Lithium: The Gift That Keeps on Giving in Psychiatry

Nassir Ghaemi, MD, MPH

June 16, 2017

 

https://www.medscape.com/viewarticle/881529

 

Wide-Ranging Benefits

At the recent American Psychiatric Association annual meeting in San Diego, an update symposium was presented on the topic of "Lithium: Key Issues for Practice."^[1] In a session chaired by Dr David Osser, associate professor of psychiatry at Harvard Medical School, presenters reviewed various aspects of the utility of lithium in psychiatry.

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 program, examined lithium use in children and adolescents, and reviewed a number of randomized trials that showed evidence for efficacy and short-term safety with lithium in acute manic episodes, especially in adolescents. Of note, similar randomized data did not show benefit with divalproex, indicating that there is relatively more evidence for lithium's efficacy and safety in adolescence.

Lithium's Safety Profile

Dana Wang, MD, a senior resident in the Harvard South Shore program, reviewed the kidney effects of lithium and the latest studies quantifying those harms. For instance, in recent data from Sweden, lithium was associated with end-stage renal failure in about 1% of all patients who were treated with it—an effect that occurred over a mean of more than 20 years of treatment.

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.

 

To paraphrase Frederick Goodwin, in bipolar illness, you don't need a reason to give lithium. You need reasons not to give it.

 

 

Antidepressants in bipolar disorder: the case for caution

S Nassir Ghaemi ¹, Douglas J Hsu, Federico Soldani, Frederick K Goodwin

Affiliations 

·        PMID: 14636365

 

·        DOI: 10.1046/j.1399-5618.2003.00074.x

Abstract

The 2002 American Psychiatric Association (APA) guidelines for the treatment of bipolar disorder recommended more conservative use of antidepressants. This change in comparison with previous APA guidelines has been criticized, especially from some groups in Europe. The Munich group in particular has published a critique of assumptions underlying the conservative recommendations of the recent APA treatment guidelines. In this paper, we re-examine the argument put forward by the Munich group, and we demonstrate that indeed, conceptually and empirically, there is a strong rationale for a cautious approach to antidepressant use in bipolar disorder, consistent with, and perhaps even more strongly than, the APA guidelines. This rationale is based on support for the following four propositions: (i) The risk of antidepressant induced mood-cycling is high, (ii) Antidepressants have not been shown to definitively prevent completed suicides and reduce mortality, whereas lithium has, (iii) Antidepressants have not been shown to be more effective than mood stabilizers in acute bipolar depression and have been shown to be less effective than mood stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood stabilizers, especially lithium and lamotrigine, have been shown to be effective in acute and prophylactic treatment of bipolar depressive episodes. We therefore draw three conclusions from this interpretation of the evidence: (i) There are significant risks of mania and long-term worsening of bipolar illness with antidepressants, (ii) Antidepressants should generally be reserved for severe cases of acute bipolar depression and not routinely used in mild to moderate cases and (iii) Antidepressants should be discontinued after recovery from the depressive episode, and maintained only in those who repeatedly relapse after antidepressant discontinuation (a minority we judge to represent only about 15-20% of bipolar depressed patients).

Link  https://pubmed.ncbi.nlm.nih.gov/14636365/