Barry Blackwell: Lithium Controversy - Hector Warnes’ comment

I think it is unfair to compare Linus Pauling’s orthomolecular excesses and Mogens Schou, who was vindicated at last for his perseverance and clinical conviction that lithium had an unquestionable therapeutic effect on acute mania and had prophylactic effect in preventing, to an important degree, the relapse of bipolar disorders.

I would agree with Mogens Schou that lithium has antidepressant effects and those patients under lithium treatment were 25% less likely to commit suicide than those that were not.  I further agree with Schou that there are ‘hidden bipolars’ and even misdiagnosed unipolars, who had periodic mild hypomanic cycles, not detected even by family members.  Schou also addressed the question of a reduction of creativity in the bipolar patients treated with lithium and out of 24 artists he studied, 12 experienced an increase of creativity, 6 a decrease and 6 remained unchanged. The more manic episodes in their background, the more the increase in their creativity.

I am impressed with the multiple sites of action in the CNS of lithium, particularly on the second messengers (inositol monophosphatase, diacylglycerol and protein kinase C),  precisely in the sites involved in the physiopathology of affective changes like the hippocampus and the prefrontal cortex. All these changes influence neurotransmission, neuronal excitability and genetic expression. Further, the inhibitory action of lithium on GSK-3 beta influences neuroplasticity and increases the expression of Bcl-2, an anti-apoptotic protein. These neurotrophic effects result in an increase of  Bcl-2 in the frontal lobe and the hippocampus.

The increasing hybrid nature of many psychiatric diagnoses with co-morbidity and unpredictable evolution, particularly noted by Akiskal and others (e.g., borderline disorders, dysthymia, chronic depression deteriorating into dementia over the long run, etc.) put us at a loss to be strictly Kraepelinian.

With age, most patients are treated with 3 to 5 different drugs (polypharmacy), which interact with lithium, particularly NSAID, ACE inhibitors, calcium channel antagonists, thiazide diuretics, immunosuppressants, piperazine phenothiazines and others.  Besides, the summer heat increases the toxicity of lithium because of dehydration and the loss of sodium.  Because of the narrow therapeutic range, I usually prescribe lithium in healthy individuals who are clearly bipolar and in other cases who have been refractory to other pharmacotherapies.  I have found lithium to be a very effective drug in most cases and besides regular lithium levels in blood, I check EKG, thyroid function and renal function every 6 months.

I have encountered cases of rapid cycling Bipolar Disorders for many years unresponsive to valproate, carbamazepine, quetiapine or olanzapine that responded readily to lithium after a less than a month of therapy. 

Another question raised by Barry Blackwell was that of imipramine.  Of course, he himself realized that it has not prophylactic properties and even many psychiatrists do not use it in bipolar disorders because it may trigger a manic state. In fact, I had patients with dysthymic disorder using imipramine, who switched to a manic state with imipramine. The same happened in my experience with obsessive compulsive disorders who, using high doses of paroxetine, switched to a manic state.

Hector Warnes

September 3, 2015