Lithium the classic mood stabilizer

Lithium the classic mood stabilizer

Bipolar disorder has classically been treated with lithium for more than 50 years. Lithium is an ion whose mechanism of action is not certain. Candidates for its mechanism of action are various signal transduction sites beyond neurotransmitter receptors ( ). This includes second messengers,Figure 8-3 such as the phosphatidyl inositol system, where lithium inhibits the

Figure 8-3. . Although lithium is the oldest treatment for bipolar disorder, itsLithium’s mechanism of action mechanism of action is still not well understood. Several possible mechanisms exist and are shown here. Lithium may work by affecting signal transduction, perhaps through its inhibition of second-messenger enzymes such as inositol monophosphatase (right), by modulation of G proteins (middle), or by interaction at various sites within downstream signal transduction cascades (left).

enzyme inositol monophosphatase; modulation of G proteins; and most recently, regulation of gene expression for growth factors and neuronal plasticity by interaction with downstream signal transduction cascades, including inhibition of GSK-3 (glycogen synthase kinase 3) and protein kinase C ( ).Figure 8-3

However lithium works, it is proven effective in manic episodes and in maintenance of recurrence, especially for manic episodes and perhaps to a lesser extent for depressive episodes. Lithium is well established to help prevent suicide in patients with mood disorders. It is also used to treat depressive episodes in bipolar disorder as an augmenting agent to antidepressants for unipolar depression, as mentioned in , but is not formally approved for these uses. A number of factors have led toChapter 7 an unfortunate decline in the use of lithium in recent years, including the entry of multiple new treatment options into the therapeutic armamentarium for bipolar disorder, the side effects of lithium, and the monitoring burden that is part of prescribing lithium. The modern use of lithium by experts departs from its classic use as a high-dose monotherapy for euphoric mania, with lithium utilized now as one member of a portfolio of treatments, often allowing once-a-day administration and lower doses when combined with other mood stabilizers. Lithium has equal or better efficacy in bipolar disorder compared to valproate for manic, depressive, or mixed episodes, although valproate is often more frequently prescribed. Anticonvulsants including valproate have been controversially and not completely convincingly linked to causing suicidality, whereas lithium actually reduces suicide in patients with bipolar disorder. In fact, some provocative studies from Austria to Texas to Japan suggest that the more lithium mobilized by rain from rocks and soil and then dissolved in drinking water, the lower the suicide rate in the general population as well! Another potential use of lithium

Downloaded from http://stahlonline.cambridge.org by IP 100.122.180.231 on Fri Mar 22 01:17:08 UTC 2019 Stahl Online © 2019 Cambridge University Press. All rights reserved. Not for commercial use or unauthorized distribution.

 

 

arises from the notion that inhibition of GSK-3 by lithium could theoretically inhibit the phosphorylation of tau () proteins and thus slow the formation of plaques and tangles in Alzheimer’s disease. A few studies have suggested that lithium can prevent progression from mild cognitive impairment to Alzheimer’s disease and reduce phosphorylated levels, especially if given for a long period of time (> 1 year), and even at low doses. This remains controversial and needs replication in larger studies, but is certainly an interesting development to monitor.

Well-known side effects of lithium include gastrointestinal symptoms such as dyspepsia, nausea, vomiting, and diarrhea, as well as weight gain, hair loss, acne, tremor, sedation, decreased cognition, and incoordination. There are also long-term adverse effects upon the thyroid and kidney. Lithium has a narrow therapeutic window, requiring monitoring of plasma drug levels. Modern use of lithium often includes dosing at the lower end of the therapeutic window and combining lithium with other mood stabilizers.

Downloaded from http://stahlonline.cambridge.org by IP 100.122.180.231 on Fri Mar 22 01:17:08 UTC 2019 Stahl Online © 2019 Cambridge University Press. All rights reserved. Not for commercial use or unauthorized distribution.

"Is this question part of your assignment? We can help"

ORDER NOW