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Crossing continents: changing ideas in bipolar disorder
Robert H. Belmaker

 

An interview with Robert Haim Belmaker

Robert Haim Belmaker has been Professor of Psychiatry at Ben Gurion University of the Negev, Israel, for the past 30 years. His career has seen the unfolding of the lithium story, and he has played roles therein both in the clinic and the laboratory.

Lithium was approved for clinical use in the treatment of mania in the US in 1970, having been first approved in some European countries in the early 1960s[1]. This of course was the era of the ‘psychopharmacological revolution’, which saw a number of drugs with psychiatric therapeutic effects coming into the clinic.

“When I started, in the 1970s – it was at Duke Medical School where I got my MD – one of my teachers, Dr John Rhoads, had just received permission to give lithium for bipolar disorder,” described Dr Belmaker. “I was a student with him, seeing the first few lithium patients."

"We were all convinced that it was a miracle. And it was, for some patients, a miracle.”

In 1974 Dr Belmaker moved to Israel and began working at the Jerusalem Mental Health Center, which very soon had several hundred bipolar patients in its care. Illustrating the pharmacological zeitgeist of those times, Dr Belmaker explained how it evolved into the more nuanced attitude of today: “We were convinced – it’s almost embarrassing to say now – that lithium should be given only as monotherapy. The patients got lithium or nothing else: if they were bipolar we expected patients to respond, and if they didn’t respond we raised doubts. Looking back 45 years, if they didn’t respond we changed the diagnosis or hoped that they would drop out of treatment and go somewhere else."

“Even after the anti-epileptic drugs, valproate and carbamazepine, began to emerge, it took quite a while for us to think that these might be reasonable options and first line in some patients. Neuroleptics were of course used often, but we didn’t admit it. This was less true in the UK, but more true in Israel and the US: patients that were treated with neuroleptics in addition to lithium were immediately rediagnosed as schizoaffective."

“In the US text books of the 1970s and 1980s, there were strong recommendations against adding neuroleptics to lithium for several reasons, especially tardive dyskinesia, but also neurotoxicity. That belief did not affect clinical practice – surveys at the time showed that two-thirds of bipolar patients were getting neuroleptics. It was only with the second generation neuroleptics that it became academically acceptable that some bipolar patients do very well on atypical antipsychotics.”

Pharmaceutical companies provided the data to allow practitioners to be comfortable with alternative regimens, noted Dr Belmaker. And from this emerged a more flexible approach to diagnosis – moving away from monolithic diagnoses towards a spectrum, for example, between schizophrenia and bipolar disorder. On this theme, Dr Belmaker gave an impressionistic view of the meandering course of research, clinical practice, and shifting paradigms within psychiatry of the past several decades: “I think that research did not lead these changes in practice, but multiple other reasons contributed; and the changes haven’t been in one direction; they have gone back and forth in a meandering way in the 45 years that I have been a visitor on this exciting planet!

“Things change; attitudes change. This is not usually the result (both in psychiatry in general, as well as in the bipolar area) of a specific study. The idea that NIMH or the Medical Research Council has to fund a perfect study that we design, and then we do it and it gives us the definitive answer: I don’t think that has been true of any of the important questions that I have been involved with over the last 45 years.

“It’s more an accumulation of studies and, even more importantly, the lack of positive results. When people try to prove something in different ways and they are not able to, they usually quietly abandon the idea. The tide turns and looks for some other central idea rather than a single study or even two answering the question definitively.”

Accompanying the changing neuroscientific notions are changes in sociocultural attitudes, something that was recently investigated by the International Society of Bipolar Disorders with the idea that a deeper understanding of the interplay of healthcare system and culture can be used to develop culturally-appropriate care. Nineteen international bipolar disorder experts from six continents (Dr Belmaker included) responded to a qualitative survey. Results indicated that stigma, access to treatment options and follow-up were pertinent to good clinical management, with these being related to socioeconomic as well as cultural factors[2].

On his observations of sociocultural differences in bipolar disorder, Dr Belmaker explained: “Early on I noticed that bipolar disorder patients in Israel seem to have more manic attacks than depressive attacks, whereas in northern Europe they have always been reported as having more depressions than manias.

“A big thrust of research in the last twenty years in northern Europe and northern America has been the findings that depression in bipolar disorder causes a larger proportion of the morbidity than mania. That was not my clinical experience and we documented our clinical experience.

There has now been a report from India that, like in Israel, the manias are more problematic than the depressions. Manias are more frequent compared to depressions in our practice; they are often more violent, more difficult to control than has been reported in other countries. But this was greeted with great scepticism. I feel that our results were dismissed.

“More recently, there is a realisation that mania in bipolar disorder is heterogeneous. As Angst taught us many years ago, there may be types of bipolar illness that are more depressive and types that have more manias, and that the polarity of the last episode may affect treatment outcome. That is only a short distance to saying that there may be cultural differences internationally; I don’t think this last statement is yet accepted, though I believe it to be true.

“The Diagnostic Statistical Manual [DSM] idea that a diagnosis is a diagnosis – that it is the same anywhere in the world and throughout time – is a very strange belief. It is not the same in other areas of medicine – the symptomatologies of heart disease, or pneumonias, asthma, and autoimmune diseases are different in different countries. Pollutants and diet are different. Although human beings are a new species, and we are all brothers really, there is no real reason to think that diseases are universally the same.”

Dr Belmaker also spoke of one of his other passions – his pursuits in local archaeology. Indeed, the act of digging up the sociocultural histories that provide foundations for contemporary culture lends us a useful physical metaphor for the acceptance and adaptation that is demanded in mental health care.

“In Israel, in almost every square metre there is something you can dig up,” said Dr Belmaker, who currently lives in Modiin, the origin of the Maccabean uprising against the Seleucid Empire and Hellenistic influence on Jewish life which took place between 100 and 200 BC.

“There are some interesting archaeological sites that are really amazing,” he continued, “Because from them you can learn a lot about culture. For example, this area of the world has always been about diversity. There has never really been a time when only Jews lived in Judea or Samaria or Israel. There was always an intermingling of cultures and – as can be seen in the Maccabean revolt – not always a friendly one!

“I have followed this closely over the last 50 years because in 1967, when I was first here with my wife on our honeymoon, the whole area immediately outside the Western Wall was basically covered in garbage. It has gradually been excavated down to various levels – the Herodian level, the street level at the time of Jesus, and then some areas below that. For instance, you can see the fire and ashes and stones pushed over by the Roman soldiers who destroyed the Jewish temple that was on the mount during the revolt of 70 AD. Those stones are still there.

“About the level of 300 AD is very interesting. The Roman Empire destroyed the Herodian Kingdom, and decided that they were going to destroy the Jewish presence in this country. The Roman Empire eventually became a Christian empire, and then the Byzantine Empire began. There was a very brief period where one of the emperors, Julian, was an apostate (to Christianity) who allowed Jews back into Jerusalem. And you can actually see that at about 300 AD there is an inscription chiselled on the Western Wall in Hebrew by a Jew who had arrived in Jerusalem reading, ‘I never believed my eyes would see this day’.”

These areas around the Western Wall have been excavated, reconstructed and opened to the public. Notably, authorities running the excavations have insisted that only scientific criteria be used in assessing how far excavations should go, and what exactly should be reconstructed: excavation necessarily destroys, or at least displaces, what comes above it. As such, explained Dr Belmaker, one finds churches, mosques, synagogues exhibited side by side, illustrating their influence over the city. “That is an important message,” he stressed.

“The message is that, both in psychiatry and archaeology, the truth is diversity and diversity is the truth. We have to be able to accept different opinions and to accept changes. In psychiatry, a lot of our dogmas about DSM and about what medicine is effective or not – these change. I have had to admit some things about how I practiced that are embarrassing today because that is the way it was done then. People have to accept others’ presence around them and in their history as well as their own.”


In 2016 Robert Belmaker gave a lecture at the 29th ECNP Congress in an
educational update session (E.04).

In
this video, Dr Belmaker talks about new developments in lithium research and his experience at the ECNP Congress.  


References
[1] Shorter E. The history of lithium therapy. Bipolar Disord. 2009 Jun; 11(0 2): 4–9.
[2] Oedegaard CH et al. An ISBD perspective on the sociocultural challenges of managing bipolar disorder: A content analysis. Aust N Z J Psychiatry. 2016 Nov;50(11):1096-1103.
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