Twenty-four studies (n=198) were included, of which seven were RCTs (n=114).
Central pain: one level II study (9 patients) and one level IV study (1 patient) found that oral and parenteral ketamine reduced continuous and evoked pain with modest side-effects.
Complex regional pain syndrome: two level IV studies (3 patients, 2 of whom also had concurrent physiotherapy and rehabilitation) found that epidural ketamine produced complete pain relief. One patient reported severe headaches and nausea.
Fibromyalgia: two level II studies (RCTs; 46 patients diagnosed using established criteria) found that ketamine increased endurance and reduced tenderness at trigger points (plus some other measures of pain) in comparison with lidocaine, naloxone and placebo.
Ischaemic pain: one level II crossover study (8 patients) found that intravenous ketamine (0.45 mg/kg) produced transient pain in all patients compared with 5 patients obtaining relief from morphine.
Orofacial pain: the results from level II and level IV studies were mixed. One level II crossover study (30 patients with trigeminal neuralgia) found little difference between ketamine and pethidine. One level IV study (7 patients) found ketamine relieved pain only in the 3 patients who had suffered pain for less than 3 years. One level II study (1 patient in n of 1 trial) found ketamine relieved pain in comparison with placebo.
Non-specific neuropathic pain: level II and level IV studies reported conflicting results. Three level II studies (24 patients with a variety of underlying conditions) found that ketamine reduced hyperalgesia and allodynia but there was less effect of continuous pain. One level IV study (1 patient) also found benefit from ketamine. One level II study (9 responders out of 21 initially entered patients) showed low response rates in n of 1 RCTs (2 of the 9 chose to continue ketamine). One level IV study (21 patients) found less favourable results and reported high drop-out rates due to side-effects and minimal benefit.
Phantom limb pain: one level II study (11 patients), one level III study (3 patients) and one level IV study (1 patient) found ketamine to be beneficial. The reviewers also reported positive results from another level IV study, but presented no details of this study.
Postherpetic neuralgia: one level II study (8 patients), one level II study (5 patients who were included in the level II study) and two level IV studies (2 patients) found that ketamine reduced pain. The level II study found that all patients reported side-effects with ketamine.
Acute on chronic episodes of severe neuropathic pain: one level IV study (1 patient unresponsive to morphine and intrathecal bupivacaine) found benefit from intravenous ketamine. The reviewers also reported results from their own experience of subcutaneous ketamine (classified as level IV evidence), but gave no supporting reference or details.