UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders

Figures & data

Table 1. Displays and describes the patient-reported outcome measures (PROMs) measured at baseline, and at 1-, 3-, and 6-months follow-up.

PROM	Description	Patient Response	Scoring
HIT-6	The 6-item headache impact test (HIT-6) is a brief tool to assess the impact of headaches, including, pain severity, social functioning, role functioning, vitality, cognitive functioning, and psychological distress.	Patients respond with ‘never’ (=6), ‘rarely’ (=8), ‘sometimes’ (=10), ‘very often’ (=11), or ‘always’ (=13) to a set of questions.	Scores are added together to a total ranging from 36–78, with a higher score being associated with a greater headache burden. A > 2.5-point reduction of HIT-6 scores is associated with a minimal clinically significant change.
MIDAS	The migraine disability assessment (MIDAS) questionnaire is designed to determine the level of pain and disability caused by a headache disorder. Five questions are used to assess the impact of a patient’s headaches during the past 3 months.	Patients are required to quantify the number of days the headaches prevented their involvement of usual activities, the total number of days headaches occurred and state pain intensity level during attacks.	Scores are added together to a total MIDAS score with scores of 0–5, 6–10, 11–20, and 21+ corresponding to little, mild, moderate, and severe disability, respectively. A > 5.0-point reduction of HIT-6 scores is associated with a minimal clinically significant change.
EQ-5D-5L	The EQ-5D-5L is NICE’s preferred standardized assessment tool for measuring HRQoL. Respondents describe their health considering 5 domains: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression.	Each domain is scored with a 5-level scale of severity: ‘no problem’ (=1), ‘slight problem’ (=2), ‘moderate problem’ (=3), ‘severe problem’ (=4) to ‘unable to’ (=5).	These scores are combined into a 5-digit code corresponding to an overall health state. This health state is mapped into a single EQ-5D-5L index value specific for a UK population. An index value of 1 represents perfect HRQoL and an index value <0 is equivalent to a health state worse than death.
GAD-7	The GAD-7 is a 7-question screening tool designed to measure the severity of generalized anxiety disorder (GAD). It encompasses 7 indicative symptoms of GAD, including feelings of worry, irritability, impending doom, and inability to relax.	Patients respond with “not at all’ (=0), ‘several days’ (=1), ‘more than half the days’ (=2) and ‘nearly every day’ (=3) over the last 2 weeks.	Scores are added together generating a score ranging from 0–21 with ≥5, ≥10, and ≥15 signifying mild, moderate, and severe anxiety symptoms, respectively.
SQS	The single-item sleep quality scale (SQS) assesses the overall quality of sleep for most nights in the past 7 days.	‘0’ represents terrible sleep quality, whilst ‘10’ denotes excellent sleep quality. Respondents are prompted to consider all components of sleep quality including hours slept, sleep onset latency, and night-time waking.	Scored 0–10
PGIC-1 PGIC-2	The Patients’ Global Impression of Change (PGIC-1) scale assesses how the patient would describe the change in their clinical status since starting treatment. Patients are asked to consider activity limitations, symptoms, emotions, and overall quality of life. PGIC-2 is an additional question where respondents are asked to signify the degree of change since beginning care at the clinic.	This is rated on a scale of 1–7, 1 = ‘no change (or the condition has got worse)’ and 7 = ‘a great deal better and a considerable improvement that has made all the difference.’ 0 = ‘much better.’ 5 = ‘no change’ and 10 = ‘much worse.’	Scored 1–7 Scored 1–10

PROM: patient-reported outcome measure; HRQoL: Health-related quality of life; HIT-6: headache-impact test-6⁽⁵¹⁾; MIDAS: migraine disability assessment score⁽⁵²⁾; GAD-7: generalized anxiety disorder-7 questionnaire⁽⁵³⁾; NICE – National Institute for Health and Care Excellence; SQS: single-item sleep-quality scale⁽⁵⁵⁾; PGIC: patient’s global impression of change⁽⁵⁶⁾.

Table 2. Patient baseline demographic data (n = 97).

Demographic Detail	n (%) / mean ± SD
Age	37.9 ± 11.1
Sex
Female	42 (43.3)
Male	55 (56.7)
BMI	28.0 ± 7.0
Occupation
Clerical support workers	1 (1.0)
Craft and related trades	2 (2.1)
Elementary occupation	7 (7.2)
Managers	6 (6.2)
Plant and machine operator and assemblers	1 (1.0)
Professional	14 (14.4)
Service and sales worker	2 (2.1)
Technician and associate professional	8 (8.2)
Other occupation	8 (8.2)
Unemployed	23 (23.7)
Unreported	25 (25.8)

BMI: Body Mass Index kg/m²; SD: standard deviation

Table 3. Primary, secondary, and tertiary indication for patients included in the analysis (n = 97).

Indication for treatment	Primary n (%)	Secondary n (%)	Tertiary n (%)
Migraine	82 (84.5)	3 (3.1)	0 (0.0)
Tension-type headache	6 (6.2)	1 (1.0)	1 (1.0)
Cluster headache	9 (9.3)	0 (0.0)	0 (0.0)
Anxiety	0 (0.0)	16 (16.5)	4 (4.1)
Attention deficit hyperactivity disorder	0 (0.0)	1 (1.0)	0 (1.0)
Chronic pain	0 (0.0)	7 (7.2)	4 (4.1)
Depression	0 (0.0)	4 (4.1)	3 (3.1)
Insomnia	0 (0.0)	7 (7.2)	3 (3.1)
Obsessive compulsive disorder	0 (0.0)	1 (1.0)	0 (0.0)
Tourette’s syndrome	0 (0.0)	1 (1.0)	0 (0.0)
Post-traumatic stress disorder	0 (0.0)	1 (1.0)	0 (0.0)
Autistic spectrum disorder	0 (0.0)	0 (0.0)	1 (1.0)
Complex regional pain syndrome	0 (0.0)	0 (0.0)	1 (1.0)
Depression	0 (0.0)	0 (0.0)	3 (3.1)
Epilepsy (adult)	0 (0.0)	0 (0.0)	1 (1.0)
Fibromyalgia	0 (0.0)	0 (0.0)	1 (1.0)

Figure 1. A) HIT-6 and b) MIDAS scores at baseline and follow-up measures at 1-, 3-, and 6-months in patients with headache disorders prescribed cannabis-based medicinal products. *<0.050; **<0.010; ***<0.001; HIT-6: 6-item headache impact test; MIDAS: migraine disability assessment score.

Table 4. Paired baseline and follow-up scores for EQ-5D-5L measures at 1-, 3-, and 6-months in patients with headache disorders prescribed cannabis-based medicinal products.

	Month	n	Baseline	Follow-up	P-value	Sig.
EQ-5D-5L Index Value	1-month	79	0.7 (0.3–0.8)	0.8 (0.6–0.8)	<0.001	***
	3-months	62	0.7 (0.3–0.8)	0.7 (0.5–0.8)	0.016	*
	6-months	34	0.7 (0.5–0.8)	0.8 (0.7–0.9)	0.009	***
EQ-5D-5L Mobility	1-month	79	1.0 (1.0–2.0)	1.0 (1.0–2.0)	0.544	ns
	3-months	62	1.0 (1.0–3.0)	1.0 (1.0–3.0)	0.830	ns
	6-months	34	1.0 (1.0–3.0)	1.0 (1.0–2.0)	0.201	ns
EQ-5D-5L Self-Care	1-month	79	1.0 (1.0–2.0)	1.0 (1.0–2.0)	0.302	ns
	3-months	62	1.0 (1.0–2.0)	1.0 (1.0–2.0)	0.825	ns
	6-months	34	1.0 (1.0–2.0)	1.0 (1.0–1.3)	0.366	ns
EQ-5D-5L Usual Activity	1-month	79	2.0 (1.0–3.0)	2.0 (1.0–2.0)	0.013	*
	3-months	62	1.5 (1.0–3.0)	2.0 (1.0–2.3)	0.180	ns
	6-months	34	1.5 (1.0–3.0)	1.0 (1.0–3.0)	0.227	ns
EQ-5D-5L Pain and Discomfort	1-month	79	3.0 (2.0–4.0)	2.0 (2.0–3.0)	<0.001	***
	3-months	62	3.0 (2.0–4.0)	2.0 (2.0–3.0)	<0.001	***
	6-months	34	3.0 (2.0–4.0)	2.0 (1.8–3.0)	0.006	**
EQ-5D-5L Anxiety and Depression	1-month	79	2.0 (1.0–3.0)	2.0 (1.0–3.0)	<0.001	***
	3-months	62	2.0 (1.0–3.0)	2.0 (1.0–2.0)	0.089	ns
	6-months	34	1.0 (1.0–3.0)	2.0 (1.0–2.0)	0.983	ns

ns: no statistically significant difference; *<0.050; **<0.010; ***<0.001

Figure 2. a) GAD-7 and b) SQS scores at baseline and follow-up measures at 1-, 3-, and 6-months in patients with headache disorders prescribed cannabis-based medicinal products. ns: no statistically significant difference; *<0.050; **<0.010; ***<0.00. GAD-7: generalised anxiety disorder-7 questionnaire; SQS: single-item sleep quality scale

Table 5. Paired baseline and follow-up scores for HIT-6, MIDAS, GAD-7, SQS, and EQ-5D-5L measures at 1-, 3-, and 6-months in patients with headache disorders prescribed cannabis-based medicinal products.

	Month	n	Baseline	Follow-up	T test statistic	Z score	P-value	Sig.
HIT-6	1-month	75	66.0 (62.0–71.0)	62.0 (57.0–67.0)	2305.0	−5.9	<0.001	***
	3-months	60	66.5 (62.0–71.0)	59.5 (52.0–68.0)	1418.5	−5.4	<0.001	***
	6-months	33	66.0 (62.0–71.0)	59.0 (52.0–66.0)	459.0	−4.1	<0.001	***
MIDAS	1-month	75	44.0 (12.0–118.0)	26.0 (6.0–102.0)	1795.5	−3.5	<0.001	***
	3-months	60	47.5 (14.3–121.0)	20.0 (4.0–70.0)	1273.5	−3/6	<0.001	***
	6-months	33	46.0 (9.0–146.0)	21.0 (3.5–69.5)	373.0	−2.9	0.004	**
GAD-7	1-month	81	5.0 (2.0–10.5)	4.0 (1.0–7.0	1600.0	−3.8	p < 0.001	***
	3-months	63	5.0 (2.0–9.0)	4.0 (1.0–6.0)	1058.5	−3.4	p < 0.001	***
	6-months	35	4.0 (1.0–10.0)	4.0(2.0–8.0)	254.5	−1.2	p = 0.239	ns
SQS	1-month	78	4.0 (3.0–7.0)	7.0 (4.0–8.0)	1730.0	−5.0	p < 0.001	***
	3-months	61	4.0 (3.0–7.0)	7.0 (6.0–9.0)	1299.5	−5.2	p < 0.001	***
	6-months	33	4.0 (3.0–7.0)	6.0(4.0–8.0)	16.12	−3.1	p = 0.002	**
EQ-5D-5L	1-month	79	0.7 (0.3–0.8)	0.8 (0.6–0.8)	1896.0	−4.4	<0.001	***
	3-months	62	0.7 (0.3–0.8)	0.7 (0.5–0.8)	1168.0	−2.4	0.016	*
	6-months	34	0.7 (0.5–0.8)	0.8 (0.7–0.9)	381.5	−2.6	0.009	***

HIT-6: headache-impact test-6⁽⁵¹⁾; MIDAS: migraine disability assessment score⁽⁵²⁾; GAD-7: generalized anxiety disorder-7 questionnaire⁽⁵³⁾; SQS: single-item sleep-quality scale⁽⁵⁵⁾

ns: no statistically significant difference; *<0.050; **<0.010; ***<0.001

Table 6. Adverse Events reported by patients prescribed cannabis-based medicinal products for headache disorders (n = 97).

	Mild N	Moderate N	Severe N	Total N (%)
Constipation	2			2 (2.1)
Somnolence		5	1	6 (6.2)
Dysgeusia	1			1 (1.0)
Blurred vision	1		1	2 (2.1)
Dry mouth	10	1		11 (11.3)
Lethargy	3		1	4 (4.1)
Urinary tract infection		2		2 (2.1)
Fatigue	3	4	1	8 (8.2)
Delirium	4			4 (4.1)
Confusion	4			4 (4.1)
Nausea	2	4		6 (5.4)
Concentration impairment	7	1		8 (8.2)
Insomnia	2	3	2	7 (6.3)
Headache	1	6	4	11 (11.3)
Pharyngitis		2		2 (2.1)
Decreased weight	2			2 (2.1)
Dizziness	2	1		3 (3.1)
Vertigo	2			2 (2.1)
Ataxia	2			2 (2.1)
Dyspepsia	2	1		3 (2.7)
Cognitive disturbance	2	1	1	4 (4.1)
Amnesia	3			3 (3.1)
Abdominal pain upper	2			2 (2.1)
Respiratory infection		2		2 (2.1)
Rash		1		1 (1.0)
Anorexia	1	1		2 (2.1)
Muscular weakness	2	2		4 (4.1)
Spasticity		1		1 (0.9)
Vomiting	1	1		2 (2.1)
Fall	1			1 (1.0)
Bloating	1			1 (1.0)
Total %	63 (64.9)	39 (40.2)	11 (11.3)	113 (116.5)