Are Psychotropic Medications Effective in Chronic Pain Management in Children and Adolescents? A Meta-Analysis of Randomized Control Trials

Abstract

Objective Data defining and subsequently guiding the use of psychotropic medications in children and adolescents is sparse. We conducted a meta-analysis of randomized control trials to examine the effectiveness of psychotropic medications in children and adolescents with chronic pain. Methods We conducted a comprehensive literature search from published studies, and annual scientific sessions of psychiatry conferences. We identified double-blind, randomized control trials (RCTs) in which psychotropic medications were compared to placebo. Data was collected for the total number of patients, baseline characteristics, and changes in pain score. Meta-analysis was performed using a random effect model evaluating average change in pain score and the number of patients with a reduction in pain score for both groups. Pooled data are expressed as standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals (CI). Results We found 5 studies that included amitriptyline (n=2), citalopram (n=1), buspirone (n=1) and duloxetine (n=1). In the pooled analysis for the difference in the average change in pain score, 4 RCTs with 395 patients were included. After 12–13 weeks of therapy, reductions in pain score were significantly greater in the psychotropic drug group as compared to placebo (SMD: −0.77, 95% CI −1.54, 0.0001, p= 0.05). For the analysis on the number of patients with a reduction in pain, data were available for 445 patients (224-medication group, 221-placebo group). More patients in the psychotropic drug group experienced a meaningful reduction in pain score at 12–13 weeks of therapy compared to placebo (OR 1.66, 95% CI 1.08–2.54, p= 0.02). Conclusion The results of this meta-analysis demonstrate significant analgesic efficacy of psychotropic medications in the management of children with chronic pain. This review is limited by the small number of studies included for analysis. There is a pressing need for more robust clinical trials to further investigate these promising findings.

Chronic Pediatric Pain and Mental Illness During the COVID-19 Era: A Case Report From Inpatient Child Psychiatry Unit

“…In the above cases, significant improvement in mental health symptoms and chronic pain of patients were noted when pharmacological and psychotherapeutic interventions were utilized. In terms of pharmacological management, the evidence of using non-opioid pharmacological agents has been limited mostly to the use of NSAIDs and anticonvulsants, with only recent evidence supporting the use of psychotropic medications, mainly from the antidepressant category [ 10 ]. Antidepressants work through pathways that involve increased norepinephrine and serotonin in the synaptic clefts near the spinal cord that have an inhibitory effect on the perception of pain [ 11 ].…”

Antidepressant in the Treatment of Chronic Pain: A Case Report of Adult-Onset Still's Disease

“…In recent years, duloxetine via 5-HT and NA has been found to modulate ascending spinal nociceptive neurotransmission via the descending inhibitory pain pathway, which is why duloxetine is used in chronic pain [ 11 , 12 ]. There have been some recent studies further establishing the role of anti-depressant medications in the treatment of chronic pain conditions in pediatric and adult populations [ 13 ]. There are many medications used to treat complex rheumatological diseases like AOSD, and clinicians should be aware of any drug-drug interactions between immunomodulators and other medications [ 14 , 15 ].…”

Systematic Review on Nonopioid Pharmacologic Treatments for Chronic Pain: Surveillance Report 2

“…9 Function, based on the Brief Pain Inventory (BPI) Interference score, was also improved, which was inconsistent with the previous findings of no effect of duloxetine on function. Updated metaanalyses with this trial continued to show duloxetine associated with a small improvement in mean pain intensity (4 RCTs, N=1,462, MD -0.54, 95% CI, -0.76 to -0.34, I 2 =0%) 9,[29][30][31] and likelihood of pain response (4 RCTs, N=1,451, 58.3% vs. 47.3%, RR 1.26, 95% CI, 1.13 to 1.39, I 2 =%), 9,[29][30][31] and no effect on function based on the BPI Interference Score (4 RCTs, N=1,437, MD -0.42, 95% CI, -0.77 to -0.14, I 2 =36%). 9,[29][30][31] Two fair-quality RCTs (N=654), added to this update, reported mixed results for pain outcomes with naproxen compared with placebo in low back pain.…”

“…Updated metaanalyses with this trial continued to show duloxetine associated with a small improvement in mean pain intensity (4 RCTs, N=1,462, MD -0.54, 95% CI, -0.76 to -0.34, I 2 =0%) 9,[29][30][31] and likelihood of pain response (4 RCTs, N=1,451, 58.3% vs. 47.3%, RR 1.26, 95% CI, 1.13 to 1.39, I 2 =%), 9,[29][30][31] and no effect on function based on the BPI Interference Score (4 RCTs, N=1,437, MD -0.42, 95% CI, -0.77 to -0.14, I 2 =36%). 9,[29][30][31] Two fair-quality RCTs (N=654), added to this update, reported mixed results for pain outcomes with naproxen compared with placebo in low back pain. 7,8 One 16-week treatment trial (n=525) found a small but statistically significant reduction in pain intensity with naproxen (MD -0.41, p=0.037) and 30-percent or greater pain response (p=0.009) with baseline observation carried forward for missing data.…”

“…The addition of one trial of duloxetine (n=236) 9 to an updated meta-analysis did not change prior conclusions of no effect of serotonin-norepinephrine reuptake inhibitors (SNRIs) on the risk of serious adverse events (SAEs) (20 RCTs, N=9,059, 1.6% vs. 2.6%, RR 0.92, 95% CI, 0.65 to 1.29, I 2 =0%) 9,[23][24][25][26][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] and a moderate risk of withdrawals due to adverse events (WAEs) (25 RCTs, N=10,207, 15.2% vs. 7.4%, RR 2.00, 95% CI, 1.72 to 2.35, I 2 =18%). 9,[23][24][25][26][27][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]…”