Posted by fachad on March 23, 2002, at 23:22:55
In reply to FACHAD again! Quick question 4 U: » fachad, posted by Janelle on March 23, 2002, at 20:55:21
Janelle, you'll have to cut me some slack if my writing is not up to par as I had some wine with dinner and my writing skills are suffering! Here's the story with drug discovery, development and marketing.
Chlorpromazine, the first anti-psychotic, was accidentally discovered. They were working on developing anti-histamines.
Imipramine, the first TCA, was accidentally discovered while trying to find other anti-psychotics that could be derived from anti-histamines.
They noticed that psychotic patients got better on chlorpromazine, and the depressed patients got better on imipramine.
They discovered that chlorpromazine blocked dopamine and the imipramine blocked serotonin and noreprenephrine reuptake.
So they postulated that psychosis was from excess dopamine, and depression was from deficient serotonin and norephinephrine. The drugs came first, then the theory as to how they worked.
Later on they saw that there was big $$ in psych drugs, so they set chemists to work on designing ones that would do what they thought would theoretically relive depression, while trying to avoid all the other receptors and side effects. That's how SSRIs were developed.
"Off-Label" is a legal term, not a medical term. In the US, the FDA requires drug companies to do trials that prove the drug is effective for the condition it is marketed for. An example is Paxil for depression.
SKB, the company that makes Paxil, did trials and showed that Paxil was more effective than placebo for depression. Then Paxil was released onto the market, with a "label indication" for depression.
Pdocs noticed that Paxil also helped their patients who had OCD or anxiety. If a pdoc gave an anxiety patient Paxil, that was considered "off label". You are not using the pill for it's official indication. That does not mean in any way that it is less effective. It is just not what the official FDA indication says.
Anyway, SKB went ahead and did trials to get Paxil labeled for anxiety, so now if a pdoc gives a patient Paxil for anxiety it is not off label.
Your original question was about TCAs and off label use. Well, because SSRIs seem more tolerable most people don't use TCAs for depression anymore.
But docs, not just pdocs, have found that TCAs work miracles for many conditions other than depression. TCAs are very effective in the prevention of migraine headaches, treatment of IBS, insomnia, chronic pain, fybromyalgia, anorexia, bed wetting in children, and on and on. But all of these uses are off label because there have not been any FDA supervised trials proving that they work. But docs do know that they work.
> Fachad,
>
> You said "TCAs were not designed - they were discovered. It was a serendipitous scientific discovery that these chemicals could relieve depression."
>
> Okay, so if TCA's were NOT originally designed for depression but it was a serendiptious discovery that they could relieve depression, WHAT were they originally designed for??!!??
>
> Also, you wrote: "if you are treating something else with a TCA, going "off-label" with the drug, the anticholinergic effects might be very useful.
>
> If TCA's were not originally designed for depression, then why would using them for something OTHER than depression be considered "off label"??
>
> Thanks!
> -Janelle
poster:fachad
thread:99599
URL: http://www.dr-bob.org/babble/20020322/msgs/99757.html