• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Effects of Bedtime Very Low Dose Cyclobenzaprine on Sleep in FM patients (2011 double-blind study)

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
http://www.jrheum.org/content/38/12/2653.long
(2011)
Effects of Bedtime Very Low Dose Cyclobenzaprine on Symptoms and Sleep Physiology in Patients with Fibromyalgia Syndrome: A Double-blind Randomized Placebo-controlled Study



Objective. To determine the effects of bedtime very low dose (VLD) cyclobenzaprine (CBP) on symptoms and sleep physiology of patients with fibromyalgia (FM), unrefreshing sleep, and the α-nonREM sleep electroencephalographic (EEG) anomaly at screening.

Methods. Of 37 patients with FM in the screened population, 36 were randomized and treated in this 8-week, double-blind, placebo-controlled, dose-escalating study of VLD CBP 1–4 mg at bedtime. We evaluated changes in subjective symptoms including pain, tenderness, fatigue, mood [Hospital Anxiety and Depression Scale (HAD)], and objective EEG sleep physiology (at screening, baseline, and Weeks 2, 4, and 8).

Results. In the VLD CBP-treated group (n = 18) over 8 weeks, musculoskeletal pain and fatigue decreased, tenderness improved; total HAD score and the HAD depression subscore decreased; patient-rated and clinician-rated fatigue improved. In the placebo-treated group (n = 18), none of these outcome measures changed significantly. Compared to placebo at 8 weeks, VLD CBP significantly improved pain, tenderness, and the HAD Depression subscore. Analysis of cyclic alternating pattern (CAP) sleep EEG revealed that significantly more subjects in the VLD CBP group than the placebo group had increased nights of restorative sleep in which CAPA2+A3/CAPA1+A2+A3 = CAPA2+A3(Norm) ≤ 33%. For VLD CBP-treated subjects, the increase in nights with CAPA2+A3(Norm) ≤ 33% was correlated to improvements in fatigue, total HAD score, and HAD depression score.

Conclusion. Bedtime VLD CBP treatment improved core FM symptoms. Nights with CAPA2+A3(Norm) ≤ 33% may provide a biomarker for assessing treatment effects on nonrestorative sleep and associated fatigue and mood symptoms in persons with FM.


I've been taking flexeril since it was first introduced in the 1980's. I take it now 10mg at a time as needed for muscle spasms, but I will ask my GP if I could try taking it as a sleep aid every night at a lower dose, and still take the larger dose as needed for muscle spasms.
 
Last edited:
Messages
3,263
Isn't the low number of participants not so great?

GG
Yea, it would be nice to see this replicated in a larger group. But then they'd probably have to drop some of their sleep measures, would be difficult to do with huge numbers of people.

It was also not a registered trial, and so not stated what the primary outcome measures were. Having pre-defined primary outcomes measures helps to limit the number of chances you have to find a significant effect somewhere. Because the authors measured 7 outcome variables, they had 7 chances to get something significant, which is probably too high. (same problem for the sleep outcomes; there were a lot of measures examined, and not all were significant).

Still, to look at it the other way, using a small group underpowers your study, so you're less likely to find significant effects. If this study were replicated with a larger group, it might be really impressive (look at how many people the PACE authors had to include to get anywhere near a statistically reliable effect - that's because the effects of GET and CBT are so minute, you need a lot of power to find them). The main reason for needing a larger group is to check your patients' responses are truly representative of the group you're studying, and not some quirk of the particualr peoe you chose for the various treatment conditions.
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
Isn't the low number of participants not so great?

GG
The size of a study can be small and yet have statistically significant results (p <0.05) if the differences between the control group and the treated group are large enough. If you look at the 7 outcome measures, all of the differences between the control group and the treated group are significant (p<0.05). Also, they compared the baseline measurements vs. the 8-week measurements for the treated group and results were statistically significant.

Bedtime musculoskeletal pain and fatigue
For subjects who received VLD CBP, the mean musculoskeletal pain score changed from 2.3 at baseline to 1.7 at Week 8, which was a decrease (or improvement) of 0.6 (26.1%; p = 0.010). In contrast, placebo treatment did not result in statistically significant changes in musculoskeletal pain, which remained at an average score of 2.1 at baseline and at Week 8 (0.0%; p = 1.000). The mean change from baseline of the VLD CBP and placebo groups at Week 8 differed significantly and revealed that VLD CBP treatment significantly improved musculoskeletal pain (p = 0.044.
For subjects who received VLD CBP, the mean fatigue score changed from 5.0 at baseline to 4.3 at Week 8, which was a decrease (or improvement) of 0.7 (14.0%; p = 0.039).

Tenderness
For subjects who received VLD CBP, the dolorimetry score changed from 14.3 kg/cm2 at baseline to 18.6 kg/cm2 at Week 8, which was an increase (or improvement) of 4.3 kg/cm2 (30.1%; p = 0.006)
The mean change from baseline of the VLD CBP and placebo groups at Week 8 revealed that VLD CBP treatment improved the dolorimetry score significantly (p = 0.029).

Hospital Anxiety and Depression Scale (HAD)
For subjects who received VLD CBP, the HAD score changed from 13.7 at baseline to 10.4 at Week 8, which was a decrease (or improvement) of 3.3 (24.1%; p = 0.012).
For subjects who received VLD CBP, the HAD depression subscale changed from 6.3 at baseline to 4.9 at Week 8, a decrease (or improvement) of 1.4 (22.2%; p = 0.017).

Our study showed bedtime treatment with VLD CBP provided benefit to FM patients by improving pain, tenderness, fatigue, mood, and sleep quality. Both the ACR28 and OMERACT1,34 recognize pain as the key feature and pain sensitivity or tenderness as another important feature. Bedtime treatment with VLD CBP over 8 weeks improved musculoskeletal pain recorded about 24 h after dosing. Bedtime VLD CBP also improved tenderness measured by pressure dolorimetry. Fatigue and depressive symptoms are recognized as special treatment-outcome features of FM by OMERACT. Bedtime VLD CBP improved fatigue recorded about 24 h after dosing and also improved fatigue measured by self-rated and clinician-rated change over the course of the study. Bedtime VLD CBP improved mood measured by the HAD scale and the HAD depression subscale. Subjects who received placebo showed no significant improvement in any of these measures. Together, these findings show that bedtime treatment with VLD CBP provided benefit to patients with FM by improving symptoms of pain, tenderness, fatigue, and depressed mood.
 
Messages
3,263
If you look at the 7 outcome measures, all of the differences between the control group and the treated group are significant (p<0.05).
I don't think that's true of the between-group comparisons, though, @CFS_for_19_years (most of the p values you report in the quote above are comparisons of baseline and after-treatment, not group comparisons*). And the group comparisons are what really count (otherwise, why bother to have a placebo control at all?)

(*Edit: You're not supposed to compare a significant p value for one group with a non-significant p value for another and conclude there is a treatment effect. p values can't be compared in this way. You need to directly compare the treatment and control groups in the same analysis. Not a criticism of you though - many smart, graduate-level Psychology students still have trouble with this issue)
 
Last edited:

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
I don't think that's true of the between-group comparisons, though, @CFS_for_19_years (most of the p values you report in the quote above are comparisons of baseline and after-treatment, not group comparisons*). And the group comparisons are what really count (otherwise, why bother to have a placebo control at all?)

You're right. Some of the outcome measures failed to show differences between and treated group and the non-treated. Thanks for noticing that. The reported measures were very tedious to read and understand, but you've got a keen eye.;)
 
Messages
3,263
You're right. Some of the outcome measures failed to show differences between and treated group and the non-treated. Thanks for noticing that. The reported measures were very tedious to read and understand, but you've got a keen eye.;)
Not really. More a reflection of what a dull nerd I am. :rolleyes: If you look at enough of these kinds of reports, the key stuff just kind of starts leaping out at you.