Alyssa Migdalski, MLIS

EVIDENCE SUMMARY

Neither corticosteroids nor platelet-rich plasma are superior to placebo

A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.¹ In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.²

In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone ­follow-up. No functional assessments were reported at 6 months.³

The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.⁴

All injections that contained “placebo” significantly improved lateral epicondylitis.

The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.⁵

Platelet-rich plasma. A meta-analysis⁶ of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.

Corticosteroids and PRP. A 2013 3-armed RCT⁷ (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.

Botulinum toxin shows modest pain improvement, but …

A 2017 meta-analysis⁸ of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).

Continue to: Prolotherapy needs further study

A 2008 RCT⁹ of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.

Hyaluronic acid improves pain, but not enough

A 2010 double-blind RCT¹⁰ (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.

Autologous blood has no advantage over placebo

The only RCT of autologous blood compared to saline injections¹¹ included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.

Editor’s takeaway

Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.

EVIDENCE SUMMARY

Neither corticosteroids nor platelet-rich plasma are superior to placebo

A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.¹ In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.²

In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone ­follow-up. No functional assessments were reported at 6 months.³

The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.⁴

All injections that contained “placebo” significantly improved lateral epicondylitis.

The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.⁵

Platelet-rich plasma. A meta-analysis⁶ of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.

Corticosteroids and PRP. A 2013 3-armed RCT⁷ (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.

Botulinum toxin shows modest pain improvement, but …

A 2017 meta-analysis⁸ of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).

Continue to: Prolotherapy needs further study

A 2008 RCT⁹ of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.

Hyaluronic acid improves pain, but not enough

A 2010 double-blind RCT¹⁰ (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.

Autologous blood has no advantage over placebo

The only RCT of autologous blood compared to saline injections¹¹ included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.

Editor’s takeaway

Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.

EVIDENCE SUMMARY

Neither corticosteroids nor platelet-rich plasma are superior to placebo

A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.¹ In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.²

In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone ­follow-up. No functional assessments were reported at 6 months.³

The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.⁴

All injections that contained “placebo” significantly improved lateral epicondylitis.

The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.⁵

Platelet-rich plasma. A meta-analysis⁶ of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.

Corticosteroids and PRP. A 2013 3-armed RCT⁷ (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.

Botulinum toxin shows modest pain improvement, but …

A 2017 meta-analysis⁸ of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).

Continue to: Prolotherapy needs further study

A 2008 RCT⁹ of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.

Hyaluronic acid improves pain, but not enough

A 2010 double-blind RCT¹⁰ (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.

Autologous blood has no advantage over placebo

The only RCT of autologous blood compared to saline injections¹¹ included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.

Editor’s takeaway

Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.

EVIDENCE SUMMARY

Higher odds of depression in youth and adolescents with concussion

A 2019 prospective cohort study used data from the 2017 Nevada Youth Risk Behavior Surveillance Survey (YRBSS) to evaluate the relationship between concussion and depression in high school students.¹ Included students were physically active for at least 60 minutes on 5 or more days per week or played on at least 1 sports team (N = 3427; 9th-12th grade students from 98 schools). When compared to the total population of included students and controlled for covariates, those who self-reported a concussion within the past 12 months (N = 664) had a higher adjusted odds ratio (aOR) of depressive symptoms (aOR = 1.5; 95% confidence interval [CI], 1.1-1.9). Depressive symptoms were reported in 38.1% of patients with a history of concussion, compared to 29.2% of patients who did not report a concussion in the past 12 months.

A 2014 retrospective cohort study examined data from the 2007-2008 National Survey of Children’s Health and evaluated the association between previous concussion and current depression diagnosis in youth ages 12 to 17 years without a current concussion (N = 36,060).² Parents were contacted by random-digit dialing, prompted with a description of depression, and asked if their child currently had a clinical diagnosis of depression and whether a concussion had ever been diagnosed. A prior diagnosis of concussion was associated with greater risk for current depression compared to youth with no concussion history (aOR = 3.3; 95% CI, 2-5.5). Current depression was reported in 10.1% of patients with a history of concussion compared to 3.4% of patients with no history of concussion.

Findings vary among college athletes

A 2015 case-control study examined the prevalence of depressive symptoms in college athletes diagnosed with concussion compared to an athletic control group.³ The intervention group (N = 84; 77% male; average age, 18.4 years) received a concussion diagnosis from the team physician or certified athletic trainer. The athletic control group (N = 42; 55% male; average age, 18.9 years) reported no concussions in the past year.

The Beck Depression Inventory–Fast Screen (BDI-FS) was administered to the concussion group at baseline and postconcussion, and to the control group at 2 time points, with an average interval of 6.8 weeks. A score of ≥ 4 on the BDI-FS (scoring range, 0-21; higher score suggestive of more severe depression) indicated athletes at risk for depression. Concussed athletes exhibited a statistically significant increase in depression symptoms compared to control participants (20% vs 5%; x²₁ = 5.2; P = .02).

A 2018 cross-sectional study examined the association between concussion and adverse health outcomes in former college football players who played at least 1 year in college (1999-2001) but had no professional football experience.⁴ The cohort (N = 204; average age, 35) self-reported (15 years after their college career ended) the number of concussions sustained during high school and college sports performance. Reports were then stratified into 3 categories: no concussions, 1 or 2 concussions, and ≥ 3 concussions. The Patient Health Questionnaire (PHQ-9) was used to screen for depression, with scores categorized to no or mild depression (< 10) and moderate-to-­severe depression (≥ 10).

Controlling for body mass index, athletes reporting ≥ 3 concussions had a higher prevalence of depression compared to those reporting no concussions (prevalence ratio [PR] = 4.2; 95% CI, 1.0-16.3) or 1 to 2 concussions (PR = 2.8; 95% CI, 1.3-6.0). No statistically significant association between concussion and depression was observed with athletes reporting 1 to 2 concussions compared to 0 concussions.

The exact relationship— degree and context— between concussion and depression remains vague.

A 2015 prospective longitudinal cohort study examined postinjury depressive symptoms in 3 groups of Division 1 male and female college student athletes (N = 21; ages 18-22).⁵ Physician-diagnosed ­concussed (N = 7) and injured but nonconcussed (N = 7) athletes completed the Center for Epidemiological Studies Depression Scale (CES-D) at baseline and at 1 week, 1 month, and 3 months postinjury. Sport-matched healthy athletes (N = 7) completed it only at baseline. A CES-D score of ≥ 16 (range, 0-60) indicated a risk for clinical depression. Participants with a history of depression or other injury resulting in ≥ 1 day of time lost within the past 3 months were excluded.

Continue to: While both groups...

While both groups showed a significant increase from baseline CES-D scores, there were no significant differences in depressive symptoms between concussed (mean CES-D score ± standard deviation [SD]: baseline, 6.7 ± 3.9; 1 week, 11 ± 5.3; 1 month, 8.3 ± 5; 3 months, 6.4 ± 5.4) and injured but nonconcussed participants (mean CES-D score ± SD: baseline, 5.7 ± 2.8; 1 week, 9.1 ± 4; 1 month, 8.9 ± 4.6; 3 months, 6.9 ± 2.8) at any of the postinjury time points.

Findings among semipro and pro athletes appear to vary by sport

A 2016 prospective cohort study assessed the impact of concussive events on incidence of depression in active semiprofessional and professional football players who had previously sustained ≥ 1 concussions.⁶ Participants (N = 27) answered an anonymous online survey that included the revised version of the CES-D (CESD-R) to determine level of depression (a score of ≥ 16 defined clinical depression). Players with a CESD-R score ≥ 16 (N = 16) sustained a significantly greater average number of concussions compared to those who scored < 16 (N = 11; 3.8 vs. 1.6, P = .0004). Players who sustained ≥ 3 concussions scored significantly higher on the CESD-R than players with ≤ 2 concussions (average score, 24 vs 15.6; P = .03).

A 2017 case-control study examined the long-term health outcomes of retired Scottish male rugby players (N = 52; mean age, 54 years) with a history of mild concussion compared to males of similar age with no previous history of concussion (N = 29; mean age, 55).⁷ The Hospital Anxiety and Depression Scale (HADS) was used to assess depression on a 21-point scale (normal = 0-7; borderline, 8-10; abnormal, 11-21). There was no significant difference observed in mean HADS scores between the rugby players and controls, respectively (2.8 ± 2.1 vs 2.6 ± 2 .8; P = .941).

A 2013 case-control study of 30 retired NFL players with 29 controls matched for age, estimated IQ, and education examined the relationship between a remote history of concussion and current symptoms of depression.⁸ Concussion history was self-reported by the retired players. Controls with a history of concussion were excluded from the study. The Beck Depression Inventory-II (BDI-II) was used to measure depression symptoms, with a score of 1 to 9 designating minimal depression and ≥ 10 mild-to-moderate depression. Retired players scored significantly higher on the BDI-II compared to the controls (8.8 vs 2.8; P = .001).

Editor’s takeaway

Concussions include cognitive compromise. An astute clinician’s concern for depression as a sequela makes sense. This evidence contributes to that conjecture. However, the authors of this Clinical Inquiry correctly outline the limitations, inconsistencies, and biases of the evidence. The exact relationship—degree and context—between concussion and depression remains vague.

EVIDENCE SUMMARY

Higher odds of depression in youth and adolescents with concussion

A 2019 prospective cohort study used data from the 2017 Nevada Youth Risk Behavior Surveillance Survey (YRBSS) to evaluate the relationship between concussion and depression in high school students.¹ Included students were physically active for at least 60 minutes on 5 or more days per week or played on at least 1 sports team (N = 3427; 9th-12th grade students from 98 schools). When compared to the total population of included students and controlled for covariates, those who self-reported a concussion within the past 12 months (N = 664) had a higher adjusted odds ratio (aOR) of depressive symptoms (aOR = 1.5; 95% confidence interval [CI], 1.1-1.9). Depressive symptoms were reported in 38.1% of patients with a history of concussion, compared to 29.2% of patients who did not report a concussion in the past 12 months.

A 2014 retrospective cohort study examined data from the 2007-2008 National Survey of Children’s Health and evaluated the association between previous concussion and current depression diagnosis in youth ages 12 to 17 years without a current concussion (N = 36,060).² Parents were contacted by random-digit dialing, prompted with a description of depression, and asked if their child currently had a clinical diagnosis of depression and whether a concussion had ever been diagnosed. A prior diagnosis of concussion was associated with greater risk for current depression compared to youth with no concussion history (aOR = 3.3; 95% CI, 2-5.5). Current depression was reported in 10.1% of patients with a history of concussion compared to 3.4% of patients with no history of concussion.

Findings vary among college athletes

A 2015 case-control study examined the prevalence of depressive symptoms in college athletes diagnosed with concussion compared to an athletic control group.³ The intervention group (N = 84; 77% male; average age, 18.4 years) received a concussion diagnosis from the team physician or certified athletic trainer. The athletic control group (N = 42; 55% male; average age, 18.9 years) reported no concussions in the past year.

The Beck Depression Inventory–Fast Screen (BDI-FS) was administered to the concussion group at baseline and postconcussion, and to the control group at 2 time points, with an average interval of 6.8 weeks. A score of ≥ 4 on the BDI-FS (scoring range, 0-21; higher score suggestive of more severe depression) indicated athletes at risk for depression. Concussed athletes exhibited a statistically significant increase in depression symptoms compared to control participants (20% vs 5%; x²₁ = 5.2; P = .02).

A 2018 cross-sectional study examined the association between concussion and adverse health outcomes in former college football players who played at least 1 year in college (1999-2001) but had no professional football experience.⁴ The cohort (N = 204; average age, 35) self-reported (15 years after their college career ended) the number of concussions sustained during high school and college sports performance. Reports were then stratified into 3 categories: no concussions, 1 or 2 concussions, and ≥ 3 concussions. The Patient Health Questionnaire (PHQ-9) was used to screen for depression, with scores categorized to no or mild depression (< 10) and moderate-to-­severe depression (≥ 10).

Controlling for body mass index, athletes reporting ≥ 3 concussions had a higher prevalence of depression compared to those reporting no concussions (prevalence ratio [PR] = 4.2; 95% CI, 1.0-16.3) or 1 to 2 concussions (PR = 2.8; 95% CI, 1.3-6.0). No statistically significant association between concussion and depression was observed with athletes reporting 1 to 2 concussions compared to 0 concussions.

The exact relationship— degree and context— between concussion and depression remains vague.

A 2015 prospective longitudinal cohort study examined postinjury depressive symptoms in 3 groups of Division 1 male and female college student athletes (N = 21; ages 18-22).⁵ Physician-diagnosed ­concussed (N = 7) and injured but nonconcussed (N = 7) athletes completed the Center for Epidemiological Studies Depression Scale (CES-D) at baseline and at 1 week, 1 month, and 3 months postinjury. Sport-matched healthy athletes (N = 7) completed it only at baseline. A CES-D score of ≥ 16 (range, 0-60) indicated a risk for clinical depression. Participants with a history of depression or other injury resulting in ≥ 1 day of time lost within the past 3 months were excluded.

Continue to: While both groups...

While both groups showed a significant increase from baseline CES-D scores, there were no significant differences in depressive symptoms between concussed (mean CES-D score ± standard deviation [SD]: baseline, 6.7 ± 3.9; 1 week, 11 ± 5.3; 1 month, 8.3 ± 5; 3 months, 6.4 ± 5.4) and injured but nonconcussed participants (mean CES-D score ± SD: baseline, 5.7 ± 2.8; 1 week, 9.1 ± 4; 1 month, 8.9 ± 4.6; 3 months, 6.9 ± 2.8) at any of the postinjury time points.

Findings among semipro and pro athletes appear to vary by sport

A 2016 prospective cohort study assessed the impact of concussive events on incidence of depression in active semiprofessional and professional football players who had previously sustained ≥ 1 concussions.⁶ Participants (N = 27) answered an anonymous online survey that included the revised version of the CES-D (CESD-R) to determine level of depression (a score of ≥ 16 defined clinical depression). Players with a CESD-R score ≥ 16 (N = 16) sustained a significantly greater average number of concussions compared to those who scored < 16 (N = 11; 3.8 vs. 1.6, P = .0004). Players who sustained ≥ 3 concussions scored significantly higher on the CESD-R than players with ≤ 2 concussions (average score, 24 vs 15.6; P = .03).

A 2017 case-control study examined the long-term health outcomes of retired Scottish male rugby players (N = 52; mean age, 54 years) with a history of mild concussion compared to males of similar age with no previous history of concussion (N = 29; mean age, 55).⁷ The Hospital Anxiety and Depression Scale (HADS) was used to assess depression on a 21-point scale (normal = 0-7; borderline, 8-10; abnormal, 11-21). There was no significant difference observed in mean HADS scores between the rugby players and controls, respectively (2.8 ± 2.1 vs 2.6 ± 2 .8; P = .941).

A 2013 case-control study of 30 retired NFL players with 29 controls matched for age, estimated IQ, and education examined the relationship between a remote history of concussion and current symptoms of depression.⁸ Concussion history was self-reported by the retired players. Controls with a history of concussion were excluded from the study. The Beck Depression Inventory-II (BDI-II) was used to measure depression symptoms, with a score of 1 to 9 designating minimal depression and ≥ 10 mild-to-moderate depression. Retired players scored significantly higher on the BDI-II compared to the controls (8.8 vs 2.8; P = .001).

Editor’s takeaway

Concussions include cognitive compromise. An astute clinician’s concern for depression as a sequela makes sense. This evidence contributes to that conjecture. However, the authors of this Clinical Inquiry correctly outline the limitations, inconsistencies, and biases of the evidence. The exact relationship—degree and context—between concussion and depression remains vague.

EVIDENCE SUMMARY

Higher odds of depression in youth and adolescents with concussion

A 2019 prospective cohort study used data from the 2017 Nevada Youth Risk Behavior Surveillance Survey (YRBSS) to evaluate the relationship between concussion and depression in high school students.¹ Included students were physically active for at least 60 minutes on 5 or more days per week or played on at least 1 sports team (N = 3427; 9th-12th grade students from 98 schools). When compared to the total population of included students and controlled for covariates, those who self-reported a concussion within the past 12 months (N = 664) had a higher adjusted odds ratio (aOR) of depressive symptoms (aOR = 1.5; 95% confidence interval [CI], 1.1-1.9). Depressive symptoms were reported in 38.1% of patients with a history of concussion, compared to 29.2% of patients who did not report a concussion in the past 12 months.

A 2014 retrospective cohort study examined data from the 2007-2008 National Survey of Children’s Health and evaluated the association between previous concussion and current depression diagnosis in youth ages 12 to 17 years without a current concussion (N = 36,060).² Parents were contacted by random-digit dialing, prompted with a description of depression, and asked if their child currently had a clinical diagnosis of depression and whether a concussion had ever been diagnosed. A prior diagnosis of concussion was associated with greater risk for current depression compared to youth with no concussion history (aOR = 3.3; 95% CI, 2-5.5). Current depression was reported in 10.1% of patients with a history of concussion compared to 3.4% of patients with no history of concussion.

Findings vary among college athletes

A 2015 case-control study examined the prevalence of depressive symptoms in college athletes diagnosed with concussion compared to an athletic control group.³ The intervention group (N = 84; 77% male; average age, 18.4 years) received a concussion diagnosis from the team physician or certified athletic trainer. The athletic control group (N = 42; 55% male; average age, 18.9 years) reported no concussions in the past year.

The Beck Depression Inventory–Fast Screen (BDI-FS) was administered to the concussion group at baseline and postconcussion, and to the control group at 2 time points, with an average interval of 6.8 weeks. A score of ≥ 4 on the BDI-FS (scoring range, 0-21; higher score suggestive of more severe depression) indicated athletes at risk for depression. Concussed athletes exhibited a statistically significant increase in depression symptoms compared to control participants (20% vs 5%; x²₁ = 5.2; P = .02).

A 2018 cross-sectional study examined the association between concussion and adverse health outcomes in former college football players who played at least 1 year in college (1999-2001) but had no professional football experience.⁴ The cohort (N = 204; average age, 35) self-reported (15 years after their college career ended) the number of concussions sustained during high school and college sports performance. Reports were then stratified into 3 categories: no concussions, 1 or 2 concussions, and ≥ 3 concussions. The Patient Health Questionnaire (PHQ-9) was used to screen for depression, with scores categorized to no or mild depression (< 10) and moderate-to-­severe depression (≥ 10).

Controlling for body mass index, athletes reporting ≥ 3 concussions had a higher prevalence of depression compared to those reporting no concussions (prevalence ratio [PR] = 4.2; 95% CI, 1.0-16.3) or 1 to 2 concussions (PR = 2.8; 95% CI, 1.3-6.0). No statistically significant association between concussion and depression was observed with athletes reporting 1 to 2 concussions compared to 0 concussions.

The exact relationship— degree and context— between concussion and depression remains vague.

A 2015 prospective longitudinal cohort study examined postinjury depressive symptoms in 3 groups of Division 1 male and female college student athletes (N = 21; ages 18-22).⁵ Physician-diagnosed ­concussed (N = 7) and injured but nonconcussed (N = 7) athletes completed the Center for Epidemiological Studies Depression Scale (CES-D) at baseline and at 1 week, 1 month, and 3 months postinjury. Sport-matched healthy athletes (N = 7) completed it only at baseline. A CES-D score of ≥ 16 (range, 0-60) indicated a risk for clinical depression. Participants with a history of depression or other injury resulting in ≥ 1 day of time lost within the past 3 months were excluded.

Continue to: While both groups...

While both groups showed a significant increase from baseline CES-D scores, there were no significant differences in depressive symptoms between concussed (mean CES-D score ± standard deviation [SD]: baseline, 6.7 ± 3.9; 1 week, 11 ± 5.3; 1 month, 8.3 ± 5; 3 months, 6.4 ± 5.4) and injured but nonconcussed participants (mean CES-D score ± SD: baseline, 5.7 ± 2.8; 1 week, 9.1 ± 4; 1 month, 8.9 ± 4.6; 3 months, 6.9 ± 2.8) at any of the postinjury time points.

Findings among semipro and pro athletes appear to vary by sport

A 2016 prospective cohort study assessed the impact of concussive events on incidence of depression in active semiprofessional and professional football players who had previously sustained ≥ 1 concussions.⁶ Participants (N = 27) answered an anonymous online survey that included the revised version of the CES-D (CESD-R) to determine level of depression (a score of ≥ 16 defined clinical depression). Players with a CESD-R score ≥ 16 (N = 16) sustained a significantly greater average number of concussions compared to those who scored < 16 (N = 11; 3.8 vs. 1.6, P = .0004). Players who sustained ≥ 3 concussions scored significantly higher on the CESD-R than players with ≤ 2 concussions (average score, 24 vs 15.6; P = .03).

A 2017 case-control study examined the long-term health outcomes of retired Scottish male rugby players (N = 52; mean age, 54 years) with a history of mild concussion compared to males of similar age with no previous history of concussion (N = 29; mean age, 55).⁷ The Hospital Anxiety and Depression Scale (HADS) was used to assess depression on a 21-point scale (normal = 0-7; borderline, 8-10; abnormal, 11-21). There was no significant difference observed in mean HADS scores between the rugby players and controls, respectively (2.8 ± 2.1 vs 2.6 ± 2 .8; P = .941).

A 2013 case-control study of 30 retired NFL players with 29 controls matched for age, estimated IQ, and education examined the relationship between a remote history of concussion and current symptoms of depression.⁸ Concussion history was self-reported by the retired players. Controls with a history of concussion were excluded from the study. The Beck Depression Inventory-II (BDI-II) was used to measure depression symptoms, with a score of 1 to 9 designating minimal depression and ≥ 10 mild-to-moderate depression. Retired players scored significantly higher on the BDI-II compared to the controls (8.8 vs 2.8; P = .001).

Editor’s takeaway

Concussions include cognitive compromise. An astute clinician’s concern for depression as a sequela makes sense. This evidence contributes to that conjecture. However, the authors of this Clinical Inquiry correctly outline the limitations, inconsistencies, and biases of the evidence. The exact relationship—degree and context—between concussion and depression remains vague.