Wednesday, January 23, 2019

First Do No Harm: Antipsychotics: Really?

This one of my early posts when I started blogging. 

Laguna Azul, Bocas del Toro©Am Ang Zhang 2013
Primum non nocere
“First do no harm” has always been attributed to Hippocrates. In his Epidemics, Bk. I, Sect. XI, he advised, "Declare the past, diagnose the present, foretell the future; practice these acts. As to diseases, make a habit of two things — to help, or at least to do no harm."
As I mentioned in my last post, schizophrenia is mercifully rare in children under 18. The best estimate is about 1 in 40,000, as opposed to 1 in 100 in adults.
I did of course see a few full blown Manic Depressives (Bipolar Disorder) in children between eleven and eighteen - single digit figure for a career in Child Psychiatry spanning 30 years must mean it is rare. With such cases, it is more important to use the right mood stabiliser and with my patients I prescribed mainly lithium.

It is now fashionable for Child Psychiatrists to diagnose Bipolar Disorder and treat with Atypical Antipsychotics, instead of mood stabilizers. Recent figures show that only a third of these so called Bipolars are prescribed mood stabilisers.

I have come to the rather unpleasant conclusion myself that parents nowadays may not have been told the full story about Antipsychotics. How many of them have been made aware of the range of side effects of Antipsychotics when it is suggested that their very young child should go on such medication? How many of them have been made aware that taking an Antipsychotic may in fact induce psychosis, a still disputed finding but one that should be a consideration? (For the latest data on side effects, see below.)

No parent would question an exotic diagnosis that absolves them of any responsibility, and a treatment that uses a fancy new medication. After all Havard is a good name and anything advocated by a psychiatrist from Harvard must be O.K.

“Branding” has inadvertently crept into child Psychiatry.

We bloggers who dare to reveal the hidden agenda cannot be the favourite of the likes of those who push the “new” treatments. So be it.

It is a challenge to the modern day Child Psychiatrist to suggest that their patient’s behaviour problem is caused by faulty parenting or family dynamics. To even suggest that is sure to bring on complaints and possibly litigations. In countries where insurers hold the purse string, writing a prescription saves the doctor valuable time. Psychotherapy or behaviour therapy costs more.

Even before the arrival of the newer Atypical Antipsychotics, their predecessors were used for behaviour control, in Russia and elsewhere. Why else should it be known as chemical lobotomy?

Many doctors feel more comfortable in prescribing Atypicals because of their purportedly better side-effect profiles. I do not mean to criticise the majority of busy Child Psychiatrists, for we have a long tradition of relying on publications of esteemed colleagues around the world.

Unfortunately, the big Pharmaceuticals too know of our trust in our colleagues, and over an extended period of time have engineered publications of favourable papers speaking for licensed and more frequently off-label use of the new drugs, especially Antipsychotics. It should not take a genius to work out that psychosis is a chronic condition that requires life long treatment, thus guaranteeing future income for pharmaceuticals.

There is also another aspect. What if the actual diagnosis of psychosis is suspect? We are entering a new era, when medical ethics seem not so important. I am not alone in doubting the validity of some of the diagnosis of childhood Bipolar Disorder. To put it plainly, the two thirds of the so called Bipolars may be just having behaviour problems and Antipsychotics are prescribed simply to control their behaviour.

The side effects of the newer Antipsychotics on children and young people

For the latest most comprehensive data on side effects of the newer Antipsychotics on children and young people we turn to an earlier article in The USA Today:
New antipsychotic drugs carry risks for children
by Marilyn Elias 5/2/2006 USA Today

The USA TODAY's analysis focused on 1,373 cases received by the FDA from 2000 to 2004 in which one of the six atypical anti-psychotic drugs was coded as the primary suspect. These cases were used to count symptoms, diagnoses and deaths.

To learn about patterns in atypical use, USA TODAY asked Medco Health Solutions, a prescription-drug benefit manufacturer, to query its member database.

• A condition called dystonia was most often cited as an "adverse event" suffered by someone taking one of the drugs, with 103 reports. Dystonia produces involuntary, often painful muscle contractions.

• Tremors, weight gain and sedation often were cited, along with neurological effects such as Tardive Dyskinesia (TD). Symptoms of TD can vary from slight twitching to full-blown jerking of the body. (No actual figure was quoted.)

• A condition called neuroleptic malignant syndrome, with 41 pediatric cases over the five years, was the most troubling effect listed, says child psychiatrist Joseph Penn of Bradley Hospital and Brown University School of Medicine. It is life-threatening and can kill within 24 hours of diagnosis. It's been linked to drugs that act on the brain's dopamine receptors, which would include the atypicals, Penn says.

The 45 deaths
Among the 45 pediatric deaths in which atypicals were the primary suspect, at least six were related to diabetes — atypicals carry warnings that the drugs may increase the risk of high blood sugar and diabetes. Other causes of death ranged from heart and pulmonary problems to suicide, choking and liver failure.

There is anecdotal evidence that even Aripiprazole (Abilify), the new Third Generation antipsychotic, still causes weight gain and quite severe extrapyramidal side effects.

There we have it.

There is often an assurance that the side effect listed on the Information Sheet is rare and it is a natural defence of most of us that somehow, bad things only happen to others. 

Next time your Child Psychiatrist said, “Antipsychotics.”

I suggest that your answer should be: “Really?”

Links: Reidbord's Reflections----Abilify for depression?

Anonymous Steven Reidbord MD said...
I just found your blog, and wanted to commend your nice mix of thoughts, links, and photos. I'm a San Francisco (California, USA) adult psychiatrist with a similar view of the over-use of atypical antipsychotics. If you like, check out my blog sometime, particularly these posts on the same topic.

Best regards,
Steven Reidbord MD
August 1, 2009 at 11:12 PM

Saturday, January 12, 2019

Finland: Lithium for Unipolar Depression.

In medicine, population wide survey has its place not forgetting that when many modern psychiatric drugs went through the so called "robust" double blind control trial, it is never really all that double blind as many of the drugs tested have side effects that could easily biased both patient and researcher. The patient realising that he/she is taking the "real" drug might want to report improvement or the opposite. The observing researcher will realise very quickly and may unfortunately be biased even if unintentional.

I remember questioning the presenters of Olanzapine on this especially as patient reported great craving for food and put on weight, the presenter refused to answer my question.

Then there is the question of Bipolar or Unipolar. Well, my view is this and Psychiatrist might not like to admit it: we might get it wrong. If risk of suicide is high why use something that might provoke suicide. The same Finnish team that did the research came up with the answer on using Lithium in Unipolar Depression!

© 2012 Am Ang Zhang

Finland & Unipolar Depression: a nationwide cohort study.

Prof Jari Tiihonen, et al/  Here are the essential points and full summary here.

Little is known about the comparative effectiveness of long-term pharmacological treatments for severe unipolar depression. We aimed to study the effectiveness of pharmacological treatments in relapse prevention in a nationwide cohort of patients who had been admitted to hospital at least once as a result of unipolar depression.

Our nationwide cohort study investigated the risk of readmission to hospital in 1996–2012 in all patients in Finland who had been admitted to hospital at least once for unipolar depression (without a diagnosis of schizophrenia or bipolar disorder) in Finland between Jan 1, 1987, and Dec 31, 2012.

Data from 123712 patients were included in the total cohort, with a mean follow-up time of 7·9 years (SD 5·3). Lithium use was associated with a lower risk of re-admission to hospital for mental illness than was no lithium use. Risk of hospital readmission was lower during lithium therapy alone.


Our results indicate that lithium, especially without concomitant antidepressant use, is the pharmacological treatment associated with the lowest risk of hospital readmission for mental illness in patients with severe unipolar depression, and the outcomes for this measure related to antidepressants and antipsychotics are poorer than lithium. Lithium treatment should be considered for a wider population of severely depressed patients than those currently considered, taking into account its potential risks and side-effects.

Suicide: The Answer, my friend may be Lithium!

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)

© Am Ang Zhang 2013

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!