Abstract: We included four studies with a total of 272 participants (6 to 18 years of age) who had either chronic neuropathic pain, complex regional pain syndrome type 1, irritable bowel syndrome, functional abdominal pain, or functional dyspepsia. All of the studies were small. One study investigated amitriptyline versus gabapentin (34 participants), two studies investigated amitriptyline versus placebo (123 participants), and one study investigated citalopram versus placebo (115 participants). Due to a lack of available data we were unable to complete any quantitative analysis. Risk of bias for the four included studies varied, due to issues with randomisation and allocation concealment (low to unclear risk); blinding of participants, personnel, and outcome assessors (low to unclear risk); reporting of results (low to unclear risk); and size of the study populations (high risk). We judged the remaining domains, attrition and other potential sources of bias, as low risk of bias. Primary outcomes No studies reported our primary outcomes of participant-reported pain relief of 30% or greater or 50% or greater, or Patient Global Impression of Change. Secondary outcomes All studies measured adverse events, with very few reported (11 out of 272 participants). All but one adverse event occurred in the active treatment groups (amitriptyline, citalopram, and gabapentin). Adverse events in all studies, across active treatment and comparator groups, were considered to be a mild reaction, such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (very low-quality evidence). There were also very few withdrawals due to adverse events, again all but one from the active treatment groups (very low-quality evidence). No serious adverse events were reported across any of the studies (very low-quality evidence). There were few or no data for our remaining secondary outcomes. Quality of evidence For the outcomes with available data, we downgraded the quality of the evidence by three levels to very low-quality due to too few data and the fact that the number of events was too small to be meaningful. We identified only a small number of studies with small numbers of participants and insufficient data for analysis. As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of antidepressants to treat chronic non-cancer pain in children and adolescents. Similarly, we could not comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life. We know from adult randomised controlled trials that some antidepressants, such as amitriptyline, can provide some pain relief in certain chronic non-cancer pain conditions.

Plain-language summary: In September 2016 we searched for clinical trials in which antidepressants were used to treat chronic nerve, menstrual, muscular, joint, or stomach pain. We found four trials with a total of 272 participants (aged 6 to 18 years old) who had nerve pain, general painful inflammation, stomach pain, or irritable bowel syndrome, for more than 3 months. No studies reported on pain relief of 30% or greater, or 50% or greater. Side effects were uncommon, and occurred only as mild reactions such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (4 due to amitriptyline, 5 due to citalopram, 1 due to gabapentin, and 1 due to placebo). These 11 participants withdrew from the study due to these mild side effects. There were no serious side effects. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The available evidence in this review was of very low-quality due to a lack of data and small study sizes.