# Clomipramine vs Imipramine



## gilmourr (Nov 17, 2011)

If you could, select one that you would use if you had major depression + panic disorder + mild agoraphobia. Right now going to try one of these two. Weighing the pros/cons.

*Imipramine*
- Shorter Half life
- Apparently cases of EPS symptoms? (Is this even likely?)
- Golden standard for panic disorder (apparently)
- Better for sleep (more antihistamine I believe)
- Better ACh profile

*Clomipramine*
- Sexual dysfunction/libido dysfunction (chances?)
- Strong potential as med
- Less NE symptoms and tachycardia I believe than imipramine.
- Insomnia? (This is one side effect I can't deal with. If I get less than 2-3 hours of sleep, I'll be off it in 1.5 weeks max.)
- Worse ACh profile

** Does anyone know what dose to start off on? Should I take these from a low dose and titrate quickly? For quite a few meds I was able to max out, cipralex, 20 mg, zoloft 200 mg, others I've needed less.

Also, do either of these leave room for augment therapies? ***


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## Inshallah (May 11, 2011)

*Based on my study of both*

I recently had to make this choice as well and I chose Clomipramine because it is the stronger serotonergic of the two. I am going to take Ritalin with it so I'll be making my own SNDRI that way and it made more sense to choose the one providing the most serotonin.

Having been on a DRI, NRI and SRI, I know for certain serotonin is the most important of the 3 for anything mood-related (anxiety, depression, panic). Note that I didn't say it is the only important neurotransmitter, but the most important of the 3 main neurotransmitters nonetheless. I do think the more severe depression cases (like mine unfortunately) have a lot that is going wrong biochemically, so it makes sense that these people would need more than just a serotonin push.

Clomipramine is specifically used for insomnia according to one of Stahl's books and it is sedating so it should only help you sleep.

For you, I'd still also go for Clomipramine. But know that I'm 100% sure the sexual dysfunction will be harsher. Clomipramine is even used for premature ejaculation ... I myself of course have Ritalin that will help me out in that department, which you won't be taking, so take that into account. Providing you think you can live with the sexual dysfunction, I'd say go for Clomipramine. If not, obviously don't hesitate to go for Imipramine.

According to the Anafranil-leaflet: you start up/build up by taking 25 mg 2-3 times a day, and every 2-3 days add 25 mg until you arrive at 150. If that doesn't work well enough, you can go to a max of 250 mg. Should you use the "retard" version (lol I know), only take it once a day instead of spread out over 2-3 times.

But they are considered to be in the top 3 tricyclics and are both better than the newer AD's, so you should make a good choice regardless of which one you choose


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## Inshallah (May 11, 2011)

Augmentation: you can take basically anything with them you can add to SSRI's/SNRI's. 

I will be taking Anafranil in max dose + Ritalin in max dose. 

You can also add Wellbutrin, Remeron, AP's, benzo's, Lyrica, ... You can even add an SSRI apparently (treatment resistant OCD) but obviously don't do this on your own.


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## Konami (Jul 5, 2011)

thanks for the info Inshallah,it was very helpful to me as i too need to decide between Anfranil and Elatrol (the Israeli Imipramine)
I think based on what you said Anafranil would be a better choice for me. 
thank you!


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## Konami (Jul 5, 2011)

do you guys know pharmacology wise, which of those two has more NE effect?


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## Inshallah (May 11, 2011)

konamitech said:


> do you guys know pharmacology wise, which of those two has more NE effect?


Imipramine!


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## jim_morrison (Aug 17, 2008)

Taking active metabolites into account they come out about equal in NE effect

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014120/table/tbl4/


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## Konami (Jul 5, 2011)

thanks for both of you. now im confused lol


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## Inshallah (May 11, 2011)

konamitech said:


> thanks for both of you. now im confused lol


I'm no expert on pharmacology, maybe jim can explain 

I just found this:

"J Clin Psychopharmacol. 1992 Aug;12(4):251-61.
Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo-controlled trial.
Modigh K, Westberg P, Eriksson E.
Source
Department of Psychiatry and Neurochemistry, University of Göteborg, Sweden.
Abstract
A double-blind, placebo-controlled trial was undertaken to compare the effects of imipramine and clomipramine in the treatment of panic disorder with or without agoraphobia. The number of dropouts in the placebo-treated group was 7; in the imipramine-treated group, 4; and in the clomipramine treated group, 0. Ten subjects fulfilled the 12 weeks of treatment in the placebo group, 25 in the imipramine group, and 22 in the clomipramine group. To minimize dropouts because of side effects, a flexible dose regimen with a careful escalation of doses was applied. The maximal dose allowed was 250 mg/day. The mean (+/- SEM) daily doses reached were 124 +/- 9 mg (range, 50-250 mg) of imipramine and 109 +/- 8 mg (range, 25-200 mg) of clomipramine. At the end of the trial, the number of panic attacks as well as the anxiety between attacks (measured using the Hamilton Rating Scale for Anxiety) were markedly reduced in patients treated with either of the two antidepressant drugs, but only slightly decreased in patients on placebo. With respect to all major outcome parameters, i.e., full panic attacks, total number of anxiety attacks (full plus mild), and anxiety between attacks, the effect of clomipramine was clearly and significantly superior to that of imipramine (p less than 0.001, p less than 0.002, and p less than 0.002, respectively). Moderate intake of diazepam was allowed; in the clomipramine group (p less than 0.006), but neither in the imipramine group nor in the placebo group, a significant decrement in diazepam intake was observed during the course of the trial. *The finding that clomipramine may have a higher potency and/or efficacy than imipramine in the treatment of panic disorder supports the concept that the antipanic effect of antidepressant drugs is due to the influence of these compounds on serotonergic rather than noradrenergic neurotransmission.*
PMID: 1527228 [PubMed - indexed for MEDLINE]"


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## Inshallah (May 11, 2011)

"Abstract
Twenty-three outpatients with primary obsessive-compulsive disorder (OCD) were started in a 12-week double-blind clinical trial of clomipramine (CLI) (n = 11) and imipramine (IMI) (n = 12). There was no placebo and no crossover. After 6 weeks of treatment, data on 19 subjects (9 CLI, 10 IMI) were available. After week 12, the sample was reduced to 16 patients (8 CLI, 8 IMI). At both time points, OCD symptoms showed modest reductions (in comparison with the pretreatment baseline) in both CLI and IMI groups. Both drugs showed a major antidepressant effect. *Analyses accounting for the differences in the baseline levels indicated a somewhat superior effect of CLI over IMI on OCD as well as depression. The effect of CLI and IMI on OCD was independent of the initial severity of depression. There were no clear differences in the safety of the treatments.*"


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## Inshallah (May 11, 2011)

"Abstract
Clomipramine and imipramine treatments were compared in a sample of 152 panic disorders. Diagnosis was according to the positive criteria of DSM-III-R, but without exclusion of comorbid affective or personality disorders. The 2-year design provides non-blind treatment under typical clinical practice conditions, and it includes random assignment, periodic assessment with standardized measures, and comparable, flexible drug dosages. Findings on six outcome measures in the first 59 cases to complete 10 weeks showed both tricyclics to be markedly and equally effective for blocking panic attacks, alleviating phobic avoidance, and reducing nonspecific aspects of anxiety. Clomipramine's predominantly serotonergic action seemed not to determine a different action spectrum. *During the first 2 weeks, clomipramine was significantly and unexpectedly superior to imipramine in both antipanic and antiphobic actions. These results require replication under double-blind conditions.*"


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## Konami (Jul 5, 2011)

Inshallah said:


> I'm no expert on pharmacology, maybe jim can explain
> 
> I just found this:
> 
> ...


Thanks for the info.
pulling up my memory from those two drugs (was on both years ago) i can say that IMI knocked me out! i mean i couldn't get farther than 50mg after about 40 days i gave up(i was sleeping my *** over the day)
as for Anafranil, i remember sweating like hell which led to stop taking it after 2 weeks. maybe i should have given it more time but it was August he he he


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## Inshallah (May 11, 2011)

"Drugs. 1990 Jan;39(1):136-53.
Clomipramine. An overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder.
McTavish D, Benfield P.
Source
ADIS Drug Information Services, Auckland, New Zealand.
Abstract
During the 20 years that have elapsed since clomipramine (chlorimipramine) was first marketed, it has become well established in the treatment of depressive illness, particularly treatment-resistant depression. However, in addition to its role as an antidepressant, attention is being focused on the use of clomipramine in 2 other areas of psychiatry: obsessive compulsive disorder and panic disorder. Short term clinical trials have shown that clomipramine is generally more effective than amitriptyline, imipramine, desipramine, nortriptyline or clorgiline in reducing obsessive compulsive symptoms. Clomipramine appears to produce some short term benefit with exposure therapy in patients with obsessive compulsive disorder. However, the efficacy of the drug after long term follow-up has not been fully investigated. The antiobsessional efficacy of clomipramine appears to be independent of its antidepressant activity. In patients with panic disorder with or without agoraphobia (DSM-IIIR), clomipramine reduces the frequency and severity of panic attacks within 7 to 21 days of beginning treatment and efficacy is maintained for at least 12 months. Clomipramine is more effective than imipramine, the generally accepted standard treatment for patients with panic disorder after 2 weeks' treatment, but after 6 or 10 weeks both drugs are similarly effective. Other double-blind studies have shown that clomipramine is more effective than placebo and at least as effective as fluvoxamine and oxitriptan (5-hydroxytryptophan) in reducing panic attacks and associated anxiety. Adverse effects associated with clomipramine treatment are mild to moderate in nature and are predominantly a result of the drug's anticholinergic activity. The incidence of seizures is dose related, occurring in 0.48% of all patients receiving clomipramine less than or equal to 250 mg/day and 2.1% of patients receiving greater than or equal to 300 mg/day. In conclusion, the available data indicate that clomipramine is a worthwhile addition to the limited treatments available for obsessive compulsive disorder and panic disorder, two psychiatric disorders which have previously been difficult to manage pharmacologically.
PMID: 2178909 [PubMed - indexed for MEDLINE]"


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## Arisa1536 (Dec 8, 2009)

less weight gain in imipromine, speaking from someone who has dabbled in taking TCA meds


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## Inshallah (May 11, 2011)

konamitech said:


> Thanks for the info.
> pulling up my memory from those two drugs (was on both years ago) i can say that IMI knocked me out! i mean i couldn't get farther than 50mg after about 40 days i gave up(i was sleeping my *** over the day)
> as for Anafranil, i remember sweating like hell which led to stop taking it after 2 weeks. maybe i should have given it more time but it was August he he he


They both get a 3/4 rating for sedation in Stahl's Essential Pharmacology so they shouldn't differ that much in that regard. I'm on 100 mg now and no tiredness/sleepiness so far.


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## gilmourr (Nov 17, 2011)

Inshallah said:


> I recently had to make this choice as well and I chose Clomipramine because it is the stronger serotonergic of the two. I am going to take Ritalin with it so I'll be making my own SNDRI that way and it made more sense to choose the one providing the most serotonin.
> 
> Having been on a DRI, NRI and SRI, I know for certain serotonin is the most important of the 3 for anything mood-related (anxiety, depression, panic). Note that I didn't say it is the only important neurotransmitter, but the most important of the 3 main neurotransmitters nonetheless. I do think the more severe depression cases (like mine unfortunately) have a lot that is going wrong biochemically, so it makes sense that these people would need more than just a serotonin push.
> 
> ...


Alright, thanks for the info on the start up milligram dosage.

What are your side effects so far for clomipramine? Any dysfunction or libido issues so far? I can have partial dysfunction but if it's 100% then yeah I won't be able to stay on it. Well the dysfunction is better than 100% decrease in libido. Because paxil didn't just make it impossible, it made me an asexual fern.

Luckily I probably won't need to max out because I don't have OCD. So maybe panic and depression will need less?

I'm still pretty torn between the two meds because I really believe based on reviews imipramine is better for panic/agoraphobia, it's just hard to get past the side effects initally.


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## gilmourr (Nov 17, 2011)

Arisa1536 said:


> less weight gain in imipromine, speaking from someone who has dabbled in taking TCA meds


Side effects so far? How much sexual dysfunction, libido dysfunction and sedation?

Also is your memory affected by the anti-cholinergic effects? And what are the odds of movement disorders that I've heard about on imipramine?

I believe that if you get them you stop the drug immediately and use a choline agonist drug. Let me know if you know anything about this or my preceding questions.


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## gilmourr (Nov 17, 2011)

Also, imipramine has a histamine blockade of 9.1 while seroquels inactive metabolite is 4 and it's active is 1. Which means that imipramine is stronger on histamine correct?

Seroquel does a good job getting me to sleep. I take 12.5 mg and that actually usually works. Sometimes I'll have to take 25 mg but that's really not that much right? So I'm not sure if I'd get used to the histamine.

Does anyone know what milligram level does seroquel max out on histamine receptors? Is it like 50 mg or something and then it moves to others mainly?

Also answer if imipramine is similar to seroquel please! ty.


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## ricca91 (Mar 11, 2012)

gilmourr said:


> Also, imipramine has a histamine blockade of 9.1 while seroquels inactive metabolite is 4 and it's active is 1. Which means that imipramine is stronger on histamine correct?
> 
> Seroquel does a good job getting me to sleep. I take 12.5 mg and that actually usually works. Sometimes I'll have to take 25 mg but that's really not that much right? So I'm not sure if I'd get used to the histamine.
> 
> ...


About the potency on histamine blockade, it depends on the measure you are using. If it's Kd (constant of dissociation) the less the number, the more potent the antagonist (to put it simply).

So I would expect seroquel to be more sedating. In my experience it hits you like a ton of bricks. 12.5 or 25 is a very low dose. At this dose you'll get histamine 1 and alpha 1 blockade.

As you move up, between 100 and 200 mg it touches serotonin receptors (5-HT2A mostly and some 5-HT2C). I don't recall if it also antagonizes 5-HT7. The name "Seroquel" derives from the antagonism on serotonin receptors quetiapine does.

After 200 mg you'll begin to get D2 blockade which in your case is almost useless.


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## jim_morrison (Aug 17, 2008)

konamitech said:


> thanks for both of you. now im confused lol


It's best to think of Clomipramine as a hybrid of a tricyclic and an SSRI.

Basically Imipramine, Clomipramine and Amitriptyline are all about equally potent at inhibiting Norepinephrine re-uptake transporters thanks to their metabolites which are strong NRI's.

Serotonin re-uptake differs though with the order of potency going Clomipramine> Imipramine> Amitriptyline. With Clomipramine being the only tricyclic antidepressant with potent enough serotonin reuptake to be comparable to an SSRI.


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## Inshallah (May 11, 2011)

gilmourr said:


> Alright, thanks for the info on the start up milligram dosage.
> 
> What are your side effects so far for clomipramine? Any dysfunction or libido issues so far? I can have partial dysfunction but if it's 100% then yeah I won't be able to stay on it. Well the dysfunction is better than 100% decrease in libido. Because paxil didn't just make it impossible, it made me an asexual fern.
> 
> ...


The sexual side effects were present from day 1 and pretty much as worse as it can get. I never really lost my libido or erection on meds but do always experience anorgasmia and it's the same again now. No other side effects so far.

Doses for depression are generallly lower than for OCD yes.


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## gilmourr (Nov 17, 2011)

Inshallah said:


> The sexual side effects were present from day 1 and pretty much as worse as it can get. I never really lost my libido or erection on meds but do always experience anorgasmia and it's the same again now. No other side effects so far.
> 
> Doses for depression are generallly lower than for OCD yes.


Anorgasmia is much more fine to me than erectile dysfunction or loss of libido. 
Cause then I can still at least be with someone, as opposed to no libido and just being like, so wait... why are we dating again?

Libido loss is awful


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## Ben12 (Jul 8, 2009)

What's the point to libido if you get anorgasmia?


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## Inshallah (May 11, 2011)

Yeah I would rather have the libido loss or even impotence (simply take Cialis or Viagra) than the anorgasmia. But if doesn't bother you that much, then go for it I'd say.


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## gilmourr (Nov 17, 2011)

Ben12 said:


> What's the point to libido if you get anorgasmia?


Without libido I couldn't see myself in a relationship because then a girl is really just a "friend." Which makes it difficult to be around them so frequently, because attraction is usually what keeps a relationship going, or it's what starts one at the very least.

Libido > erection > orgasm

Anorgasmia mainly affects one person, though the other two usually greatly affect both people. Libido keeps you interested, erections show that you're interested.

Regardless, it'd suck to lose any of these 3 haha


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## gilmourr (Nov 17, 2011)

Inshallah said:


> Yeah I would rather have the libido loss or even impotence (simply take Cialis or Viagra) than the anorgasmia. But if doesn't bother you that much, then go for it I'd say.


You're right that maybe erectile dysfunction can be last and anorgasmia the 2nd most important sex function, since there is viagra. But really, I don't see myself using viagra at this age even if I had erectile dysfunction.


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## Ben12 (Jul 8, 2009)

For me it just wouldn't be worth staying on a medication long term if there were any sexual side effects. Everyone is different though.


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## gilmourr (Nov 17, 2011)

Ben12 said:


> For me it just wouldn't be worth staying on a medication long term if there were any sexual side effects. Everyone is different though.


Agreed. But major insomnia is the worst side effect I believe. Actually suicidal thoughts are. Then major insomnia. The kind where you literally get 1 hour a day. It's awful.


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## Ben12 (Jul 8, 2009)

gilmourr said:


> Agreed. But major insomnia is the worst side effect I believe. Actually suicidal thoughts are. Then major insomnia. The kind where you literally get 1 hour a day. It's awful.


Yeah I'd definitely have to agree with you on that one. Insomnia is just the worst. The main reason why I started seroquel years ago. Interestingly enough I was on Effexor though before I got the really bad insomnia. So I then went on to seroquel. Wish I just didn't bother with the whole going to a psychiatrist to get meds. No antidepressant really helped me in the long term.


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## Konami (Jul 5, 2011)

gilmourr said:


> Anorgasmia is much more fine to me than erectile dysfunction or loss of libido.
> Cause then I can still at least be with someone, as opposed to no libido and just being like, so wait... why are we dating again?
> 
> Libido loss is awful


well said gilmourr,
I started Anafranil yesterday and guess what my dr said about Anafranil and sex drive?
"this med will actually increase your drive"
really??????


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## gilmourr (Nov 17, 2011)

konamitech said:


> well said gilmourr,
> I started Anafranil yesterday and guess what my dr said about Anafranil and sex drive?
> "this med will actually increase your drive"
> really??????


Lol. Well at least the positive is that you're on a new med and not in withdrawal. Nardil withdrawal is taking a beating on my head. Nausea, headaches, depressive mood swings that are really tough (resorting to writing and reading to try and shake them off).

I just hope I can get on zoloft + lamictal with minimal pain and suffering from major depression.


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## Konami (Jul 5, 2011)

gilmourr said:


> Lol. Well at least the positive is that you're on a new med and not in withdrawal. Nardil withdrawal is taking a beating on my head. Nausea, headaches, depressive mood swings that are really tough (resorting to writing and reading to try and shake them off).
> 
> I just hope I can get on zoloft + lamictal with minimal pain and suffering from major depression.


i was on Remeron 60mg for 3 months and it helped me tremendously , i stopped it yesterday cold turkey so i am too having horrible withdrawal(shaking anxiety even suicidal thoughts)
the reasons i stooped were because it was giving me horrible nightmares and migraines. but the nightmares were the worse!
im not a 100% comfortable to continue Anafranil. friends have been telling me i should stick to remeron and find an add on to help with the nightmares.
what do u think?


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## Inshallah (May 11, 2011)

gilmourr said:


> You're right that maybe erectile dysfunction can be last and anorgasmia the 2nd most important sex function, since there is viagra. But really, I don't see myself using viagra at this age even if I had erectile dysfunction.


Me neither but a man's got to do what a man's got to do :teeth


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## Inshallah (May 11, 2011)

konamitech said:


> well said gilmourr,
> I started Anafranil yesterday and guess what my dr said about Anafranil and sex drive?
> "this med will actually increase your drive"
> really??????


With "drive" I assume they mean libido. This is very possible, especially if you were depressed before the Anafranil. I mostly experienced increased drive/libido on AD's, but decreased ability (slight impotence, genital anesthesia, anorgasmia) at the same time.

It's basically a recipe for disaster :b


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## Rob25 (Mar 30, 2012)

This is probably a really dumb question but as I'm about to start on Imipramine in the next two weeks I have been doing some reading on how it works and it seems its quite a potent reuptake inhibitor of noradrenaline. How can that be a good thing for anxiety? I thought noradrenaline was the "fight or flight" response chemical.


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## adidasman (Feb 27, 2015)

Side effects are more likely to wear off in time, just be patient and don't exacerbate them. Amitriptyline made my left hand's nerves all numb, but I was desperate to not be depressed - I couldn't play my guitar for a long time, but after five months suddenly everything was OK again. I'm willing to wait it out if it helps my behavior change. I am sad that people gave up Clomipramine without waiting the effects out, I am in it for the long run I guess.


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