Monday, June 18, 2018

Gold Standard: Clozapine & Finland.

Autumn Gold and Gold Standard in Finland:

Tiihonen said the pharmaceutical industry is partly to blame for why clozapine has often been overlooked. "Clozapine's patent expired long ago, so there's no big money to be made from marketing it," he said.

© 2012 Am Ang Zhang

There have been many challenges to Clozapine but to the Cockroach Catcher it will remain the Gold Standard for the treatment of Schizophrenia for a long long time.

An extract from The Cockroach Catcher:

……...Martina was already at the adolescent inpatient unit when I arrived. She was supposed to be schizophrenic. The family were refugees from Sudan. They were a small Sect of Catholics that were said to be persecuted.
Martina was not very communicative but her records and observations by her outpatient psychiatrist indicated that the diagnosis was robust enough. However, after over a year in hospital she was not improving and we had tried the newer antipsychotic without making much headway.
There was one thing left to do – to put her on Clozapine.
I was once at one of these big drug firm meetings when all the big boys on the newer antipsychotics were there.
Having filled my plate from the delicious buffet, I sat next to two nicely clad representatives.
“So you ladies are from Novartis?” I did my usual stunt.
“How did you work that one out?”
“Well, you two have the best designer outfits and I guessed you must be from the makers of Clozapine.”
They were there to see what the opposition might come up with but as far as I was concerned no other pharmaceutical would touch them for decades.

After today’s Lancet publication they might not need to worry at all!

The Lancet, Early Online Publication, 13 July 2009
11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study) Jari Tiihonen et al. 

According to Reuters:
…………An analysis of 10 years' records for 67,000 patients in Finland found that, compared to treatment with the first-generation drug perphenazine, the risk of early death for patients on clozapine was reduced by 26 percent.

By contrast, mortality risk was 41 percent higher for those on Seroquel, known chemically as quetiapine; 34 percent higher with Johnson & Johnson's Risperdal, or resperidone; and 13 percent higher with Eli Lilly's Zyprexa, or olanzapine.
"We know that clozapine has the highest efficacy of all the antipsychotics and it is now clear, after all, that it is not that risky or dangerous a treatment," study leader Jari Tiihonen of the University of Kuopio said in a telephone interview.
"We should consider whether clozapine should be used as a first-line treatment option."Tiihonen estimates clozapine is given to around one fifth of Finnish schizophrenia patients, but less than 5 percent in the United States.Clozapine's side effects include agranulocytosis, a potentially fatal decline in white blood cells, and current rules stipulate the drug can only be used after two unsuccessful trials with other antipsychotics.Tiihonen and colleagues wrote in the Lancet medical journal that these restrictions should be reassessed in the light of their findings, since not using the drug may have caused thousands of premature deaths worldwide.
According to AP:

James MacCabe, a consultant psychiatrist at the National Psychosis Unit at South London and Maudsley Hospital, called the research "striking and shocking." He was not linked to the study.
"There is now a case to be made for revising the guidelines to make clozapine available to a much larger proportion of patients," he said.
Tiihonen and colleagues found that even though the use of anti-psychotic medications has jumped in the last decade, people with schizophrenia in Finland still die about two decades earlier than other people.

Tiihonen said the pharmaceutical industry is partly to blame for why clozapine has often been overlooked. "Clozapine's patent expired long ago, so there's no big money to be made from marketing it," he said.

Clozapine Data: FinlandRCPU.K.NEJM
Abstract:The Lancet.

Related Posts
Abilify/aripiprazole: Akathisia-gate
Alaska Zyprexa: DOJ at last.
Alaska, Good Friday Earthquake and Zyprexa 
Alaska Zyprexa: Follow Up
Bipolar and ADHD: Boys and Breasts
Antipsychotics: Really?
Humber Mental Health Teaching NHS Trust: Learning From The Past.

Tuesday, June 5, 2018

Antidepressants or Lithium! Side Effects but you will live to experience it!

One of my ex-juniors, now retired, called to ask if I have read about another celebrity suicide. How very sad!

Dr. Baldessarini of Harvard:

“Lithium is far from being an ideal medicine, but it’s the best agent we have for reducing the risk of suicide in bipolar disorder,” Dr. Baldessarini says, “and it is our best-established mood-stabilizing treatment.” If patients find they can’t tolerate lithium, the safest option is to reduce the dose as gradually as possible, to give the brain time to adjust. The approach could be lifesaving.

In recent write ups about antidepressants, there is no mention of Lithium. The Cockroach Catcher first worked with one Australian Psychiatrist that worked with Cade and I was, so to speak, very biased towards Lithium. Yes, Lithium has side effects that might be serious. But hang on, you get to live to experience it. Think about it.

"Many psychiatric residents have no or limited experience prescribing lithium, largely a reflection of the enormous focus on the newer drugs in educational programs supported by the pharmaceutical industry."

One might ask why there has been such a shift from Lithium.

Could it be the simplicity of the salt that is causing problems for the younger generation of psychiatrists brought up on various neuro-transmitters?

Could it be the fact that Lithium was discovered in Australia? Look at the time it took for Helicobacter pylori to be accepted.

Some felt it has to do with how little money is to be made from Lithium. After all it is less than one eighth the price of a preferred mood stabilizer that has a serious side effect: liver failure.

Thank goodness: someone is talking about it.

 Atacama where Lithium is extracted  © Am Ang Zhang 2015

Lithium: The Gift That Keeps on Giving in Psychiatry

Nassir Ghaemi, MD, MPH
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!

Monday, June 4, 2018

NYBG: Peony time!

It is that wonderful time of the year to enjoy peonies as they lasted just a very short time!

 All photos ©2018 Am Ang Zhang

Book I recently read: 

Fragile Lives by Stephen Westaby

Hello Summer: BBG4.

Photography: Best lens for portrait & landscape!

A unique picture book consisting of 20 beautiful 9 x7 in. full bleed photos by the author of: corals, turtles, anhinga, blue tang, file fish, butterfly fish, cleaner shrimp, pompano, barracuda, flounder, star fish, and sting ray. A first of the kind tale of aquatic creatures in child-speak. A good introduction of nature to a young child, especially good as a follow-up to a visit to the aquarium; plus two pages of detailed companion

A coffee table quality photobook for a special child, introducing wild life in Africa. Photos of the animals (impala, nyala, kudu, wildebeest, warthog, gruffalo, zebra, rhinoceros, waterbuck, hippopotamus, giraffe, buffalo, elephant, saddlebilled stock) were taken by the author himself during safari trips in Africa.

Multiple Sclerosis: Never say never!

Latest from Dr Weldon:

Over the course of the last ten years I have received a number of emails from persons who, having read these pages, assert that Sarah never had multiple sclerosis. These persons inform me that she had Acute Disseminated Encephalomyelitis (ADEM). Some of these amateur neuroscientists (who have never spoken to, taken a history from, or examined the lady) have been quite strident in their assertions.

Well, Sarah's illness was completely typical of Relapsing-Remitting MS developing into Secondary Progressive disease. Sarah experienced seven relapsing-remitting episodes involving different parts of the CNS over two decades; remissions became partial; then her illness began to slide into the secondary progressive form over two years. This is not seen in ADEM, where the picture is of acute post-infective encephalitis. Although ADEM is seen in adults, it is more often seen in children, peaking between 3 and 10 years. ADEM is rare (7 per 1,000,000); MS is common (1.2 per 1,000). MRI imaging shows different appearances; lesions in ADEM have poorly defined margins; those of MS are more sharply defined. The spatial arrangement and the shape of lesions in the two diseases is different. Sarah's MRI showed lesions typical of MS.

Here is a link to an article on the differences between ADEM and MS:
So, it is certain that Sarah had Secondary Progressive MS, a diagnosis made by a consultant neurologist. She (and others) recovered because she was treated rationally using evidence-based medicine. And by evidence-based I mean evidence-based.
Sarah's story has been made public, to assist others, at her request.


There is suddenly a great interest in one of my earliest posts: 

Multiple Sclerosis, Iguanas and Wrong Foot

In the summer of 2005 I read a rather compelling story in Hospital Doctor. The headline was: “Ignoring the EvidenceDiagnosis of his wife’s progressive multiple sclerosis would not have taken so long had doctors taken a proper history, says Dr David Wheldon.”

It was an extremely well written article. It had to be, as Dr Wheldon’s hobby is poetry writing. He is a microbiologist by profession.
His wife is an accomplished painter and a violin restorer and dealer. As early as 2000, she noticed that she was dragging her right foot on a walking holiday in the Auvergne. She was referred to an orthopaedic surgeon. “Congenital spinal stenosis,” he confidently diagnosed. She got worse. In 2003 she was referred to a neurologist but during the months when she was made to wait for an MRI (why was it not done immediately?) she deteriorated rapidly and was soon unable to walk unaided and had a multitude of other neurological symptoms.
“Progressive multiple sclerosis,” proclaimed the neurologist. "No treatment is available. Just let the disease evolve."
Dr Wheldon at this point commented that a proper history would have allowed for the diagnosis to be made earlier, as his wife had had two transient episodes of weakness of an arm and dimmed vision in one eye.
There was no time to waste and having been given a “no hope” verdict, Dr Wheldon thought that alternatives had to be found. How often have we found patients seeking alternative treatment and sometimes very very alternative treatments once they were told what was thought to be the “truth”? Luckily I learned early on in my medical training that one should “never say never” (as mentioned in the chapter “Miracles” in my book.)
He found the Vanderbilt University work on Chlamydia pneumoniae. The rest, so to speak, was history. His wife was put on two antichlamydial agents and later metronidazole. After some typical reactions his wife started to recover. Eighteen months later, she was able to paint and walk a mile or so.
Some may argue that the recovery had nothing to do with the treatment, but was just one of those rare spontaneous recoveries. I am aware that this is only an isolated case, but there is ongoing research in this area.

Iguana iguana, Costa Rica

So what is the iguana doing in today’s blog? Many iguanas kept as pets are wild, truly wild caught and they carry various bacteria including Chlamydia pneumoniae, which also infect and cause diseases in Koalas, snakes, chameleons, frogs, and green turtles.
According to National Geographic, one of my favourite reads,
“Green, or common, iguanas are also among the most popular reptile pets in the United States, despite being quite difficult to care for properly. In fact, most captive iguanas die within the first year, and many are either turned loose by their owners or given to reptile rescue groups.”
Perhaps we should leave them to stay in the wild.
Dr Zhang should have checked if Tommy, his Wrong Foot patient, kept an iguana. His mother was diagnosed with multiple sclerosis.

Chlamydia pneumoniae site: CPNHELP.ORG

Other Posts on Multiple Sclerosis:

Multiple Sclerosis Treatment – an Update


“Multiple Sclerosis:  A Curable Infectious Disease?”, July 7, 2010,
“Is Multiple Sclerosis an Autoimmune Disease?”, July 5, 2010,
“Eleven Steps for Overcoming Alzheimer’s and Other Chronic Infectious Diseases,” July 1, 2010,
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Sarah Longlands said...
Dear Dr Zhang,

My name is Sarah Longlands, the wife of Dr Wheldon, mentioned above. I found your blog by accident when looking up "David Wheldon" on Google, something I do from time to time to see who is linking to both our web sites.

I thought I would give you a small update:nearly three years on again since the publication of "Ignoring the Evidence" I am still going strong, not having had an adverse MS event since starting treatment in August 2003. When I started I couldn't even hold a paintbrush but now I have worked through watercolours to acrylics and have now moved back to my favourite medium of oil paints and of no mean size. My progressive multiple sclerosis was so aggressive, I really shouldn't be here now, but I am.

I have not seen my neurologist since being given the diagnosis. David has, since they work in the same hospital, but although at one point the man showed some interest, this soon passed and the man has never looked at my subsequent improved scans. In fact, he once ran out of the radiologists room exclaiming "I can't look at this!" He is obviously very good at saying "Never."

There are always going to be people willing to put my recovery down to "spontaneous recovery" but I think it very odd that this should have happened within a few hours of downing my first ever doxycycline, after having my first multiple sclerosis relapse twenty years previously, age 24. Then and for many years it was untroubling, with few, easily resolved relapses. Over the years I had been able to forget about it, so I readily accepted the diagnosis of the orthopaedic surgeon. I have since discovered that David married me thinking I might well have MS, because of my clumsiness although by that time I has already decided that it couldn't possibly be the case.

Since starting to recover, David has seen many patients abandoned by the neurological establishment and has written two papers with Charles Stratton of Vanderbilt University about chlamydia pneumoniae and multiple sclerosis. I started writing on, where a psychologist named Jim Kepner, a sufferer of another disease caused by chlamydia pneumoniae, saw me and started to treat himself. Two and a half years ago this led to him starting a wonderful site: where people from all over the world suffering from any of the many diseases in which CPn is implicated can come together for freely given help and reassurance.

Very best wishes,

Sarah Longlands. 12th April, 2008
Am Ang Zhang said...
Many thanks Sarah for taking the time to make the comment. All the best.

Dr Am Ang Zhang
Anonymous said...
Copied from CPNhelp because I thought you might not see it there:

"Hello again Dr Zhang! I hope you enjoyed your hols, but it was only a tiny flurry really, like the small snowfall we had the other Sunday morning which was gone before most people knew it had been there.

I totally agree with you about the state controls, first set in place in our country when the fat man in hush puppies was health minister, I had only recently both got my MA and acquired MSi and chlamydia pneumoniae was not even realised to be a serious pathogen. I'm glad we have original thinkers over at Vanderbilt and I am so glad I am married to one here, who discovered what they were doing and thought that it was better to get on with treating me rather than waiting for endless double blind trials that would never happen, antibioticsi not being profitable things.......Sarah

An Itinerary in Light and Shadow by a real "Painter of Light"...........Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent. Still slowly improving and no exacerbation since starting. EDSS was 7, now 2, less on a good day."
Anonymous said...
that is the case too, the antibiotics on the protocol used to treat are long off patent & sport the least amount of side effects from the abx themselves. The pharma companies have no interest.

but wow, they now have something they can make money on! a drug for Fibromyalgia pain (packed with a plethora of side effects)!
Gill said...
Hi, I have been recently diagnosed with MS and was also told there was nothing that could be done. My options appeared to be nil or joining the MS Society for group hugs and "learning how to live with my disease". Not a chance I was putting up with that so I started to scour the web and talk to friends recently diagnosed.

I thank my lucky stars that one friend pointed me straight to David Wheldon's site and having met with him, I'm about to start on the protocol. With the help of the pioneering stalwarts on the CPn Help forum mentioned above, David Wheldon, and the inspirational Sarah, I fully intend to see this through. If it's possible to cure it then I'll have a darn good try.

My GP and Neurologist have refused to have anything to do with the Protocol which I find exceedingly strange. I always thought the medical profession were tasked with making patients well by whatever means, it seems however that unless the drug companies are waving some new miracle drug at them, they're not open to looking at old medication used in a new way.

Having read your blog though, I'm going to spend the afternoon scouring the house in case I have a recalcitrant Iguana hiding in a dark corner. Or maybe I'll round up the frogs in the pond and force them to take a Chlamydia Pneumoniae test. :-)
Am Ang Zhang said...
Hello all, back from Hols and the blog engine has restarted.
Am Ang Zhang said...
Sarah's letter is now posted here.

The Cockroach Catcher