Coanalgesic Drugs

Coanalgesic, or adjuvant drugs, are medications whose primary indication is for a purpose other than pain relief, but that demonstrate some analgesic effects. Antidepressants, anticonvulsants, corticosteroids, and other drugs may be used as coanalgesics. Coanalgesics may be used in addition to other analgesics or alone as primary treatment for specific painful conditions. Most experience with coanalgesics has been in the treatment of chronic pain, but adjuvant analgesics are increasingly being used to treat acute pain.

An opioid analgesic should be introduced and titrated to a maximum effect before a coanalgesic is added to the pain management regimen. The reason for this is that when both drugs are introduced together, the risk of toxicity is increased and it may be difficult to determine which drug is responsible for producing analgesia or for causing side effects. Fewer patients experience pain relief from coanalgesics than from opioid analgesics.

Most coanalgesics have a slower onset of analgesic action:

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When using a coanalgesic with an opioid, the coanalgesic drug should be introduced first.

For patients with chronic nonmalignant pain, who are not medically ill, a coanalgesic may be the only drug taken by the patient on a regular basis. In the palliative care setting, coanalgesics are often given to patients who are also receiving multiple drugs. Although this strategy is accepted practice for the care of terminally ill patients, the potential for additive side effects and unpredictable adverse effects must be anticipated whenever a coanalgesic is added to an existing drug regimen. If a coanalgesic enhances pain relief without serious risk or side effects that impair quality of life, their use is justified. Additional pain relief at the expense of sedation or mental clouding is not acceptable for patients whose goals include restoration of function, but may be very appropriate for individuals who have pain relief as their only goal.

Antidepressant drugs – this group of drugs may be used as coanalgesics for many types of chronic pain syndromes. Antidepressant drugs enhance pain modulation by interfering with the reuptake of serotonin and norepinephrine to decrease the perception of pain. Antidepressant drugs are started at a low dose. If the patient does not benefit from the usual analgesic dose and has no side effects, the dose may be titrated upward until the antidepressant dose is reached. A favorable analgesic effect is usually observed within a week. In some patients, maximal effect appears to evolve over several days or weeks. This delay, combined with the many days needed to increase the dose to a therapeutic level, may result in a prolonged period during which patients experience troublesome side effects and little positive pain relief benefit. Unless the patient is well informed about this potential, he or she is likely to discontinue the drug. Drug concentrations may be monitored during therapy.

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It may take some time for an antidepressant coanalgesic to relieve pain.

Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) may be used to treat chronic neuropathic pain.

Examples of tricyclic antidepressants include:
Amitriptyline (Elavil)
Doxepin (Sinequan)
Imipramine (Tofranil)
Nortriptyline (Pamelor, Aventyl)

Examples of SSRIs include:
Citalopram hydrobromide (Celexa)
Fluvoxamine maleate (Luvox)
Paroxetine hydrochloride (Paxil)
Sertraline hydrochloride (Zoloft)

There are a number of side effects associated with antidepressants. Tricyclic antidepressants can cause orthostatic hypotension. This side effect is common in elderly individuals and, combined with the sedating effects of these drugs, place the patient at an increased risk for falls. Tricyclic antidepressants may also cause mental clouding, confusion, and somnolence. These drugs also produce anticholinergic effects, such as dry mouth, blurred vision, and constipation. The most serious side effect of the tricyclic antidepressants, cardiotoxicity, is uncommon. Patients at increased risk of this complication include those who have significant heart disease, including conduction disorders and heart failure. Both tricyclic antidepressants and SSRIs can produce sexual dysfunction. Because of the side effects associated with tricyclic antidepressants, these drugs are usually used at low doses in addition to regular doses of SSRIs for concurrent depression.

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Elderly patients may be at increased fall risk when taking tricyclic antidepressants.

Anticonvulsants - Anticonvulsant drugs help control the ectopic, spontaneous firing of neurons in the central nervous system that produce seizures. It is thought that anticonvulsant drugs may also decrease the spontaneous firing of neurons in the peripheral nervous system that are associated with neuropathic pain.

Examples of anticonvulsant drugs include:
Carbamazepine (Tegretol)
Oxcarbazepine (Trileptal)
Topiramate (Topamax)
Valproic acid (Depacon)
Tiagabine (Gabitril)
Levetiracetam (Keppra)
Phenytoin (Dilantin)
Lamotrigine (Lamictal)
Zonisimade (Zonegran)
Gabapentin (Neurontin)

Corticosteroids - Corticosteroid drugs (Prednisone and others) may be used as coanalgesics in a variety of chronic pain syndromes. Their anti-inflammatory and analgesic effects are attributed to several mechanisms including:

The risk of serious toxicity increases with the dose of the corticosteroid drug, the duration of therapy, and other factors associated with the patient’s medical condition. Corticosteroids are usually given on a short-term basis and tapered off gradually. Potential toxicities include neuropsychological effects, hyperglycemia, fluid retention, and gastrointestinal disturbances that range from minor problems such as dyspepsia to potentially life threatening events such as bowel perforation.