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Adjuvant Medications
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By definition, adjuvant analgesics are drugs whose initial use was not for pain but rather for other conditions. They are a diverse group of drugs that includes antidepressants, anticonvulsants (antiseizure drugs), and others.

View lecture: Update on Adjuvant Analgesics (.pdf)


The best studied adjuvant analgesics are the tricyclic antidepressants (TCAs), such as amitriptyline (Elavil®), and desipramine. There is overwhelming evidence that this class of drugs can be effective for migraine headache, tension-type headache, postherpetic neuralgia, painful diabetic neuropathy, arthritis, low back pain, and other painful conditions. These drugs have been shown to relieve pain independent of their effects on depression; that is, patients who are not depressed may experience pain relief. Once the correct dose is found for the individual patient, favorable results are usually seen within a week; however, side effects, including weight gain, dry mouth, blurred vision and constipation, are possible.

There are many newer antidepressants, such as the selective serotonin reuptake inhibitors (like fluoxetine [Prozac®], paroxetine [Paxil®], sertraline [Zoloft®]), and others (like venlafaxine [Effexor®] and nefazadone [Serzone®]. Most of these antidepressant drugs have not been shown to be effective pain relievers in clinical studies, but some have, and many pain specialists believe that most, if not all, can potentially relieve pain. They are usually better tolerated than the TCA's.


Drugs that are primarily used to treat epilepsy (seizures) have been used to treat nerve pain conditions and migraine headache for several decades. Many anticonvulsant drugs have been shown in clinical studies to be effective.

The first-line drugs for neuropathic pains are two related anti-seizure medicines, gabapentin (Neurontin®) and pregabalin (Lyrica®), and a number of analgesic antidepressants. Gabapentin and pregabalin have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific neuropathic pains, including painful diabetic neuropathy and shingles. They are also used for migraine headache and for fibromyalgia. The most common side effects associated with these drugs are mental clouding and sleepiness. Other anti-seizure drugs also may be useful as second-line agents for neuropathic pain. These include carbamazepine [Tegretol®], phenytoin [Dilantin®], valproate [Depakote®], clonazepam [Klonopin®], topiramate [Topamax®], and lamotrigine [Lamictal®]. Some of these drugs, such as valproate and topiramate also are used for headache.

Alpha-2-Adrenergic Agonists

Currently, there are two alpha-2-adrenergic agonists that have some evidence as pain relievers: tizanidine (Zanaflex®) and clonidine (Catapres®). There are some studies showing that tizanidine can be effective for tension-type headache, back pain, neuropathic pain, and myofascial pains. Clonidine has been used to treat refractory neuropathic pain. Tizanidine tends to be better tolerated than clonidine and, unlike clonidine, rarely decreases blood pressure.

Local Anesthetics

Mexiletine is a drug that was first approved to treat irregular heart rhythms. However, several scientific studies have shown this drug to be effective in chronic nerve pain syndromes. Other oral local anesthetics are also used. Intravenous infusion of a local anesthetic is a special technique that may be used by pain specialists.


Corticosteroids can be used as an effective analgesic for treating some cancer pain syndromes. Also, corticosteroids given as short-term tapers can be effective in treating migraine headache and complex regional pain syndrome (reflex sympathetic dystrophy).

Other Adjuvant Analgesics

Baclofen is on the market as a muscle relaxant and is used to treat nerve pain syndromes. There is very good evidence that it works in trigeminal neuralgia.

Drugs that block a specific receptor involved in the experience of pain, the N-methyl-D-aspartate (NMDA) receptor, may also be analgesic in nerve pain. These include dextromethorphan (the cough suppressant, but at higher doses than those needed to block cough), ketamine (an anesthetic), and amantadine.

There are many drugs that are called "muscle relaxants" and are used to treat minor musculoskeletal pains. These include carisoprodol (Soma®), cyclobenzaprine (Flexeril®), metaxolone (Skelaxin®), and others. These drugs do not actually relax skeletal muscle, but they can relieve pain, and they are commonly used.

Topical Drugs

Topical drugs are applied directly to the skin, as a patch, gel, or cream and have their pharmacologic activity directly under the skin site without any significant amount of drug entering the blood stream. Thus, true topical drugs should not produce any systemic side effects, that is, side effects caused by the drug's effects throughout the body. Currently, only one topical drug has an FDA approved indication for pain treatment -- a topical lidocaine patch (Lidoderm®) -- for the treatment of postherpetic neuralgia. This patch can be tried for many types of nerve pain.

A widely used topical pain reliever is capsaicin, which is available as an over-the-counter cream. There have been some studies that show pain relief with capsaicin and others that do not. This drug is being used to treat nerve pain and arthritis pain.

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