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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 8 to 32 of 33. Go back in thread:
Posted by SLS on July 12, 2008, at 17:06:32
In reply to Re: nortriptyline))SLS any thoughts?, posted by Roslynn on July 12, 2008, at 16:09:34
Dear Roslynn,
5 years ago, I could not have imagined that any of the psychotropics would turn out to be genotoxic. Unfortunately, there are more than just a handful of studies implicating most of the tricyclics. Desipramine is one of them. It is considered to be an initiator rather than a promoter. In other words, it can cause damage to the gene to initiate a cancer cell, but does not promote its growth thereafter. I have been on and off both imipramine and desipramine for years. It is only now that I have some concern. Still, I don't have a good "feel" as to the propensity for genotoxic events to occur with these drugs at normal dosages. I guess I should look into it more. Perhaps Linkadge has some numbers to cite.
I would choose nortriptyline first. It is not on the list of genotoxic TCAs, and I believe it has a broader spectrum of activity. For me, nortriptyline produces more of an improvement in anhedonia than does desipramine.
If I were responsive to solely desipramine, I would take it. However, I would go with nortriptyline 50-100mg first. Measuring blood levels can help determine therapeutic dosages, but not always. Besides, the range is very wide. You can take too much of this drug. It has a therapeutic window. 75mg might work great, but then moving up to 100mg might cause a loss of response.
Until this genotoxic thing becomes more formalized with numbers of human events, I would have to suggest the nortriptyline first.
- Scott
> > one that may have less of these problems that is supposed to be similar to desipramine is nortriptyline, if you are needing to go back on something like desipramine. (i wish i could, but i have such a fear of it now.) SLS may have advice on this.
> >
> > i'll try to write more later, but my mind is very paralysed and useless right now.
>
>
>
> Dear SLS do you have any thoughts on this? (Desipramine being genotoxic/carcinogenic??)
> Thank you for any help!!!
>
>
Posted by linkadge on July 12, 2008, at 18:16:35
In reply to Re: please clarify on Desipramine being genotoxic, posted by Roslynn on July 12, 2008, at 16:15:10
reboxetine and atomoxatine are not TCA's. Also, not all TCAs exhibit genotoxicity.
Linkadge
Posted by linkadge on July 12, 2008, at 18:21:16
In reply to Re: nortriptyline))SLS any thoughts? » Roslynn, posted by SLS on July 12, 2008, at 17:06:32
>5 years ago, I could not have imagined that any >of the psychotropics would turn out to be >genotoxic.
I am confused. There is no way to tell that a substance is genotoxic besides tests for genotoxicity.
Its not like you can intuitively feel genotoxicity.
Perhaps you mean that you 'trusted' doctors to give you something that wouldn't kill you?
Clomipramine was a great antidepressant, but I wouldn't touch it again with a 10 foot pole.
Lot of cancer around here and I don't need another agent capable of initiating it.
Linkadge
Posted by iforgotmypassword on July 12, 2008, at 19:35:10
In reply to Re: nortriptyline))SLS any thoughts?, posted by linkadge on July 12, 2008, at 18:21:16
sls, do you still have your chart?
sorry, i am still trying to make a more developed post. but i can't concentrate, my head is just useless, and the possible human genotoxicity issue has me pretty scattered, given it's possible impact on my situation.
Posted by Jay_Bravest_Face on July 12, 2008, at 20:13:47
In reply to Re: nortriptyline))SLS any thoughts?, posted by linkadge on July 12, 2008, at 18:21:16
> >5 years ago, I could not have imagined that any >of the psychotropics would turn out to be >genotoxic.
>
> I am confused. There is no way to tell that a substance is genotoxic besides tests for genotoxicity.
>
> Its not like you can intuitively feel genotoxicity.
>
> Perhaps you mean that you 'trusted' doctors to give you something that wouldn't kill you?
>
> Clomipramine was a great antidepressant, but I wouldn't touch it again with a 10 foot pole.
>
> Lot of cancer around here and I don't need another agent capable of initiating it.
>
>
> Linkadge
>I hope I am not out of my place here, but I just ask that we dont jump too far with causality and conclusions about cancer and tricyclic antidepressants. It also may put unwarranted fear into people on these medications.
Jay
Posted by linkadge on July 12, 2008, at 21:50:20
In reply to what are protriptyline's affinities? genotoxicity?, posted by iforgotmypassword on July 12, 2008, at 19:35:10
Don't freak out. There are genotoxic substances that we all likely ingest on a daily basis.
The body is often able to repair damage to genetic material. Toxicity to DNA does not directly imply cancer.
Don't freak out if you have taken it. Millions of american schoolchildren take the genotoxic methyphenidate - they're not all going to get cancer. I would just personally advise avoiding exposure to genotoxic drugs as they may be a dose dependant / exposure dependant risk factor for cancer.
Linkadge
Posted by linkadge on July 12, 2008, at 21:52:22
In reply to Re: caution...., posted by Jay_Bravest_Face on July 12, 2008, at 20:13:47
I agree, theres no need to panic or to jump to conclusions. But, I would still advise those who are taking substances with known genotoxic potential to change to an alternative. I think its best to err on the side of caution.
Linkadge
Posted by SLS on July 13, 2008, at 5:09:16
In reply to Re: caution...., posted by Jay_Bravest_Face on July 12, 2008, at 20:13:47
Thanks for the caution.
You are right. I am not normally an alarmist. Results using mice and fruit flies are preliminary, and I don't know if there is a statistical correlation between these drugs and cancer in humans. You would think it would have shown up in the human population by now. Genotoxicity is a scary proposition, though. I am glad that nortriptyline works better for me than desipramine. I would like nothing better than to be able to use desipramine were I to need it. I guess when it comes to risk versus benefit, there has not been enough of a quantification to make an informed decision.
What are you basing your caution on?
- Scott
Posted by SLS on July 13, 2008, at 5:17:08
In reply to Re: caution.... » Jay_Bravest_Face, posted by linkadge on July 12, 2008, at 21:52:22
> I agree, theres no need to panic or to jump to conclusions. But, I would still advise those who are taking substances with known genotoxic potential to change to an alternative. I think its best to err on the side of caution.
If there is no need to panic or jump to conclusions, why do you recommend not taking these genotoxic drugs based upon the facts you found?
Can you convey the magnitude of your concern about genotoxic antidepressants and why?
I sway back and forth on the issue and would like more facts or description of your perspectives on the risk factors.
- Scott
Posted by SLS on July 13, 2008, at 5:30:35
In reply to please clarify on Desipramine being genotoxic, posted by Roslynn on July 11, 2008, at 16:47:55
Previous to examining the most current literature on the subject of desipramine toxicity, I would not have been deterred to use it. The truth be told, I suffer too much and lose so many experiences in life because of depression. I would now decide to continue with desipramine until more definite results are obtained through investigation. 20 years ago, there was a feeling among psychiatrists that desipramine responders and nortriptyline responders were mutually exclusive. I'm not so sure of this right now. However, if you fail to respond to desipramine, it does not mean that you will also fail to respond to nortriptyline.
If desipramine works for you, I would continue with it. There is probably an increased rate of cancer due to the depressive illness itself such that it represents a greater risk than any genotoxicity that might exist.
You can see that I am ambivalent regarding the genotoxicity issue.
Another reason to try nortriptyline is that you don't know if you will respond to it more robustly than you do with desipramine.
I guess the bottom line is that I don't feel that I am qualified to make a decision for you.
How do you feel about things after having read the responses to your question?
- Scott
Posted by linkadge on July 13, 2008, at 12:20:46
In reply to Re: caution.... » Jay_Bravest_Face, posted by SLS on July 13, 2008, at 5:09:16
>Results using mice and fruit flies are >preliminary, and I don't know if there is a >statistical correlation between these drugs and >cancer in humans.
Iforgotmypasword hinted at a bone marrow genotoxicity study. I'd be interested in reading that.
>You would think it would have shown up in the >human population by now.
I'd say no! The thing that *can* separate genotoxicity from cancer is time. Its a very difficult thing to study. If you take a substance that might initiate tumor growth, you might not detect cancer till decades later. One study associated use of the genotoxic TCA's with a higher incidence of breast cancer in women. I am *very* hesitent when people say, "we'd know by now", because I don't think thats true. Unless you directly look for an association, it can be very difficult to detect. People get cancer, its not something one immediately blames on the use of an antidepresant, especially before the knowledge of the genotoxicity of these substances was available.
>Genotoxicity is a scary proposition, though. I >am glad that nortriptyline works better for me >than desipramine. I would like nothing better >than to be able to use desipramine were I to >need it.
I'd keep my eye on all relavant research. In some of the studies, certain TCA's displayed mixed results (ie genotoxic one study, then not in the next study). The issue of drug safety is a dynamic process. We learn more each day.
>I guess when it comes to risk versus benefit, >there has not been enough of a quantification to >make an informed decision.
Still, its about potential risk. If a genotoxic TCA were the *only* available antidepressant that was capable of sufficiantly elevating depression, then it could possibly be justified. But for those in whom a nongenotoxic alternitive is close in efficacy, then it would just make sense to make the switch.
>What are you basing your caution on?
Common sense. Choose the path with the least potential risk.
Linkadge
Posted by SLS on July 13, 2008, at 13:03:07
In reply to Re: caution...., posted by linkadge on July 13, 2008, at 12:20:46
Imipramine has been used since 1959.
How would you factor this into evaluating its lack of association with cancer?
- Scott
Posted by linkadge on July 13, 2008, at 13:03:50
In reply to Re: caution.... » linkadge, posted by SLS on July 13, 2008, at 5:17:08
>If there is no need to panic or jump to >conclusions, why do you recommend not taking >these genotoxic drugs based upon the facts you >found?
To panic would be to assume that one is going to get cancer due to past or current exposure to a genotoxic TCA. On the other hand, I would not consider it to be foolish to want to make a change to a potentially safer agent.
The drug is already approved. It takes a lot more health risk for a drug to be unaproved then it does for the drug not to be approved in the first place.
Secondly, exactly who is working on the patient's behalf to assure that the genotoxicity is an acceptable risk?
>Can you convey the magnitude of your concern >about genotoxic antidepressants and why?
To me its not so much about concern than it is about common sense. The genotoxic TCA's have fairly consistenly displayed the ability to damage genetic material. Many of the tests for geneotoxicity appear to be highly predictive of the carcinogenic potential of many environmental toxins. I would consider it to be common sense to switch to a nongenotoxic alternative if it is as effective.
It is easy for somebody (who isn't taking the drug) to tell you not to be alarmed. If you were currently taking desipramine, you might think of the issue in a different light.
No, nobody has proven that the genotoxic TCA's cause cancer, but there is a possability. Desipramine/clomipramine seems to be the most reliably genotoxic and I would have a very hard time feeling comfortable ingesting a theraputic dose (for me 150mg clomipramine) day after day. There has been cancer in my family and a higher risk of cancer in this geographical region (for one reason or another). It would make sense (in my mind) for me to reduce any controllable potential risk factors.
>I sway back and forth on the issue and would >like more facts or description of your >perspectives on the risk factors.
If you want me to prove an association I obviously can't do that. I am also not capable of
conveying any idea of any true risk as there is an unacceptable paucity of followup studies.The TCA's are very effective antidepressants. The side effect profile is of course a concern for certain conditions. Some research, for instance, directly contraindicates the use of TCA's in patients with heart disease. There seems to be an attempt to phase the TCA's out. What I mean, is that there seems to be a push to discribe the TCA's as dirty and a move to advise against their general use.
Because of this, I don't think there is adequate concern over just how much of a risk the TCA's might pose in terms of cancer. If half of the SSRI's were discovered to be genotoxic, there would be more drive to clarify the issue. As for TCA's I don't think anyone cares, they're old and 'we don't use them anymore'.
Most doctors will take the preliminary findings as further justification for avoiding their use, but will probably have no further concern or motivation to follow up.
I would personally think that because genotoxicity does seem to present itself as a risk factor for cancer and because of the lack of likelyhood of prompt followup studies, one would be best advised to err on the side of caution and switch to a safer option if at all medically feasable.
Linkadge
Posted by linkadge on July 13, 2008, at 13:13:15
In reply to Re: please clarify on Desipramine being genotoxic » Roslynn, posted by SLS on July 13, 2008, at 5:30:35
>Another reason to try nortriptyline is that you >don't know if you will respond to it more >robustly than you do with desipramine.
I would agree if she were currently taking desipramine, it might be advised not to switch off of it for fear of relapse. But, she is wondering if, in the future, she could restart it. It would seem like common sense to me to at least try a different TCA first, perhaps nortryptaline.
I realize you are may be currently ambivilant, but again, you are not currently on a genotoxic TCA!
I agree that depression is associated with cancer. It is also associated with heart disease. That doesn't mean that treating the core disease will necessarily ofset the risk of the associated illnesses. For instance, in many recent studies for heart disease patients, TCA's worsened medical stability in cardiac patients, while SSRI's seemed to improve it.
You could also think of it this way. Smoking ciagrettes is, for some, the only think the keeps depression at bay. That doesn't mean that smoking is a good way to reduce the risk of cancer that is associated with depression.
Linkadge
Posted by SLS on July 13, 2008, at 13:18:59
In reply to Re: please clarify on Desipramine being genotoxic » SLS, posted by linkadge on July 13, 2008, at 13:13:15
Are you chasing me again?
- Scott
Posted by linkadge on July 13, 2008, at 13:29:18
In reply to Re: caution.... » linkadge, posted by SLS on July 13, 2008, at 13:03:07
>Imipramine has been used since 1959.
>How would you factor this into evaluating its >lack of association with cancer?
Because an association has not been directly studied. There are likely thousands of carcinogens that have not been identified as such simply because they have not been directly studied as such.
Keep in mind, the overal risk of cancer is relatively low. Imipramine may double, triple, quadruple etc. the chance of getting cancer, but the overal risk may be still low and therefore an association is not generally abundantly obvious.
When somebody gets cancer, there is generally not an exhaustive search done on the part of the medical doctor to determine the exact cause. Cancer can also be a drug side effect that does not show up for decades. Its not like you take imipramine, then wake up the next day with a tumor.
Suppose I took imipramine for a year, 20 years ago, then I get cancer today. Who the hell knows what caused it? It could have been the small quanitiy of pot I smoked. It could have been the breif inadvertent inhalation of dishwasher detergent powder.
Sure, I envision a future where each indidence of cancer routienly entered into a sohpisticated computer system along with a comprehensive list of potentially carcinogenic drugs and environemental toxins, after which the information is then compared and crosschecked with the records of millions of others to produce a valid epidemological esimate model of which substances may the most likely contributor.But alas, we are living in today, where most diagnosis of cancer are essentaially comprised of: "I'm sorry to say, you've got cancer".
Linkadge
Posted by linkadge on July 13, 2008, at 13:33:14
In reply to Re: please clarify on Desipramine being genotoxic » linkadge, posted by SLS on July 13, 2008, at 13:18:59
>Are you chasing me again?
Ultimately, I am not trying to suggest that your line of thinking is wrong, I am just discussing the reasoning behind my decisison.
Linkadge
Posted by SLS on July 13, 2008, at 13:45:54
In reply to Re: please clarify on Desipramine being genotoxic » SLS, posted by linkadge on July 13, 2008, at 13:33:14
Well, I suppose this is a good place for me to leave things.
Roslynn: This is such a difficult decision to make with the lack of certainty regarding the role desipramine may play in the development of cancer. I did a bit of reading on this issue, and I would prefer that you use Google to see some of these reports for yourself. You will see why I am ambivalent about how great a risk desipramine poses in producing cancer.
http://www.google.com/search?hl=en&q=desipramine+cancer&btnG=Search
- Scott
Posted by linkadge on July 13, 2008, at 13:53:34
In reply to Re: please clarify on Desipramine being genotoxic, posted by SLS on July 13, 2008, at 13:45:54
type in desipramine + genotoxicity, or tricyclic antidepressant + genotoxicity.
Linkadge
Posted by SLS on July 13, 2008, at 14:36:47
In reply to Re: please clarify on Desipramine being genotoxic, posted by linkadge on July 13, 2008, at 13:53:34
Back on.
> type in desipramine + genotoxicity, or tricyclic antidepressant + genotoxicity.
Exactly, my friend. Exactly.My desire to have Roslynn do her own literature search was to demonstrate to her that there exist papers that describe genotoxicity, and even a link to breast cancer in humans.
I would have preferred that she find these things on her own rather than to trust either one of us to be accurate.
Roslynn: If you have any trouble understanding what you read, ask Linkadge to explain it to you, and then come to your own conclusions.
As I have already said, my personal preference would be to try nortriptyline before going back to desipramine. However, if nothing else worked, I would go with desipramine rather than live the rest of my life depressed. People have been on imipramine and desipramine for decades without contracting cancer. What are the numbers? What is the percentage risk? I don't know. In fifty years, nothing has become visibly consistent as to confirm carcinogenesis. I find it difficult to not be ambivalent when trying to decide just how high is the risk factor for desipramine to produce cancer. I will say this, though. There are some reports that desipramine promotes the growth of colon tumors in animals after they have already been initiated.
- Scott
Posted by Roslynn on July 13, 2008, at 15:59:38
In reply to Re: please clarify on Desipramine being genotoxic, posted by SLS on July 13, 2008, at 14:36:47
> Back on.
>
> > type in desipramine + genotoxicity, or tricyclic antidepressant + genotoxicity.
>
>
> Exactly, my friend. Exactly.
>
> My desire to have Roslynn do her own literature search was to demonstrate to her that there exist papers that describe genotoxicity, and even a link to breast cancer in humans.
>
> I would have preferred that she find these things on her own rather than to trust either one of us to be accurate.
>
> Roslynn: If you have any trouble understanding what you read, ask Linkadge to explain it to you, and then come to your own conclusions.
>
> As I have already said, my personal preference would be to try nortriptyline before going back to desipramine. However, if nothing else worked, I would go with desipramine rather than live the rest of my life depressed. People have been on imipramine and desipramine for decades without contracting cancer. What are the numbers? What is the percentage risk? I don't know. In fifty years, nothing has become visibly consistent as to confirm carcinogenesis. I find it difficult to not be ambivalent when trying to decide just how high is the risk factor for desipramine to produce cancer. I will say this, though. There are some reports that desipramine promotes the growth of colon tumors in animals after they have already been initiated.
>
>
> - Scott
Hi Scott,Thanks for your thoughtful responses to my questions. I pulled up several studies and I'm concerned enough by what I read to avoid those particular TCAs, if I should need a TCA in the future. I appreciate your help.
Roslynn
Posted by Roslynn on July 13, 2008, at 16:04:57
In reply to Re: please clarify on Desipramine being genotoxic, posted by Roslynn on July 13, 2008, at 15:59:38
Just wanted to thank everyone who responded to this thread for all the information you provided.
--Roslynn
Posted by linkadge on July 13, 2008, at 16:23:52
In reply to Re: please clarify on Desipramine being genotoxic, posted by SLS on July 13, 2008, at 14:36:47
>my personal preference would be to try >nortriptyline before going back to desipramine. >However, if nothing else worked, I would go with >desipramine rather than live the rest of my life >depressed.
Yes, this is what I had recomended too.
Linkadge
Posted by iforgotmypassword on July 13, 2008, at 19:00:31
In reply to please clarify on Desipramine being genotoxic, posted by Roslynn on July 11, 2008, at 16:47:55
this may indicate that it is not just mutagenic on specific cells, but very literally mutagenic, causing mutated offspring?
if it causes low sperm count by killing many of them, perhaps by being especially damaging towards germ (sex) cells (not diploid, cannot repair as if diploid, may represent special vulnerability?), it doesn't defend any idea that those surviving are reliably harmless, and may possibly or likely have mutations that can pass in a sperm cell, but for unfortunate offspring who may not even have obvious defects, but may have gene coding defects for say their D1 receptors or something and they end up with lovely immobilizing symptoms doctors shrug at for their whole lives while they wish they were dead...
i'll post links later. it takes so much time and is a mess for me to post due to my executive and organization trouble. it ruins so many posts, and i give up all the time.
Posted by SLS on July 14, 2008, at 4:52:12
In reply to how does desipramine cause low sperm count?, posted by iforgotmypassword on July 13, 2008, at 19:00:31
I can completely empathize with you for having such cognitive impairments. Me too.
Please give up less often. Your contributions are important. I hope you feel well-supported here.
I look forward to seeing the links you are to provide.
NO PRESSURE, THOUGH!
Thanks for the effort.
- Scott
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