Collaborative Care for Chronic Pain After Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Chronic pain after traumatic brain injury (TBI) is prevalent and associated with poor outcomes. By providing multidisciplinary care through expert consultation, a collaborative care (CC) treatment approach may reduce pain interference. Objective: To compare CC with usual care (UC) in decreasing pain interference. Design, Setting, and Participants: This randomized clinical trial was conducted from July 2018 through April 2021 at 2 hospital-based academic rehabilitation medicine clinics in Seattle, Washington. Participants included adults with mild-to-severe TBI (at least 6 months before enrollment) and chronic pain. Data analysis was performed from March 30, 2022, to August 30, 2023. Intervention: The CC intervention (called TBI Care) included up to 12 in-person or telephone visits over 16 weeks with a care manager (CM) who provided person-centered cognitive behavioral treatment. The CM met weekly with members of the expert team to review participants and discuss recommendations to optimize treatment. Main Outcomes and Measures: The primary outcome was pain interference on the Brief Pain Inventory at treatment conclusion (4 months after randomization). Secondary outcomes included pain interference at 8 months; pain severity; symptoms of depression, anxiety, and sleep disturbance; pain-related emergency department visits; community participation; and participant satisfaction. Linear mixed-effects regression was used for analysis. Results: A total of 1379 individuals were screened for eligibility, and 158 were randomized (79 to CC and 79 to UC). The participants were mostly women (92 participants [58%]) with a mean (SD) age of 46.8 (13.2) years and a mean (SD) of 15.3 (3.0) years of education. TBI occurred a mean (SD) of 4.0 (5.9) years (median [IQR], 1.9 [0.8-4.5] years) before enrollment. All TBI severities were included, and of 149 participants for whom TBI severity was known, the majority (97 participants [65%]) had mild TBI. In the CC group, 71 participants (90%) completed at least 11 sessions, and, at 4 months, this group had significantly lower pain interference scores compared with the UC group (mean [SD], 3.46 [2.17] vs 5.03 [2.28]). This difference was maintained at 8 months after randomization, with mean (SD) TBI care pain interference scores of 3.61 (2.22) for CC vs 4.68 (2.51) for UC. At 4 months, there was significantly lower pain severity in the CC group vs UC group (mean [SD] score, 3.63 [1.95] vs 4.90 [1.96]), as well as symptoms of depression (mean [SD] score, 8.07 [5.34] vs 11.31 [6.37]) and anxiety (mean [SD], 6.20 [5.17] vs 9.58 [6.00]). Satisfaction with pain treatment (mean [SD] score, 2.99 [1.23] vs 2.52 [1.25]), clinical care (mean [SD] score, 3.28 [1.00] vs 2.84 [1.26]), and overall health care (mean [SD] score, 3.25 [0.88] vs 2.82 [1.00]) were significantly higher in the CC group vs the UC group; global impression of change was significantly lower in the CC group vs the UC group (mean [SD] score, 2.74 [1.02] vs 3.47 [1.26]) (lower scores denote a better impression of change). Conclusions and Relevance: In this randomized clinical trial of CC compared with UC for patients with TBI, CC was effective at reducing pain interference and was sustained at 8-month follow-up. Further research is needed to examine the implementation and cost-effectiveness of CC for TBI in other health care settings. Trial Registration: ClinicalTrials.gov Identifier: NCT03523923.

Pharmacovigilance: reporting requirements throughout a product's lifecycle.

Comprehensive methods for evaluating safety are needed to objectively assess the full risk profile of a medication. The confidence of the prescribing provider in the safety and effectiveness of pharmaceuticals is extremely important. Pharmacovigilance is a key component of drug safety regulatory processes and is paramount for ensuring the safety profile of medications used to treat patients. All participants in the healthcare system, including healthcare providers and consumers, should understand and meaningfully engage in the pharmacovigilance process; healthcare providers should integrate pharmacovigilance into everyday practice, inviting feedback from patients. This narrative review aims to give an overview of the main topics underlying pharmacovigilance and drug safety in pharmaceutical research phase after the authorization of a drug in the United States. The US Food and Drug Administration guidance and post-approval regulatory actions are considered from an industry perspective. Plain language summary: Regulatory processes that ensure the safety of drugs is monitored Government agencies regulate the safe use of medicinal products. By determining and enforcing pharmacovigilance, the monitoring of drugs for potential risks, they safeguard the welfare of consumers of medicines. Comprehensive, documented methods for evaluating the safety of a drug during its development and its subsequent use allow identification of any risks associated with the drug's use throughout its lifetime. The comprehensive identification of safety issues associated with a drug is improved when all parties involved in the development and use of drugs participate in the pharmacovigilance process. For example, clinicians should regularly ask their patients if they are experiencing any issues with their treatment, and patients should be encouraged to report problems they encounter with a particular medication to their healthcare provider. This narrative review provides an overview of the main topics underlying pharmacovigilance and drug safety after approval of a drug in the United States. Guidelines and actions from the US Food and Drug Administration are considered from an industry perspective.

Timing and durability of response to erenumab in patients with chronic migraine.

BACKGROUND: Erenumab is a human anti-calcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. We sought to further assess the temporal patterns of response to erenumab in patients with chronic migraine (CM), specifically the onset and sustainability of monthly migraine day (MMD) response. METHODS: This is a post hoc analysis of a 12-week, randomized, double-blind, placebo-controlled study of erenumab for migraine prevention in patients with CM (≥15 headache days/month, including ≥8 migraine days/month). Onset and sustainability were assessed according to MMD reduction from baseline, with the following response categories: responders (≥50% reduction), partial responders (≥30% and <50%), or nonresponders (<30%). RESULTS: Among the erenumab 140 mg group (n = 187), 54.0% (101/187) achieved a response at any month during the study with a median time to onset of monthly response of 1 month. This improvement was maintained in most patients with continued treatment. An initial response was achieved at Month 1 by 28.3% (53/187) of patients; 69.8% (37/53) of whom maintained a response at Months 2 and 3. Although many patients responded early, some patients required longer treatment to achieve a response; 79.4% (27/34) of initial partial responders and 21.0% (21/100) of initial nonresponders subsequently achieved a response. Similar findings were observed for the erenumab 70mg group (n = 188). CONCLUSION: A majority of erenumab-treated patients with CM who achieved an initial response at Month 1 sustained this benefit. Many patients responded later with continued treatment. Our data support recommendations to assess outcomes after ≥3 months of preventive treatment with erenumab in CM.

A narrative review of the importance of pharmacokinetics and drug-drug interactions of preventive therapies in migraine management.

OBJECTIVE: To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug-drug interactions (DDIs) with the use of these therapies in migraine management. BACKGROUND: Preventive treatments for migraine are recommended for a large proportion of patients with frequent migraine attacks. These patients often exhibit a number of comorbidities, which may lead to the introduction of multiple concomitant therapies. Potential DDIs must be considered when using polytherapy to avoid increased risk of adverse events (AEs) or inadequate treatment of comorbid conditions. METHODS: A literature search was performed to identify pharmacokinetic properties and potential DDIs of beta-blockers, antiepileptic drugs, antidepressants, calcium channel blockers, gepants, and monoclonal antibody therapies targeting the calcitonin gene-related peptide pathway with medications that may be used for comorbid conditions. RESULTS: Most DDIs occur through alterations in cytochrome P450 isoenzyme activity and may be complicated by genetic polymorphism for metabolic enzymes. Additionally, drug metabolism may be altered by grapefruit juice ingestion and smoking. The use of migraine preventive therapies may exacerbate symptoms of comorbid conditions or increase the risk of AEs associated with comorbid conditions as a result of DDIs. CONCLUSIONS: DDIs are important to consider in patients with migraine who use multiple medications. The development of migraine-specific evidence-based preventive treatments allows for tailored clinical management that reduces the risk of DDIs and associated AEs in patients with comorbidities.

A Framework for Estimating the Eligible Patient Population for New Migraine Acute Therapies in the United States.

INTRODUCTION: Migraine is associated with considerable disability for patients not adequately managed with current standards of care. New acute therapies may offer relief for this population of patients; however, population size and associated potential costs of new therapies are unclear. In this study, a conceptual framework was developed to estimate anticipated use of new acute therapies. METHODS: Targeted literature review (TLR) was conducted to identify factors affecting access to migraine-specific acute therapies, and characteristics of individuals who would be eligible for new acute therapies. Findings from the TLR were combined to create a framework for estimating the size of the eligible patient population. This framework was used to calculate two estimates of the eligible patient population by applying parameters (i) identified in the TLR and (ii) from a recent budget-impact analysis (BIA). RESULTS: The primary factors affecting access to migraine-specific acute therapies identified in the TLR were consulting a healthcare professional for headache, receiving a migraine diagnosis, and receiving a prescription for migraine-specific treatment. Characteristics of individuals likely to use new acute therapies reflected in the TLR were contraindication to triptans, or failure to respond to/tolerate at least two oral triptans. Application of the framework suggested that 15-25% of individuals with migraine would be eligible for new acute therapies. CONCLUSION: A limited number of patients currently use migraine-specific acute therapies. Among such patients, a significant proportion do not have adequate symptom control. Accordingly, a minority of individuals with migraine may be expected to use new acute therapies. The framework developed in this study is intended to facilitate estimating the eligible patient population in assessments of costs of new acute therapies. Such assessments should also consider recommendations that patients have access to multiple types of acute therapies, which may yield savings from reduced medication-overuse headache (MOH), progression to chronic migraine, and urgent-care costs.

On the authorship and publication dates of the nomina emTheraphosa/em and Theraphosidae (Araneae: Mygalomorphae).

The family Theraphosidae is the most speciose in the infraorder Mygalomorphae Pocock, 1892 with over one thousand described species (World Spider Catalog 2021). The taxonomy of the group has been subjected to considerable attention in modern times, with a focus on delineation based predominantly on genital organ and stridulatory organ morphology which has shown promise, both alongside molecular methods (where possible) and as a stand-alone line of evidence, in stabilising the group (e.g. Hamilton et al. 2016; Fabiano-da-Silva et al. 2020; see also Sherwood 2020). The predominant reference to the family is as Theraphosidae Thorell, 1870 with almost as many references to Theraphosidae Thorell, 1869. This non-congruence of dates is because Tord Tamerlan Teodor Thorell (1830-1901) had his important work On European Spiders published in two parts during its publication by the Royal Society of Upsala in its journal Nova Acta Regiae Societatis Scientiarum Upsaliensis. The first half (pages 1-108 and the supplement I-XIII) was published in 1869 whereas pages 109-242 (despite being dated on the cover page as 1869) were published in 1870 (see Roewer 1942; Bonnet 1945; World Spider Catalog 2021). In the second part, the secretary of the society notes: "L'auteur avait proposé comme titre du présent mémoire: Remarks on Synonyms of European Spiders, preceded by some observations on Zoological Nomenclature and a Review of the European Genera of Spiders; mais, la partie, insérée dans le Tome VII, étant seule présentée à la Société des Sciences le 13 Fevr. 1869, il a été nécessaii'e d'y conformer le titre." [= The author proposed as the title of this memoir: Remarks on Synonyms of European Spiders, preceded by some observations on Zoological Nomenclature and a Review of the European Genera of Spiders; but, the part, inserted in Volume VII, being the only one presented to the Société des Sciences on 13 Feb. 1869, it was necessary to conform the title to it.].

Taxonomy of the genus Cyrtopholis Simon, 1892 (Araneae, Mygalomorphae, Theraphosidae): Cuban species described by Pelegrín Franganillo Balboa.

Cyrtopholis Simon 1892 is a spider genus from the Caribbean islands characterized by the presence of stridulatory setae on trochanter of palps and legs I. Franganillo Balboa described eight species of Cyrtopholis Simon 1892 from Cuba between 1926-1936. The type-material is deposited in the Instituto de Ecología y Sistematica do Ministerio de Ciencias, Tecnologia e Meio Ambiente, La Habana, Cuba. Four species are redescribed here: Cyrtopholis plumosa Franganillo, 1931, Cyrtopholis major Franganillo, 1926, Cyrtopholis unispina Franganillo, 1926 and Cyrtopholis gibbosa Franganillo, 1936. Cyrtopholis ischnoculoformis Franganillo, 1926 is based on a juvenile specimen without stridulatory setae, and it is therefore considered here as species inquirenda. The type-material of two other species were not located: Cyrtopholis anacanta Franganillo, 1935 and Cyrtopholis obsoleta (Franganillo, 1935), and are considered to be lost. These two species are here considered as species inquirenda, since the original descriptions do not permit identification. Cyrtopholis respina Franganillo 1935 is considered a nomen dubium, due to the lack of a formal description and a doubtful citation.

Clinical Perspectives on Headache After Traumatic Brain Injury.

BACKGROUND: Headache after traumatic brain injury (TBI) is frequent and persistent over the first year after injury. Providers may need to focus on different symptom presentations depending on their patient's TBI severity. OBJECTIVE: We evaluated headache symptoms in patients with moderate-to-severe TBI compared to patients with mild TBI and examined our data from two perspectives: (1) from providers who treat individuals after TBI and manage multiple postinjury symptoms including headache, and (2) from headache specialists who see individuals after TBI to manage headache. DESIGN: Prospective enrollment of individuals after TBI with telephone follow-up at 1-year postinjury. SETTING: Enrollment from hospital and then community followup. PARTICIPANTS: Three hundred forty-six individuals with moderate-to-severe TBI were enrolled during acute inpatient rehabilitation across seven TBI Model System Centers. One hundred eighty-nine individuals with mild TBI were enrolled within 1 week of injury at a single center. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Headache frequency, headache type, pain intensity, Headache Impact Test-6 (HIT-6), and depressive symptoms measured 1 year after injury. RESULTS: Headache prevalence is high in both TBI groups. TBI providers are more likely to evaluate and treat headache from individuals sustaining a mild TBI versus moderate-to-severe TBI. Patients with mild TBI are most likely to report tension-type headache followed by migraine-type headache. The migraine-type headache has higher impact (HIT-6) and greater pain intensity. Headache specialists may encounter patients with moderate-to-severe TBI who report more frequent headache and higher average pain scores compared to patients with mild TBI. The severity of TBI was unrelated to depressive symptoms 1 year after injury, but patients with headache were significantly more likely to have higher scores. CONCLUSIONS: TBI providers versus headache specialists should be aware of differences in patient symptom presentation to their respective clinics. Ongoing assessment of headache and depression over time is important following TBI of any severity.

Use of Amitriptyline in the Treatment of Headache After Traumatic Brain Injury: Lessons Learned From a Clinical Trial.

OBJECTIVES: The primary outcome of this study was to assess the efficacy and safety of preventive treatment with amitriptyline on headache frequency and severity after mild traumatic brain injury (mTBI). BACKGROUND: Despite the fact that headache is the most common and persistent physical symptom after TBI, there has been little research on the longitudinal course or pharmacologic treatment of this disorder. Of those who have headache after injury, about 60% continue to complain of headache at 3 months post injury, with higher levels of disability than those without headache. There have been no prospective, randomized, controlled trials of a pharmacologic agent for headache after TBI. Additionally, a brain-injured population may be more susceptible to side effects of medication. DESIGN: This is a single-center phase II trial of amitriptyline to prevent persistent headache after an mTBI. Medication dose was gradually increased from 10 to 50 mg daily. RESULTS: Fifty participants were enrolled and 33 who completed the 90-day assessment were included in the final analysis. In order to detect a possible cognitive impact of the study drug, 24 participants were randomly assigned to start amitriptyline immediately after study enrollment and 26 were assigned to start 30 days after enrollment. Forty-nine percent (18/37) of those assigned to take medication took none throughout the study period, with less compliance in younger participants with mean ages of 32.7 in those who did not take any medication, 33.4 who were less than 80% compliant, and 42.3 who were compliant (P = .013). Compliance in keeping a daily headache diary was low, with 29/50 participants (58%) meeting daily entry completion, and only 10 participants maintaining 100% diary completion. No differences were found between those who started medication immediately vs at day 30 in headache frequency or severity. CONCLUSIONS: While headache is the most common symptom following mTBI, current evidence does not support a specific treatment. No differences were noted in headache frequency compared to our prior study. However, the current sample had significantly lower headache severity (15% vs 36% with pain rating of 6 or above, P = .015) compared to our prior study. Our current study was not able to determine whether there is any benefit for the use of amitriptyline as a headache preventive because of difficulty with study recruitment and compliance. The challenges with recruitment and retention in the mTBI population were instructive, and future research in this area will need to identify strategies to improve recruitment, diary compliance, and medication adherence in this population.

Migraine and Other Headache Disorders: ACOG Clinical Updates In Women's Health Care Primary and Preventive Care Review Summary Volume XVIII, Number 4.

Migraine is a common headache disorder for which women are likely to seek care. This primary headache disorder, which often may be debilitating, has a higher prevalence in women than in men that is likely related to times of hormonal changes throughout the reproductive life cycle, such as menarche, pregnancy, postpartum period, lactation, perimenopause, and menopause, as well as to external hormonal changes associated with the use of oral contraceptives and hormone therapy. The obstetrician-gynecologist is well positioned to recognize and treat migraine and to recognize a potential relationship between estrogen fluctuation and migraine exacerbation. Migraine frequency is likely to decrease during pregnancy, but migraine often recurs during breastfeeding. Because headache does occur during these reproductive events, a careful evaluation and possible medication change may be necessary. Women also have unique risks for secondary headache during pregnancy, particularly pregnant women with a history of migraine. Therefore, a large portion of this monograph is devoted to evaluation, management, and drug safety in pregnant or breastfeeding women.

Telephone-delivered cognitive behavioral therapy for veterans with chronic pain following traumatic brain injury: Rationale and study protocol for a randomized controlled trial study.

BACKGROUND AND OBJECTIVES: Chronic pain is a highly prevalent and potentially disabling condition in Veterans who have had a traumatic brain injury (TBI) and access to non-pharmacological pain treatments such as cognitive behavioral therapy is limited and variable. The purpose of this randomized controlled trial (RCT) is to evaluate the efficacy of a telephone-delivered cognitive behavioral therapy (T-CBT) for pain in Veterans with a history of TBI. METHODS: Veterans with a history of TBI and chronic pain of at least six months duration (N = 160) will be randomized to either T-CBT or a telephone-delivered pain psychoeducational active control condition (T-Ed). The eight-week T-CBT intervention builds on other efficacious CBT interventions for chronic pain in the general population but is novel in that it is conducted via telephone and adapted for Veterans with a history of TBI. Outcome variables will be collected pre, mid-, and post-treatment, and 6 months following randomization (follow-up). PROJECTED OUTCOMES: In addition to evaluating the effects of the interventions on pain intensity (primary outcome), this study will determine their effects on pain interference, sleep, depression, and life satisfaction. We will also examine potential moderators of treatment outcomes such as cognition, PTSD, and alcohol and drug use. This non-pharmacologic one-on-one therapeutic intervention has the potential to reduce pain and pain-related dysfunction, improve access to care, and reduce barriers associated with geography, finances, and stigma, without the negative effects on physical and cognitive performance and potential for addiction as seen with some pharmacologic treatments for pain. This trial is registered at ClinicalTrials.gov, protocol NCT01768650.

Basic Considerations for the Use of Monoclonal Antibodies in Migraine.

BACKGROUND: Migraine impacts more than 36 million people in the United States and 1 billion people worldwide. Despite the increasing availability of acute and preventive therapies, there is still tremendous unmet need. Potential treatments in development include monoclonal antibodies (mAbs). Appropriate use of these "biologic" treatments will necessitate an understanding of the aspects that distinguish them from traditional medications. AIM: Many drug classes are prescribed for migraine treatment, but all have limitations. Recently, calcitonin gene-related peptide (CGRP) activity has shown a significant promise as a target for preventive therapy. In this review, we provide an overview of the potential role of CGRP mAbs in migraine, with a focus on their design, pharmacokinetics, safety, and immunogenicity. CONCLUSIONS: The CGRP mAbs are an innovative new therapy for migraine and address the need for effective and tolerable preventive options. MAbs, including those that target CGRP or its receptor, bind to a target with high specificity and affinity and lead to few off-target adverse effects, although mechanism-based adverse reactions may occur. Unlike other therapeutic antibodies used to treat neurologic disease, CGRP mAbs do not have a target within the immune system and have been designed to avoid altering the immune system. The safety and efficacy of mAbs against CGRP or its receptors are being investigated in clinical development programs, and the first of these therapies has received regulatory approval in the United States.

Posttraumatic Headache: Classification by Symptom-Based Clinical Profiles.

There are currently no accepted therapies for posttraumatic headache (PTH). In order to meet the urgent need for effective therapies for PTH, we must continue to address fundamental gaps in our understanding of the clinical course and impact of PTH. Here we examine the existing schema used to characterize the clinical characteristics of PTH, including the International Classification of Headache Disorders (ICHD). There remain unresolved questions about whether to classify patients based on the extent of brain injury or on clinical symptom profiles. There also remain problematic issues of definition such as continuous headache, and chronic daily headache with features of "embedded" migraine-type within these headaches, which will need to be studied further. We make the case that a symptom-based classification is needed to begin an examination of these unresolved questions, and to establish clinically relevant endpoints for research and clinical trials for effective therapies.

Sport-Related Headache.

Headache occurring in a sports setting may be primary or secondary headache. Headache is the primary symptom reported after concussion. Cumulative incidence and prevalence of posttraumatic headache (PTH) are higher following mild traumatic brain injury (TBI) compared with moderate to severe TBI. Frequency is higher in those with more severe PTH. Migraine or probable migraine is the most common headache type after any severity TBI using primary headache disorder criteria. Management is empiric. Expert opinion recommends treating PTH according to clinical characteristics of primary headache. The most important factor in this approach is the recognition of the severity of headache.

Six new species of silk-lined burrow spider genus Stenoterommata Holmberg, 1881 (Araneae, Nemesiidae) from southern Brazil.

A new diagnosis for the genus Stenoterommata Holmberg, 1881 is presented and six new species are described from Santa Catarina state, southern Brazil: S. pavesii sp. nov. and S. leticiae sp. nov. from Blumenau and Balneário Camboriú; S. sevegnaniae sp. nov. from Blumenau; S. gugai sp. nov., S. peri sp. nov. and S. pescador sp. nov. from Santa Catarina Island, Florianópolis. New records of S. palmar Goloboff, 1995 from southern Brazil are provided. Information on the natural history and habitat are included for all the species. In addition, Hermacha iricolor Mello-Leitão, 1923, described from Blumenau, is transferred to Rachias Simon, 1892.

Natural History of Headache Five Years after Traumatic Brain Injury.

Headache is one of the most frequently reported symptoms following traumatic brain injury (TBI). Little is known about how these headaches change over time. We describe the natural history of headache in individuals with moderate to severe TBI over 5 years after injury. A total of 316 patients were prospectively enrolled and followed at 3, 6, 12, and 60 months after injury. Individuals were 72% male, 73% white, and 55% injured in motor vehicle crashes, with an average age of 42. Pre-injury headache was reported in 17% of individuals. New or worse headache prevalence remained consistent with at least 33% at all time points. Incidence was >17% at all time points with first report of new or worse headache in 20% of participants at 60 months. Disability related to headache was high, with average headache pain (on 0-10 scale) ranging from 5.5 at baseline to 5.7 at 60 months post-injury, and reports of substantial impact on daily life across all time points. More than half of classifiable headaches matched the profile of migraine or probable migraine. Headache is a substantial problem after TBI. Results suggest that ongoing assessment and treatment of headache after TBI is needed, as this symptom may be a problem up to 5 years post-injury.

The Pharmacology of Indomethacin.

BACKGROUND: Over 50 years ago, indomethacin emerged as an extremely potent non-steroidal anti-inflammatory drug (NSAID) during a massive effort to find effective anti-inflammatory and analgesic medications. The 1960s saw acetic acid derivatives developed into indomethacin, diclofenac, and sulindac, and propionic derivatives into ibuprofen, naproxen, and ketoprofen. Indomethacin was likely the most potent of these compounds and one of the earliest to enter clinical trials. It is not surprising that indomethacin was among the first of the NSAID medications to be used in treatment of migraine and for headaches that eventually became known as "indomethacin-responsive" headache disorders. Potential pharmacokinetic and bio-mechanistic differences between indomethacin and other NSAIDs are of great clinical and research interest to explain this observation. METHODS/RESULTS: The present article summarizes pharmacologic properties of indomethacin, including pharmacokinetics with particular attention to its distribution into the central nervous system, adverse effects, drug interactions, and mechanisms of action. Data are emphasized where differences in biomechanisms are found between indomethacin and other NSAIDs. The use of indomethacin in pregnant and lactating women is reviewed. CONCLUSIONS: NSAIDs easily enter the brain, but their high protein binding limits absolute amount of entry. All work similarly as either nonselective or selective cyclooxygenase inhibitors, but indomethacin may have more potent vasoconstrictive activity and unique direct neuronal or nitric oxide-dependent inhibitory pathway activity.

Comorbidity of Headache and Depression After Mild Traumatic Brain Injury.

OBJECTIVE: To examine headache and depression over time in individuals who sustained mild traumatic brain injury (mTBI). Prevalence of headache and depression early after mTBI and at 1 year postinjury as well as the relationship between the two are evaluated. BACKGROUND: Headache is the most common physical symptom and depression is among the most common psychiatric diagnosis after traumatic brain injury regardless of severity. Headache and depression have been found to be two independent factors related to poor outcome after mTBI, yet there appears to be a paucity of research exploring the comorbidity of these two conditions after injury. METHOD/DESIGN: Longitudinal survey design over 1 year of 212 participants with mTBI who were admitted to a Level 1 trauma center for observation or other system injuries. Depression was based on a score ≥10 on the Patient Health Questionnaire-9. Headache was based on participant report of new or worse-than-preinjury headache since hospitalization (baseline) or within the previous 3 months at 1 year postinjury. RESULTS: The prevalence of headache and depression at baseline was 64% (135/212) and 15% (31/212), respectively. The prevalence of headache and depression at 1 year was 68% (127/187) and 27% (50/187), respectively. The co-occurrence of headache and depression increased from 11% (23/212) at baseline to 25% (46/187) at 1 year. At 1 year, the risk ratio of individuals who had headache to be depressed was 5.43 (95% CI 2.05-14.40) compared to those without headache (P < .001). The corresponding risk ratio at baseline was 1.64 (95% CI .77-3.49; P = .23). CONCLUSIONS: While prevalence of headache is consistently high over the first year after injury, rate of depression increased over the first year for those who were followed. Given the high rate of comorbidity, those with headache may develop depression over time. Evaluation for possible depression in those with headache after mTBI should be conducted to address both conditions over the year following injury.

Posttraumatic Headache: Clinical Characterization and Management.

Headache is the most common symptom after traumatic brain injury (TBI). TBI has become a global health concern with an estimated 2.5 million reported TBIs per year in the USA alone. Recent longitudinal studies of posttraumatic headache (PTH) show a high cumulative incidence of 71 % after moderate or severe TBI and an even higher cumulative incidence of 91 % after mild TBI (mTBI) at 1 year after injury. Prevalence remains high at over 44 % throughout the year after moderate or severe TBI and over 54 % after mTBI. A prior history of headache is associated with a higher risk for PTH, whereas older age appears to be protective. Gender does not appear to be a risk factor for PTH. Most PTH has clinical diagnostic criteria meeting that of migraine or probable migraine when primary headache disorder classification criteria are used, followed by tension-type headache. There are no evidence-based treatment guidelines for PTH management; however, expert opinion has suggested treating the PTH using primary headache disorder treatment recommendations according to its type.