psychiatry. In: Ayd FJ, Blackwell B, editors.  Discoveries in Biological. Psychiatry Philadelphia, JB Lippincott. 1970.

Stroup TS, McEvoy JP, Swartz MS, Byerly MJ, Glick ID, Canive JM, McGee MF, Simpson GM, Stevens MC, Lieberman JA. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project: Schizophrenia Trial Design and Protocol Development. Schizophrenia Bulletin, 2003; 29(1):15–31.

April 2, 2020