BACKGROUND: Antidepressants are commonly used to treat low back pain and spine-related leg pain. However, their benefits and harms are uncertain. This is an update of a 2008 Cochrane review of antidepressants for non-specific low back pain.
OBJECTIVES: To assess the benefits and harms of antidepressants for non-specific low back pain and spine-related leg pain.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register from inception to 14 November 2024.
SELECTION CRITERIA: We included randomised controlled trials that compared antidepressants with placebo, usual care, or no treatment/waiting list. Participants were 18 years of age or older with non-specific low back pain or spine-related leg pain of any duration. We excluded participants with low back pain due to spinal fracture, inflammatory disease, aortic dissection, malignancy, or infection. Primary outcomes were pain intensity and disability, measured at short-term follow-up (> 4 to 14 weeks post-randomisation), and total adverse events. Secondary outcomes were serious adverse events, withdrawals due to adverse events, depressive symptoms, and health-related quality of life.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened records to determine study inclusion, extracted data, and evaluated risk of bias using RoB 1 tool. Where possible, we conducted meta-analyses. We used GRADE to assess the certainty of evidence.
MAIN RESULTS: We included 26 randomised controlled trials. Eighteen studies included 2535 participants with non-specific low back pain, seven studies included 329 participants with spine-related leg pain, and one study included 68 participants with either condition. Most participants had pain lasting more than three months, with a mean duration between 18 months and 20 years. Mean ages ranged from 27 to 59 years. Studies evaluated serotonin and norepinephrine reuptake inhibitors (SNRIs; eight studies), selective serotonin reuptake inhibitors (SSRIs; two studies), tricyclic antidepressants (TCAs; 14 studies), tetracyclic antidepressants (TeCAs; two studies), or 'other antidepressants' (two studies). All studies were placebo-controlled. Outcomes were measured at short-term follow-up in 73% of studies. All included studies had at least one domain judged at high risk of bias, with 69% at high risk of attrition bias. Non-specific low back pain (benefits) Moderate-certainty evidence demonstrated that SNRIs probably have a small effect on pain intensity (mean difference (MD) (0 to 100 scale) -5.25, 95% confidence interval (CI) -7.17 to -3.34; I2 = 0; 4 studies, 1415 participants) and a trivial effect on disability (MD (0 to 24 scale) -0.91, 95% CI -1.30 to -0.51; I2 = 0; 4 studies, 1348 participants) at short-term follow-up. Low-certainty evidence showed that SSRIs may have little to no effect on pain intensity (MD 1.20, 95% CI -4.90 to 7.30; I2 = 0; 3 studies, 199 participants) and disability (MD -2.20 (0 to 100 scale), 95% CI -8.11 to 3.71; 1 study, 92 participants) at short-term follow-up. Moderate-certainty evidence demonstrated that TCAs probably have little to no effect on pain intensity (MD -2.00, 95% CI -7.25 to 3.24; I² = 31%; 4 studies, 417 participants), but probably have a small effect on disability (MD (0 to 24 scale) -1.76, 95% CI -2.70 to -0.82; I2 = 0; 3 studies, 330 participants) at short-term follow-up. The effects of TeCAs (MD -4.50, 95% CI -17.59 to 8.59; 1 study, 52 participants) and other antidepressants (MD -5.40, 95% CI -23.08 to 12.28; 1 study, 39 participants) on pain intensity at short-term follow-up are unclear (very low-certainty evidence). No studies assessed the effects of TeCAs or other antidepressants on disability. Spine-related leg pain (benefits) The effects of SNRIs on pain intensity (MD -46.10, 95% CI -89.29 to -2.91; 1 study, 11 participants) and disability (MD (0 to 100 scale) -4.40, 95% CI -20.25 to 11.45; 1 study, 11 participants) at short-term follow-up are very uncertain (very low-certainty evidence). Low-certainty evidence showed TCAs may have a large effect on pain intensity at short-term follow-up (MD -23.00, 95% CI -32.12 to -13.88; 1 study, 60 participants), and a moderate effect on disability (MD (0 to 100 scale) -13.00, 95% CI -19.42 to -6.58; 1 study, 60 participants). There were no studies that assessed the effects of SSRIs, TeCAs, or other antidepressants in people with spine-related leg pain. Non-specific low back pain and spine-related leg pain (harms) Moderate-certainty evidence demonstrated that SNRIs probably increase the risk of adverse events (risk ratio (RR) 1.17, 95% CI 1.07 to 1.27; I2 = 0%; 5 studies, 1510 participants), but it is unclear whether they increase the risk of serious adverse events (Peto odds ratio (OR) 1.75, 95% CI 0.79 to 3.89; 5 studies, 1510 participants; very low-certainty evidence). It is unclear whether TCAs increase the risk of adverse events (RR 1.76, 95% CI 0.79 to 3.90; 7 studies, 474 participants; low-certainty evidence) or serious adverse events (Peto OR 6.64, 95% CI 0.41 to 106.72; I² = 0%; 1 study, 142 participants; very low-certainty evidence). It is unclear whether SSRIs (RR 1.83, 95% CI 0.14 to 24.19; I² = 95%; 2 studies, 107 participants; very low-certainty evidence) or TeCAs increase the risk of adverse events (RR 0.93, 95% CI 0.79 to 1.09; 1 study, 52 participants; very low-certainty evidence). No studies assessed the risk of serious adverse events for these classes. No studies measured total adverse events for other antidepressants. It is unclear whether other antidepressants increase the risk of serious adverse events (Peto OR 0.90, 95% CI 0.16 to 4.96; 1 study, 42 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS: We found that in people with non-specific low back pain, SNRIs probably have small effects on pain intensity, trivial effects on disability, and are probably associated with adverse effects. TCAs probably do not reduce low back pain intensity, but may have a small effect on disability. The effects of antidepressants on spine-related leg pain are uncertain, though SNRIs and TCAs might be prioritised over other classes for future investigations. Evidence for the safety of SSRIs, TCAs, TeCAs, and other antidepressants in non-specific low back pain and spine-related leg pain remains unclear.
BACKGROUND: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
OBJECTIVE: To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020.
ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis.
DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework.
RESULTS: 33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference -5.30, 95% confidence interval -7.31 to -3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (-9.72, -12.75 to -6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (-18.60, -31.87 to -5.33) but not at 3-13 weeks (-17.50, -42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (-7.55, -18.25 to 3.15) but did at 3-13 weeks (-15.95, -31.52 to -0.39) and 3-12 months (-27.0, -36.11 to -17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (-3.55, -5.22 to -1.88) and disability due to osteoarthritis at two weeks or less (-5.10, -7.31 to -2.89), with low certainty evidence at 3-13 weeks (-6.07, -8.13 to -4.02). TCAs and other antidepressants did not reduce pain or disability from back pain.
CONCLUSION: Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020158521.
BACKGROUND: A 2007 American College of Physicians guideline addressed pharmacologic options for low back pain. New evidence and medications have now become available.
PURPOSE: To review the current evidence on systemic pharmacologic therapies for acute or chronic nonradicular or radicular low back pain.
DATA SOURCES: Ovid MEDLINE (January 2008 through November 2016), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists.
STUDY SELECTION: Randomized trials that reported pain, function, or harms of systemic medications versus placebo or another intervention.
DATA EXTRACTION: One investigator abstracted data, and a second verified accuracy; 2 investigators independently assessed study quality.
DATA SYNTHESIS: The number of trials ranged from 9 (benzodiazepines) to 70 (nonsteroidal anti-inflammatory drugs). New evidence found that acetaminophen was ineffective for acute low back pain, nonsteroidal anti-inflammatory drugs had smaller benefits for chronic low back pain than previously observed, duloxetine was effective for chronic low back pain, and benzodiazepines were ineffective for radiculopathy. For opioids, evidence remains limited to short-term trials showing modest effects for chronic low back pain; trials were not designed to assess serious harms. Skeletal muscle relaxants are effective for short-term pain relief in acute low back pain but caused sedation. Systemic corticosteroids do not seem to be effective. For effective interventions, pain relief was small to moderate and generally short-term; improvements in function were generally smaller. Evidence is insufficient to determine the effects of antiseizure medications.
LIMITATIONS: Qualitatively synthesized new trials with prior meta-analyses. Only English-language studies were included, many of which had methodological shortcomings. Medications injected for local effects were not addressed.
CONCLUSION: Several systemic medications for low back pain are associated with small to moderate, primarily short-term effects on pain. New evidence suggests that acetaminophen is ineffective for acute low back pain, and duloxetine is associated with modest effects for chronic low back pain.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014014735).
Journal»European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
INTRODUCTION: The objective of this study was to obtain parameter estimates for the efficacy of duloxetine versus alternative oral therapies for the treatment of chronic low back pain.
MATERIALS AND METHODS: Electronic databases were searched to identify randomised, double-blind placebo-controlled trials. Studies reporting pain intensity, with parallel-group design of oral treatments with length of treatment of more than 8 weeks were included. A Bayesian approach to indirect comparisons was applied, using standardised mean difference as a measure of relative treatment effect.
RESULTS: Fifteen studies were identified comparing duloxetine with the following oral drug classes: non-scheduled opioids, cyclooxygenase-2 inhibitors, scheduled opioids, selective serotonin reuptake inhibitors, and 'other' (i.e. glucosamine). The primary analysis found scheduled opioids to be more effective than duloxetine for the fixed effects model. However, the estimate of the treatment difference reflected a less than small magnitude of effect (|standardised mean difference| <0.2), and there was no difference for the random effects model. No differences were found in sensitivity analyses involving the subset of patients not receiving concomitant non-steroidal anti-inflammatory medication.
CONCLUSION: The available evidence shows that there does not seem to be any difference in efficacy between duloxetine and other oral pharmacological therapies, providing a valuable alternative for this disabling condition.
Journal»European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
The objective of this review was to determine the effectiveness of pharmacological interventions [i.e., non-steroid anti-inflammatory drugs (NSAIDs), muscle relaxants, antidepressants, and opioids] for non-specific chronic low-back pain (LBP). Existing Cochrane reviews for the four interventions were screened for studies fulfilling the inclusion criteria. Then, the literature searches were updated. Only randomized controlled trials on adults (≥18 years) with chronic (≥12 weeks) non-specific LBP and evaluation of at least one of the main clinically relevant outcome measures (pain, functional status, perceived recovery, or return to work) were included. The GRADE approach was used to determine the quality of evidence. A total of 17 randomized controlled trials was included: NSAIDs (n = 4), antidepressants (n = 5), and opioids (n = 8). No studies were found for muscle relaxants; 14 studies had a low risk of bias. The studies only reported effects on the short term (<3 months). The overall quality of the evidence was low. NSAIDs and opioids seem to lead to a somewhat higher relief in pain on the short term, as compared to placebo, in patients with non-specific chronic low back pain; opioids seem to have a small effect in improving function for a selection of patients who responded with an exacerbation of their symptoms after stopping their medication. However, both types of medication show more adverse effects than placebo. There seems to be no difference in effect between antidepressants and placebo in patients with non-specific chronic LBP.
A systematic review involving 50 randomized controlled trials (4,863 patients) published since 1980 was undertaken with the objective of assessing efficacy and safety of low back pain (LBP) medications. The methodological quality of each trial was evaluated based on a standardized system. Quality scores ranged from 26 to 82 points on a 100-point scale (from 0 to 100), indicating an overall moderate quality of the trials reviewed. Limited evidence was found regarding the effectiveness of drug treatments for LBP and current studies focused on short-term usage of the therapies. Available evidence supported the effectiveness of non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) in acute and chronic LBP, of muscle relaxants in acute LBP, and of antidepressants in chronic LBP; safety results were heterogeneous. More rigorously designed trials should be implemented to establish comparative efficacy and safety of drugs used to treat chronic and acute LBP.
BACKGROUND: Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor.
OBJECTIVES: To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression.
SEARCH METHODS: Electronic search of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966-), EMBASE (1980-), CINAHL (1982-), PsycLIT (1974-), PSYNDEX (1977-) and LILACS (1982-1999) and hand searches of major psychiatric and medical journals. Reference search and SciSearch of the identified studies. Personal contact with authors of significant papers.
SELECTION CRITERIA: All randomised controlled trials 1) comparing low dosage TCA (=< 100 mg/d on average at the end of trial) with placebo or 2) comparing low and standard dosages of the same TCA, in acute phase treatment of depressive disorder
DATA COLLECTION AND ANALYSIS: Two independent reviewers examined eligibility of the identified studies, and extracted data for outcomes at 1 week, 2 weeks, 4 weeks, 6-8 weeks and later. Main outcome measures were relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression according to the last-observation-carried-forward intention-to-treat method, and relative risks of overall dropouts and dropouts due to side effects. Other outcome measures included worst-case-scenario intention-to-treat analysis of response as defined above (in which dropouts were considered non-responders in the active treatment group and as responders in the comparison group), and standardised weighted mean scores of continuous depression severity scales (usually calculated by last-observation-carried-forward method).
MAIN RESULTS: 35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics.
AUTHORS' CONCLUSIONS: Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.
BACKGROUND: Three previous reviews have reached conflicting conclusions regarding the efficacy of antidepressants for patients with back pain. OBJECTIVES: To systematically review the efficacy of antidepressants for the treatment of patients with back pain and to determine whether there is evidence that outcomes vary between classes of antidepressants. MATERIALS AND METHODS: Best evidence synthesis of randomized, placebo-controlled trials of oral antidepressive agents in patients with back pain. Studies were identified by searching MEDLINE, PsycINFO, and the Cochrane Controlled Trials Registry. Two independent reviewers performed data extraction and assessed included studies with a 22-point methodologic quality assessment scale. Effect sizes were calculated if sufficient data were available. RESULTS: Twenty-two trials of antidepressants for the treatment of back pain were identified, of which seven studies of chronic low back pain met inclusion criteria. Among studies using antidepressants that inhibit norepinephrine reuptake (tricyclic or tetracyclic antidepressants), four of five found significant improvement in at least one relevant outcome measure. Assessment of these agents' impact on functional measures produced mixed results. No benefit in pain relief or functional status was found in three studies of antidepressants that do not inhibit norepinephrine reuptake. CONCLUSIONS: Based on a small number of studies, tricyclic and tetracyclic antidepressants appear to produce moderate symptom reductions for patients with chronic low back pain. This benefit appears to be independent of depression status. SSRIs do not appear to be beneficial for patients with chronic low back pain. There is conflicting evidence whether antidepressants improve functional status of patients with chronic low back pain.
Antidepressants are commonly used to treat low back pain and spine-related leg pain. However, their benefits and harms are uncertain. This is an update of a 2008 Cochrane review of antidepressants for non-specific low back pain.
OBJECTIVES:
To assess the benefits and harms of antidepressants for non-specific low back pain and spine-related leg pain.
SEARCH METHODS:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register from inception to 14 November 2024.
SELECTION CRITERIA:
We included randomised controlled trials that compared antidepressants with placebo, usual care, or no treatment/waiting list. Participants were 18 years of age or older with non-specific low back pain or spine-related leg pain of any duration. We excluded participants with low back pain due to spinal fracture, inflammatory disease, aortic dissection, malignancy, or infection. Primary outcomes were pain intensity and disability, measured at short-term follow-up (> 4 to 14 weeks post-randomisation), and total adverse events. Secondary outcomes were serious adverse events, withdrawals due to adverse events, depressive symptoms, and health-related quality of life.
DATA COLLECTION AND ANALYSIS:
Two review authors independently screened records to determine study inclusion, extracted data, and evaluated risk of bias using RoB 1 tool. Where possible, we conducted meta-analyses. We used GRADE to assess the certainty of evidence.
MAIN RESULTS:
We included 26 randomised controlled trials. Eighteen studies included 2535 participants with non-specific low back pain, seven studies included 329 participants with spine-related leg pain, and one study included 68 participants with either condition. Most participants had pain lasting more than three months, with a mean duration between 18 months and 20 years. Mean ages ranged from 27 to 59 years. Studies evaluated serotonin and norepinephrine reuptake inhibitors (SNRIs; eight studies), selective serotonin reuptake inhibitors (SSRIs; two studies), tricyclic antidepressants (TCAs; 14 studies), tetracyclic antidepressants (TeCAs; two studies), or 'other antidepressants' (two studies). All studies were placebo-controlled. Outcomes were measured at short-term follow-up in 73% of studies. All included studies had at least one domain judged at high risk of bias, with 69% at high risk of attrition bias. Non-specific low back pain (benefits) Moderate-certainty evidence demonstrated that SNRIs probably have a small effect on pain intensity (mean difference (MD) (0 to 100 scale) -5.25, 95% confidence interval (CI) -7.17 to -3.34; I2 = 0; 4 studies, 1415 participants) and a trivial effect on disability (MD (0 to 24 scale) -0.91, 95% CI -1.30 to -0.51; I2 = 0; 4 studies, 1348 participants) at short-term follow-up. Low-certainty evidence showed that SSRIs may have little to no effect on pain intensity (MD 1.20, 95% CI -4.90 to 7.30; I2 = 0; 3 studies, 199 participants) and disability (MD -2.20 (0 to 100 scale), 95% CI -8.11 to 3.71; 1 study, 92 participants) at short-term follow-up. Moderate-certainty evidence demonstrated that TCAs probably have little to no effect on pain intensity (MD -2.00, 95% CI -7.25 to 3.24; I² = 31%; 4 studies, 417 participants), but probably have a small effect on disability (MD (0 to 24 scale) -1.76, 95% CI -2.70 to -0.82; I2 = 0; 3 studies, 330 participants) at short-term follow-up. The effects of TeCAs (MD -4.50, 95% CI -17.59 to 8.59; 1 study, 52 participants) and other antidepressants (MD -5.40, 95% CI -23.08 to 12.28; 1 study, 39 participants) on pain intensity at short-term follow-up are unclear (very low-certainty evidence). No studies assessed the effects of TeCAs or other antidepressants on disability. Spine-related leg pain (benefits) The effects of SNRIs on pain intensity (MD -46.10, 95% CI -89.29 to -2.91; 1 study, 11 participants) and disability (MD (0 to 100 scale) -4.40, 95% CI -20.25 to 11.45; 1 study, 11 participants) at short-term follow-up are very uncertain (very low-certainty evidence). Low-certainty evidence showed TCAs may have a large effect on pain intensity at short-term follow-up (MD -23.00, 95% CI -32.12 to -13.88; 1 study, 60 participants), and a moderate effect on disability (MD (0 to 100 scale) -13.00, 95% CI -19.42 to -6.58; 1 study, 60 participants). There were no studies that assessed the effects of SSRIs, TeCAs, or other antidepressants in people with spine-related leg pain. Non-specific low back pain and spine-related leg pain (harms) Moderate-certainty evidence demonstrated that SNRIs probably increase the risk of adverse events (risk ratio (RR) 1.17, 95% CI 1.07 to 1.27; I2 = 0%; 5 studies, 1510 participants), but it is unclear whether they increase the risk of serious adverse events (Peto odds ratio (OR) 1.75, 95% CI 0.79 to 3.89; 5 studies, 1510 participants; very low-certainty evidence). It is unclear whether TCAs increase the risk of adverse events (RR 1.76, 95% CI 0.79 to 3.90; 7 studies, 474 participants; low-certainty evidence) or serious adverse events (Peto OR 6.64, 95% CI 0.41 to 106.72; I² = 0%; 1 study, 142 participants; very low-certainty evidence). It is unclear whether SSRIs (RR 1.83, 95% CI 0.14 to 24.19; I² = 95%; 2 studies, 107 participants; very low-certainty evidence) or TeCAs increase the risk of adverse events (RR 0.93, 95% CI 0.79 to 1.09; 1 study, 52 participants; very low-certainty evidence). No studies assessed the risk of serious adverse events for these classes. No studies measured total adverse events for other antidepressants. It is unclear whether other antidepressants increase the risk of serious adverse events (Peto OR 0.90, 95% CI 0.16 to 4.96; 1 study, 42 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS:
We found that in people with non-specific low back pain, SNRIs probably have small effects on pain intensity, trivial effects on disability, and are probably associated with adverse effects. TCAs probably do not reduce low back pain intensity, but may have a small effect on disability. The effects of antidepressants on spine-related leg pain are uncertain, though SNRIs and TCAs might be prioritised over other classes for future investigations. Evidence for the safety of SSRIs, TCAs, TeCAs, and other antidepressants in non-specific low back pain and spine-related leg pain remains unclear.
