![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 4 to 28 of 434. Go back in thread:
Posted by Sunnely on June 25, 2001, at 19:54:27
In reply to Re: Maprotiline (Ludiomil): » Elizabeth, posted by SalArmy4me on June 25, 2001, at 18:06:07
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.
***************************************
> I'd like to see what others have to say about this.
Posted by Elizabeth on June 26, 2001, at 3:06:29
In reply to Re: Maprotiline (Ludiomil): » SalArmy4me, posted by Sunnely on June 25, 2001, at 19:54:27
> Sorry, but I have to agree with Elizabeth's counterpoint.
LOL! Maybe Sal and I should go on Politically Incorrect sometime.
BTW, when amoxapine first came out, they tried to claim that it would work faster than other TCAs, too. Amoxapine, although it too shares the usual TCA problems, is interesting and novel, at least, in that it's a mixed-action antidepressant (NE reuptake inhibitor/DA antagonist). Anecdotally, I've heard of amoxapine being used successfully in combination with Parnate. (When I tried adding amoxapine to Parnate, I started getting ravenously hungry at about 75 mg. Having had an unpleasant weight-gain experience on Nardil, I chickened out.)
Weird that maprotiline (like most TCAs, an antihistamine) would cause pruritis; I didn't know about that one.
-elizabeth
Posted by Salilyn on June 26, 2001, at 3:44:10
In reply to Re: Maprotiline (Ludiomil): » SalArmy4me, posted by Sunnely on June 25, 2001, at 19:54:27
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.
Salilyn
> 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.
>
> ***************************************
>
> > I'd like to see what others have to say about this.
Posted by Salilyn on June 26, 2001, at 5:06:31
In reply to Re: Maprotiline (Ludiomil): » SalArmy4me, posted by Sunnely on June 25, 2001, at 19:54:27
Asendin is another drug, in my opinion, that's best left forgotten. In the early to mid-80's, my psychiatrist used it as an antidepressant, and as an antipsychotic (in his schizophrenic patients). Its antipsychotic properties, I think, are due to its dopamine-blocking action. I stopped it within several days because of its side effects, which can include extrapyramidal symptoms (e.g., dystonia).
Salilyn
>
> 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
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.
++++++++++++++++++++++++++++++++
> 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.
>
> Salilyn
>
>
>
>
> > 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.
> >
> > ***************************************
> >
> > > I'd like to see what others have to say about this.
Posted by Sunnely on June 26, 2001, at 23:32:18
In reply to Re: Maprotiline (Ludiomil):, posted by Salilyn on June 26, 2001, at 5:06:31
Hi Salilyn,
Agree, again!
Not only that amoxapine (Asendin) reported to cause acute dystonia, it has also been reported to cause tardive dyskinesia (TD). Any doctor or prescriber choosing this drug as a first line treatment for depression, when newer safer antidepressants are available, is asking for a malpractice suit.
**********************************
> Asendin is another drug, in my opinion, that's best left forgotten. In the early to mid-80's, my psychiatrist used it as an antidepressant, and as an antipsychotic (in his schizophrenic patients). Its antipsychotic properties, I think, are due to its dopamine-blocking action. I stopped it within several days because of its side effects, which can include extrapyramidal symptoms (e.g., dystonia).
>
> Salilyn
>
> >
> > 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
Posted by Elizabeth on June 27, 2001, at 12:19:27
In reply to Re: Maprotiline (Ludiomil): » Salilyn, posted by Sunnely on June 26, 2001, at 23:27:29
> 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.
I don't agree about the tolerability -- that's a YMMV thing, and SSRIs, which were initially touted as free of side effects, turned out to be not so great in that department (sexual dysfunction (which seems to be almost universal with SSRIs), activation syndrome, sleep disruption, apathy, GI side effects, etc.).
Safety is the main issue. SSRIs are almost never lethal in overdose. Tricyclics can be, although I think you exaggerate a bit. People who don't metabolise tricyclics properly (due to genetic enzyme deficiencies or to interactions with other drugs) can kill themselves with a week's supply; normal metabolisers probably won't. SSRIs are also, as you say, safe for people with cardiac conduction defects (so are MAOIs, incidentally: they used to be the drugs of choice in these cases).
TCAs also carry an increased risk of mania and seizures, compared to SSRIs and MAOIs.
> SSRIs affect fewer sites of action and hence cause fewer types of adverse effects.
There are lots of different TCAs (about 10 of them in the US, if you count amoxapine and maprotiline), and some of them -- notably desipramine and nortriptyline -- have low binding affinity at cholinergic, adrenergic, and histaminic receptors, and unsurprisingly, these drugs have fewer side effects than other TCAs (amitriptyline, doxepin, and protriptyline are especially nasty).
> The orthostatic hypotension (marked drop in blood pressure upon arising) can occur on TCAs may cause falls with resultant trauma.
This is especially relevant in older adults (women in particular) who may have brittle bones. Serious injuries, such as hip fractures, can result.
> The chronic anticholinergic effects can lead the patient to discontinue treatment during the maintenance phase of treatment and thus increase the risk of relapse.
They can also cause dental problems (due to dry mouth) and hemorrhoids (due to chronic constipation).
> 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).
Which is why I brought up the secondary amines (DMI and NOR).
> E - Efficacy (overall response rate, unique spectrum of activity in subpopulations, rate of onset, maintenance, prophylactic)
This is important: certain types of depression tend to respond poorly to SSRIs and well to TCAs.
> S - Simplicity (ease of optimal dosing, drug administation schedule, need for blood levels, etc.)
Tricyclic serum levels should be monitored (although they often aren't), especially if a TCA-SSRI combination is going to be used. Also, one should have a cardiac workup because of the effects of TCAs on cardiac conduction.
> Based on the above, it's a no brainer that the newer generation of antidepressants such as the SSRIs are clear choice.
I'm afraid it's not always that simple. Depression isn't a single disease: it's a syndrome that can have different causes and different effective treatments. SSRIs don't work for everyone, and they aren't the most tolerable drugs for everyone, either. (This is especially true of patients who have panic disorder; this group has a lower risk of suicide attempts, and panic patients frequently have a *very* hard time tolerating the activating effects of SSRIs.)
-elizabeth
Posted by Elizabeth on June 27, 2001, at 12:20:31
In reply to Re: Amoxapine (Asendin): » Salilyn, posted by Sunnely on June 26, 2001, at 23:32:18
> Not only that amoxapine (Asendin) reported to cause acute dystonia, it has also been reported to cause tardive dyskinesia (TD). Any doctor or prescriber choosing this drug as a first line treatment for depression, when newer safer antidepressants are available, is asking for a malpractice suit.
Woah! Nobody said amoxapine should be a first-line treatment for depression. What it should be considered for is *psychotic* depression.
-elizabeth
Posted by Elizabeth on June 27, 2001, at 12:22:09
In reply to Re: Maprotiline (Ludiomil):, posted by Salilyn on June 26, 2001, at 5:06:31
> Asendin is another drug, in my opinion, that's best left forgotten. In the early to mid-80's, my psychiatrist used it as an antidepressant, and as an antipsychotic (in his schizophrenic patients). Its antipsychotic properties, I think, are due to its dopamine-blocking action. I stopped it within several days because of its side effects, which can include extrapyramidal symptoms (e.g., dystonia).
I didn't get any EPS on amoxapine -- I stopped because of appetite increase (I'm such a chicken about that). You're right that it's a D2 receptor antagonist, but the rate of EPS is lower than it is with conventional antipsychotics. It seems like a reasonable choice for psychotic depression, in particular. (All the antipsychotics in current use are dopamine antagonists. They *all* have the potential to produce EPS and TD.)
-elizabeth
Posted by Sunnely on June 28, 2001, at 0:09:24
In reply to TCAs do have their good points » Sunnely, posted by Elizabeth on June 27, 2001, at 12:19:27
> There are lots of different TCAs (about 10 of them in the US, if you count amoxapine and maprotiline), and some of them -- notably desipramine and nortriptyline -- have low binding affinity at cholinergic, adrenergic, and histaminic receptors, and unsurprisingly, these drugs have fewer side effects than other TCAs (amitriptyline, doxepin, and protriptyline are especially nasty).
I'm not sure I understand your logic here. I believe I was comparing SSRIs in general with TCAs in general and not subclasses of TCAs. I can't argue with you in the differences in receptor affinities you described above between tertiary amine TCAs and secondary amine TCAs. But as a class, SSRIs have less affinity to the receptors you described above than the TCAs, as a group.
>
> > The orthostatic hypotension (marked drop in blood pressure upon arising) can occur on TCAs may cause falls with resultant trauma.
>
> This is especially relevant in older adults (women in particular) who may have brittle bones. Serious injuries, such as hip fractures, can result.Again, can't argue with you on this. But again, as a class, SSRIs are less liable to cause orthostatic hypotension compared to the TCAs, when used in used in any group of age or gender population.
>
> Which is why I brought up the secondary amines (DMI and NOR).Both of which are also TCAs, metabolite of imipramine and amitriptyline (tertiary amine TCAs), respectively.
> Tricyclic serum levels should be monitored (although they often aren't), especially if a TCA-SSRI combination is going to be used. Also, one should have a cardiac workup because of the effects of TCAs on cardiac conduction.
Agree with you. Prolonged QTc and subsequent "torsades" and even sudden deaths can occur with SSRI-TCA combination. As you said TCA levels should be monitored, and IMHO, at least for a couple of reasons: 1. possible toxic levels, 2. "therapeutic levels," and 3. compliance. Desipramine which is mainly metabolized by CYP2D6 can lead to toxic blood levels when combined with Prozac and Paxil (both potent inhibitors of CYP2D6). Also, approximately 5-10% of Caucausians have polymorphism for CYP2D6 and can become markedly toxic even when given the "normal" recommended dose. Nortriptyline, believed to have a "therapeutic window" is one TCA that definitely requires periodic monitoring of blood levels, especially if it seems to be losing its antidepressant effect.
> I'm afraid it's not always that simple. Depression isn't a single disease: it's a syndrome that can have different causes and different effective treatments. SSRIs don't work for everyone, and they aren't the most tolerable drugs for everyone, either. (This is especially true of patients who have panic disorder; this group has a lower risk of suicide attempts, and panic patients frequently have a *very* hard time tolerating the activating effects of SSRIs.)
Again, I agree with you on this that SSRIs are not for everyone and not everyone who is depressed requires an SSRI (or an antidepressant). Indeed, depression is not uncommonly co-morbid with other conditions such as panic disorder, OCD, PTSD, schizophrenia, bipolar disorder, substance abuse, Parkinson's disease, dementing processes, etc. I guess I was mainly referring to the uncomplicated type of major depression. However, with the extra potentially serious baggage that TCAs carry with them, it has been relegated (per prescribers' choice) to second-line therapy when it comes to treating major depression (per se). This is not to imply that TCAs themselves are inferior to SSRIs when it comes to antidepressant efficacy. In fact, I believe in some studies, TCAs appear to be more efficacious than SSRIs in severe depression.
Posted by Sunnely on June 28, 2001, at 0:29:06
In reply to Re: Amoxapine » Sunnely, posted by Elizabeth on June 27, 2001, at 12:20:31
Technically speaking, amoxapine (Asendin) is classified as an antidepressant. Amoxapine, which is a demethylated metabolite of the antipsychotic drug loxapine (Loxitane), has classic neuroleptic activity, so its use eventually included, aside from depression per se, also psychotic depression, as you mentioned. This avoids combining the use of an antidepressant and an antipsychotic for patients with psychotic depression or schizoaffective disorder, depressed. Similar to other antipsychotics with D2 blocking effect, it carries with it a full range of extrapyramidal side effects - acute dystonic reactions, akathisia, pseudoparkinsonism, and tardive dyskinesia.
***************************
> > Not only that amoxapine (Asendin) reported to cause acute dystonia, it has also been reported to cause tardive dyskinesia (TD). Any doctor or prescriber choosing this drug as a first line treatment for depression, when newer safer antidepressants are available, is asking for a malpractice suit.
>
> Woah! Nobody said amoxapine should be a first-line treatment for depression. What it should be considered for is *psychotic* depression.
>
> -elizabeth
Posted by Elizabeth on June 29, 2001, at 18:50:34
In reply to Re: TCAs do have their good points » Elizabeth, posted by Sunnely on June 28, 2001, at 0:09:24
> I'm not sure I understand your logic here. I believe I was comparing SSRIs in general with TCAs in general and not subclasses of TCAs.
Right: you were comparing them in general, while I was comparing the more benign TCAs with the SSRIs. (For the most part, it's not clear what the differences in toxicity among the SSRIs are: fluoxetine has a reuptation for being more stimulating, fluvoxamine seems to cause nausea more often, paroxetine may carry greater risk of weight gain, etc.)
What I'm saying is that there are TCAs that have relatively benign side effect profiles, and these TCAs are often more tolerable than SSRIs because they lack the characteristic side effects of the SSRIs (notably the near-universal sexual dysfunction).
I don't believe it's useful to make generalisations about the relative tolerability of TCAs and SSRIs: although some TCAs (notably amitriptyline) are very poorly tolerated, and some of them also have increased risk of cardiac complications (protriptyline) and/or seizures (maprotiline), there are TCAs available that have relatively benign side effect and safety profiles. (Lofepramine is an excellent one, but we don't have it here in the USA.)
> I can't argue with you in the differences in receptor affinities you described above between tertiary amine TCAs and secondary amine TCAs.
That's true, although you can't predict TCA pharmacological properties based on the structure of the side chain alone: although the side chain plays a major role, the core "tricyclic" (dibenzazepine) structure is undoubtedly involved in the pharmacology of these drugs too; for example, consider the differences among the secondary amines nortriptyline, desipramine, protriptyline, and maprotiline.
> Again, can't argue with you on this. But again, as a class, SSRIs are less liable to cause orthostatic hypotension compared to the TCAs, when used in used in any group of age or gender population.
And again, it depends which TCA you are talking about -- practically speaking, lumping them all together (and lumping all patients together too) isn't useful, and to make a generalisation that tricyclics are unsafe and poorly tolerated is misleading.
SSRIs have their own side effects which should not be ignored and which make them less tolerable for many patients than the preferred TCAs (nortriptyline, desipramine). Some patients even prefer tricyclics with more side effects, such as imipramine, doxepin, protriptyline or amitriptyline, to the SSRIs.
Differences among the various SSRIs in their propensity to cause characteristic side effects are less predictable, probably because we don't have as good an understanding of the differences among the SSRIs and the clinical consequences of these differences. (We do know that citalopram and paroxetine are the more selective SSRIs, that fluoxetine and norfluoxetine are less selective, and that sertraline is less potent, but we haven't been able to make much of this information.)
The safety issue is more generalisable, although it should be emphasised that tricyclics *can* be used safely with appropriate monitoring and consideration for individual patient characteristics (such as the risk of suicide attempts, various cardiac risk factors, the possibility of a seizure disorder, use of other drugs, etc.).
> As you said TCA levels should be monitored, and IMHO, at least for a couple of reasons: 1. possible toxic levels, 2. "therapeutic levels," and 3. compliance.
Therapeutic ranges aren't established for all TCAs (therapeutic monitoring is also complicated by the presence of active metabolites). In practise (and this may be the most practical way to go about using TCAs), doctors usually resort to serum level monitoring only if there are specific risk factors such as other drugs or medical conditions (the person should be checked for these *before* trying TCA therapy), or deficiency in the cytochrome enzyme p450 2d6 (a fairly common genetic condition, particularly, as you point out, in people of European descent), which can be tested for relatively easily (and I believe this test should be given before treatment as well).
> Desipramine which is mainly metabolized by CYP2D6 can lead to toxic blood levels when combined with Prozac and Paxil (both potent inhibitors of CYP2D6).
I found this out abount 5 years ago, when I had a problem combining a low dose of DMI (50 mg) with fluoxetine. (I later had a pecular reaction to a normal dose of dextromethorphan (in one of those OTC cough syrups that don't work < g >), and several other bad experiences with TCAs by themselves, so it's possible that I'm one of the unlucky people who can't use these drugs in normal doses; if I do try using them again, I would definitely want to get serum level monitoring.
It should also be noted that, although "Caucasians" (i.e., whites) represent the majority of people with this enzyme deficiency, it does occur in other races. (Recall that many Americans who would be considered "black," for example, have some "white" ancestry. This is one of the many reasons I'm not into classifying people by their race.)
> Nortriptyline, believed to have a "therapeutic window" is one TCA that definitely requires periodic monitoring of blood levels, especially if it seems to be losing its antidepressant effect.
Nortriptyline and amitriptyline (of course: part of the therapeutic activity of AMI results from significant metabolism into NOR) do have a therapeutic window (their dose-response curves are shaped like an inverted U: if the serum level becomes too high, they can start to become less effective).
> Again, I agree with you on this that SSRIs are not for everyone and not everyone who is depressed requires an SSRI (or an antidepressant).Not just that: not all types of depression respond well to SSRIs. Admittedly, my sample is skewed, but I've encountered a lot of people with moderate to severe endogenous depression (and a few with more severe cases of atypical depression) who simply didn't respond to SSRIs at all (one of these people is myself), as well as many folks with panic disorder (which doesn't respond to all antidepressants) who cannot tolerate the activating side effects of the SSRIs. The other new antidepressants, especially Effexor and Remeron (and, to a lesser extent, Serzone and Wellbutrin), offer hope for non-SSRI-responsive depressed patients, but sometimes the TCAs turn out to be the most effective and are tolerated well (particularly if you choose the right TCA for the individual patient -- NOR and DMI are both relatively benign, but DMI can cause more activation and jitters while NOR has more sedating and anticholinergic effects, although these are mild with both drugs).
> Indeed, depression is not uncommonly co-morbid with other conditions such as panic disorder, OCD, PTSD, schizophrenia, bipolar disorder, substance abuse, Parkinson's disease, dementing processes, etc. I guess I was mainly referring to the uncomplicated type of major depression.
Classic (so-called "endogenous") depression may actually respond better to TCAs than to SSRIs. SSRIs seem to be better suited, however, for milder depressions such as dysthymia; atypical depression; and depression with certain comorbid anxiety disorders such as OCD, PTSD, social phobia, and borderline personality disorder.
> However, with the extra potentially serious baggage that TCAs carry with them, it has been relegated (per prescribers' choice) to second-line therapy when it comes to treating major depression (per se).
*Usually*, an SSRI is the first choice treatment, yes. There are prescribers who feel, based on their clinical experience, that in some cases a TCA is preferable, even if the patient needs to be given very small prescriptions (e.g., only 5 days at a time) or even hospitalised in order to prevent suicide attempts.
TCAs don't have the broad-spectrum efficacy of SSRIs and MAOIs. They're best suited to classic major depression or panic disorder (serotonergic TCAs such as imipramine and clomipramine may be more effective, although some patients with PAD do respond to NOR or DMI; maprotiline has been found to be ineffective in PAD -- which puts it even lower on the list of "best tricyclics" < g >).
> In fact, I believe in some studies, TCAs appear to be more efficacious than SSRIs in severe depression.
Not so much for severe depression in general, but when they specifically look at a subtype called "melancholic features," the results are more compelling. (Although atypical depression and mood-reactive depressions have traditionally been regarded as less severe than melancholia (AKA "endogenous depression" -- this older terminology should not be taken to mean that other types of depression are not endogenous), I've encountered people with nonmelancholic depression whose illness would be considered "severe.")
> Technically speaking, amoxapine (Asendin) is classified as an antidepressant.
That's not what I'd call a "technical" classification. It's mainly a legal and marketing designation: amoxapine is labelled and marketed as an antidepressant. Drugs can be chemically similar but have different pharmacological and clinical effects. (TCAs as a group are chemically similar to phenothiazines, e.g.) For that matter, they can also be pharmacologically similar but be marketed for different purposes: for example, Compazine is marketed for nausea (more so than for psychosis), but other dopamine-antagonist phenothiazines (and possibly atypical antipsychotics as well) have robust antinausea effects. So does promethazine, a phenothiazine which is a weak dopamine antagonist but a strong antihistamine, and is often used as an antiemetic, an antianaphylactic, and a sedative, but not as an antipsychotic: although chemically of the same class as chlorpromazine (Thorazine), fluphenazine (Prolixin), trifluoperazine (Stelazine), thioridazine (Mellaril), etc., promethazine (Phenergan) is not an effective antipsychotic nor should it be referred to as an antipsychotic. Then there's the case of Luvox -- the SSRI (and perfectly good antidepressant) -- that is labelled only for OCD!
Drugs can be classified by their chemical structures (phenothiazine, benzodiazepine), by their clinical uses (antidepressant, antipsychotic, anxiolytic), by their pharmacology (selective serotonin reuptake inhibitor, monoamine oxidase inhibitor, nicotinic-cholinergic agonist, etc.), or by their clinical uses (anxiolytic, antidepressant, antipsychotic), depending upon information what you want to convey. Amoxapine could be called a mixed antidepressant-antipsychotic, a dibenzazepine compound, a mixed norepinephrine reuptake inhibitor/dopamine antagonist with alpha-1 adrenergic, histaminic, and muscarinic cholinergic antagonist activity. All of these descriptions are equally accurate, but the information they convey is different.
The "tricyclics" -- the class of dibenzazepine drugs including imipramine, desipramine, amitriptyline, nortriptyline, clomipramine, protriptyline, trimipramine, doxepin, amoxapine, and maprotiline (as well as others, such as lofepramine and dothiepin, that are not used in the USA) is described according to a common chemical structure, but the name "tricyclic" is imprecise and it is only by convention that it is generally taken to refer to these drugs. There are plenty of "tricyclic" compounds (for example, some of the antipsychotics, and the anticonvulsant carbamazepine) that are not antidepressants (although both antipsychotics and CBZ sometimes can be used as AD augmentors, and CBZ alone is sometimes effective in TRD, these aren't their primary uses and they aren't the most effective drugs for depression) and don't share the pharmacological features of the "tricyclic antidepressants."
Tricyclics are norepinephrine reuptake inhibiting drugs with a range of other effects, and classifying them by their pharmacology would be rather unwieldy. "Norepinephrine reuptake inhibitor" or "mixed serotonin-norepinephrine reuptake inhibitor" would adequately describe the pharmacologic effects of these drugs that are known to contribute to their therapeutic effects in depression, though.
Re amoxapine:
> Similar to other antipsychotics with D2 blocking effect, it carries with it a full range of extrapyramidal side effects - acute dystonic reactions, akathisia, pseudoparkinsonism, and tardive dyskinesia.
It does have a risk of these effects. So do all the antipsychotic drugs used today. The risk is *lower* with amoxapine when compared with the older antipsychotics (it's more comparable, I think, to the atypical antipsychotics such as risperidone).
After I failed to tolerate nortriptyline, a psychiatric researcher with whom my pdoc was consulting suggested adding amoxapine to the MAOI I was already taking (I was trying to augment the MAOIs with TCAs). He said that he's found this combination helpful (and safe and generally well-tolerated) for patients like me who have classic melancholia along with chronic milder depression (dysthymia or residual depression). I would like to give another try to MAOI-TCA combinations, although I would insist on using desipramine and on monitoring serum levels. (Secondary amines are a little simpler to monitor and to use in combination with other drugs because they have less complicated metabolic pathways than their tertiary precursors.)
-elizabeth
Posted by Lorraine on June 30, 2001, at 12:26:10
In reply to Re: TCAs do have their good points » Sunnely, posted by Elizabeth on June 29, 2001, at 18:50:34
> SSRIs have their own side effects which should not be ignored and which make them less tolerable for many patients than the preferred TCAs (nortriptyline, desipramine). Some patients even prefer tricyclics with more side effects, such as imipramine, doxepin, protriptyline or amitriptyline, to the SSRIs.
None of the SSRIs have worked for me; Effexor worked first time with intolerable side effects (40 lb weight gain; sexual dysfunction); Wellbutrin and Serzone also don't work for me. I'm knocking at TCAs door, I'm afraid.
>
> Differences among the various SSRIs in their propensity to cause characteristic side effects are less predictableOK. How about Effexor reset my anger set point so that I just NEVER got angry and, for the first time in my life, could not understand why other people created so much havor in their lives with anger. Or, Wellbutrin made me "jealous", which is not typically one of my issues and also made me compulsive about time--shock the h*** out of my hubby when I was the first one in the car for an outting or yelling at everyone else to get in the car for gods sake because WE ARE GOING TO BE LATE. These experiences though have made me very tolerant of other people (ie my time police husband) and their "peculiarities" which I now understand may not be changable.
> The safety issue is more generalisable, although it should be emphasised that tricyclics *can* be used safely with appropriate monitoring and consideration for individual patient characteristics (such as the risk of suicide attempts, various cardiac risk factors, the possibility of a seizure disorder, use of other drugs, etc.).With Wellbutrin, I outright hallucinated when I went from a dark room into a light room or upon awaking in the morning (i now believe that this may have been seizure like activity). Imagine the hazard of driving like that a night with headlights coming at you
>In practise (and this may be the most practical way to go about using TCAs), doctors usually resort to serum level monitoring only if there are specific risk factors such as other drugs or medical conditions (the person should be checked for these *before* trying TCA therapy), or deficiency in the cytochrome enzyme p450 2d6 (a fairly common genetic condition, particularly, as you point out, in people of European descent), which can be tested for relatively easily (and I believe this test should be given before treatment as well).
I believe that I may be one of those people with a cytochrome enzyme p450 issue because I require very low doses of meds usually and develop side effects easily. How would I get this test?
> Not just that: not all types of depression respond well to SSRIs.I would be among those who don't, though I am probably a partial responder.
>but sometimes the TCAs turn out to be the most effective and are tolerated well (particularly if you choose the right TCA for the individual patient -- NOR and DMI are both relatively benign, but DMI can cause more activation and jitters while NOR has more sedating and anticholinergic effects, although these are mild with both drugs).
Elizabeth: I am on currently on Selegiline, Adderral and Neurontin. I have played with varying doses of each of these trying to find the "right" combo, without success. I increase the Neurontin and get sedated; increase the Adderral or Selegiline and my physical anxiety becomes unbearable. As it is I do not have sufficient mood support and am hyperventilating as well. I hate the thought of a washout and a long "start up" time. It's summer; I have kids. I'm diagnosed with depression and the anxiety is a new component that started last November with Moclobemide and has never gone away--even when I am drug free. So can I augment with something? I've tried Lomictal and Depokote in place of the Neurontin (no go) and tried Dexidrine in place of the Adderral (no go). Also tried T3. I've been playing with the stimulants and anti-convulsants for about 6 months and nothing has really held it's own. Is it time to move on to a TCA? (which given the withdrawal reports on Parnate seems like a better way to go). How long do TCA's take to become effective?
Also--if you don't mind--what is the difference between major depression and meloncholy depression.
Posted by pellmell on June 30, 2001, at 12:35:23
In reply to Re: TCAs do have their good points » Sunnely, posted by Elizabeth on June 29, 2001, at 18:50:34
Elizabeth, Sunnely...fascinating discussion.
Thanks for sharing with us that triple-scoop bananna split of yummy pharmaceutical info!
-pm
Mmmm...psychotropic ice cream...
Posted by Indubious on July 1, 2001, at 2:53:46
In reply to Re: Great xchange: comments Qs » Elizabeth, posted by Lorraine on June 30, 2001, at 12:26:10
> > SSRIs have their own side effects which should not be ignored and which make them less tolerable for many patients than the preferred TCAs (nortriptyline, desipramine).
Desipramine is my TCA of choice. SSRI's have not been good for me. The orthostatic hypotension has resulted in two falls, one that could have killed me. DMI, I think that is how it's referred to, has worked every time I've used it. My depressions are spent in bed mostly, crying alot, I do work, I have to. Wellbutrin was totally worthless, even at 450 mg, I took Serzone 400 mg a day, split dose for 3 years, but it occurred to me, it was as if I had been lobotomized, like a stepford person, no real emotion, apathetic, but not crying...creepy really. I have side effects from DMI, it makes my heart race, I'm a 45 yo woman that smokes, but it's the only thing that works. Maybe reboxetine would but it's not available here. I don't understand the chemistry of it, I know it's a norepinephrine thing and not a serotonin thing. If the FDA would approve these cleaner drugs, we might not have to deal with these dangerous side effects. As it stands, I don't feel like I have a choice.
Some patients even prefer tricyclics with more side effects, such as imipramine, doxepin, protriptyline or amitriptyline, to the SSRIs.
>
> None of the SSRIs have worked for me; Effexor worked first time with intolerable side effects (40 lb weight gain; sexual dysfunction); Wellbutrin and Serzone also don't work for me. I'm knocking at TCAs door, I'm afraid.
>
> >
> > Differences among the various SSRIs in their propensity to cause characteristic side effects are less predictable
>
> OK. How about Effexor reset my anger set point so that I just NEVER got angry and, for the first time in my life, could not understand why other people created so much havor in their lives with anger. Or, Wellbutrin made me "jealous", which is not typically one of my issues and also made me compulsive about time--shock the h*** out of my hubby when I was the first one in the car for an outting or yelling at everyone else to get in the car for gods sake because WE ARE GOING TO BE LATE. These experiences though have made me very tolerant of other people (ie my time police husband) and their "peculiarities" which I now understand may not be changable.
>
>
> > The safety issue is more generalisable, although it should be emphasised that tricyclics *can* be used safely with appropriate monitoring and consideration for individual patient characteristics (such as the risk of suicide attempts, various cardiac risk factors, the possibility of a seizure disorder, use of other drugs, etc.).
>
> With Wellbutrin, I outright hallucinated when I went from a dark room into a light room or upon awaking in the morning (i now believe that this may have been seizure like activity). Imagine the hazard of driving like that a night with headlights coming at you
>
> >In practise (and this may be the most practical way to go about using TCAs), doctors usually resort to serum level monitoring only if there are specific risk factors such as other drugs or medical conditions (the person should be checked for these *before* trying TCA therapy), or deficiency in the cytochrome enzyme p450 2d6 (a fairly common genetic condition, particularly, as you point out, in people of European descent), which can be tested for relatively easily (and I believe this test should be given before treatment as well).
>
> I believe that I may be one of those people with a cytochrome enzyme p450 issue because I require very low doses of meds usually and develop side effects easily. How would I get this test?
>
>
>
> > Not just that: not all types of depression respond well to SSRIs.
>
> I would be among those who don't, though I am probably a partial responder.
>
> >but sometimes the TCAs turn out to be the most effective and are tolerated well (particularly if you choose the right TCA for the individual patient -- NOR and DMI are both relatively benign, but DMI can cause more activation and jitters while NOR has more sedating and anticholinergic effects, although these are mild with both drugs).
>
> Elizabeth: I am on currently on Selegiline, Adderral and Neurontin. I have played with varying doses of each of these trying to find the "right" combo, without success. I increase the Neurontin and get sedated; increase the Adderral or Selegiline and my physical anxiety becomes unbearable. As it is I do not have sufficient mood support and am hyperventilating as well. I hate the thought of a washout and a long "start up" time. It's summer; I have kids. I'm diagnosed with depression and the anxiety is a new component that started last November with Moclobemide and has never gone away--even when I am drug free. So can I augment with something? I've tried Lomictal and Depokote in place of the Neurontin (no go) and tried Dexidrine in place of the Adderral (no go). Also tried T3. I've been playing with the stimulants and anti-convulsants for about 6 months and nothing has really held it's own. Is it time to move on to a TCA? (which given the withdrawal reports on Parnate seems like a better way to go). How long do TCA's take to become effective?
>
> Also--if you don't mind--what is the difference between major depression and meloncholy depression.
Posted by Lorraine on July 1, 2001, at 11:13:39
In reply to Re: Great xchange: comments Qs, posted by Indubious on July 1, 2001, at 2:53:46
> Desipramine is my TCA of choice. SSRI's have not been good for me. The orthostatic hypotension has resulted in two falls, one that could have killed me. DMI, I think that is how it's referred to, has worked every time I've used it. I have side effects from DMI, it makes my heart race.**********************
Thanks for sharing your experiences. Is there nothing you can take for the orthohypotension? (I think I have read that drinking a lot of water can help because it increases the blood volume in the veins.) The racing heart must be troublesome. I know that omega 3 is supposed to be good for heart beat irregularities. Is yours just racing (this, alone, might drive me nuts) or irregular? How quickly did DMI become effective? Does it have sexual dysfunction as a side effect? What about weight gain? I'm 48. When did your depression start? Mine started when I became perimenopausal at about 43, although my gyn was unwilling to acknowledge that that's what was going on. It could be a component with you. If so, estrogen might help, which in turn might allow you to lower your dosage and reduce the side effects. (Just a possibility.) The smoking is increasing your heart rate too. Course, because I started getting anxiety sort of attacks, I had to give up caffiene. I resent each one of these little comfort I give up.
Posted by Lorraine on July 1, 2001, at 11:15:34
In reply to Re: Great xchange: comments Qs » Elizabeth, posted by Lorraine on June 30, 2001, at 12:26:10
I am bringing my 6/30 post to the top in hopes of a response:-)
> > SSRIs have their own side effects which should not be ignored and which make them less tolerable for many patients than the preferred TCAs (nortriptyline, desipramine). Some patients even prefer tricyclics with more side effects, such as imipramine, doxepin, protriptyline or amitriptyline, to the SSRIs.
>
> None of the SSRIs have worked for me; Effexor worked first time with intolerable side effects (40 lb weight gain; sexual dysfunction); Wellbutrin and Serzone also don't work for me. I'm knocking at TCAs door, I'm afraid.
>
> >
> > Differences among the various SSRIs in their propensity to cause characteristic side effects are less predictable
>
> OK. How about Effexor reset my anger set point so that I just NEVER got angry and, for the first time in my life, could not understand why other people created so much havor in their lives with anger. Or, Wellbutrin made me "jealous", which is not typically one of my issues and also made me compulsive about time--shock the h*** out of my hubby when I was the first one in the car for an outting or yelling at everyone else to get in the car for gods sake because WE ARE GOING TO BE LATE. These experiences though have made me very tolerant of other people (ie my time police husband) and their "peculiarities" which I now understand may not be changable.
>
>
> > The safety issue is more generalisable, although it should be emphasised that tricyclics *can* be used safely with appropriate monitoring and consideration for individual patient characteristics (such as the risk of suicide attempts, various cardiac risk factors, the possibility of a seizure disorder, use of other drugs, etc.).
>
> With Wellbutrin, I outright hallucinated when I went from a dark room into a light room or upon awaking in the morning (i now believe that this may have been seizure like activity). Imagine the hazard of driving like that a night with headlights coming at you
>
> >In practise (and this may be the most practical way to go about using TCAs), doctors usually resort to serum level monitoring only if there are specific risk factors such as other drugs or medical conditions (the person should be checked for these *before* trying TCA therapy), or deficiency in the cytochrome enzyme p450 2d6 (a fairly common genetic condition, particularly, as you point out, in people of European descent), which can be tested for relatively easily (and I believe this test should be given before treatment as well).
>
> I believe that I may be one of those people with a cytochrome enzyme p450 issue because I require very low doses of meds usually and develop side effects easily. How would I get this test?
>
>
>
> > Not just that: not all types of depression respond well to SSRIs.
>
> I would be among those who don't, though I am probably a partial responder.
>
> >but sometimes the TCAs turn out to be the most effective and are tolerated well (particularly if you choose the right TCA for the individual patient -- NOR and DMI are both relatively benign, but DMI can cause more activation and jitters while NOR has more sedating and anticholinergic effects, although these are mild with both drugs).
>
> Elizabeth: I am on currently on Selegiline, Adderral and Neurontin. I have played with varying doses of each of these trying to find the "right" combo, without success. I increase the Neurontin and get sedated; increase the Adderral or Selegiline and my physical anxiety becomes unbearable. As it is I do not have sufficient mood support and am hyperventilating as well. I hate the thought of a washout and a long "start up" time. It's summer; I have kids. I'm diagnosed with depression and the anxiety is a new component that started last November with Moclobemide and has never gone away--even when I am drug free. So can I augment with something? I've tried Lomictal and Depokote in place of the Neurontin (no go) and tried Dexidrine in place of the Adderral (no go). Also tried T3. I've been playing with the stimulants and anti-convulsants for about 6 months and nothing has really held it's own. Is it time to move on to a TCA? (which given the withdrawal reports on Parnate seems like a better way to go). How long do TCA's take to become effective?
>
> Also--if you don't mind--what is the difference between major depression and meloncholy depression.
Posted by Indubious on July 1, 2001, at 15:05:32
In reply to Re: Great xchange: comments Qs » Indubious, posted by Lorraine on July 1, 2001, at 11:13:39
>
> > Desipramine is my TCA of choice. SSRI's have not been good for me. The orthostatic hypotension has resulted in two falls, one that could have killed me. DMI, I think that is how it's referred to, has worked every time I've used it. I have side effects from DMI, it makes my heart race.
>
> **********************
>
> Thanks for sharing your experiences. Is there nothing you can take for the orthohypotension? (I think I have read that drinking a lot of water can help because it increases the blood volume in the veins.)I drink alot of water already, I take topomax and this is the south so with the threat of kidney stones, well I drink alot of water.
The racing heart must be troublesome. I know that omega 3 is supposed to be good for heart beat irregularities. Is yours just racing (this, alone, might drive me nuts) or irregular?
Actually, it's the resting heart rate, my pdoc never checked it, my primary care doc did, it was 120 beats per...she made me stay for an EKG, an ECHO...I don't notice it all the time..
How quickly did DMI become effective?
The crying stopped in 48 hours, I was wanting to get OUT of bed after I woke up on the third day....after a week and a half I really was feeling pretty human again.
Does it have sexual dysfunction as a side effect?
I can't speak to that, I can't remember what a sex drive is, and it's isn't important enough to me to address, don't know if this is related to PTSD due to long term DV, could be hormonal...don't know, don't care....have just begun therapy to deal with the ptsd..will see what happens...but it was gone long before this.
What about weight gain? No..not really...Serzone was bad...I put on 50 pounds..
I'm 48. When did your depression start?
In my early 20's...
Mine started when I became perimenopausal at about 43, although my gyn was unwilling to acknowledge that that's what was going on. It could be a component with you.
I had a hysterectomy at 40, but still have my ovaries so , yeah, it could be...have an exam scheduled next mo...I guess a blood test will tell...
If so, estrogen might help, which in turn might allow you to lower your dosage and reduce the side effects. (Just a possibility.) The smoking is increasing your heart rate too.
I know...I'm one of those smokers..I quit for a year, I smoke for six mo...I quit for a couple of years...my anxiety gets the best of me...I'm a very high stress person and it immobilizes me, smoking is my familiar stress response which sucks because I hate it.
Course, because I started getting anxiety sort of attacks, I had to give up caffiene. I resent each one of these little comfort I give up.
I absolutely understand that!
I responded to this thread because some people seem to feel a need to spread the notion that TCA's are evil and hurt people and bla bla bla...well, the only AD's that ever hurt me or made me sick were SSRI's and the only drug that ever saved me from myself was a TCA. I hope you find the information you need to make a good decision.
Posted by Lorraine on July 1, 2001, at 23:17:00
In reply to Re: Great xchange: comments Qs, posted by Indubious on July 1, 2001, at 15:05:32
> I drink alot of water already, I take topomax and this is the south so with the threat of kidney stones, well I drink alot of water.
*************
Well, my memory is not what it used to be. I meant to eat a lot of salt--which makes you retain water so that your blood volume increases.
I really appreciate your response. It does help me put some of my (probably irrational) fears into perspective.
Posted by Elizabeth on July 3, 2001, at 14:38:51
In reply to Re: Elizabeth-hold my hand on this one, please, posted by Lorraine on July 1, 2001, at 11:15:34
Oops, was there a post I should have responded to but didn't? I'm sorry about that!
> None of the SSRIs have worked for me; Effexor worked first time with intolerable side effects (40 lb weight gain; sexual dysfunction); Wellbutrin and Serzone also don't work for me. I'm knocking at TCAs door, I'm afraid.
Same general situation here -- SSRIs and Serzone don't seem to do anything, Effexor caused miscellaneous bad things to happen ("serotonin syndrome"), Wellbutrin just made it worse. The MAOIs have been relatively helpful, but they don't solve the problem completely either (still have lots of fatigue, disinterest). I just started on desipramine (just 25mg). It doesn't seem to have any side effects so far. I feel like I should give the TCAs a chance before throwing in the towel altogether.
> OK. How about Effexor reset my anger set point so that I just NEVER got angry and, for the first time in my life, could not understand why other people created so much havor in their lives with anger.
That's an interesting one. Did it bother you, or did you feel better?
> Or, Wellbutrin made me "jealous", which is not typically one of my issues and also made me compulsive about time--shock the h*** out of my hubby when I was the first one in the car for an outting or yelling at everyone else to get in the car for gods sake because WE ARE GOING TO BE LATE.
Wellbutrin is a weak stimulant (structurally, it's related to methcathinone ("khat")). As such, it can be expected to make obsessive-compulsive type thoughts and behaviours worse rather than better. A number of people become irritable (or more irritable) on it, although I don't recall specifics.
> These experiences though have made me very tolerant of other people (ie my time police husband) and their "peculiarities" which I now understand may not be changable.
Hmm. I think that if those "traits" could be brought on by drugs, then they probably could be alleviated by drugs too (different drugs, obviously). We've all heard the stories of dramatic personality change in response to SSRIs; MAOIs, Wellbutrin, Effexor, benzos, etc. can definitely bring on major changes too.
A question I've always had in my mind is, can people who experience "personality changes" on drugs use that experience to teach themselves to be different without the drugs?
> With Wellbutrin, I outright hallucinated when I went from a dark room into a light room or upon awaking in the morning (i now believe that this may have been seizure like activity).
What sort of hallucinations? (if you don't mind talking about it)
> Imagine the hazard of driving like that a night with headlights coming at you
I don't drive, but I certainly can imagine.
> I believe that I may be one of those people with a cytochrome enzyme p450 issue because I require very low doses of meds usually and develop side effects easily. How would I get this test?
A hospital or internal medicine clinic could do it. The only such test that is used clinically that I'm aware of is for CYP 2D6 ("debrisoqin hydroxylase") deficiency. They give you a drug metabolised by CYP 2D6 (I think they usually use dextromethorphan, but I'll use debrisoquin as an example). Then, 8 hours later (the length of the wait may differ depending on the drug used), they check the ratio of the urinary concentration of the drug to the concentration of its main hydroxylated metabolite (e.g., 4-hydroxydebrisoquin). If the ratio is unusually high, it means you failed to metabolise the drug normally. (This could be because you're a slow hydroxylator, or it could be because you're taking another drug that inhibits and/or competes for the enzyme.)
> Elizabeth: I am on currently on Selegiline, Adderral and Neurontin. I have played with varying doses of each of these trying to find the "right" combo, without success. I increase the Neurontin and get sedated; increase the Adderral or Selegiline and my physical anxiety becomes unbearable.
How rapidly do you try increasing one or the other of these? Have you tried, for example, increasing the Neurontin by 100 mg (taking the extra 100 mg at bedtime, of course)? Sedation and activation are side effects to which people often grow tolerant; it might just require patience.
You could also try increasing both the Neurontin and one of the stimulant drugs simultaneously, by a small amount (100 mg of Neurontin and, e.g., 2.5 mg of Adderall). Alternatively, you could try adding a different drug that is neutral with regard to activation/sedation. (Although I hate to suggest that to someone who's already on 3 different meds.)
> As it is I do not have sufficient mood support and am hyperventilating as well.
Tried Inderal for the hyperventilation? (Works well for me -- I had some hyperventilation problems when I first started taking Parnate.)
> I hate the thought of a washout and a long "start up" time. It's summer; I have kids.
I understand.
> I'm diagnosed with depression and the anxiety is a new component that started last November with Moclobemide and has never gone away--even when I am drug free.
Agitation/jitteriness is a common side effect of moclobemide (one of the many reasons I decided not to go to the trouble of trying it!).
> So can I augment with something?
Yes. I don't think that other anticonvulsants would substitute for the Neurontin, though. What about adding Klonopin on an as-needed basis?
> Is it time to move on to a TCA? (which given the withdrawal reports on Parnate seems like a better way to go). How long do TCA's take to become effective?
A few weeks, same as most antidepressants. You could probably safely add one of the ones with little effect on serotonin (like nortriptyline or desipramine) without having to go off the MAOI.
MAOI withdrawal sucks, but it's not unmanageable and usually doesn't last very long. (I think that tapering is best, but not a very slow taper like you would use if you were going off, say, Xanax.) I find benzos helpful (that, and staying away from other people as much as possible!).
> Also--if you don't mind--what is the difference between major depression and meloncholy depression.
"Major depression" is a very broad category. "Melancholic depression" is a subtype of major depression that is characterised by nonreactive mood (i.e., pleasant occurrences don't cheer you up significantly), complete or near-complete loss of the ability to feel pleasure, early-morning awakenings, feeling worst in the morning, appetite loss, psychomotor agitation or retardation, and inappropriate or excessive guilt. Melancholic depressions are experienced as being qualitatively different from feelings of grief or loss: the depression can't be described by comparison to other feelings the person has had (whereas nonmelancholic depressions may resemble grief, in quality if not in magnitude).
Some data suggest that TCAs, Remeron, and Effexor work better than SSRIs do for melancholic depression. The efficacy of ECT is best-established in this subtype. I would expect MAOIs to work too (possibly in higher dose ranges than for nonmelancholic depression), but there has been little research on MAOIs for melancholic depression. (I'd like to see a well-designed and -executed RCT comparing, say, Parnate to imipramine.)
I hope this helps. Keep in touch. :-)
-elizabeth
Posted by Elizabeth on July 3, 2001, at 14:59:09
In reply to Re: Great xchange: comments Qs, posted by Indubious on July 1, 2001, at 15:05:32
Hi. Just so you know, it's sort of hard to tell who said what in this exchange because of the way the quoting is done. (I guess I could go back and read previous posts, but, well, you know.)
> > Thanks for sharing your experiences. Is there nothing you can take for the orthohypotension? (I think I have read that drinking a lot of water can help because it increases the blood volume in the veins.)
>
> I drink alot of water already, I take topomax and this is the south so with the threat of kidney stones, well I drink alot of water.Some people find salt tablets helpful; keeping yourself well-hydrated is crucial. It's also helpful to make a practise of getting up very slowly (especially first thing in the morning).
There's a steroid called fludrocortisone (Florinef) that you can use if the OH is really bad and other strategies don't work.> The racing heart must be troublesome. I know that omega 3 is supposed to be good for heart beat irregularities. Is yours just racing (this, alone, might drive me nuts) or irregular?
If it's racing, a beta blocker should help (these also help with tremors, rapid breathing or hyperventilating, etc.). If it's irregular, or if you're not sure, I recommend seeing a GP or cardiologist to try to figure out what type of abnormal rhythm you have, as different types of arrhythmias require different treatments (and the treatment for one type may worsen another type).
> Actually, it's the resting heart rate, my pdoc never checked it, my primary care doc did, it was 120 beats per...she made me stay for an EKG, an ECHO...I don't notice it all the time..
Good for your GP. What did the EKG and echo show?
> Does it have sexual dysfunction as a side effect?
Desipramine is less likely than most other ADs to cause this type of problem. Sexual dysfunction can be linked to serotonin (as with SSRIs and MAOIs), or it can be caused by anticholinergic drugs (like TCAs, drugs which block muscarinic acetylcholine receptors). Of all the TCAs, desipramine has the weakest anticholinergic and antihistamininic activity, and it is among the most selective norepinephrine reuptake inhibitors. It also is less likely to cause weight gain, dry mouth, constipation, etc. than other TCAs.
> > I'm 48. When did your depression start?
>
> In my early 20's...Age of onset makes a big difference, for one reason or other, in presentation, time course, and response to various treatments. (My depression was first diagnosed when I was 14, but I believe I had an episode when I was 10 or 11.)
> If so, estrogen might help, which in turn might allow you to lower your dosage and reduce the side effects. (Just a possibility.) The smoking is increasing your heart rate too.
Taking estrogens can be a bad thing if you smoke. But yeah, hormone supplementation can have an AD effect for some people.
> I know...I'm one of those smokers..I quit for a year, I smoke for six mo...I quit for a couple of years...my anxiety gets the best of me...I'm a very high stress person and it immobilizes me, smoking is my familiar stress response which sucks because I hate it.
Have you tried junk food as an alternative? < g > (Sorry.) Seriously -- Wellbutrin is supposed to be a good way to quit tobacco and stay off it; selegiline might help as well.
> > Course, because I started getting anxiety sort of attacks, I had to give up caffiene. I resent each one of these little comfort I give up.
I don't exactly resent them, but I get sad when I think about it.
> I responded to this thread because some people seem to feel a need to spread the notion that TCA's are evil and hurt people and bla bla bla...well, the only AD's that ever hurt me or made me sick were SSRI's and the only drug that ever saved me from myself was a TCA.
Yeah; TCAs are more toxic and more dangerous in overdose than other ADs (yes, including MAOIs), but they're a good, viable option for many people, and the only option for some. They should never be ruled out completely (especially since there are so many to choose from).
> I hope you find the information you need to make a good decision.
I second that.
-elizabeth
Posted by Lorraine on July 3, 2001, at 20:00:38
In reply to I'll hold your hand if you'll hold mine » Lorraine, posted by Elizabeth on July 3, 2001, at 14:38:51
elizabeth: I'm honored to hold your hand. I'm going to try the propranolol. We'll see. I'm off for 5 days. I'll give this post the detailed response it deserves when I get back. Meanwhile, thanx.
Posted by Elizabeth on July 6, 2001, at 22:49:33
In reply to Re: I'll hold your hand if you'll hold mine » Elizabeth, posted by Lorraine on July 3, 2001, at 20:00:38
> elizabeth: I'm honored to hold your hand.
< giggle >
> I'm going to try the propranolol. We'll see. I'm off for 5 days. I'll give this post the detailed response it deserves when I get back. Meanwhile, thanx.
Sure thing.
-elizabeth
Posted by Lorraine on July 8, 2001, at 22:04:27
In reply to I'll hold your hand if you'll hold mine » Lorraine, posted by Elizabeth on July 3, 2001, at 14:38:51
> Oops, was there a post I should have responded to but didn't? I'm sorry about that!
This is good to know. I thought it might have been intentional. What can I say? Depression talks and I listen.
>
> > None of the SSRIs have worked for me; Effexor worked first time with intolerable side effects (40 lb weight gain; sexual dysfunction); Wellbutrin and Serzone also don't work for me. I'm knocking at TCAs door, I'm afraid.
>
> Same general situation here -- SSRIs and Serzone don't seem to do anything, Effexor caused miscellaneous bad things to happen ("serotonin syndrome"), Wellbutrin just made it worse. The MAOIs have been relatively helpful, but they don't solve the problem completely either (still have lots of fatigue, disinterest). I just started on desipramine (just 25mg). It doesn't seem to have any side effects so far. I feel like I should give the TCAs a chance before throwing in the towel altogether.I will be interested in your progress because desipramine is my next stop. What happens when you throw in the towel?
>
> > OK. How about Effexor reset my anger set point so that I just NEVER got angry and, for the first time in my life, could not understand why other people created so much havor in their lives with anger.
>
> That's an interesting one. Did it bother you, or did you feel better?It made me feel like I finally "got" something that had elluded me. It's better to be without anger generally--you still need to confront people and so on but you are not angry and that does not get in the way as it is prone to do.
>
> > Or, Wellbutrin made me "jealous", which is not typically one of my issues and also made me compulsive about time--shock the h*** out of my hubby when I was the first one in the car for an outting or yelling at everyone else to get in the car for gods sake because WE ARE GOING TO BE LATE.
>
> Wellbutrin is a weak stimulant (structurally, it's related to methcathinone ("khat")). As such, it can be expected to make obsessive-compulsive type thoughts and behaviours worse rather than better. A number of people become irritable (or more irritable) on it, although I don't recall specifics.>
> > These experiences though have made me very tolerant of other people (ie my time police husband) and their "peculiarities" which I now understand may not be changable.
>
> Hmm. I think that if those "traits" could be brought on by drugs, then they probably could be alleviated by drugs too (different drugs, obviously). We've all heard the stories of dramatic personality change in response to SSRIs; MAOIs, Wellbutrin, Effexor, benzos, etc. can definitely bring on major changes too.Oh yeah, this is also true, but the question becomes when does a trait rise to the level of requiring medication? When it annoys me? :-)
>
> A question I've always had in my mind is, can people who experience "personality changes" on drugs use that experience to teach themselves to be different without the drugs?Yes. I am more punctual now. I "get" it. I fully realize now how anger gets in the way of communicating. But, since I am no longer on Effexor, I blow my top occassionally and unfortunately give people a bit more than their share of my temper when I blow. Which means I have to apologize (don't you hate that? especially if you were right, but blew it on the delivery?)
>
> > With Wellbutrin, I outright hallucinated when I went from a dark room into a light room or upon awaking in the morning (i now believe that this may have been seizure like activity).
>
> What sort of hallucinations? (if you don't mind talking about it)The hallucinations were dancing lights--like the light reflecting off the walls refracting into dazzling, bouncing displays. I had visual trails as well--the type you get on MJ--with the movement of my hands or body sometimes. Nothing scarey. I hallucinate on Neurontin as well from time to time before sleep--but here vivid colorful images and again not scarey although sometimes a bit more gorey than I would prefer.
>
> > Imagine the hazard of driving like that a night with headlights coming at you
>
> I don't drive, but I certainly can imagine.Why not? (if you don't mind the intrusion?)
>
> > I believe that I may be one of those people with a cytochrome enzyme p450 issue because I require very low doses of meds usually and develop side effects easily. How would I get this test?
>
> A hospital or internal medicine clinic could do it. The only such test that is used clinically that I'm aware of is for CYP 2D6 ("debrisoqin hydroxylase") deficiency. They give you a drug metabolised by CYP 2D6 (I think they usually use dextromethorphan, but I'll use debrisoquin as an example). Then, 8 hours later (the length of the wait may differ depending on the drug used), they check the ratio of the urinary concentration of the drug to the concentration of its main hydroxylated metabolite (e.g., 4-hydroxydebrisoquin). If the ratio is unusually high, it means you failed to metabolise the drug normally. (This could be because you're a slow hydroxylator, or it could be because you're taking another drug that inhibits and/or competes for the enzyme.)Thanks for the info. I'll look into it.
>
> > Elizabeth: I am on currently on Selegiline, Adderral and Neurontin. I have played with varying doses of each of these trying to find the "right" combo, without success. I increase the Neurontin and get sedated; increase the Adderral or Selegiline and my physical anxiety becomes unbearable.
>
> How rapidly do you try increasing one or the other of these? Have you tried, for example, increasing the Neurontin by 100 mg (taking the extra 100 mg at bedtime, of course)? Sedation and activation are side effects to which people often grow tolerant; it might just require patience.
>
> You could also try increasing both the Neurontin and one of the stimulant drugs simultaneously, by a small amount (100 mg of Neurontin and, e.g., 2.5 mg of Adderall). Alternatively, you could try adding a different drug that is neutral with regard to activation/sedation. (Although I hate to suggest that to someone who's already on 3 different meds.)
>These are all great suggestions. Some I've tried (all the dose variations); some I'm reluctant to do but may (adding a nuetral drug--hadn't thought of this--it really is a good idea!)
> > As it is I do not have sufficient mood support and am hyperventilating as well.
>
> Tried Inderal for the hyperventilation? (Works well for me -- I had some hyperventilation problems when I first started taking Parnate.)I am trying Inderal. Interesting drug. does stop the hyperventilating generally (not today). Causes some wild fluctuations in pulse rate (from 60 to 120 in one day). Heart rate goes up very quickly on exertion, but the 120 occurred while waiting in line at KMart. Allows me to sleep normally again without getting up in the middle of the night and staying awake AND I feel rested after the sleep. Trying to figure out how to take it. My script is 10 mg, which I'm supposed to split into 5 mg 2x day. Can't figure out if the 2x day is on waking and before bed or when I take my activating drugs (on waking and 1pm). Also, can't figure out if 3x day is better. What did you do?
> > So can I augment with something?
>
> Yes. I don't think that other anticonvulsants would substitute for the Neurontin, though. What about adding Klonopin on an as-needed basis?I'm afraid of Konopin. Not of becoming addicted, but of the withdrawel if I need to quit using it.
>
> You could probably safely add a TCA one of the ones with little effect on serotonin (like nortriptyline or desipramine) without having to go off the MAOI.That seems to be where my pdoc is heading, which is lovely in terms of washout avoidance.
>
> MAOI withdrawal sucks, but it's not unmanageable and usually doesn't last very long. (I think that tapering is best, but not a very slow taper like you would use if you were going off, say, Xanax.) I find benzos helpful (that, and staying away from other people as much as possible!).I'll keep this in mind when I get there. I have decided that I need some benzos for tough times, dips in the road.
Melancholy does not apply to me--fortunately I guess.
> Some data suggest that TCAs, Remeron, and Effexor work better than SSRIs do for melancholic depression. The efficacy of ECT is best-established in this subtype. I would expect MAOIs to work too (possibly in higher dose ranges than for nonmelancholic depression), but there has been little research on MAOIs for melancholic depression. (I'd like to see a well-designed and -executed RCT comparing, say, Parnate to imipramine.)
>what is RCT? And, yeah, wouldn't we all like to see some studies after FDA approval?
> I hope this helps. Keep in touch. :-)
>Elizabeth--it helps a lot. Sometimes I just get paralysed with fear of making a decision--just stuck and any nudge helps. :-)
Posted by Elizabeth on July 9, 2001, at 21:45:18
In reply to Re: I'll hold your hand if you'll hold mine » Elizabeth, posted by Lorraine on July 8, 2001, at 22:04:27
> This is good to know. I thought it might have been intentional. What can I say? Depression talks and I listen.
Low self-esteem, you mean (in particular)? Don't listen to it too closely.
> I will be interested in your progress because desipramine is my next stop. What happens when you throw in the towel?
Despite having tried a lot of things, I'm a long way from throwing in the towel.
[re Effexor]
> It made me feel like I finally "got" something that had elluded me. It's better to be without anger generally--you still need to confront people and so on but you are not angry and that does not get in the way as it is prone to do.I agree, actually. Confrontation is much more effective when not accompanied by emotional outbursts.
> Oh yeah, this is also true, but the question becomes when does a trait rise to the level of requiring medication? When it annoys me? :-)
"You know it when you see it." (Attributed to various people as a legal definition for "pornography.")
> Yes. I am more punctual now. I "get" it. I fully realize now how anger gets in the way of communicating.
Some people have a really hard time getting that. The way they describe it to me (and I feel this way about some things, too) is that there must be a manual for "how to be a human being" that everybody else got but they didn't. For others, it's something they learn as they mature, and for a few lucky ones, it just comes naturally.
> But, since I am no longer on Effexor, I blow my top occassionally and unfortunately give people a bit more than their share of my temper when I blow. Which means I have to apologize (don't you hate that? especially if you were right, but blew it on the delivery?)
Heh. That does suck, but I try to take it in stride. I'm not so big on the right-wrong/win-lose/etc. thing; I try to do my best, and when I screw up I try to be graceful about it. That's all one can do, really.
[re Wellbutrin]
> The hallucinations were dancing lights--like the light reflecting off the walls refracting into dazzling, bouncing displays. I had visual trails as well--the type you get on MJ--with the movement of my hands or body sometimes.I think those are more what would be described as "illusions" than outright hallucinations -- you saw things in subtly different ways, but you didn't really see things that just weren't there at all (if that makes sense). I saw visual trails when I had the serotonin syndrome (on Effexor XR), BTW. I've heard speculation that LSD (a serotonin-related psychedelic drug which also tends to cause visual trails, among other things) works by blocking some sort of sensory filtering mechanism.
I also had some innocuous auditory illusions -- hearing music in the shower -- on Nardil. I interpreted it as my mind trying to make sense out of the chaos of white noise that the shower makes.
> Nothing scarey. I hallucinate on Neurontin as well from time to time before sleep--but here vivid colorful images and again not scarey although sometimes a bit more gorey than I would prefer.
Those might be hypnagogic hallucinations. These are visions that happen as you're falling asleep. They're usually not narrative like REM sleep dreams are. I've had them a number of times. (Most people have them at some point, but they're much more common among people who have narcolepsy. My guess is that in my case they're related to my sleep disorder.)
> > > Imagine the hazard of driving like that a night with headlights coming at you
> >
> > I don't drive, but I certainly can imagine.
>
> Why not? (if you don't mind the intrusion?)Left home (suburbs) for college when I was 16. Boston (where I went to college) has good public transit, so I never needed to learn to drive (I'm trying to learn now, although it's a pain).
[re cytochrome p450 2d6 deficiency test]
> Thanks for the info. I'll look into it.It's not a common test; a doctor might not be interested in ordering it unless there's a really good reason to believe you might be a slow metaboliser. (What counts as "really good" probably depends on the doctor.)
> > Tried Inderal for the hyperventilation? (Works well for me -- I had some hyperventilation problems when I first started taking Parnate.)
>
> I am trying Inderal. Interesting drug. does stop the hyperventilating generally (not today).I like it for as-needed use. I wouldn't want to take it around the clock, though. It does lower your pulse (which can be a good thing if you're on MAOIs or TCAs, actually). It can cause nightmares as a side effect, which isn't too great.
> Trying to figure out how to take it.
Based on the duration of action, most people with hypertension take it 4 times daily. I take 10-20 mg as needed.
> I'm afraid of Konopin. Not of becoming addicted, but of the withdrawel if I need to quit using it.
Understandable. My experience has been that you can take it on a short-term trial basis -- for a week, say -- without any withdrawal symptoms. (I took it for close to a month once without having problems stopping, but I'm not sure this would be so harmless for everybody.)
> > You could probably safely add a TCA one of the ones with little effect on serotonin (like nortriptyline or desipramine) without having to go off the MAOI.
>
> That seems to be where my pdoc is heading, which is lovely in terms of washout avoidance.I'm considering starting Parnate again cautiously if I tolerate the desipramine and if the DMI helps somewhat. MAOI-TCA combinations generally aren't much of an improvement over one drug or the other, but for some people they work wonders.
> Melancholy does not apply to me--fortunately I guess.
(Do you mean "melancholia," "melancholic featueres," "melancholic depression," etc.?)
> what is RCT?
"randomised controlled trial"
> And, yeah, wouldn't we all like to see some studies after FDA approval?
Hey, occasionally it happens! < g >
> > I hope this helps. Keep in touch. :-)
>
> Elizabeth--it helps a lot.That's nice to read. Thanks.
> Sometimes I just get paralysed with fear of making a decision--just stuck and any nudge helps. :-)
That's a depression thing (indecisiveness). It's a big problem for me too.
-elizabeth
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