Lithium: The Gift That Keeps on Giving in Psychiatry
http://www.medscape.com/viewarticle/881529_2
Nassir Ghaemi, MD, MPH
June 16, 2017
Wide-Ranging Benefits
At the recent American Psychiatric Association
annual meeting in San Diego Harvard Medical School
Leonardo Tondo, MD, a prominent researcher on
lithium and affective illness, who is on the faculty of McLean Hospital/Harvard
Medical School and the University of Cagliari, Italy, reviewed studies on
lithium's effects for suicide prevention. Ecological studies in this field have
found an association between higher amounts of lithium in the drinking water
and lower suicide rates.
These "high" amounts of lithium are
equivalent to about 1 mg/d of elemental lithium or somewhat more. Conversely,
other studies did not find such an association, but tended to look at areas
where lithium levels are not high (ie, about 0.5 mg/d of elemental lithium or
less). Nonetheless, because these studies are observational, causal
relationships cannot be assumed. It is relevant, though, that lithium has been
causally associated with lower suicide rates in randomized clinical trials of
affective illness, compared with placebo, at standard doses (around 600-1200
mg/d of lithium carbonate).
Christoforos Giakoumatos, MD, from the Harvard
South Shore Psychiatry residency training program, reviewed the scientific
literature on lithium's neuroprotective effects. Extensive animal studies have
shown that lithium keeps neurons alive longer. Some human studies also suggest
a benefit of lithium in prevention or amelioration of dementia, consistent with
its neurobiological benefits. These data support further work to clarify how
much, and to what extent, lithium could be useful in human neurodegenerative
diseases.
Othman Mohammad, MD, also from the Harvard South Shore
Lithium's Safety Profile
Dana Wang, MD, a senior resident in the Harvard South Shore Sweden
The rate is somewhat higher if the sample is
limited to those who take lithium for a minimum of 10 years; in that case, up
to 5% of patients may develop end-stage renal disease eventually. Although
these numbers are important, they also indicate that over 95% of
lithium-treated persons never develop end-stage renal disease.
Multiple daily dosing of lithium is a major
risk factor for such chronic renal harm, and it is a preventable one, because
lithium has a half-life of 24 hours and only needs to be dosed once daily.
Furthermore, keeping lithium levels low, and thus avoiding acute lithium
toxicity, is another preventable risk factor for chronic renal impairment. By
dosing lithium once daily at night and at the lowest dose feasible, the risk
for long-term kidney harm with lithium can be reduced even further.
Dr Osser ended the symposium by discussing how
to manage other lithium-related side effects. He noted that lithium causes less
weight gain than divalproex or commonly used antipsychotics, such as olanzapine
and quetiapine. Thus, if those agents are used, so should lithium. He also
noted some ways in which weight gain can be ameliorated with lithium: for
example, educating patients to avoid consuming caloric beverages (such as
sodas) when managing lithium-related thirst. Water retention with lithium can
be managed by using amiloride. Carbohydrate craving is an important aspect of
lithium-related weight gain, and the most difficult to manage.
Conclusion
I provided a commentary at the end of the
symposium, where I noted that our oldest drugs are our most effective:
electroconvulsive therapy, lithium, monoamine oxidase inhibitors, and
clozapine. All of the new drugs developed since the 1970s have not advanced
greater efficacy for any major psychiatric condition. They do have fewer side
effects, which is important. But the case of lithium reminds us that we should
not assume that newer is better.
All patients should be told about the
potential range of benefits of lithium, in terms of mortality/suicide and
neuroprotection/dementia prevention, in addition to its well-proven mood benefits.
If this is understood, then many patients and doctors would perhaps also
understand how these benefits could outweigh the risks of lithium. Such risks
should be considered limited, with about 1% long-term kidney risk and less
weight gain than other commonly used agents.
