Those who were taking the “old Nardil” (an MAOI antidepressant) formulation for depression know that it worked quite well. Many people had taken it for years, in some cases decades with relief from depressive symptoms. Although this drug didn’t work for everyone, those who found it effective usually experienced long-lasting relief from depression. As noted in 2003, the manufacturing of the drug was sold from the company Parke-Davis to Pfizer.
The original Nardil contained 15 ingredients and a slower release compared to the newer one which is a quicker release with only 9 ingredients. Currently there are no formulations in the United States that are the same as the “old” Nardil formula. Initially when complaints began to surface, Gavis Pharmaceuticals decided to manufacture Phenelzine (generic Nardil) to provide an alternative for those upset with the Pfizer variant.
The Gavis “brand” of generic Nardil is regarded by many as being the closest to the old formula in regards to ingredients and absorption. However, efficacy compared to the Pfizer version is still up for debate. Most people do still regard the old version created by Parke-Davis as being the best formula. Besides the Pfizer “name brand” version of the drug, there is only one other generic formula created by Greenstone LLC (a subsidiary of Pfizer); this contains the same inactive ingredients as the Pfizer version.
Old Nardil (Parke-Davis) vs. New Nardil (Pfizer)
Below is a comparison of the old version of the drug with the newer version. Understand that although only the inactive ingredients were modified, these modifications affected many people taking the drug.
Old Nardil (pre-2003)
In comparison to the newer version of the drug, this older version had more ingredients that contributed to a harder shell casing of the pill. You can compared the ingredients listed below to the ones associated with the new formula.
Acacia NF, Calcium carbonate, Carnauba wax NF, Corn starch NF, FD and C yellow No. 6, Gelatin NF, Kaolin USP, Magnesium stearate NF, Mannitol USP, Pharmaceutical glaze NF, Povidone USP, Sucrose NF, Talc USP, White wax NF, White wheat flower
Absorption: It is thought that the older version of Nardil took considerably longer to get broken down in the system. This is believed to have a lot to do with the outer-coating of the drug, which was thought to be superior in this pill design.
Efficacy: Superior. The efficacy of the old version is widely regarded by many as being superior to the new formula. Although not everyone will agree that the efficacy was superior, many found that they couldn’t tolerate the medication after the newer version was released.
Peak plasma levels: The peak plasma concentration for the old Nardil was thought to occur between 2 and 4 hours after someone took their dose. This falls in line with the absorption theory and the fact that the outer coating takes longer to dissolve than the newer version.
Pill Design: The older version of the pill had a hard, shiny candy-like coating; resembling an M&M. This has a lot to do with the inactive ingredients, which are thought to influence absorption of the drug. This older version is thought to take considerably longer to get broken down once ingested.
Long-term success: Many people who had been on the older Nardil noticed that they could keep taking the drug for years to treat depression without problems. Once they began to take the new pill, they noticed that it stopped working, never worked, and/or pooped out. There are reports of people who had taken Nardil for decades that could no longer tolerate it once the pill formula changed.
New Nardil (2003 – Present)
This newer version of Nardil was released by Pfizer in the fall of 2003. As you can see, the ingredients have changed. Several of the inactive ingredients were removed and replaced.
Mannitol USP, Croscarmellose sodium NF, Povidone USP, Edetate disodium USP, Magnesium stearate NF, Isopropyl alcohol USP, Purified water USP, Opadry orange Y30-13242A, Simethicone emulsion USP
Absorption: Some have hypothesized that the new Nardil is absorbed before actually reaching the small intestines. Even if it is not absorbed before reaching the small intestine, many believe that once the drug reaches the small intestine, the absorption may be disproportionate and unbalanced, inevitably leading to poorer responses from users.
Efficacy: Reduced. Many people began to notice a decline in tolerability and efficacy of this newer version of Nardil. Although this contained the same active ingredients at the old version, the inactive ingredients clearly played a role in influencing the way the drug was absorbed and tolerated.
Peak plasma levels: The peak plasma concentration for the new Nardil was thought to occur approximately 45 minutes after someone took their dose. This follows reports from people who say that the new version of Nardil seems as though it dissolves in the mouth if it isn’t swallowed immediately.
Pill Design: The coating of the new Nardil is considerably softer and is engraved with “PD 270.” It is noticeably less shiny and looks less like a candy M&M than the last version. Many believe it is the outer shell that played a role in contributing to the decline in efficacy. It’s very easy to tell the difference between this pill and the older version.
Side effects: Many people have noted many unwanted side effects associated with the newer version of the drug. Prior to the new drug, many agreed that the side effect profile was relatively manageable. As soon as the new drug hit the market, many people began to notice changes in how they were responding to the drug.
Theory: Below is one theory that has been circulating around a few years following the inception of the new version.
The new Nardil is regarded by some as being problematic due to the fact that it dissolves quickly in the stomach, which allows too much of the drug to get filtered through the liver as opposed to getting absorbed by the small intestine. This would result in significantly less of the active ingredient to travel through the bloodstream and ultimately reach the brain; resulting in minimized antidepressant effects.
Additionally, the newer version of the drug could be introducing larger quantities of the active ingredient (phenelzine) to get filtered through the liver, which would result in increased levels of phenylethylamine (PEA). The level of PEA would become too high and less PEA would get destroyed as a result of MAO-B inhibition. The increase in PEA would result in increases in levels of dopamine and stimulation of dopamine receptors.
The dopamine in the brain could potentially reach high levels – perhaps too high for those dealing with depression and/or anxiety. The problem with the new Nardil is perhaps a lack of inhibition of MAO-A and MAO-B, could be raising dopamine levels at a ratio considerably greater than that of serotonin and norepinephrine, resulting in poorer responses from depression and anxiety sufferers.
Consumer Complaints: The newer version of the drug made by Pfizer came with a backlash of complaints from consumers. Many people on forums and message boards began to file complaints against this new version of the drug. This gained the attention of Gavis Pharmaceuticals who attempted to make a version of the drug closer to the old Nardil. Unfortunately many people did not find the Gavis version of the drug as effective as the older version as the ingredients still did not match the old formula.
Why did Pfizer change the Nardil pill in 2003?
An FDA report from Pfizer indicates that only inert buffering ingredients were changed. Despite the relatively minor changes, many people believe that it doesn’t dissolve the same as the old pill (it dissolves more quickly) and has a worse taste. Minor changes to the inactive ingredients have lead many to believe that the new version is considerably less effective.
Pfizer claimed they made these changes to Nardil to increase the drug’s shelf life. Their argument was that the newer version of Nardil still contains the same active ingredients, so these changes shouldn’t matter. As many people learned, the inactive fillers used in drugs can sometimes play an important role in influencing how the body absorbs and responds to the drug.
Upset consumers argue that Pfizer’s real motivation for changing the drug was likely to save money by utilizing cheaper manufacturing methods. Additionally many have stated that the claims made in regards to extending shelf life are completely false.
Note: A minority of individuals have considered that the ingredient change may have been due to the fact that companies were advised against using ingredients that contained gluten in medications.
What can be done to get the old Nardil back? Nothing.
As of now you’ll just have to try one of the available versions of this drug if you think that Nardil is the best treatment option for your depression. Many that were taking the older version of the drug simply no longer respond to the new version, so they’ve discontinued usage and moved on. Some people have attempted to boost the efficacy of the new Nardil through various tweaks, but whether these tweaks work is highly questionable.
Hypotheses: How to Boost The Efficacy of Nardil
Some people have claimed that they’ve come up with ways to boost the efficacy of the newer Nardil formulation. Whether these actually work is highly debatable and cannot be medically recommended. These are merely some suggestions that some have reported as being successful.
- Absorption aids: It may be the fact that Nardil was manufactured in enteric tablets that was responsible for its decline in efficacy. Although these tabs ensure more of the active ingredient making it through the stomach, once the tab dissolves, the active ingredient may not get absorbed to maximum capacity without an aid. Certain individuals have experimented with invert sugar combined with small amounts of ethanol.
- Bioperine: Some have claimed that by combining Nardil with Bioperine, they’ve gotten a better response. It is thought that this may aid in the absorption of drugs. These claims are completely subjective though and cannot be verified.
- Enteric coated capsules: Some individuals claim to have had a degree of success by purchasing enteric coated capsules and putting the new Nardil inside these capsules. It is thought that this may affect absorption of the drug and make it more similar to the older formulation.
- Gavis version: Many believe that although the Gavis Pharmaceutical generic version of Nardil isn’t as effective as the original, it is still superior to that made by Pfizer. Whether these claims are true is up for debate. What you could do is experiment with both brands and determine which gives you the best response.
- Try the UK version: Some people have claimed that the version made in the United Kingdom by Archimedes is significantly better than that in the United States. Others have tried the Australian version with limited success compared to the old version.
- Gastric emptying: This method involves taking Nardil on an empty stomach with large quantities of water. One technique that has been reported is to take Nardil with a copious amount of water it should (in theory) empty into the intestines. This is all assuming the stomach doesn’t recognize the Nardil and absorb it. Whether there is any merit to these suggestions is questionable at best.
Note: None of these techniques are medically recommended or supported, these are merely things that people have tried with varying degrees of success.
Did the change from “old” Nardil to “new” affect everyone?
No. Not everyone who was taking the medication in 2003 experience problems with the change in formula and manufacturer. Some have proposed that the “majority” of people taking this medication were affected by the changes, however the accuracy of these claims are disputed. There are many cases of people who were taking the medication with the first manufacturer and transitioned to the new formula without any problems.
As of now, it remains unclear as to what percentage of Nardil users prior to 2003 were affected by the changes made by Pfizer. Many people would agree that the old version was more tolerable and effective than the newer version. In the assessment of many people, this drug went from being very helpful for depression to being average with a higher frequency of unwanted side effects as well as a tendency to stop working.
Unless the old manufacturer of Nardil put out the product with the same original formula and comparison studies were conducted, there’s no way to truly know if it was more effective. As of now we can only assume that since people on the older version of the drug noted awful transitions to the new drug, it was more than mere coincidence.
Write to the FDA about Nardil
The FDA should be somewhat ashamed for letting such a change happen, but then again they can approve whatever they want. Many people were on this drug for extended periods of time without any problems. As soon as the patent was sold to Pfizer in 2003, certain ingredients were altered and many would agree that these alterations were for the worse.
Some individuals had reported being on this medication for years (in some cases decades) and found that as soon as the formula changed the drug stopped working and had significantly more unfavorable side effects. These experiences align perfectly with the time that the drug formula changed, suggesting more than a mere coincidence.
If you are disappointed in what happened, you should let your voice be heard by writing to the FDA. Although it may be too late to change things back, you really never know. If enough people voice their opinion the FDA may take some time to reconsider the changes made by Pfizer.