Alda, 2011¹¹³

6 months

Years since diagnosis: 12.9 vs. 11.2 vs.11.7

Fair

A. CBT (n=57): 10-12 week program; 10 weekly 90-minute group sessions of cognitive restructuring and training in cognitive and behavioral coping strategies.

B. Recommended pharmacological treatment (n=56): pregabalin (300-600 mg/day); duloxetine (60-120 mg/day) for patients with major depressive disorder.

C. Usual care (n=56): standard care offered by general practitioners at subjects’ health centers who received a guide for the treatment of FM in primary care.

A vs. B vs. C

Age: 46 vs. 47 years vs. 47 years

Females: 95% vs. 93% vs. 96%

Race NR

Baseline FIQ (mean, 0-100): 65.9 vs. 66.4 vs. 64.5

Baseline Pain VAS (mean, 0-100): 64.2 vs. 68.1 vs. 64.7

A vs. B

6 months:

FIQ: 48.8 vs. 52.8; difference −4.0 (95% CI −7.730 to −0.270)

Pain VAS: 40.7 vs. 40.5; difference 0.2 (95% CI −3.996 to 4.396)

A vs. C

6 months:

FIQ: 48.8 vs. 53.3, difference −4.5 (95% CI −7.91 to −1.09)

Pain VAS: 40.70 vs. 44.3, difference −3.6 (95% CI −7.617 to 0.417)

A vs. B

6 months:

HAM-D (0-50): 7.9 vs. 8.2; difference −0.3 (95% CI −1.226 to 0.626)

HAM-A (0-50): 7.3 vs. 7.4; difference −0.1 (95% CI −1.247 to 1.047)

A vs. C

6 months:

HAM-D: 7.9 vs. 8.6, difference −0.7 (95% CI −1.719 to 0.319)

HAM-A: 7.3 vs. 7.6, difference −0.3 (95% CI −1.361 to 0.761)

Ang, 2010¹¹⁴

1.5 months

Duration of fibromyalgia, years: 11.8 vs. 12.3

Poor

A. CBT (n=17): 6 weekly 30-40 minute sessions of telephone-delivered CBT (activity pacing, pleasant activity scheduling, relaxation, automatic thoughts and pain, cognitive restructuring, and stress management)

B. Usual care (n=15): customary care from subject’s treating physician

A vs. B

Age: 51 vs. 47 years

Female: 100% vs. 100%

White: 81% vs. 80%

Baseline FIQ total (mean, 0-100): 62.2 vs. 67.8

Baseline FIQ Physical Impairment (PI) (0-10): 5.6 vs. 5.4

Baseline FIQ Pain (0-10): 7.6 vs. 7.8

A vs. B

1.5 months:

Proportion of patients with clinically meaningful improvement from baseline FIQ total (14%): 33% vs. 15%, RR 2.2 (95% CI 0.5 to 9.3)

mean change from baseline:

FIQ PI: −0.6 vs. 0.5, adjusted p=0.13;

FIQ Pain: −0.6 (1.6) vs. −0.3 (1.7), adjusted p=0.60

A vs. B

1.5 months:

PHQ-8 (0-24): mean change from baseline −0.9 (5.2) vs. 0.0 (4.1), adjusted p=0.80; overall effect size=0.60

Baumueller 2017¹²⁵

3 months

Duration of symptoms: 12.4 vs. 16.4 years

Fair

[New trial]

A. Electromyogram-Biofeedback (n=18): 14 sessions over 8 weeks

B. Attention control (n=18): 2 encounters with a therapist over 8 weeks

A vs. B

Age: 55 vs. 56 years

Smoking: 6% vs. 22%

Baseline FIQ-total: 42.59 vs. 40.44

A vs. B

3 months

FIQ: 37.87 vs. 38.28, p=0.52

A vs. B

3 months

SF-36 Physical function: 51.64 vs. 50.9, p=0.35

SF-36: Role-physical: 15.62 vs. 20.83, p=0.57

SF-36 Bodily pain: 36.88 vs. 36.17, p=0.81

SF-36 General health: 43.50 vs. 44.44, p=0.44

SF-36 vitality: 28.63 vs. 38.80, p=0.59

SF-36 social functioning: 53.68 vs. 61.11, p=0.65

SF-36 Role-emotional: 35.42 vs. 59.26, p=0.83

SF-36 Mental health: 51.06 vs. 57.50, p=0.75

BDI: 16.91 vs. 12.30, p=0.31

SCL-90-R Global Severity Index: 66.11 vs. 63.22, p=0.27

Buckelew, 1998⁷⁸

3, 12, and 24 months

Duration of symptoms, years: 11.6 vs. 10.0 vs. 11.6

Poor

A. Electromyographic biofeedback and relaxation training (n=29): 1 session for 1.5-3 hours per week for 6 weeks and instructions to train 2 times independently per week; taught cognitive and muscular relaxation strategies; 6-week individual training was followed by 2-year group maintenance phase of 1-hour groups once per month.

B. Attention control (n=30): 1 session for 1.5-3 hours per week for 6 weeks; educational information on diagnosis and treatment of FM and general health topics information; followed by one hour groups once per month for 2 years.

C. Combination Exercise (n=30): 1 session for 1.5 hours per week for 6 weeks and instructions to train 2 times independently per week. Sessions consisted of active range of motion exercises, strengthening exercises, low to moderate intensity aerobic exercise, proper posture and body mechanics instruction, and instructions on the use of heat, cold, and massage. 6-week individual training was followed by 2-year group maintenance phase of 1-hour groups once per month.

A vs. B vs. C

Age: 44 vs. 44 vs. 46 years

Female: 97% vs. 90% vs. 93%

Race NR

Baseline AIMS physical activity subscale (median, 0-10): 6.0 vs. 6.0 vs. 4.0

Baseline pain VAS (median, 0-10): 5.8 vs. 5.9 vs. 6.3

A vs. B

3 months:

AIMS physical activity subscale, median (median change from baseline): 6.0 (0) vs. 6.0 (0), NS

Pain VAS, median (median change from baseline): 5.2 (−0.2) vs. 5.8 (−0.5), NS

24 months:

AIMS physical activity subscale, median (median change from baseline): 6.0 (0) vs. 6.0 (0), NS

Pain VAS, median (median change from baseline): 5.2 (−1.1) vs. 5.4 (−0.6), NS

A vs. C

3 months:

AIMS physical activity subscale, median (median change from baseline): 6.0 (0) vs. 4.0 (0), p≤0.05

Pain VAS, median (median change from baseline): 5.2 (−0.2) vs. 5.4 (−0.8), NS

24 months:

AIMS physical activity subscale, median (median change from baseline): 6.0 (0) vs. 4.0 (0), p≤0.05

Pain VAS, median (median change from baseline): 5.2 (−1.1) vs. 5.5 (−1.2), NS

A vs. B

3 months:

SCL-90-R Global Severity Index, median (median change from baseline): 65.0 (−2) vs. 65.0 (0), NS

CES-D, median (median change from baseline): 10.0 (−2) vs. 13.0 (3), NS

Sleep scale, median (median change from baseline): 7.0 (0) vs. 5.0 (0), NS

24 months:

SCL-90-R Global Severity Index, median (median change from baseline): 64.0 (−1) vs. 67.0 (−1), NS

CES-D, median (median change from baseline): 10.0 (−2) vs. 12.0 (−2), NS

Sleep scale, median (median change from baseline): 6.0 (−2) vs. 6.0 (0), NS

A vs. C

3 months:

SCL-90-R Global Severity Index, median (median change from baseline): 65.0 (−2) vs. 65.5 (−3), NS

CES-D, median (median change from baseline): 10.0 (−2) vs. 13.5 (−2.5), NS

Sleep scale, median (median change from baseline): 7.0 (0) vs. 8.0 (0), NS

24 months:

SCL-90-R Global Severity Index, median (median change from baseline): 64.0 (−1) vs. 65.5 (−2.5), NS

CES-D, median (median change from baseline): 10.0 (−2) vs. 11.5 (−3.5), NS

Sleep scale, median (median change from baseline): 6.0 (−2) vs. 7.5 (0), NS

Castel, 2012¹¹⁵

3 and 6 months

A vs. B

Pain duration, years: 13.6 vs. 11.6

Poor

A. CBT plus usual pharmacological care (n=34): CBT conducted in groups (except for one individual session); 14 weekly 2 hour sessions. CBT included education about FM and pain, autogenic training, cognitive restructuring, CBT for insomnia, assertiveness training, activity pacing, pleasant activity scheduling, goal setting, and relapse prevention.

B. Usual care (n=30): usual pharmacological care, including analgesics, antidepressants, anticonvulsants, and myorelaxants

A vs. B

Age: 50 vs. 49 years

Female: 94% vs. 100%

White: 100% vs. 100%

Baseline FIQ (scale NR): 62.7 vs. 66.1

Baseline pain NRS (0-10): 6.1 vs. 6.9

A vs. B

3 months:

Proportion of patients with MCSD (≥14% improvement from baseline):

FIQ: 55.9% vs. 20%; OR 5.1 (95% CI 1.7 to 15.6); RR 2.8 (95% CI 1.3 to 6.1)

Pain (≥30% improvement from baseline):: 14.6% vs. 10%; RR 1.5 (95% CI 0.4 to 5.7)

FIQ: 52.8 vs. 66.3; difference −13.5 (95% CI −15.5 to −11.5)

Pain NRS: 5.9 vs. 6.8; difference −0.9 (95% CI −1.1 to −0.7)

6 months:

Proportion of patients with MCSD:

FIQ: 58.8% vs. 20%; OR 5.7 (95% CI 1.9 to 17.8); RR 2.9 (95% CI 1.4 to 6.3)

Pain: 17.6% vs. 13.3%; RR 1.3 (95% CI 0.4 to 4.2)

FIQ: 50.5 vs. 68.5; difference −18.0 (95% CI −20.095 to −15.905)

Pain NRS: 5.7 vs. 6.8; difference −1.1 (95% CI −1.333 to −0.867)

A vs. B

3 months:

HADS (scale NR): 15.4 (1.3) vs. 22.3 (1.4); difference −6.9 (95% CI −7.685 to −6.115)

MOS Sleep quantity (scale NR): 6.9 (0.2) vs. 5.5 (0.3); difference 1.4 (95% CI 1.254 to 1.546), p <0.0001

MOS Sleep index problems (scale NR): 40.1 (1.6) vs. 28.8 (1.7); difference 11.3 (95% CI 10.340 to 12.260)

6 months:

HADS: 15.7 (1.3) vs. 23.7 (1.4); difference −8.0 (95% CI −8.785 to −7.215)

MOS Sleep quantity: 6.7 (0.2) vs. 5.6 (0.3); difference 1.1 (95% CI 0.954 to 1.25)

MOS Sleep index problems: 39.9 (1.5) vs. 28.0 (1.6); difference 11.9 (95% CI 10.998 to 12.802)

Falcão, 2008¹³⁰

3 months

Disease duration, years: 3.5 vs. 3.7

Fair

A. CBT plus Amitriptyline (n=30): 1 group CBT session per week for 10 weeks, consisting of progressive relaxation training with electromyographic biofeedback, cognitive restructuring, and stress management; also received amitriptyline as in control group

B. Amitriptyline only (control) (n=30): amitriptyline 12.5/mg per day during first week, then increase dose to 25 mg/day; those with intolerance or side effects to amitriptyline were given cyclobenzaprine 5 mg/day in the first week and then 10 mg/day. Routine medical visits once a week for 10 weeks

A vs. B

Age: 45 vs. 46 years

Female: 100% vs. 100%

Caucasian: 80% vs. 77%

Baseline FIQ (0-100): 64.9 vs. 69.6

Baseline pain VAS (0-10): 6.9 vs. 7.0

A vs. B

3 months:

FIQ: 38.7 vs. 42.8; difference −4.1 (95% CI −18.765 to 10.565)

Pain VAS: 4.4 vs. 5.1; difference −0.7 (95% CI −2.841 to 1.441)

A vs. B

3 months:

BDI (0-63): 10.6 vs. 15.6; difference −5.0 (95% CI −11.122 to 1.122)

STAI-State scale (20-80): 45.8 (2.5) vs. 46.8 (2.3); difference −1.0 (95% CI −2.351 to 0.351)

SF-36 Physical Capacity (0-100): 59.6 vs. 54.0; difference 5.6 (95% CI −11.905 to 23.105)

SF-36 Pain (0-100): 48.4 vs. 45.5; difference 2.9 (95% CI −10.783 to 16.583)

SF-36 Mental Health (0-100): 69.9 vs. 56.2; difference 13.7 (95% CI 0.070 to 27.330)

Jensen, 2012¹¹⁶

Wicksell, 2013¹¹⁹

3-4 months

Time since FM onset, years: 10.5 vs. 11.8

Fair

A. ACT (n=25): 12 weekly 90-minute group sessions: exposure to personally important situations and activities previously avoided due to pain and distress, training to distance self from pain and distress.

B. Waiting list control (n=18)

A vs. B

Age: 45 vs. 47 years

Female: 100% vs. 100%

Baseline FIQ (0-100): 49.3 vs. 48.7

Baseline PDI (scale NR): 40.0 vs. 39.0

Baseline pain VAS (0-100): 61 vs. 65.0

Baseline pain NRS (0-10): 4.2 vs. 4.3

A vs. B

3-4 months

FIQ: 37.4 vs. 45.7, Cohen’s d=0.66 (95% CI −0.06 to 1.37); difference −8.3 (95% CI −17.056 to 0.456)

PDI: 28.1 vs. 38.1, Cohen’s d=0.73 (95% CI −0.00 to 1.44); difference −10.0 (95% CI −19.740 to −0.260)

Pain VAS: means NR but group X time interaction p=0.26

Pain NRS: 3.9 vs. 4.8, Cohen’s d= 0.82 (95% CI 0.08 to 1.54); difference −0.90 (95% CI −1.674 to −0.126)

A vs. B

3-4 months

BDI (0-63): 10.7 vs. 16.4, Cohen’s d=0.64 (95% CI −0.08 to 1.35); difference −5.7 (95% CI −12.044 to 0.644)

STAI-State: 39.8 vs. 45.4; Cohen’s d=0.55 (95% CI −0.17 to 1.26); difference −5.6 (95% CI −12.751 to 1.551)

SF-36 Mental: 46.0 vs. 34.7, Cohen’s d=1.06 (95% CI 0.28 to 1.82); difference 11.3 (95% CI 3.761 to 18.839)

SF-36 Physical (0−100): 28.4 vs. 31.1, Cohen’s d=0.28 (95% CI −0.45 to 1.00); difference −2.7 (95% CI −9.401 to 4.001),

Karlsson, 2015¹²⁶

6 month (end of treatment)

Duration of pain: 10.7 vs. 12 years

Duration of FM diagnosis: 5.3 vs. 5 years

Fair

[New trial]

A. CBT stress management program (n=24): 20, 3 hour group sessions over 6 months

Median attendance rate: 93%

B. Waitlist (n=24)

A vs. B

Age: 48 vs. 49 years

Female: NR

Baseline MPI pain severity: 3.85 vs. 3.38

Baseline MPI pain interference: 4.04 vs. 3.37

Baseline MADRS-S: 17.38 vs. 13.04

A vs. B

6 months

MPI pain severity: 4.20 vs. 3.37

MPI pain interference: 4.07 vs. 3.45

MADRS-S: 13.09 vs. 16.45

A vs. B

6 months

MADRS-S: 13.09 vs. 16.45

Kayiran, 2010¹³¹

4 to 5 months

Duration of symptoms: 5 years

Poor

A. EEG Biofeedback (Neurofeedback) (n=20): 5 sessions based on sensorimotor rhythm training protocol per week for 4 weeks. Each session consisted of 10 sensorimotor rhythm training periods lasting for 3 minutes for a total of 30 minutes

B. Escitalopram (n=20): 10 mg/day for 8 weeks (control group)

A vs. B

Age: 32 vs. 32 years

Female: 100% vs. 100%

Baseline FIQ (mean, 0−100): 70 vs. 74*

Baseline pain VAS (mean, 0−10): 8.9 vs. 9.1

A vs. B

4-5 months:

FIQ: 19 vs. 48*, p=NR

Pain VAS: 2.6 vs. 5.3; difference −2.7 (95% CI −3.7 to −1.7)

A vs. B

4-5 months:

HAM-D (0-50): 6.3 vs. 13.4; difference −7.1 (95% CI −9.1 to −5.1)

BDI (0-63): 4.7 vs. 12.3; difference −7.6, 95% CI −9.7 to −5.5)

HAM-A (0-56): 7.1 vs. 15.2; difference −8.1 (95% CI −11.0 to −5.2)

BAI (0-63): 7.2 vs. 16.7; difference −9.5 (95% CI −13.9 to −5.1)

SF-36*:

Physical functioning (0-100): 77 vs. 65, p<0.05

Bodily pain: 70 vs. 45, p<0.05

Role-physical (0-100): 90 vs. 43, p<0.05

Role-emotional (0-100): 95 vs. 51, p<0.05

Social functioning (0-100): 76 vs. 65, p<0.05

General mental health (0-100): 74 vs. 59, p<0.05

General health (0-100): 72 vs. 28, p<0.05

Vitality (0-100): 70 vs. 50, p<0.05

Lami, 2017¹²¹

3 months

Duration of symptoms: Mean 8.5 to 11.6 years

Poor

[New trial]

A. Cognitive Behavioral Therapy for Pain (n=24): weekly, 90-minute group sessions for 9 weeks

B. Cognitive Behavioral Therapy for Pain and Insomnia (n=22): weekly, 90-minute group sessions for 9 weeks

C. Usual Care (n=26)

A vs. B vs. C

Age: 49 vs. 50 vs. 51 years

Female: 100% vs. 100% vs. 100%

Baseline FIQ (0-100): 65.5 vs. 62.0 vs. 55.6

Baseline pain VAS (0-10): 7.6 vs. 7.4 vs. 7.2; p<0.05

A vs. C

3 months

FIQ: 53.3 vs. 53.2, difference 0.1 (95% CI −8.9 to 9.1)

VAS: 7.2 vs. 7.2, difference 0.0 (95% CI −0.9 to 1.0)

B vs. C

3 months

FIQ: 56.5 vs. 53.2, difference 3.3 (95% CI −5.7 to 12.3)

VAS: 6.6 vs. 7.2, difference −0.6 (95% CI −1.5 to 0.3)

A vs. C

3 months

PSIQ Total Sleep Quality (0-21): 13.8 vs. 11.9, difference 1.91 (95% CI −0.6 to 4.5)

MFI (0-5): 4.4 vs. 4.0, difference 0.32 (95% CI −0.1 to 0.7)

SCL-90-R Depression (0-4): 2.1 vs. 1.5, difference 0.6 (95% CI 0.2 to 1.1)

SCL-90-R Anxiety (0-4): 1.6 vs. 1.2, difference 0.42 (95% CI −0.1 to 0.9)

PCS (0-52): 22.8 vs. 24.2, difference −1.4 (95% CI −8.7 to 6.0)

CPAQ (0-120): 53.5 vs. 57.5, difference −4.1 (95% CI −15.8 to 7.6)

B vs. C

3 months

PSIQ Total Sleep Quality: 13.6 vs. 11.9, difference 1.7 (95% CI −0.8 to 4.2)

MFI: 4.1 vs. 4.0, difference 0.0 (95% CI −0.4 to 0.4)

SCL-90-R Depression: 2.0 vs. 1.5, p<0.05

SCL-90-R Anxiety: 1.6 vs. 1.18, difference 0.44 (95% CI −0.05 to 0.9)

PCS: 24.1 vs. 24.2, difference −0.2 (95% CI −7.7 to 7.4)

CPAQ: 53.7 vs. 57.5, difference −3.9 (95% CI −15.1 to 7.4)

Larsson, 2015¹³⁵

13 to 18 months

Duration of symptoms: 10 years

Poor

A. Relaxation therapy (n=63): Two group sessions of 5-8 subjects per week for 15 weeks. The intervention was preceded by an individual meeting covering instructions and allowing for adjustments to the intervention. The sessions lasted 25 minutes and consisted of autogenic training guided by physiotherapist and were followed by stretching.

B. Resistance exercise (Strength) (n=67): Two group sessions of 5-7 subjects per week for 15 weeks. The intervention was preceded by an individual meeting going over instructions on the intervention, testing, and modifications of specific exercises. Sessions were based on a resistance exercise program aiming to improve muscle strength, focusing on large muscle groups in the lower extremity.

A vs. B

Age: 52 vs. 51

Female: 100% vs. 100%

Baseline FIQ (0-100): 61.1 vs. 60.5

Baseline pain VAS (0-100): 52.4 vs. 49.3

Baseline PDI (0-70): 35.0 vs. 35.3

A vs. B

13-18 months

FIQ: 55.4 vs. 57.1, (difference −1.7, 95% CI −9.3 to 5.9)

Pain VAS: 52.1 vs. 49.2, (difference 2.9, 95% CI −5.5 to 11.3)

PDI: 33.7 vs. 33.0, (difference 0.7, 95% CI −4.0 to 5.4)

A vs. B

13-18 months

SF-36 PCS (0-100): 32.0 vs. 32.2, (difference −0.2, 95% CI −3.8 to 3.4)

SF-36 MCS (0-100): 40.0 vs. 39.2, (difference 0.8, 95% CI −4.6 to 6.2)

Patient global impression of change (mean, 1-7): Values NR but difference was NS

Luciano, 2014/2017^122,123

6 months

Duration of Disease: Mean 11.4 to 14.1 years

Fair

[New trial]

A. ACT (n=51): Eight 2.5 hour group sessions. Additional daily 15-30 minute homework sessions.

-Received eight sessions: 43.1% (22/51)

-Received seven sessions: 31.4% (16/51)

-Received six sessions: 9.8% (8/51)

-Received three sessions: 2% (1/51)

-Received two sessions: 7.8% (4/51)

B. Pharmacological Treatment (n=52): Treatment with pregabalin (300–600 mg/d) was administered. In addition, patients who fulfilled the criteria for major depression also received duloxetine (60–120 mg/d).

C. Waitlist (n=53)

A vs. B vs. C

Age: 49 vs. 48 vs. 48

Female: 96.1% vs. 98.1% vs. 94.3%

Baseline FIQ (0-100): 68.2 vs. 69.9 vs. 65.9

Baseline pain VAS (0-100): 65.4 vs. 63.0 vs. 64.0

A vs. C

6 months

FIQ: 49.5 vs. 67.5, difference −18.0 (95% CI −21.4 to −14.5)

VAS: 49.6 vs. 64.4, difference −14.8 (95% CI −20.0 to −9.6)

A vs. B

6 months

FIQ: 49.49 (8.77) vs. 65.11 (8.87), difference −15.6 (95% CI −19.1 to −12.2)

VAS: 49.6 vs. 56.3, difference −6.7 (95% CI 11.0 to −2.3)

A vs. C

6 months

CPAQ (0-120): 58.6 vs. 39.5, difference 19.1 (95% CI 13.9 to 24.4)

PCS (0-52): 23.1 vs. 30.3, difference −7.2 (95% CI −10.5 to −3.9)

EQ5D (0-100): 63.3 vs. 51.2 (11.8, difference 12.2 (95% CI 7.9 to 16.5)

HADS-A (0-21): 8.7 vs.12.2, difference −3.4 (95% CI −4.7 to −2.1)

HADS-D (0-21): 5.8 vs. 9.3, difference −3.5 (95% CI −4.4 to −2.5)

Total Cost for Treatment (in 2014 Euro): 2,267.3 vs. 4,163.6, difference −1896.3 (95% CI −3018 to −775)

A vs. B

6 months

CPAQ: 58.6 vs. 42.5, difference 16.1 (95% CI 10.8 to 21.5)

PCS: 23.1 vs. 28.0, difference −4.9 (95% CI −7.9 to −1.8)

EQ5D: 63.3 vs. 53.8, difference 9.6 (95% CI 5.2 to 14.0)

HADS-A: 8.7 vs. 9.7, difference −1.0 (95% CI −1.8 to −0.06)

HADS-D: 5.8 vs. 7.5, difference −1.7 (95% CI −2.6 to −0.8)

Total Cost for Treatment (in 2014 Euro): 2,267.3 vs. 2,654.6, difference −387.3 (95% CI −1205 to 430)

Lumley, 2017¹²⁴

6 months

Duration of diagnosis: Mean 13.5 to 13.8 years

Fair

[New trial]

A. CBT (n=75): 8, 90-minute, weekly group sessions.

B. Emotion and Awareness Expression Therapy (n=79): 8, 90-minute, weekly group sessions.

C. Fibromyalgia Education (attention control) (n=76): 8, 90-minute, weekly group sessions.

All patients continued their usual care.

A vs. B. vs. C

Age: 48 vs. 49 vs. 50 years

Female: 91% vs. 92% vs. 99%

Baseline BPI (0-10): 5.4 vs. 5.3 vs. 5.5

Baseline WPI (1-12): 9.9 vs. 11.2 vs. 10.7

Baseline SF-12 Physical component score: 35.5 vs. vs. 35.2 vs. 34.9

6 months

A vs. C

BPI: 4.8 vs. 4.9, difference −0.12 (95% CI −0.7 to 0.5)

Proportion of patients reporting at least 50% pain reduction: 8.3% vs. 12%

Proportion of patients reporting much/very much pain improvement: 22.9% vs. 15.4%

WPI: 8.40 vs. 9.14, difference −0.74 (95% CI −2.2 to 0.7)

B vs. C

BPI: 4.4 vs. 4.9, difference −0.54 (95% CI −1.2 to 0.1)

Proportion of patients reporting at least 50% pain reduction: 22.5% vs. 12%, p=0.07

Proportion of patients reporting much/very much pain improvement: 34.8% vs.15.4%, p=0.015

6 months

A vs. C

FSS (0-31): 15.0 vs. 16.0, difference −1.1 (95% CI −3.1 to 0.9)

SF-12 Physical (0-100): 39.1 vs. 36.9, difference 2.2 (95% CI −0.9 to 5.3)

SWLS (0-35): 19.6 vs. 18.6, difference 1.1 (95% CI −1.4 to 3.6)

PSQI (0-21): 10.1 vs. 10.7, difference −0.61 (95% CI −2.0 to 0.8)

PANAS-positive score (10-50): 30.1 vs. 27.6, difference 2.5 (95% CI −0.2 to 5.3)

PANAS-negative score (10-50): 18.6 vs. 19.4, difference −0.8 (95% CI −3.2 to 1.7)

MASQ (0-190): 92.6 vs. 96.9, difference −4.3 (95% CI −10.5 to 1.9)

CES-D (0-60): 17.3 vs.18.5, difference −1.1 (95% CI −5.0 to 2.7)

GAD-7 (0-21): 5.8 vs. 7.1, difference −1.3 (95% CI −2.9 to 0.3)

PROMIS-SF-F (0-100): 58.4 vs. 59.0, difference −0.62 (95% CI −2.4 to 1.2)

Healthcare utilization: 3.4 vs. 4.8, difference −1.4 (95% CI −3.1 to 0.3)

B vs. C

WPI: 7.2 vs. 9.1, difference −1.9 (95% CI −3.4 to −0.4)

FSS: 13.2 vs. 16.0, difference −2.9 (95% CI −4.9 to −0.8)

SF−12 Physical: 39.4 vs. 36.9, difference 2.5 (95% CI −0.6 to 5.5)

SWLS: 18.9 vs. 18.6, difference 0.3 (95% CI −2.3 to 2.9)

PNAS−negative score: 20.0 vs. 19.4, difference 0.62 (−1.7 to 2.9)

PNAS−positive score: 28.5 vs. 27.6, difference 0.97 (95% CI −1.8 to 3.7)

MASQ: 94.5 vs. 96.9, difference −2.37 (95% CI −8.8 to 4.0)

CES−D: 19.3 vs. 18.5, difference 0.79 (95% CI −2.9 to 4.5)

GAD−7: 7.2 vs. 7.1, difference 0.12 (95% CI −1.4843 to 1.7243)

PROMIS−SF−F: 58.2 vs. 59.0, difference −0.84 (95% CI −2.9 to 1.2)

Healthcare utilization: 4.1 vs. 4.8, MD −0.70 (95% CI −2.6 to 1.2)

McCrae, 2019¹²⁷

6 months

Duration of FM diagnosis: 9.5 vs. 7.9 vs. 9.1 years

Fair

[New trial]

A. CBT for Insomnia (n=39): 8, 50-minute sessions over 8 weeks

B. CBT for Pain (n=37): 8, 50-minute sessions over 8 weeks

C. Waitlist (n=37)

A vs. B vs. C

Age: 54 vs. 52 vs. 52 years

% Female: 100% vs. 92% vs. 100%, p=0.04

Baseline McGill Pain: 25.85 vs. 29.95 vs. 28.53

Baseline morning pain: 53.49 vs. 54.04 vs. 54.72

Baseline evening pain: 47.26 vs. 54.26 vs. 54.18

Baseline pain disability index: 34.14 vs. 37.27 vs. 37.59

A vs. C

6 months

McGill Pain: 23.62 vs. 23.30

Morning VAS: 43.29 vs. 50.60

Evening VAS: 41.99 vs. 49.26

Pain Disability Index: 27.76 vs. 34.87

B vs. C

6 months

McGill Pain: 28.99 vs. 23.30

Morning VAS: 47.78 vs. 50.60

Evening VAS: 49.77 vs. 49.26

Pain Disability Index: 36.37 vs. 34.87

A vs. C

6 months

Sleep Quality Rating (1-5): 3.27 vs. 2.65

BDI (0-63): 8.22 vs. 15.01

State-Trait Anxiety Inventory (20-80): 38.07 vs. 43.87

B vs. C

6 months

Sleep Quality Rating (1-5): 3.14 vs. 2.65

BDI (0-63): 14.38 vs. 15.01

State-Trait Anxiety Inventory (20-80): 43.86 vs. 43.87

Redondo, 2004¹³⁶

6 and 12 months

Pain duration NR

Poor

A. CBT (n=21): 1, 2.5 hour session per week for 8 weeks. Sessions included information about chronic pain and FM, relaxation techniques, and pain coping strategies training.

B. Combination Exercise (n=19): 5, 45-minute sessions per week for 8 weeks. Each week included 1 session of aquatic exercises, 2 sessions of flexibility and endurance exercises, and 2 sessions of cardiovascular exercises.

All subjects: Offered ibuprofen or diclofenac, 25 mg of amitriptyline a day, and acetaminophen.

A vs. B

Age NR

Female: 100% vs. 100%

Baseline FIQ total (mean, 0-80): 52.0 vs. 52.0

Baseline FIQ pain (mean, 0-10): 7.3 vs. 6.8

A vs. B

6 months:

FIQ total: 47.4 vs. 48.0, (difference −0.6, 95% CI −12.6 to 11.4)

FIQ pain: 5.9 vs. 6.9, (difference −1.0, 95% CI −2.8 to 0.8)

12 months:

FIQ: 47.8 vs. 47.7; (difference 0.1, 95% CI −10.5 to 10.7)

FIQ pain: 6.3 vs. 6.6; (difference −0.3, 95% CI −2.0 to 1.3)

A vs. B

6 months:

FIQ depression (0-10): 5.2 vs. 5.3, (difference −0.1, 95% CI −2.6 to 2.4)

FIQ anxiety (0-10): 6.0 vs. 5.8, (difference 0.2, 95% CI −2.2 to 2.6)

BAI: 25.2 vs. 22.1, (difference 3.1, 95% CI −5.1 to 11.3)

BDI (0-63): 17.1 vs. 15.0, (difference 2.1, 95% CI −6.6 to 10.8)

SF-36 physical functioning (0-100): 52.2 vs. 43.9, (difference 8.3, 95% CI −6.4 to 23.0)

SF-36 physical role (0-100): 22.4 vs. 18.3, (difference 4.1, 95% CI −21.2 to 29.4)

SF-36 bodily pain (0-100): 31.4 vs. 32.9, (difference −1.5, 95% CI −16.1 to 13.1)

SF-36 social functioning (0-100): 66.4 vs. 66.9, (difference −0.5, 95% CI −21.6 to 20.6)

SF-36 emotional role (0-100): 68.4 vs. 66.0, (difference 2.4, 95% CI −28.2 to 33.0)

SF-36 mental health (0-100): 48.9 vs. 51.8, (difference −2.9, 95% CI −19.3 to 13.5)

12 months:

FIQ depression: 5.4 vs. 4.9; (difference 0.5, 95% CI −2.0 to 3.0)

FIQ anxiety: 6.0 vs. 5.8; (difference 0.2, 95% CI −2.1 to 2.5)

BAI: 20.0 vs. 20.0; (difference 0.0, 95% CI −7.4 to 7.4)

BDI: 13.0 vs. 13.6; (difference −0.6, 95% CI −7.9 to 6.7)

SF-36 physical functioning: 38.9 vs. 41.6; (difference −2.7, 95% CI −19.5 to 14.1)

SF-36 physical role: 26.1 vs. 31.0; (difference −4.9, 95% CI −27.9 to 18.1)

SF-36 bodily pain: 33.8 vs. 34.3; (difference −0.5, 95% CI −20.9 to 19.9)

SF-36 social functioning: 60.7 vs. 57.2; (difference 3.5, 95% CI −17.2 to 24.2)

SF-36 emotional role: 66.7 vs. 58.7; (difference 8.0, 95% CI −19.2 to 35.2)

SF-36 mental health: 56.5 vs. 53.8; (difference 2.7, 95% CI −19.1 to 24.5)

Thieme, 2006¹¹⁷

6 and 12 months

Duration of symptoms, years: 9.1 vs. 8.7

Poor

A. CBT (n=42): 2-hour group sessions weekly for 15 weeks. Sessions focused on changing patients’ thinking and problem-solving, stress and pain coping strategies, and relaxation exercises performed during and between sessions.

B. Attention control (n=40): 2-hour group sessions weekly for 15 weeks: general discussions about medical and psychosocial problems of fibromyalgia.

A vs. B

Age: 49 vs. 47 years

Female: 100% vs. 100%

Baseline FIQ physical impairment (mean, 0-10): 4.4 vs. 4.2

Baseline WHYMPI pain intensity (mean, 0-6): 4.2 vs. 3.8

A vs. B

6 months

FIQ physical impairment: 3.0 vs. 4.8; difference −1.8 (95% CI −2.899 to −0.701)

WHYMPI pain intensity: 3.7 vs. 4.1; difference −0.4 (95% CI −0.841 to 0.041)

12 months

FIQ physical impairment: 3.4 vs. 5.2; difference −1.8 (95% CI −2.855 to −0.745)

WHYMPI pain intensity: 3.2 vs. 4.1; difference −0.9 (95% CI −1.537 to −0.263)

A vs. B

6 months

WHYMPI affective distress: 2.6 vs. 4.0; difference −1.4 (95% CI −1.952 to −0.848)

12 months

WHYMPI affective distress: 2.6 vs. 4.2; difference −1.6 (95% CI −2.172 to −1.028)

Van Santen, 2002⁹⁷

Post 6-month intervention

Duration of symptoms, years: 10.1 vs. 15.4 vs. 15.4

Poor

A. Electromyographic biofeedback (n=56): Progressive muscle relaxation and frontalis EMG biofeedback; 30-minute individual sessions 2 times per week for 8 weeks; subjects encouraged to practice at home twice daily for the 8 weeks then for 16 more weeks. Subjects randomized to education aimed at compliance with biofeedback training (6 90-minute sessions over 24 weeks).

B. Usual care (n=29): General physicians informed not to prescribe or encourage aerobic exercises and relaxation. Intervention duration: 6 months

C. Combination Exercise (n=58): 60-minute group sessions of twice a week for 24 weeks; aerobic exercises, postural strengthening, general flexibility and balance exercises, and isometric muscle strengthening; subjects encouraged to attend third, unsupervised, 60-minute session and to use sauna or swimming pool after sessions.

A vs. B

Age: 44 vs. 43 vs. 46 years

Female: 100% vs. 100% vs. 100%

Race NR

Baseline SIP Physical score (0-100): 11.4 vs. 9.8 vs.11.3

Baseline SIP Total score (0-100): 14.0 vs. 11.4 vs. 14.4

Baseline AIMS (0-10): 3.1 vs. 5.4 vs. 1.9

Baseline pain VAS (0-100): 59.1 vs. 62.4 vs. 66.8

A vs. B

6 months:

SIP physical score, mean change: −1.6 (95% CI −3.4 to 0.2) vs. −0.6 (95% CI −2.9 to 1.7)

SIP total score, mean change: −2.3 (95% CI −4.3 to −0.3) vs. −1.4 (95% CI −3.4 to 0.6)

AIMS, mean change: 0.4 (95% CI −0.1 to 0.9) vs. 0.8 (95% CI −1.8 to −0.2)

SIP total score, mean change: −2.3 (95% CI −4.3 to −0.3) vs. −1.4 (95% CI −3.4 to 0.6)

Pain VAS, mean change: −0.6 (95% CI −6.5 to 5.3) vs. 1.3 (95% CI −4.5 to 7.1)

A vs. C

6 months:

SIP physical score, mean change: −1.6 (95% CI −3.4 to 0.2) vs. −1.7 (95% CI −3.7 to 0.3), NS

SIP total score, mean change: −2.3 (95% CI −4.3 to −0.3) vs. −1.9 (95% CI −3.9 to 0.1)

AIMS, mean change: 0.4 (95% CI −0.1 to 0.9) vs. 0.1 (95% CI −0.6 to 0.8)

Pain VAS, mean change: −0.6 (95% CI −6.5 to 5.3) vs. −5.5 (95% CI −10.9 to −0.1), NS

A vs. B

6 months:

SIP psychosocial score (0-100), mean change: −3.7 (95% CI −4.9 to −2.5) vs. −3.5 (95% CI −7.0 to 0.0)

Patient global assessment of well-being, mean change: 0.3 (95% CI 0.0 to 0.6) vs. 0.5 (95% CI 0.2 to 0.8)

A vs. C

6 months:

SIP psychosocial score, mean change: −3.7 (95% CI −4.9 to −2.5) vs. −3.2 (95% CI −6.2 to 0.2)

Patient global assessment of well-being, mean change: 0.3 (95% CI 0.0 to 0.6) vs. 0.5 (95% CI 0.2 to 0.8)

Verkaik, 2014¹¹⁸

1.5 months

Duration of symptoms, NR

Poor

A. Guided imagery (n=33): Two 1.5 hour group sessions of 6-12 subjects. The first sessions consisted of group discussion, the theoretical background of guided imagery, and instructions to practice at least one exercise daily for 4 weeks. Each exercise was a CD and contained relaxation techniques, music, positive imagery, and pain management techniques. The second group session took place after the 4 weeks and consisted of a group discussion.

B. Attention control (n=37): Two 1.5 hour group sessions of 6-12 subjects held 4 weeks apart. Group sessions were a group discussion and did not contain any information or training on guided imagery.

A vs. B

Age: 47 vs. 48

Female: 100% vs. 97%

Baseline FIQ (0-100): 53.7 vs. 56.4

Baseline pain VAS (0-10): 5.9 vs. 5.8

A vs. B

1.5 months

FIQ: 54.2 vs. 53.0, difference 1.2, 95% CI −0.2 to 2.6)

Pain VAS: NR

Wigers, 1996⁹⁸

48 months

Fibromyalgia duration

A vs. B vs. C

Mean: 11 vs. 9 years

Poor

A. Stress management (n=20): 90 minute group sessions of 10 patients done 2 times a week for 6 weeks followed by 1 session per week for the next 8 weeks. Sessions consisted of equal portions of presentations stress mechanisms and strategies for improving quality of life, group discussions on patients’ experiences of stress and coping with pain, and relaxation training aimed at helping cope with stress and pain.

B. Usual care (n=20): Subjects continued treatments they had been using at baseline.

C. Aerobic exercise (n=20): 45 minute group sessions of 10 patients done 3 times a week for 14 weeks. The exercise program involved the whole body and aimed to minimize eccentric muscle strain. Sessions consisted of training to music (further details not given) and aerobic games.

A vs. B

Age: 44 vs. 46 vs. 43 years

Female: 90% vs. 95% vs. 90%

Baseline pain VAS (0-100): 72 vs. 65 vs. 72

A vs. B

48 months

Pain VAS: 70 vs. 69, (difference 1, 95% CI −12.6 to 14.6)

A vs. C

48 months

Pain VAS: 70 vs. 68, (difference 2, 95% CI −11.6 to 15.6)

A vs. B

48 months

Depression VAS (0-100): 40 vs. 30, (difference 10, 95% CI −8.9 to 28.9)

Global subjective improvement: 47% (6/13) vs. 12% (2/16), (RR 3.7, 95% CI 0.9 to 15.3)

A vs. C

48 months

Depression VAS: 40 vs. 32, (difference 8, 95% CI −11.9 to 27.9)

Global subjective improvement: 47% (6/13) vs. 75% (11/15), (RR 0.6, 95% CI 0.3 to 1.2)

Williams, 2002¹²⁰

12 months

Fibromyalgia duration, 8.6 years

Poor

A. Group CBT plus Usual Care (n=76): 6 1-hour group sessions over 4-week period: progressive muscle relaxation, imagery, activity pacing, pleasant activity scheduling, communication skills and assertiveness training, cognitive restructuring, stress management and problem-solving.

B. Usual Care (n=69): Standard pharmacological management (typically low-dose tricyclic antidepressant medication, analgesics, and/or antidepressants) plus suggestions to engage in aerobic fitness.

A + B

Age, mean, years: 47.7

Females: 90%

Race: White non-Hispanic 88%, black non-Hispanic 9%, Hispanic 2%, Asian American 1%

Baseline MPQ-Sensory (scale NR): 14.8

Baseline MPQ-Affective pain score (scale NR): 4.6

A vs. B

12 months

Mean (SD): NR

Proportion of subjects who improved more than 12 points from baseline on MPQ-Sensory scale: 3.9% vs. 7.2%; RR 0.54 (95% CI 0.14 to 2.2)

A vs. B

12 months

Mean (SD) NR

Proportion of subjects who improved more than 6.5 points from baseline on SF-36 PCS Score: 25% vs. 11.6%, OR 2.9; RR 2.2 (95% CI 0.98 to 4.99)

Proportion of subjects who improved more than 5 points from baseline on MPQ-Affective scale: 9.2% vs. 8.7%, RR 1.1 (95% CI 0.37 to 3.0)