Table 1.
Study Characteristics According to Population and Setting
| Author, Year | Country | Number of Randomized Participants | Mean Age Per Studied Group | Sex (Male, n) | Inclusion Criteria | Exclusion Criteria | Follow-Up (Weeks) |
|---|---|---|---|---|---|---|---|
| Eide, 199438 | Norway | 8 (cross-over study) |
I: 71.9 P: 71.9 (cross-over study) |
I: 4 C: 4 (cross-over study) |
Patients with post-herpetic neuralgia attending the Pain Clinic, The National Hospital, Oslo, Norway, that were able to and willing to participate. | Patients not to use analgesic medication the last 2 days before each test session. | 3 weeks |
| Max, 199539 |
USA | 8 (cross-over study) |
I:40 P:40 (cross-over study) |
I: 0 C: 0 (cross-over study) |
Patients with chronic posttraumatic pain and widespread mechanical allodynia that need to demonstrate symptoms and signs suggesting altered central nervous system processing of sensory input. All patients were required to have mechanical allodynia to light stroking with a cotton gauze pad extending at least 5cm from site of injury. | Not reported | 3 days |
| Mercadante, 200040 | Italy | 10 (cross-over study) |
I: 57 C: 57 (cross-over study) |
I: 7 C: 7 (cross-over study) |
Patients with cancer and pain unrelieved by their dose of morphine and a Karnofsky status of 50 or more were selected for this study. No adjuvant drugs had been previously used. | Patients with coexisting liver or renal disease or with encephalopathy were excluded. | 3 days |
| Lauretti, 200241 | Brazil | 26 | I: 46 ± 12 C: 47 ± 10 |
I: 6 C: 8 |
Patients aged between 21 and 65years, with neuropathic chronic pain for more then six months, refractory to NSAID, physiotherapy, antidepressants, tramadol or intravenous meperidine, were included. | Not reported | 3 weeks |
| Kvarnstrom, 200335 | Denmark | 12 (cross-over study) | I: 47 C: 47 |
I: 3 C: 3 |
Patients should be affected by peripheral nerve or root lesions of traumatic origin, with spontaneous and evoked pain in the cutaneous territory supplied by the injured nerve together with clinically demonstrable sensory deficit or sensory hyperfunction. The age of the patients should be between 20 and 75 years | Patients with drug abuse, cardiovascular disease or previous treatment with intravenous ketamine or lidocaine were not considered for the study. | 1 week |
| Lynch, 200536 | Canada | 92 | Ketamine: 51 Amitriptyline: 51 Ketamine+Amitriptyline: 52 C: 52 |
Ketamine: 9 Amitriptyline: 11 Ketamine+Amitriptyline: 12 C: 15 |
Nonpregnant adult; Established diagnosis of postherpetic neuralgia, diabetic neuropathy, or postsurgical/post traumatic neuropathic pain; Moderate to severe pain all or most of the time persisting despite other treatment modalities; Pain has persisted for 3 months or longer; Presence of dynamic tactile allodynia or pinprick hyperalgesia in pain; Normal cognitive and communicative ability as judged by clinical assessment and ability to complete self-report questionnaires. | Evidence of another type of pain as severe as the pain understudy; Evidence of another type of neuropathic pain not included in this study; Major depression requiring treatment; Allergy to amitriptyline or ketamine; Ongoing use of a monoamine oxiDase inhibitor. | 3 weeks |
| Vranken, 200537 | Netherlands | 33 | I (50 mg): 58.4 ± 12.3 I (75mg): 51.2 ± 14.3 C: 51.8 ± 11 |
I (50 mg): 5 I (75mg): 6 C: 5 |
Age 18 years or older; patients suffering from neuropathic pain caused by lesion or dysfunction in the central nervous system, and insufficiently responding to conventional medical therapy (including opioids, anticonvulsants, antidepressants, baclofen, a-adrenergic agonists, oral anesthetic antiarrhythmic agents). Neuropathic pain was described by at least one of the following: burning pain, paroxysmal episodes of shooting pain, or pain on light touch. Additionally, patients had to score above 12 on the Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. | Patients were excluded from the study if they: were pregnant; had a history of intolerance, hypersensitivity, or known allergy to ketamine; had a known history of significant hepatic, renal, or psychiatric disorder; had a history of cardiac events including arrhythmias, congestive heart failure, or unstable angina; had poorly controlled hypertension (systolic BP above180 mmHg, or diastolic BP above 90 mmHg despite anti-hypertensive therapy); had a history of substance abuse. | 1 week |
| Tonet, 200842 | Brazil | 30 | Not specified | Not specified | Adult patients with chronic neuropathic pain. | Not specified | 4 weeks |
| Sigtermans 200925 | Netherlands | 60 | I: 43.7 ± 11.5 C: 47.5 ± 13.1 |
I: 8 C: 4 |
Patients who were diagnosed with Complex Regional Pain Syndrome Type-1, that was based on the International Association for the study of pain criteria. | Pain score of less than 5 of 10, age < 18 years, pregnancy/lactation, increased intracranial pressure, a history of psychosis, a serious medical disease (eg, cardiovascular, renal, or liver disease) and use of strong opioid medication. |
12 weeks |
| Schwartzman 200926 | USA | 19 | I: 38 (mean) C: 45.5 (mean) |
I: 0 C: 1 |
Patients diagnosed with CRPS based on the revised IASP (International Association for the Study of Pain) criteria; whose condition was intractable for a minimum of 6 months and had failed at least three therapies. The patients were ketamine naive and were of either gender including all racial or minority groups. The patient’s age was between 18 and 65 years. | Patients who were pregnant or had known substance abuse issues, glaucoma or thyrotoxicosis were excluded. Any subject that was unable to provide consent due to cognitive difficulties was not enrolled in this study. Patients with active litigation, compensation or disability issues related to their CRPS, and subjects on calcium channel or beta blockers due to the need to utilize clonidine with ketamine were excluded. |
12 weeks |
| Amr, 201028 | Egypt | 40 | I: 48.6±10.1 C:48.7 ± 9.7 |
I: 16 C: 17 |
All patients had been exhibiting symptoms for over 6 months. The study’s inclusion process continued until the requested number of patients was reached. | Patients who had SCI at or above the C-4 level were excluded because of the risk of respiratory arrest. Other exclusion factors were: pre existing hypertension, angina, congestive cardiac failure, hepatic impairment, renal impairment, and an allergy to any drugs used in the study. | 4 weeks |
| Amr, 201127 | Egypt | 40 | I: 48.6±10.1 C:48.7 ± 9.7 |
I: 16 C: 17 |
Duration of symptoms was more than six months in all patients. The process of inclusion into the study went on until the target number of patients was reached. | Patients with previous chronic anticoagulation therapy, coagulation disorders, infection in the back, bed sores, spine deformity, hepatic or renal impairment were excluded from the study. | 8 weeks |
| Barros, 201229 | Brazil | 12 (cross-over study) |
I: 71.7 P: 71.7 (Cross-over study) |
I:4 C:4 |
Post Herpetic Neuralgia patients seen at the Pain Management Clinic (HC-FMB-Unesp, Botucatu-SP), older than 18 years old and able to understand the Numerical Verbal Scale (NVS: 0 to 10) were invited to take part in the study. | Those presenting abnormal biochemical blood tests and skin lesions in the area of pain were not included in the study. | 5 weeks |
| Niesters, 201330 | Netherlands | 10 (cross-over study) |
I: 54.4 ±4,2 C: 54.4 ±4,2 (cross-over study) |
I: 2 C: 2 (cross-over study) |
Patients were required to have at least two of the following symptoms in legs, arms, or both (in a stocking-glove distribution): (i) symmetrical dysesthesias or paresthesias; (ii) burning or painful feet with night-time worsening; or (iii) peripheral tactile allodynia. With respect to the QST, subjects were included if they had an abnormal warm and cold detection threshold, an abnormal warm and cold pain threshold, or allodynia. | Age18 or.80 yr; presence or history of a medical disease such as renal, cardiac, vascular (including hypertension), or infectious disease; presence or history of a neurological and psychiatric disease such as increased cranial pressure, epilepsy or psychosis; glaucoma; pregnancy; obesity (BMI.30); or use of strong opioid medication. | 1 day |
| Kim, 201531 | South Korea | 30 | I: 69 C: 69 |
I: Not specified C: Not specified |
Patients with reported pain resistant to conventional treatments, including stellate ganglion block, local anesthetic infiltration, epidural block, and systemic administration of anticonvulsants and antidepressants. Spontaneous pain with a visual analog scale (VAS) scoreN7 and lasting for≥6 months. | Patients were excluded if they had hypermagnesemia, hypercalcemia, abnormal electrocardiogram, asthma, any degree of heart block, or renal impairment (blood ureaN12 mmol/L and creatinineN150μmol/L) or were taking digoxin. | 2 weeks |
| Rigo, 201732 | Brazil | 42 | Ketamine: 54 ± 12.4 Methadone: 52 ± 13.6 Keta+Metha: 45 ± 8.5 |
Ketamine: 6 Methadone: 6 Keta+Metha: 5 |
Patients who had experienced neuropathic pain for more than 6 months and who were poorly responsive to drugs used to treat neuropathic pain who were 22 to 77 years old from the Clinical Care & Pain Management. (HUSM) | Patients with a history of severe psychiatric disorder, misuse of illegal drugs, or hepatic disease were excluded. | 12 weeks |
| Fallon, 201833 | UK | 214 | I: Not specified C: Not specified |
I: Not specified C: Not specified |
≥18 years old; histological cancer diagnosis; written informed consent; Index neuropathic pain related to underlying malignancy or resulting from treatment received for this; Index neuropathic pain (worst pain) ≥ 4 on 0–10 (VAS); McGill Sensory Scale Score > 5; Patient has had a trial of at least one adjuvant analgesic (gabapentin, pregabalin, amitriptyline) or has been offered these and declined; patient is able to comply with study procedures. | Patients who have received chemotherapy or radiotherapy in the preceding six weeks; who may have a change in tumoricidal treatment during the period of study; Diastolic pressure > 100 mmHg at screening; History seizures in last 2 years; currently taking class I-antiarrhythmic drugs; life expectancy less than two months; patient who are actively hallucinating; women of childbearing potential not using adequate contraception, patients with cerebrovascular disease; patients with psychotic disorders. | 4 weeks |
| Pickering, 201934 | France | 20 (cross-over study) |
I: 55 ± 12 C: 55 ± 12 (cross-over study) |
I:10 C: 10 (cross-over study) |
Patients with at least 18 year of age, chronic pain for more than 3 months, peripheral or central pain requiring IV ketamine infusion, and no previous ketamine treatment (naïve patients). | Previous IV ketamine treatment; contraindication (1) to ketamine (hypersensitivity, uncontrolled high blood pressure, severe heart failure), (2) to magnesium (severe kidney failure), or (3) to sodium chloride (water inflation, fluid retention); medical/surgical history or drug treatment judged by the investigator to be incompatible with the trial; women of childbearing age without effective contraceptive method; pregnancy or lactation; involvement in another clinical trial; and inability to comply with protocol requirements. | 35 days |
Abbreviations: I, intervention group; C, control; NSAIDS, nonsteroidal anti-inflammatory drugs; CRPS, Complex Regional Pain Syndrome; IASP, International Association for the Study of Pain; SCI, spinal cord injury; QST, quantitative sensory testing; BMI, body mass index; VAS, visual analogic scale.