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Strongest painkiller

Dr Karen Martin
Reviewed by Dr Karen MartinReviewed on 19.10.2023 | 6 minutes read

When wandering around the pharmacy and faced with a multitude of choices, how do we know what’s going to hit the spot? What's the strongest painkiller?

Here at Healthwords, we'd usually say the right painkiller is the lowest strength painkiller that can solve the pain problem, hopefully reducing the risk of side effects from stronger medications. But we've also all been there with a nasty toothache and just wanting to make it go away – just give me the strongest one! Below we'll discuss options in decreasing order of strength, although normally we'd say it is best to start with the mildest pain relief (acetaminophen) and work your way upwards to the strongest.

Certain classes of painkiller might be better for particular pains, and within each class there are increasing strengths, from those available from the pharmacy at the mildest end, to those prescribed by your doctor.

It’s also good to be aware of side effects, and if these are intolerable, there may be other medications that can be added, such as ones to treat nausea with opioid medications, that help you feel more comfortable. The following relates to tablets or oral medications: we discuss gels, creams, patches and other modes of pain relief in other articles.

You may also need other medications to reduce risks if you’re taking pain medications for a long time, such as protecting against excess stomach acid caused by nonsteroidal anti-inflammatories. Let’s start with the science behind the main classes of pain relievers, or analgesics, as we call them.

Doctor’s advice

The strongest painkillers

Opioids include a wide-ranging scope of pain relief, from codeine at the mildest end, to tramadol as a medium strength, and different forms of morphine at the strongest end. Depending on strength, these drugs make up steps two and three on the pain ladder. Side effects become more pronounced with stronger doses – commonly constipation, drowsiness and feeling dizzy, sick or slightly out of it. Certain people seem more susceptible to this “wooziness” than others.

Opioids are only available on prescription and they’re often combined with acetaminophen.

Strong opioids are particularly good for ischemic pain (after a heart attack), visceral pain (organ-related, after an operation), and palliative care, when a patient has pain with a terminal illness.

Opioids carry with them a burden of addiction if taken for a long period of time – the higher the dose, the stronger the dependency. They also produce tolerance, which means that quite quickly you need to take a higher dose for the same effect.

They can become drugs of abuse. The street drug heroin is a strong opioid, used for its “high” or feeling of euphoria, but carries a risk of reduced breathing rate. In an overdose, a person may stop breathing and die unless they receive an emergency antidote (naloxone). We don’t understand the brain very well, but it’s a known phenomenon that when opioids are taken by people really in pain, such as those with a terminal illness, it targets the pain center of the brain, and they are less likely to suffer euphoria or mental disturbance, or dependency and tolerance. Reduced breathing rate is weighed up as a risk against the benefits of being pain-free with opioids in patients nearing the end of their life. Nausea can be a problem, but they can be given medications to avoid this side effect.


Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medications that work on pain and reduce inflammation. They are considered step one on the pain ladder. Ibuprofen and naproxen are available to buy from any pharmacy, but stronger NSAIDs such as diclofenac or indomethacin require a prescription. Acetaminophen can be used in place of an NSAID, the two can be alternated in dosing, or they can be combined.

NSAIDs have a similar effect on pain as acetaminophen, but can be particularly effective in cases such as arthritis, where a joint is inflamed, causing much of the pain. They are also effective for an acute flare of gout, where one joint such as the toe is inflamed and can be extremely painful for a few days or weeks.

They act on prostaglandins, a hormone released in inflammation and present in high levels in period pain. NSAIDs are the class of choice to effectively combat period pain and are best if taken a couple of days before period pain is anticipated. The ones above are effective, but mefenamic acid is another NSAID that is often prescribed.

NSAIDs can cause increased acid production in the stomach, causing some discomfort, so you should always take them with food. Because of this, they carry the risk of gastrointestinal bleeding, which means those with a history of bleeding or a stomach ulcer, or the elderly, should avoid them. If taking for several weeks or more, your doctor may prescribe a proton pump inhibitor (PPI), to reduce the risk of a stomach ulcer forming.

Newer medications specifically target COX-2 receptors, which reduces the risk of gastrointestinal bleeding, but these are only available by prescription.

NSAIDs may also trigger certain types of asthma and can exacerbate existing kidney disease, so should be avoided in these cases.

Aspirin is sometimes included in the NSAID group but has fallen out of favor as a preferred pain relief, and its anti-inflammatory actions only kick in at a higher dose. It’s still regularly used at low dose to reduce the risk of heart disease, but this is anti-platelet action rather than anti-pain or anti-inflammatory.

Acetaminophen – step one for pain

This is the usually the first step on the pain relief ladder, and with relatively few risks or side effects if taken as instructed. It’s well-tolerated and may be sufficient for occasional mild pain that occurs for just a brief time. For a drug that’s been around for more than 100 years, it’s not well understood how acetaminophen works or in which area of the brain it works, but it likely stops chemical neurotransmitters from transmitting a pain message.

It’s most effective if taken regularly, and for a short period of time, up to a few days. It’s preferred over ibuprofen as it’s considered safer, but they offer a similar level of pain relief.

It’s less likely to help if you have longstanding or chronic pain, such as chronic back pain or arthritis. And it’s worth trying, but evidence suggests it may not help everyone with post-operative pain or a tension-type headache, but it will help some.

You should be careful to take no more than the recommended maximum, and beware of other products that might contain acetaminophen such as cold and flu treatments, so you don’t double-dose. It’s cleared by the liver, so if you have any liver problems, you should check with a doctor first. It causes liver toxicity if taken above the recommended dose.

Rarely people may experience stomach upset, a rash or blood disorders. You don’t need a prescription for acetaminophen, it’s available to buy from any pharmacy. But you should consult your doctor if you’re taking it for more than a couple of weeks, or needing to turn to it very often.

Treating nerve injury: neuropathic pain relief

Nerve pain is approached in the same stepwise way with the ladder of pain relief. If the above medications are having only minimal effect, or you’re needing a long-term solution, or side effects or risks are not acceptable, your doctor may move you on to medications that specifically target nerve, or neuropathic, pain. These are only available by prescription. They can be used in place of, or in addition to, the drugs discussed above.

Neuropathic pain is usually more complex in its nature and is often longstanding, therefore it’s more difficult to treat effectively. You should expect to be more comfortable with pain but probably not pain-free.

The oldest of these are amitriptyline and nortriptyline, which used to be commonly used in higher doses to treat depression. They can make you feel drowsy, groggy and sluggish, and for that reason many people find them intolerable.

Gabapentin is an alternative that is usually less sleep-inducing, but at higher doses may cause grogginess. Along with carbamazepine, they can treat epilepsy, but seem slightly better tolerated than amitriptyline. They seem to block a neurotransmitter that activates the pain pathway, but it’s not well understood. A newer version with less side effects is pregabalin.

They have a cumulative effect, meaning you need to take them regularly for a few days until you see results, and build up the dose gradually until effective, then continue them regularly to keep pain under control. They may be used to reduce reliance on other pain relievers, or you could turn to the other classes for so-called breakthrough pain at times.

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Dr Karen Martin
Reviewed by Dr Karen Martin
Reviewed on 19.10.2023
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