Review article
Neuropsychopharmacology and the genetics of schizophrenia
A history of the diagnosis of schizophrenia
Thomas A. Ban
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
Accepted 10 May 2004 - Available online 25 July 2004
5. Pharmacotherapy
Introduction of morphine, potassium bromide, chloral hydrate, hyoscine, and paraldehyde during the 19th century provided the necessary means for the day- and night-time sedation (Shorter, 1997). By the time Kraepelin (1899) introduced his diagnostic concept of dementia praecox, subcutaneously administered combinations of morphine (or apomorphine) and scopolamine (hyoscine) were the prevailing treatments for excitement, agitation, and aggression (Ban, 2001a).
Early pharmacological treatments of schizophrenia included cocaine (Becker, 1921), manganese (Reed, 1929), castor oil (Ingham, 1930), or the injection of sulfur oil (Croce, 1932) to induce fever (Lehmann, 1993). Other early pharmacologically based treatments included sleep therapy and inulin coma (Ban, 2001b).
Sleep therapy was of marginal benefit but of considerable risk. Klaesi’s (1922) original sample of 26 schizophrenic patients, improvement rate with Somnifen (a barbiturate combination) was about 30%, i.e., 10% higher than the spontaneous remission rate found in a similar population. This relatively small gain was offset by a higher than 5% fatality from pneumonia or circulatory collapse. Sakel’s (1935) insulin coma therapy dominated the treatment of schizophrenia from the late 1930s to the mid-1950s. It doubled spontaneous remission rates, i.e., increased social remission from about 17% to 34%, when used within the first year of the illness. The risk with insulin coma therapy were relatively low; fatality rate was below 0.5% (Mayer-Gross et al., 1960).
The first generally accepted and widely used drug in the treatment to schizophrenia was chlorpromazine, synthesized in 1950 (Charpentier et al., 1952) and introduced for clinical use in 1953 (Delay et al., 1952). The second, reserpine, was isolated from the Rauwolfia root in 1952 (Mueller et al., 1952) and introduced in 1954 (Delay et al., 1954). Haloperidol, for many years, one of the most extensively prescribed treatments, was synthesized in 1958 (Janssen, 1996) and introduced in 1959 (Divry et al., 1959).
Introduction of chlorpromazine promptly decreased the need for physical restraint and clamed disturbed wards (Brill and Patton, 1957). Nevertheless, it took approximately eight years to demonstrate its superiority to placebo in the treatment of schizophrenia (Casey et al., 1960). Another 5 years passed before it was revealed that symptoms, such as slow speech and movements, lack of self-care, and indifference to environment (Goldberg et al., 1965), assumedly related to Bleuler’s (1911) fundamental (basic) symptoms of schizophrenia, respond only to treatment with antipsychotic (neuroleptic) phenothiazines, whereas symptoms, such as auditory and non-auditory hallucinations, memory deficit, and feelings of unreality, respond also to placebo (Ban, 1972). And it was only in the mid-1970s that it was established that at least one out of every three schizophrenic patients was definitely responsive to treatment with new drugs. A meta-analysis conducted with the data of 24 patients revealed, that in 68% of the patients on active treatment, and in 30% of the patients on placebo continuation or maintenance treatment prevented relapse or modified recurrence (Davis, 1975).
Since the introduction of chlorpromazine, over 50 years have passed and many antipsychotic (neuroleptic) drugs have become available for the treatment of schizophrenia (Lehmann and Ban, 1997). Conventionally, they are divided into first generation antipsychotics, identified on the basis of structural or pharmacological similarities to chlorpromazine, and second generation antipsychotics, developed with specific theories in mind. To date, well over 30 antipsychotic drugs have been introduced for schizophrenia; the exact number varies from country to country. In Canada, for example, 28 antipsychotics are in clinical use (CPS, 2003).