A History of the Pharmacological Treatment of Bipolar Disorder

Abstract

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

Keywords: antiepileptic drugs; antipsychotic drugs; bipolar disorder; lithium; mood stabilizer drugs; pharmacological treatment.

Figure 1

Illustrations of the most relevant plants in the Solanaceae family, from which several alkaloids were obtained to be used in psychiatric practice as sedatives prior to modern psychopharmacology: (A) Mandrake (Mandragora officinalis); (B) Stramonium (Datura estramonio); (C) Eléboro (Helleborus niger); (D) Hellebore (Hyosciamus niger); (E) Belladonna (Atropa belladonna).

Figure 2

Portrait of Sir Charles Locock (1799–1875) dated 1862. Locock was an obstetrician, First Physician Accoucheur to the Queen Victoria and a member of the St. Albans Medical Club.

Figure 3

Adolf von Baeyer (1835–1917), discoverer of barbituric acid, in the centre with a hat in his hands, together with his team from the Chemistry Laboratory of the Munich Academy of Sciences, in 1893.

Figure 4

Jakob Klaesi (right) (1883–1980) with the Burghölzli Hospital psychiatric staff, including its director, Eugen Bleuler (centre), in a photograph taken around 1910 (A) and a container of Somnifen drops of the first third of the century 20th century, commercialized in Spain by F. Hoffmann-La Roche & Cie, Paris (B).

Figure 5

Mid-nineteenth century lithographs of the two Swedish chemists responsible for the discovery of lithium: Johann August Arfwedson (1792–1841) (A) and Jöns Jakob Berzelius (1779–1848) (B), Professor of Chemistry and Pharmacy at the Karolinska Institute. Both were members of the Royal Swedish Academy of Sciences.

Figure 6

Two examples of the popularity of lithiated waters at the end of the 19th century: a commercial of Londonderry Lithia (Londonderry Lithia Spring Water and Co., Nashua, NH, USA), showing all its supposed therapeutic properties (A) and a photograph of the late 19th century of the head office and distribution system of Atlanta Mineral Water and Supply Co. (Atlanta, GA, USA) (B), advertising its Lithia Water.

Figure 7

Sir Alfred Baring Garrod (1819–1907), professor of Materia Medica and Therapeutics at King’s College Hospital and President of the Medical Society of London in 1860. He was knighted as “Sir Alfred Baring Garrod” and in 1890 was appointed “Physician Extraordinary” to Queen Victoria.

Figure 8

Pioneers in the use of lithium in the treatment of mental disorders: William Alexander Hammond (1828–1900) (A), Surgeon General of the United States Army, professor of anatomy and physiology at the University of Maryland School of Medicine, professor of Nervous and Mental Diseases at Bellevue Hospital and at the New York University; and Carl Georg Lange (1834–1900) (B), Danish physician who made contributions to the fields of neurology, psychiatry and psychology.

Figure 9

John Frederick Cade (1912–1980), authentic pioneer of modern psychopharmacology with his experiments on lithium.

Figure 10

The kitchen at Bundoora Repatriation Mental Hospital where John Cade conducted some of his lithium experiments.

Figure 11

Laboratory notes by Cade regarding the effects of the injection of different compounds and lithium salts to guinea pigs.

Figure 12

Medical Journal of Australia, Volume 3, September 1949, in which the results of the clinical experiments by John Cade about lithium salts and the handling of hectic manic and schizophrenic patients were published [61].

Figure 13

Three great pioneers of the clinical introduction of lithium: Poul Christia Baastrup (a), John Cade (b) and Mogens Schou (c).

Figure 14

Pierre A. Lambert, French psychiatrist, a pioneer in the field of psychopharmacology. He was a member and president of the prestigious Comité Lyonnais de Recherches Thérapeutiques en Psychiatrie. His role in the conceptualization of mood stabilizers gained great importance in the early stages of the psychopharmacological era.

Figure 15

Carbamazepine (Tegretol^®) advertisements in the Japanese medical press during the 1970s, which emphasized its anticonvulsant and sedative effects. Ads published in the journal Psychiatria et Neurologia Japonica in (A) 1970 and (B) 1978.