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Medical Cannabis for Headache Pain: a Primer for Clinicians

Duarte, Robert A; Dahmer, Stephen; Sanguinetti, Shayna Y; Forde, Grace; Duarte, Diana P; Kobak, Lawrence F
PURPOSE OF REVIEW/OBJECTIVE:Public acceptance of Cannabis sativa L. (cannabis) as a therapeutic option grows despite lags in both research and clinician familiarity. Cannabis-whether as a medical, recreational, or illicit substance-is and has been commonly used by patients. With ongoing decriminalization efforts, decreased perception of harms, and increased use of cannabis in the treatment of symptoms and disease, it is critical for clinicians to understand the rationale for specific therapies and their medical and practical implications for patients. In view of the opioid crisis, overall patient dissatisfaction, and lack of adherence to current chronic pain and headache therapies, this review provides up-to-date knowledge on cannabis as a potential treatment option for headache pain. RECENT FINDINGS/RESULTS:Research into the use of cannabinoids for disease treatment have led to FDA-approved drugs for seizures, nausea, and vomiting caused by cancer chemotherapy; and for decreased appetite and weight loss in people with HIV/AIDS. For a wide variety of conditions and symptoms (including chronic pain), cannabis has gained increasing acceptance in society. The effects of cannabidiol (CBD) and tetrahydrocannabinol (THC) in pain pathways have been significantly elucidated. An increasing number of retrospective studies have shown a decrease in pain scores after administration of cannabinoids, as well as long-term benefits such as reduced opiate use. Yet, there is no FDA-approved cannabis product for headache or other chronic pain disorders. More is being done to determine who is likely to benefit from cannabis as well as to understand the long-term effects and limitations of the treatment. Cannabis can refer to a number of products derived from the plant Cannabis sativa L. Relatively well-tolerated, these products come in different configurations, types, and delivery forms. Specific formulations of the plant have been shown to be an effective treatment modality for chronic pain, including headache. It is important for clinicians to know which product is being discussed as well as the harms, benefits, contraindications, interactions, and unknowns in order to provide the best counsel for patients.
PMID: 34628531
ISSN: 1534-3081
CID: 5262882

Managing Chronic Headache Disorders

Forde, Grace; Duarte, Robert A; Rosen, Noah
Headaches are a very common disorder, more common than asthma and diabetes combined. Migraine is the most common headache disorder, but it remains underdiagnosed and therefore undertreated. The treatment of migraines is divided into acute and prophylaxis. Patients who are experiencing 8 or more headaches a month or those who experience disability with their headaches as determined by the Migraine Disability Assistance Score or MIDAS should be placed on prophylaxis.
PMID: 26614723
ISSN: 1557-9859
CID: 2040882

Practical management strategies for the chronic pain patient [Case Report]

Forde, Grace; Stanos, Steven
When presented with a chronic pain patient, a thorough diagnostic workup and clinical assessment are essential. A key component of this initial evaluation is to obtain the information necessary to identify the underlying cause of the pain. Although a definitive diagnosis is not always possible, pain is most effectively managed when the underlying cause is identified. Chronic pain is now viewed as a biopsychosocial phenomenon, in which biological, psychological, and social factors are at work. Although one or more chronic diseases may be responsible for at least some of the pain experienced by chronic pain patients, psychological factors also play a prominent role. According to several published reports, major depression occurs in up to 60% of chronic pain patients, and an adjustment disorder with anxious mood can be found in up to nearly a third. In addition, numerous studies have identified a high rate of substance abuse in those suffering from chronic pain, with lifetime prevalence rates ranging from 23% to 41%, according to one source. A pain history is another essential component of the initial workup. A thorough pain history includes questions on any previous therapies tried (including nonpharmacologic interventions) and the success rate of those therapies, an assessment of patient function and overall quality of life, and a review of any personal or family history of substance abuse. One of the complexities of pain diagnosis is the subjective nature of the condition. Simple validated measures, such as the 0 to 10 numerical scale, pictorial scales (eg, faces), and visual analog scales can assist in the assessment of pain intensity and the guidance of subsequent treatments. Of no less relevance in the initial workup of a patient with chronic pain is the establishment of a secure physician-patient relationship. Open and clear communication between these parties is a key component in the treatment process and will help guide the therapy more safely and efficaciously. Realistic expectations and exit strategies for each therapeutic intervention should also be discussed at the initial evaluation and again at the onset of treatment
PMID: 18667140
ISSN: 1533-7294
CID: 98989

Analysis of pooled data from two pivotal controlled trials on the efficacy of topiramate in the prevention of migraine

Freitag, Fred G; Forde, Grace; Neto, Walter; Wang, Daniel Z; Schmitt, Jennifer; Wu, Shu-Chen; Hulihan, Joseph
CONTEXT: A substantial proportion of the patient population with migraine headache should be considered for preventive treatment based on the frequency and disability associated with this disorder. Use of the anticonvulsant topiramate was previously examined in two large, double-blind, randomized, placebo-controlled clinical trials of a subset of patients who have 3 to 12 migraine episodes per month. OBJECTIVE: To better characterize the efficacy of topiramate for prevention of migraine, with or without aura, by pooling and analyzing data from the two large clinical trials. METHODS: The pooled intent-to-treat population included 937 patients receiving topiramate at one of three dosages (50 mg/d, 100 mg/d, 200 mg/d) or placebo. Outcome measures included change in mean monthly migraine frequency and categorical responder rate throughout the 26-week doubleblind phase. Results: At daily doses of 100 and 200 mg, topiramate was associated with significant reductions in mean monthly migraine frequency throughout the double-blind phase compared with placebo (P<.001). Significantly more patients treated with these topiramate doses exhibited high-percentage reductions in monthly migraine frequency (>/=50% [P<.001], >/=75% [P<.001], 100% [P=.049]) versus placebo. The most common adverse events included anorexia, cognitive deficits, diarrhea, fatigue, nausea, and paresthesia. Topiramate (100 mg/d, 200 mg/d) was associated with significant and sustained reductions in mean monthly migraine frequency beginning as early as 1 week into therapy. CONCLUSION: Pooled efficacy data from two large, similarly designed, placebo-controlled migraine-prevention trials demonstrated that a statistically significant proportion of patients using topiramate met or exceeded two main outcome guidelines recommended by the International Headache Society (>/=50% and >/=75% reduction in frequency of monthly attacks). Based on efficacy and tolerability, topiramate at a dosage of 100 mg per day (50 mg twice daily) should be the target dosage for most patients with migraine
PMID: 17682112
ISSN: 0098-6151
CID: 96077

Adjuvant analgesics for the treatment of neuropathic pain: evaluating efficacy and safety profiles

Forde, Grace
PMID: 17270113
ISSN: 1533-7294
CID: 73290

The impact of migraine on daily activities: effect of topiramate compared with placebo

Silberstein, Stephen D; Loder, Elizabeth; Forde, Grace; Papadopoulos, George; Fairclough, Diane; Greenberg, Steven
OBJECTIVE: Assess the impact of migraine preventive therapy on patient-reported routine daily activities using the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study Short Form-36 (SF-36) in patients with migraine who participated in a 26-week, randomized, double-blind, placebo-controlled trial of topiramate for migraine prevention. METHODS: Patients were required to have 3-12 migraines and < or = 15 headache days/month during the baseline phase. Patients who failed > 2 adequate regimens of migraine preventive therapy were excluded. MSQ and SF-36 data were collected at baseline, weeks 8, 16, and 26 from 469 patients receiving either topiramate 50, 100, or 200 mg/day or placebo. Patients entered a double-blind, 8-week titration period followed by an 18-week maintenance period. Two activity-related MSQ domains (Role Restrictive [RR] and Role Prevention [RP]) and two activity-related SF-36 domains (Role Physical [SF-36-RP] and Vitality [SF-36-VT]) were prospectively designated as the outcome measures. Changes in MSQ and SF-36 scores during the double-blind phase relative to prospective baseline scores were compared between topiramate- and placebo-treated groups. Specifically, a mixed-effect piecewise linear regression model was used to estimate average domain score over time, and areas under the domain-over-time curve (AUC) were compared using a 2-sided t-test, with multiplicity adjustment. RESULTS: In the intent-to-treat population (N = 469), topiramate (all doses) significantly improved mean MSQ-RR domain scores versus placebo (topiramate 50 mg/day, p = 0.035; topiramate 100 mg/day; p < 0.001; topiramate 200 mg/day, p = 0.001). Topiramate-associated improvements in mean MSQ-RP domain scores were significant versus placebo only for topiramate 100 mg/day (p = 0.045). SF-36-RP and SF-36-VT domain scores improved (not significant versus placebo) for topiramate 100 and 200 mg/day. Changes in these MSQ and SF-36 domain scores significantly correlated with changes in mean monthly migraine frequency. CONCLUSION: Improvements in patient-reported outcomes specific for migraine (measured by the MSQ) were significantly better for patients receiving topiramate than for those receiving placebo. Improvements in the prospectively selected MSQ and SF-36 domains were significantly correlated with the decrease in mean monthly migraine frequency observed with topiramate treatment
PMID: 16846536
ISSN: 0300-7995
CID: 96078

Cutaneous innervation density in the allodynic form of postherpetic neuralgia

Rowbotham MC; Yosipovitch G; Connolly MK; Finlay D; Forde G; Fields HL
The relationship between deafferentation, sensory function, and pain was explored in 18 subjects with chronic postherpetic neuralgia (PHN). Subjective thresholds for warmth, cooling, and heat pain were measured quantitatively in painful skin areas and compared with normal contralateral skin. The severity of allodynia was graded in the affected area. Two 3-mm punch biopsies were taken from the most painful skin area and one from unaffected contralateral mirror-image skin. Immunofluorescence with the axonal marker PGP 9.5 revealed a reduction in density of innervation of the epidermis, the dermal-epidermal junction, and the eccrine sweat glands in PHN skin. In painful PHN skin, the reduction in innervation density was positively correlated with the magnitude of the thermal sensory deficits. However, loss of cutaneous innervation was inversely correlated with allodynia, indicating that surviving cutaneous primary afferent nociceptors that are spontaneously active and/or sensitized contribute to PHN pain and allodynia
PMID: 8980021
ISSN: 0969-9961
CID: 21798