Neuropathic Pain
Antidepressants and anti-epileptics are often of benefit when used as single agents in 'pure' non-cancer nerve pain (e.g., diabetic neuropathy and post-herpetic neuralgia), but when nerve pain is caused by an infiltrating malignancy, the combination of an opioid and and NSAID should be tried first. When this is not effective, adjuvant medications may be considered. The most common classes of drugs used for neuropathic pain include antidepressants, anticonvulsants, and antiarrhythmics. Selection of the most useful adjuvant is based on each drug's indications, potential adverse effects, drug interactions, and dosing guidelines.
The burning, tingling sensation of neuropathic pain can often be relieved with a low dose (10-100mg) of a tricyclic antidepressant such as amitriptyline, nortriptyline, doxepin, or desipramine. These drugs can also help treat insomnia and depression. The mechanism of action probably depends on several factors. Because these drugs act in so many places, there are also multiple side effects.
The drug works in the following ways:
Blockade of re-uptake at presynaptic terminals of the following compounds (responsible for antidepressant and analgesic effects)
Serotonin
Norepinephrine
Receptor Blockade
Muscarinic (responsible for effect on urinary urgency and bladder spasms)
Histaminergic (responsible for sedation effects)
α-adrenergic (responsible for postural hypertension)
NMDA
Sodium
Calcium
Desipramine and nortriptyline are more selective norepinephrine re-uptake inhibitors and exhibits less antimuscarinic and antihistaminergic effect, making them more appropriate in the elderly population. Amitriptyline also has more active metabolites and a longer half-life. Caution must be used in patients with underlying cardiac disease because of these drugs' effects on QT prolongation and potential for cardiac arrhythmias. For patients unable to tolerate the side effects associated with TCAs, other anti-depressants that have been shown to be helpful in the treatment of neuropathic pain include SSRIs (e.g., paroxetine and citalopram), and newer SNRIs (e.g., venlafaxine and duloxetine). Due to concerns for serotonin syndrome, caution should be used when combining SSRIs or SNRIs with TCAs or tramadol. Antiepileptic drugs (e.g., gabapentin, valproic acid, carbamazepine, and pregabalin) dampen the neuronal excitability that is characteristic of neuropathic pain by reducing electrical excitability of cell membranes (usually by blocking sodium channels) and enhancing GABA-mediated synaptic inhibition. When neuropathic pain is characterized by shooting or stabbing pain, consider using anticonvulsants. Full anticonvulsant dosages may be required. Since they do not work like antidepressants, they may be used in combination.
In addition to antidepressants and anticonvulsants, antiarrhythmics such as lidocaine or mexiletine and other agents, have alleviated neuropathic pain in some patients. IV or SC lidocaine can be used for neuropathic pain that is unresponsive to other treatment. Some types of neuropathic pain are mediated by the abnormal activation of sodium channels, and lidocaine acts as a sodium channel antagonist. IV lidocaine has been shown to have effects for up to three to four weeks. The lidocaine patch has also been used as a topical analgesic and is FDA approved for postherpetic neuralgia. It has been reported to relieve localized pain from a multitude of conditions, although clinical trials are lacking. Up to three patches can be applied simultaneously for a maximum of 12 hours per day. The analgesic effect can be seen within a few hours, and the side effects are minimal (primarily rashes); however, it is contraindicated for patients with advanced liver failure or with heart blocks, and its significant cost must be considered.
Cannabinoids may help treat pain experienced by patients with HIV-related neuropathies.