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Adjuvant analgesics are drugs that are used primarily for treating conditions other than pain. Adjuvant analgesics are not analgesics in the true pharmacological sense, but may contribute significantly to pain relief when used either alone or in combination with other analgesics. Adjuvant analgesics comprise a various group of medications with different primary indications and include antidepressants (such as triclyclic antidepressants (TCAs), antiepileptic drugs, muscle relaxants. These drugs may be used alone or in combination with an opioid or a nonopioid analgesic to treat persistent pain conditions, particularly neuropathic pain.

Antidepressants have been used for decades as primary analgesics. They may be considered multipurpose analgesics, appropriate for a trial in any persistent pain condition.

The tricyclic antidepressants have been well studied and are most likely to be effective. Tricyclic antidepressants (TCAs) such as amitriptyline, nortriptyline and desipramine have demonstrated efficacy for migraine, diabetic peripheral neuropathy, post-herpetic neuralgia (PHN), arthritis pain and post-stroke pain. The most evidence exists for amitriptyline but some patients cannot tolerate its sedating, anticholinergic, and appetite-stimulating effects. Desipramine or nortriptyline may be better tolerated in such cases.

Controlled studies of the tricyclic antidepressants (TCAs) have shown that the usually effective analgesic dose is often lower than that required to treat depression, and the onset of analgesic action usually is earlier.

TCAs are probably more effective at relieving neuropathic pain than the newer antidepressants, but their side effect liability is higher than newer drugs. Unfortunately, newer serotonin-selective reuptake inhibitors (SSRIs) lack efficacy in pain relief. Paroxetine (Paxil) is the only SSRI that has some evidence for efficacy in treating chronic pain. There has recently been some published evidence for the effectiveness of Venlafaxine (Effexor) and Bupropion (Wellbutrin) for neuropathic pain.

The newer antidepressants, selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and SSRIs have fewer side effects than TCAs. SNRIs appear to be more effective analgesics than the SSRIs. Venlafaxine (Effexor) provides inconsistent effects while duloxetine (Cymbalta), the newest of the SNRIs has been approved by the FDA as a treatment for pain due to diabetic neuropathy.

Drugs that are predominantly noradrenergic, such as bupropion, also may be analgesic. Bupropion inhibits neuronal norepinephrine and serotonin uptake and, less potently, dopamine reuptake. The drug is commonly used for smoking cessation therapy as well as depression. It can be activating and therefore useful in patients with hypoactive depression, fatigue, or sedation. Bupropion is associated with a low risk for somnolence or sexual dysfunction, which is common with other antidepressants.

Anticonvulsants are commonly used to treat neuropathic pain. There is strong evidence that anticonvulsant drugs are useful in the management of neuropathic pain. They act by suppressing the spontaneous neuronal discharges and neuronal hyperexcitability that occur after nerve injury and may also have a central effect.

Although these drugs have been used for decades, their widespread use for pain did not begin until several years after the FDA approval of gabapentin (Neurontin). Gabapentin (Neurontin) is currently the most commonly prescribed drug for this indication. It is FDA approved for the treatment of diabetic painful polyneuropathy and postherpetic neuralgia. Pregabalin, which is a distinct compound but has the same mechanism of action, was recently approved for the same indications. This drug has more stable pharmacokinetics than gabapentin and should be simpler to use. Other antiepileptics, such as phenytoin, carbamazepine, clonazepam and valproic acid, and newer drugs, such as lamotrigine, topiramate, tiagabine, and oxcarbazepine, also are used as analgesics for neuropathic pain.

The most common adverse effects of the different anticonvulsants are gastric intolerance (nausea and vomiting), sedation, ataxia, dizziness and confusion being.

Anticonvulsants are given at similar doses as for seizure management.

• 1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.

Published: May 05, 2007
Last updated: January 07, 2009