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4
Treatment for
Chronic Multisymptom Illness
This chapter assesses the evidence on interventions for treatment for
symptoms associated with, or that define, chronic multisymptom illness
(CMI). The 38 studies and nine systematic reviews (described in 51 manu-
scripts) reviewed were found in the systematic search detailed in Chapter 3
for treatments of multiple physical symptoms associated with CMI. A nar-
rative synthesis of the evidence is presented here by type of treatment: phar-
macologic treatments and other biologic interventions, psychotherapies,
mind–body approaches (including biofeedback, cognitive rehabilitation
therapy, and complementary and alternative therapies), and exercise inter-
ventions. The committee looked for evidence of efficacy or effectiveness1
of interventions in alleviating symptoms and improving quality of life in
all populations affected by multiple symptoms or syndromes similar to
CMI. This chapter also includes the committee’s evaluation of the body
of evidence on each treatment on the basis of the Agency for Healthcare
Research and Quality (AHRQ) strength-of-evidence grading (Owens et al.,
2010) and conclusions about the effectiveness of the evaluated treatments.
The committee did not limit its investigation to particular types of
treatments but rather chose to evaluate all treatments on which there
was evidence. The treatments considered varied widely and included non-
traditional medicine, such as complementary and alternative medicine,
1
Efficacy is benefit from an intervention under the best possible conditions, such as in a
randomized controlled trial in which a selected sample of a specific population is carefully
monitored by physicians, whereas effectiveness is benefit in real life as shown by many types
of research studies (Agency for Healthcare Research and Quality, 2011).
37
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38 GULF WAR AND HEALTH
psychologic therapies, and stress-management techniques. The committee
also considered various outcomes, including symptoms, functioning, qual-
ity of life, health care use, and harms. Although the symptoms of CMI are
physical, the committee embraced the need for a “whole-person” approach
because of the complexity of CMI and its potential comorbidities. The
nontraditional treatments were included in an effort to identify potentially
effective pathways for treatment of the whole person instead of focusing
on each specific symptom.
Only three studies that were identified were conducted in samples of
veterans. Each reported the effects of a different intervention: cognitive
rehabilitation therapy (Jakcsy, 2002), doxycycline (Donta et al., 2004),
and cognitive behavioral therapy (CBT) and exercise (Donta et al., 2003;
Guarino et al., 2001; Mori et al., 2006). The veteran populations were
generally male (85% in Donta et al., 2003, and Mori et al., 2006; 86% in
Donta et al., 2004, and 50% in Jakcsy, 2002), and the average age ranged
from 37.5 years (Jakcsy, 2002) to 40.7 years (Donta et al., 2004). The
committee considers those studies with others of similar interventions but
different populations below.
The committee believed it necessary to consider additional evidence
so that it could offer recommendations about the best treatment and man-
agement approaches for veterans who have CMI. Thus, the recommen-
dations presented in Chapter 8 result from careful consideration of the
evidence presented in the present chapter, evidence on the best treatments
for comorbid and related conditions in Chapter 5, and issues surrounding
patient care and communication in Chapters 6 and 7.
PHARMACOLOGIC INTERVENTIONS
People who have many of the conditions described in this report are
treated with pharmacologic agents that are also used to treat for other con-
ditions. Often, the mechanisms of action of the pharmacologic agents are
unknown. For example, patients who have fibromyalgia may benefit from
duloxetine, which works independently of depression (which duloxetine
is often prescribed for). Such agents include selective serotonin reuptake
inhibitors, serotonin–norepinephrine reuptake inhibitors (for example,
duloxetine), tricyclic medications (for example, amitriptyline), mono-
amine oxidase inhibitors (for example, phenelzine), dopaminergic blockers
(for example, haloperidol), anxiolytics (for example, enzodiazepines),
b
and medications that potentiate gaba-ergic transmission (for example,
g
abapentin), potentiate binding of voltage-gated calcium channels (for
example, pregabalin), and potentiate voltage-dependent sodium channels
(for example, topiramate). Analgesic medications include nonsteroidal anti-
inflammatory analgesics, acetaminophen, opioid analgesics, and tramadol,
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 39
which is serotonergic and partially binds to the mu-opiate receptor. Because
of the variety of effects of these pharmacologic agents and their varied
biologic targets, the committee considered the evidence on specific agents
rather than broad classes.
The committee reviewed 11 studies: nine clinical studies and two sys-
tematic reviews. Of the clinical trials, five were randomized (Donta et
al., 2004; Han et al., 2008a; Kroenke et al., 2006; Muller et al., 2008;
Volz et al., 2000), six were blinded (Altamura et al., 2003; Donta et
al., 2004; Han et al., 2008a; Kroenke et al., 2006; Muller et al., 2008;
Volz et al., 2000), and three were pre–post2 studies (Garcia-Campayo and
S
anz-Carrillo, 2002; Han et al., 2008b; Menza et al., 2001). Six of the clini-
cal trials included agents typically known as antidepressants ( irtazapine,
m
venlafaxine, nefazodone, escitalopram, paroxetine, and opipramol), one an
anti sychotic (sulpiride), one an anticonvulsant (topiramate), and one
p
an antibiotic (doxycycline).
Most of the pharmacologic studies were limited by a high number of
dropouts in both treatment and placebo arms. Only one study involved
the veteran population (Donta et al., 2004); it was the only study that
used a nonpsychopharmacologic intervention (doxycycline), and it did not
demonstrate efficacy. The other eight studies enrolled people in the general
population, most of them female, who had somatoform disorder variously
described as multisomatoform disorder, undifferentiated somatoform dis-
order, and somatization disorder. Two studies excluded patients who had
comorbid major depressive disorder, social anxiety disorder, or generalized
anxiety disorder but used anxiolytics, alprazolam, or lorazepam in over
50% of the subjects in addition to the medications being assessed (Han et
al., 2008a,b). The generalizability of studies of nonveteran populations to
the veteran population is unclear.
In all the studies except the doxycycline study (Donta et al., 2004), the
authors concluded that there may be benefit from specific drug interventions
but that future research should include larger cohorts of patients and fixed
doses of medications. The evidence is limited by small sample sizes, high
dropout rates, and potentially confounding effects of depression and anxiety.
The influence of pharmaceutical manufacturers, who funded or employed the
authors of several of the clinical trials, may have affected the reported results
(Altamura et al., 2003; Donta et al., 2004; Han et al., 2008a; Kroenke et al.,
2006; Menza et al., 2001). Publication bias may also be an issue if it limited
the evidence available for consideration by the committee.
Regarding the risk of bias in each study, the committee judged four of
the studies (Donta et al., 2004; Kroenke et al., 2006; Muller et al., 2008;
2
Pre–post is used to describe clinical study designs where pre-intervention measures are
compared to post-intervention measures.
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40 GULF WAR AND HEALTH
Volz et al., 2000) to be at low risk for bias and five to be at high risk
(Altamura et al., 2003; Garcia-Campayo and Sanz-Carrillo, 2002; Han et
al., 2008a,b; Menza et al., 2001).
The two systematic reviews were of relatively good quality. A review
by Sumathipala et al. (2007) was particularly relevant in that the studies
reviewed focused on adults who had medically unexplained symptoms and
excluded symptom syndromes such as chronic fatigue syndrome (CFS), fibro-
myalgia, and irritable bowel syndrome (IBS). The studies that were reviewed
were limited by high dropout rates, focus on short-term outcomes, and use
of varied methods but did indicate support for antidepressants. A review
by Kroenke (2007) noted that pharmacologic studies were limited by short
follow-up and included drugs that are not available in the United States.
On the basis of guidance provided by AHRQ (Owens et al., 2010),
the committee rated the strength of evidence as shown in Table 4-1 and
concluded that
• There is insufficient strength of evidence to determine the effective-
ness of paroxetine, nefazodone, and opipramol in people who have
somatoform disorders.
• There is low strength of evidence that venlafaxine, escitalopram,
levosulpiride, and topiramate improved symptoms in people who
had somatoform disorders.
• There is high strength of evidence that doxycycline is not effective
in improving symptoms and functioning in veterans who have CMI
(referred to as Gulf War illnesses in Donta et al., 2004).
Each of the studies on pharmacologic interventions is summarized in
Table 4-2. Clinical trials are presented first, followed by systematic reviews.
OTHER BIOLOGIC INTERVENTIONS
Fontani et al. (2011) studied the use of noninvasive radioelectric asym-
metric conveyer brain stimulation (REAC-BS) to treat for pain and physical
problems related to stress. REAC-BS is a series of painless electric pulses
applied to specific reflex auricular points. The authors found that patients
treated with REAC-BS reported fewer pain and physical symptoms after
treatment after a 4-week treatment cycle than those treated with a placebo.
The study was limited because there was a lack of follow-up and because
the dose was not standardized but varied on the basis of patient response.
Patients may have been able to sense the stimulations and deduce their
allocation to the treatment or placebo group. The clinical significance of
pre–post score change from 122 to 96 on the psychologic stress measure
questionnaire is unclear (Fontani et al., 2011).
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 41
TABLE 4-1 Strength of Evidence on Pharmacologic Interventions
No. Studies Strength of
(No. Subjects) RoB Consistency Directness Precision Evidence
Venlafaxine
RCT: 2 (207)a High Consistent Indirect Imprecise Low
Paroxetine
Pre–post: 1 (22)b High N/A Indirect Imprecise Insufficient
Nefazodone
Pre–post: 1 (15)c High N/A Indirect Imprecise Insufficient
Escitalopram
RCT: 1 (31)d Low N/A Indirect Imprecise Low
Opipramol
RCT: 1 (208)e Unclear N/A Indirect Imprecise Insufficient
Levosulpiride
RCT: 1 (74)f High N/A Indirect Imprecise Low
Topiramate
Pre–post: 1 (35)g High N/A Direct Imprecise Low
Doxycycline
RCT: 1 (491)h Low N/A Direct Precise Highi
NOTES: RCT = randomized controlled trial; RoB = risk of bias.
aHan et al., 2008a; Kroenke et al., 2006.
bHan et al., 2008b.
cMenza et al., 2001.
dMuller et al., 2008.
eVolz et al., 2000.
fAltamura et al., 2003.
gGarcia-Campayo and Sanz-Carrillo, 2002.
hDonta et al., 2004.
iNo beneficial effect was found in the study.
On the basis of guidance provided by AHRQ (Owens et al., 2010), the
committee rated the strength of evidence as shown in Table 4-3 and found
that there was insufficient evidence to draw conclusions about the effective-
ness of REAC-BS in treating for CMI. Details of Fontani et al. (2011) are
summarized in Table 4-4.
PSYCHOTHERAPIES
Cognitive Behavioral Interventions
The committee reviewed five individual CBT studies and five group
CBT studies that assessed CBT for patients who presented with somatic
symptoms. Somatic-focused CBT, reviewed below, is not general CBT but
rather targets somatic symptoms directly and includes relaxation and activ-
ity components.
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42 GULF WAR AND HEALTH
TABLE 4-2 Pharmacologic Interventions
Study Type Intervention Population
Altamura et al., 2003 RCT, Levosulpiride 50 mg/ 64.9% female, mean age
crossover day vs placebo for 4 38.1 years
Somatoform disorders weeks.
N levosulpiride = 37
Italy N placebo = 37
Donta et al., 2004 RCT Doxycycline 200 mg/ 14% female, mean age
day vs identically 41 years
Veterans with Gulf matched placebo
War veterans illness capsules for 12 N screened = 2,712
and positive for months. N doxycycline = 245
mycoplasma DNA N placebo = 246
US VA and DOD
medical centers
Garcia-Campayo and Pre–post Topiramate starting 68.6% female, mean age
Sanz-Carrillo, 2002 at 50 mg, increased 41.8 years
by 50 mg every 4
Multisomatoform days to a maximum N screened = 84
disorder of 300–400 mg N enrolled = 35
(150–200 mg bi-daily)
Zargoza, Spain or until adverse event
occurred; trial lasted 6
months; dose averaged
365.7 mg (range
300–400 mg).
Han et al., 2008a RCT Venlafaxine vs 61% female, mean age
mirtazapine. 45 years
Undifferentiated Venlafaxine starting at
somatoform disorder 37.5 mg/day, increased N venlafaxine = 45
each week by 37.5–75 N mirtazapine = 50
Ansan, Korea mg/day to maximum
of 225 mg/day.
Mirtazapine starting
at 15 mg/day,
increased by 15 mg/
day to maximum of
60 mg/day.
Both were adjusted
for tolerability and
clinical response.
Conducted over 12
weeks.
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 43
Outcomes and Results
After treatment, levosulpiride patients reported fewer symptoms (measured by CISSD-SDS)
compared with baseline (1,709 vs 1,205 symptoms, p = 0.007) and compared with placebo
at 4 weeks (1,205 vs 1,597 symptoms, p < 0.001).
No difference between treatments in anticholinergic or neuroendocrine side effects reported;
extrapyramidal system involvement was reported more frequently by levosulpiride-treated
patients (9 vs 2 patients, p < 0.03).
After treatment, treatment and placebo groups did not differ significantly in any outcome
measured. In primary outcome, physical health functioning (SF-36), treatment and
placebo groups’ average scores were 30.2 and 30.1 (physical) and 37.4 and 36.2 (mental),
respectively, at baseline; at 12 months, treatment and placebo groups’ average scores were
32.0 and 30.9 (physical) and 37.6 and 36.7 (mental). No differences in pain (MPQ), fatigue
(MFI), or cognition (Cognitive Failures Questionnaire). After 12 months, 154 of 200
doxycycline and 159 of 211 placebo patients were negative for mycoplasma DNA.
Increased adverse events considered related to study drug were myalgia in placebo group
(4.5% vs 1.2%, p = 0.05), nausea in doxycycline group (37.1% vs 10.2%, p < 0.001), and
photosensitivity in doxycycline group (14.7% vs 6.1%, p = 0.002); all other reported events
were in the two groups.
Blood doxycycline concentrations were undetectable in 38.9% of treatment-group patients
and 98% of placebo-group patients at 12 months (adherence).
From baseline to 6-month follow-up, improvements in severity (CGI, 3.8 to 3.3, p < 0.001)
and functioning (GAF, 52.4 to 58.5, p < 0.001) were significant; no significant changes
were seen in pain (pain VAS, 68.8 to 68.7; MPQ, 36.6 to 36.2) or anxiety and depression
(HADS, 9.5 to 9.6).
Most frequently reported side effects were somnolence (25.7%), fatigue (20%), paresthesia
(14.2%), nervousness (8.5%), and nausea (5.7%).
After treatment, mean somatic symptom severity scores (PHQ-15) decreased significantly for
mirtazapine (–8.4, p < 0.0001) and venlafaxine (–6.1, p < 0.0001) over 12 weeks; between-
group difference was significant (p = 0.046) in favor of mirtazapine.
For mirtazapine, scores for psychologic distress (GHQ-12) and depression (BDI) decreased
significantly between baseline and end of study (–4.9, p < 0.0001 and –13.5, p < 0.0001,
respectively); for venlafaxine, psychologic distress and depression scores also decreased
significantly (–4.3, p = 0.001 and –9.02, p < 0.0001) with no significant difference between
groups.
Adverse effects reported by participants were dry mouth in both groups; somnolence,
yawning, and dizziness in mirtazapine group; and nausea in venlafaxine group.
continued
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44 GULF WAR AND HEALTH
TABLE 4-2 Continued
Study Type Intervention Population
Han et al., 2008b Pre–post Paroxetine 59% female, mean age
Immediate Release 37.4 years
Undifferentiated (IR) administered
somatoform disorder starting at 10 mg/ N screened = 43
day and increased N enrolled = 22
Ansan, Korea to a maximum of
40 mg/day on basis
of patient’s response
over 8 weeks; average
dose was 19.5 mg/day
(range 10–40 mg/day).
Kroenke et al., 2006 RCT Venlafaxine ER vs 80% female, mean age
placebo. Capsules 47 years
Multisomatoform given once a day in
disorder following doses: week N screened = 231
1 = 75 mg; week 2 = N venlafaxine ER = 55
USA 150 mg; weeks 3–12 = N placebo = 57
225 mg.
Dose was decreased
to tolerable level
for participants
who experienced
intolerance.
Conducted over 12
weeks, with up to 2
weeks of taper.
Menza et al., 2001 Pre–post Nefazodone 86% female, mean age
administered starting 48.6 years
Somatization disorder at 50 mg bi-daily,
increased to 100 mg N screened = 46
Piscataway, bi-daily after first N enrolled = 15
New Jersey week, increased to
150 mg bi-daily in
weeks 2–8.
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 45
Outcomes and Results
After treatment, average symptom severity (PHQ-15) score dropped significantly, by 75%,
from 17.2 to 4.3 (p = 0.001) between baseline and 8 weeks. Average depression (BDI)
scores also decreased significantly, 50.8% (p < 0.001), and average psychologic distress
(GHQ-12) scores decreased by 13%, but difference was not significant.
Most common adverse events reported were nausea, dry mouth, and somnolence.
After treatment, both treatment and placebo groups had significant (p < 0.0001) decrease
in somatic symptoms (PHQ-15 change of –8.3 and –6.6 respectively) but no significant
difference between groups (p = 0.097). From baseline to 12 weeks, greater improvement
was seen in Venlafaxine ER participants than in those who received placebo for pain (PHQ-
15 pain subscale, –3.3 and –2.6, respectively, p = 0.03), psychic anxiety (HAM-A, –8.6
and –5.9, respectively, p = 0.02), clinical improvement (CGI-Improvement, –1.8 and –1.4,
respectively, p = 0.009), physical symptoms (MQOL Physical symptoms, –11.7 and –6.0,
respectively, p = 0.01), mental health (SF-36, 28.6 and 16.8, respectively, p = 0.03), bodily
pain (SF-36, 26.1 and 14.5, respectively, p = 0.03), and concentration (MOS-CS, 30.1 and
15.3, respectively, p = 0.007).
Significant (p ≤ 0.001) improvement from baseline to week 12 was noted for several
measures without difference between groups (depression, HAM-D; HAM-A total score and
HAM-A somatic anxiety score; CGI-Severity score; and SF-36 physical health score).
Percentage of patients reporting bothersome headache and stomach pain symptoms
decreased significantly more in venlafaxine ER than in placebo-treated patients (both p =
0.03).
Venlafaxine ER–treated participants reported more adverse effects than placebo; more than
10% of venlafaxine ER patients reported nausea, headache, fatigue, dizziness, constipation,
and tremor.
11 of 15 patients who completed study showed nonsignificant improvement by 24% in
symptom severity on VAS after 8 weeks of treatment compared with baseline. From baseline
to week 8, 73% of participants showed improvement on CGI (significance not noted),
and 73% showed significant improvement in functioning (SF-36, p < 0.025). Significant
improvement in depression (p < 0.005) and cognitive and somatic subscales (both
p < 0.025) of HAM-D and HAM-A were reported, but there was no correlation with VAS,
CGI, or SF-36 score.
Most common adverse effects were sedation, GI discomfort, anxiety, and dry mouth.
continued
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46 GULF WAR AND HEALTH
TABLE 4-2 Continued
Study Type Intervention Population
Muller et al., 2008 RCT Escitalopram vs 90% female, mean age
placebo. Administered 40 years
Multisomatoform at 10 mg/day and
disorder could be increased to N screened = 60
20 mg/day after week N escitalopram = 25
Cape Town, South 4 (dose decreased N placebo = 26
Africa to 10 mg/day for
intolerance). Dosage
was constant for
weeks 8–12; after 12
weeks, dosage was
tapered and stopped
over 1 week.
Entire study took
place over 18 months.
Volz et al., 2000 RCT Opipramol vs placebo. 64% female, mean age
Started at 50 mg/day, 46 years
Somatoform disorders increased by 50–200
(ICD-10 codes F45.0, mg/day on day 4. N opipramol = 104
F45.1, F45.3) Number of placebo N placebo = 104
capsules was identical
Germany with number of
opipramol capsules.
Treatment lasted 6
weeks.
Systematic Reviews
Kroenke, 2007 Systematic Multiple N RCTs = 34
review
Somatoform disorders
Sumathipala, 2007 Systematic Multiple N abstracts screened
review = 368
Somatoform disorders N systematic reviews
=6
N RCTs = 14
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 47
Outcomes and Results
After treatment, symptom severity (PHQ-15) scores in treatment group decreased
significantly more than in placebo group (14.6 vs 17.3 at baseline and 5.6 vs 12.5 at 12
weeks, respectively, p < 0.0001). Clinical improvement (CGI-Improvement, treatment: 3.0
to 1.6 vs placebo: 3.4 to 3.2, at baseline and 12 weeks, respectively) and severity (CGI-
Severity, treatment: 4.5 to 2.6 vs placebo: 4.7 to 4.1, at baseline and 12 weeks, respectively)
also showed significant improvement in treatment subjects (p < 0.05).
Likewise, escitalopram showed improvement on somatic anxiety (HAM-A somatic subscore,
p < 0.0001, and HAM-A psychic subscore, p = 0.0002), depression (MADRS, p = 0.017),
and disability (SDS, p = 0.015) scores after 12 weeks compared with placebo. No difference
between treatment and placebo in illness behavior (SAIB) was detected.
After 12 weeks, 80% of treatment and 26.9% of placebo subjects met criteria for being
responsive to treatment, and 52% of treatment and 3.8% of placebo subjects met criteria
for remission.
Most common adverse events were headache, nausea, and abdominal discomfort in first
2 weeks and headache, nasopharyngitis, and diarrhea in weeks 2–12, with no significant
differences between treatment and placebo groups in reported adverse events.
Average dose was 14.4 mg of escitalopram per day and 18.1 mg of placebo per day.
After treatment, anxiety scores decreased significantly more in opipramol group than in
placebo group for somatic anxiety (HAM-A somatic subscore, 16.8 to 7.3 vs 16.9 to 9.1, p
= 0.013) and total anxiety (HAM-A, 25.1 to 11.8 vs 25.3 to 14.5, p = 0.013), and decrease
in psychic anxiety score was nearly significant (HAM-A psychic subscore, 8.3 to 4.5 vs 8.4
to 5.4, p = 0.052). Scores followed same trend with greater decrease in opipramol group
and in placebo group for depression (HAM-D, 14.6 to 8.0 vs 14.3 to 9.5, p = 0.006) and
for symptoms (SCLR-90-R, 0.95 to 0.57 vs 0.77 to 0.55, p = 0.041), including somatic
symptoms (1.61 to 0.93 vs 1.40 to 0.98, p = 0.043) and anxiety symptoms (1.15 to 0.63 vs
0.94 to 0.64, p = 0.049).
Adverse events were reported by 37% of opipramol patients and 38% of placebo patients—
gastrointestinal complaints in 7.1% of opipramol patients and 20.8% of placebo patients
and musculoskeletal complaints in 14% of opipramol patients and 7% of placebo patients.
Tiredness occurred more frequently in opipramol group than in placebo group (9% vs 2%).
Positive results for at least one outcome (symptoms, functional, or psychologic) were
noted in 11 of 13 CBT studies and 4 of 5 antidepressants studies, and 8 of 16 studies of
other interventions reported improvement—consultation letter to primary care physician
(4 studies), primary care physician training (2 studies), and non-CBT psychotherapies (2
studies), hypnosis (2 studies), and one study each investigating multicomponent nurse-care
management, aerobic exercise, writing disclosure, paradoxic intention, and explanatory
therapy.
CBT is most effective for variety of somatoform disorders and outcomes.
Studies assessed interventions with antidepressants (1 review and 3 RCTs), CBT (5 reviews
and 2 RCTs), psychiatric consultation (3 RCTs), other forms of psychotherapy (3 RCTs),
exercise (2 RCTs), and collaborative care (1 RCT).
Studies have many limitations and varied methods, so interventions cannot be compared.
Authors note support for antidepressants and CBT and limited evidence on other
interventions.
continued
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82 GULF WAR AND HEALTH
TABLE 4-12 Continued
Study Type Intervention Population
Payne and Stott, 2010; Pre–post BMA with DMP. 83% of participants
Payne, 2009 Four parts comprising female, mean age 48
4 sessions lasting 2 years
MUS hours each for 12
weeks. N screened = 31
United Kingdom N enrolled = 18
Volz et al., 2002 RCT SJW vs control. 72% of treatment group
Participants received female, mean age 46.9
Somatoform disorders placebo or SJW years; 62% of placebo
tablets twice daily for group female, mean age
Germany 6 weeks. SJW was 48.6 years
administered as 300-
mg tablets. N treatment = 75
N control = 74
Yamada et al., 2005 Pre–post Kampo (with 74% of participants
supportive female, mean age 47.1
USD and CD psychotherapy). years; 94 met criteria
Duration of treatment for USD, 26 criteria
Japan 3 months. for CD
N = 120
NOTES: BE = bioenergetic exercise; BMA = body–mind approach; CD = conversion dis
order; CGI = Clinical Global Impressions Scale; CORE-OM = Counseling Outcome Routine
E
valuation–Outcome Measure; DMP = dance-movement psychotherapy; EQ-5D = EuroQol
health status questionnaire; ES = effect size; HAM-A = Hamilton Anxiety Rating Scale;
MUPS = medically unexplained physical symptoms; MUS = medically unexplained symptoms;
MYMOP = Measure Yourself Medical Outcome Profile; SCL-90-R = Symptom Checklist-90-
Revised; SJW = St. John’s wort (Hypericum); SOMS-7 = Screening for omatoform ymptoms-7;
S S
STAXI = State-Trait Anger Expression Inventory; USD = undifferentiated somatiform disorder;
W-BQ12 = 12-Item Well-Being Questionnauire; WHOQoL-BREF = World Health Organization
Quality of Life Scale Brief Version.
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 83
Outcomes and Results
At 3-month follow-up, significant mean changes (CORE-OM, baseline to follow-up) were
reported for well-being –0.76 (95% CI –1.15 to –0.38), p < 0.001, ES = 0.72; problems
–0.70 (95% CI –1.13 to –0.26), p < 0.004, ES = 0.65; function –0.54 (95% CI –0.93 to
–0.14), p < 0.011, ES = 0.58; risk –0.15 (95% CI –0.38 to 0.09), p < 0.204, ES = 0.31; all
nonrisk –0.64 (95% CI –1.03 to –0.25), p < 0.003, ES = 0.66; all items –0.56 (–0.90 to
–0.21), p < 0.003, ES = 0.66.
Significant improvements for specific symptoms were also shown (MYMOP, baseline to
follow-up) for symptom one –1.7 (95% CI –2.6 to –0.8), p < 0.001, ES = 0.71; activity –2.1
(95% CI –3.4 to –0.9), p < 0.003, ES = 0.66; well-being –1.7 (95% CI –2.6 to –0.8), p <
0.001, ES = 0.71; symptom two –1.8 (95% CI –3.2 to –0.5), p < 0.012, ES = 0.67.
Facilitator and participant perceptions were compared and found to be largely congruent;
participants learned how their emotions are linked to physical well-being and how to avoid
or cope with symptoms in different ways.
At end of treatment, statistically significant differences were reported between treatment and
control groups from day 0 to day 42 with regard to somatic anxiety (HAM-A somatization
subscale SJW 15.39–6.64 vs placebo 15.55–11.97, p = 0.001), anxiety (HAM-A SJW
22.09–10.0 vs placebo 22.47–17.0, p = 0.0001), psychic anxiety (HAM-A psychic subscale
SJW 6.71–3.36 vs placebo 6.92–5.03, p = 0.0001), depression (HAM-D SJW 10.59–5.43
vs placebo 10.80–8.08, p = 0.0001), psychic symptoms (SCL-90-R SJW 61.65–29.39 vs
placebo 66.37–50.50, p = 0.0001), somatic symptoms (SCL-90-R somatization subscale
SJW 15.57–6.84 vs placebo 15.95–12.50, p = 0.0001).
9 adverse events were observed in 8 participants in treatment group and 5 adverse events in
4 participants in control group.
After treatment, 13 participants were “very much improved,” 37 “much improved,” 39
“minimally improved,” 9 “no change,” 1 “minimally worse,” and 1 “much worse.”
Quality-of-life (WHOQoL-BREF) score improved from 3.08 at baseline to 3.21 after 3
months (p = 0.0001). Subscores also showed significant improvement in “physical health”
(p = 0.0004) and “psychological health” (p = 0.0006), and nonsignificant changes were
found in “social relationships” and “environment.”
Adverse events were reported in 6 patients.
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84 GULF WAR AND HEALTH
TABLE 4-13 Strength of Evidence on Exercise Interventions
No. Studies Strength of
(No. Subjects) RoB Consistency Directness Precision Evidence
RCT: 2 (1,320)a Intermediate Inconsistent Indirect Imprecise Insufficient
NOTES: RCT = randomized controlled trial; RoB = risk of bias.
aDonta et al., 2003/Mori et al., 2006; Peters et al., 2002.
TABLE 4-14 Exercise Interventions
Study Type Intervention Population
Donta et al., 2003; RCT CBT vs CBT + Gulf War Veterans
Mori et al., 2006 exercise. deployed August 1990
CBT was 60–90 min to August 1991; 15%
Gulf War Veterans’ long; groups met female, mean (SD) age
Illnesses weekly for 12 weeks. 40.7 (8.7) years; 24%
Aerobic exercise was with disability claim
18 VA and 2 DOD one 1-hour session
medical centers per week with an N screened = 2,793
exercise therapist for N CBT + exercise = 266
12 weeks and 2 or 3 N CBT only = 286
independent sessions N exercise only = 269
per week for 12 N usual care = 271
weeks.
Peters et al., 2002 RCT Aerobic exercise vs 53% female, mean age
stretching, 1-hour 44 years (range 9–73),
PUPS sessions twice weekly 46% employed
for 10 weeks.
Liverpool, United Homework: exercise N screened = 323
Kingdom or stretch for 20 min N aerobic training =
3 times weekly. 114
N stretching training
= 114
NOTES: CBT = cognitive behavioral therapy; GP = General Practitioner; HADS = Hospital
Anxiety and Depression Scale; MSPQ = Modified Somatic Perception Questionnaire; PUPS =
persistent unexplained physical symptoms; RCT = randomized controlled trial; SD = standard
deviation; V/SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey for Veterans.
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 85
Outcomes and Results
At 12-month follow-up, physical functioning (V/SF-36): CBT + exercise adj OR = 1.84
(95% CI 0.95–3.55); CBT adj OR = 1.72 (95% CI 0.91–3.23); exercise adj OR = 1.07
(95% CI 0.63–1.82); CBT vs no CBT OR = 1.71 (95% CI 1.21–2.41); exercise vs no
exercise adj OR = 1.07 (95% CI 0.76–1.50). Mean change from baseline: CBT 0.59, CBT +
exercise 1.03, exercise 0.97.
Exercise alone or in combination with CBT significantly improved fatigue, cognitive
symptoms, mental health functioning; CBT alone significantly improved cognitive symptoms
and mental health functioning, p < 0.025. Neither had significant impact on pain.
In treatment phase, 44.9% in exercise group and 40.2% in CBT + exercise group complied
(p = 0.28); in maintenance phase, 24.9% of exercise and 21.1% of CBT + exercise patients
complied (p = 0.29).
6 months after training, aerobic exercise and stretching resulted in improvement from
baseline with fewer symptoms recorded by GP; fewer GP consultations; fewer prescriptions;
fewer secondary-care contacts; and fewer new referrals to secondary care (all p < 0.01).
Anxiety and depression (HADS) and somatization (MSPQ) declined from start of program
to 6-month follow-up (all p < 0.01). Reported life interference, energy, mental health, and
social function improved from randomization to 6-month follow-up (all p < 0.001). No
significant changes were noted in SF-36 scores. Most improvement occurred during training
and did not continue in 6 months after.
No significant difference between effects of stretching and aerobic exercise on any variable.
Regression models show that treatment attendance significantly reduced visits to GPs
(p < 0.001), number of prescriptions (p < 0.01), number and type of prescription refills
(p < 0.001) from start of treatment to 6-month follow-up but was not related to measures
of symptoms and somatization.
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86 GULF WAR AND HEALTH
evidence had methodologic limitations and biases that may have masked
true treatment effects, and there was great diversity in study populations,
types of interventions conducted, controls used, and types of outcomes
assessed and measures used.
Study quality was generally poor, and samples were small (from 10
to 1,092 participants, median 87, mean 150), and many studies had high
dropout rates. Most of the studies reviewed were subject to multiple sources
of bias or did not clearly describe methods, and this resulted in a high pro-
portion of studies at high or unclear risk of bias. Confounding diagnoses,
such as depression and anxiety, may affect the magnitude of treatment
effect and were not examined. For example, using an antidepressant to treat
patients who have CMI with minor depression may improve symptoms
because of changes in mood rather than changes in CMI symptoms. Some
of the studies attempted to avoid that problem by excluding people who
met diagnostic criteria for some psychiatric disorders or medical illnesses,
but subsyndromal or undiagnosed conditions may have remained in study
samples.
The heterogeneous nature of the literature limited the committee’s abil-
ity to compare the efficacy of different interventions. With the exception of
CBT, each intervention was the subject of only a few studies that evaluated
its efficacy. The study populations were defined in different ways; some
studies examined only a few symptoms not explained by medical illness,
and others required diagnosis of a specific disorder for various durations
and of various degrees of severity. Methods differed greatly as well: there
were few blinded RCTs, and many clinical trials were influenced by varied
sources of bias. The literature also used a variety of outcomes to define
treatment success—such as number of symptoms, severity of symptoms,
health care use, functional improvement, and changes in mood—and this
made comparison difficult in that different studies used different outcomes.
In addition, the numerous outcomes were measured in different ways with
different tools, so comparability of studies was limited further.
Generalizability among the populations studied is questionable. Only
three studies were conducted in military or veteran populations. Almost all
the other study samples were dominated by middle-aged women. Thus, it
is difficult to extrapolate the efficacy and acceptability of an intervention to
the veteran population of interest, which is slightly younger on the average
and mostly male.
Adverse effects of pharmaceuticals are typically reported, but other
types of interventions may have harmful effects that are not identified or
investigated. The method of adverse-event reporting may be important;
use of a standardized list of adverse events may cause study participants
who are suggestible (such as people who are seeking psychologic health
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TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 87
care) to report more events than they would have otherwise (Kroenke and
Rosmalen, 2006).
Length of follow-up was variable, although generally short, ranging
from 1 week to 18 months (median 3 months) between the start of a study
and the last assessment. Many studies collected data only immediately after
treatment, whereas others assessed the effect of treatment many months
after treatment had ceased.
The committee’s recommendations—based on the weight of the evi-
dence described above, treatments for comorbid and other related condi-
tions (Chapter 5), and issues related to patient care and communication
(Chapters 6 and 7)—are presented in Chapter 8.
REFERENCES
Abbass, A., S. Campbell, K. Magee, and R. Tarzwell. 2009a. Intensive short-term dynamic
psychotherapy to reduce rates of emergency department return visits for patients with
medically unexplained symptoms: Preliminary evidence from a pre-post intervention
study. Canadian Journal of Emergency Medical Care 11(6):529-534.
Abbass, A., S. Kisely, and K. Kroenke. 2009b. Short-term psychodynamic psychotherapy for
somatic disorders: Systematic review and meta-analysis of clinical trials. Psychotherapy
and Psychosomatics 78(5):265-274.
AHRQ (Agency for Healthcare Research and Quality). 2011. Effective Health Care Pro-
gram. Glossary of Terms. http://effectivehealthcare.ahrq.gov/index.cfm/glossary-of-terms/
(
accessed July 1, 2012).
Aiarzaguena, J. M., G. Grandes, I. Alonso-Arbiol, J. L. del Campo Chavala, M. B. Oleaga
Fernandez, and J. Marco De Juana. 2002. Bio-psychosocial treatment approach to
s
omatizing patients in primary care: A pilot study. Atencion Primaria 29(9):558-561.
Allen, L. A., J. I. Escobar, P. M. Lehrer, M. A. Gara, and R. L. Woolfolk. 2002. Psychosocial
treatments for multiple unexplained physical symptoms: A review of the literature.
sychosomatic Medicine 64(6):939-950.
P
Allen, L. A., R. L. Woolfolk, J. I. Escobar, M. A. Gara, and R. M. Hamer. 2006. Cognitive-
behavioral therapy for somatization disorder: A randomized controlled trial. Archives of
Internal Medicine 166(14):1512-1518.
Altamura, A. C., A. Di Rosa, A. Ermentini, G. P. Guaraldi, G. Invernizzi, N. Rudas, G.
T
acchini, R. Pioli, M. T. Coppola, V. Tosini, E. Proto, E. Bolognesi, and B. Marchio.
2003. Levosulpiride in somatoform disorders: A double-blind, placebo-controlled cross-
over study. International Journal of Psychiatry in Clinical Practice 7:155-159.
Arnold, I. A., M. W. de Waal, J. A. Eekhof, W. J. Assendelft, P. Spinhoven, and A. M. van
Hemert. 2009. Medically unexplained physical symptoms in primary care: A controlled
study on the effectiveness of cognitive-behavioral treatment by the family physician.
Psychosomatics: Journal of Consultation Liaison Psychiatry 50(5):515-524.
Barrios-Choplin, B., R. McCraty, and B. Cryer. 1997. An inner quality approach to reduc-
ing stress and improving physical and emotional wellbeing at work. Stress Medicine
13(3):193-201.
Bleichhardt, G., B. Timmer, and W. Rief. 2004. Cognitive-behavioural therapy for patients
with multiple somatoform symptoms: A randomised controlled trial in tertiary care.
Journal of Psychosomatic Research 56:449-454.
OCR for page 88
88 GULF WAR AND HEALTH
CDC (Centers for Disease Control and Prevention). 2011. Physical Activity and Health. http://
www.cdc.gov/physicalactivity/everyone/health/index.html (accessed September 27, 2012).
Chappell, H., and S. Chasee. 2006. The effect of biofeedback-assisted stress management
training on migrant college students’ anxiety and personal growth initiative. Disserta-
tion Abstracts International: Section B: The Sciences and Engineering 66(11-B):62-65.
Donta, S. T., D. J. Clauw, C. C. Engel, Jr., P. Guarino, P. Peduzzi, D. A. Williams, J. S. kinner,
S
A. Barkhuizen, T. Taylor, L. E. Kazis, S. Sogg, S. C. Hunt, C. M. Dougherty, R. D.
Richardson, C. Kunkel, W. Rodriguez, E. Alicea, P. Chiliade, M. Ryan, G. C. Gray, L.
Lutwick, D. Norwood, S. Smith, M. Everson, W. Blackburn, W. Martin, J. M. Griffiss,
R. Cooper, E. Renner, J. Schmitt, C. McMurtry, M. Thakore, D. Mori, R. Kerns, M.
Park, S. Pullman-Mooar, J. Bernstein, P. Hershberger, D. C. Salisbury, J. R. Feussner.
2003. Cognitive behavioral therapy and aerobic exercise for Gulf War veterans’ ill-
nesses: A randomized controlled trial. Journal of the American Medical Association
289(11):1396-1404.
Donta, S. T., C. C. Engel, Jr., J. F. Collins, J. B. Baseman, L. L. Dever, T. Taylor, K. D.
B
oardman, L. E. Kazis, S. E. Martin, R. A. Horney, A. L. Wiseman, D. S. Kernodle, R. P.
Smith, A. L. Baltch, C. Handanos, B. Catto, L. Montalvo, M. Everson, W. Blackburn,
M. Thakore, S. T. Brown, L. Lutwick, D. Norwood, J. Bernstein, C. Bacheller, B. Ribner,
L. W. P. Church, K. H. Wilson, P. Guduru, R. Cooper, J. Lentino, R. J. Hamill, A. B.
G
orin, V. Gordan, D. Wagner, C. Robinson, P. DeJace, R. Greenfield, L. Beck, M. Bittner,
H. R. Schumacher, F. Silverblatt, J. Schmitt, E. Wong, M. A. K. Ryan, J. Figueroa, C.
Nice, J. R. Feussner. 2004. Benefits and harms of doxycycline treatment for Gulf War
veterans’ illnesses: A randomized, double-blind, placebo-controlled trial. Annals of In-
ternal Medicine 141(2):85-94.
Escobar, J. I., M. A. Gara, A. M. Diaz-Martinez, A. Interian, M. Warman, L. A. Allen, R. L.
Woolfolk, E. Jahn, and D. Rodgers. 2007. Effectiveness of a time-limited cognitive behav-
ior therapy type intervention among primary care patients with medically unexplained
symptoms. Annals of Family Medicine 5(4):328-335.
Fontani, V., S. Rinaldi, L. Aravagli, P. Mannu, A. Castagna, and M. L. Margotti. 2011. Non-
invasive radioelectric asymmetric brain stimulation in the treatment of stress-related pain
and physical problems: Psychometric evaluation in a randomized, single-blind placebo-
controlled, naturalistic study. International Journal of General Medicine 4:681-686.
Garcia-Campayo, J., and C. Sanz-Carrillo. 2002. Topiramate as a treatment for pain in multi-
somatoform disorder patients: An open trial. General Hospital Psychiatry 24(6):417-421.
Guarino, P., P. Peduzzi, S. T. Donta, C. C. Engel, D. J. Clauw, D. A. Williams, J. S. Skinner,
A. Barkhuizen, L. E. Kazis, and J. R. Feussner. 2001. A multicenter two by two factorial
trial of cognitive behavioral therapy and aerobic exercise for Gulf War veterans’ illnesses:
Design of a Veterans Affairs cooperative study (CSP #470). Controlled Clinical Trials
22(3):310-332.
Han, C., C. U. Pae, B. H. Lee, Y. H. Ko, P. S. Masand, A. A. Patkar, S. H. Joe, and I. K. Jung.
2008a. Venlafaxine versus mirtazapine in the treatment of undifferentiated somatoform
disorder—a 12-week prospective, open-label, randomized, parallel-group trial. Clinical
Drug Investigation 28(4):251-261.
Han, C., D. M. Marks, C. U. Pae, B. H. Lee, Y. H. Ko, P. S. Masand, A. A. Patkar, and I.
K. Jung. 2008b. Paroxetine for patients with undifferentiated somatoform disorder: A
prospective, open-label, 8-week pilot study. Current Therapeutic Research—Clinical and
Experimental 69(3):221-231.
Jakcsy, S. D. 2002. Remediation of Acquired Memory Problems (Post War) in Gulf War Vet-
erans Using Computer Technology. University of Idaho.
OCR for page 89
TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 89
Katsamanis, M., P. M. Lehrer, J. I. Escobar, M. A. Gara, A. Kotay, and R. Liu. 2011. Psycho-
physiologic treatment for patients with medically unexplained symptoms: A randomized
controlled trial. Psychosomatics 52(3):218-229.
Kleinstäuber, M., M. Witthoft, and W. Hiller. 2011. Efficacy of short-term psychotherapy for
multiple medically unexplained physical symptoms: A meta-analysis. Clinical Psychology
Review 31(1):146-160.
Kroenke, K. 2007. Efficacy of treatment for somatoform disorders: A review of randomized
controlled trials. Psychosomatic Medicine 69(9):881-888.
Kroenke, K., and J. G. M. Rosmalen. 2006. Symptoms, syndromes, and the value of psychiatric
diagnostics in patients who have functional somatic disorders. Medical Clinics of North
America 90(4):603-626.
Kroenke, K., and R. Swindle. 2000. Cognitive-behavioral therapy for somatization and symp-
tom syndromes: A critical review of controlled clinical trials. Psychotherapy and Psycho-
somatics 69(4):205-215.
Kroenke, K., N. Messina, I. Benattia, J. Graepel, and J. Musgnung. 2006. Venlafaxine xtended
e
release in the short-term treatment of depressed and anxious primary care patients with
multisomatoform disorder. Journal of Clinical Psychiatry 67(1):72-80.
Lidbeck, J. 1997. Group therapy for somatization disorders in general practice: Effective-
ness of a short cognitive-behavioural treatment model. Acta Psychiatrica Scandinavica
96(1):14-24.
Lidbeck, J. 2003. Group therapy for somatization disorders in primary care: Maintenance of
treatment goals of short cognitive-behavioural treatment one-and-a-half-year follow-up.
Acta Psychiatrica Scandinavica 107(6):449-456.
Looper, K. J., and L. J. Kirmayer. 2002. Behavioral medicine approaches to somatoform dis-
orders. Journal of Consulting & Clinical Psychology 70(3):810-827.
Martin, A., E. Rauh, M. Fichter, and W. Rief. 2007. A one-session treatment for patients
suffering from medically unexplained symptoms in primary care: A randomized clinical
trial. Psychosomatics 48(4):294-303.
McCraty, R., B. Barrios-Choplin, D. Rozman, P. Atkinson, and A. D. Watkins. 1998. The
impact of a new emotional self-management program on stress, emotions, heart rate
variability, DHEA and cortisol. Integrative Physiological and Behavioral Science
33(2):151-170.
McCraty, R., M. Atkinson, and D. Tomasino. 2003. Impact of a workplace stress reduction
program on blood pressure and emotional health in hypertensive employees. Journal of
Alternative and Complementary Medicine 9(3):355-369.
Menza, M., M. Lauritano, L. Allen, M. Warman, F. Ostella, R. M. Hamer, and J. Escobar.
2001. Treatment of somatization disorder with nefazodone: A prospective, open-label
study. Annals of Clinical Psychiatry 13(3):153-158.
Mori, D. L., S. Sogg, P. Guarino, J. Skinner, D. Williams, A. Barkhuizen, C. Engel, D. Clauw,
S. Donta, and P. Peduzzi. 2006. Predictors of exercise compliance in individuals with Gulf
War veterans illnesses: Department of Veterans Affairs cooperative study 470. Military
Medicine 171(9):917-923.
Muller, J. E., I. Wentzel, L. Koen, D. J. Niehaus, S. Seedat, and D. J. Stein. 2008. Escitalopram
in the treatment of multisomatoform disorder: A double-blind, placebo-controlled trial.
International Clinical Psychopharmacology 23(1):43-48.
Muller, T., M. Mannel, H. Murck, and V. W. Rahlfs. 2004. Treatment of somatoform disorders
with St. John’s wort: A randomized, double-blind and placebo-controlled trial. Psycho-
somatic Medicine 66(4):538-547.
Nanke, A., and W. Rief. 2003. Biofeedback-based interventions in somatoform disorders: A
randomized control trial. Acta Neuropsychiatrica 15(4):249-256.
OCR for page 90
90 GULF WAR AND HEALTH
Nezu, A. M., C. M. Nezu, and E. R. Lombardo. 2001. Cognitive-behavior therapy for
medically unexplained symptoms: A critical review of the treatment literature. Behavior
Therapy 32 (3):537-583.
Nickel, M., B. Cangoez, E. Bachler, M. Muehlbacher, N. Lojewski, N. Mueller-Rabe, F. O.
Mitterlehner, P. Leiberich, N. Rother, W. Buschmann, C. Kettler, F. Pedrosa Gil, C.
L
ahmann, C. Egger, R. Fartacek, W. K. Rother, T. H. Loew, and C. Nickel. 2006. Bio-
energetic exercises in inpatient treatment of Turkish immigrants with chronic somato-
form disorders: A randomized, controlled study. Journal of Psychosomatic Research
61(4):507-513.
NIH (National Institutes of Health). 2012. What Is Complementary and Alternative Medicine?
http://nccam.nih.gov/health/whatiscam (accessed September 27, 2012).
Owens, D. K., K. N. Lohr, D. Atkins, J. R. Treadwell, J. T. Reston, E. B. Bass, S. Chang, and
M. Helfand. 2010. AHRQ Series Paper 5: Grading the strength of a body of evidence
when comparing medical interventions: Agency for Healthcare Research and Quality
and the Effective Health-Care Program. Journal of Clinical Epidemiology 63(5):513-523.
Paterson, C., R. S. Taylor, P. Griffiths, N. Britten, S. Rugg, J. Bridges, B. McCallum, and G.
Kite. 2011. Acupuncture for “frequent attenders” with medically unexplained symptoms:
A randomised controlled trial (CACTUS study). British Journal of General Practice
61(587):e295-305.
Payne, H., and D. Stott. 2010. Change in the moving bodymind: Quantitative results from
a pilot study on the use of the bodymind approach (BMA) to psychotherapeutic group
work with patients with medically unexplained symptoms (MUS). Counselling & Psycho
therapy Research 10(4):295-306.
Peters, S., I. Stanley, M. Rose, S. Kaney, and P. Salmon. 2002. A randomized controlled trial
of group aerobic exercise in primary care patients with persistent, unexplained physical
symptoms. Family Practice 19(6):665-674.
Posse, M. 2004. Jungian psychotherapy for somatization. European Journal of Psychiatry
18:23-29.
Reineke, A. 2008. The effects of heart rate variability biofeedback in reducing blood pressure
for the treatment of essential hypertension. Dissertation Abstracts International: Section
B: The Sciences and Engineering 68(7-B):4880.
Rembold, S. M. E. 2011. Somatoform disorders in primary care settings: Construction and eval-
uation of a psychosocial group programme. Gruppenpsychotherapie und Gruppendynamik
47(1):2-21.
Reuber, M., C. Burness, S. Howlett, J. Brazier, and R. Grunewald. 2007. Tailored psycho-
therapy for patients with functional neurological symptoms: A pilot study. Journal of
Psychosomatic Research 63(6):625-632.
Rief, W., G. Bleichhardt, and B. Timmer. 2002. Group therapy for somatoform disorders:
Treatment guidelines, acceptance, and process quality. Verhaltenstherapie 12(3):183-191.
Rugg, S., C. Paterson, N. Britten, J. Bridges, and P. Griffiths. 2011. Traditional acupuncture
for people with medically unexplained symptoms: A longitudinal qualitative study of
patients’ experiences. British Journal of General Practice 61(587):e306-e315.
Russell, M. C. 2008. War-related medically unexplained symptoms, prevalence, and treatment:
Utilizing EMDR within the armed services. Journal of EMDR Practice and Research
2(3):212-225.
Saldanha, D., S. Chaudhury, A. A. Pawar, V. Ryali, and K. Srivastava. 2007. Reduction in
drug prescription using biofeedback relaxation in neurotic and psychosomatic disorders.
Medical Journal Armed Forces India 63(4):315-317.
OCR for page 91
TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 91
Sattel, H., C. Lahmann, H. Gundel, E. Guthrie, J. Kruse, M. Noll-Hussong, C. Ohmann, J.
Ronel, M. Sack, N. Sauer, G. Schneider, and P. Henningsen. 2012. Brief psychodynamic
interpersonal psychotherapy for patients with multisomatoform disorder: Randomised
controlled trial. British Journal of Psychiatry 200:60-67.
Sharpe, M., J. Walker, C. Williams, J. Stone, J. Cavanagh, G. Murray, I. Butcher, R. Duncan,
S. Smith, and A. Carson. 2011. Guided self-help for functional (psychogenic) symptoms:
A randomized controlled efficacy trial. Neurology 77(6):564-572.
Shea, B. J., J. M. Grimshaw, G. A. Wells, M. Boers, N. Andersson, C. Hamel, A. C. Porter, P.
Tugwell, D. Moher, and L. M. Bouter. 2007. Development of AMSTAR: A measurement
tool to assess the methodological quality of systematic reviews. BMC Medical Research
Methodology 7(10).
Strack, B., R. Gevirtz, and W. Sime. 2004. Effect of heart rate variability (HRV) biofeed-
back on batting performance in baseball. Applied Psychophysiology and Biofeedback
29(4):299.
Sumathipala, A. 2007. What is the evidence for the efficacy of treatments for somatoform
disorders? A critical review of previous intervention studies. Psychosomatic Medicine
69(9):889-900.
Sumathipala, A., S. Hewege, R. Hanwella, and A. H. Mann. 2000. Randomized controlled
trial of cognitive behaviour therapy for repeated consultations for medically unexplained
complaints: A feasibility study in Sri Lanka. Psychological Medicine 30(4):747-757.
Sumathipala, A., S. Siribaddana, M. Abeysingha, P. De Silva, M. Dewey, M. Prince, and A.
Mann. 2008. Cognitive-behavioural therapy v. structured care for medically unexplained
symptoms: Randomised controlled trial. British Journal of Psychiatry 193(1):51-59.
Tanis, C. 2008. The effects of heart rhythm variability biofeedback with emotional regula-
tion on the athletic performance of women collegiate volleyball players. Dissertation
Abstracts International: Section B: Sciences and Engineering 69(4-B):2666.
van Rood, Y. R., and C. de Roos. 2009. EMDR in the treatment of medically unexplained
symptoms: A systematic review. Journal of EMDR Practice and Research 3(4):248-263.
Volz, H. P., H. J. Moller, I. Reimann, and K. D. Stoll. 2000. Opipramol for the treatment of
somatoform disorders: Results from a placebo-controlled trial. European Neuropsycho-
pharmacology 10(3):211-217.
Volz, H. P., H. Murck, S. Kasper, and H. J. Moller. 2002. St. John’s wort extract (Li 160) in
somatoform disorders: Results of a placebo-controlled trial. Psychopharmacology (Berl)
164(3):294-300.
Yamada, K., R. Den, K. Ohnishi, and S. Kanba. 2005. Effectiveness of herbal medicine
(Kampo) and changes of quality of life in patients with somatoform disorders. Journal
of Clinical Psychopharmacology 25(2):199-201.
Zaby, A., J. Heider, and A. Schroder. 2008. Waiting, relaxation, or cognitive-hehavioral ther-
apy: How effective is outpatient group therapy for somatoform symptoms? Zeitschrift
für Klinische Psychologie und Psychotherapie 37(1):15-23.
OCR for page 92
