Low-Dose Dextromethorphan for the Treatment of Fibromyalgia Pain: Results from a Longitudinal, Single-Blind, Placebo-Controlled Pilot Trial

Figures & data

Figure 1 Participant flow chart.

Table 1 Individual and Group-Level Illness Characteristics, Comorbid Medical Conditions, and Medications Reported in the Sample

PID	Age	FM Duration (Years)	WPI (0–19)	SSS (0–12)	FM Severity (0–31)	Comorbid Conditions	Medications
001	56	12.0	11	6	17	Osteoarthritis	Ibuprofen PRN*, acetaminophen PRN*, naproxen PRN*
002	23	5.0	19	9	28	None	Phenazopyridine*
003	41	4.0	16	9	25	CFS, hypothyroidism (non-Hashimoto), sleep apnea, hypercholesterolemia, anxiety, depression	Acetaminophen PRN*, meloxicam PRN, sumatriptan PRN*, melatonin*, trazodone* diphenhydramine PRN*, ranitidine, famotidine, bismuth subsalicylate PRN*, cyclobenzaprine PRN*, Armor Thyroid, atorvastatin, rosuvastatin, amlodipine, sertraline, lorazepam PRN, iron
004	48	20.0	14	7	21	CFS, HTN, GERD, hypercholesterolemia, interstitial cystitis, depression, anxiety	Ranitidine, dexlansoprazole, fluoxetine, atorvastatin, amlodipine, carvedilol
005	46	6.2	15	8	23	Depression, anxiety	Tizanidine, topiramate, escitalopram, biotin, Vitamin D, iron, Vitamin B12 (injections)
006	48	10.0	14	5	19	Osteoarthritis, tendonitis	Ibuprofen PRN*, acetaminophen PRN*, naproxen PRN*, fenofibrate, aspirin, duloxetine, pseudoephedrine (cold), Vitamin D, Vitamin B12, turmeric, magnesium
007	34	19.0	12	12	24	CFS, idiopathic hypersomnia, sleep apnea, chronic migraines, hypothyroidism (non-Hashimoto), fatty liver disease (non-alcoholic), OCD, anxiety	Ibuprofen PRN*, acetaminophen PRN*, clonazepam*, omeprazole, fluoxetine, levothyroxine, Adderall, doxycycline (sinus infection), multivitamin, Vitamin D3, turmeric
008	51	4.0	16	12	28	Migraines, HTN, IBS, carpal tunnel syndrome, depression, anxiety	Ibuprofen PRN*, amitriptyline PRN*, tizanidine PRN*, melatonin PRN*, diphenhydramine PRN*, losartan, duloxetine, Vitamin B12, fish oil, calcium, iron
009	57	15.0	16	9	25	Osteoarthritis, sleep apnea, degenerative disk disease, hypercholesterolemia, pre-diabetes	Acetaminophen PRN*, naproxen PRN*, melatonin PRN*, meloxicam, aspirin, mirabegron, ketorolac injection, ceftriaxone injection, liraglutide, omeprazole, montelukast, cetirizine, vortioxetine, fenofibrate, fluticasone inhaler PRN, sulfamethoxazole/trimethoprim (UTI), multivitamin, calcium
010	61	21.2	13	8	21	Osteoporosis	Acetaminophen PRN*, meloxicam PRN*, gabapentin, duloxetine, diphenhydramine (acute allergic reaction), cortisone topical (acute allergic reaction), steroid injection (poison ivy exposure), alendronic acid, CBD oil
011	39	5.0	9	10	19	CFS, hypothyroidism (non-Hashimoto)	Acetaminophen PRN*, chlorpheniramine PRN*
012	46	1.5	17	7	24	None	Ibuprofen PRN*, Vitamin D
013	46	3.8	11	9	20	CFS, HTN, mitral valve prolapse, acoustic neuroma, migraines, trigeminal neuralgia, cervical disk herniation, hypothyroidism (non-Hashimoto), carpal tunnel syndrome, anxiety, depression	Diclofenac, duloxetine, gabapentin, Adderall XR, carbamazepine, lorazepam, pantoprazole
014	63	16.0	10	6	16	Osteoarthritis, chronic constipation, insomnia, hypercholesterolemia	Aspirin PRN*, tizanidine PRN*, zolpidem PRN*, pravastatin, ranitidine, calcium, magnesium
Average (SD)	47.07 (10.74)	10.19 (6.90)	13.79 (2.91)	8.36 (2.10)	22.14 (3.76)	–	–

Note: *Medication use was reported on daily questionnaires during the trial.

Abbreviations: ACR, American College of Rheumatology; CFS, chronic fatigue syndrome; FM, fibromyalgia; GERD, gastroesophageal reflux disease; HTN, hypertension; IBS, irritable bowel syndrome; OCD, obsessive-compulsive disorder; SD, standard deviation; SSS, Symptom Severity Scale; WPI, Widespread Pain Index.

Table 2 Individual and Group-Level Characteristics and Questionnaire Results from the Screening Visit

PID	BPI Severity (0–10)	BPI Interference (0–10)	HADS-A (0–21)	HADS-D (0–21)	HADS Total (0–42)	DAST-10 (0–10)	SETS Positive Expectations (1–7)	SETS Negative Expectations (1–7)
001	5.25	4.33	6	6	12	0	4.00	1.00
002	7.00	6.11	16	4	20	1	4.33	2.00
003	3.25	6.22	10	10	20	0	4.00	1.67
004	6.75	4.44	15	14	29	0	3.67	1.00
005	4.25	7.67	10	10	20	1	4.00	4.00
006	3.50	2.78	10	7	17	0	3.67	1.00
007	7.00	7.78	10	9	19	0	4.00	2.67
008	7.00	7.67	15	14	29	0	6.00	2.67
009	4.25	6.00	10	7	17	0	4.00	1.00
010	6.25	5.22	2	3	5	0	4.00	1.33
011	5.50	4.11	8	6	14	0	5.33	1.00
012	7.75	8.78	14	14	28	0	3.00	1.00
013	6.00	5.89	17	11	28	1	3.33	1.00
014	8.25	6.78	5	2	7	0	4.67	3.67
Group Average (SD)	5.86 (1.57)	5.98 (1.68)	10.57 (4.43)	8.36 (4.03)	18.93 (7.78)	0.21 (0.43)	4.14 (0.77)	1.79 (1.06)

Abbreviations: BPI, Brief Pain Inventory; HADS, Hospital Anxiety and Depression Scale; SETS, Stanford Expectations of Treatment Scales.

Table 3 Group Means and Standard Deviations on the Primary, Secondary, and Exploratory Treatment Outcomes (Raw Scores)

	Baseline	Placebo	DXM	End Baseline
Generalized Pain	55.30 (17.46)	45.55 (24.69)	41.09 (24.32)	44.90 (26.23)
Physical Activity	52.56 (17.87)	50.10 (19.70)	46.92 (19.79)	45.32 (22.07)
Highest Pain	62.26 (19.06)	50.94 (27.06)	45.26 (26.24)	49.05 (27.87)
Muscle Pain	55.30 (20.55)	44.12 (26.42)	40.11 (25.74)	42.31 (28.61)
Fatigue	67.52 (10.95)	51.69 (16.89)	45.92 (21.88)	50.56 (23.88)
Depression	26.67 (16.66)	21.40 (18.07)	20.95 (20.00)	24.05 (21.74

Note: Averages were calculated over the entire treatment period.

Abbreviation: GI, gastrointestinal.

Figure 2 Individual changes in generalized pain ratings between the placebo and DXM conditions. The bold dashed line represents the change from mean placebo and mean DXM scores across participants.

Table 4 GEE Model Estimates from Sensitivity Analyses Predicting Study Outcomes Over the Entire Treatment Period

Parameters	Estimate (b)	SE	Z	p
Generalized Pain
Intercept	9.009	3.323	2.71	0.007
Day	−0.251	0.087	−2.89	0.004
Condition (DXM)	−9.933	3.987	−2.49	0.013
Day*Condition	0.241	0.079	3.04	0.002
Physical Activity
Intercept	4.221	2.171	1.940	0.052
Day	−0.071	0.048	−1.47	0.142
Condition (DXM)	−3.732	3.131	−1.19	0.233
Day*Condition	0.045	0.061	0.75	0.456
Muscle Pain
Intercept	8.294	3.390	2.45	0.014
Day	−0.244	0.094	−2.59	0.010
Condition (DXM)	−6.738	4.789	−1.41	0.159
Day*Condition	0.208	0.094	2.21	0.027
Highest Pain
Intercept	9.768	2.996	3.26	0.001
Day	˗0.264	0.077	−3.41	<0.001
Condition (DXM)	−9.657	4.012	−2.41	0.016
Day*Condition	0.236	0.075	3.17	0.002
Fatigue
Intercept	8.019	4.216	1.90	0.057
Day	−0.177	0.104	−1.70	0.088
Condition (DXM)	−5.383	5.244	−1.03	0.305
Day*Condition	0.114	0.092	1.25	0.213
Depression
Intercept	2.937	1.651	1.78	0.075
Day	−0.101	0.052	−1.94	0.053
Condition (DXM)	−5.322	2.789	−1.91	0.056
Day*Condition	0.132	0.070	1.88	0.060

Abbreviation: SE, standard error.

Table 5 Adverse Event Occurrences During Placebo and DXM Treatment

Event	Placebo	DXM
Anxiety	–	002, 010
Bloating	004	004
Chest Tightness	–	002
Cold/Respiratory Infection	012	–
Constipation	–	002, 004
Depressed Mood	003	002
Diarrhea	–	002, 004
Ear Infection	011	–
Elevated Alk Phosphatase	–	004, 005
Elevated ALT	–	001, 004, 007
Elevated Chloride	–	005
Eye Redness	–	014
Fever	009	–
Gallbladder Dysfunction	–	005
Gastrointestinal Upset	002	002, 009
Hot Flashes	–	006, 010
Low Alk Phosphatase	012	–
Low ALT	–	014
Low AST	012	012
Muscle Weakness	004	–
Nausea	–	004, 013
Rash	010	–
Sore Throat	–	009
Vomiting	–	004, 013

Abbreviations: ALT, alanine aminotransferase; ESR, erythrocyte sedimentation rate; HCG, human chorionic gonadotropin; HS CRP, high-sensitivity C-reactive protein; TSH, thyroid-stimulating hormone.