![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 22 to 46 of 46. Go back in thread:
Posted by Robert_Burton_1621 on February 11, 2015, at 21:13:42
In reply to Re: Starting Parnate after 15 yrs treatment-resistance, posted by ed_uk2010 on February 4, 2015, at 4:29:13
Posted by Robert_Burton_1621 on February 11, 2015, at 21:19:58
In reply to Re: Starting Parnate after 15 yrs treatment-resistance (nm) » ed_uk2010, posted by Robert_Burton_1621 on February 11, 2015, at 21:13:42
I have just posted an update after being on parnate for a week, but I'm not sure where my post has ended up?
Posted by Robert_Burton_1621 on February 11, 2015, at 22:39:17
In reply to Re: Starting Parnate after 15 yrs treatment-resistance, posted by ed_uk2010 on February 4, 2015, at 4:29:13
> Welcome to p-babble and do keep us up-to-date with your Parnate experience>
I'll give this another go.
I'm at the one-week point now, and have worked up to 40mg of parnate daily, all taken in one dose in the morning (or late morning).
For what they're worth, here are my observations of the drug's effects on me thus far:
1. Efficacy
Anti-depressant effects are mild, but it is, of course, early days. Then again, I suppose it depends what indicators of anti-depressant action you take as being central. I have experienced no "turning on of the lights" effect. But one very noticeable change has been my capacity to adhere to appointments I've committed myself to. I have not cancelled one appointment since being on parnate, even in the midst of pretty significant tiredness. This is in quite striking contrast to my state over Dec-Jan, directly before starting, when I cancelled 90% of appointments and suffered a not insignificant loss of income as a result.
My cognition and capacity for concetration has also moderately improved.
Some people speak of a stimulating (or, in its negative aspect, an agitating) effect over the two or so hours subsequent to taking their dose. I have not experienced this. The feeling I experience is like that which tends to accompany occassions of pleasurable anticipation, and it starts in the gut. The analogy that occured to me is the pleasant mixture of excitement and suspense that you tend to feel while waiting for news (e.g.) about a positive opportunity, prize, etc, which you believe you have good chances, respectively, of benefiting from or winning. The difference is that whereas experience of such a feeling in those circumstances tends to be transient or episodic, this parnate feeling is prolonged.
This feeling tends not to be stimulating but moderately anxiolytic. It is welcome.
2. Side-Effects
No orthostatic hypotension to speak of.
Insomnia and sleep disregulation are the only troubling side-effects, but they are getting more tolerable.
I experienced what I identified to be a mild tyramine-induced episode of hypertension one hour after consuming an Indian takeaway. Perhaps the food had been heated, stored, then reheated a few times, and had been stewing in the bain-marie for some time. I can't point to any obvious ingredient as being responsible (mushrooms, peas?), though perhaps the sauces had something in them. The main symptom was a hot and throbbing sensation in the back of my neck. It resolved after a couple of hours and did not affect my activities.
I have a constant, moderately painful tension-type headache which has settled in my forehead and across my eyes, but this may be a function of my insomnia.
All in all, my experience thus far has definitely been more positive than negative, though I hope for improvements in the weeks to come.
Posted by ed_uk2010 on February 12, 2015, at 12:43:47
In reply to Re: Starting Parnate - Update » ed_uk2010, posted by Robert_Burton_1621 on February 11, 2015, at 22:39:17
You see it says 'nm' after my posting name above? nm means no message. You accidentally ticked the box saying 'no message, just post above subject'. You'll see that message when posting next time. Don't click on it!
Posted by ed_uk2010 on February 12, 2015, at 13:09:44
In reply to Re: Starting Parnate - Update » ed_uk2010, posted by Robert_Burton_1621 on February 11, 2015, at 22:39:17
Hello and thanks for re-posting,
>Anti-depressant effects are mild, but it is, of course, early days.
I think it is very encouraging that you're feeling improvements already. Do you plan to stay at your current dose for a few weeks? It might be a good idea. You've already experienced benefits (early on) as well as insomnia (+tiredness). Parnate is clearly 'doing something' and you might not need any more than 40mg.
>But one very noticeable change has been my capacity to adhere to appointments I've committed myself to.
A very positive change.
>The feeling I experience is like that which tends to accompany occassions of pleasurable anticipation, and it starts in the gut. The analogy that occured to me is the pleasant mixture of excitement and suspense that you tend to feel while waiting for news (e.g.) about a positive opportunity, prize, etc, which you believe you have good chances, respectively, of benefiting from or winning.
It sounds like a sort of acute sensation of hopefulness. Almost like the opposite of the feelings of dread so common during depression.
>No orthostatic hypotension to speak of.
That may occur later, in a couple of weeks, but hopefully not.
>an Indian takeaway. Perhaps the food had been heated, stored, then reheated a few times, and had been stewing in the bain-marie for some time. I can't point to any obvious ingredient as being responsible (mushrooms, peas?), though perhaps the sauces had something in them.
The majority of vegetables contain very little tyramine, even when not fresh. Tyramine is produced during the degradation of protein-rich foods, from the amino acid tyrosine. Few vegetables contain enough tyrosine to convert to tyramine when spoiled.
Was there any meat or fish in the takeaway? If not, it was probably something in the sauce.
Takeaways are difficult due to problems knowing what you're actually eating. Sauces containing soy sauce, various soybean products, yeast extracts and meat extracts may be a problem. A large proportion of flavour enhancers, stock cubes and flavour cubes used in sauces contain one or more of the above ingredients. Takeaways often use a lot of flavour enhancers!
>I have a constant, moderately painful tension-type headache which has settled in my forehead and across my eyes, but this may be a function of my insomnia.
Do you have a BP monitor? Be careful what you take for the headache. A lot of over-the-counter medicines are not advisable. Plain single-ingredient paracetamol (acetaminophen) tablets have no interaction with MAOIs.
Good luck for the next few weeks!
Posted by Robert_Burton_1621 on February 13, 2015, at 9:25:21
In reply to Re: Starting Parnate - Update » Robert_Burton_1621, posted by ed_uk2010 on February 12, 2015, at 13:09:44
> I think it is very encouraging that you're feeling improvements already. Do you plan to stay at your current dose for a few weeks? It might be a good idea. You've already experienced benefits (early on) as well as insomnia (+tiredness). Parnate is clearly 'doing something' and you might not need any more than 40mg.>
I really appreciate your comprehensive feedback, Ed.
I may have progressed to 40mg too quickly, as mid-yesterday and today I've been feeling extremely weak. My limbs feel (paradoxically) both weightless and very heavy. It takes a conscious effort to stand up, hop up, walk, etc.
I've checked my BP and it was 127/71, so that is not the cause. It may be the cumulative effect of the insomnia hitting me. I've now got some temazepam from my specialist to help counter the insomnia. First time taking a drug from the benzo class.
I've also lost pretty much all of my appetite. Having eaten only some almonds, blueberries, and toast over the last two days wouldn't be helping my blood sugar. Perhaps that's why I'm feeling physically weak.
> >But one very noticeable change has been my capacity to adhere to appointments I've committed myself to.
>
> A very positive change.>Yes, thank you. Today, though, because of my extreme weakness, I had no choice but to cancel.
> >The feeling I experience is like that which tends to accompany occassions of pleasurable anticipation, and it starts in the gut. The analogy that occured to me is the pleasant mixture of excitement and suspense that you tend to feel while waiting for news (e.g.) about a positive opportunity, prize, etc, which you believe you have good chances, respectively, of benefiting from or winning.
>
> It sounds like a sort of acute sensation of hopefulness. Almost like the opposite of the feelings of dread so common during depression.
>That is a good description, though I should emphasise that it feels, at this stage, exclusively physiological rather than affective/personal, as it were. I hope, though, that the physiological functions as the precursor of the personal, in time.
> >No orthostatic hypotension to speak of.
>
> That may occur later, in a couple of weeks, but hopefully not.
>
> >an Indian takeaway. Perhaps the food had been heated, stored, then reheated a few times, and had been stewing in the bain-marie for some time. I can't point to any obvious ingredient as being responsible (mushrooms, peas?), though perhaps the sauces had something in them.
>
> The majority of vegetables contain very little tyramine, even when not fresh. Tyramine is produced during the degradation of protein-rich foods, from the amino acid tyrosine. Few vegetables contain enough tyrosine to convert to tyramine when spoiled.
>
> Was there any meat or fish in the takeaway? If not, it was probably something in the sauce.
>
> Takeaways are difficult due to problems knowing what you're actually eating. Sauces containing soy sauce, various soybean products, yeast extracts and meat extracts may be a problem. A large proportion of flavour enhancers, stock cubes and flavour cubes used in sauces contain one or more of the above ingredients. Takeaways often use a lot of flavour enhancers!
>This is very helpful, thank you. There was meat: lamb and chicken. And it's lack of freshness may have been disguised by the sauces. I can't know. But I will take it as a cautionary experience.
> >I have a constant, moderately painful tension-type headache which has settled in my forehead and across my eyes, but this may be a function of my insomnia.
>
> Do you have a BP monitor? Be careful what you take for the headache. A lot of over-the-counter medicines are not advisable. Plain single-ingredient paracetamol (acetaminophen) tablets have no interaction with MAOIs.
>I have a history of terrible migraine, so this tension-headache is, in comparision, tolerable. Yes, thanks, I have been advised about OTC analgesics. And I will be purchasing a BP monitor next week, just saved up, since they are a bit pricey.
Incidentally, would it be possible to take sandomigran [pizotifen] (which, in the past, solved my chronic transformed-migrainous state overnight)with parnate? It's a serotonin antagonist, so I'm assuming yes. I know triptans would be out of the question.
> Good luck for the next few weeks!>Thank you indeed. I will be persevering!
Posted by ed_uk2010 on February 13, 2015, at 11:33:58
In reply to Re: Starting Parnate - Update » ed_uk2010, posted by Robert_Burton_1621 on February 13, 2015, at 9:25:21
Hello.
>I've been feeling extremely weak. My limbs feel (paradoxically) both weightless and very heavy. It takes a conscious effort to stand up, hop up, walk, etc.
>
> I've checked my BP and it was 127/71, so that is not the cause.MAOIs don't usually cause much in the way of sitting or lying (supine) hypotension. The major effect is to impair normal postural autonomic nervous system reflexes. The ability to maintain BP at a relatively constant level on changing position, particularly standing up for a sitting or lying position, is impaired (orthostasis - postural hypotension).
To detect postural hypotension with a home BP monitor, measure your BP after sitting quietly for 5 minutes or more. Use a BP monitor with a properly fitting upper arm cuff. Take a couple of measurements to ensure consistency eg. one in each arm. The cuff/arm should be at approx. heart (nipple) level! Then.... standing up abruptly and wait about 3 minutes. At this point, measure BP again with the arm/cuff at heart level. Examine the difference, looking for a substantial drop on standing.
Postural hypotension does not necessarily develop immediately after starting an MAOI, it can take a couple of weeks to set in. Although it may not disappear over time ie. a drop may still occur, the body can often adjust so that symptoms no longer occur. It seems the brain can adjust so that normal function still occurs at lower perfusion pressures.
Most people have a high salt intake anyway so there's rarely any need to increase.... but certainly, do not attempt a low salt diet while titrating the MAOI. Inadequate fluid and salt intake aggravates the postural BP drop. As well as eating adequately, you need to maintain a decent fluid intake. Becoming dehydrated whilst on an MAOI is likely to cause substantial weakness and postural hypotension.
>It may be the cumulative effect of the insomnia hitting me. I've now got some temazepam from my specialist to help counter the insomnia. First time taking a drug from the benzo class.
Temazepam is often helpful for short-term or 'as needed' use. How much are you taking, 10-20mg?
If you don't respond well to temazepam, you could still consider zolpidem 5-10mg or zopiclone 3.75-7.5mg, or perhaps cyproheptadine as mentioned below.
>I've also lost pretty much all of my appetite. Having eaten only some almonds, blueberries, and toast over the last two days wouldn't be helping my blood sugar. Perhaps that's why I'm feeling physically weak.
I think that will have made a huge difference. In fact, it could be the main problem. Do you live alone? Anyone who can help you out?
You need some calories even if you're not hungry. Maybe go for something starchy and filling (but easy) like a baked potato with baked beans, or pasta with tomato sauce (and no cheese in the sauce!)... or how about wholemeal bread and cooked chicken pieces as a sandwich with a bit of tomato, rocket salad and mayo? Fruit is good but it's definitely not going to give you enough calories to feel well considering how little you've eaten lately. Would be better to have an egg sandwich!
>I should emphasise that it feels, at this stage, exclusively physiological rather than affective/personal, as it were.
To be fair, it's only been a week, so a full response would be rare at this stage. It's good that you are sticking with it. If you think taking 40mg at once might be making you feel strange, you could try 20mg when you get up and 20mg a few hours later.
>There was meat: lamb and chicken. And it's lack of freshness may have been disguised by the sauces. I can't know. But I will take it as a cautionary experience.
Considering you still have a headache and feel weak, maybe just make some really basic high energy meals to safely boost you calorie intake until you feel better. Seriously, who knows what they stick in takeaway food.
>Incidentally, would it be possible to take sandomigran [pizotifen] (which, in the past, solved my chronic transformed-migrainous state overnight)with parnate? It's a serotonin antagonist, so I'm assuming yes. I know triptans would be out of the question.
Interesting, phenelazine (Nardil) has been used as a migraine prophylactic, although it takes several weeks to work. I don't know what effect Parnate has on migraine.
Pizotifen is a serotonin antagonist yes, at 5-HT2a and 2c. It is related to the tricyclic antidepressants and I'm not sure how thoroughly its reuptake inhibitor potency has been studied... probably not much! I do not believe it's a serotonin reuptake inhibitor but the pharmacology of many old drugs is not well known.
An alternative possibility is the closely related serotonin antagonist and antihistamine drug cyproheptadine (Periactin). It is structurally similar to pizotifen and has also been used for migraine prophylaxis. In addition, cyproheptadine has been used to treat serotonin syndrome. Cyproheptadine is generally rather sedating at first, so might be of benefit for insomnia when taken as a single dose in the evening eg. 4mg. Rarely, depression has been reported as a side effect, but I have heard other people say it helped their depression. Anyway, you could ask you doctor about it. Cyproheptadine improves sleep, stimulates appetite and reduces headaches. Daytime doses are likely to make you sleepy if you're not used to it.
I think it would be best to wait a few weeks in order to determine whether any additional drugs are needed for headache prophylaxis. In the mean time, you could take paracetamol or ibuprofen (or naproxen) for relief. NSAIDs often help headaches more than paracetamol but side effects are more common and they do have a variety of contra-indications. If you need an NSAID for more than a few days in a row, a PPI such as lansoprazole or omeprazole is recommended for gastro-protection.
And yeah, the triptans are metabolised by MAO so it's not recommended to take them with MAOIs. Side effects have been reported.
Good luck!
Posted by Robert_Burton_1621 on February 14, 2015, at 7:33:20
In reply to Sleep, FOOD, fluids and hypotension. » Robert_Burton_1621, posted by ed_uk2010 on February 13, 2015, at 11:33:58
> To detect postural hypotension with a home BP monitor, .....>
This is extremely practically helpful. I was told to measure my orthstatic BP, but not told how to do so optimally (or even adequately).
I appreciate your advice on hydration and calorie intake. I agree (from what you've explained) that my lack of calories over the last three days is likely to be the main problem.
In regards to fluids - and dehydration - for the sake of full-disclosure, and at the risk of embarassment, I am having difficulty with alcohol. This has been a long-standing issue. I only drink at night, probably 7 standard drinks. I suppose Oprah would assess me as "self-medicating". And she'd be right. I am only drinking white wine since the move to parnate. But I don't want to, and I know that it is just another confounding factor. To be honest, I was secretely hoping that, being on parnate, I would not be able to tolerate *any* alcohol: that would have been an absolute barrier. I am going to stop it all from tomorrow.
As a side note, the astonishing thing about Effexor when it worked was that it not eradicated any *desire* for alcohol; i.e., it just didn't help me in avoiding the temptation, but totally eliminated the temptation itself. It do so within a week and I was alcohol free for close to six months.
I do live alone and alas there's no one I can call on to give me a hand. Or rather, there's no-one whom I would be *willing* to ask (a qualification which points perhaps to a pride or shame on my part). Outside of medical or uni officers (to whom I was required to disclose it), I have told no family and only one friend of my condition. As for the later, though he has known me for 20 years, he affected disbelief. He had a brief episode of depression himself years ago and recovered immediately on fluoxetine. I suspect he assumes that his experience of recovery would be replicable if I were genuine. It's because of the likelihood of reactions like this that I am very reluctant to disclose the severity of my depression or even that I am affected by it.
Be that as it may, what I think I will do is prepare some meals in advance and freeze them, so I can eat even if I am feeling weak.
I was interested in your stress on high-calorie meals. Was this made for the purpose of negating quickly my minimum-calorie consumption over the last three days, or because there's something about Parnate which makes a (within reason) high-calorie diet beneficial or important?
> Temazepam is often helpful for short-term or 'as needed' use. How much are you taking, 10-20mg?>
That's right, I've been told to take one or two tablets, up to 20mg. I took one and it had no effect, and two had a small effect though it was already 5am then and I suspect I may have fallen asleep soon thereafter anyway!
I've had some itching from the temazepam, I assume - scalp, eyes, ears, lips, tongue. It's not unbearable, but it is annoying.
Thanks for the list of alternatives. Would you consider doxepin potentially useful? We can't get trazadone here in Australia.
Mirtazapine (small dose) knocked me out in 15 minutes when i was taking it at night with Effexor. Is taking that out of the question?
Sorry - I'm imposing on you with all of these questions!
> Pizotifen is a serotonin antagonist yes, at 5-HT2a and 2c. It is related to the tricyclic antidepressants and I'm not sure how thoroughly its reuptake inhibitor potency has been studied... probably not much! I do not believe it's a serotonin reuptake inhibitor but the pharmacology of many old drugs is not well known.>I see; that's instructive. The odd thing is that, i know pizotifen is prescribed as a prophylactic, but when I took it it actually "cured" the transformed-migrainous state I was in for many weeks - overnight.
I have just learnt from your comment that it's possible for something to be a serotonin antagonist and yet have serotonin reuptake inhibition as well. My "common-sense" would have concluded these properties were mutually exclusive. I do have a lot to learn.
> I think it would be best to wait a few weeks in order to determine whether any additional drugs are needed for headache prophylaxis.>
I agree.
> Good luck!
Thanks, again!
Posted by SLS on February 14, 2015, at 7:49:01
In reply to Re: Starting Parnate - Update » ed_uk2010, posted by Robert_Burton_1621 on February 11, 2015, at 22:39:17
I'm currently taking 120 mg/day of Parnate along with nortriptyline and a few other wonder drugs (I wonder why they aren't working). I increased the dosage of Parnate from the 100 mg/day I had been taking. For the first 2 days, I experienced more mental energy, but no antidepressant effect. Last night, I was not feeling well enough to go out, so I question how much benefit I am currently gleaning.
Parnate 120 mg/day
nortriptyline 100 mg/day
Lamictal 300 mg/day
lithium 450 mg/day
Abilify 10 mg/day
prazosin 30 mg/dayDegree of improvement: 35-40%
- Scott
Posted by Robert_Burton_1621 on February 14, 2015, at 8:23:21
In reply to Re: Starting Parnate - Update » Robert_Burton_1621, posted by SLS on February 14, 2015, at 7:49:01
I like your mordant whimsy about "wonder" drugs, Scott!
> I'm currently taking 120 mg/day of Parnate along with nortriptyline and a few other wonder drugs (I wonder why they aren't working). I increased the dosage of Parnate from the 100 mg/day I had been taking. For the first 2 days, I experienced more mental energy, but no antidepressant effect. Last night, I was not feeling well enough to go out, so I question how much benefit I am currently gleaning.
>
> Parnate 120 mg/day
> nortriptyline 100 mg/day
> Lamictal 300 mg/day
> lithium 450 mg/day
> Abilify 10 mg/day
> prazosin 30 mg/day
>
> Degree of improvement: 35-40%
>To someone, like myself, who is equipped with very little psychopharmaceutical knowledge (and none that he could explain from first principles), this regime strikes me as such an aggressive one that I am sorry to hear that the degree of improvement thus far has only been modest. The disjunction between the personal effort required in medication compliance across 7 separate drugs and the degree of clinical benefits you've so far reaped must generate considerable frustration.
The combination and augmentation therapy you're on is so specialised I wouldn't know where to being to comment constructively. And it is proverbially reckoned most prudent for one to remain silent and only be thought a fool, than to open one's mouth and remove all doubt. But just FYI, have you come across this paper?
http://www.ncbi.nlm.nih.gov/pubmed/24972362
The addition of dextroamphetatime to the high-dose (120mg) parnate you are taking induced "remission" (definition?) in patients when parante alone did not.
And there is this case study on the use of N-Acetylcysteine as an augmenting agent to parnate:
(read and download paper on the right of screen)
These suggestions are no doubt ridiculously ingenue. I hope they're not presumptuously so, though.
Posted by ed_uk2010 on February 14, 2015, at 10:25:13
In reply to Re: Sleep, FOOD, fluids and hypotension. » ed_uk2010, posted by Robert_Burton_1621 on February 14, 2015, at 7:33:20
Hi,
>I am only drinking white wine since the move to parnate. But I don't want to, and I know that it is just another confounding factor.
Perhaps it will help you to resist if you bear in mind that white wine does sometimes contain tyramine, so it's best to avoid drinking a lot. The tyramine content may vary between batches. A small amount of white white is likely to be safe, but may not provide the 'self medication' effect which makes you drink it in the first place. Large amounts are obviously best avoided. So maybe just avoid it? Easier said than done, but I think you can do it.
>Be that as it may, what I think I will do is prepare some meals in advance and freeze them, so I can eat even if I am feeling weak.
Some bulk preparation sounds like a good idea.
>Was this made for the purpose of negating quickly my minimum-calorie consumption over the last three days
Yes, exactly. You hadn't had enough calories to feel well.
>there's something about Parnate which makes a (within reason) high-calorie diet beneficial or important?
No, not at all.
>I've had some itching from the temazepam, I assume - scalp, eyes, ears, lips, tongue. It's not unbearable, but it is annoying.
I'd request something else. Temazepam is anxiolytic, but obviously wasn't sedating enough for you, and the itching is not a good sign. I would consider zopidem, zopiclone... or perhaps cyproheptadine, if available.
>Thanks for the list of alternatives. Would you consider doxepin potentially useful?
Possibly. Doxepin is a very potent antihistamine, a serotonin 5-HT2 receptor antagonist and a weak serotonin reuptake inhibitor. Because there isn't much experience combining it with MAOIs, I would suggest something lacking the SRI effect first. Doxepin is also very long-acting to use as a sleep aid.
>Mirtazapine (small dose) knocked me out in 15 minutes when i was taking it at night with Effexor. Is taking that out of the question?
No, it's not out of the question at all, but I don't know whether your doc would agree to it. He might feel worried simply by the fact it's another antidepressant. Although drugs with moderate or strong SRI effects are the major concern by far, doctors who do not use MAOIs regularly may not be too comfortable prescribing any other antidepressants at the same time. I think it depends a lot on the psychiatrist. I do suspect cyproheptadine would help. It shares a strong sedative antihistamine effect and 5-HT receptor blocking property with mirtazapine.
>Sorry - I'm imposing on you with all of these questions!
No problem!
>i know pizotifen is prescribed as a prophylactic, but when I took it it actually "cured" the transformed-migrainous state I was in for many weeks - overnight.
In that case, I wouldn't be surprised if the closely related serotonin antagonist cyproheptadine might do the same. Cyproheptadine is shorter-acting than pizotifen and possibly more sedating; I would suggest it might be more suitable as a sleep aid. If used for migraine, cypro is taken during the day as well as at night, but the first few doses should be given at night.
I feel like I'm selling cypro! This is uncommon - it just seems to fit your symptoms and med history particularly well!
>I have just learnt from your comment that it's possible for something to be a serotonin antagonist and yet have serotonin reuptake inhibition as well.
A lot of antidepressants have both properties, amitriptyline is a good example.
>I do have a lot to learn.
I don't know about that, but... I wrote you a post at the top of the page in the Effexor + Remeron vs Parnate thread. I called it 'pharmacology'. It might be of some use.
Take care.
Posted by SLS on February 14, 2015, at 18:04:00
In reply to Re: Starting Parnate - Update » SLS, posted by Robert_Burton_1621 on February 14, 2015, at 8:23:21
Thanks Robert!
I will think seriously about adding NAC.
- Scott
> I like your mordant whimsy about "wonder" drugs, Scott!
>
> > I'm currently taking 120 mg/day of Parnate along with nortriptyline and a few other wonder drugs (I wonder why they aren't working). I increased the dosage of Parnate from the 100 mg/day I had been taking. For the first 2 days, I experienced more mental energy, but no antidepressant effect. Last night, I was not feeling well enough to go out, so I question how much benefit I am currently gleaning.
> >
> > Parnate 120 mg/day
> > nortriptyline 100 mg/day
> > Lamictal 300 mg/day
> > lithium 450 mg/day
> > Abilify 10 mg/day
> > prazosin 30 mg/day
> >
> > Degree of improvement: 35-40%
> >
>
> To someone, like myself, who is equipped with very little psychopharmaceutical knowledge (and none that he could explain from first principles), this regime strikes me as such an aggressive one that I am sorry to hear that the degree of improvement thus far has only been modest. The disjunction between the personal effort required in medication compliance across 7 separate drugs and the degree of clinical benefits you've so far reaped must generate considerable frustration.
>
> The combination and augmentation therapy you're on is so specialised I wouldn't know where to being to comment constructively. And it is proverbially reckoned most prudent for one to remain silent and only be thought a fool, than to open one's mouth and remove all doubt. But just FYI, have you come across this paper?
>
> http://www.ncbi.nlm.nih.gov/pubmed/24972362
>
> The addition of dextroamphetatime to the high-dose (120mg) parnate you are taking induced "remission" (definition?) in patients when parante alone did not.
>
> And there is this case study on the use of N-Acetylcysteine as an augmenting agent to parnate:
>
> http://www.researchgate.net/publication/253647461_N-Acetylcysteine_Augmentation_to_Tranylcypromine_in_Treatment-Resistant_Major_Depression
>
> (read and download paper on the right of screen)
>
> These suggestions are no doubt ridiculously ingenue. I hope they're not presumptuously so, though.
>
Posted by Robert_Burton_1621 on February 15, 2015, at 5:26:27
In reply to Re: Sleep, FOOD, fluids and hypotension. » Robert_Burton_1621, posted by ed_uk2010 on February 14, 2015, at 10:25:13
> So maybe just avoid it? Easier said than done, but I think you can do it.>Thanks, Ed. No time like the present, so I've stopped today.
> I'd request something else. Temazepam is anxiolytic, but obviously wasn't sedating enough for you, and the itching is not a good sign. I would consider zopidem, zopiclone... or perhaps cyproheptadine, if available.
>I will definitely pursue this as far as hypnotic effect goes.
I am still itching after stopping temazepam a day and-a-half ago.
It's just occured to me that the itching may not be a reaction to it at all. I have been experiencing this symptom on and off for the last 18 months, ever since I withdrew from a high dose of amitriptyline. What's been happening is that every two or three weeks i get itching symptoms, slight at first but then within four day unbearable. This persisted while i was on Effexor and I took 5mg - 10mg of amitriptyline and the problem was solved for a couple of weeks. I didn't need to do this while on mirtazapine, nor when I was on nortriptyline. *But*, what strikes me as not coincidental, is that I stopped nortriptyline 10 days ago now: and the itching has come back.
Because I am taking nothing with H1 antagonism, I guess that's why the itching isn't being suppressed?
As I said, this has been a totally consistent pattern for the last 18 months - 2 years.
Are such symptoms heard of when people withdraw from amitriptyline, and is it not uncommon for them to persist so long?
I've stopped the temazepam: how long should I wait to be able to exclude it as a possible cause of the itching?
And the only other possible cause is parnate itself. But I haven't read anything about itching except as a case of severe allergic reaction and I don't seem to have the accompanying signs for that to be plausible.
Given the above, I think - instead of taking a small dose of amitriptyline every two weeks - your suggestion to use Cyproheptadine with its strong anithistamine sedative effect may be a way of killing two birds with one stone. (Well, three, actually, given its use in headache management, too)
> >Sorry - I'm imposing on you with all of these questions!
>
> No problem!
>It's very generous of you - this stage of the parnate process would be so much more difficult were it not for this forum and the pretty amazing feedback I get from members like you.
>I wrote you a post at the top of the page in the Effexor + Remeron vs Parnate thread. I called it 'pharmacology'. It might be of some use.
>Yes, noticed that right away. I have printed it out and read it once. But I need to take time and read it with full attention. It's the best outline (for someone like me) I've come across!
Would you recommend a basic, reliable, introductory textbook on psychopharmacology? Something a little more rigorous that (e.g.) "Prozac for Dummies" but not forbiddingly specialised.
Posted by ed_uk2010 on February 15, 2015, at 13:26:09
In reply to Re: Itching: Temazepam, Parnate or Amitriptyline? » ed_uk2010, posted by Robert_Burton_1621 on February 15, 2015, at 5:26:27
>I am still itching after stopping temazepam a day and-a-half ago.
Itching really isn't a common side effect of benzos at all. Given your history, I think you can almost rule it out as the likely cause if you're still itching today... unless you came out in a rash after you took it.
>Because I am taking nothing with H1 antagonism, I guess that's why the itching isn't being suppressed?
It could be. Some antihistamines are safe with MAOIs and others are not (in no case does the risk of side effects appear to have anything to do with histamine itself). I suggest you try cetirizine 10mg/day, if you haven't already. It's non-prescription in most countries and produces very potent H1 antagonism in the skin. Do not buy chlorphenamine/chlorpheniramine, it's a weak SRI. Cetirizine rarely cause side effects, about 1 in 10 people experience drowsiness and very uncommonly an upset stomach.
>Are such symptoms heard of when people withdraw from amitriptyline, and is it not uncommon for them to persist so long?
I've heard of problems when stopping other antihistamine ADs such as mirtazapine. Do you have any allergies or skin problems? If so, amitriptyline may have been suppressing a reaction to something in the environment.
>I've stopped the temazepam
Yeah, there's no point taking it unless it really helps. You can get something else now.
>And the only other possible cause is parnate itself.
It doesn't really correlate.
>Cyproheptadine. (Well, three, actually, given its use in headache management, too).
Four now!
Itching, insomnia, headache and maybe appetite.
You could buy some cetirizine 10mg tablets while you wait to see your doctor. Cyproheptadine is non-prescription in some countries but not others, and may not be kept in stock or routinely sold.>Would you recommend a basic, reliable, introductory textbook on psychopharmacology? Something a little more rigorous that (e.g.) "Prozac for Dummies" but not forbiddingly specialised.
I must admit I tend to use quite a lot of different sources rather than one, and don't have a favourite book.
Take care.
Posted by Robert_Burton_1621 on February 17, 2015, at 8:44:03
In reply to Re: Itching: Temazepam, Parnate or Amitriptyline? » Robert_Burton_1621, posted by ed_uk2010 on February 15, 2015, at 13:26:09
> Itching really isn't a common side effect of benzos at all. Given your history, I think you can almost rule it out as the likely cause if you're still itching today... unless you came out in a rash after you took it.
>No rash. I think you're bang-on. It's not the benzo.
> Some antihistamines are safe with MAOIs and others are not (in no case does the risk of side effects appear to have anything to do with histamine itself). I suggest you try cetirizine 10mg/day, if you haven't already. It's non-prescription in most countries and produces very potent H1 antagonism in the skin. Do not buy chlorphenamine/chlorpheniramine, it's a weak SRI>
Thanks, Ed, that's important advice. I bought some Zyrtec (cetirizine) today
> I've heard of problems when stopping other antihistamine ADs such as mirtazapine. Do you have any allergies or skin problems? If so, amitriptyline may have been suppressing a reaction to something in the environment.
>No pre-existing allergies or skin problems at all. No other sensitivities. No change in environmental circustances for 12 years. So my tentative conclusion is the ferocious pruritis is not an allergic reaction which the endep was surpressing. It seems that my H1 receptors are going haywire and are hyper-sensitive after having been anatgonised by the endep at high doses. I've tried to find information on this but so far nothing has come up.
> >And the only other possible cause is parnate itself.
>
> It doesn't really correlate.That is a relief to hear!
Posted by ed_uk2010 on February 17, 2015, at 14:16:52
In reply to Re: Itching: Temazepam, Parnate or Amitriptyline? » ed_uk2010, posted by Robert_Burton_1621 on February 17, 2015, at 8:44:03
Hello,
>I bought some Zyrtec (cetirizine) today.
Cetirizine is a potent antihistamine, so good luck.
>It seems that my H1 receptors are going haywire and are hyper-sensitive after having been antagonised by the endep at high doses.
Assuming cetirizine helps and resolves the itching, you may then be able to taper off it gradually eg. by breaking the tablets and taking a bit less over time. I would not anticipate any side effects.
How are you doing?
Posted by Robert_Burton_1621 on February 22, 2015, at 8:17:37
In reply to Re: Itching: Temazepam, Parnate or Amitriptyline? » Robert_Burton_1621, posted by ed_uk2010 on February 17, 2015, at 14:16:52
> Cetirizine is a potent antihistamine, so good luck.>
Itching resolved! I only need to take one tablet every second day. No side-effects, either.
> How are you doing?>
Thanks for asking, Ed.
Well, my recent (self-assessed) depression scores were:
19/2/14
oHDRS= 35
oMADRS = 4722/2/14
oHDRS= 29 (severe > or = 28)
oMADRS= 35 (severe > or = 35)I have progressed up to 80mg daily, as of today. I am having no side-effects to speak of. But there has been no improvement in mood. There is transient improvement in focus and motivation when I first take my dose (and for that reason I'm spreading the tablets out through the day), but my affect remains blunted and my anticipatory anhedonia is disabling. Psychomotor retardation has slightly improved, though, and I am keeping my appointments.
I also managed to go the gym for the first time in 10 weeks. I was very apprehensive about this, since I had little confidence I would have the sufficient drive to do anything. But my trainer was perceptive and took me at a slow pace. I did manage to do some low-intensity weight and core training. This was reasurring, though it resulted in no improvement in mood or my "default" state.
I am now approaching my third week on parnate. But I understand that it may still be considered early (ish) days.
I have read some interesting speculative research (a bit old now) which attempts to explain the reported "delay" in clinical onset of MAOIs even though brain levels of catecholamines and 5-HT become elevated pretty quickly. The first explanation for this "lag" which I have read is (if I understand it correctly) that the mechanism of action of MAOIs is more complex than merely elevating dopamine, noradrenaline and serotonin. The inhibition of MAO also results in the elevation in the brain of levels of trace amines. These amines have a "marked" effect on uptake and/or release of catecholamines and 5-HT at nerve endings and/or may act as neuromodulators through direct actions on receptors for the catecholamines and 5-HT. Changes in pre- and post-synaptic receptors may occur *subsequent* to the increased levels of catecholamines, 5-HT and the trace amines. Therefore, "[t]hese delayed effects may be associated with the lag between administration of the MAO inhibitors and onset of clinical effect."
See, "Insights into the Mechanisms of Action of the MAO Inhibitors Phenelzine and Tranylcypromine" (1992) J Psych Neurosci 17(5).
The other hypothesis posits, as a cause of or contributor to this "lag", a critical role for 5-HT. The hypothesis is that acute administration of large doses of tranylcypromine preferentially increases (extra-cellular - not sure what significance this qualification has?) 5-HT levels in the midbrain (dorsal + median) raphe nuclei, as compared to the frontal cortex. Apparently, "these nuclei contain the cell bodies and dendrites of most serotonergic neurones that project to the forebrain." Thus, according to the hypothesis, "this characteristic regional selectivity,. . ., may be relevant to understanding [tranylcypromine's] mechanism of action, and particularly,[its] delayed clinical effects."
See, "Effects of single and chronic treatment with tranylcypromine on extracellular serotonin in rat brain" (1994) Europ J Pharmaco 263.
Perhaps supporting the role of 5-HT in the delayed onset, I read that an old case report relates how a patient improved rapidly with the addition of lithium to parnate. The explanation for this rapid response in improvement was suggested to be related to lithium's putative capacity to enhance serotonergic activity "synergistically" with the serotonergic effect of an MAOI.
See, "Rapid Antidepressant Effect of Addition of Lithium to Tranylcypromine" (1986) J Clin Psychopharm 6(3).
Needless to say, I don't possess the competence to assess the merits of these theories, but they cropped up when I did a few searches seeking information on when parnate can be expected to kick in.
Any thoughts?
Posted by Robert_Burton_1621 on February 22, 2015, at 8:27:12
In reply to Re: Starting Parnate - Update » Robert_Burton_1621, posted by SLS on February 14, 2015, at 7:49:01
> I'm currently taking 120 mg/day of Parnate along with nortriptyline and a few other wonder drugs ...:
> Parnate 120 mg/day...
> lithium 450 mg/day...
> Degree of improvement: 35-40%
Hello Scott. I just recalled this post of yours from earlier in the thread, and I was wondering if you were able to comment on whether the degree to which the addition of lithium to parnate in your case improved your condition?
I have come across this old case report which relates how a patient improved rapidly with the addition of lithium to parnate. The explanation for this rapid response in improvement was suggested to be related to lithium's putative capacity to enhance serotonergic activity "synergistically" with the serotonergic effect of an MAOI.
See, "Rapid Antidepressant Effect of Addition of Lithium to Tranylcypromine" (1986) J Clin Psychopharm 6(3).
Thanks for any comments you might like to make based on your experience.
Posted by ed_uk2010 on February 22, 2015, at 15:19:29
In reply to Progress on Parnate - Three-week point » ed_uk2010, posted by Robert_Burton_1621 on February 22, 2015, at 8:17:37
Hi Robert,
Good to hear from you.
>Itching resolved! I only need to take one tablet every second day. No side-effects, either.
Thought it would work :) You can buy other antihistamines but they are not generally as effective.... or they cause more adverse effects.
>I have progressed up to 80mg daily, as of today. I am having no side-effects to speak of.
Good to hear you're tolerating it well. How are you doing in terms of weakness/dizziness and insomnia?
>But there has been no improvement in mood.
I'm sorry to hear that. What were you depression ratings before you started tranyl?
>I did manage to do some low-intensity weight and core training. This was reasurring, though it resulted in no improvement in mood or my "default" state.
It promising you were able to go. I imagine you'd have to go regularly to get the most benefit, both mentally and physically.
>Needless to say, I don't possess the competence to assess the merits of these theories, but they cropped up when I did a few searches seeking information on when parnate can be expected to kick in.
Any thoughts?It's the case with all amine elevating antidepressants (SSRIs, tricyclics, MAOIs etc) that clinical improvement is delayed, even though elevation of monoamines occurs rapidly. All theories appear to revolve around the idea that adaptations must occur in the brain following the increased amine levels, in order for the full AD effect to occur.
I think it's a bit of a waiting game now. I wouln't increase the dose beyond 80mg right now. You can reassess in a few weeks.
Are you still getting headaches?
Posted by Robert_Burton_1621 on March 2, 2015, at 9:20:15
In reply to Re: Progress on Parnate - Three-week point » Robert_Burton_1621, posted by ed_uk2010 on February 22, 2015, at 15:19:29
I appreciate your reply, Ed. I thought it best to wait another week so that I would be in a position to respond constructively.
> Thought it would work :) You can buy other antihistamines but they are not generally as effective.... or they cause more adverse effects.
>Thanks again for your suggestion. I haven't been taking the zyrtec daily for a week now. Just once a week seems sufficient.
> >I have progressed up to 80mg daily, as of today. I am having no side-effects to speak of.
>
> Good to hear you're tolerating it well. How are you doing in terms of weakness/dizziness and insomnia?
>The physical weakness is no very mild. No dizziness at all. No troublesome orthostatic hypotension. Parnate has been the most side-effect minimal medication I have ever taken.
> >But there has been no improvement in mood.
>
> I'm sorry to hear that. What were you depression ratings before you started tranyl?
>Good question. The psychiatrist who started me on parnate did not take them (and neither did I self-assess), but I suspect they would have been significantly higher than HDRS = 35 and MADRS = 47, especially given the marked degree of psychomotor fatigue and retardation I experienced over December and January. I took my most recent self-assessment on 27/2 and scored HDRS= 23 and MADRS = 25. Those scores can be described as nothing other than improvements, though there is a way to go.
> >I did manage to do some low-intensity weight and core training. This was reasurring, though it resulted in no improvement in mood or my "default" state.
>
> It promising you were able to go. I imagine you'd have to go regularly to get the most benefit, both mentally and physically.
>Another good point. I kept my appointment last week, too, even though I anticipated failing miserably at the prescribed tasks. I was able to go to the gym, and to participate with moderate capacity. I was quite pleased. My PT is clearly very intuitive, and is adapting the routines to my observed physical and mental state. I find the low-intensity, repetitive tasks (especially those which help regulate breathing) to be the most beneficial.
> It's the case with all amine elevating antidepressants (SSRIs, tricyclics, MAOIs etc) that clinical improvement is delayed, even though elevation of monoamines occurs rapidly. All theories appear to revolve around the idea that adaptations must occur in the brain following the increased amine levels, in order for the full AD effect to occur.
>That is a very succinct summary. It had been bothering me why I had not experienced with parnate - after a week, after two weeks - the sudden "the lights are on!" experience I had with fluoxetine and effexor. I still have not reached that point. However, the effect both of fluoxetine and effexor was very short-lived. Parnate is at least consistent, in my experience thus far.
From my experience with fluoxetine and effexor, I am inferring that I haven't quite yet had the benefit of parnate's serotonergic potency. But I don't know whether that is a legitimate conclusion to draw. For instance, parnate is definitely anxioloytic (though I find myself getting more irritable and angry, too, but it may well be that such responses are wholly explicable by objective triggers: the depression may well have suppressed the normal range of emotion, particularly reactive emotion, I was capable of feeling and acting on).
I think the most positive benefits I have experienced thus far are attributable to dopamine (my movement has improved - I have not had one day of pronounced psychomotor retardation since starting parnarte, whereas before I would have such days at least twice a week) and noradrenaline (I have kept all of my appointments, and during my appointments my attention and cognitive focus and capacity for articulation has improved noticeably).
I actually went up to 100mg five days ago. I did find that dosage the closest I have experienced in inducing the kind of positive effects I associated with fluoxetine and effexor (on serotonin?), but I decided to go down because I do not wish to push the boundaries with my doctor.
I note that treatment-resistant patients are prescribed up to 120 - 160 mg per day.
At the moment, I am taking 50mg in the morning and 20 mg in the late morning. I find the more I take in the morning, the better I feel through the day.
The insomnia is definitely improving, though I find I need an hour to two hours' sleep in the late afternoon. I am not fighting this.
> Are you still getting headaches?
No headaches at all anymore, thankfully!
Posted by Robert_Burton_1621 on March 5, 2015, at 4:56:35
In reply to Re: Progress on Parnate - Four-week point » ed_uk2010, posted by Robert_Burton_1621 on March 2, 2015, at 9:20:15
Erratum: "The physical weakness is no very mild" should have been *"the physical weakness is very mild".
Posted by ed_uk2010 on March 5, 2015, at 15:02:36
In reply to Re: Progress on Parnate - Four-week point » ed_uk2010, posted by Robert_Burton_1621 on March 2, 2015, at 9:20:15
HI Robert,
Good to hear from you.
>I haven't been taking the zyrtec daily for a week now. Just once a week seems sufficient.
Perhaps you'll be able to stop it soon?
>Parnate has been the most side-effect minimal medication I have ever taken.
That's interesting. You did appear to have adverse effects initially, but they have worn off. Good news.
>I took my most recent self-assessment on 27/2 and scored HDRS= 23 and MADRS = 25. Those scores can be described as nothing other than improvements
I'm delighted to hear of your progress, even though there's still a way to go. It's great to hear you've been back to the gym. I should really go myself.
>I decided to go down because I do not wish to push the boundaries with my doctor.
Has your doctor expressed any opinions on how high the dosage should be pushed, if necessary?
It is not clear what the maximum dose should be. I suggest doing a full blood count (including a platelet count) every couple of months if titration to a higher dose is planned. A reduced platelet count ie. thrombocytopaenia (with occasional bleeding/bruising) is one of the major toxic effects reported from very high doses.
Posted by Robert_Burton_1621 on March 8, 2015, at 6:53:48
In reply to Re: Progress on Parnate - Four-week point » Robert_Burton_1621, posted by ed_uk2010 on March 5, 2015, at 15:02:36
> HI Robert,
Hi Ed, I hope you are going well. I am very pleased, as usual, to read your response. Thanks indeed.
> Perhaps you'll be able to stop it soon?
That is the aim; I will see how the itching goes. The cetirizine is definitely becoming less necessary.
> >Parnate has been the most side-effect minimal medication I have ever taken.
>
> That's interesting. You did appear to have adverse effects initially, but they have worn off. Good news.
>Yes, you're right about the initial side-effects, but even those weren't as troubling as some of the side-effects I had with SSRIs and SNRIs. But I may have spoken too soon!
I am experiencing pretty profound weakness again at various times during the day and night. My appetite has improved considerably, so it's not owing to a lack of callories. The weakness is both physical and mental. I have been taking my BP everyday, and there is no clear sign at all of postural hypotension within the three minute period (today's result was: sitting = 124/76; immediate standing = 118/75; three minute standing = 121/83).
But my BP is lowering at various points to systolic 105-110 and I can't figure out why.
I have been taking ibuprofen 3 x 200mg over the last four days because of an inflammed throat, but stopped today to exclude it as a possible cause (though I am aware that it should raise BP).
> >I took my most recent self-assessment on 27/2 and scored HDRS= 23 and MADRS = 25. Those scores can be described as nothing other than improvements
>
> I'm delighted to hear of your progress, even though there's still a way to go. It's great to hear you've been back to the gym. I should really go myself.
>Thanks, Ed. This week the gym, because of my weakness, was a real challenge and I just had to stop. But the breathing and core work is beneficia. I probably wouldn't go if I didn't have an understanding and attentive PT. He's very good.
> >I decided to go down because I do not wish to push the boundaries with my doctor.
>
> Has your doctor expressed any opinions on how high the dosage should be pushed, if necessary?
>No, none, but that's because the first I will see him since starting is this Thursday. His advice was to titrate up to 40mg until I see him again, but I pushed it beyond. At the moment I'm taking 50mg in the morning on waking up, and 20mg at about noon. I am going very well in the mornings. And my sleep has been (touch wood!) excellent. It seems I have adapted into a pattern, so I am able to sleep at about 12 midnight and get up at 6:30 - 7:30 am *consistently*! This is a major turn around for me, since mornings had always been, for close to two decades, extremely challenging. Before this change, I cannot recall that last time I have been able to wake up at 7:30 say for two days in a row, let alone regularly for a week.
> It is not clear what the maximum dose should be. I suggest doing a full blood count (including a platelet count) every couple of months if titration to a higher dose is planned. A reduced platelet count ie. thrombocytopaenia (with occasional bleeding/bruising) is one of the major toxic effects reported from very high doses.
Thanks for this heads-up. I will raise this with my doctor on Thursday.
Posted by Robert_Burton_1621 on March 9, 2015, at 7:59:11
In reply to Re: Progress on Parnate - Four-week point » ed_uk2010, posted by Robert_Burton_1621 on March 8, 2015, at 6:53:48
> I am experiencing pretty profound weakness again at various times during the day and night. My appetite has improved considerably, so it's not owing to a lack of calories. The weakness is both physical and mental. I have been taking my BP everyday, and there is no clear sign at all of postural hypotension within the three minute period (today's result was: sitting = 124/76; immediate standing = 118/75; three minute standing = 121/83).
>
> But my BP is lowering at various points to systolic 105-110 and I can't figure out why.
>The lowered BP throughout the day is starting to become troubling. I was conducting a tutorial today and after 1.5 hours of talking I was becoming very light-headed, weak, and irritable. On getting home at 6pm, my BP was 79/50.
I ate a huge meal 30 minutes ago (I could cut the meat only with some difficulty, I feel so weak). My BP is now 96/61.
This is not postural hypotension since I have not recorded any significant drop in BP from lying/sitting to standing within the three minute period. It's hypotension induced by activity, I think. But I don't understand why.
Posted by ed_uk2010 on March 21, 2015, at 17:28:29
In reply to Re: Progress on Parnate - Four-week point » ed_uk2010, posted by Robert_Burton_1621 on March 8, 2015, at 6:53:48
Hi Robert,
How are you doing? Sorry about the delay in replying. I hope your depression and weakness have improved. What dose of Parnate are you taking now?
>But my BP is lowering at various points to systolic 105-110 and I can't figure out why.
Reduced BP is a common side effect of MAOIs. Certain MAOIs, such as pargyline, were occasionally used (years ago) as a treatment for high blood pressure. MAOIs probably reduce BP by altering the function of the sympathetic nervous system.
Have you tried increasing your salt intake?
>I have been taking ibuprofen 3 x 200mg over the last four days because of an inflammed throat, but stopped today to exclude it as a possible cause (though I am aware that it should raise BP).
Low doses shouldn't affect BP. High doses might raise BP slightly.
.
This is the end of the thread.
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