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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by linkadge on June 2, 2004, at 21:51:01
Does this med produce tachycardia to the same extent that meds like despiramine and nortrypaline do ?? How were other side effects.
Linkadge
Posted by Pluto on June 3, 2004, at 2:20:25
In reply to Anyone tried Anafranil, posted by linkadge on June 2, 2004, at 21:51:01
Hi
Anafranil seems to be the best OCD medication for patients like me. I am not using it now, but was on it for a long time. The only problem with it was dry mouth and delayed ejaculation(Which my wife enjoyed). I didn't experience any tachycardia while on it. Nortryptiline and desipramine, both have high affinity on noradrenaline, while clomipramine mainly targets serotonin. Tachycardia is a problem with noradrenergic drugs. If you are too concerened with it, try to add prazosine or doxazosine at low doses. Don't give up a medication if you find it effective, but has mild treatable problem.
PLS
Posted by Keith Talent on June 4, 2004, at 10:56:50
In reply to Anyone tried Anafranil, posted by linkadge on June 2, 2004, at 21:51:01
Linkadge,
I've said to many people at Psycho-Babble, and I'll say it again, that clomipramine was THE best antidepressant I've ever been on. It's no wonder that it is used to successfully treat some of the most severely depressed inpatients. But it made me so much better than I could no longer tolerate the side effects.
> Does this med produce tachycardia to the same extent that meds like despiramine and nortrypaline do?
In my experience (but I have never taken desipramine), yes.
> How were other side effects.
The worst was anorgasmia, which caused me to stop taking it. It also caused some short-term memory impairment.
Oh, and by the way, Pluto:
> Nortryptiline and desipramine, both have high affinity on noradrenaline
What does this mean? Do you mean that these drugs mainly work by inhibiting noradrenaline reuptake? Or that they have alpha-1 receptor antagonism as a side effect?
> while clomipramine mainly targets serotonin.
Again, what does that mean? Blocking the serotonin transporter? Blocking serotonin-2 receptors? In point of fact, clomipramine is an extremely potent serotonin reuptake inhibitor and a moderately potent noradrenaline reuptake inhibitor. Its active metabolite, desmethylclomipramine, is an extremely potent noradrenaline reuptake inhibitor (about as powerful as desipramine at this). After steady-state concentrations of both clomipramine and its desmethyl- metabolite have been reached (about a week or two), the concentration of the desmethylclomipramine is substantially higher. Therefore, it is misleading to state, as you did, that "clomipramine mainly targets serotonin".
> Tachycardia is a problem with noradrenergic drugs.
Very vague. Beta blockers are "noradrenergic drugs" but they can cause severe bradycardia. I suppose you mean drugs that inhibit noradrenaline reuptake.
> If you are too concerened with it, try to add prazosine or doxazosine at low doses.
Are you for real? Prazosin and doxazosin are alpha-1 antagonists (the tricyclics possess this property to varying degrees and it causes postural hypotension, impotence and can contribute to tachycardia). They cause vasodilation on the arterial side, which will lead to, not ameliorate, (reflex) tachycardia! Also, you forgot to mention that tricyclic-induced tachycardia is in large part due to muscarinic acetylcholine receptor antagonism (reducing the parasympathetic influence on the heart, and altering the balance in favour of sympathetic input to the heart).
Linkadge,
If you are in the midst of a Major Depressive Episode of any severity, I commend this drug to you. If you're treatment resistant or getting to the point of needing admission, I would especially urge you to consider clomipramine.
Best of luck, mate,
Keith.
Posted by Pluto on June 6, 2004, at 3:18:32
In reply to Re: Anyone tried Anafranil, posted by Keith Talent on June 4, 2004, at 10:56:50
Hi Keith,
>What does this mean? Do you mean that these drugs mainly work by inhibiting noradrenaline reuptake? Or that they have alpha-1 receptor antagonism as a side effect?
Nortriptyline and desipramine, both works by inhibiting noradrenaline rather than the other main neurotransmitter involved in the case of depression that is serotonin. Yes, they both have effects on alpha receptor too, that may be the cause of high incidence of erectile difficulties attributed to these drugs. Reboxetine, a specific noradrenaline reuptake inhibitor has more pronounced action on erction even at lower doses. Alpha 2 antagonism usually leads to better erections in man and in extreme cases priapism can occur. Almost all alpha 2 antagonists have priapism as a side effect, though this drug induced priapism doesn't usually lead to permenant sexual dysfunction. (Trazodone is an exception, which can cause treatment resistant priapism and consequently permenant erectile dysfunction).
>Again, what does that mean? Blocking the serotonin transporter? Blocking serotonin-2 receptors? In point of fact, clomipramine is an extremely potent serotonin reuptake inhibitor and a moderately potent noradrenaline reuptake inhibitor. Its active metabolite, desmethylclomipramine, is an extremely potent noradrenaline reuptake inhibitor (about as powerful as desipramine at this). After steady-state concentrations of both clomipramine and its desmethyl- metabolite have been reached (about a week or two), the concentration of the desmethylclomipramine is substantially higher. Therefore, it is misleading to state, as you did, that "clomipramine mainly targets serotonin".
Clomipramine's high affinity on serotonin is doubtlessly proved and it is this preciousness that makes it the most effective anti-OCD medication. This doesn't mean it doesn't possess other properties too. Remember sertraline is a selective serotonin re-uptake inhibitor, but has pronounced dopaminergic actions too at doses higher than 100mg, but still we rate sertraline as a serotonin re-uptake inhibitor. Clomipramine's affinity on noradrenaline is the reason for it's use in narcolepsy. But it's main indication is OCD, not narcolepsy.>They cause vasodilation on the arterial side, which will lead to, not ameliorate, (reflex) tachycardia! Also, you forgot to mention that tricyclic-induced tachycardia is in large part due to muscarinic acetylcholine receptor antagonism (reducing the parasympathetic influence on the heart, and altering the balance in favour of sympathetic input to the heart).
Peripheral vasodilation on both resistance vessels and capacitance vessels does not provoke reflex tachycardia, but can be beneficial in some cases of tachycardia. (Check the data sheets of both drugs in ABPI Medicines compendium)
Best of luck. Please correct me, if I am wrong.
PLS
Posted by Keith Talent on June 7, 2004, at 13:10:55
In reply to Re: Anyone tried Anafranil » Keith Talent, posted by Pluto on June 6, 2004, at 3:18:32
> Nortriptyline and desipramine, both works by inhibiting noradrenaline
Inhibiting reuptake or antagonising receptors?
> rather than the other main neurotransmitter involved in the case of depression that is serotonin.
THE other main neurotransmitter? What about all the patients who require dopaminergic agents to fully recover from a Major Depressive Episode?
> Reboxetine, a specific noradrenaline reuptake inhibitor has more pronounced action on erction even at lower doses.
Is there is any scientific research supporting this assertion (that "reboxetine ... has more pronounced action on erction" than desipramine and/or nortriptyline)?
> Alpha 2 antagonism usually leads to better erections in man and in extreme cases priapism can occur. Almost all alpha 2 antagonists have priapism as a side effect, though this drug induced priapism doesn't usually lead to permenant sexual dysfunction. (Trazodone is an exception, which can cause treatment resistant priapism and consequently permenant erectile dysfunction).
I'm too lacking in knowledge of psychopharmacology to know anything about the validity of the above statements re alpha-2 antagonism and erectile function. But how is alpha-2 antagonism relevant to clomipramine, desipramine, nortriptyline or reboxetine?
> Clomipramine's high affinity on serotonin
Do you mean affinity for the serotonin transporter or for one or more serotonin receptors?
> is doubtlessly proved and it is this preciousness that makes it the most effective anti-OCD medication. This doesn't mean it doesn't possess other properties too.
Pluto, I'm glad that we agree on some things!
> Remember sertraline is a selective serotonin re-uptake inhibitor, but has pronounced dopaminergic actions too at doses higher than 100mg
Actually, I used to sort of believe this, but when you consider how high a concentration in the brain of sertraline (compared to the concentration produced by typically used doses) that you would need to cause a useful occupancy rate of dopamine transporters (say 70%-80%), and the daily dose needed to achieve such a concentration, and the basically 100% blockade of serotonin transporters that such a concentration would cause (with all the attendant side effects), then in practical terms sertraline does NOT have "pronounced dopaminergic actions too". I can't remember the exact ratio of potencies of sertraline at serotonin reuptake inhibition compared to dopamine reuptake inhibition, but I think it's around 10 000. My knowledge of pharmacology is insignificant, such that I don't know whether you can simply multiply the 10 000 by the typical 100 mg daily dose to arrive at a "dopaminergically effective" dose, but such a dose would have to be at least one gram per day, and perhaps ten or 100 grams. The side effects (and even the cost) of such doses would be intolerable.
> Clomipramine's affinity on noradrenaline
Again, affinity for the noradrenaline transporter and/or receptors?
> Peripheral vasodilation on both resistance vessels and capacitance vessels does not provoke reflex tachycardia, but can be beneficial in some cases of tachycardia.
Interesting. You learn something new every day. Does alpha-1 antagonism have greater vasodilatory effects on resistance or capacitance vessels? Also, do you accept that anticholinergic activity is, in large measure, responsible for the tachycardia caused by tricyclic antidepressants? It's a pleasure to converse with such an educated person. May I ask your educational and occupational backgrounds? As for myself, I quit med school and am doing a finance major (but am at Pyscho-Babble for the usual - personal health - reasons).
Thanks for your time,
Keith.
Posted by linkadge on June 7, 2004, at 19:37:50
In reply to Re: Anyone tried Anafranil, posted by Keith Talent on June 7, 2004, at 13:10:55
I was really sensitive to effexor induced tachycardia and high blood pressure.
How does this compare to clomipramine. IS this drugs a likely cause of tachycardia or not. Is this risk less likely with clomimpramine then say nortiptaline ??
Linkadge
Posted by Keith Talent on June 8, 2004, at 10:08:45
In reply to sorry I'm a little confused, posted by linkadge on June 7, 2004, at 19:37:50
> I was really sensitive to effexor induced tachycardia and high blood pressure.
>
> How does this compare to clomipramine.Clomipramine will cause tachycardia, but will reduce blood pressure (especially when moving from a lying to a standing position). I don't remember experiencing tachycardia whilst taking Effexor.
> IS this drug a likely cause of tachycardia?
Assuming you're referring to clomipramine, yes, it's a definite cause.
> Is this risk less likely with clomipramine than, say, nortriptyline?
From my memories of the two, clomipramine probably caused a bit worse tachycardia than nortriptyline. But then, I found nortrtiptyline to be hopeless for my depression. You could probably find some laboratory data to check this against at preskorn.com (look at which drug more potently antagonises muscarinic acetylcholine receptors).
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