Monday, December 26, 2022

Lithium & Alzheimer! Really!

Lithium & Alzheimer

The most fascinating research recently, however, has been on the use of lithium for Alzheimer’s disease. Given its being the only cause of death in the top 10 in America that cannot be prevented, cured, or slowed, researchers are spending billions of dollars on Alzheimer’s disease. There is a fast-growing community of researchers suggesting that lithium may provide significant benefits in the treatment and prevention of Alzheimer’s.

In a recent trial published in Current Alzheimer's Research, a nutritional dose of just 300 mcg of lithium was administered to Alzheimer's patients for 15 months. When compared with the control, those on low-dose lithium showed significant improvements in cognitive markers after just 3 months of treatment. Furthermore, these protective effects appeared to strengthen as the study proceeded, with many of the lithium-treated individuals showing marked cognitive improvements by the end of the trial. These results suggest that lithium could be a viable treatment for Alzheimer's disease when used at low doses over the long term.

Dr. Nassir Ghaemi, one of the more notable and respected advocates of lithium use in the medical community, recently published a review in 2014 in Australian and New Zealand Journal of Psychiatry summarizing the benefits of low-dose lithium therapy. Ghaemi and his colleagues performed a systematic review of 24 clinical, epidemiological, and biological reports that assessed standard or low-dose lithium for dementia along with other behavioral or medical benefits. Five of the seven epidemiological studies established a correlation with standard-dose lithium therapy and low dementia rates, while four other randomized clinical trials demonstrated that low-dose lithium yielded more benefit for patients with Alzheimer's dementia versus placebo. Based on these findings, Ghaemi stressed that "lithium is, by far, the most proven drug to keep neurons alive, in animals and in humans, consistently and with many replicated studies."

LINK: Lithium: The Untold Story of the Magic Mineral That Charges Cell Phones and Preserves Memory — Great Plains Laboratory

Maudsley and Lithium

First, why a small group from the Maudsley Hospital in the 1960s could, in an almost malicious manner, have sown scholarly confusion about the true effectiveness of lithium. Aubrey Lewis, professor of psychiatry and head of the Maudsley, considered lithium treatment “dangerous nonsense” (47). Lewis’s colleague at the Maudsley, Michael Shepherd, one of the pioneers of British psychopharmacology, agreed that lithium was a dubious choice. In his 1968 monograph, Clinical Psychopharmacology, Shepherd said that lithium was toxic in mania and that claims of efficacy for it in preventing depression rested on “dubious scientific methodology” (48). Shepherd also scorned “prophylactic lithium” in an article with Barry Blackwell (). Moreover, Shepherd was publicly contemptuous of Schou. He told interviewer David Healy that Schou had put his own brother on it, and that Schou was such a “believer” in lithium that he seemed to think “really there ought to be a national policy in which everybody could get lithium”

Atacama where Lithium is extracted © Am Ang Zhang 2015

Lithium: The Gift That Keeps on Giving in Psychiatry

Nassir Ghaemi, MD, MPH

DISCLOSURES

June 16, 2017

At the recent American Psychiatric Association annual meeting in San Diego, an update symposium was presented on the topic of "Lithium: Key Issues for Practice." In a session chaired by Dr David Osser, associate professor of psychiatry at Harvard Medical School, presenters reviewed various aspects of the utility of lithium in psychiatry.

Leonardo Tondo, MD, a prominent researcher on lithium and affective illness, who is on the faculty of McLean Hospital/Harvard Medical School and the University of Cagliari, Italy, reviewed studies on lithium's effects for suicide prevention. Ecological studies in this field have found an association between higher amounts of lithium in the drinking water and lower suicide rates.

These "high" amounts of lithium are equivalent to about 1 mg/d of elemental lithium or somewhat more. Conversely, other studies did not find such an association, but tended to look at areas where lithium levels are not high (ie, about 0.5 mg/d of elemental lithium or less). Nonetheless, because these studies are observational, causal relationships cannot be assumed. It is relevant, though, that lithium has been causally associated with lower suicide rates in randomized clinical trials of affective illness, compared with placebo, at standard doses (around 600-1200 mg/d of lithium carbonate).

Many shy away from Lithium not knowing that not prescribing it may actually lead to death by suicide. As such all worries about long term side effects become meaningless.

Will the new generation of psychiatrists come round to Lithium again? How many talented individuals could have been saved by lithium?

APA Nassir Ghaemi, MD MPH

In psychiatry, our most effective drugs are the old drugs: ECT (1930s), lithium (1950s), MAOIs and TCAs (1950s and 1960s) and clozapine (1970s)
- We haven’t developed a drug that’s more effective than any other drug since the 1970’s
- All we have developed is safer drugs (less side effects), but not more effective
Dose lithium only once a day, at night
For patients with bipolar illness, you don’t need a reason to give lithium. You need a reason not to give lithium (Originally by Dr. Frederick K. Goodwin)

Cade, John Frederick Joseph (1912 - 1980)

Taking lithium himself with no ill effect, John Cade then used it to treat ten patients with chronic or recurrent mania, on whom he found it to have a pronounced calming effect. Cade's remarkably successful results were detailed in his paper, 'Lithium salts in the treatment of psychotic excitement', published in the Medical Journal of Australia (1949). He subsequently found that lithium was also of some value in assisting depressives. His discovery of the efficacy of a cheap, naturally occurring and widely available element in dealing with manic-depressive disorders provided an alternative to the existing therapies of shock treatment or prolonged hospitalization.

In 1985 the American National Institute of Mental Health estimated that Cade's discovery of the efficacy of lithium in the treatment of manic depression had saved the world at least $US 17.5 billion in medical costs.

And many lives too!

I have just received a query from a reader of this blog about Lithium, and I thought it worth me reiterating my views here. It is no secret that I am a traditionalist who believes that lithium is the drug of choice for Bipolar disorders.

Could Lithium be the Aspirin of Psychiatry? Only time will tell!

Latest: British Journal of Psychiatry

Paper:

Suicide risk in bipolar disorder during treatment with lithium and divalproex - PubMed

https://pubmed.ncbi.nlm.nih.gov/13129986/

Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics | Molecular Psychiatryhttps://www.nature.com/articles/mp20154

Lithium for Manic-Depressive Disorder (Bipolar Disorder):

Bipolar Disorder: Lithium-The Aspirin of Psychiatry?

Australian Trilogy:

Bipolar Disorder: Lithium-The Aspirin of Psychiatry?

Fremantle: Medical Heresy & Nobel

Tasmania & SIDS: The wasted years!

Cockroach Catcher-Seven Minute Cure

AMAZON-UK The Cockroach Catcher II: Attempted Living

Saturday, October 1, 2022

Boquete: Answer to Prayers!

According to old Chinese advice, it is wise never to discuss politics or religion even amongst best friends.

Religious belief can often blur judgment in the wisest of people.

Thirty years ago, a patient of mine was unconscious for 23 days and it was mother's belief that it was through prayer that her daughter was saved. I did not argue with her then.

But perhaps God works through his people in his own way. Discoveries in Medicine should therefore enhance our faith rather than the other way round.

It took nearly 30 years for the real answer to her prayers to really emerge.

I was staying at our resort in Boquete and was having dinner with three friends all of them with medical connections. One was in hospital administration and one a nurse. The husband of the nurse was a pharmacist. Somehow the conversation drifted into medical topics and knowing that I am a Child Psychiatrist the pharmacist started talking about his nephew who was nearly sent to a mental institution as he suffers from catatonia and doctors eventually diagnosed schizophrenia and put him on antipsychotics. Luckily the catatonic symptom probably saved him as some bright young thing just read the book Brain On Fire and gave him the Clock Test. That led to the NMDAR antibody testing that proved positive. He responded well to the treatment regime that has been developed and is off all antipsychotic medication.

My Teratoma patient was lucky as she belong to that group that improved without further treatment once the Teratoma was removed. She eventually had a baby.

The Power of Prayers & Teratoma: Brain & NMDA!

Anti-NMDA Receptor Encephalitis

Early Treatment Improves Outcomes in Rare, Often Undiagnosed Form of Encephalitis, Penn Researchers Find

NEW ORLEANS — A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called Anti-NMDA Receptor Encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research is being presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

565 cases! Not so rare!

The condition occurs most frequently in women (81 percent of cases), and predominately in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults.

My patient was under 18 and presented with catatonia symptoms. She later lose consciousness and was ventilated.

"Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten Titulaer, MD, PhD, clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania. "In addition, the study provides an important update on the spectrum of symptoms, frequency of tumor association, and the need of prolonged rehabilitation in which multidisciplinary teams including neurologists, pediatricians, psychiatrists, behavioral rehabilitation, and others, should be involved."

The disease was first characterized by Penn's Josep Dalmau, MD, PhD, adjunct professor of Neurology, and David R. Lynch, MD, PhD, associate professor of Neurology and Pediatrics, in Annals of Neurology in 2007. One year later, the same investigators in collaboration with Rita Balice-Gordon, PhD, professor of Neuroscience, characterized the main syndrome and provided preliminary evidence that the antibodies have a pathogenic effect on the NR1 subunit of the NMDA receptor in the Lancet Neurology in December 2008. The disease can be diagnosed using a test developed at the University of Pennsylvania and currently available worldwide. With appropriate treatment, almost 80 percent of patients improve well and, with a recovery process that may take many months and years, can fully recover.

Teratoma: finally!

In earlier reports, 59 percent of patients had tumors, most commonly ovarian teratoma, but in the latest update, 54 percent of women over 12 years had tumors, and only six percent of girls under 12 years old had ovarian teratomas. In addition, relapses were noted in 13 percent of patients, 78 percent of the relapses occurred in patients without teratomas.

As Anti-NMDA Receptor Encephalitis, the most common and best characterized antibody-mediated encephalitis, becomes better understood, quicker diagnosis and early treatment can improve outcomes for this severe disease.

The study was presented in a plenary session on Wednesday, April 25, 2012 ET at 9:35 AM at the American Academy of Neurology's annual meeting.

[PL01.001] Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Related paper:

Anti-NMDA Receptor Encephalitis: Diagnosis, Psychiatric Presentation, and Treatment

Chapter 29 The Power of Prayers

The following is extracted from The Cockroach Catcher: Chapter 29 The Power of Prayers.

According to old Chinese advice, it is wise never to discuss politics or religion even amongst best friends.

Religious belief can often blur judgement in the wisest of people. In psychiatry it is sometimes not easy. This is particularly true in cases of florid psychosis, which often presents with symptoms of hallucination, delusion and even vision.

I remember my early days of psychiatry in a mental hospital in Hong Kong. Yes, it was the days of 2000-bed hospitals. Yes, it was the days of Medical Superintendents who had supreme power and all doctors of whatever rank and experience were Mental Health Officers with special authority to sign papers for compulsory admissions. The forensic unit was contained within the same complex. Those were the days when we encountered psychosis in the raw so to speak. All the colony’s really mad people were admitted to this one place set in the furthest corner of the colony. In our year seven of us decided without much discussion that we all wanted to go into psychiatry. That was over 10% and all had quite idealistic reasons. It was perhaps a bit of a disappointment to our parents that we did not pursue a more conventional specialty that might provide us with more status and financial reward. Then there was the fear of contamination that somehow one might become mad too. Recent day medical students are said to shy away from psychiatry for these same reasons. Education seems to have little effect on superstition.
......................................….read the full Chapter: HERE

Brain on Fire

Anti-NMDAR or Autoimmune Encephalitis:$1 Million Investigation:

Scientific America: https://www.scientificamerican.com/article/brain-on-fire-my-month-of/

AMAZON-UK The Cockroach Catcher II: Attempted Living

Cockroach Catcher-Seven Minute Cure

Tuesday, August 30, 2022

Black Vinyl Days & Inverted Therapy: My first adolescent patient!

In the late 50s I and a few school friends used to sit in the back yard of one friend's village hut, grinding away a black vinyl.

This friend had a single record and so we got to know the music pretty well. He had a very old fashioned integrated system, turntable, amplifier and speaker all housed in a neat upright cabinet. The image came back to me of him using his finger to clear the dust collected on the cartridge needle. It was strange that my friend who lived in a hut should own an old gramophone player and one single record. But it turned out that his father was a Traditional Chinese Medicine practitioner and managed to leave China early enough to have his record player.

That was how my classical music appreciation started, with two of my favourite pieces of music. On one side of my friend's record was Bruch's violin concerto and on the other Mendelssohn's. Years later, I went to the Royal Festival Hall in London to hear the violinist Chloe Hanslip perform the Mendelssohn. It was hard to suppress my emotions when I saw her coming on stage and starting to play on her Guarneri del Gesu 1737. Of course she played exquisitely.

I have talked about my radio making days in another episode. From radio, I moved on to assembling my own pre-amplifier and amplifier, and finally my own record player from a kit as it was the cheapest way to get good sound. One of my uncles gave me my first vinyl: Brahms Symphony No. 1 with Karl Böhm conducting the Vienna Symphony Orchestra. Another village friend lent me his Beethoven's 3rd Symphony.

Moving to England meant that my music playing equipment had to be left behind, but my passion never dwindled. After saving enough, I ended up getting one of the best vinyl players, the Linn Sondek coupled with Exposure Pre and Power Amplifiers.

The music world soon progressed to digital vinyl recordings, the precursor to CDs. Now everything is in the air so to speak, with all the streaming going on.

Still I treasure our old black vinyl days.

I am lost to the world

with which I used to waste so much time,

It has heard nothing from me for so long

that it may very well believe that I am dead!

It is of no consequence to me

Whether it thinks me dead;

I cannot deny it,

for I really am dead to the world.

I am dead to the world's tumult,

And I rest in a quiet realm!

I live alone in my heaven,

In my love and in my song.

Mahler

I did not know Mahler's music. No, not when I started at the Tavistock Clinic in 1973.

One day at our referral meeting, a very interesting case turned up from none other than the much revered paediatrician Dr. B at the Royal Free up the road from us. In the early 70s referrals were specific to the individual teams. I had a suspicion that Dr. B liked to refer cases to my consultant as most of her cases landed on our team. Dr. C's solid history of working with the eminent Paediatrician, Donald Winnicott might have something to do with it. Dr. B was a very flamboyant character and I had met her at a couple of child protection conferences where she spoke with great authority and commanded much esteem and fear. I must admit I prefer her kind of consultant that knows her specialty and shows great respect for similarly capable colleagues.

Dr. C did not routinely put patients on psychotherapy and very often managed patients and their parents through good practical advice, and Dr. B was aware of this. To our surprise, with this case Dr. B specifically asked if the 14-year old could have psychotherapy and preferably with someone that knew a bit about music. We all gasped but nobody made any comment.

I joined the Tavistock Clinic, London's premiere psychoanalytic centre, not knowing what to expect. In my nearly three years of training there, it had never crossed my mind that one should use medication on children with psychiatric problems, and I never once wrote a prescription. This is in stark contrast to practices in the US.

My prime years of child psychiatric training in a drug free environment were fantastic in ways that I only realised years later. I am what you would call a true organic free range Child Psychiatrist!

Miss Weiss the Quaker social worker spoke up for me.

"Dr. Zhang is very fond of music and he is forever carrying boxes of records borrowed from the Swiss Cottage Library!"

It was Miss Weiss who tipped me off about the extensive classical music collection at the local library.

Well, that settled it, and I got the fourteen-year old boy, my first adolescent. The small kids I could cope with by playing with them. This new case would involve real talking therapy. All eyes were on me and I put on a brave face.

I told my colleagues that from an early age, I sat in on my cousin's piano lessons, and I listened to vinyls first played on my village friend's entry level integrated gramophone system, and then on my own home built one. In high school I even ran the lunch-time school music club, selecting classical music repertoire for introduction to new devotees. I had never worked out why, but at that time there might be the belief that even just listening was good enough. China has now embraced music in a big way, more so because Mao banned it for a number of years. It is now the world's largest piano producer and piano playing is growing fast, with more than 40 million children estimated to be learning the instrument.

"Who is your favourite composer?"

"I now pick up some unusual and less well-known works. Because older records are rather scratchy, at Swiss Cottage Library I tend to go for the brand new ones and often complete box sets.."

"Like complete Mozart's Quintets?"

Nothing seemed to escape the eyes of Miss Weiss, who was also an avid music lover. She lived virtually next door to the Royal Festival Hall and regularly went there for concerts.

"And Peter Grimes, which of course is Dr. C's territory!"

I loved the way the referral meeting turned into a cultural discussion. The significance of my early child psychotherapy training has never been lost on me.

As mentioned in another episode, Dr. C had a nice bungalow in Aldeburgh, the home of Benjamin Britten and Peter Pears. The opera 'Peter Grimes' I had never heard of until one day in Swiss Cottage Library when the librarian was placing new records onto the shelves and enthusiastically recommended it to me. A few years later Dr. C invited our family to spend a week at Aldeburgh and we paid pilgrimage to The Maltings, attending a Peter Pears recital. At the seafront, we also met Imogen Holst, daughter of the composer. It took another thirty years before we first saw a performance of Peter Grimes at the Royal Opera House.

Joshua, the fourteen-year old boy referred to us, was said to be struggling with everything and most seriously of all with his mother, and Dr. B thought he would benefit from some fairly deep therapy.

By then, I had seen quite a few children and on the whole conversant with the use of toys and drawings as vehicles of communication. For children who were a bit too old for the toys, I threw in Winnicott's squiggle game[1] now and again. Interestingly, most other junior doctors were more at ease with the older adolescents and often came round to our case presentations to hear about the management of younger kids. It was only when I became a consultant that I realised that while I enjoyed working with the very young children, many of my colleagues avoided them.

Now that I had been thrown into the deep end, I had no idea what to do. I had learned from Winnicott's squiggle game the importance of the therapist's quick response and spontaneity. Why should talking to the older child be any different? This approach helped the doctor to establish rapport very quickly especially with parents and served me well all the way through to my Consultant days. I learned from my gurus and teachers that we did not have to be held back by rigidity.

At the clinic, the team set-up was such that parents were seen by the lead social worker Miss Weiss or her social worker trainee, and occasionally by Dr. C; the child was seen by the junior doctor and only assessed by the psychologist if referred by the consultant.

As it turned out, Joshua's father was a Surgeon at the Hospital where Dr. B worked, and his mother taught piano at his school, one of the best known state school in the area. The school had such a good reputation that many of the professional class living in Hampstead sent their children there. Do we still wonder why good areas have good schools? It is only natural that good areas with intelligent pupils attract good teachers. It goes on.

Joshua first noticed the Mondrian on the wall.

"Did some kid do that? Very neat!"

Perhaps he was right. Picasso wanted to draw like a kid too.

Then he noticed the records I was about to return to the library: Mozart Quintets.

"Mozart's best. He wrote these for himself!"

That was how we started. Some might think I plotted it by putting the records on my desk. I wish I could have claimed to have planned it. Even to this day, I believe spontaneous responses are best.

Joshua was very knowledgeable as far as music was concerned. Yet I was not quite prepared for what he bestowed on me as the sessions progressed.

Some therapists thought they were supposed to be a mirror to let the patient see more clearly their own psyche. Others were more assertive and felt compelled to make interpretations, not realising that often one was limited by one's own psyche or understanding of it. Hence the need for some personal analysis to deal with that aspect.

There is of course a world of difference between reflection and interpretation. My personal feeling is that there needs to be a balance between the two.

Psychotherapy is thus quite far removed from medical history taking. In a serious medical episode, there is a need to get a clear view of the events leading up to the episode. This enables appropriate investigations to be carried out, and the right course of treatment determined.

Psychotherapy affords us the luxury of a deeper understanding of the patient without having to ask probing questions. It goes without saying that with the more frequent therapy sessions, the therapist gains a very profound insight of the patient without the need to go through an intensive and compact history taking. We also tend to remember these patients literally forever.

Joshua hardly saw his father as he was busy with his patients. His mother would have been a concert pianist but she had to make a choice and she chose bringing up Joshua and looking after a rather nice house on the Heath. But she had high hopes for Joshua, her only child. Yes, to be something she could only dream of, a concert pianist.

Joshua had been a good piano player but when he turned nine he told mother he would like to learn the violin.

He picked that up in no time and at sixteen was ready for his Grade 8 violin examination. He quit piano playing at Grade 5.

As I progressed with Joshua, the very strange role I played became clear. I was his mother that he could talk to, argue with and more importantly confide in. And perhaps also somebody with whom to practise crossing swords with his parents. It was easier for him, as I was not his mother and on the other hand I was. But I was the one who could provide some answer his mother would not give him.

One day I had a complete set of Brahms Symphonies on my desk, from the library of course, and he casually asked if Brahms was my favourite composer or not.

Brahms 1st Symphony was a present given to me by one of my uncles when I made my amplifier. He worked for Abbotts in Hong Kong and when I got to medical school, he gave me my Littmann Stethoscope.

"I love the First, especially the solo violin part in the last movement."

"Well, you should listen to Mahler as he composed solo singing parts to go with the orchestra, unlike Beethoven's Choral Symphony. And my best Mahler is his Third Symphony, though everybody else I know prefers the Second."

I had two commuting friends that cared about music and they had not talked about Mahler once.

I tried that day to secure any Mahler recording at the library and could only find one: Das Lied von der Erde.

It was a revelation to my commuting friends and they could not believe what they read on the record sleeve: Chinese poems translated by a German!

At the next session, Joshua was at his most enthused and energetic. He could not wait to tell me more about Mahler.

"The Third Symphony is all about nature and so positive and invigorating!"

I have to say now that I have probably gained more from this one patient than I have from any other. To have been introduced to Mahler at the time when London was just waking up to it, and wake up it did!

Joshua and I were able to talk about Mahler's struggles, the sadness brought by the death of his daughter and the Rheumatic Heart Disease that eventually led to his death

One day he was able to declare that his struggles were nothing compared to Mahler's.

It is interesting that he never really talked about his own sadness as Mahler's overshadowed his and yet in true traditional psychotherapy style he gained his own insight.

His time with me or my time with him was coming to an end. Dr. C was highly intuitive and on the recommendation of my psychotherapy supervisor helped me to terminate the therapy. It was a credit to a state funded system like the NHS that one did not need to hang on to therapy for ensuring an adequate income stream. The main risk attached to privately funded psychotherapy is the unnecessary prolongation of therapy period, thus leading to the addiction of the patient to the therapist or vice versa.

At the last session, he told me he got distinction in Grade 8 Violin but he did not want to be a violinist.

He wanted to be a conductor.

In 2009, Das Lied von der Erde was performed in Hong Kong. As I wrote this, I Googled and found that Joshua was the conductor at a European opera house.

[1] https://www.ncbi.nlm.nih.gov/pubmed/7005855