Adjuvant Medications

 

Definitions

Nociceptive pain: pain that is aching and throbbing. For example arthritic pain is usually nociceptive.

Neuropathic pain: this pain is described as sharp, shooting, stabbing, burning, tingling or stinging. Sometimes referred to as nerve pain.

Muscular pain: is described as aching, throbbing, pressure and stiffness.

Adjuvant pain medications: are drugs that are primarily used for conditions other than pain but are also helpful in relieving pain. Adjuvant pain medications can include antidepressants, anti-seizure medications or muscle relaxants.

Fibromyalgia: a pain condition that causes widespread pain, IE pain that is all over, rather than regional pain, along with other symptoms such as fatigue, sleep problems, headaches, depression, and anxiety.

Analgesia: the action of an analgesic medication to provide relief of pain.

Opioid: a natural or synthetic drug used to relieve pain with characteristics similar to opium derived from the poppy plant. A partial list includes oxycodone (Percocet or Oxycontin), hydrocodone (Vicodin or Norco), morphine (MsContin, MSIR or Kadian), fentanyl (Duragesic), and hydromorphone (Dilaudid or Exalgo). The term opioid has replaced narcotic, which was an older and less accurate term.

Opioid-sparing: the ability of a treatment or drug to cause equal or better analgesia at a lower opioid dose.

First-line therapy: a class of drugs or type of treatment that should be tried first, because it is most likely to produce the best results.

 

Antidepressants

Some antidepressants can be used to:

  1. reduce neuropathic pain,

  2. prevent migraine headaches,

  3. relieve fibromyalgia symptoms,

  4. treat chronic musculoskeletal pain and rheumatoid arthritis. 

 

Usually lower doses than those needed to treat depression are effective for pain. Just because antidepressants are helpful for pain does not mean that the pain is caused by depression. People who do not have depression can experience pain relief from antidepressants.

 

The tricyclic antidepressants, amitriptyline (Elavil), and nortriptyline (Pamelor) have been extensively studied, and there is compelling evidence for their analgesic properties in a variety of chronic pain conditions. Elavil is a very strong pain relieving adjuvant medication, but does have side effects for most patients. Sometimes we can take advantage of the side effects. For example, if a patient has insomnia, a nighttime dose of Elavil will help the pain and the insomnia.

 

Other Antidepressants

There is evidence from randomized controlled trials that several other antidepressants are also analgesic, and are generally safer and better tolerated, IE less side effects.

 

Venlafaxine (Effexor) has been shown to be analgesic in several studies. Randomized controlled trials showed good pain relief for painful polyneuropathy and for neuropathic pain following treatment of breast cancer. May elevate blood pressure and may cause sexual dysfunction.

Mirtazapine (Remeron) is effective for chronic pain and migraine prophylaxis with additional benefits of sleep improvement. It also improves digestive function which is very helpful for people with heartburn, GERD or Irritible Bowel Syndrome. Does not cause sexual dysfunction.

Duloxetine (Cymbalta) has analgesic effects in neuropathic and arthritic pain. It is FDA approved for the treatment of neuropathy, as well as fibromyalgia and chronic musculoskeletal pain. Don't use with liver disease.

Milnaciprin (Savella) is in the same family of drugs as Cymbalta but is only approved for the treatment of fibromyalgia in the U.S.

Bupropion (Wellbutrin) is analgesic in neuropathic pain and often is activating (helps patients feel more energetic). The activating effect is very helpful for patients with low energy level. Does not cause sexual dysfunction.

 

Antidepressants are thought to work by increasing the levels of certain chemicals (norepinephrine, serotonin) at nerve endings that help to inhibit pain signals. A favorable analgesic effect is usually observed within a week. In summary, there is substantial evidence that antidepressant drugs have analgesic effects in diverse types of chronic pain.

 

Anti-seizure medications

Anti-seizure medications such as gabapentin, pregabalin or topiramate are also helpful for nerve-related pain. The most common side effects with these medications are drowsiness, dizziness, and balance problems, but they usually improve with continued use.

 

Gabapentin. The analgesic efficacy of gabapentin (Neurontin) has been established in several types of neuropathic pain, and it is now widely used to treat neuropathic pain. Due to its proven analgesic effect, its good tolerability, and a rarity of drug-drug interactions, gabapentin is now recommended as a first-line therapy for the treatment of neuropathic pain of diverse etiologies, especially in the medically ill population. It should be initiated at a daily dose of 100–300 mg at bedtime and can be increased every 3 days. The usual maximum dose is 3,600 mg daily, but occasionally patients report benefits at higher doses. An adequate trial should include 1–2 weeks at the maximum-tolerated dose. The most common adverse effects are somnolence, dizziness, and unsteadiness. If titrated carefully, gabapentin is usually well tolerated, but in medically ill patients, somnolence can be a limiting factor.

Pregabalin (Lyrica) is a new anticonvulsant with a mechanism similar to that of gabapentin and strong evidence of analgesic efficacy. Lyrica is probably stronger than gabapentin and works faster but does have more side effects.

Topiramate (Topamax) is very effective for nerve pain, has few side effects and is also FDA approved for migraine prevention.

 

Muscle relaxants

Muscle relaxants such as cyclobenzaprine (Flexeril), methocarbamol (Robaxin), metaxalone (Skelaxin), orphenadrine (Norflex) or tizanidine (Zanaflex) may also be used to help with muscular pain. These medicines act at several sites in the body to reduce muscle tone and relax tight, tense muscles. Some of these medicines have direct effects on skeletal muscle fibers, while others influence both nerves and muscles. Drugs like Flexeril, Robaxin, Skelaxin, and Norflex work at the spinal cord level and aid in relieving muscle pain and tightness.

 

Tizanidine or Zanaflex reduces spasticity at the level of the spinal cord and is used for the treatment of pain caused by  muscle spasticity associated with spinal cord injury and multiple sclerosis or other causes. It may have additional pain relieving properties that may be useful for treating general chronic pain conditions as well as muscle pain.

 

Side effects of muscle relaxants typically include sedation, and, therefore, you may need to reserve the medication for nighttime use.

 

First-Line Therapy

Severe chronic pain can be nociceptive pain or neuropathic pain or muscular pain. (see definitions above). Opioids are not first-line therapy for muscular pain or neuropathic pain. Muscle relaxants are more likely to help muscle pain than opioids. Antidepressants and anti-seizure medications are more likely to produce better analgesia for neuropathic pain than opioids.

 

Opioid-Sparing

Almost all patients with severe chronic pain will have some neuropathic and/or muscular pain. Hence the addition of adjuvant drugs, described above, will have an opioid-sparing effect in almost all cases.

 

Give adjuvant medications a full trial. The key is to fully evaluate a well selected adjuvant medication, which in most cases will produce a better analgesia than opioids alone. One must bear in mind the differences between opioids and most adjuvant medications.

 

Opioids have first dose effectiveness, whereas most adjuvant drugs have to be slowly titrated up to the correct dose, with full benefit coming 1-2 weeks after reaching the correct dose. Most patients know if an opioid is going to help within a day of taking the first dose. With adjuvant drugs it may take a month or longer to work up to the correct dose, and then 1-2 more weeks to see the benefits.

 

The most common mistake I see is a patient quitting an adjuvant medication during the first week, based on a relatively minor side effect, that would have subsided in the next week or so. Many times if that patient will stick with it a little while longer the side effects will subside and when the beneficial effects kick in the patient will have a much higher quality of life.

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