Wednesday, 28.10.2020

 

Thomas A.Ban, editor. Lithium in Psychiatry in Historical Perspective.

Aitor Castillo’s comment

Walking with lithium in Peru

 

        This story began on a distant gray morning during a cloudy winter at Lima city at the end of the ‘70s. There was a large auditorium in the very ancient psychiatric hospital “Victor Larco Herrera” (100 years old), surrounded by antique buildings and romantic gardens,  occupied by a group of medical students who were attending their course of psychiatry organized by a local university. Every week we gathered there to listen to some talks and perform some clinical practices with patients.

        I enjoyed going to that particular psychiatric hospital because, at the very beginning, it was pretty close to my beloved  Pacific Ocean  and also because I could walk along wide roads under tall trees full of peace while being away from the  noisy and busy city. However, I have to say that those psychiatric lessons were not very interesting, even though I was considering entering a residency training program in psychiatry when I finished my studies. The lectures used to be boring and the faculty spoke in such very low voices that the only thing one could hear were the sound of the waves coming from the sea. Maybe more important, the concepts were pretty abstract and difficult to understand.

        On that cold morning, the students were silently listening to the teacher who was standing up there on the stage dreaming, maybe, of being a rock star. I was among them accomplishing the same routine duty. Suddenly, the teacher, whose name and face I do not remember now, mentioned something about a medicine that apparently could help some special patients. He mentioned a kind of stone, a molecule, an ion, something that could change the way the brain works. Its name was lithium. Then, after the class was over, I left the room with that name echoing in my head. I thought that maybe this mineral could show me the way to understand all those patients who were talking to themselves, smiling without reason and behaving in such strange ways. Then  I told myself,  this issue is related to all these people around us who are waiting for something to help them leave this big impersonal hospital.

        Finally, a couple of years after finishing my medical studies, I entered the psychiatric residency training program of the Universidad Nacional Mayor de  San Marcos in Lima city, Perú. While there, the old mineral name came back to my memory. In this way, lithium started to become some kind of a special hope for helping people during my professional life. I studied it, I prescribed it to my first appropriate patients and I realized that apparently we could do  more  personalized  psychopharmacology. It was clear that lithium required  a dose titration until reaching a therapeutic  concentration level  that helped me feel more confident about my medical skills. In some way, lithium could let me anticipate the therapeutic results. At the same time, it helped me keep updated regarding my knowledge about pharmacology and pharmacokinetics, neurological, renal and thyroid functions among others, and integrate them with pharmacodynamics and clinical psychiatry.

        In parallel, step by step, I started to notice that, in general, lithium increased concerns among doctors and patients.  They imagined lithium to be a sort of toxic monster reserved only for lost causes.  Some of them believed (and still do) that lithium only works in people “who lack it inside their bodies.” For that reason, the first step in the treatment strategy is to educate people that there is no evidence that bipolar patients (or any person) have a lithium deficit in their organisms.

        A few years ago, as a very interesting anecdote, during an electoral campaign conducted in Perú a very charismatic presidential candidate known by the nickname of “crazy horse” was asked  on a television program interview if it was true that he was treated with lithium. Obviously, the answer was negative but most of the public was convinced that he really took lithium. Curiously  enough, he won the election with an ample margin. Although there never was any evidence about his medical treatment with lithium, he was really a very clever, ingenious and emphatic person. Regretfully, he committed suicide in 2019 while on the verge of serious judicial affairs. In the field of private practice, many patients did not want to be identified with him when I suggested lithium for them and refused the prescription.

        Now, I must go back to my wonderful training period with Tom Ban at the Tennessee Neuropsychiatric Institute in Nashville during 1978-1979. I remember my conversations with Stuart Berney, who was at that time the head of the laboratory there, about the methods to measure the blood  levels of psychotropic drugs in order to get a more personalized treatment for the patients. During the following couple of  years I continued my training at the Institute of Experimental Medicine in Caracas-Venezuela with Luis Ordoñez and at the Psychiatric Research Institute of Tokyo-Japan with Takashi Moroji where I had the opportunity to get deep insight about psychopharmacology and biological psychiatry.

        By 1982 I had returned to Perú and joined a very small group of senior people in order to develop the country’s National Institute of Mental Health. I want to be honest and say that it was a kind of political-academic  agreement between the governments of Perú and Japan, taking into account that the Japanese International Cooperation Agency  donated a lot of money for the implementation of the project. I was then named head of the Biological Psychiatric Laboratory, where  one of the first pieces of equipment that arrived at my lab from Tokyo was an Atomic Absorption Spectrophotometer.

        The institute was administered by the Peruvian Ministry of Health and served a vast economically deprived population from  northern Lima city, but, at the same time, was a reference center for the rest of the country. Beside some administrative, academic and research duties, this institution faced a huge amount of clinical work with psychiatric out- and in-patients.

        Regarding the measurement of lithium plasma levels, we were the only public facility in the whole country able to do that in the context of very low prices. So, I decided to study how long a sample of lithium  serum arriving from a distant health center would be available for doing such work. The study results were published in Anales de Salud Mental (Castillo and Miyahira 1986), in a paper whose title translated to “Stability of serum lithium under ambient conditions.” The abstract reads:

        “Serum samples from 52 out-patients treated with lithium salts were studied in order to assess the stability of the ion under ordinary laboratory conditions. Aliquots were taken on day 0 and kept in the laboratory at room temperature. The analyses were performed on days 0, 7, 14, 21 and 30 using a standard atomic absorption spectrophotometric technique. The lithium concentrations remained constant throughout the study period. No significant differences were found among the evaluations. The results show that it is possible to handle and send serum samples for lithium analyses from distant places to the appropriate laboratories without any special care.”

        Sure, this was a very simple study, but let me encourage doctors to prescribe lithium with the support of the laboratory assuring them of a correct approach to dose titration.

        As the years went by, I always kept in contact with the world of lithium. I used to give lectures from time to time about lithium and put special emphasis on it during my seminars  in psychopharmacology for first-year residents at Universidad Nacional Mayor de San Marcos psychiatric training program. Very often, I try to create a real-life atmosphere for the audience by remembering the tragic suicide of  Kurt Cobain, lead singer of the rock band  Nirvana,  who wrote a song called “Lithium” but, apparently, never tried it as a part for his treatment of bipolar disorder.

        I have also observed that most doctors still do not use lithium with confidence. Anticonvulsants used to be their first choice, maybe following the American psychiatrists’ practice. I understand that in Europe lithium is given greater consideration. As a matter of fact, I have to recognize that sometimes I lost some patients in my private practice when I suggested they take lithium for their bipolar disorders. They simply ran away. To the best of my knowledge, lithium is not a panacea but still it is the gold standard for the treatment of bipolar disorder, especially as expressed in the classic manic-depressive clinical presentation.

        Lithium continues guiding my interest in trying to understand the complexity of brain function and I share the naive experience of Aretaeus of Cappadocia in those ancient times  when he observed the cyclical mood fluctuations of people living together in the mountain caves in order to survive (Tekiner 2015). In those times, obviously they did not have lithium and their suffering remained unrelieved.

 

References:

Castillo A, Miyahira A. Estabilidad del Litio Serico en Condiciones Ambientales. Anales de Salud Mental, 1986; 2:67-71.

Tekiner H. Aretaeus of Cappadocia and his treatises on diseases. Turk Neurosurg. 2015; 25(3):508-12.

 

July 2, 2020