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Tuesday, 28.03.2017

Barry Blackwell’s reply to Malcolm Lader’s comment

It was especially informative and pleasing to read Malcolm Lader’s erudite reflection on the “Lithium Controversy”, commentary that did indeed “add light rather than heat to the issues.” His knowledge and opinions are of particular value for a number of reasons.

Professor Lader is better known in Europe than America, an active member of CINP since 1964 and Vice President for four subsequent years. He is the author of more than 630 publications, 20 authored and 50 edited books covering many topics including seminal early research on the benzodiazepines (Blackwell, 2014).

Before joining the Maudsley Hospital in London, where we were fellow registrars (residents), Malcolm had trained in both medicine and physiology and obtained a doctoral degree in medicine as well as a Ph.D. in clinical psychopharmacology for work supervised by Michael Shepherd, co-author on our provocative Lancet article. Elsewhere Malcolm (Lader, 2005) described his mentor in terms that may alleviate some of the hurt feelings and opprobrium Shepherd and I evoked.

“Some people found Michael very disconcerting and thought that he was a very difficult person to cope with. He was certainly a shy man, but in a way he had a breadth of knowledge that was even broader than Aubrey Lewis’s but without necessarily the depth. He was one of the most well-read people I have ever come across - philosophy and so on, and the quirky psychiatry he taught.”

I appreciate the way in which Professor Lader dissects the diagnostic and therapeutic problems that underlie the current debate about lithium. Especially important is his prescient experience working as (probably) Sir Aubrey Lewis’s last resident before retirement where they discussed diagnosis in terms laid down by Adolph Meyer and saw patients referred by naïve registrars, (like me), with a diagnosis of unipolar depression. Expert scrutiny uncovered, “mood changes that could be interpreted above the normal range, thus raising the possibility of a bipolar type II diagnosis.”  This may well have been the diagnostic dilemma that Schou was investigating at the time of his death, triggered by his brother’s ‘unipolar’ depression that was eradicated by lithium. Recently Janusz Rybakowski reported a similar early experience that contributed to his career long devotion to studying lithium.  (Rybakowski, 2015).

It is interesting to note that Lader and Schou discussed the prophylactic trial “amicably and concluded that the design had strength and weaknesses.” Malcolm also provides an elegant synopsis of the problems in research design extant today that plague not only lithium research but most of clinical psychopharmacology. These include the etiologic poverty of the DSM criteria and “artificially constructed trials” that have revealed a lack of valid specificity in treatment choices and outcomes. Professor Lader suggests a logical response to this ambiguity is N=1 trials of treatment with “properly organized … observations before, during and after treatment”, perhaps akin to Schou’s mirror image design with lithium. This is the approach most sophisticated clinician’s employ today, at odds with the pharmaceutical industry’s glamorous but misleading advertisements that imply product specificity based on spurious science.

Finally it is good to see that Professor Lader acknowledges the early work of Trautner and Gershon in developing a valid and reliable method of monitoring lithium as “a key advance.” His own experience in documenting lithium neurotoxicity, usually associated with poor management, is corroborated in an April issue of JAMA based on thousands of emergency room visits for psychotropic drug side effects often prescribed, presumably, by primary care physicians untrained in appropriate monitoring. (Olsen, 2015).


Blackwell B. The Anxiety Enigma at in Controversies 30.10.2014.

Lader M. A conversation with Malcolm H. Lader. Addiction 2005; 100 (8): 1057-65.

Olsen M. Surveillance of adverse psychiatric medication events .JAMA 2015; 313:1273.

Rybakowski J.  Comment. Lithium Controversy. in Controversies 14.05.2015.


Barry Blackwell

May 21, 2015