View Full Version : Chlorphenamine (OTC antihistamine) for Anxiety. Research and speculation.


NotoriousPyro
12-06-12, 03:08 PM
I made a thread in another forum, but thought it would be more appropriate to post it in here. So here goes.

I have been taking this medicine with Concerta for a couple of weeks now, originally the chlorphenamine was used for allergies but I noticed an anxiolytic and antidepressant effect of it. I was also no longer grumpy of a morning, slept better and felt generally happier. Coupled with the typical, antidepressant side effects of increased sweating, dry mouth and some digestive complaints for a short while, I felt confident it was somewhat acting like an antidepressant. I researched and then explained this to my psychiatrist and he agreed with me, asking for me to email him the literature I've been reading. He also prescribed me long-action (12-hour) chlorphenamine on the basis it seems to be helping. My psychiatrist had told me that during the pre-stimulant era, they used various antihistamines, including chlorphenamine for those with ADHD to calm them down.

The research I conducted brought up the following information, which I have based my conclusions on.

Take a peak at the following image, the structures of methylphenidate and chlorphenamine are distantly similar. But compared to the antidepressant zimelidine, chlorphenamine is extremely similar:
https://dl.dropbox.com/u/24882205/images/structure.png

The first marketed SSRI was zimelidine, which was based off the structure of chlorphenamine and brompheniramine. By the time the neurological effects of chlorphenamine had been noticed, the drug had gone off-patent, and there was no more money to be made besides generic formulations. This led to the development of non-sedating, but less effective antihistamines and antidepressants that were little to no more effective than chlorphenamine.

Chlorphenamine has shown appreciable affinity for SERT (serotonin transporter) (http://en.wikipedia.org/wiki/Serotonin_transporter), to a lesser extent NET (norepinephrine transporter) (http://en.wikipedia.org/wiki/Norepinephrine_transporter), and possibly to a negligible amount DAT (dopamine transporter) (http://en.wikipedia.org/wiki/Dopamine_transporter). Although the literature on which transporter it inhibits the most is inconsistent. Furthermore, diphenhydramine (Benadryl) appears to inhibit SERT but not NET or DAT.

There is also some possible evidence of binding to various receptors (although which receptors and whether they are agonised, antagonised or inversely agonised is not apparent), including D1 (http://en.wikipedia.org/wiki/D1_receptor), α1 (http://en.wikipedia.org/wiki/Alpha-1_adrenergic_receptor) and 5-HT (http://en.wikipedia.org/wiki/5-HT_receptor). The muscarinic and histamine receptor blockade, plus the inhibition of the monoamine transporters makes it is highly likely that chlorphenamine and its lack of receptor selectivity will cause it to bind to various other receptors similar to the action imipramine and other tricyclics. Though receptor binding and effects are partly speculative from me, based on the evidence I've read.

Although the antihistamine effects of chlorphenamine are believed to only work for roughly 6 hours, the half life of the drug is 21-27 hours, this corresponds with me feeling less anxious, happier, etc. even in the absence of a dose within 6 hours. The therapeutic neurological effects appear to remain beyond the indicated antihistamine effects.

Interestingly, according to http://www.ncbi.nlm.nih.gov/pubmed/16413139. Chlorphenamine "compares favourably with amitriptyline and imipramine with respect to actions on both serotonergic and noradrenergic neurons." and that it "might also be called a selective serotonin and noradrenaline reuptake inhibitor (SSNRI) and be compared with new drugs, such as venlafaxine."
It's possible that a drug as old as chlorphenamine is just as good, and with less side effects than venlafaxine or the tricyclics amitriptyline and imipramine, is available over the counter, for a cheap price, has had information pertaining to it's therapeutic effects withheld in the name of corporate greediness?

This evidence is further strengthened with the warning to not take chlorphenamine with an MAOI within the last 14 days of one another due to a risk of fatal serotonin syndrome.

I don't believe chlorphenamine to be for everyone, nor do I believe it to be as effective in some severe cases of depression in which the likes of mirtazapine (another extremely effective antidepressant, far more effective than SSRIs) and the daddy of all - MAOIs should dominate.

However, if anyone is suffering from anxiety and/or depression, then I'd like to ask is anyone willing to test my success on themselves? If anyone is, please let me know and also make sure you READ THE LABEL for chlorphenamine and do NOT combine it with MAOIs or other antidepressants without first consulting your doctor. Please also be aware that chlorphenamine is an opiate potentiator so opiates become stronger than they normally would.

If anyone has any questions, I'll be more than happy to attempt to answer them.

Further reading:
http://www.newebgroup.com/panicdisorder/
http://www.newebgroup.com/panicdisorder/ltrtoedmar03a.pdf

http://www.hedweb.com/bgcharlton/
http://www.hedweb.com/bgcharlton/sdtm.html
http://www.hedweb.com/bgcharlton/subtypes-depression.pdf

Some PubMed literature:
http://www.ncbi.nlm.nih.gov/pubmed/19823805
http://www.ncbi.nlm.nih.gov/pubmed/16876927
http://www.ncbi.nlm.nih.gov/pubmed/16413139
http://www.ncbi.nlm.nih.gov/pubmed/16156843
http://www.ncbi.nlm.nih.gov/pubmed/17328889

And the "Introduction" to the book "Let Them Eat Prozac":
http://www.healyprozac.com/Book/Introduction.pdf

425runner
12-07-12, 11:36 AM
I took it when I had a cold and was surprised by its effects on my mood. I felt super calm yet energetic to clean my house, it felt really strange - in a good way! Almost like a mild opiate high...

NotoriousPyro
12-08-12, 05:04 AM
I took it when I had a cold and was surprised by its effects on my mood. I felt super calm yet energetic to clean my house, it felt really strange - in a good way! Almost like a mild opiate high...

Sounds about right. I take it daily and it really improves my mood.

Phoenix Ash
12-09-12, 01:33 PM
I'm really intrigued by all of this. I read the intro to the Let Them Eat Prozac book and found that quite fascinating, too.

On top of that, this whole topic is synergistic with my world right now cos I have a cold and was wondering if it was my imagination that my cold medication was improving my mood.

As it turns out, there's no chlorphenamine in it; rather, it's the dextromethorphan (cough suppressant) that's making me feel less depressed. I never knew it was also an SRI! But since the box is almost empty, I think I just might look at chlorphenamine meds when I go back to the drugstore. I'm intrigued by the possibilities! :)

ginniebean
12-09-12, 05:35 PM
What brand can this be found in?

425runner
12-09-12, 09:09 PM
I bought it at CVS, generic 4mg

NotoriousPyro
12-09-12, 10:27 PM
Just an FYI: When you buy:
Chlorphenamine/chlorpheniramine is typically supplied in 4mg instant release tablets (though there are slow-release varieties at 12mg).
Dex-chlorphenamine/dex-chlorpheniramine is typically supplied in 2mg instant release tablets.

You are usually getting both the levo, and dextrorotary isomer of the drug in the racemic 4mg mixture. The dextrorotary isomer is considered to have psychopharmacological effects, while the levorotary version has little to no efficacy. So in a 4mg pill, you effectively get 2mg of the most active drug. This is not a problem, however.

A therapeutic dose seems to be around the range of 12mg to an absolute maximum of 32mg per day (and 6mg - 16mg for dex-chlorphenamine). Lower doses tend to be more sedating, while higher doses tend to be more stimulating.

I would seriously recommend nobody drive or operate machinery, as the label says for a while until you know how this drug will affect you.

NotoriousPyro
12-10-12, 01:52 PM
I've been reading up a little more. It turns out that anticholinergic drugs, such as chlorphenamine have quite unique antidepressant effects.

Literature:
http://www.ncbi.nlm.nih.gov/pubmed/17015814
http://www.biopsychiatry.com/antimuscarinic.htm

Phoenix Ash
12-14-12, 02:05 PM
I had a little bit of a challenge finding just the chlor. without other added ingredients (like acetaminophen). Finally did, though.

What brand can this be found in?

I don't know if you have this drugstore in Canada but I found it at Rite-Aid last night. Store branded "allergy relief", $8.49 for #100 4mg tabs of chlorpheniramine maleate. Pretty good deal.

ADDinHDefgHi?!
12-15-12, 06:17 AM
Interesting. I just bought a pack of 24 4mg tablets and I'm going to try it out. I'll let you know how it goes. Thanks for the info.

425runner
12-15-12, 10:21 PM
Oh shoot...I keep forgetting about it! Gotta get my tablets out...I took 0.25mg Klonopin today for anxiety. Will try those chlorphenir...something tomorrow.

NotoriousPyro
12-18-12, 10:39 AM
I look forward to hearing your results :-).

Phoenix Ash
12-19-12, 10:00 AM
Been trying this for 6 days so far. So far I can definitely say I have noticed the sedating effects. In fact I am able to treat it like a sleep aid. One 4 mg pill and I am drowsy within 20 minutes. The longer I've gone without sleep, the greater the drowsy effect.

I am not sure about this yet, but it is possible I may be experiencing some slight mood improvement, but I can't be sure yet. Could be placebo, could be some other things.

What dosages do you take, ccrawford? You noted that higher doses are stimulating... what dose do you find stimulating, and what dose improves your mood? And how quickly does it do so?

Any other pointers about when/how to take it? Food/med interactions, etc?

Thanks for all your info so far on this! I'm feeling hopeful about the possibilities.

NotoriousPyro
12-19-12, 12:36 PM
After a while, the direct sleepiness side-effects disappear due to histamine receptor sensitisation. Though it may indirectly improve sleep through anxiolysis and antidepressant effects.

For me, it tends to "stabilise" my mood rather than directly improve it. Such as things not bothering me as much anymore, being less anxious and thus happier because I can be settled, etc. Remember: antidepressants do not make you happy, they simply try to stop you thinking negatively, thus improving your overall mood.

Roughly, I aim for around 4-5 pills per day, at 3-5 hour intervals. This totals to around 20-24mg per day.

I've noticed that I feel less boredom-derived lethargy, anxiety, and my mood seems to be more stable. Combined with Concerta they appear to complement each other. Concerta alone doesn't alleviate my mood swings, it makes my anxiety worse and I get quite lethargic and sick. The comedown from methylphenidate appears to be smoother and less irritable with chlorphenamine too.

Recently, I've been taking a 27mg Concerta tablet at 7am and 3pm, this really improves my mood yet I don't feel the same "overdrive" anxious feelings which I used to feel beyond 27mg. In fact, I've taken far much more than I've ever took and still no anxiety. I used to have to steer away from caffeine while on Concerta as this would make me super-anxious and really jittery, now I can drink what I want and take much more Concerta and experience the positive benefits without the anxiety.

The first day of taking chlorphenamine I noticed the anxiolytic effects, shortly afterwards (3-4 days) my mood started to improve. Whether or not this is related to the anxiolysis, I don't know.

The only interactions with other medications I can explicitly name are the ones I listed:
If you're taking any other antidepressant, first consult your doctor.
Do NOT combine with MAOIs, especially irreversible ones.

A list of interactions are here:
http://drugs.webmd.boots.com/drugs/drug-92-CHLORPHENAMINE.aspx?drugid=92&drugname=CHLORPHENAMINE&source=2&isTicTac=false#interactions

As far as I'm aware, it doesn't interact with any foods and can be taken with or without food. Alcohol consumption isn't recommended as it increases the sedative effects, though alcohol makes you depressed anyway, so it's probably a good thing that you shouldn't drink it!

Phoenix Ash
12-19-12, 01:43 PM
Thank you again for sharing your experience. This is great information! :)

So far I've only been at 4 mg/day. I'm considering bumping it up soon, to 8 mg.

However, I dislike having to remember to take pills multiple times a day. What made you decide to space them out? Do you think there would be a difference between taking, say, 12 mg chlorpheniramine all at once in the morning vs spaced out in 3 doses over 12 hours? Have you tried anything like that?

NotoriousPyro
12-19-12, 02:28 PM
I would wait a while for your histamine receptors to desensitise a while before upping the dose.

The reason I decided to space them out was the information on the packet, to take one 4-5 times a day, as required. Although there are stronger formulations, such as 8mg so I don't see how two pills could harm you. The drug's half life is 21-27 hours so I'm not sure why this information is used on the package, if it was, say 4-6 hours then I can imagine this would be a good way to take it.

The information listed on http://www.medicines.org.uk/emc/medicine/22635/spc states:
"Chlorphenamine maleate is absorbed relatively slowly from the gastrointestinal tract and peak plasma concentrations occur between 2.5 and 6 hours after oral administration. It is reported that only 25 to 50% of an oral dose is absorbed as it appears that chlorphenamine undergoes considerable first pass metabolism. Metabolites include desmethyl- and didesmethylchlorphenamine. Chlorphenamine distributes widely in the body and penetrates into the CNS. In the circulation, about 70% of chlorphenamine is bound to plasma proteins.
Excretion of unchanged drug and metabolites is mainly via the urine and is dependent on urinary pH and flow rate. The elimination half-life is widely variable and has been reported to range from 2 to 43 hours. However, the duration of action is only 4-6 hours which is shorter than might be predicted.
It is reported that in children, absorption is faster and more extensive, and there is a quicker clearance with a shorter half-life."

But the information listed on http://www.drugs.com/mmx/chlorpheniramine-maleate-phenyltoloxamine-citrate-and-phenylephrine-hydrochloride.html states:
Half-life:
Chlorpheniramine: 21 to 27 hours.

Onset of action:
Most first generation antihistamines: 15 to 60 minutes.

Time to peak concentration:
Chlorpheniramine: 2 to 6 hours.

Time to peak effect:
Chlorpheniramine: 6 hours.

Though again, the literature is not consistent in this respect. And considering very little research has been done on this drug, especially in regards to its "other" effects, I can imagine that some of this information does not apply and that chlorphenamine lasts much longer in the CNS than it does in the body. As I've stated earlier, the antihistamine activity appears, according to literature, to last only 4-6 hours.

Could you possibly take a 4mg pill, while you are awake one day and see how long the sedation lasts?

It's a possibility that first-pass metabolism of chlorphenamine produces metabolites which have a shorter half-life but are more active on the histamine system. While chlorphenamine itself may be directly responsible for the non-histamine related actions.

And to answer your question on taking it all-at-once; according to the first link I posted, the estimated lethal dose of chlorphenamine is 25 - 50mg/kg body weight. Symptoms and signs include sedation, paradoxical excitation of the CNS, toxic psychosis, convulsions, apnoea, anticholinergic effects, dystonic reactions and cardiovascular collapse and arrhythmias. So you'd need 1,750 - 3,500mg in the blood stream at any one time for a person who weighs 70kg. I don't think overdose is possible as long as you don't exceed the maximum daily dosages, although taking it all in one go may be highly sedating until you desensitise.

425runner
12-19-12, 10:21 PM
OK, guys...I seriously need to get on this stuff. I quit my lousy job today and had to take Zanaflex (muscle relaxant) for back pain which oddly relieves all my anxiety and puts me in a good mood/coupled with a jack on the rocks ehhm...anyway, does this really help supress histamine? If so, this could have a great potential in my regimen as I suffer from IC - auto immune condition where the body produces too much histamine...normally I take Zantac 150mg and Quercetin 800mg/day...

NotoriousPyro
12-20-12, 06:20 AM
I believe I also have quite a high histamine level. I'm allergic to a lot of pets, have hay fever and excess stomach acid.

I used to be on lansoprazole, though strangely, since taking chlorpohenamine I haven't had heartburn anywhere near as bad even though it's not indicated for heartburn, nor does it act on H2 receptors.

It doesn't interfere, as I believe, with histamine production or metabolism. So I cannot comment on your problem 425runner. And I'm no doctor, so this is completely your decision, though it can't hurt to try it :-).

NotoriousPyro
12-20-12, 08:14 PM
Oh and a further note. My girlfriend has a dog which, when he's around I get an itchy throat and sneeze. Ever since I started chlorphenamine, I haven't had this issue. Even when my last dose was over 6 hours ago.

425runner
12-24-12, 08:05 PM
Would getting the time released 12mg Chlorphenamine be a good idea? It's easily available through amazon.com

I'd like to stop the Wellbutrin as it makes me angry and agitated and switch to this instead but worried about the sedation. Took one last night and slept like a baby, will probably not taky any tonite as I had a small amount of Klonopin (0.125mg) and 50mg of tramadol (for back pain). The tramadol has SNRI properties and works like a charm on my anxiety/depression/ability to focus. No wonder some people find it addictive....

NotoriousPyro
12-28-12, 10:42 PM
Until your body has adjusted to the antihistamine effects, it's best not to take long-action chlorphenamine until you've adapted.

I'd recommend taking it every night for at least a month to desensitise. But please have a long think before switching from wellbutrin to this as I'm not a doctor and can't be held responsible to lack of efficacy compared to wellbutrin in everyone's scenarios.

425runner
01-05-13, 08:58 PM
Day 4 of 4mg at night, with no Wellbutrin, and I like it a lot! Feels good to get a good night's rest and I always wake up refreshed and ready to face the day. While on Wellbutrin I'd always wake up angry and be grumpy all morning.

I'm not sure if it's safe to have a beer or two while on it so skipping my dose tonite.

NotoriousPyro
02-10-13, 02:23 PM
Yes, it's safe to drink on. Just be aware of the extra sedation.

ndjokovic
04-15-13, 09:35 PM
Hi everyone, im from morocco, so im not an english speaker, but i will try my best to write in english :).
Well, i have allergy to olive tree pollen, every spring, it's a nightmare for me, millions of sneezing per minute, itchy eyes, itchy nose, continuous feeling of sneezing. but despite this, a part of me loves this because, that means i should take the "drug of confidence":

Drug name: Rhumix
•Paracétamol (400 mg)
•Vitamine C (300 mg)
• Ibuprofène (200 mg)
•Pseudoéphédrine HCl (50 mg)
• Caféine (25 mg)
• Chlorphénamine maléate (4 mg)




which contains Chlorphenamine and pseudoephedrine (which apparetly has also a brain effect), believe me, i am more intersted by the brain effect then the antihistamine effect of the drug. i have a lot of antihistamine in my house, but i always choose the one with Chlorphenamine. I suffer sine my childhood from being shy, low self confidence, and i suffer from stuttering, i feel nervous in front of people, but when i take that drug to heal my hay fever, i feel confident, my stuttering disappears, i feel calm, i got a great power in convincing people, i feel happy, i feel sober, brillant ideas come to my mind (im preparing a PHD in mathematics), then i was sure that this is caused by the drug a take, i first believed pseudoephedrine who caused this, until i read about Chlorphenamine.
i give this antihistamine to my mother and sister when they brawl (they are always fighting), or on nerves, and they feel a very positive effect on their mood. i really want to know which molecule is responsible of this very good effect on mood: pseudoephedrine or Chlorphenamine both present on the drug i take.

I have never visited doctors for the problem of social anxiety, doctors in my country are poor. that drug designed for healing cold can miraculously solve my social anxiety problems.

ndjokovic
04-15-13, 10:16 PM
i just found an interesting scientific paper who claim that Chlorphenamine may be the safest antidepressant:

you can view the paper's abstract here. (http://www.medical-hypotheses.com/article/S0306-9877(05)00647-X/abstract)

Phoenix Ash
06-16-13, 03:07 PM
Drug name: Rhumix
•Paracétamol (400 mg)
•Vitamine C (300 mg)
• Ibuprofène (200 mg)
•Pseudoéphédrine HCl (50 mg)
• Caféine (25 mg)
• Chlorphénamine maléate (4 mg)

which contains Chlorphenamine and pseudoephedrine (which apparetly has also a brain effect), believe me, i am more intersted by the brain effect then the antihistamine effect of the drug. i have a lot of antihistamine in my house, but i always choose the one with Chlorphenamine. I suffer sine my childhood from being shy, low self confidence, and i suffer from stuttering, i feel nervous in front of people, but when i take that drug to heal my hay fever, i feel confident, my stuttering disappears, i feel calm, i got a great power in convincing people, i feel happy, i feel sober, brillant ideas come to my mind (im preparing a PHD in mathematics), then i was sure that this is caused by the drug a take, i first believed pseudoephedrine who caused this, until i read about Chlorphenamine.


Interesting. You may also be experiencing positive social effects from the paracetamol (known as acetaminophen in the US) in your Rhumix. A 2010 study showed that acetaminophen (paracetamol) not only reduces physical pain, but also reduces the pain of social rejection. Here's a link to the study: http://www.ncbi.nlm.nih.gov/pubmed/20548058

Be careful of taking paracetamol long-term, however; prolonged use increases the risks to your liver, kidneys and GI tract. More info: http://en.wikipedia.org/wiki/Paracetamol

black hawk
07-26-13, 11:07 PM
thank you so much , very imprtant topic i am proud of you , but mr i would ask if the chlorphenaramine used to treat social phobia , or if it has some effects on social phobia ? secondly i want to ask if the dexo form has a stronger effect as antidepressent ? thank you in advance.

425runner
10-03-13, 08:15 PM
Anyone still using it? I've got a terrible cold/eye infection and doctor said to take anti-histamine so I took the 4mg. No sedation like Benadryl, just calm. I get very agitated during the day, many things bother me at work so going to try that during the day the next week and see how it goes.

Tulip7171
10-11-13, 10:35 AM
Anyone still using it? I've got a terrible cold/eye infection and doctor said to take anti-histamine so I took the 4mg. No sedation like Benadryl, just calm. I get very agitated during the day, many things bother me at work so going to try that during the day the next week and see how it goes.

Giving it a try myself. Took 4mg last night before bed. There was some sedation but not even to the extent of Benadryl & I don't seem to have the "hangover" I usually get from Benadryl.

I'm hoping it takes the edge off the anxiety I've been getting from the Adderall.