Tag Archives: Thalidomide

Stock tip

The past performance of stock recommendations is no guarantee that it will continue — which is fortunate as my first tip (ONTX) was a disaster.  I knew it was a 10 to one shot but with a 100 to 1 payoff.  People play the lottery with worse odds.  Anyway ONTX had a rationale — for the gory details see — https://luysii.wordpress.com/2016/06/01/in-a-gambling-mood/

For those brave souls who followed this recommendation (including yours truly) here’s another.

On 4 March 2019 if the FDA approves esketamine for depression, buy Johnson and Johnson.  Why?  Some people think that no drug for depression works that well, as big Pharma in the past only was reporting positive studies.  The following is from Nature 21 February 2019.

Depression drug A form of the hallucinogenic party drug ketamine has cleared one of the final hurdles towards clinical use as an antidepressant. During a 12 February meeting at the US Food and Drug Administration (FDA) in Silver Spring, Maryland,an independent advisory panel voted 14 to 2 in favour of recommending a compound known as esketamine for use in treating depression.

What’s so hot about esketamine?  First its mechanism of action is completely different than the SSRIs, Monoamine oxidase inhibitors, or tricyclic antidepressants.

As you likely know, antidepressants usually take a few weeks to work at least in endogenous depression.  My clinical experience as a neurologist is slightly different, as I only used it for patients with disease I couldn’t help (end stage MS etc. etc.) where the only normal response to the situation was depression.  They often helped patients within a week.

I was staggered when I read the following paper back in the day.  But there was no followup essentially.

archives of general psychiatry volume 63 pp. 856 – 864 2006
The paper is not from St. Fraudulosa Hospital in Plok Tic, but from the Mood Disorders Research Unit at the National Institute of Mental Health.
Here are the basics from the paper

Patients  Eighteen subjects with DSM-IV major depression (treatment resistant).

Interventions  After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion.

Main Outcome Measure  Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale.

Results  Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week.

Read this again: showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week.

This is absolutely unheard of.  Yet the paper essentially disappeared.

What is esketamine?  It’s related to ketamine (a veterinary anesthetic and drug of abuse) in exactly the same way that a glove for your left hand is related to a right handed glove.  The two drugs are optical isomers of each other.

What’s so important about the mirror image?  It means that esketamine may well act rather differently than ketamine (the fact that ketamine worked is against this).  The classic example is thalidomide, one optical isomer of which causes horrible malformations (phocomelia) while the other is a sedative used in the treatment of multiple myeloma and leprosy.

If toxic side effects can be avoided, the market is enormous.  It is estimated that 25% of women and 10% of men will have a major depression at some point in their lives.

Initially, Esketamine ( SPRAVATOTM)  will likely be limited to treatment resistant depression.  But depressed people will find a way to get it and  their docs will find a way to give it.  Who wants to wait three weeks.  Just think of the extremely sketchy ‘medical indications’ for marihuana.

 

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