Lithium: How Good is it?

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Many people worry that lithium is one of psychiatry’s “Big Guns”, something we use for patients with really severe mental illnesses.  They think, “Hey, I’m not that sick”, and conclude that lithium is not right for them.

They don’t know that lithium, in lower doses, is used in plain depression (not bipolar, not severe).  In fact, for depression that hasn’t fully responded to an antidepressant, lithium is a standard option for “augmentation”, adding it to the antidepressant.

But one of the strongest arguments for lithium is the way it appears to protect neurons.  So I wanted to show you the world’s expert on how lithium works, talking about this aspect of lithium’s potential benefits.  His full comments, on a range of topics, from his interview with a great bipolar advocacy organization, can be read on this link at the Child and Adolescent Bipolar Foundation (CABF).

Here are Dr. Manji’s comments about lithium (it’s a little technical; look for the few ideas I put in bold if you’re getting bogged down):

CABF: Speaking of lithium, your research has uncovered some of its intriguing beneficial properties. Can you highlight the most important ones?

MANJI: Many of the genes that are considered neuroprotective [keep brain cells from dying when stressed] are being remarkably turned on by lithium. Is lithium actually neuroprotective? We hadn’t thought this way before. A number of studies have taken animal cells and tried to kill them by causing stroke, etc. These studies have consistently shown that lithium, if administered before you try to do the bad things (such as induce a stroke),protects the animal’s neurons. In lithium-treated brains, the size of the resulting stroke is smaller, the number of neurons that die is lower, etc. That was amazing. Since these studies were done in rats, you need to be careful about jumping to conclusions that lithium is neuroprotective in people.

Wayne Drevets’ group published a finding in Nature about five years ago that in a part of the pre-frontal cortex of bipolar patients or patients with familial recurring unipolar depression, there was almost a 40% reduction in the amount of gray matter. That was a remarkable finding that you have such a reduction in a discrete part of brain. We spoke to him about our lithium findings and asked him to reanalyze the data. He had a small group of patients who had been treated with lithium for a long time and they did not show the brain atrophy compared with the bipolar patients. Interestingly all of the patients with unipolar depression, whether or not they had been treated with antidepressants, still showed the atrophy. That was a suggestion that bipolar treatments might have a protective effect.


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