View Full Version : Chlorpheniramine/Chlorphenamine with Methylphenidate

12-05-12, 08:48 AM
Have been taking this combo for a couple of weeks now, originally the chlorphenamine was used for allergies but I noticed an anxiolytic and antidepressant effect of it. I did some research and apparently, chlorphenamine was what they based the first SSRI zimelidine from. Since chlorphenamine had gone off-patent, there was no money to make on it, hence zimelidine.

A fair bit of research has been conducted on it, and it has shown appreciable affinity for SERT, NET and slightly DAT. With some agonism/antagonism of various 5-HT receptors. Furthermore, diphenhydramine (Benadryl) appears to inhibit SERT but not NET or DAT.

As I said, the only reason I looked into this was because how I can have a higher dose of methylphenidate, have the beneficial effects without the usual anxiety it causes me when combined with chlorphenamine.

I was also no longer grumpy of a morning, slept better and felt generally happier. I 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. Furthermore, although the antihistamine effects of chlorphenamine are believed to only work for roughly 6 hours, the half life of the drug is 22-27 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.

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. Plus, the chemical structure of chlorphenamine is extremely similar to fluoxetine (derived from diphenhydramine) and zimelidine (derived from chlorphenamine).

Further reading:

Some PubMed literature:

And the "Introduction" to the book "Let Them Eat Prozac":

12-05-12, 02:07 PM
The funny thing about chlorphenamine is that 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.

Interestingly, according to 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?

By the time chlorphenamine's neurological effects 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.

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.