Results of a large meta-analysis that included 18 studies and more than 9,000 patients showed a fourfold higher risk of developing depressive symptoms in those with PPCS versus those without PPCS.
“In this meta-analysis, experiencing PPCS was associated with a higher risk of experiencing depressive symptoms,” write the investigators, led by Maude Lambert, PhD, of the School of Psychology, University of Ottawa, and Bloorview Research Institute, Toronto.
“There are several important clinical and health policy implications of the findings. Most notably, the development of strategies for effective prevention and earlier intervention to optimize mental health recovery following a concussion should be supported,” they add.
The study was published online in JAMA Network Open.
‘Important minority’
An “important minority” of 15%-30% of those with concussions continue to experience symptoms for months, or even years, following the injury, the investigators note.
Symptoms vary but can include headaches, fatigue, dizziness, cognitive difficulties, and emotional changes, which can “significantly impact an individual’s everyday functioning.”
The association between PPCS and mental health outcomes “has emerged as an area of interest” over the past decade, with multiple studies pointing to bidirectional associations between depressive symptoms and PPCS, the researchers note. Individuals with PPCS are at significantly higher risk of experiencing depressive symptoms, and depressive symptoms, in turn, predict more prolonged postconcussion recovery, they add.
The authors conducted a previous scoping review that showed individuals with PPCS had “greater mental health difficulties than individuals who recovered from concussion or healthy controls.”
But “quantitative summaries evaluating the magnitude and nature of the association between PPCS and mental health outcomes were not conducted,” so they decided to conduct a follow-up meta-analysis to corroborate the hypothesis that PPCS may be associated with depressive symptoms.
The researchers also wanted to “investigate potential moderators of that association and determine whether the association between depressive symptoms and PPCS differed based on age, sex, mental illness, history of concussion, and time since the injury.”
This could have “significant public health implications” as it represents an “important step” toward understanding the association between PPCS and mental health, paving the way for the “development of optimal postconcussion intervention strategies, targeting effective prevention and earlier intervention to enhance recovery trajectories, improve mental health, and promote well-being following concussion.”
To be included in the meta-analysis, a study had to focus on participants who had experienced a concussion, diagnosed by a health care professional, or as classified by diagnostic measures, and who experienced greater than or equal to 1 concussion symptom lasting greater than 4 weeks.
There was no explicit upper limit on duration, and individuals of all ages were eligible.
Depressive symptoms were defined as “an outcome that must be measured by a validated and standardized measure of depression.”
Biopsychosocial model
Of 580 reports assessed for eligibility, 18 were included in the meta-analysis, incorporating a total of 9,101 participants, with a median (range) sample size of 154 (48-4,462) participants and a mean (SD) participant age of 33.7 (14.4) years.
The mean length of time since the concussion was 21.3 (18.7) weeks. Of the participants, a mean of 36.1% (11.1%) had a history of greater than or equal to 2 concussions.
Close to three-quarters of the studies (72%) used a cross-sectional design, with most studies conducted in North America, and the remaining conducted in Europe, China, and New Zealand.
The researchers found a “significant positive association” between PPCS and postinjury depressive symptoms (odds ratio, 4.87; 95% confidence interval, 3.01-7.90; P < .001), “representing a large effect size.”
Funnel plot and Egger test analyses “suggested the presence of a publication bias.” However, even after accounting for publication bias, the effect size “of large magnitude” remained, the authors report (OR, 4.56; 95% CI, 2.82-7.37; P < .001).
No significant moderators were identified, “likely due to the small number of studies included,” they speculate.
They note that the current study “does not allow inference about the causal directionality of the association” between PPCS and postinjury depressive symptoms, so the question remains: Do PPCS induce depressive symptoms, or do depressive symptoms induce PPCS?”
Despite this unanswered question, the findings still have important clinical and public health implications, highlighting “the need for a greater understanding of the mechanisms of development and etiology of depressive symptoms postconcussion” and emphasizing “the necessary emergence for timely and effective treatment interventions for depressive symptoms to optimize the long-term prognosis of concussion,” the authors note.
They add that several research teams “have aimed to gain more insight into the etiology and underlying mechanisms of development and course of mental health difficulties in individuals who experience a concussion” and have arrived at a biopsychosocial framework, in light of “the myriad of contributing physiological, biological, and psychosocial factors.”
They recommend the establishment of “specialized multidisciplinary or interdisciplinary concussion care programs should include health care professionals with strong clinical foundations and training in mental health conditions.”
Speedy multidisciplinary care
Commenting on the research, Charles Tator, MD, PhD, professor of neurosurgery, University of Toronto, Division of Neurosurgery, Toronto Western Hospital, said the researchers “performed a thorough systematic review” showing “emphatically that depression occurs in this population.”
Dr. Tator, the director of the Canadian Concussion Centre, who was not involved with the current study, continued: “Nowadays clinical discoveries are validated through a progression of case reports, single-center retrospective cohort studies like ours, referenced by [Dr.] Lambert et al., and then confirmatory systematic reviews, each adding important layers of evidence.”
“This evaluative process has now endorsed the importance of early treatment of mental health symptoms in patients with persisting symptoms, which can include depression, anxiety, and PTSD,” he said.
He recommended that treatment should start with family physicians and nurse practitioners “but may require escalation to psychologists and social workers and then to psychiatrists who are often more skilled in medication selection.”
He encouraged “speedy multidisciplinary care,” noting that the possibility of suicide is worrisome.
No source of study funding was listed. A study coauthor, Shannon Scratch, PhD, has reported receiving funds from the Holland Bloorview Kids Rehabilitation Hospital Foundation (via the Holland Family Professorship in Acquired Brain Injury) during the conduct of this study. No other disclosures were reported. Dr. Tator has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.