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Dr. Bob is Robert Hsiung, MD,
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Posted by Phillipa on June 28, 2010, at 12:56:13
In reply to what is 50mg anafranil = to as SSRI ?, posted by kizzie2 on June 28, 2010, at 12:25:53
No idea how do you convert a different class of meds to another? Different chemicals? Phillipa
Posted by SLS on June 28, 2010, at 15:34:17
In reply to what is 50mg anafranil = to as SSRI ?, posted by kizzie2 on June 28, 2010, at 12:25:53
> Hi I am currently on this dose - and just wondering what would be an equivalent dose of paxil or prozac. ( I have taken both in the past and am just curious as to how high/low my dose is at the moment compared to in the past. I have asked my dr but he is not sure.
> Thanks for any help.
> KizzieOff the top of my head:
Anafranil 50mg
Prozac 10mg
Paxil 10mg
Zoloft 50mg
Luvox 50mg
Celexa 10mg
Lexapro 5mg
Effexor 75mg
Cymbalta 30mg
Pristiq 25mgThese are just my impressions. They are not established quantifications.
- Scott
Posted by SLS on June 28, 2010, at 15:36:31
In reply to Re: what is 50mg anafranil = to as SSRI ? » kizzie2, posted by SLS on June 28, 2010, at 15:34:17
> > Hi I am currently on this dose - and just wondering what would be an equivalent dose of paxil or prozac. ( I have taken both in the past and am just curious as to how high/low my dose is at the moment compared to in the past. I have asked my dr but he is not sure.
> > Thanks for any help.
> > Kizzie> Off the top of my head:
>
> Anafranil 50mg
> Prozac 10mg
> Paxil 10mg
> Zoloft 50mg
> Luvox 50mg
> Celexa 10mg
> Lexapro 5mg
> Effexor 75mg
> Cymbalta 30mg
> Pristiq 25mg
>
> These are just my impressions. They are not established quantifications.You might be able to use a TCA blood test to help establish a therapeutic dosage if necessary.
- Scott
Posted by Brainbeard on June 29, 2010, at 6:10:28
In reply to Re: what is 50mg anafranil = to as SSRI ? » kizzie2, posted by SLS on June 28, 2010, at 15:34:17
With 50mg clomipramine, you would have about 80%+ saturation of serotonin receptors. I think this would demand the following corrections to Scott's numbers:
Anafranil 50mg:
Prozac 20mg
Paxil 20mg
Zoloft 50mg
Luvox 150mg
Celexa 20mg
Lexapro 5mg
Effexor 75mg
These are just my impressions too.
Posted by SLS on June 29, 2010, at 7:06:07
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on June 29, 2010, at 6:10:28
> With 50mg clomipramine, you would have about 80%+ saturation of serotonin receptors.
Is that transporter inhibition? That's interesting, because most people don't get much from clomipramine until they get up to 100-150mg, with a maximum recommended dosage being 250mg. Where can I find out more about the 80% saturation number?
- Scott
Posted by Brainbeard on June 29, 2010, at 17:44:50
In reply to Re: what is 50mg anafranil = to as SSRI ? » Brainbeard, posted by SLS on June 29, 2010, at 7:06:07
> > With 50mg clomipramine, you would have about 80%+ saturation of serotonin receptors.
>
> Is that transporter inhibition? That's interesting, because most people don't get much from clomipramine until they get up to 100-150mg, with a maximum recommended dosage being 250mg. Where can I find out more about the 80% saturation number?
>
>
> - ScottI thought Preskorn (http://www.preskorn.com/books/ssri_s3.html) talked about that, but it turns out he's talking about 80% inhibition of the transporters.
Anyway, only 10mg of clomipramine is equivalent to 50mg of fluvoxamine as for serotonin occupancy*, so you would expect that about 50mg of clomipramine would already yield some pretty impressive SRI.
Raising the dose will favour the noradrenergic metabolite more and more, since this has a longer half-life. So for higher doses, it may really be the noradrenergic boost that is important, plus all the bonuses that come with TCA therapy.
Posted by linkadge on June 29, 2010, at 18:20:42
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on June 29, 2010, at 17:44:50
Further doses may also result in higher occupancy of neurotransmitter receptors (ie 5-ht2a)
Linkadge
Posted by SLS on June 29, 2010, at 18:36:57
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on June 29, 2010, at 17:44:50
I am relating dosage to clinical response, not to isolated measurements of various physiological effects.
- Scott
Posted by Brainbeard on June 30, 2010, at 0:13:58
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by SLS on June 29, 2010, at 18:36:57
> I am relating dosage to clinical response, not to isolated measurements of various physiological effects.
>
>
> - ScottYeah. I was thinking more of SRI potency. When you're thinking of clinical response in general, even 2.5mg of Prozac can be a therapeutic dose. While Luvox is such a weak SSRI that 50mg is unlikely to do much for most people. A 10mg dose of Celexa also seems to be a subtherapeutic level. Same goes for 10mg Paxil. Thing is that 50mg of clomipramine is not a subtherapeutic dose, generally speaking, in my opinion. When you put Zoloft on 50mg in your list, a full therapeutic dose, I can't see why you'd put the drugs mentioned below their full therapeutic levels. But opinions might differ on what's a full therapeutic dose, of course. Preskorn takes 80% inhibition of serotonin receptors as the norm and consequently mentions higher doses for the drugs in question (also 20mg for Prozac).
> Off the top of my head:
>
> Anafranil 50mg
> Prozac 10mg
> Paxil 10mg
> Zoloft 50mg
> Luvox 50mg
> Celexa 10mg
> Lexapro 5mg
> Effexor 75mg
> Cymbalta 30mg
> Pristiq 25mg
Posted by linkadge on June 30, 2010, at 7:10:07
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on June 30, 2010, at 0:13:58
Actually, remember reading a study on pubmed (will look for it) which suggested that 10mg of paxil and celexa were virtually as effective as 20. The difference in response and remission rates were like 3%. They did notice however, that side effects were noticably less in the 10mg groups.
Linkadge
Posted by kizzie2 on June 30, 2010, at 7:43:35
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by linkadge on June 30, 2010, at 7:10:07
Thank you so much for all this information.
Im not sure I completely understand all of it :-) but it is really really useful.
Im slightly disappointed as I think I was hoping that 50mg would be equivalent to 10mg paxil/prozac. Just a psychological thing really because I am a long term user of medication. (11 years now).
Anyway - thank you again.
Posted by Phillipa on June 30, 2010, at 20:51:35
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by linkadge on June 30, 2010, at 7:10:07
I can attest to that as l0mg of paxil first SSRI after three months very effective and don't forget the poster who was here that had been on paxil l0 mg for 13 years no poop out. Phillipa
Posted by Conundrum on July 2, 2010, at 0:54:49
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by linkadge on June 30, 2010, at 7:10:07
this is probably not what you found. its an article from LEF, but the doctor refers to studies where only low doses of drugs were needed for most people but since another 10% responded to higher doses they made the higher dose the standard for everyone.
Posted by ed_uk2010 on July 3, 2010, at 15:49:45
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on June 29, 2010, at 6:10:28
Thanks for the link to the PET study. Fascinating results RE clomipramine.
Here is my impression of comparable doses of SRIs as far as serotonin transporter (SERT) occupancy is concerned........
Sertraline 50mg
Fluoxetine 20mg
Paroxetine 20mg
Citalopram 20-40mg
Escitalopram 10mg
Fluvoxamine 100mg
Venlafaxine XL 75mg
Duloxetine 60mg
Clomipramine, could be as little as 10-20mgAccording to the PET study, even 10mg of clomipramine demonstrated around 80% SERT occupancy. 20mg clomipramine occupied well above 80% of transporters.
I'm not claiming that 20mg of clomipramine is the optimal dose for severe depression, although it could well be sufficient to 'replace' an SSRI. Clomipramine's potent and selective noradrenergic metabolite may contribute to the overall antidepressant efficacy of clomipramine at higher doses. Also, the antihistamine, anticholinergic, and serotonin 5-HT2 antagonist properties of clomipramine will be more prominent at high doses.
In my opinion, psychiatry should completely discard the traditional idea that *all* TCAs (except nortriptyline) should be dosed at 100mg+ per day for optimal efficacy. This is clearly nonsense because the potency of the various TCAs at monoamine reuptake sites and receptors varies greatly. In addition, individual response to TCAs is extremely variable, both clinically and in terms of pharmacokinetics. In the absense of anything better, all we can really do at the moment is 'start low and go slow', avoiding the temptation to make any inflexible pre-treatment decisions about what the final therapeutic dose ought to be.
Posted by SLS on July 3, 2010, at 19:32:59
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on June 29, 2010, at 17:44:50
Potency as an SRI given as tissue concentration is not the same as therapeutic efficacy given as dosage.
- Scott
Posted by RocketMan on July 3, 2010, at 22:54:17
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by SLS on July 3, 2010, at 19:32:59
Lets forget about all the "potential a+g-q5c2 with frontal cortex reabsorption...bla bla bla bla!!!
Bottom line, I was on clomipramine 150mg from 1987 - 1994. My PERSONAL experience indicates clomipramine @150mg is somewhat equivalent to effexor at 150mg or zoloft @ 100mg. All three at the above quoted doses worked very similar in treating my depression, ocd and anxiety.
I'm not going to bother with the unlimited array of factors that may effect therapeutic dosing per individual.... age, other meds on board, endocrinology system, life stressors etc. Bottom line, as my user-name indicates, it's not "rocket" science. Patient response to psych drugs is certainly not about who can come the closest to drug/drug equivalency. Hell, if someone here feels confident in sharing such factual information, perhaps they could also share it with p/docs, pharmaceutical companies etc, it might help alleviate allot of the suffering us people experience when looking for another med to cross over to?
Posted by SLS on July 4, 2010, at 6:22:19
In reply to Re: what is 50mg anafranil = to as SSRI ? » kizzie2, posted by SLS on June 28, 2010, at 15:34:17
It would be interesting to see the full article represented by this abstract. However, taken as a whole, the results appearing here indicate that higher dosages of clomipramine produce greater therapeutic effect than the lower dosages as tested using clinical outcome as the measurement.
- Scott
--------------------------------------------
Clin Pharmacol Ther. 1999 Aug;66(2):152-65.
Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG).[No authors listed]
AbstractOBJECTIVE: To examine the problems of establishing dose-effect and concentration-effect relationships of antidepressant therapy with clomipramine. METHODS: This randomized double-blind study compared five fixed doses of clomipramine hydrochloride: 25, 50, 75, 125, and 200 mg/day in hospitalized or day patients at nine clinical centers in Denmark. A 1-week washout period was followed by 6 weeks of active treatment and weekly depression ratings. In total, 151 patients (100 women and 51 men) with major depression scoring > or =18 on the Hamilton Depression Scale (HDS) or > or =9 on the Hamilton Depression subscale (HDSS) before and after the washout period were randomized. The treatment groups (n = 29 to 32) were well balanced with respect to sex, age, and depression rating. Serum concentrations of clomipramine plus metabolites were measured at weekly intervals. A sparteine test was performed before and during drug treatment. RESULTS: There was pronounced interpatient variability in response and kinetics at each dose. Drop-outs attributable to adverse events increased with rising doses, whereas drop-outs caused by worsening or lack of effect or nonresponse declined with increasing dose. Completer analyses showed a moderate and statistically significant relationship between depression rating and dose at all ratings after 1 to 6 weeks of treatment (trend analysis). HDS items representing core symptoms of depression showed a particularly consistent dose-effect relationship. Early sustained response occurred more frequently with the two highest doses. Serum levels of clomipramine and desmethylclomipramine showed weak correlation with depression ratings (Rs = -0.18 to -0.27; P < .05 to P < .01). A few blood pressure measurements and a few typical side-effect ratings showed a statistically significant dose-effect and concentration-effect relationship. Serum concentration of clomipramine and desmethylclomipramine showed a pronounced disproportionate increase with increasing dose. Clomipramine inhibited in a dose-dependent fashion CYP2D6 (sparteine oxidation). CONCLUSION: The dose-effect curves, indicating the probability of a certain outcome at a given dose, were flat and overlapping suggesting a narrow therapeutic range. This pattern is similar to that observed with newer antidepressants.
Posted by ed_uk2010 on July 4, 2010, at 8:20:34
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by SLS on July 3, 2010, at 19:32:59
>Potency as an SRI given as tissue concentration is not the same as therapeutic efficacy given as dosage.
Definitely, but no one is suggesting that.
What the PET studies show is that citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine and venlafaxine all demonstrate approximately 80% SERT occupancy at the minimum doses which have been demonstrated to be effective in clinical trials. These are the doses which I listed in my post above. Higher doses produce slightly greater occupancy but the difference is not large.
Clomipramine is different because although 10-20mg per day is now believed to produce approximately 80% SERT occupancy in the 'average patient', such low doses have not been proven to be effective in clinical trials. One of the reasons for this could be that very low doses of clomipramine do not appear to have been studied - all trials used higher doses.
Unlike SSRIs, which have a relatively flat dose-response curve at usual doses, I would expect clomipramine to show increased efficacy at high doses because it produces many other effects apart from SERT inhibition. Even so, I do think it's very likely that 20mg clomipramine would be more effective than placebo as an antidepressant.
Posted by ed_uk2010 on July 4, 2010, at 8:26:14
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by RocketMan on July 3, 2010, at 22:54:17
>Hell, if someone here feels confident in sharing such factual information, perhaps they could also share it with p/docs, pharmaceutical companies etc, it might help alleviate allot of the suffering us people experience when looking for another med to cross over to?
Pharmaceutical companies are already well aware of the PET studies which have been performed on SSRIs. In the case of duloxetine, the manufacturer actually used PET studies to help them decide which dose to test again placebo in their phase III clinical trials.
Posted by SLS on July 4, 2010, at 18:50:43
In reply to Potency of clomipramine? - very high! » Brainbeard, posted by ed_uk2010 on July 3, 2010, at 15:49:45
> In my opinion, psychiatry should completely discard the traditional idea that *all* TCAs (except nortriptyline) should be dosed at 100mg+ per day for optimal efficacy.
That's an interesting thought. It goes against what I have been taught, but I don't know the details as to how the dosage ranges for these drugs were arrived at.
- Scott
Posted by ed_uk2010 on July 5, 2010, at 0:54:08
In reply to Re: Potency of clomipramine? - very high!, posted by SLS on July 4, 2010, at 18:50:43
>It goes against what I have been taught, but I don't know the details as to how the dosage ranges for these drugs were arrived at.
Part of the problem seems to have been that when new TCAs (such as clomipramine) were brought out, it was assumed that they should be administered at the same dose as earlier TCAs. The huge variations in potency and receptor binding between the different TCAs doesn't seem to have been considered. Another problem was that doses were increased before giving lower doses a change to work eg. by titrating to 150mg over 2 weeks.
Posted by Brainbeard on July 5, 2010, at 13:04:34
In reply to Re: what is 50mg anafranil = to as SSRI ? » SLS, posted by ed_uk2010 on July 4, 2010, at 8:20:34
I once switched from 150mg fluvoxamine (Luvox) to 10mg clomipramine. Based on the study quoted, I thought 10mg clomipramine should be enough to compensate for the loss of SRI by quitting fluvoxamine. It wasn't by far enough to counter fluvoxamine's withdrawal syndrome, though. Subjectively, 10mg of clomipramine was more in the neighbourhood of placebo.
There is a study showing good results for patients with panic disorder with only 10mg of clomipramine. But panic people often get away with taking subtherapeutic doses.
I think that about 40, 50mg of clomipramine could be enough to provide robust SRI.
Posted by ed_uk2010 on July 5, 2010, at 14:47:57
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by Brainbeard on July 5, 2010, at 13:04:34
> I once switched from 150mg fluvoxamine (Luvox) to 10mg clomipramine. Based on the study quoted, >I thought 10mg clomipramine should be enough to compensate for the loss of SRI by quitting fluvoxamine. It wasn't by far enough to counter fluvoxamine's withdrawal syndrome, though. Subjectively, 10mg of clomipramine was more in the neighbourhood of placebo..........I think that about 40, 50mg of clomipramine could be enough to provide robust SRI
According to one of the graphs in the article that you posted a link to, 10mg clomipramine appears to give less than 80% occupancy. 20mg gave more than 80%, both after a single dose and on repeated dosing. I expect you are correct that 40-50mg would provide robust serotonin reuptake inhibition. I've seen a clinical study which used 30mg per day for depression.
Posted by kizzie2 on July 6, 2010, at 12:59:32
In reply to Re: what is 50mg anafranil = to as SSRI ? » Brainbeard, posted by ed_uk2010 on July 5, 2010, at 14:47:57
Thank you all so much for taking part in this discussion. It has given me a lot to think about - although i cant pretend to understand a lot of it :-)
I am hoping to be able to stay on 50mg for at least 6 months and then slowly reduce to 25mg and stay there for the foreseeable future if possible.
I seem to be ok on lower doses (fngers crossed that continues) but when i get down to 0 (even after very slow withdrawal I go from having a succesful career and happy family life - to being incapable of leaving the house and severe panic /depression.
Im a bit disappointed that from what you all say it seems that 50mg is probably equal to 20mg paxil as i was hoping i was on less than that (just for psychological reasons really because i am on the medication long term.)
Anyway - thanks again
Posted by Brainbeard on July 6, 2010, at 13:14:54
In reply to Re: what is 50mg anafranil = to as SSRI ?, posted by kizzie2 on July 6, 2010, at 12:59:32
Well, from all I know and have heard, you're far better off to be on Anafranil long-term than you would be on an SSRI long-term, especially Paxil (because of its withdrawal syndrome). All SSRI's tend to 'poop out', i.e. quit working, after some two to seven years. This phenomenon is uncommon with Anafranil.
If you were ever to quit Anafranil, you could try switching to Prozac to have a really, really slow taper because of Prozac's long half-life (i.e. it stays in your blood a loooong time). But I suspect the benefits Anafranil is giving you outweigh its cost.
This is the end of the thread.
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