Psycho-Babble Medication | about biological treatments | Framed
This thread | Show all | Post follow-up | Start new thread | List of forums | Search | FAQ

Re: Globe and Mail Article From dj on ADs (long)

Posted by SLS on April 17, 2001, at 21:25:46

In reply to Globe and Mail Article From dj on ADs, posted by Cam W. on April 17, 2001, at 16:20:13

> dj is having trouble with his modem and asked me to post this article which appeared in today's Globe & Mail
> - Cam


Although a rare occurence, I have a few comments and corrections. I hope someone will be kind enough to correct my corrections as needed. :-)


> When one antidepressant isn't enough
> Patients who don't respond to one type of drug
> are finding new hope with combination therapies
> WALLACE IMMEN
>
> Tuesday, April 17, 2001
>
>
> Because Gwen's condition improved only slightly when she took Paxil, one of the most commonly prescribed antidepressants, her doctor switched her to Wellbutrin, another antidepressant that has a different action in the brain.
>
> Only when her doctor prescribed both drugs together did the depression subside.


To me, it makes sense to take inventory of drugs that have produced even the mildest of improvements so as to create a list of drugs that might be the best candidates for effective combinations. There might also be clues as to which new drugs to try when taking into consideration which drugs produced improvement as well as those that have produced an exacerbation of depression.


> "We can't tell just by examination what person will respond to which combination.


I am optimistic that one day this will be possible. An examination might comprise of using various brain imaging techniques to determine baseline regional brain activity as well as the brain's reaction to an algorithm of pharmacological challenges.


> "The medication situation is a bit of a mess because drugs for depression were developed in a haphazard manner," explained Dr. Robert G. Cooke, head of the centre's depression clinic.


I disagree with this extreme characterization of haphazard the manner in which these drugs have been developed. The search for effective medications using a "designer" approach based upon chemical structure and binding sites has been around for at least fifteen years. However, without an exact understanding of how the brain works in health and disease, these "ideal" designs often just plain don't work. This is why there still exist paradigms for the screening for antidepressants using animal models.

A good example of the purposeful design of a drug is gabapentin (Neurontin). It was developed because of its nearly indentical chemical structure with GABA (gamma aminobutyric acid). However, it failed to bind to the GABA receptor at all. However, fortuitously, gabapentin turned out to act at other sites in such a way as to produce anticonvulsive effects. This was unforseen.


> The first family of antidepressants -- the tricyclics -- were developed almost by accident, when doctors in the 1950s found that patients taking a drug for tuberculosis.


Just for the sake of accuracy, the antituberculosis drug was an MAO-inhibitor known as iproniazid. I believe this serendipitous discovery occured in 1954 and explored more fully by 1957.

From: http://www.csusm.edu/DandB/AD.html

"History of Antidepressants

The first two classes of drugs used to treat major depression, the monoamine oxidase inhibitors (MAOIs) and the tricyclic antidepressants were discovered by serendipity. Iproniazid, the first modern antidepressant, was originally developed as an antitubercular drug in the early 1950's. In addition to its ability to treat tuberculosis, iproniazid was observed to elevate mood and stimulate activity in many patients. These effects led researchers to investigate the ability of iproniazid to treat the symptoms of depression. After promising preliminary findings reported in 1957, iproniazid was prescribed widely to patients with major depression. Within the first year it was available as an antidepressant, four hundred thousand depressed people were treated with iproniazid. Subsequent studies demonstrated the ability of this drug to block the activity of monoamine oxidase, the enzyme that destroys the monoamine neurotransmitters (norepinephrine, serotonin and dopamine). Although iproniazid is no longer used as an antidepressant because of toxic side-effects, the effectiveness of this drug led to further interest in the idea that depression might be alleviated by appropriate drugs.

The first tricyclic antidepressant, imipramine, was originally developed in a search for drugs useful in the treatment of schizophrenia. Although clinical trials demonstrated a lack of effect in treating schizophrenia, an astute clinician decided to examine its effectiveness in depressed patients. Early studies in 1957 and 1958 reported that imipramine significantly alleviated symptoms in patients with major depression. Interestingly, although imipramine elevated mood and increased energy in depressed patients, the drug proved to be sedating in individuals without major depression. These effects led to the idea that imipramine was selectively reversing the depression, rather than simply producing a general activating effect. Subsequent biochemical studies on imipramine demonstrated that this drug increased the activity of the monoamine neurotransmitters, norepinephrine and serotonin, by inhibiting their reuptake into neurons."


> About 18 per cent of people who did not respond to drugs responded to them after a year's use of the implant.


The only investigated I know of designed specifically to test VNS for treatment-resistant depression is a pilot study that yielded a 40% response rate. Perhaps the results of a large-scale study have been recently reported. I don't know.


- Scott

Biol Psychiatry 2000 Feb 15;47(4):276-86

Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study.

Rush AJ, George MS, Sackeim HA, Marangell LB, Husain MM, Giller C, Nahas Z, Haines S, Simpson RK Jr, Goodman R.

Departments of Psychiatry and Neurosurgery, University of Texas Southwestern Medical Center, Dallas 75235-9086, USA.

BACKGROUND: Vagus Nerve Stimulation (VNS) delivered by the NeuroCybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects. METHODS: Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar I (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS. RESULTS: In the current MDE (median length = 4.7 years), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS(28)) scores averaged 38.0. Response rates ( > or =50% reduction in baseline scores) were 40% for both the HDRS(28) and the Clinical Global Impressions-Improvement index (score of 1 or 2) and 50% for the Montgomery-Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long-term follow-up to date. CONCLUSIONS: These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions.

Publication Types:
Clinical trial
Multicenter study

PMID: 10686262 [PubMed - indexed for MEDLINE]

 

Thread

 

Post a new follow-up

Your message only Include above post


Notify the administrators

They will then review this post with the posting guidelines in mind.

To contact them about something other than this post, please use this form instead.

 

Start a new thread

 
Google
dr-bob.org www
Search options and examples
[amazon] for
in

This thread | Show all | Post follow-up | Start new thread | FAQ
Psycho-Babble Medication | Framed

poster:SLS thread:60209
URL: http://www.dr-bob.org/babble/20010417/msgs/60254.html