داروهای ضدافسردگی برای دردهای مزمن غیرسرطانی در کودکان و نوجوانان
References
References to studies included in this review
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References to studies excluded from this review
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Additional references
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Characteristics of studies
Characteristics of included studies [ordered by study ID]
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| Methods | Allocation: randomised Blinding: double‐blind Controlled: placebo Centre: single Arm: 2 arms, parallel groups Study dates: 4‐year trial (2002 to 2005) | |
| Participants | Inclusion criteria: adolescents newly diagnosed with IBS based on Rome II criteria Exclusion criteria: currently receiving any concurrent pharmacotherapy for depression, anxiety, or chronic pain syndromes Baseline characteristics N = 33 Age: 12 to 18 years Gender: male (9); female (24) Number randomised: intervention (16); placebo (17) Setting and location: private outpatient practice paediatric gastroenterology clinic, California, USA | |
| Interventions | Intervention group (N = 16): amitriptyline oral capsule (10 mg: < 50 kg, 20 mg: 50 to 80 kg, 30 mg: > 80 kg) Control group (N = 17): oral placebo tablet Study duration: 13 weeks' duration: enrolment and symptom scoring, 8 weeks of intervention, washout and symptom scoring | |
| Outcomes | Primary outcomes
Secondary outcomes
| |
| Notes | Sources of funding: Brooks Medical Research Foundation of the California Community Foundation (Los Angeles, California), and AstraZeneca, LP (Wayne, Pennsylvania) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "subjects were randomized in a double‐blind, placebo controlled fashion to receive amitriptyline or placebo" |
| Allocation concealment (selection bias) | Unclear risk | Comment: Not stated |
| Blinding of participants and personnel (performance bias) | Unclear risk | Quote: "double‐blind study" Comment: insufficient information provided regarding observer or reporter knowledge. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: Insufficient information provided. |
| Incomplete outcome data (attrition bias) | Low risk | Comment: All participants stated to have completed the trial. |
| Selective reporting (reporting bias) | Low risk | Comment: All planned outcomes listed in the methods were reported in the results. |
| Size | High risk | Comment: Total participants = 33. Participants < 50 per treatment arm. |
| Other bias | Low risk | Comment: No other potential sources of bias |
| Methods | Allocation: randomised Blinding: double‐blind Controlled: active comparator Centre: single Arm: 2 arms, parallel groups Study dates: 38‐month trial (April 2006 to July 2010) | |
| Participants | Inclusion criteria: CRPS‐I or neuropathic pain and recommendation for pharmacological treatment with gabapentin or amitriptyline by a clinic physician during the patient's intake appointment. Exclusion criteria: unable to speak English, lactose intolerant, pregnant, previously using either gabapentin or amitriptyline for the treatment of CRPS‐I or neuropathic pain or if they were unable to swallow a size “0” gelatin capsule. Children were also excluded if study medications were contraindicated by additional health conditions or the treatment of such conditions, including the regular use of any of the following medications or classes of medications: anticholinergics, antihypertensives, anticonvulsants, H2 receptor antagonists, antidepressants, sympathomimetics, thyroid replacements, antacids, and analgesics. Baseline characteristics N = 34 Age: 7 to 18 years Gender: male (6); female (28) Number randomised: intervention (17); active comparator (17) Number completed: intervention (15); active comparator (14) Setting and location: Chronic Pain Clinic (The Hospital for Sick Children, Toronto, Canada) | |
| Interventions | Intervention group (N = 17): oral amitriptyline 10 mg/day Control group (N = 17): oral gabapentin 900 mg/day (300 x 3) Study duration: 6 weeks' duration | |
| Outcomes | Primary outcomes
Secondary outcomes
| |
| Notes | Sources of funding: Canadian Institutes of Health Research (CIHR) New Emerging Team (NET) Grant (GHL‐63209) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "The randomization sequence generation was completed by the research support service pharmacist (not involved in patient care) and the allocation list was concealed from the participants and the study team" Quote: "Since some neuropathic pain conditions disproportionately affect boys and girls, randomization was stratified by sex to ensure that equivalent numbers of boys and girls were randomized to each treatment group. The randomization sequence of 1:1 ratio of amitriptyline to gabapentin was a block 4 design with the possible sequence combinations (e.g., AABB, ABAB) assigned a number and then a point on a page of printed random numbers picked" |
| Allocation concealment (selection bias) | Low risk | Quote: "The research support pharmacy held the allocation sequence schedule, with a copy of participant‐specific medications in sealed manila envelopes available to the research coordinator for emergency purposes or unblinding at the end of the study period" |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "To maintain blinding due to differences in dosing frequency for the two study drugs, participants were prescribed one capsule at night (∼20:00 h) for the first 3 days, then added a second capsule in the morning (∼08:00 h) for the next 3 days and then added a third capsule mid‐afternoon (∼14:00 h) for the remainder of the trial. Children randomized to the amitriptyline group received amitriptyline in the evening pill and placebo in the morning and afternoon pills; while children randomized to gabapentin received 300 mg of gabapentin in each pill." Quote: "Both study and placebo medications were made to be similar in composition, odour, colour and taste by over encapsulating the untouched original dosage form with a larger opaque hard gelatin capsule (7.34 ml in length) and filling any space with lactose powder." |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: Insufficient information provided. |
| Incomplete outcome data (attrition bias) | Low risk | Comment: All participants were accounted for. |
| Selective reporting (reporting bias) | Unclear risk | Comment: Not all planned outcomes were reported; disruption of school, social, and sports not reported. |
| Size | High risk | Comment: Total participants = 34. Participants < 50 per treatment arm. |
| Other bias | Low risk | Comment: No other potential sources of bias |
| Methods | Allocation: randomised Blinding: double‐blind Controlled: placebo Centre: single Arm: 2 arms, parallel groups Study dates: 11‐month trial (February 2013 to December 2013) | |
| Participants | Inclusion criteria: school‐aged children who fulfilled Rome III diagnostic criteria for functional abdominal pain Exclusion criteria: other concomitant gastrointestinal disorders and those with a history of receiving psychotropic drugs, antibiotics, or probiotics in the preceding 2 months Baseline characteristics N = 115 Age: 6 to 18 years Gender: male (30); female (56) Number randomised: intervention (59); placebo (56) Number completed: intervention (43); placebo (43) Setting and location: tertiary outpatient clinic of paediatric gastroenterology, Isfahan, Iran | |
| Interventions | Intervention group (N = 56): oral tablet citalopram 10 mg/day (week 1); 20 mg/day (weeks 2, 3, and 4) Control group (N = 59): placebo tablet/day Study duration: 4 weeks' duration | |
| Outcomes | Primary outcomes
Secondary outcomes
| |
| Notes | Sources of funding: support from the Isfahan University of Medical Sciences, grant #391299 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "... coded by a pharmacist using random numbers generated by the random allocation software" |
| Allocation concealment (selection bias) | Low risk | Quote: "Allocation was concealed and the attending physician, participants, and outcome assessor were unaware of the drug codes." |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "The placebo group received placebo tablets (similar in shape, colour, and size with citalopram) in a same order." |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "The interviewer was blinded to the allocation sequence and study arms." Quote: "Allocation was concealed and the attending physician, participants, and outcome assessor were unaware of the drug codes." |
| Incomplete outcome data (attrition bias) | Low risk | Comment: All participants were accounted for. |
| Selective reporting (reporting bias) | Low risk | Comment: All planned outcomes listed in the methods were reported in the results. |
| Size | High risk | Comment: Total participants = 115. Participants > 50 per treatment randomised; participants < 50 per treatment arm completed. |
| Other bias | Low risk | Comment: No other potential sources of bias |
| Methods | Allocation: randomised Blinding: double‐blind Controlled: placebo Centre: multicentre Arm: 2 arms, parallel groups Study dates: 42‐month trial (January 2003 to August 2006) | |
| Participants | Inclusion criteria: diagnosis of functional abdominal pain, functional dyspepsia, or IBS according to the Rome II criteria Exclusion criteria: diagnosed with an organic disease, plotted below the 5th percentile for weight or height, had abnormal testing (electrocardiogram, complete blood count, erythrocyte sedimentation rate, albumin, pancreatic and liver enzymes, urine analysis, stool examination for occult blood and ova and parasites, tissue transglutaminase), a positive lactose breath test or a history of symptoms resolving after 2 weeks of a lactose‐free diet Baseline characteristics N = 90 Age: 8 to 17 years Gender: male (24); female (66) Number randomised: intervention (46); placebo (44) Number completed: intervention (43); placebo (40) Setting and location: paediatric gastroenterology clinics of 6 tertiary care centres geographically dispersed in the USA | |
| Interventions | Intervention group (N = 46): amitriptyline oral capsule, 10 mg/day < 35 kg or 20 mg/day > 35 kg for 4 weeks Control group (N = 44): oral placebo tablet for 4 weeks Study duration: 5 weeks' duration | |
| Outcomes | Primary outcomes
Secondary outcomes
| |
| Notes | Sources of funding: supported in part by: (a) the 2003 Clinical Research Award of the American College of Gastroenterology, (b) the CHP19596 RA501 grant and the grants M01 RR‐00048, M01 RR‐00084, and MO1 RR‐02172 from the National Center for Research Resources, National Institutes of Health | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomized to receive either placebo or amitriptyline" |
| Allocation concealment (selection bias) | Unclear risk | Quote: Not stated |
| Blinding of participants and personnel (performance bias) | Unclear risk | Quote: "double‐blind study" Comment: Insufficient information provided regarding observer or reporter knowledge. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Comment: Insufficient information provided. |
| Incomplete outcome data (attrition bias) | Low risk | Comment: All participants were accounted for. |
| Selective reporting (reporting bias) | Low risk | Comment: All planned outcomes listed in the methods were reported in the results. |
| Size | High risk | Comment: Total participants = 90. Participants < 50 per treatment arm randomised and completed study. |
| Other bias | Low risk | Comment: No other potential sources of bias |
CRPS‐I: complex regional pain syndrome; IBS: irritable bowel syndrome
Characteristics of excluded studies [ordered by study ID]
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| Study | Reason for exclusion |
| Participants: adult population | |
| Participants: adult population | |
| Analysis: intervention arm had < 10 participants | |
| Participants: adult population | |
| Participants: adult population | |
| Intervention: N‐of‐1 trial | |
| Participants: adult population | |
| Participants: adult population | |
| Participants: adult population |
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
| Amitriptyline compared with gabapentin for chronic non‐cancer pain | ||||||
| Patient or population: children and adolescents (birth to 17 years) with chronic non‐cancer pain Settings: single‐centre, chronic pain clinic, Canada Intervention: amitriptyline Comparison: gabapentin | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Gabapentin | Amitriptyline | |||||
| Participant‐reported pain relief of 30% or greater | No data | No data | No data | No data | No evidence to support or refuteb | |
| Participant‐reported pain relief of 50% or greater | No data | No data | No data | No data | No evidence to support or refuteb | |
| Patient Global Impression of Change: much improved or very much improved | No data | No data | No data | No data | No evidence to support or refuteb | |
| Adverse events | 1/17 | 2/17 | N/A | 34 participants (1 study) | ⊕⊝⊝⊝ | |
| Serious adverse events | 0/17 | 0/17 | N/A | 34 participants (1 study) | ⊕⊝⊝⊝ | |
| Withdrawals due to adverse events | 2/17 | 1/17 | N/A | 34 participants (1 study) | ⊕⊝⊝⊝ | |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; N/A: not applicable; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
| aDowngraded three levels due to too few data and number of events were too small to be meaningful. bNo data available for this outcome, and therefore no GRADE rating has been applied and there is no evidence to support or refute. | ||||||
| Amitriptyline compared with placebo for chronic non‐cancer pain | ||||||
| Patient or population: children and adolescents (birth to 17 years) with chronic non‐cancer pain Settings: single‐ and multicentre; (1) private outpatient practice paediatric gastroenterology clinic, California, USA; (2) paediatric gastroenterology clinics, (6) tertiary care centres, USA Intervention: amitriptyline Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Placebo | Amitriptyline | |||||
| Participant‐reported pain relief of 30% or greater | No data | No data | No data | No data | No evidence to support or refuteb | |
| Participant‐reported pain relief of 50% or greater | No data | No data | No data | No data | No evidence to support or refuteb | |
| Patient Global Impression of Change: much improved or very much improved | No data | No data | No data | No data | No evidence to support or refuteb | |
| Adverse events | 1/61 | 2/62 | N/A | 123 participants (2 studies) | ⊕⊝⊝⊝ | |
| Serious adverse events | 0/61 | 0/62 | N/A | 123 participants (2 studies) | ⊕⊝⊝⊝ | |
| Withdrawals due to adverse events | 1/61 | 2/62 | N/A | 123 participants (2 studies) | ⊕⊝⊝⊝ | |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; N/A: not applicable; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
| aDowngraded three levels due to too few data and number of events were too small to be meaningful. bNo data available for this outcome, and therefore no GRADE rating has been applied and there is no evidence to support or refute. | ||||||
| Citalopram compared with placebo for chronic non‐cancer pain | ||||||
| Patient or population: children and adolescents with functional abdominal pain Settings: single‐centre, tertiary outpatient clinic of paediatric gastroenterology, Iran Intervention: citalopram Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Placebo | Citalopram | |||||
| Participant‐reported pain relief of 30% or greater | No data | No data | No data | No data | No evidence to support or refuteb | |
| Participant‐reported pain relief of 50% or greater | No data | No data | No data | No data | No evidence to support or refuteb | |
| Patient Global Impression of Change: much improved or very much improved | No data | No data | No data | No data | No evidence to support or refuteb | |
| Adverse events | 0/56 | 5/59 | N/A | 115 participants (1 study) | ⊕⊝⊝⊝ | |
| Serious adverse events | 0/56 | 0/59 | N/A | 115 participants (1 study) | ⊕⊝⊝⊝ | |
| Withdrawals due to adverse events | 0/56 | 5/59 | N/A | 115 participants (1 study) | ⊕⊝⊝⊝ | |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; N/A: not applicable; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
| aDowngraded three levels due to too few data and number of events are too small to be meaningful. bNo data available for this outcome, and therefore no GRADE rating has been applied and there is no evidence to support or refute. | ||||||
