Posted by Sunnely on June 26, 2001, at 23:27:29
In reply to Re: Maprotiline (Ludiomil):, posted by Salilyn on June 26, 2001, at 3:44:10
Hi Sallilyn,
Agree!
Except for the cost, the tricyclic (and tetracyclic) antidepressants offer no great advantage to the newer generation of antidepressants.
The main reason as to why the newer generation of antidepressants (e.g., SSRIs) are now the first drugs of choice for depression over the TCAs is Safety, Tolerability, and Simplicity.
Due to the fact that the SSRIs do not inhibit sodium fast channels (prolonged heart conduction), there is essentially no risk of lethality, even with a substantial overdose of these medications. In contrast, overdoses of a TCA of as little as 5 times the daily dose can be lethal. This issue is important because of the delay between starting an antidepressant of any class and achieving a meaningful improvement in the depressive syndrome. The risk of a suicide attempt is a serious concern during this delayed onset of interval. For many years, TCAs have been a leading cause of death due to drug overdose because of their serious toxicity profile, coupled with the fact that they are given to patients at risk for making serious suicide attempts. Because SSRIs avoid this problem, the prognosis (outcome) of patients suffering from this condition has significantly improved. You can overdose on 3 month's supply of Prozac (20 mg/day) and it won't kill you but, 1 week supply of Elavil (at 150-200 mg/day) most likely will.
Another important difference between the newer generation antidepressants such as SSRIs and TCAs is a better overall tolerability profile in terms of a lower incidence of both nuisance and serious adverse effects. SSRIs affect fewer sites of action and hence cause fewer types of adverse effects. The TCAs, OTOH, are associated with a considerably higher rate of adverse effects mediated by the blockade of specific neuroreceptors such as muscarinic acetylcholine receptors (e.g., dry mouth, constipation) and alpha1-adrenergic receptors (e.g., dizziness). In contrast, SSRIs as a group have a higher rate of adverse effects mediated by the indirect activation of serotonin via the inhibition of reuptake pump (e.g., nausea).
While these adverse effects are less dramatic than the potentially life-threatening toxicity problems that can occur while taking TCAs, they can have serious consequences. The orthostatic hypotension (marked drop in blood pressure upon arising) can occur on TCAs may cause falls with resultant trauma. The chronic anticholinergic effects can lead the patient to discontinue treatment during the maintenance phase of treatment and thus increase the risk of relapse. In clinical studies, the discontinuation of tertiary amine TCAs such as imipramine (Tofranil) can be 3 times higher than the discontinuation rate on an SSRI (e.g., 22% versus 7%, respectively).
Incidentally, the following mnenomic is usually employed by doctors when selecting an antidepressant for a patient: STEPS
S - Safety (Acute therapeutic index, long-term safety, risk of drug-drug interactions, overdose lethality risk, alcohol potentiation)
T - Tolerability (Acute and Long-term)
E - Efficacy (overall response rate, unique spectrum of activity in subpopulations, rate of onset, maintenance, prophylactic)
P - Payment (cost-effectivenes)
S - Simplicity (ease of optimal dosing, drug administation schedule, need for blood levels, etc.)
Based on the above, it's a no brainer that the newer generation of antidepressants such as the SSRIs are clear choice. Therefore, it is very unlikely that the TCAs (and tetracyclic e.g., maprotiline) antidepressants will ever regain their position as the drugs of (antidepressant) choice for depression.
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> I tried Ludiomil when it was first marketed, and ever since have referred to it as "Ludicrousmil". With all the alternatives (unless you're going through the book), in my opinion, it makes no sense to try Ludiomil in this day and age. My experience was that it was even worse (side effects) than other ADs available at the time.
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> Salilyn
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> > Sorry, but I have to agree with Elizabeth's counterpoint.
> >
> > If I may just emphasize a couple of concerns with the use of maprotiline (Ludiomil): 1. seizures and 2. rashes.
> >
> > Of the less-common side effects, maprotiline-induced seizures have received the most attention. Case reports have indicated that maprotiline, like the TCAs, can cause seizures at therapeutic doses. (Amoxapine or Asendin is also known to induce seizures at therpeutic doses. In overdoses with this drug, seizures are severe and frequent.) In one study, the prevalence of seizures in patients receiving maprotiline was 16% versus 2% in TCA-induced patients.
> >
> > Rashes occur twice as frequently with maprotiline as with amitriptline (Elavil) or imipramine (Tofranil). These are usually described as small and localized but occasionally as large, exanthemic, pruritic.
> >
> > To sum, maprotiline is a monomethylated tetracyclic antidepressant with no obvious advantages over the TCAs. Evidence that this drug has a more rapid onset of action is debatable. Its pharmacological profile is similar to that of the monomethylated TCAs nortriptyline (Pamelor) and desipramine (Norpramin) and its side-profile is practically indistinguishable from the TCAs, with the exceptions of causing a higher rate of seizures and rashes.
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> > ***************************************
> >
> > > I'd like to see what others have to say about this.
poster:Sunnely
thread:67742
URL: http://www.dr-bob.org/babble/20010625/msgs/68032.html