The general principle is to start with first step drugs, and then to climb the ladder if pain is still present.
Then, if complete pain relief is not achieved or disease progression necessitates more aggressive treatment, a weak opioid such as codeine, dihydrocodeine or tramadol is added to the existing non-opioid regime.
If the initial presentation is severe pain, this stepping process should be skipped and a strong opioid should be started immediately in combination with a non-opioid analgesic.
Some authors challenge the pharmacological validity of the step and, pointing to their higher toxicity and low efficacy, argue that a weak opioid, with the possible exception of tramadol due to its unique additional actions (see tramadol § Pharmacology), could be replaced by smaller doses of a strong opioid.
Tricyclic antidepressants, class I antiarrhythmics, or anticonvulsants are the drugs of choice for neuropathic pain.