06/01/2026What Can I About Drug-Drug Interactions?
If you are taking more than one medication, for example something for mental health, something for pain, and something for your stomach or heart, you are not alone. This is incredibly common, especially as we get older or manage more than one condition. The medical term for this is polypharmacy, which simply means taking multiple medications at the same time. Polypharmacy usually refers to taking five or more medications, but even with just two medications, interactions can occur. The risk increases as more drugs are added.
The obvious question most people have is:
“Do these drugs interact with each other, and should I be worried?”
The short answer is yes, drug–drug interactions are not un-common, but they are usually manageable once you understand what is going on.
What Do We Actually Mean by a Drug–Drug Interaction?
A drug–drug interaction does not mean two medicines are dangerous together by default. It usually means one of two things:
- One drug changes how quickly another drug is broken down
- One drug increases the side effects of another
You might have heard the lock and key metaphor used to describe enzymes. In this story, the enzyme is the lock and the medicine is the key. In some drug–drug interactions, two different medicines act as keys for the same lock. If one key occupies or interferes with the lock, it can slow down how the other key, or medicine, is processed. This can cause one drug to build up in the body or behave differently than expected. Most interactions are predictable, well documented, and manageable, but they can feel confusing from the outside.
A Real-World Example: Paroxetine and Tramadol
Let us use a common and clinically important combination.
Paroxetine is a prescription antidepressant commonly used to treat depression, anxiety disorders, panic disorder, and post-traumatic stress disorder. It belongs to a class of medications known as selective serotonin reuptake inhibitors, or SSRIs. While paroxetine is an SSRI, it differs from some others because it strongly affects certain metabolic enzymes. This can influence both side effects and drug–drug interactions.
Tramadol is a prescription pain medication commonly used to treat moderate pain, including musculoskeletal pain, post-operative pain, and some forms of chronic pain. Tramadol is sometimes described as an opioid or opiate-like medication. While it does act on opioid receptors, it is pharmacologically distinct because it also affects serotonin and noradrenaline signalling in the brain. This dual action is one reason tramadol can be effective for pain, but it is also why tramadol side effects and drug interactions can vary significantly between individuals.
Prescribing Paroxetine and Tramadol Together
This combination is seen regularly in clinical practice and is well documented in prescribing guidance. It often arises in patients who are managing both chronic or recurrent pain and depression or anxiety at the same time. For example, someone with long-standing back pain, neuropathic pain, or musculoskeletal injury may be prescribed tramadol for pain relief, while paroxetine is used to help manage mood or anxiety symptoms. Because these conditions commonly occur together, this pairing is not unusual.
Paroxetine is a strong inhibitor of an enzyme called CYP2D6, which plays a key role in how tramadol is processed in the body. Tramadol relies on this enzyme to be converted into its active pain-relieving form and also has serotonin reuptake inhibitor activity.
Because of this, paroxetine can significantly alter how tramadol behaves, increasing the risk of reduced pain control, side effects, or serotonin-related adverse effects. This interaction is known and can be clinically significant.
So far, so sensible. This is where pharmacogenomics adds important context.
PGx and Metaboliser Type
Everyone breaks down medications at a different speed. This is largely driven by your genes. Pharmacogenetic, or PGx, testing looks at how your genes influence how medications behave in your body. Some of this relates to drug metabolism, meaning how quickly a drug is broken down, while other aspects relate to how drugs act at their target sites. When it comes specifically to metabolism, people tend to fall into groups such as:
- Slow metabolisers – drugs are broken down more slowly
- Normal metabolisers – drugs behave largely as expected
- Fast metabolisers – drugs are broken down more quickly
If You Are a Slow Metaboliser of Tramadol
Tramadol relies on CYP2D6 to form its active pain-relieving metabolite. If you are already a slow metaboliser, your body produces less of this active component. Adding paroxetine, which strongly inhibits CYP2D6, can further reduce tramadol’s effectiveness while increasing the risk of side effects related to serotonin activity. In this case, options might include:
- Lowering the tramadol dose
- Switching to a different pain medication
- Considering an alternative antidepressant that does not strongly inhibit CYP2D6
If You Are a Normal or Fast Metaboliser of Tramadol
Some people may tolerate this combination better, particularly if their baseline metabolism is faster. However, paroxetine can still significantly slow CYP2D6 activity, effectively shifting someone from a normal or fast metaboliser into a functional slow metaboliser. This is why some people manage this combination well, while others experience poor pain control or side effects, even at standard doses. Monitoring, dose adjustment, or medication changes may be required depending on the individual.
When Interactions Get Harder: Five, Six, or Eight Medications
Checking interactions between two drugs is fairly straightforward. But what if you are taking:
- An antidepressant
- A pain medication
- A stomach medication
- A blood pressure tablet
- Something for sleep
- Plus supplements
At that point, interactions can stack, even if no single pair looks problematic. This is where pharmacogenomic information becomes invaluable. PGx can help answer questions such as:
- Which pathways are already busy in your body
- Which medications compete for the same enzymes
- Whether spacing medications by time of day might help
- Which drug classes are more likely to work smoothly togetherInstead of guessing, you get a detailed guide designed to maximise benefit while minimising side effects.
So What Should You Actually Do?
The more medications you take, the greater the chance that one medicine may interact with another. Your GP will usually check for well-known drug–drug interactions using trusted tools such as the BNF Medication Interaction Checker. Adding a pharmacogenomic test provides an extra layer of detail, helping to further refine these decisions based on how your body processes medications. If you are having trouble finding the right medications for you, you can purchase a PGx test from our website. The goal is not fewer medicines, but better-matched medicines, informed by your genes.
The Bottom Line
Drug–drug interactions are common. Drug–gene interactions are even more common. According to UK Biobank data, around one in four people have been prescribed a medication for which they are likely to have an atypical response. Most problems are not caused by bad drugs. They are caused by mismatches between medications, genetics, and the number of drugs involved. Once you understand how your body processes medication, decisions such as dose changes, timing adjustments, or switching medications become logical rather than trial and error.
FAQs
Are drug–drug interactions common?
Yes. They are especially common if you take more than three medications.
Why do antidepressants work differently for different people?
Genetics strongly influence how drugs are broken down and tolerated. These are known as drug–gene interactions.
Can drug interactions cause side effects even at low doses?
Yes, particularly in slow metabolisers or when medications share the same metabolic pathways.
How do doctors check drug interactions?
They use interaction checkers, clinical judgement, and a review of your medication history.
What is pharmacogenomic testing?
Pharmacogenomic, or PGx, testing looks at how your genes affect medication response and metabolism.
Is PGx useful if I am on lots of medications?
Yes. PGx becomes more valuable as the number of medications increases, especially if you are a slow metaboliser in more than one pathway.