Shridhar Sharma: Insulin coma treatment: Facts and controversies

Hector Warnes’ comment

Professor Shridhar Sharma could have started off with the increased risk for type II diabetes mellitus in schizophrenia and the relationship between negative symptoms of schizophrenia, deficiency in plasma levels of insulin-like growth factor-I, faulty modulation of dopaminergic neurotransmission and dysfunctional insulin receptor expression.  Thus, insulin receptor expression and or function may be altered in the brains of patients with schizophrenia and there is a modulation of dopaminergic neurotransmission by insulin. I think these findings alone would justify the re-evaluation of insulin coma treatment (ICT).

Dwyer et al (2001) elaborated on the findings that the schizophrenic population have an about 2 to 3 fold increased risk for type II diabetes mellitus. They also noted a correlation between plasma levels of Insulin Growth Factor I (deficiency) and negative symptoms in schizophrenic patients. Venkata Subramanian et al. (2007) studied anti-psychotic naïve schizophrenics and found a deficiency of Insulin Growth Factor I which might be the cause of insulin resistance. Gunnell et al. (2004) studied Insulin Growth Factor I and suggested that it regulates neural development including neurogenesis, myelination, synaptogenesis, dendritic branching, tyrosine kinase activity and neuroprotection after neuronal damage.

How do these findings translate clinically?

It has been shown and I personally have seen that schizophrenics who are undergoing ICT have a much higher insulin resistance than patients with other diagnoses (neurotics or alcoholics).  Hence schizophrenics require a higher dose of insulin to develop coma than patients with other psychopathologies.

I had some experience with insulin coma therapy in the late 1950s while I was in Lima, Peru, doing my residency in psychiatry under C. Alberto Seguin. I was, in fact, in charge of the ICT unit.  I must say that I was impressed with its immediate positive effects on severe acute schizophrenic patients. Some of them had a prolonged recovery after the treatment regardless of whether they had a hypoglycemic seizure or not during the procedure.

 I agree with Professor Sharma that we certainly need more research on ICT before throwing it out.

I am not going to replicate Prof. Sharma’s excellent overview of the literature on ICT. Most studies have shown that ICT was a cumbersome treatment that was surpassed by more effective treatments with ECT and phenothiazines. There have been a few comparative studies between phenothiazines and ICT. Phenothiazine therapy was superior and could be continued indefinitely to prevent relapse.  

References:

Dwyer DS, Bradley RJ, Klabinger AS Freedman AM. Glucose metabolism in relation to schizophrenia and antipsychotic drug treatment. Annals of Clinical Psychiatry 2001; 13:  203-113,

Gunnell D, Holly JMP. Insulin-like growth factor, insulin resistance and schizophrenia. The British Journal of Psychiatry 2004; 185: 353-4.

Venkata Subramanian G, Chittiprol S, Neelakantachar N. et al. Insulin and Insulin-like Growth factor abnormalities in anti-psychotic naive schizophrenics. Am J Psychiatry 2007; 164: 1557-60.

Hector Warnes

July 21, 2016