A Cure for CTE?

Nassir Ghaemi, MD, MPH; Sivan Mauer, MD


January 15, 2016

In This Article


The recent movie Concussion has raised public awareness of the potential harmful effects of head trauma in contact sports. Chronic traumatic encephalopathy (CTE) is the diagnosis that was discovered and described in that movie in the context of American football. It is a type of traumatic brain injury that most notably occurs in physically violent sports but can also occur in other settings, such as during military duty, where explosive blasts can cause subconcussive impacts to the head. The main clinical features of CTE involve three aspects: mood/impulsivity, suicide, and dementia.[1] To date, there are no proven treatments for CTE. In this essay, we would like to describe—for the first time anywhere—the hypothesis that lithium, at standard or even low doses, can improve or prevent CTE in all three aspects, including preventing suicide and dementia.

Preventing Suicide

The only medication proven in the psychiatric literature to prevent suicide is lithium. This has been shown over decades in dozens of randomized clinical trials in thousands of people. These data have been meta-analyzed compared with placebo. The effect size is huge, with 87% reduction of suicide risk on lithium (odds ratio, 0.13; 95% confidence interval, 0.03-0.66).[2] Hence, we can say with about as much certainty as anything in evidence-based medicine that lithium prevents suicide. Furthermore, no other medication has been proven in the same way to prevent suicide.

Clozapine, a neuroleptic, has been shown to reduce suicide attempts versus placebo in a randomized clinical trial (and received FDA approval to put that language into its marketing), but there were zero suicides in that study.[3] In other words, clozapine was not proven to prevent completed suicide. Epidemiologic data have been provided for lower actual suicide rates with clozapine, as has also been shown extensively with lithium, but such prevention of actual suicide has not been shown with clozapine, or any other agent besides lithium, in randomized studies.

It is well known that depression is perhaps the most important risk factor for suicide. Also widely known is the controversy about whether the most extensively used class of medication for depression, serotonin reuptake inhibitors (SRIs), prevents or even causes suicide.[4] What is clear is that SRIs do not have an extensive, large, replicated suicide prevention benefit proven without evidence to the contrary, as is the case with lithium—hence, the statement that lithium is the only medication proven to prevent suicide in psychiatry.

In the above randomized clinical trials, lithium was given to patients with mood illness, both unipolar depression and bipolar illness (although mostly the latter), and it was used in standard doses (usually about 600-1200 mg/d of lithium carbonate). Besides these randomized data, there is an extensive epidemiologic literature that lithium can prevent suicide even in non-mood-illness subjects, such as the general population.[5] These studies are based on analyses of populations where "high" levels of naturally occurring lithium are present in the geology of a region. Lithium is a metal, present in rocks, which seeps into the ground and water supply and is taken up by vegetables and then animals. It is a trace mineral that is natural and normal to have in the human body. Normal amounts probably reflect about 1 mg/d of exposure to elemental lithium in the diet. "High" amounts of lithium in the diet would reflect more, such as 5 mg/d. "Low" amounts of lithium would occur with less, meaning < 1 mg/d or even complete absence of lithium exposure. In multiple epidemiologic studies of tens of thousands of persons in different countries, much lower suicide rates have been identified in regions with "high" versus "low" lithium geological content.[5]

If lithium prevents suicide in mood illnesses, as the randomized data show, and if low-dose lithium also prevents suicide in non-mood-illness subjects, as the epidemiologic geology studies suggest, then low-dose lithium may also prevent suicide in persons with CTE, who have mood symptoms but do not technically have unipolar depression or bipolar illness as primary psychiatric diseases. This lithium treatment may be feasible even at lower than standard doses so as to address concerns regarding side effects and toxicity, which we'll return to later.


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