A 35-year-old military officer leads an expedition to the west coast for 18 months. During this journey he has episodes lasting 1 to 6 weeks in which he exhibits a decreased need for sleep, feeling rested after only 3 hours of sleep. He becomes very goal-directed, which aids in his documentation of findings, but in his journals he jumps from one idea to another quickly. Between these episodes he becomes morose and far less talkative. Upon his return from the expedition, he takes an administrative job in St Louis, but becomes unable to keep up with the demands of his work. He acquires debts he cannot repay. While on a business trip to Washington, D.C., to try and secure a loan, he stops at Grinder's Stand, in Tennessee. Later that evening, shots are heard. He is found deceased, with contact range gunshot wounds to the chest and forehead.

The following synopsis was written by his "Chief Executive" and friend: "Governor L. had, from early life, been subject to hypochondriac affections. It was a constitutional disposition in all the nearer branches of the family of his name, and was more immediately inherited by him from his father. They had not, however, been so strong as to give uneasiness to his family. While he lived with me in Washington I observed at times sensible depressions of mind: but knowing their constitutional source, I estimated their course by what I had seen in the family. During his western expedition, the constant exertion which that required of all the faculties of body and mind; suspended these distressing affections; but after his establishment at St. Louis in sedentary occupations, they returned upon him with redoubled vigour, and began seriously to alarm his friends. He was in a paroxysm of one of these, when his affairs rendered it necessary for him to go to Washington." (from http://www.gutenberg.org/files/16565/16565-h/16565-h.htm)

Questions:

8.1 What is the most likely diagnosis? Who is this? Who is the Chief Executive? What is the manner of death?

He has bipolar disorder. This is Meriwether Lewis, who died May 15, 1809, at the age of 35. The Chief executive was Thomas Jefferson, 3rd President of the United States. The probable manner of death is suicide.

8.2 What pharmacotherapy currently available would have been helpful in treating this man?

Lithium carbonate, carbamazepine, and valproate are all useful for treating bipolar disorder, particularly for mania. Lithium is the first choice, but valproic acid is near equal in efficacy. Carbamazepine is somewhat less effective.

8.3 Explain the neurophysiology of this disorder and how the drugs work.

Lithium stabilizes neuronal membranes and is exchanged similar to sodium across cell membranes. It increases levels of inositol triphosphates (IP3), and that in some way stabilizes neuronal function modulating effect. Interestingly, the other drugs used are anticonvulsants which also stabilize neuronal function. It may take a week to 10 days for lithium to have an effect.