Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Figures & data

Table 1. Demographic data for the ME/CFS patients at initiation of treatment.

	Total	Men	Women
Entire cohort (%)	218	51 (23%)	167 (77%)
Follow-up data available (%)	201	47 (23%)	154 (77%)
Sex ratio (men = 1)		1	3.3
Age (mean, yrs)	48.4	38.1	49.6
Age (range, yrs)	19–86	20–73	19–86
Response to LDN (n, %/218)	161 (73.9%)	32 (62.7%)	129 (77.2%)

Table 2. Most common treatment responses to LDN therapy in ME/CFS (N = 218).

Response	Total		Men		Women
	n	%	n	%	n	%
Improved vigilance/alertness	112	51.4	25	49.0	87	52.1
Improved physical performance	52	23.9	13	25.5	39	23.4
Improved cognition	46	21.1	5	9.8	41	24.6
Pain relief	36	16.5	10	19.6	26	15.6
Less fever	33	15.1	6	11.8	27	16.2
Improvement in one of more another symptoms	53	24.3	11	21.6	41	24.6

Table 3. Prevalence of adverse symptoms during the initial phase of LDN treatment (N = 201).

	Total		Men		Women
	n	%	n	%	n	%
Insomnia	31	15.3	10	21.3	21	13.5
Nausea	31	15.3	8	17.0	27	17.4
Dizziness	14	6.9	0	0	14	9.0
Gastrointestinal symptoms	13	6.4	4	8.5	9	5.8
Headache	11	5.4	1	2.1	10	6.5
Sleepiness	10	5.0	2	4.3	8	5.2
Hot flashes/sweating	10	5.0	2	4.3	8	5.2
Anxiety/panic	8	4.0	1	2.1	7	4.5
Nightmares	7	3.5	3	6.4	4	2.6
Tachycardia	7	3.5	0	0	7	4.5
Depression	6	3.0	1	2.1	5	3.2
Paresthesias	6	3.0	1	2.1	5	3.2
Muscle and joint pain	5	2.5	1	2.1	4	2.6

Table 4. Adverse symptoms that occurred rarely (2% or less) during the initiation of LDN (N = 201). These symptoms are common in untreated ME/CFS population.

	n	%		n	%
Lethargy/Fatigue	4	2.0	Restlessness	2	1.0
Excessive thirst	4		Sensations in the head	2
Increased irritability	4		Chest pain	2
Dyspnea	4		Impaired cognition	2
Tremor	3	1.5	Palpitations	2
Increased frequency of infections	3		Lack of appetite	2
Heartburn	3
Urinary symptoms	3		Others: See Table 5	1	0.5

Table 5. Adverse symptoms that were reported only once (0.5%/N = 201). Connection with LDN therapy unsure.

Neurological symptoms	Loss of field of vision, muscle fasciculation, muscle tension in the back, worsening of migraine, feeling hungover, feeling drunk, ringing in the ears, restless legs
Autonomic symptoms	Low blood pressure, blood pressure instability, facial flushing, feeling wired, dry mouth, increased urination, edema in the ankles, increased sensitivity to electricity
Skin symptoms	Hair loss or loss of eyelashes, rash, itching, change in odor of sweat/skin
Endocrinologic	Aggravation of hypothyroidism
Psychiatric symptoms	Loss of volition, suicidal thoughts

Table 6. Nausea was the most common reason for discontinuing LDN. Altogether, 15 patients (7.5%) discontinued LDN due to adverse symptoms (N = 201).

	n	%
Nausea	5	2.5
Anxiety	2	1.0
Nightmares	1	0.5
Insomnia	1
Muscle and joint pain	1
Muscle fatigue	1
Dizziness	1
Sweating	1
Feeling feverish	1
Facial flushing	1
Total	15	7.5

Figure 1. The follow-up periods of individual patients who responded to LDN and continued with the treatment. The average follow-up period was 1.7 years (0.1–6.8 years). 91 patients (63%) were followed up for more than one year.

Figure 2. LDN alleviated the symptoms of ME/CFS in a minimum of 73.9% of the patients. Despite symptom alleviation, 1.8% discontinued with LDN because of adverse symptoms. 18.3% were non-responders. In a subset of them (5.5% of the entire cohort) the discontinuation was caused by adverse symptoms (Table 6). 7.8% of patients were lost to follow-up. These patients were included in the non-responder group.

Figure 3. The quantified treatment response in 201 patients on a scale of 0–6. Points (0–5) were scored for improved vigilance/alertness, improved physical performance, improved cognition, pain reduction, less fever. One additional point was scored if the patient experienced improvement in some (one or more) other ME/CFS symptoms of ME/CFS. Patients 1–40 (18.3%) were non-responders.

Figure 4. The frequency of adverse symptoms in 201 individual patients during the initiation of LDN (N = 201).