![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 9 to 33 of 434. Go back in thread:
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
Posted by Lorraine on July 10, 2001, at 14:27:49
In reply to Re: I'll hold your hand if you'll hold mine » Lorraine, posted by Elizabeth on July 9, 2001, at 21:45:18
> [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.You're right--there are more like an interference with proper eye functioning and yes, they do remind me of LSD trails--when I was much younger in the 60s. I suspect that once you have taken LSD illusions and so forth is a state much more easily slipped into. (Sort like once your mind knows the way there, it's easy to return.)
>
> 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.I think I've had something like this before.
[re: hallucinate on Neurontin]
> 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.This sounds right.
> {re: learning to drive}I think it's much easier when you are younger.
> [re cytochrome p450 2d6 deficiency test]
> 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.)Then I suspect they won't do it on me.
[re Inderal] 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.
Well, my hyperventilating is not short term unfortunately and I suspect that the Inderal isn't going to be my long term solution because of the pulse lowering effect--it kind of takes the wind out of my sails. Although it REALLY helps with the sleeping. So I may end up using it at night. I think I need to get on a med that handles the hyperventilating and the depression at the same time. So, given my problems with SSRI's, it's TCA time I think.
> > Trying to figure out how to take Inderal.
>
> Based on the duration of action, most people with hypertension take it 4 times daily. I take 10-20 mg as needed.That would really knock me out. I'm at 5 mg 2x day and it knocks me out and, yet, doesn't completely solve the hyperventilating thing.
{ re: Konopin.} My experience has been that you can take it on a short-term trial basis -- for a week, say -- without any withdrawal symptoms.My hunch is that I should have it in the med cabinet for emergencies (family visits).
[re: MAOI-TCA combinations] generally aren't much of an improvement over one drug or the other, but for some people they work wonders.
Well, I'm hoping that I just transition over to the TCA and wean off the MAO. I think the Selegiline is making the hyperventilating worse. How is the DMI working for you?
> (Do you mean "melancholia," "melancholic featueres," "melancholic depression," etc.?)
Yeah, that's what I mean. Sounds like it is a particularly tough kind of depression.
> That's a depression thing (indecisiveness). It's a big problem for me too.
Boy, isn't that the truth. Decisions can seem like riddles and then poof when the depression lifts the knots unravel themselves before your eyes and you wonder what the fuss was all about.
Lorraine
Posted by Elizabeth on July 11, 2001, at 1:22:15
In reply to Re: I'll hold your hand if you'll hold mine » Elizabeth, posted by Lorraine on July 10, 2001, at 14:27:49
[re visual illusions from Wellbutrin]
> You're right--there are more like an interference with proper eye functioning and yes, they do remind me of LSD trails--when I was much younger in the 60s. I suspect that once you have taken LSD illusions and so forth is a state much more easily slipped into. (Sort like once your mind knows the way there, it's easy to return.)Maybe, but it's quite possible to experience "trails" without ever having taken psychedelics of any kind.
> > {re: learning to drive}
> I think it's much easier when you are younger.I think that learning in general is much easier when you're younger.
> > [re cytochrome p450 2d6 deficiency test]
> > 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.)
>
> Then I suspect they won't do it on me.If there's a specific reason (unusually extreme side effects on low doses of TCAs, lack of effect on high doses of TCAs, or other relevant drug reactions) they might. An alternative is TCA serum level monitoring (this is mainly useful for imipramine, desipramine, amitriptyline, and nortriptyline, as therapeutic ranges haven't really been established for the other TCAs).
> > [re Inderal]
> Well, my hyperventilating is not short term unfortunately and I suspect that the Inderal isn't going to be my long term solution because of the pulse lowering effect--it kind of takes the wind out of my sails.It can do that, although I would expect you to adjust to the effect. There are alternative beta blockers, including one (nadolol?) that is non-cardioselective (like propranolol) but longer-acting than propranolol and so is better suited for long-term use.
> Although it REALLY helps with the sleeping.
That's great. I never heard of anyone taking propranolol for sleep disorders (especially given its propensity to cause nightmares), but I'll keep that in mind. (Maybe I should give it a try.)
> I think I need to get on a med that handles the hyperventilating and the depression at the same time. So, given my problems with SSRI's, it's TCA time I think.
I'm not sure those would reduce the hyperventilation. They're worth a try, though. For your purposes, imipramine or nortripytline might be the best choices: they have moderate effects at muscarinic ACh receptors (anticholinergic side effects), H1 receptors (antihistaminic effects -- sedation in particular), and alpha1-adrenergic receptors (blood pressure effects).
My concern is that a TCA would not be an effective drug for you. What can you tell me about your depression (and/or other disorders)?
> That would really knock me out. I'm at 5 mg 2x day and it knocks me out and, yet, doesn't completely solve the hyperventilating thing.
It's too sedating for you, then (5 mg is a very low dose). Consider a different beta blocker, maybe.
> My hunch is that I should have it in the med cabinet for emergencies (family visits).
For my purposes, Xanax is better in emergencies because of the rapid onset of action. But Klonopin works for a long time, and I can see where it might be better for other people. Klonopin is definitely easier to use if you're taking it on a regular, around-the-clock basis, because it needs to be taken 2-3 times/day instead of 4 or so (like Xanax).
> I think the Selegiline is making the hyperventilating worse.
Definitely a possibility. Two of its metabolites (as I'm sure you know) are l-amphetamine and l-methamphetamine. I experienced jitters, agitation, and worsened insomnia and appetite on it.
> How is the DMI working for you?
I'm only up to 75 mg (not a very high dose). I'm supposed to increase by 25 mg every 3 days or so. The side effects (if any) are minimal, at least.
> > (Do you mean "melancholia," "melancholic featueres," "melancholic depression," etc.?)
>
> Yeah, that's what I mean. Sounds like it is a particularly tough kind of depression.It's "classic" depression. It tends to be rather severe, but it responds well to TCAs and ECT. That's why I'm hoping desipramine will be good for me.
> > That's a depression thing (indecisiveness). It's a big problem for me too.
>
> Boy, isn't that the truth. Decisions can seem like riddles and then poof when the depression lifts the knots unravel themselves before your eyes and you wonder what the fuss was all about.Heh. Well put.
-elizabeth
Posted by Lorraine on July 11, 2001, at 10:15:48
In reply to Re: I'll hold your hand if you'll hold mine » Lorraine, posted by Elizabeth on July 11, 2001, at 1:22:15
> > > [re Inderal]
> > Well, my hyperventilating is not short term unfortunately and I suspect that the Inderal isn't going to be my long term solution because of the pulse lowering effect--it kind of takes the wind out of my sails.
>
> It can do that, although I would expect you to adjust to the effect. There are alternative beta blockers, including one (nadolol?) that is non-cardioselective (like propranolol) but longer-acting than propranolol and so is better suited for long-term use.Thanks for the tip. I'll look into nadolol.
> > I never heard of anyone taking propranolol for sleep disorders (especially given its propensity to cause nightmares), but I'll keep that in mind. (Maybe I should give it a try.)My hunch is the sleeping issue with me (which is a very recent thing) is due to being overstimulated by my meds and the propranolol cuts through that like a hot knife thru butter < vbg >
[re: TCAs and hyperventilating]
> For your purposes, imipramine or nortripytline might be the best choices: they have moderate effects at muscarinic ACh receptors (anticholinergic side effects), H1 receptors (antihistaminic effects -- sedation in particular), and alpha1-adrenergic receptors (blood pressure effects).
Sounds like weight gain and sedation--(sexual dysfunction as well?) Yeah, I know, picky, picky, picky. But sedation is not good with me.
>
> My concern is that a TCA would not be an effective drug for you. What can you tell me about your depression (and/or other disorders)?I thought you'd never ask < vbg >. My depression is like walking through mud--no energy, weepy weepy hopeless stuff at its worst, poor working memory, impairment of cognitive skills (can not think my way out of a box--this from someone who graduated in the top of her class law school and 15 years later top of class in business school--"of all the things I've lost, it's my mind I miss the most".) What I do when I am depressed is hybernate--all my systems wink out bit-by-bit until I sit alone (social withdrawal) in a room (no activity) in the dark. I do not have eating disruption or sleep disruption normally. Since last November anxiety (especially physical as in hyperventilating--but also some mental, I don't read the newspaper, I can't follow the stock market--I used to run some portfolios for friends, family and so forth). I am not a big ruminator. Before the anxiety hit, after reading Stahl's book I decided I was NE deficient as opposed to Serotonin deficient.
At the end of the day, it may be MAOs that make the difference for me, although the Selegiline and Moclobemide were not the ticket. I think I should give the TCAs a try first because of their lower side effect profile, especially desipramine.
>
> [re: low dose propranolol sedating]
> It's too sedating for you, then (5 mg is a very low dose). Consider a different beta blocker, maybe.I'll think about this. The reason I suspect that there may be a P450 issue is because very low doses of meds affect me strongly and I am hypersensitive to side effects.
> For my purposes, Xanax is better in emergencies because of the rapid onset of action. But Klonopin works for a long time, and I can see where it might be better for other people. Klonopin is definitely easier to use if you're taking it on a regular, around-the-clock basis, because it needs to be taken 2-3 times/day instead of 4 or so (like Xanax).Probably Klonopin would do it for me--my emergencies are not very immediate and I took Xanax for a couple of days while I was working (long ago far away on a distant planet) and found it too sedating.
>
> > I think the Selegiline is making the hyperventilating worse.
>
> Definitely a possibility. Two of its metabolites (as I'm sure you know) are l-amphetamine and l-methamphetamine. I experienced jitters, agitation, and worsened insomnia and appetite on it.Yes, but then dexidrine didn't have this effect; nor is adderral having this effect.
>
> > How is the DMI working for you?
>
> I'm only up to 75 mg (not a very high dose). I'm supposed to increase by 25 mg every 3 days or so. The side effects (if any) are minimal, at least.I'll keep my fingers crossed. Low side effects are good. By the way, even tho "weeks" is the official time table for meds--I felt Wellbutrin within a couple days, Moclobemide and Selegiline as well. (maybe it's the puppy upper effect of these drugs).
>
> > > (Do you mean "melancholia," "melancholic featueres," "melancholic depression," etc.?)
> >
> > Yeah, that's what I mean. Sounds like it is a particularly tough kind of depression.
>
> It's "classic" depression. It tends to be rather severe, but it responds well to TCAs and ECT. That's why I'm hoping desipramine will be good for me.It also responds well to MAOs, doesn't it?
Lorraine
Posted by Elizabeth on July 11, 2001, at 16:08:04
In reply to Re: I'll hold your hand if you'll hold mine » Elizabeth, posted by Lorraine on July 11, 2001, at 10:15:48
> Thanks for the tip. I'll look into nadolol.
I'm not positive that's the one. There are oodles of beta blockers in clinical use, and it's hard to keep track of all of them.
> My hunch is the sleeping issue with me (which is a very recent thing) is due to being overstimulated by my meds and the propranolol cuts through that like a hot knife thru butter < vbg >
Lucky that you discovered it, then.
> > For your purposes, imipramine or nortripytline might be the best choices: they have moderate effects at muscarinic ACh receptors (anticholinergic side effects), H1 receptors (antihistaminic effects -- sedation in particular), and alpha1-adrenergic receptors (blood pressure effects).
>
> Sounds like weight gain and sedation--(sexual dysfunction as well?) Yeah, I know, picky, picky, picky. But sedation is not good with me.Weight gain and sedation are both attributed to the antihistaminic actions of tricyclics. Nortriptyline would be better than imipramine if you're concerned about this; it's generally well tolerated. Desipramine might be too activating.
> > My concern is that a TCA would not be an effective drug for you. What can you tell me about your depression (and/or other disorders)?
>
> I thought you'd never ask < vbg >. My depression is like walking through mud--no energy, weepy weepy hopeless stuff at its worst, poor working memory, impairment of cognitive skills (can not think my way out of a box--this from someone who graduated in the top of her class law school and 15 years later top of class in business school--"of all the things I've lost, it's my mind I miss the most".) What I do when I am depressed is hybernate--all my systems wink out bit-by-bit until I sit alone (social withdrawal) in a room (no activity) in the dark. I do not have eating disruption or sleep disruption normally. Since last November anxiety (especially physical as in hyperventilating--but also some mental, I don't read the newspaper, I can't follow the stock market--I used to run some portfolios for friends, family and so forth). I am not a big ruminator. Before the anxiety hit, after reading Stahl's book I decided I was NE deficient as opposed to Serotonin deficient.I think that it's been pretty well-established that the original monoamine hypothesis of depression was a vast oversimplification. Anyway, this is just a hunch, but if I were in your situation I'd give MAOIs a try before TCAs. Well, it's not entirely a hunch: the "hibernation," lethargy, social withdrawal, and anxiety/panic symptoms, and the lack of disturbances in eating or sleeping, suggest to me that TCAs might not be the best meds for you. OTOH, there are always surprises. I just think it'd be better to try a TCA only if MAOIs fail. FWIW, the traditional antidepressant MAOIs -- Nardil, Parnate, and Marplan -- worked pretty well for me, but selegiline sucked when I tried it.
> I think I should give the TCAs a try first because of their lower side effect profile, especially desipramine.
Having taken several TCAs and several MAOIs, I have to disagree about the side effects. The desipramine seems to be going okay for me so far (comparable to Parnate), but I'm not generally prone to overstimulation from ADs. If overstimulation has been a problem for you in the past, you might want to stay away from desipramine.
> The reason I suspect that there may be a P450 issue is because very low doses of meds affect me strongly and I am hypersensitive to side effects.
It's a possibility, but side effect sensitivity is very common among people with anxiety disorders. My pdoc described people with panic disorder as typically being "somatically attuned" -- they are very aware of what's going on in their bodies, and sometimes they overreact to minor changes.
> Probably Klonopin would do it for me--my emergencies are not very immediate and I took Xanax for a couple of days while I was working (long ago far away on a distant planet) and found it too sedating.
They're not exactly equipotent -- you might have taken more Xanax than you needed. But anyway, if Klonopin works for you, then that's probably for the best; its effects last a long time, which is nice.
> > Definitely a possibility. Two of its metabolites (as I'm sure you know) are l-amphetamine and l-methamphetamine. I experienced jitters, agitation, and worsened insomnia and appetite on it.
>
> Yes, but then dexidrine didn't have this effect; nor is adderral having this effect.Dexedrine is d-amphetamine -- fewer peripheral side effects. Adderall is a weird combination of isomers of amphetamine salts, but it seems (for whatever reason) to cause less "jittery"-type side effects than plain d,l-amphetamine.
> By the way, even tho "weeks" is the official time table for meds--I felt Wellbutrin within a couple days, Moclobemide and Selegiline as well. (maybe it's the puppy upper effect of these drugs).
Yes, those are all stimulating drugs. I also think that MAOIs sometimes work faster than other types of ADs.
[re melancholia]
> > It's "classic" depression. It tends to be rather severe, but it responds well to TCAs and ECT. That's why I'm hoping desipramine will be good for me.
>
> It also responds well to MAOs, doesn't it?The available evidence says yes (it's important to use a sufficient dose of the MAOI -- older studies used low doses, e.g., 45 mg of phenelzine). My experience is that MAOIs work as well as any other AD I've tried has. TCAs are still the ADs of choice for this type of depression, though, and I'm hoping that desipramine will help with the problems that Parnate didn't address. (It is possible to combine them safely, which I may try if I respond partially to the desipramine.)
-elizabeth
Posted by Lorraine on July 12, 2001, at 11:49:25
In reply to Re: I'll hold your hand if you'll hold mine » Lorraine, posted by Elizabeth on July 11, 2001, at 16:08:04
> > My hunch is the sleeping issue with me (which is a very recent thing) is due to being overstimulated by my meds and the propranolol cuts through that like a hot knife thru butter < vbg >
>
> Lucky that you discovered it, then.Luck. I also found out that a supplement called stablium stopped me from "skin picking". You know if you try enough things something will work, but usually not for the reason you are taking it < vbg >
[re: Desipramine might be too activating.] I haven't generally been too activated by my meds--usually it's been the other way around. Right now all of the drugs that I am on are activating. The problem I have had is the gas pedal/brake pedal dilemma. When I take enough puppy upper to be awake and alert and active, I hyperventilate. When I take enough doggy downer to control the hyperventilation, I am too sedated. So it's a three legged potatoe sack race I'm running. My hunch is that imipramine is going to be too sedating. I think what I found when I was just taking dexedrine and neurontin was that the hyperventilation was under control, but I didn't have mood support. Because I won't have a washout period to try Desipramine and because I will be weaning off of a more activating drug (Selegiline), I have little to lose by trying it. If it doesn't work out, then I'll have one more drug to cross off my list in my little experiment. Say--minor research on Desipramine suggests it increases the release of HGH.
: Laakmann G, Schumacher G, Benkert O.
Stimulation of growth hormone secretion by desimipramin and chlorimipramin in man.
J Clin Endocrinol Metab. 1977 May;44(5):1010-3.
PMID: 870511 [PubMed - indexed for MEDLINE]Also, stumbled on this article (that I can't access--no password):
The desipramine cortisol test--a selective noradrenergic challenge (relationship to other cortisol tests in depressives and normals).
This would probably be a good read, huh?
This one too, maybe:
: Barry S, Dinan TG. Related Articles
Neuroendocrine challenge tests in depression: a study of growth hormone, TRH and cortisol release.
J Affect Disord. 1990 Apr;18(4):229-34.
PMID: 2140374 [PubMed - indexed for MEDLINE]
Thought you might be interested in what they have to say about its effect on sleep patterns:Desipramine increases the percentage of Stage 4 sleep (deep sleep) and decreases the percentage of REM sleep. A partial recovery of REM sleep is seen after 3 to 5 weeks of drug administration. However, in spite of this recovery, a REM rebound occurs following rapid drug withdrawal, which is experienced as an increase in dreaming. The significance of these effects on the sleep cycle remains to be clarified. "
This latter is from:
http://www.mentalhealth.com/drug/p30-n03.html#Head_10
> > > My concern is that a TCA would not be an effective drug for you.You may be right. I'm really torn on this.
> > > I think that it's been pretty well-established that the original monoamine hypothesis of depression was a vast oversimplification.
I read an article recently, that you might enjoy: "Serotonergic and Noradrenergic Reuptake Inhibitors: Prediction of clinical effects From In Vitro Potencies by Alan Frazer, Ph.D. J Clin Psychiatry 2001; 62 (supp 12). I found it free on line, but I don't know where anymore.
> > >Well, it's not entirely a hunch: the "hibernation," lethargy, social withdrawal, and anxiety/panic symptoms, and the lack of disturbances in eating or sleeping, suggest to me that TCAs might not be the best meds for you. OTOH, there are always surprises. I just think it'd be better to try a TCA only if MAOIs fail. FWIW, the traditional antidepressant MAOIs -- Nardil, Parnate, and Marplan -- worked pretty well for me, but selegiline sucked when I tried it.
elizabeth: I appreciate the thought you put into this. I will need to reconsider what to do here.
> > The reason I suspect that there may be a P450 issue is because very low doses of meds affect me strongly and I am hypersensitive to side effects.
>
> It's a possibility, but side effect sensitivity is very common among people with anxiety disorders.Yeah, but I've had side effect sensitivity for 5 years and the anxiety is just a recent problem (since November). But then again, I am VERY aware of physical changes in my body.
[re overstimulation on Selegiline]
> > > Two of its metabolites (as I'm sure you know) are l-amphetamine and l-methamphetamine. I experienced jitters, agitation, and worsened insomnia and appetite on it.
> >
> > Yes, but then dexidrine didn't have this effect; nor is adderral having this effect.
>
> Dexedrine is d-amphetamine -- fewer peripheral side effects. Adderall is a weird combination of isomers of amphetamine salts, but it seems (for whatever reason) to cause less "jittery"-type side effects than plain d,l-amphetamine.Doesn't all this suggest that my response to Desipramine may be different than my response to Selegiline?
elizabeth: I hope the Desipramine works for you. Do keep me updated. It's nice to know that I am not that only playing medication roulette. Shelli also seems to be on this path. Anyway, i appreciate your thoughts and just knowing that someone else out there is struggling with their meds helps keep me sane.
Lorraine
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