Posts Tagged ‘Mania’

The Psychopharmacology of Lithium

The Psychopharmacology of Lithium

F. Neil Johnson

New York, Oxford University Press, 1984. 327 pp.

Lithium is, at the same time, one of the most effective and one of the most poorly understood psychiatric medications. In this text, Johnson reviews a broad range of basic research and clinical data in an attempt to derive a cohesive model which explains the behavioral effects of the drug. Johnson is an experimental psychologist, and his work underlies many of the chapters which suggest that lithium decreases the behavioral response to novel external stimuli. He then utilizes this foundation to propose a cognitive model for lithium’s anti-manic action, its inhibition of violent impulsivity, and its prophylactic effects in recurrent depression.

Previous formulations which were clinically based, such as that of Mabel Blake Cohen and her associates, stressed the primacy of depression and noted the “manic defense” as an attempt to ward off intolerable depression. In direct contrast, Johnson views mania as the primary disturbance in bipolar disorder. He considers depression in bipolar disease as an over-zealous homeostatic inhibitory response to a mania-associated cognitive overload. Consistent with this, he believes, littium exerts its anti-manic effect by decreasing cognitive processing in a manner analogous to his animal studies. Johnson also suggests that lithium exerts its prophylactic effect in recurrent depressions by treating subclinical mania. These concepts are supported by the work of Johnson’s associate, Kukopulos, to whom the book is dedicated. The bulk of the research which describes the cognitive disturbance in mania is complex, however, and uncomfortably open to multiple interpretations. Recognized as a preliminary effort, Johnson’s formulation may help to guide further research.

Although Johnson clearly traces lithium actions through a broad range of subjects, his discussion of the neurophysiological aspects of this drug is notably spotty. In particular, Johnson ignores the work of Svensson, DeMontigny, Aghajanian, and others who suggest that serotonergic systems may play an important role in the antidepressant actions of lithium. As a result, he fails to discuss one of the most important current uses of lithium: as an agent used in conjunction with antidepressant medications to increase treatment response in medication-resistant forms of depression. Lithium augmentation of antidepressant medication also challenges the formulation presented by Johnson. This formulation suggests that lithium should have no therapeutic value in patients, such as those with endogenous depression, who already “under-process” cognitive information. The omission of lithium augmentation in depression is clearly unfortunate in this text.

Overall, this volume demonstrates the benefits of a single-authored text. It it clearly organized and readable. The bibliography is also broad and useful. In this book, Johnson primarily addresses a research audience, and his model seems designed to stimulate thought rather than to improve clinical technique. In this capacity, his book will be of most interest to behavioral psychologists. Other books, focusing purely on clinical data, may be more useful to clinicians. Nevertheless, the clear organization, the large bibliography, and the thoughtful presentation may make this text a useful addition to a clinical library as well.

The Natural History of Mania, Depression and Schizophrenia

The Natural History of Mania, Depression and Schizophrenia

G Winokur, MT Tsuang

Washington (DC): American Psychiatric Press; 1996. 372 p

The resident had just presented his formulation of a case. I posited that hysteria might be an important aspect. He seemed genuinely puzzled, even when I told him that terms like “hysteria” and “hypochondriasis” had been available for more than 2 millennia. “But,” he said, “for my boards, I only need to know DSM-IV.”

“Well,” I thought, “if you’re so keen on cookbook psychiatry, why did you not stay with cooking rather than spoiling psychiatry?”

So here is the rub. What are we to do with this charming, scholarly work full of medical science when the psychiatric world has moved as it were, from bookshelves to the Internet? Or is that being too generous? While I acknowledge that the American Psychiatric Association committees have slaved to obtain syndromes made up of a concatenation of symptoms, it might be an overstatement to suggest that these have the same historical significance as the stirrup, the Gothic arch, and the printing press. They might conceivably be compared with gunpowder, however, since it changed the overthrow of castles from sieges lasting several years to crumbling walls in a few days. So the biopsychosocial anamnesis that can take a considerable time to collect might well be thought in the modern era to be replaceable by a convenient American Psychiatric Association cluster analysis.

Nevertheless, the book The Natural History of Mania, Depression and Schizophrenia is based upon the approach recommended by Adolph Meyer at Johns Hopkins at the beginning of this century. What is now called the “biopsychosocial” model is really the same model with a new name and the same methodology by which psychiatric diagnoses and formulations are developed all over the world. Thus psychiatrists in Iowa, London, Sydney, and Bombay have for decades collected the history of the present illness, the family and personal history, and a mental state examination before proposing a formulation for a patient. Examples of these, in copperplate handwriting, lie in the archives of mental hospitals everywhere.

So what is different about Iowa? The answer is professors George Winokur and Ming T Tsuang. Winokur moved to Iowa from Washington University in St Louis a quarter of a century ago. That university, like several in North America and many in Western Europe, did not see psychoanalysis as the Second Coming and fastidiously kept psychiatry on the Meyerian track. In Iowa, Winokur was joined by Tsuang, who eventually became a professor of psychiatry at Harvard. In the best tradition of psychiatric nosology, generously referred to in the preface, they dug like archeologists into their archives and collected a fascinating cache of data hitherto known as the Iowa 500. Case material was available from 1920 and seemed to be comprehensive; thus, “the quality of material in terms of documenting symptomology was quite sufficient for making diagnoses according to modern diagnostic criteria that had been published for research purposes.”

Nevertheless, there is a caveat. Old data have to be updated and massaged as psychiatry goes through another convulsive spasm in terms of the lexicon and nosology. As seen in the Stirling County and Lundby studies, this can be done. So what did they find? A lot. The Iowa 500 was made up of admissions to the Iowa Psychopathic Hospital (later the Iowa Psychiatric Hospital) between 1934 and 1944 and consisted of 100 bipolar disorder, 225 unipolar disorder, and 200 schizophrenia patients (with a few subsequent changes in diagnosis). The study started in 1971 and completed a 27- to 30-y follow-up of a psychiatric population originally “treatment-naive” in modern terms.

The book itself is made up of 15 chapters, and each contains reams of facts. Each chapter requires careful scrutiny. Perhaps the most salutatory is number 15 entitled “The Contribution of the Iowa 500 to Diagnosis and Classification of the Affective Disorders and Chronic Non-affective Psychosis.” Using symptoms, demographic criteria, and admission criteria, the authors demonstrated that the original diagnoses were stable over time. Thus: “These data strongly suggest an unequivocal separation of the primary affective disorders from the chronic non-affective psychoses according to the factors involved in the medical model.”

The authors worked, albeit inconclusively, on schizoaffective disorder (the border state) and on the types of affective disorder and chronic nonaffective psychoses. They concluded that “the Iowa 500 has presented new ways of investigating clinical entities and family illness… However it is clear that psychiatric illnesses or diseases are often composed of overlapping syndromes and . . . subsequent studies should be planned in a different fashion and less clear cut diagnostic groups should be included as index cases.”

Essentially, what we have here is a wonderful, though somewhat old-fashioned (especially the font), longitudinal study in the best psychopathological fashion. It is descriptive, as psychiatry has remained to this day, but many residents will likely, and regrettably, find it anachronistic. For those of us trained in the Meyerian sense in the best psychiatric institutions of Europe, North America, and Australasia, it validates what we have been doing all of these years. It is not about receptors and cookbooks, but it does provide a warm, fuzzy feeling. All who like a historical perspective to their work should read it.