One of my modules this year is Psychopharmacology- the study of drugs and how they affect people. One topic I often come across when researching drugs and medicines, which is often ill-explained, is what “generic drugs” are and whether generic drugs are ineffective, or different from brand-name medications.
When medicines are created,they are usually patented to one person or company, who become the only people who can make that medication. After a period of time, often 15 years, the active ingredient of that medicine (the medicinal molecule) goes off-patent, so can now be developed by other people. (This is similar to how music and books go out of copyright, and into the public domain).
Because the drug can now be made by multiple companies, many versions of the same medication will start to appear in the years after it goes off-patent. These versions, created after a product is not copyrighted, are known as generic versions.
It is cheaper for pharmaceutical companies to use an existing substance instead of researching a new one, so developing new versions of a tested molecule is an attractive financial decision. Each pharmaceutical company has to use a different name for their generics, which is why common medications can appear under many different names.
In the majority of cases, there is little difference between using generic and brand- name drugs: by FDA rule, generics have to contain the same amount of active ingredient as the brand name. Generics also have the advantage of being a lot cheaper and (importantly for the USA and other countries without an NHS), easier to cover by health insurance than brand-names.
There are a few situations where generics need to be used with caution, and where may be better to stick with the brand name. However, there are also situations generics are preferable to the brand name.
One factor that is often missed is how medications are designed. Tablets need to have a coating around the active ingredient, for many reasons: to protect moisture-soluble or oxidisable parts of the tablet; to strengthen a tablet so it doesn’t break in the packet or stick to other tablets; to cover up a bad-tasting ingredient; or to protect the persons’ stomach from an acidic or irritant ingredient. Coatings used to be made from sugar, which has now been phased out in place of polysaccharide coatings.
In normal cases, coatings are inert- they shouldn’t affect the patient or the medication at all. However, that isn’t always true: sometimes people are allergic to an ingredient in the generic coating (e.g. its colour) or the binding materials used in the tablet (e.g. if the binder contains lactose) so therefore need to stick to a specific brand-name that doesn’t use this ingredient. Conversely, people could be allergic to the coating or binding of a brand-name drug, so need use its generic instead.
Another consideration is people with diabetes: if one version of a medication still uses a sugar-coating, then that medication needs to be avoided or used differently so it doesn’t affect the persons’ sugar levels. So, if a brand-name medication is sugar-coated, or uses a polysaccharide that can affect sugar levels, then a generic with a different coating should be used.
Some medications, most notably ADD medications, come in different speeds: IR (instant/immediate release) releases the drug over 1-2 hours, while ER (extended release), disperses the medication over 6-8 hours. Release time is controlled by smaller “beads” within each tablet, which have various coatings that each last varying amounts of time.
One problem with using generic medications can be each supplier of a drug’s generics may use different ER coatings, resulting in sudden changes how long the drug works for. For someone in school or work, this could be very difficult to deal with, so in this case it may be better to stick with a brand-name.
A critical variable in safely prescribing medications is their therapeutic window. A therapeutic window is the dose range in which a drug is useful without causing more side effects than beneficial effects. For example, ibuprofen has a very wide therapeutic window: one 500 mg tablet is an effective painkiller, but a toxic overdose would require about sixty 500mg tablets (dependent on the person).
This can also be expressed as a therapeutic index (ratio of minimum useful dose to minimum dangerous dose): ibuprofen would have a therapeutic index of 50-60.
Drugs such as Lithium (a mood stabiliser) or Tegretol (an antiepileptic) have a typical TI of <2, meaning twice the minimum useful dose for a person could be toxic to them. With a range that narrow, people taking these kind of medications have to be regularly monitored and have frequent blood tests to ensure the amount in their blood doesn’t vary.
This is important because while a generic drug has to contain the same amount of active ingredient as a brand-name, that doesn’t mean it will be processed in exactly the same way. The FDA defines “equivalent” as that within the time it takes a drug to work, the generic has to have between 80-125% of the brand name’s bioavailability.
For example, person A takes a name-brand painkiller, while person B takes an equivalent generic painkiller of the same strength. After an hour person the name-brand will create 50mg of the drug active in person A’s system. This means person B has to have between 40-60mg of the drug active in their system. In a lot of cases, these amounts are small enough to not make a difference. However, when dealing with drugs with narrower windows such as mood stabilisers and antiepileptic drugs, that difference could be enough to increase side-effects without an obvious reason.
In the majority of cases, each particular generic version of a medication will have almost exactly the same effect as the brand-name. After all, they are statistically almost identical.
However, where I mentioned earlier about sticking with one type of generic, or one brand-name, leads us on to one of the biggest potential problems with using generics. Because the main advantage of generics is their lower price, and because so many are available, a pharmacy will not always keep to the same generic. Unless a pharmacy has a strong preference for, or link to, a certain supplier, they will generally go with whichever supplier is the cheapest. This means that every so often, patients will be given a different generic version: the problem lies with them switching, especially if it is often.
For example, take a patient who has been prescribed an antidepressant (here I’ll use Wellbutrin, as it has a lot of generics so makes a good example), and has been taking generic A for it for a year. Generic A is bioequivalent to the original, as the amount in the persons’ system is 95% of the original- so when the patient switches, they don’t get any negative effects. One month, they arrive at their pharmacy to find they have been switched to Generic B. This is also functionally equivalent to the original, as the amount in the persons’ system is 110% of that in the original drug.
This wouldn’t be much of a difference, if they were switching from the original. However, they switched from Generic A, meaning the increase in bioavailable drug is just under 20% instead of just over 10%, twice as much. So, the patient is twice as likely to suffer a negative effect from switching to a different generic than someone who stayed on one generic or who stayed on the brand-name. Furthermore, this effect of changing availability is usually not covered in psychopharmacological research, as studies are normally comparing the effectiveness between one dose of each, rather than people who have used one every day then switched to another.
It’s complicated and personal effects like this that make psychopharmacology research sometimes very far removed from the realities of dealing with medicines and drugs. However, despite me explaining this issue to an extent here, there are even more arguments on both sides of the story, and it is of course very dependent on the individual person, and the individual drug. It is impossible to study the effects of switching generics, and the differences between generics and brand-names, purely theoretically.
The most important way to make information like this available to more people, especially those who need it most, is to bring it into debates: to ask doctors what generic medication is the same as ones on your prescription, and whether people have studied the difference; to ask pharmacies if they keep a certain generic available for people who have trouble with others; and to ask researchers about their methodologies in comparing medications.