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Re: Benzodiazepine, Mood stabiliser, Stimulant

Posted by dennison on July 1, 2001, at 21:38:18

In reply to Benzodiazepine, Mood stabiliser, Stimulant, posted by PaulB on July 1, 2001, at 20:12:39

> Hi,I just wanted to get some views on a cocktail. I am generally against over prescribing as is my pdoc but sometimes it can be a good idea.
>
> First of all I was going to go for the 1xdaily dose of klonopin rather than let it build up in my body by taking it more than once a day. However I read recently that the benzodiazepines inhibit the enzymes that make up the cytochrome P450 system and the benzodiazepine cannot be metabolised because of this and instead they build up in the liver until they begin to sift into the blood stream and accumulate in the body. The same situation occur with the SSRI's as they are potent inhibitors of the cytochrome P450 CYP2D6 enzyme and after a short while levels of these drugs accumulate to high levels in the blood stream. This is new to me so correct me if I have made a mistake here.
>
> So my pdoc decided if the Klonopin was going to work I couldnt take it 1x daily to get an immediate response each morning when I took it but instead let the drug build up in my body. You know what it seems to be working better this way. The Clonazepam being present all the time allows my body to adjust to the drug so that the side effects are not intolerable. We are following the guidelines outlined in the Brazilian guide to treatment of social anxiety disorder which states that the initial dose should be 1mg 2 xdaily. This sounds reasonable and if I get too tired then I can stay at 1 mg for one week only as suggested in the article.
>
> My biggest worry is the cognitive impairment that this drug may and is causing. Because I have always suffered from anxiety and obsessive behaviour I worry that I may lose my 'edge' and 'shrewdness', a charcteristic that has helped me to overcome anxiety as well as depression but has up until this point stopped me from living.
>
> However I see various solutions:
>
> 1) In the period of 11th April of Psycho Babble I mentioned my concerns about the cognitive impairments of Klonopin and one positive response from AndrewB was the augmentation with Modafinil. Modafinil has a reasonably long-half life and AndrewB commented that it helped with the groggy side-effects and sedation with Klonopin. I agree that this sound a feasible option particulaly because Modafinil is a smart-drug and would mean not having to rely on another strong prescription medication. I think augmentation with Lamotrigine would improve th situation even more by evening things out so that the Klonopin can do its job and the Modafinil its without interfering with each other. What also great about this cocktail is that it is unlikely to cause hyperactivity behaviour. Klonopin as a depressant calms behaviour if used appropriately, Modafinil is a stimulant that provides alertness where 'alertness is required' and Lamotrigine role speaks for itself-a decently solid Mood Stabiliser
>
> Question 1) What do you think about this cocktail?
> Question 2) Once and for all, is Modafinil a DA re-uptaker like ritalin or an alpha1 adrenergic agonist
>
> Something else that I may mention to my pdoc is the use of a full benzodiazepine antagonist occassionaly. I mentioned this when Dr Richardson was answering questions in April but in regards to selective bz omega receptor antagonists and there are none available although Flumenzenil(spelling?) is widely used to reverse the effects of the benzodiazepines. Big drawback though-half-life of one hour. If other similar drugs with longer half-lives become available I may consider them if I fancy time-out from Klonopin.
>
> Take care Dr-Bob and your extended family

Hi--well I can tell you that indeed modafinil is a dopamine uptake blocker but this isn't the basis of it's action as it's effects are not blocked by classic "post" synaptic dopamine blockers neuroleptics (as is the case with ritalin and dexedrine). The central alpha 1 adrenergic effects yes as central but not peripheral alpha 1 adrenergic blockers do decrease modafinils effects. The most widely held correlation of modafinil's basis of action is the glutamine increase in the brain and the gaba A decrease effect specifically in the medial preoptic area and the posterior hypothalamus. Disinhibition by the blocking of or lessening of gaba A activity is said to allow increased glutaminergic function, glutamine being an "excitatory" amino acid in the c.n.s.!!! By the way I'm currently on a trial of provigil "modafinil" and with me the results have been quite disappointing, but don't let me discourage you :):):)


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poster:dennison thread:68657
URL: http://www.dr-bob.org/babble/20010701/msgs/68672.html