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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by kizzie2 on August 2, 2010, at 7:28:09
Hello - my last message was a few weeks ago. I am currently on 50mg anafranil.
Brief history: Anxiety based PND 11 years ago (aged 29). No previous history. Took Seroxat and eventually improved but unable to get off seroxat because of withdrawal. Eventually on anafranil in 2004 - got better. Slowly withdrew in 2006 but crashed again.
Slowly withdrew lat 09 and '10 but crashed again in Feb.
(Was very well on 25mg and below 2007/08 and 09.)Have now been back on thereapeutic dose of anafranil for 5 months. Initially 75mg. Had a small amount of improvement bust still significant anxiety/depression. As I had been better on 50mg in the past dr suggested reducing.
Reduced to 50mg over a number of weeks and had about 5 weeks of feeling much much better.
But then 3 weeks ago anxiety and depression kicked in again. (this was 3 weeks after I had dropped to 50mg) Very severe at times. Very negative and intrusive thoughts.
Im sorry this is a bit of a confusing story but would really appreciate any input. I have read a lot about 'poop out' - could this be what is happening?
I dont know whether this is true but my anxiety/depression 'appear' to be a chemical/hormonal thing. When I am well I am very happy and content. And then i just seems to come in from nowhere. x
Posted by Phillipa on August 2, 2010, at 12:23:27
In reply to Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 2, 2010, at 7:28:09
Have you corrolated it to any monthly cycle times? If so could be hormonal. Maybe a dose inbetween the 75 and 50mg would work? What does your pdoc say? Phillipa
Posted by Justherself54 on August 2, 2010, at 19:43:14
In reply to Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 2, 2010, at 7:28:09
Have you had your blood levels checked? I was taking 150 mg. My blood work showed that I was in the lower levels of the theraputic range. I've increased it to 175 mg. a week ago and it's working even better.
You may not be taking a high enough dose. Your pdoc should be checking the levels of clomi in your blood and go from there.
Posted by Phillipa on August 2, 2010, at 21:46:49
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by Justherself54 on August 2, 2010, at 19:43:14
That's great still helping pain too? Phillipa
Posted by kizzie2 on August 3, 2010, at 6:23:12
In reply to Re: Sorry - another anafranil/clomipramine q. In UK » Justherself54, posted by Phillipa on August 2, 2010, at 21:46:49
Thank you for replyling. I am seeing the dr next week - although they dont do blood tests here to check levels of things like anafranil.
I have been monitoring my cycle Phillipa - but there doesnt seem to be a hormonal link.
Posted by Phillipa on August 3, 2010, at 20:43:16
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 3, 2010, at 6:23:12
Thought was worth asking. Why no blood levels done? Phillipa
Posted by kizzie2 on August 4, 2010, at 3:50:06
In reply to Re: Sorry - another anafranil/clomipramine q. In UK » kizzie2, posted by Phillipa on August 3, 2010, at 20:43:16
I just think they dont do them in uk unless you are on something like lithium (?)
Posted by Justherself54 on August 4, 2010, at 11:26:10
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 4, 2010, at 3:50:06
That's unfortunate that they won't do the blood tests. I thought I was on a fairly high dose of clomi, however, my blood work said differently. How can your pdoc know if you are in the "theraputic" zone if he doesn't order blood work?
Would going to another doctor help? Perhaps it's only your particular doc who doesn't know he should be doing blood work. It was one of the first things my pdoc spoke about when we discussed trying clomi.
I'm feeling very well at 175 mg. As I said before, I thought it was a very high dose, but for me it's not. I was a bit relieved that I still have room for increases, if necessary.
Posted by ed_uk2010 on August 4, 2010, at 15:40:15
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 4, 2010, at 3:50:06
>I just think they dont do them in the UK unless you are on something like lithium...
You are correct. Clomipramine blood levels are almost never performed in the UK. There are are several reasons for this, for example:
1. The therapeutic range for clomipramine (in terms of blood level) is not well established. This is further complicated by the fact that clomipramine has numerous active metabolites.
2. The dosage of antidepressants is generally adjusted according to efficacy and adverse effects, not according to the blood level.
3. Most hospital labs do not offer this test, because there is little demand for it.
4. Specialist blood tests are expensive (and so they are generally avoided unless there is a clear justification for performing them). Because the alleged therapeutic range for clomipramine is not based on good evidence, the justification for performing this test is not clear.
Basically, if you current dose of clomipramine is not sufficiently effective, you should consider an increase (assuming that side effects permit).
Posted by Brainbeard on August 5, 2010, at 15:24:23
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by ed_uk2010 on August 4, 2010, at 15:40:15
>
> You are correct. Clomipramine blood levels are almost never performed in the UK. There are are several reasons for this, for example:
>
> 1. The therapeutic range for clomipramine (in terms of blood level) is not well established. This is further complicated by the fact that clomipramine has numerous active metabolites.
>
> 2. The dosage of antidepressants is generally adjusted according to efficacy and adverse effects, not according to the blood level.
>
> 3. Most hospital labs do not offer this test, because there is little demand for it.
>
> 4. Specialist blood tests are expensive (and so they are generally avoided unless there is a clear justification for performing them). Because the alleged therapeutic range for clomipramine is not based on good evidence, the justification for performing this test is not clear.
>
> Basically, if you current dose of clomipramine is not sufficiently effective, you should consider an increase (assuming that side effects permit).The therapeutic range of blood levels is established well enough to distinguish between low, medium or high blood levels versus toxic blood levels.
The main reason why there are no blood tests for the newer antidepressants is that they are usually non-toxic even in (very) high doses.
Clomipramine blood levels should always be taken, not just to see wether the dose is therapeutic, but also to avoid toxicity, which could occur even with low doses in a slow metabolizer and/or a rapid absorber. The narrow therapeutic range of TCA's, meaning the difference between an effective and a lethal dose is only rather small, is precisely why blood work is imperative for any responsible doctor prescribing TCA's.
Also, blood levels can vary enormously between different individuals.
There's no way of knowing wether your dose is effectively low, medium or high (or toxic) without doing blood work.I have tried 75mg of clomipramine before, without blood work, and suffered from such severe side-effects that I was sure my blood levels were very high. I tapered down before really reaping any therapeutic benefit. Now, years later, I'm on 125mg of clomipramine boosted by 25mg of fluvoxamine (which increases clomipramine levels up to tenfold while decreasing the noradrenergic metabolite, the main suspect when it comes to toxicity), and my blood levels turn out to be in the subtherapeutic range... Hence I'm going further up.
Clomipramine doesn't have numerous active metabolites; it has only one active metabolite (just like the other tertiaty amine TCA's), which is desmethylclomipramine, a potent NRI.
Posted by ed_uk2010 on August 5, 2010, at 18:00:18
In reply to 'Bloody' Clomipramine, posted by Brainbeard on August 5, 2010, at 15:24:23
>Clomipramine blood levels should always be taken.....
Perhaps you could post a link to a study which demonstrates that measuring clomipramine blood levels improves clinical outcome.
>(high blood levels) which could occur even with low doses in a slow metabolizer and/or a rapid absorber...
It is certainly true that blood levels can vary greatly between individuals, mainly due to differences in metabolism. I am not aware of the phenomenon of a 'rapid absorber'.
>......to avoid toxicity, which could occur even with low doses in a slow metabolizer.
In general, the most appropriate way to avoid toxicity is to start at a low dose (eg. 10mg/day) and to increase the dose gradually whilst carefully monitoring for adverse effects.
>blood work is imperative for any responsible doctor prescribing TCAs
In that case, I can only assume that the majority of doctors are irresponsible.
>Clomipramine doesn't have numerous active metabolites; it has only one active metabolite (just like the other tertiaty amine TCA's), which is desmethylclomipramine, a potent NRI.
Thank you Brainbeard, I am well aware that desmethylclomipramine is a potent NRI. Clomipramine does, however, have numerous metabolites. I would not like to presume that desmethylclomipramine is its only active metabolite. Not enough research has been done in this area.
Thank you for your comments.
Posted by MaybeSo on August 5, 2010, at 20:34:36
In reply to Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 2, 2010, at 7:28:09
I really liked Anafranil, and took it for many years. Drs here in the US would always try to take me off of it for a newer drug, but the Anafranil was always the best.
But it did eventually quit working for me. It was a gradual decline; I didn't realize it was pooping out until I woke up one morning and realized the horrible black-dog depression was sitting on my chest. (Then I could look back and realize I'd been slipping for a few months.)
I wish Anafranil were more widely used here in the US, as it is in Canada and the UK. I think it's a great drug for certain kinds of ~psych profiles~ (I don't know what else to call it).
Sorry you're not doing well. It may be time for an adjunctive drug, perhaps prozac or wellbutrin?
Not to freak you out, but you may also want to look at bipolar type II symptoms and see if that seems familiar.
Posted by MaybeSo on August 5, 2010, at 20:38:02
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by MaybeSo on August 5, 2010, at 20:34:36
BTW, I never had even one psychiatrist suggest a blood test for any psych medicine I have taken except lithium. That's 30 years of psych treatment.
Thyroid tests, Liver function, Blood sugar, yes. Never for a med level.
Posted by Brainbeard on August 6, 2010, at 4:28:03
In reply to Re: 'Bloody' Clomipramine » Brainbeard, posted by ed_uk2010 on August 5, 2010, at 18:00:18
> Perhaps you could post a link to a study which demonstrates that measuring clomipramine blood levels improves clinical outcome.
Sure, no problem.
"Clinical significance of plasma levels of clomipramine, its hydroxylated and desmethylated metabolites: prediction of clinical outcome in mood disorders using discriminant analysis of therapeutic drug monitoring data": http://www.ncbi.nlm.nih.gov/pubmed/8126313:
"(...) the overall correlations between drug concentrations and daily doses of clomipramine were highly significant. (...) Discriminant analysis of the data from drug concentrations and scores of Global Assessment of Functioning revealed that it is useful to monitor the concentrations of both desmethylated and hydroxylated metabolites in order to predict the clinical effects of clomipramine."
From a testing lab:
http://www.childrensmn.org/Manuals/Lab/Chemistry/028768.asp:
"Studies investigating the relationship between serum concentrations of clomipramine and norclomipramine and therapeutic response have yielded conflicting results. However, the probability of therapeutic failure seems to increase if the sum of the clomipramine and norclomipramine serum concentrations is <150 ng/mL. Summed serum concentrations of clomipramine and norclomipramine which exceed 450 ng/mL seem to result in no additional enhancement in therapeutic response and may predispose the patient to greater risk of adverse side affects."
For OCD, there has been more research concerning plasma levels and clinical outcome:
'The relationship of plasma clomipramine and N-desmethylclomipramine to response in obsessive-compulsive disorder':
http://www.ncbi.nlm.nih.gov/pubmed/2371366:
"A significant degree of correlation was also obtained between plasma levels of clomipramine, but not N-desmethylclomipramine, and post-treatment outcome measures."
'Clomipramine: plasma levels, side effects and outcome in obsessive-compulsive neurosis':
http://www.ncbi.nlm.nih.gov/pubmed/7393824:
"In general the response was best in the middle range of plasma concentrations, showing the inverted U curve well recognized with nortriptyline. However, the results of this study suggest that the response of compulsive rituals correlates with levels of plasma clomipramine, while depression appears to correlate with plasma levels of desmethylclomipramine."
'High blood concentrations of imipramine or clomipramine and therapeutic failure: a case report study using drug monitoring data':
http://www.ncbi.nlm.nih.gov/pubmed/2741190
>
> >blood work is imperative for any responsible doctor prescribing TCAs
>
> In that case, I can only assume that the majority of doctors are irresponsible.In the UK, perhaps, yes. As you may have noticed from the other reactions, outside the UK, it is common procedure to do blood work when prescribing TCA's, especially for the more toxic tertiary amine TCA's.
>
> >Clomipramine doesn't have numerous active metabolites; it has only one active metabolite (just like the other tertiaty amine TCA's), which is desmethylclomipramine, a potent NRI.
>
> Thank you Brainbeard, I am well aware that desmethylclomipramine is a potent NRI. Clomipramine does, however, have numerous metabolites. I would not like to presume that desmethylclomipramine is its only active metabolite. Not enough research has been done in this area.As the articles mentioned above already make clear, I indeed found out that clomipramine has a whole bunch of metabolites, which may be active. I stand corrected!
>
> Thank you for your comments.
>Most welcome, thank YOU.
Posted by ed_uk2010 on August 6, 2010, at 14:59:29
In reply to Clomipramine plasma levels and clinical outcome » ed_uk2010, posted by Brainbeard on August 6, 2010, at 4:28:03
Hi BB,
Thanks for the links.
Due to its potential toxicity, prudent psychiatrists always initiate clomipramine treatment at a low dose and increase gradually (in small steps) according to response. Adjustments to the dose (either up or down) are normally guided by clinical efficacy, subjective adverse effects such as dry mouth and sometimes by objective adverse effects such as hypotension, increased pulse rate and ECG (EKG) changes.
If a particular dosage of clomipramine was not effective, the dose would generally be increased - unless adverse effects were a problem (or the dose was already high). If a particular dosage of clomipramine caused unpleasant adverse effects, the dose would need to be decreased.
Although it may be necessary to measure blood levels in some cases, I am still not sure that it is needed for everyone. Just as an example, if 30mg per day caused severe anticholinergic adverse effects, the prescriber would have no option but to reduce the dose. Measuring the blood level wouldn't change this.
Similarly, if an OCD patient's dose was gradually increased from 10mg to 100mg over a period of two weeks, subjective response could be used to guide further adjustments. If 100mg/day was ineffective after several weeks and there were no troublesome side effects, an increased dose would be suitable.
Requirements for bloodwork vary from patient to patient. For example, in an elderly patient on diuretic treatment for hypertension, pre-treatment assessment of serum potassium would be essential. For a young person with no medical problems who was on no other medication, this would not be necessary.
Posted by Brainbeard on August 6, 2010, at 15:33:59
In reply to Re: Clomipramine plasma levels and clinical outcome » Brainbeard, posted by ed_uk2010 on August 6, 2010, at 14:59:29
It does involve guesswork. Subjective measurements are suspect by nature, especially when dealing with hypochondrics and people focused on negative experiences.
Blood work (and, true, EKG's and the like) can help with enduring unpleasant side-effects, since it gives the patient an objective counter-value against which to evaluate such side-effects.
Clomipramine has non-linear pharmacokinetics: on higher doses, blood levels increase exponentially in relation to dose, supposedly because of its self-inhibiting metabolism. People have died from toxic doses without experiencing severe side-effects in advance.
Posted by Roslynn on August 6, 2010, at 16:48:01
In reply to Sorry - another anafranil/clomipramine q. In UK, posted by kizzie2 on August 2, 2010, at 7:28:09
Hmmmm...regarding blood levels, I have had doctors order levels for me for nortriptyline and desipramine.
The discussion regarding whether or not to test blood levels on clomipramine is quite confusing!
I am currently at Prozac 40mg and clomipramine 50mg (which will shortly increase to 100mg.) Hence my interest in this thread. Don't know if the doc will order a blood level or not.
Roslynn
Posted by ed_uk2010 on August 6, 2010, at 17:09:52
In reply to Guess work, blood work, death work » ed_uk2010, posted by Brainbeard on August 6, 2010, at 15:33:59
>It does involve guesswork. Subjective measurements are suspect by nature....
Depression is all about subjective experiences though. Only the patient can say whether or not they are finding any given dose to be effective.
>Clomipramine has non-linear pharmacokinetics: on higher doses, blood levels increase exponentially in relation to dose, supposedly because of its self-inhibiting metabolism.
Especially at 150mg/day plus. I do think it makes sense to perform blood levels for patients on very high doses. If someone was experiencing relief on 30mg/day and they weren't suffering from any side effects, I do not think that it would generally be necessary to measure the blood level.
>People have died from toxic doses without experiencing severe side-effects in advance.
There is a risk of cardiac arrhythmias with most TCAs. Sinus tachycardia is extremely common and generally benign; more serious arrhythmias such as torsades de points occur rarely. This risk of serious arrhythmias is highly dependent on the patient eg. increased likelihood in ischemic heart disease, serum electrolyte disturbances, chronic heart failure etc. Such factors should be taken into account when deciding whether bloodwork and other tests are needed before (and during) treatment with TCAs. Performing the same tests on everyone is not appropriate. Interestingly, clomipramine appears to be considerably less toxic in overdose than amitriptyline. Its cardiotoxicity is less but there is a risk of seizures. Patients on very high doses should carefully consider whether or not it is appropriate for them to drive.
Posted by ed_uk2010 on August 6, 2010, at 17:12:34
In reply to Re: Sorry - another anafranil/clomipramine q. In UK, posted by Roslynn on August 6, 2010, at 16:48:01
>I am currently at Prozac 40mg and clomipramine 50mg (which will shortly increase to 100mg.) Hence my interest in this thread. Don't know if the doc will order a blood level or not.
Since you are receiving a high dose of fluoxetine, you might be an ideal candidate for a blood level. Also, I would definitely advise you to increase your clomipramine dose gradually. 50mg to 100mg is a large jump for someone on an interacting drug.
Posted by Justherself54 on August 6, 2010, at 17:48:50
In reply to Guess work, blood work, death work » ed_uk2010, posted by Brainbeard on August 6, 2010, at 15:33:59
>>People have died from toxic doses without >>experiencing severe side-effects in advance.
I'm currently taking 175 mg. daily. This appears to be quite a large dose. Now I don't know what to do. This med has allowed me to start living again. I'm scared to keep taking it and I'm scared not to take it.
Am I at a dose high enough to die from?
Posted by Phillipa on August 6, 2010, at 20:02:06
In reply to Re: Guess work, blood work, death work, posted by Justherself54 on August 6, 2010, at 17:48:50
Your pdoc has always sounded like very caring person from your postings will he do a blood test for you? Phillipa
Posted by Brainbeard on August 7, 2010, at 1:21:29
In reply to Re: Guess work, blood work, death work, posted by Justherself54 on August 6, 2010, at 17:48:50
> >>People have died from toxic doses without >>experiencing severe side-effects in advance.
>
> I'm currently taking 175 mg. daily. This appears to be quite a large dose. Now I don't know what to do. This med has allowed me to start living again. I'm scared to keep taking it and I'm scared not to take it.
>
> Am I at a dose high enough to die from?No, I'm sorry if I scared you, concentrations only begin to climb steeply from doses of 250mg and beyond, generally. And Ed is right, if you don't have cardiac (heart) problems to begin with nor a family history of cardiac diseases, plus you don't experience severe side-effects, there is no reason to be worried. 175mg is a normal dose; the maximum recommended dose is 250mg, at least where I live.
Clomipramine is a fantastic med, let's not forget that, and when it has allowed you to start living again, don't worry, be happy.
Posted by Justherself54 on August 7, 2010, at 9:21:18
In reply to Trust the shoes that make you walk, posted by Brainbeard on August 7, 2010, at 1:21:29
Thanks Brainbeard!!
Posted by ed_uk2010 on August 7, 2010, at 12:45:01
In reply to Re: Guess work, blood work, death work, posted by Justherself54 on August 6, 2010, at 17:48:50
>I'm currently taking 175 mg daily. This appears to be quite a large dose.
It's fairly high but not very high. It's typical of the doses used to treat severe depression or obsessive-compulsive disorder.
>Now I don't know what to do. This med has allowed me to start living again. I'm scared to keep taking it and I'm scared not to take it.
You should keep taking it.
So long as it is prescribed with care, clomipramine is generally a safe medication. There are certain circumstances in which it is potentially unsafe, as outlined below.
If any of the following apply to you, please contact your doctor for advice....
1. You have previously had a myocardial infarction (heart attack) or stroke
2. You suffer from angina
3. You suffer from chronic heart failure or structural heart disease.
4. You have ever experienced cardiac arrhythmias (or have a family history of long QT syndrome)
5. You take other medications which are known to interact with clomipramine - check the product information leaflet if you are unsure. Some of the commonly used SSRIs such as Paxil can interact with clomipramine. Also, certain cardiovascular medications such as diuretics can be problematic.
6. You have an (uncontrolled) overactive thyroid>Am I at a dose high enough to die from?
That is extremely unlikely!! So long as none of the above conditions apply, there is really no need to worry.
This is the end of the thread.
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