Barry Blackwell: Lithium Controversy

Hector Warnes’ response to Barry Blackwell’s reply to his comments

I would like to congratulate Barry Blackwell for his insightful reply to Paul Grof and Jules Angst and further for his reply to Sam Gershon, in particular, on the theme of priority and cryptomnesia.  Regarding this latter word, it has been adopted as meaning unconscious plagiarizing (from the Greek plagios, oblique or crooked), a kind of literary thief who does not know it or has forgotten the source of his supposed discovery.  Barry’s example of Freud is correct. In his correspondence with W. Fliess there are many examples of cryptomnesia attributed to Freud.  Also, many examples of plagiarism in science and literature were exposed in the last half a century.

Regarding Barry’s disagreement with me on his comparing Linus Pauling’ work in orthomolecular medicine (1968) and Mogens Schou’s on lithium, all I can say is that in most controlled trials of vitamin E in cardiovascular disorders, vitamin C in prophylaxis of infectious disease and nicotinic acid in schizophrenia the respective hypotheses were not supported, whereas in most controlled trials Schou’s hypotheses about lithium in manic-depressive disorder were supported.

I fully agree with Barry’s statement that “we all make mistakes and owning them may benefit posterity”, but I disagree with Barry regarding his perfunctory statement that on page “Lithium does not benefit depression”. There are numerous reports in favor of lithum’s effectiveness in the treatment of depression, eg, Cipriani et al 2005, Crossley and Bauer 2007, Guzzetta et al 2007, Kessing et al 2005, Schou 1998, Tondo et al 2001, Walenstein et al 2006.

I very much like his endorsement of the “occult bipolar diathesis” in relationship to lithium responders.

In his reply to my comment Barry apparently made a mistake when he wrote: “full blown manic disorders with agnosia”. The term agnosia has been limited to the realm of the aphasias. Perhaps Barry meant anosognosia, loss of reality testing or insight into the illness.

 Forgive me for rambling but in my opinion the toxicity of a drug should be taken into consideration when prescribing a substance for treatment (Stahl 2011).  We still see adults with phocomelia whose mother while pregnant had taken thalidomide in the sixties.  Now we see the same psychotropic drugs which had been taken off the market because of their toxicity reintroduced with another indication as they were found useful as anti-proliferative immuno-modulators, inhibitor of angiogenesis, modulators of natural killer cells, inhibitors of cyclooxygenase - 2 activity and inhibitors of tumor necrosis factors. The British Bradcasting Corporation has recently presented a documentary review called “Thalidomide, the fifty year fight, May 15, 2014”.  

                      We have used too many drugs with deleterious adverse effect, such as tardive dyskinesia, which increased risk for seizures, agranulocytosis when compared to the risk for seizures or agranulocytosis, in the general population.  In spite of the fact that we have alternative treatments (Bowden 1995), we are now using atypical antipsychotics in bipolar disorder without considering that atypical antipsychotics can induce a “metabolic syndrome” and weight gain which in turn pave the way for other illnesses. Hibbard and his  associates paper on “Fatalities associated with clozapine-related constipation and bowel obstruction”, published in 2009,  reminded me of a similar clinical paper  we published with  Heinz Lehmann and Thomas. Ban in 1967 on “Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases”.

The question of risk- benefit  when using a drug are always talked about, but the clear statistical evidence of increased fatalities with some psychotropic compounds are still not explicitly communicated.  

References:

Berridge MJ, Downes CP, Hanley RR: Neural and developmental action of lithium: a unifying hypothesis. Cell  1989; 59: 411-419.

Bowden Ch. Predictors of response to divalproex and lithium. J Clin Psychiatry 1995; 56 (suppl 3): 23-30.

Cipriani A, Pretty H, Hawton K and Geddes JR. Lithium in the prevention of suicidal behaviour and all-cause mortality in  patients with mood disorders: a systematic review of randomized trials. Am. J. Psychiatry 2005; 162:1805-19.

Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders:  two meta-analyses of randomized, placebo-controlled trials. J Clin. Psychiatry 2007; 68 (6): 935-40.

Guzzetta F, Tondo L, Centorrino F, Baldessarini RJ. Lithium treatment reduces suicide risk in recurrent major depressive disorder. J Clin. Psychiatry 2007; 68(3): 380-3.

Hibbard, KR, Propst A, Frank DE, Wyse J. Fatalities associated with clozapine-related constipation and bowel obstruction: Psychosomatics 2009; 50 (4): 416-9.

Kessing LV, Sondergard L, Kvist K, Anderson PK. Suicide risk in patients treated with lithium. Arch Gen. Psychiatry 2005; 62: 860-6.

Schou M: The effect of prophylactic lithium treatment on mortality and suicidal behavior: a review for clinicians. J. Affect. Disord. 1998; 50: 253-

Stahl S M. Stahl’s essential psychopharmacology: the prescriber’s guide. 4th edition. Cambridge: Cambridge University Press; 2011.

Tondo L, Hennen, J. Baldessarini RJ.  Lower suicide risk with long-term lithium treatment in  major affective illness: a meta-analysis. Acta Psychiatr Scand 2001; 104: 163-72.

Valenstein M. McCarthy JF, Austin K L, Greden JF, Young EA, Blow FC. What happened to  lithium? Antidepressant augmentation in clinical settings. Am J of Psychiatry 2006; 163: 1219-25.

Warnes H, Lehmann HE, Ban TA: Adynamic Ileus during psychoactive medication: a report of three fatal and five severe cases. Can Med J 1967; 96: 1112-3.

Hector Warnes
November 26, 2015