Lithium: A Case Study

Introduction
Lithium has been used as a form of treatment since the middle of the 19th century, although its purpose then was not the same as what is currently used for. Like many famous discoveries, the therapeutic effects of Lithium were discovered by accident but it has had a major impact on the development and understanding of psychopharmacology. As American psychiatrist Nathan Kline said, (Johnson, 1984)
“If we were to eliminate from science all great discoveries that had come about as a result of mistaken hypothesis or fluky experimental data, we would be lacking half of what we know (or think we know).”
Now a leading drug in the treatment of Bipolar disorder, Lithium is a highly influential drug in the treatment of psychiatric disorders,

He flipped a coin to choose which mania patients received Lithium and which received the placebo. His trial was effective in confirming the anti-manic effects og Lithium. In 1967, Baastup and Schou presented further findings in a paper, claiming that lithium treatment could decrease the frequency of both manic and depressive recurrences by 87%, thus encouraging its eventual use as a prophylactic agent. Despite all the evidence presented at this time to suggest that Lithium therapy is in fact a highly effective form of treatment for patients with Bipolar disease and even those suffering from schizophrenia and shizo-affective patients, the reintroduction of Lithium therapy was met with stiff opposition. It was not until 1970, when Baastrup and Schou (Gerson, 2013) used 100 patients with recurrent mood disorders for a double blind discontinuation study. This study again confirmed the prophylactic efficiency of

However, the effect that Lithium has on certain pathways in the brain has led to the development of the major current working hypothesis. It is know that the activity of the phosphoinositol diphosphate dependant pathway is notably increased during mania and that Lithium affects phosphoinositol second messenger system. (Katzung et al. 2009) Inositol triphosphate and diacylglycerol play an important role as second messenger for both α-adrenergic and muscarinic transmission. Phosphoinositol diphosphate membrane lipid is converted to diacylglycerol and inositol triphosphate, while the G protein mediates the conversion of these synaptic messengers. Inositol triphosphate is then further broken down into inositol monophosphate and then, through reaction with the enzyme inositol monophosphatase, is broken down to free inositol (Principles of Neural Science, ). Lithium’s therapeutic effect (Katzung, 2009) is due to its inhibition of inositol monophosphatase and other important enzymes in the normal recycling of membrane phosphoinositides. Inositol triphosphate begins to accumulate in the cytpoplasm as a result out the reduction in responsiveness of these neurons. In normal brain function, inositol triphosphate is active in regulating the intracellular levels of Ca2+, so phosphoinositol diphosphate dependant pathway activity would be expected to decrease. The effects that Lithium