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J Neuropsychiatry Clin Neurosci 16:1, Winter 2004 19
Acupuncture Increases
Nocturnal Melatonin
Secretion and Reduces
Insomnia and Anxiety:
A Preliminary Report
D. Warren Spence, M.A.
Leonid Kayumov, Ph.D., DABSM
Adam Chen, Ph.D.
Alan Lowe, M.D.
Umesh Jain, M.D.
Martin A. Katzman, M.D.
Jianhua Shen, M.D.
Boris Perelman, Ph.D.
Colin M. Shapiro, MBBCh, Ph.D., FRCP(C)
Received April 16, 2002; revised September 13, 2002; accepted October
1, 2002. From the Centre for Addiction and Mental Health, Toronto,
Ontario; Sleep Research Laboratory, University Health Network, To-
ronto, Ontario; The Michener Institute for Applied Health Sciences,
Toronto, Ontario; St. Michael’s Hospital, Toronto, Ontario; Dept. of
Psychiatry, University of Toronto, Toronto, Ontario; Toronto Western
Research Institute, Toronto, Ontario. Address correspondence to Dr.
Kayumov, Sleep Research Laboratory, University Health Network,
ECW 3D-035, 399 Bathurst St. Toronto, Ontario M5T-2S8, lkayumov@
uhnres.utoronto.ca (E-mail).
Copyright 䉷 2004 American Psychiatric Publishing, Inc.
The response to acupuncture of 18 anxious adult
subjects who complained of insomnia was assessed
in an open prepost clinical trial study. Five weeks
of acupuncture treatment was associated with a
significant (p ⳱ 0.002) nocturnal increase in en-
dogenous melatonin secretion (as measured in
urine) and significant improvements in polysom-
nographic measures of sleep onset latency (p ⳱
0.003), arousal index (p ⳱ 0.001), total sleep
time (p ⳱ 0.001), and sleep efficiency (p ⳱
0.002). Significant reductions in state (p ⳱
0.049) and trait (p ⳱ 0.004) anxiety scores were
also found. These objective findings are consistent
with clinical reports of acupuncture’s relaxant
effects. Acupuncture treatment may be of value
for some categories of anxious patients with in-
somnia.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 2004; 16:19–28)
T
he incidence of insomnia is estimated to be 35% to
40% of the adult population. It currently affects
more than 60 million Americans, and this figure is ex-
pected to grow to 100 million by the middle of the 21st
century.
1,2
The defining characteristic of insomnia in the
context of anxiety is a pattern of multiple arousals from
sleep. Anxious subjects have difficulty maintaining
sleep, spend less time in deep sleep, and their sleep is
more fragmented than that of normal subjects.
3–5
Con-
versely, sleep deprivation may produce symptoms that
fall within the total complex of anxiety.
4
Although cur-
rent opinion suggests that insomnia and anxiety are
separate entities, their symptoms overlap considerably.
Individuals with insomnia and individuals with anxiety
have elevated psychosomatic profiles on psychological
tests,
6–8
maintain chronically high states of arousal, and
rely on an “internalizing” style of conflict resolution
20 J Neuropsychiatry Clin Neurosci 16:1, Winter 2004
ACUPUNCTURE, INSOMNIA, AND ANXIETY
(DSM-IV, 4th Edition).
9
These commonalities have
prompted speculation
10
that a common thread underlies
the conditions, although their exact relationship, namely
whether insomnia is the product of or simply a correlate
of anxiety, is still inconsistently viewed in current di-
agnostic systems (i.e., the ICD-10, DSM-IV and ICSD [In-
ternational Classification of Sleep Disorders]).
11
It is nev-
ertheless true that the dual diagnostic pattern of anxious
insomnia is the most commonly seen problem in sleep
disorder clinics today.
12
The high rate of comorbidity
between anxiety and insomnia, coupled with the high
population incidence of insomnia, undoubtedly account
for this phenomenon. Although we are unaware of any
epidemiological studies on the incidence of anxiety
which does not fulfill the criteria for a defined anxiety
disorder, it is reasonable to infer that a large segment of
the population may have “subsyndromal” anxiety,
symptoms that are not associated with debilitating psy-
chopathology, but which nevertheless produce a signifi-
cant degree of mental discomfort.
Traditional treatment strategies for anxious insomnia
have emphasized benzodiazepines. The useful anxio-
lytic effects of these agents have made them the most
widely prescribed of all pharmaceuticals.
13
The risks of
benzodiazepines, however, are well documented and in-
volve physical as well as psychological effects. These
include their potential to promote dependence or acute
toxicity in overdose.
14,15
Other adverse effects include
sedation, psychomotor and cognitive impairment,
memory loss, potentiation of other CNS depressants,
and treatment-emergent depression.
16
Acupuncture,
which relies on the release of neurally active agents from
endogenous stores, has been shown to have a superior
side effect profile compared to some psychoactive
drugs
17,18
and may thus represent a means for address-
ing the concerns about benzodiazepine therapy.
Evidence supporting acupuncture’s utility as a treat-
ment for insomnia has come from a variety of sources,
including the non-western scientific literature. Among
these, investigations by Nan and Qingming,
19
Jiarong,
20
and Cangliang
21
showed positive results. The shortcom-
ing of these studies, however, is that their dependent
measures have usually been inexact, relying mainly on
subjective accounts of sleep experience or duration, and
consequently, despite the consistency of their support
for acupuncture, they are difficult to evaluate. Several
European studies
22–24
used polysomnography to mea-
sure acupuncture effects on sleep disorders, but all
failed to monitor nocturnal neurochemical changes
which would have strengthened their experimental de-
sign.
It is known that stress mediation is multifactorial and
strongly influenced by GABAergic
25
and dopaminergic
neurotransmission.
26–27
The neurohormone melatonin
may also be involved in these effects. Melatonin is a
CNS depressant with anxiolytic,
28–29
mild hypnotic
30
and anticonvulsant actions
31
which may be related to its
enhancements of GABAergic
32–33
and striatal dopami-
nergic
34–35
transmission. The effect of melatonin on
mood and chronobiological functions has been estab-
lished in a number of studies. The pattern of melatonin
secretion over a 24-hour period is widely accepted as a
measure of circadian activity in humans.
36–37
This pat-
tern is disrupted in insomnia. Compared to normal pa-
tients, those with insomnia have suppressed nocturnal
outputs of melatonin
38–39
and are more likely to have
histories of depression.
40
As noted above, the anxiolytic
effects of melatonin have been recently established in
rodent models.
41–43
In humans, abnormalities in mela-
tonin secretion have been confirmed in patients with bi-
polar I disorder.
44
Taken together these findings support
the inference that melatonin deficiency may play a key
role in anxiety-associated insomnia.
Some evidence has also been provided that melatonin
interacts with the opioid peptides.
45–46
Melatonin is both
utilized and synthesized following acute pain episodes
in humans,
47
the function of which may be to modulate
fluctuations in opioid receptor expression and levels of
beta-endorphin.
48
The relationship of melatonin with
the opioidergic system is complex and not completely
understood, although there is evidence that it has mixed
opioid receptor agonist-antagonist activity.
49
In aggre-
gate these findings lend support to the postulate of a
“melatonin-opioid axis”
48
possibly serving a variety of
protectant functions.
Evidence of the endogenous opioid basis of acupunc-
ture analgesia has been supported both in human
50–51
and animal studies.
52–53
These have shown that acu-
puncture analgesia treatment increases CSF levels of
met-enkephalin, beta-endorphin, and dynorphin and can
be reversed by the opiate receptor blocker naloxone.
These findings are relevant to the present study inasmuch
as the opioids not only mediate analgesia they also play
a central role in subjectively experienced stress. In normal
human subjects plasma beta endorphin levels are in-
creased just before or after a stressful experience,
54–55
and are associated with feelings of euphoria that is re-
ported following, for example, bungee jumping.
56
In
J Neuropsychiatry Clin Neurosci 16:1, Winter 2004 21
SPENCE et al.
depressed patients elevated plasma beta endorphin lev-
els are positively correlated with severe stress and pho-
bia,
57
while anxious subjects show increases in beta en-
dorphin immediately before and after cognitive and
social stressors.
58
There is thus a reasonable basis for the
inference that acupuncture modulates anxious re-
sponses and that these effects are mediated by the en-
dogenous opioid system.
At the present time there have been only a few studies
of acupuncture’s effects on melatonin. In one of these
however
59
acupuncture was found to promote increases
in melatonin in the pineal, the hippocampus, and in se-
rum in rats.
The present study sought to use objective measures,
including an analysis of 24-hour melatonin levels in
urine, to evaluate acupuncture’s effects on insomnia and
anxiety. The hypotheses for this study were that a 5-
week regimen of acupuncture would promote statisti-
cally significant improvements in polysomnographic
markers of sleep quality, reduce anxiety (scores on the
STAI), and enhance endogenous melatonin production
in individuals scoring high on measures of anxiety and
insomnia.
METHODS
Eighteen adult volunteers served as subjects in the
study. To fulfill the inclusion criteria they had to report
having symptoms of insomnia for at least two continu-
ous years immediately prior to the study and to score
above 50 (anxiety range) on the Zung Anxiety Self Rat-
ing Scale. The Zung is a validated self-administered rat-
ing scale
60
employing a 20-item list of symptoms in a
Likert scale response format. The selected subjects had
symptoms of anxiety but did not fulfill DSM-IV criteria
for any particular anxiety disorder (i.e., their condition
was subsyndromal). Of the 18 subjects 11 were women
and 7 were men. All subjects were between the ages of
18 and 55. Their mean age was 39.0 Ⳳ 9.6 years. One
was of Chinese descent, two were black, and 15 were
Caucasian. Prior to participation in the study all had
heard of acupuncture and three reported having had
acupuncture treatment in the past for conditions unre-
lated to their sleep problems. In no instance did any of
the subjects have acupuncture treatment in the two
years prior to participation in the study. The subjects
were recruited through several sources, including news-
paper advertising, posters placed on hospital bulletin
boards, announcements made through the local chapter
of an independent sleep-wake disorders patient support
group, and occasional notices on a public service pro-
gram of a local television station.
An initial screening interview was carried out by a
psychiatrist or by an associate qualified in psychological
interviewing. A preliminary diagnosis for inclusion in
the study was made on the basis of the International
Classification of Sleep Disorders. The subjects had to re-
port having at least two symptoms of insomnia (frag-
mented sleep, frequent awakenings, early morning
awakenings followed by an inability to fall back to sleep,
feeling tired in the morning despite having spent a nor-
mal period of time in bed) for at least two years duration
and that this experience was not related to an obvious
environmental stressor. Potential participants with any
concurrent medical, psychological, or psychiatric factors
which might account for their sleep difficulties were ex-
cluded from the study. Other exclusion criteria were: a
history of shift work within five years prior to the study,
presence of other sleep disorders, age of less than 18 or
greater than 55, a history of alcohol or drug abuse, cur-
rent use of neurally active medications, or concurrently
undergoing psychotherapy. The study protocol was ap-
proved by the Human Ethics Committee of the Univer-
sity of Toronto, and written informed consent was ob-
tained from all participants after the procedures had
been fully explained. All subjects were asked to sign a
Committee-approved consent form confirming that they
understood the goals, risks, and potential benefits of the
study and their right to withdraw from the study at any
time.
The study investigated the use of traditional (symp-
tomatic) acupuncture without augmentation from
herbs, pharmaceuticals or hormonal agents. Concentra-
tions of a major melatonin metabolite 6-sulpha toxy-
melatonin (aMT6s) in urine were measured before and
after the study (as described below). This was to eval-
uate changes in the neurohormone as released from en-
dogenous sources (melatonin was not administered as an
experimental treatment). For each subject the trial was
conducted over a 7-week period during which the active
phase of acupuncture therapy was 5 weeks (two ses-
sions per week, 10 sessions in total). The acupuncture
was administered by a master acupuncturist (AC) who
was also the director of an acupuncture training pro-
gram and clinic. The acupuncture needles were dis-
posed of immediately after use and sterile technique
was strictly observed. Each acupuncture session lasted
22 J Neuropsychiatry Clin Neurosci 16:1, Winter 2004
ACUPUNCTURE, INSOMNIA, AND ANXIETY
FIGURE 1. Pre-post Experimental Design: Procedure and
Chronology
Pre-Experiment
Screening Interview
Day 1 (eve.)
before acupuncture
Day 2 (eve.)
before acupuncture
Day 1 (eve.)
after acupuncture
Day 2 (eve.)
after acupuncture
Baseline 5 weeks
Post Tx.
Measures
Acupuncture
treatment
(2 x per week
for 5 weeks)
Polysomno-
graphy
Polysomno-
graphy
Psychometric
testing
Psychometric
testing
Urine
collection
(24 hr.
melatonin)
Urine
collection
(24 hr.
melatonin)
approximately one hour. During the 1-week period pre-
ceding and following the active treatment phase, sub-
jects were tested with polysomnography at an admin-
istratively convenient time in the Sleep Research
Laboratory of the University Health Network, Toronto
Western Hospital site. Figure 1 illustrates the design of
the study.
Two consecutive overnight polysomnographic stud-
ies were performed at baseline (before treatment) and at
the end of the 5 weeks of treatment with acupuncture.
Polysomnographic results obtained on the first night
during the before and after stages of the experiment
were not included in the analysis to avoid a possible
“first-night” effect.
61
The sleep parameters included the
sleep latency, sleep efficiency, the total sleep time, the
arousal index, the percentage of REM sleep and REM
latency, and the amount of time spent in stages 1
through 4. Additionally data were collected on the Al-
pha rating, an evaluative index of sleep quality
62
which
included an assessment of sleep fragmentation. For the
baseline recordings, subjects chose their own retiring
and wake up times as was consistent with their normal
routine. Just before retiring on the second night of po-
lysomnographic testing subjects were also asked to fill
out several paper and pencil tests of mood and cognitive
efficiency. These included the Toronto Alexithymia
Scale,
63
a standard pre-sleep questionnaire; the Stanford
Sleepiness Scale (SSS)
64
; and a seven-item Fatigue Scale.
Additionally they were asked to fill out the State-Trait
Anxiety Inventory
65
to gauge the effect of acupuncture
on anxiety. The Center for Epidemiological Studies De-
pression Scale (CES-D)
66
was used to assess the presence
of depressive symptoms.
On the following morning, immediately after awak-
ening, each subject completed a standard post-sleep
questionnaire, the SSS, and the Fatigue Scale. Approxi-
mately 20 minutes after awakening, subjects assessed
their level of fatigue and sleepiness using the following
scales: the Fatigue Severity Scale, the Epworth Sleepi-
ness Scale,
67
the Toronto Western Hospital Fatigue Ques-
tionnaire, the Fatigue Scale, and the FaST Adjective
Checklist. The results from testing were consolidated to
form a composite fatigue score (comfatigue), which has
been validated in studies on patients with multiple scle-
rosis.
68
After completing the fatigue questionnaires, the sub-
jects were asked to complete a complex verbal reasoning
task.
69
Accuracy and time to complete the test were as-
sessed.
During both the pre- and posttest assessment phases
urine samples were collected and the concentration
changes of aMT6s (which reflects the changes in endog-
enous levels of melatonin) were subsequently measured
with a commercially available competitive immunoas-
say ELISA kit (Buhlmann Laboratories AG, Allschwil,
Switzerland). At aMT6s concentrations 2.0 and 12.5 ng/
ml the intraassay coefficients of variation were 5.5% and
3.5%; at concentrations 5.0 and 40.0 ng/ml the inter-
assay coefficients of variation were 0.7% and 9.7%. As
discussed above, the pattern of melatonin secretion has
been widely accepted as a measure of circadian activity
in humans,
36,37
and there is further evidence of de-
creases in melatonin output in patients suffering from
insomnia.
39,40,70
Statistical Analysis
The results of the polysomnographic recordings and
psychometric testing were compared on a before and
after basis for all subjects and are shown here as mean
scores. The matched pairs t test was used to assess the
statistical significance of these changes. The melatonin
analysis was treated as a “two within-subjects variables
experiment,” a type of multiple repeated measures test,
where the two within-subject factors were (a) “time of
day” and (b) “phase of the experiment” (i.e., before or
after the experiment). These comparisons were carried
out using the Statistical Package for the Social Sciences
software (SPSS for Windows). The null hypothesis was
J Neuropsychiatry Clin Neurosci 16:1, Winter 2004 23
SPENCE et al.
TABLE 1. Sleep Polysomnographic Variables During a 7-Week
Study of Subjects With Insomnia and Anxiety
Symptoms: Results at Baseline and After 5 Weeks of
Acupuncture Treatment (N ⴔ 18)
Sleep Variable Mean
Mean
Difference SD
Sig
(2 tailed)
Sleep Continuity
Sleep onset latency
Before tx 28.6 8.9 10.8 0.003
After tx 19.7
Total sleep time
Before tx 5.1 ⳮ1.4 1.1 0.001
After tx 6.5
Sleep efficiency
Before tx 76.1 ⳮ12.1 14.7 0.002
After tx 88.6
Alpha Index
Before tx 2.2 0.4 0.7 0.017
After tx 1.8
Arousal Index
Before tx 14.3 8.1 6.6 0.001
After tx 6.17
Sleep Architecture (%)
Stage 1
Before tx 7.4 0.7 4.3 NS
After tx 6.7
Stage 2
Before tx 46.0 ⳮ6.1 14.3 NS
After tx 52.1
Stage 3
Before tx 4.2 ⳮ1.9 3.2 0.023
After tx 6.1
Stage 4
Before tx 3.0 ⳮ1.3 3.4 NS
After tx 4.5
REM sleep
REM percentage
Before tx 17.3 ⳮ1.9 4.8 NS
After tx 19.2
REM latency
Before tx 77.1 ⳮ4.3 61.3 NS
After tx 81.4
rejected if the differences were significant at the 5%
level.
RESULTS
The major objective and subjective measures obtained
in the before and after stages of the experiment are dis-
played separately for convenience in Table 1 and Table
2. Objective measures (i.e., the polysomnographic re-
cordings) are separated into three categories: sleep con-
tinuity, sleep architecture, and REM sleep, as shown in
Table 1. The subjective variables, based on self-report
questionnaires and performance tests, are separately
identified in Table 2. The means, their differences, stan-
dard deviations, and two-tailed significance levels are
also shown for each sleep and test variable.
Sleep Duration and Sleep Quality Variables
The acupuncture treatment used in this study improved
several polysomnographic parameters of sleep architec-
ture. Among the sleep continuity variables, sleep onset
latency (SOL) and the arousal index dropped signifi-
cantly (p ⳱ 0.003 and p ⳱ 0.001, respectively), reflecting
improvements in both sleep initiation and maintenance.
The total sleep time (TST) and sleep efficiency similarly
increased (p ⳱ 0.001 and p ⳱ 0.002, respectively). The
Alpha index also improved significantly (p ⳱ 0.017).
Some improvement in sleep quality was confirmed by
the increase in the amount of time spent in stage three
(slow wave) sleep (p ⳱ 0.023), but the amount of time
spent in stage four sleep did not significantly change in
the before-after comparison. The percentage of REM
sleep and REM sleep latency, as well as the amount of
time spent in stages one and two sleep remained un-
changed following acupuncture.
Subjective Variables: Psychological Factors, Sleepiness,
Fatigue, and Alertness
As shown in Table 2, both state and trait anxiety scores
significantly improved (p ⳱ 0.049 and p ⳱ 0.004, re-
spectively) following acupuncture. Additionally, scores
on the CES-D showed significant improvements (p ⳱
0.001). Scores on the Alexithymia Scale did not change
significantly.
Scores on the Stanford Sleepiness Scale (SSS) indi-
cated no significant differences (in the before and after
comparison) when the test was administered just before
the second night of sleep, but did show significant im-
provements (p ⳱ 0.019) when subjects were asked to
report on their subjective sleepiness in the morning after
the second night of sleep. The Fatigue Scale scores re-
vealed a somewhat similar profile, with scores before
sleep not showing any significant differences, but scores
on the following morning indicated a significant im-
provement (p ⳱ 0.045) after 5 weeks of acupuncture.
The improvement in fatigue scores were not paralleled
by increases in alertness however: the ZOGIM-A, a test
which measures alertness, indicated that the subjects felt
significantly (p ⳱ 0.004) less alert following acupunc-
ture. The composite fatigue scores (comfatigue) did not
indicate any significant change. The timed test of cog-
nitive skill indicated that subjects were able to perform
the test more quickly (p ⳱ 0.001) following acupuncture,
but the performance accuracy, while showing a small
improvement, was not statistically significant.
24 J Neuropsychiatry Clin Neurosci 16:1, Winter 2004
ACUPUNCTURE, INSOMNIA, AND ANXIETY
TABLE 2. Assessment of Psychological Factors and Sleepiness, Fatigue, and Alertness: Results at Baseline and After 5 Weeks of
Acupuncture Treatment (N ⴔ 18)
Test Variable Mean Mean Difference SD Sig (2 tailed)
Psychometric
State Anxiety
Before tx 86.0 16.9 31.5 0.049
After tx 66.0
Trait Anxiety
Before tx 93.0 20.1 23.7 0.004
After tx 72.0
CESD Depression Inventory
Before tx 26.3 12.1 7.4 0.001
After tx 14.2
Toronto Alexithymia Scale
Before tx 49.8 0.6 8.2 NS
After tx 49.3
Sleepiness, Fatigue, and Alertness
ZOGIM-A
Before tx 36.1 6.3 8.0 0.004
After tx 29.78
Fatigue Scale Before Sleep
Before tx 2.9 ⳮ0.6 1.9 NS
After tx 3.5
Fatigue Scale After Sleep
Before tx 3.4 0.9 1.7 0.045
After tx 2.6
Stanford Sleepiness Scale
Evening, before sleep 3.0 ⳮ0.6 1.5 NS
Before treatment
Evening, before sleep 3.5
After treatment
Morning, after sleep, before treatment 3.1 0.9 1.5 0.019
Morning, after sleep, after treatment 2.2
Comfatigue
Before tx 10.5 0.3 3.4 NS
After tx 10.2
Performance Time
Before tx 5.1 2.0 1.8 0.001
After tx 3.2
Performance Accuracy
Before tx 72.7 ⳮ6.8 19.6 NS
After tx 79.5
6-Sulphatoxymelatonin Analysis
Urine analysis showed that nocturnal physiological
levels of aMT6s increased following acupuncture and
decreased during the morning and early afternoon
(Figure 2).
Analysis of the main effects showed a significant (p ⳱
0.001) interaction between the two variables “time of
day” (representing the four measurement periods 9 p.m.
to midnight; midnight to 8 a.m.; 8 a.m. to 3 p.m. and 3
p.m. to 9 p.m.) and “phase of the experiment” (before
versus after acupuncture), thus supporting the validity
of individual time period comparisons on a pre- and
post-treatment basis. No detectable changes (in urinary
concentrations of aMT6s) were found for pairwise com-
parisons of periods 1 and 4 (9 p.m. to midnight, and 3
p.m. to 9 p.m.). Differences for periods 2 (midnight to 8
a.m.) and 3 (8 a.m. to 3 p.m.) however were significant
(p ⳱ 0.002 and p ⳱ 0.037) reflecting postacupuncture
increases in melatonin production at night and de-
creases during the morning and afternoon.
DISCUSSION
Our initial hypotheses were confirmed by the results of
the present investigation. In an open clinical trial of 18
subjects, the administration of 5 weeks of acupuncture,
totaling ten treatment sessions, was associated with nor-
malization in a 24-hour profile of urinary aMT6s and a
number of objectively measured improvements in sleep
continuity and sleep architecture. Additionally, signifi-
cant improvements in self-reported fatigue and sleepi-
ness paralleled these changes. The exception to this
trend was the reduction in alertness as measured by the
J Neuropsychiatry Clin Neurosci 16:1, Winter 2004 25
SPENCE et al.
FIGURE 2. Urinary concentrations of the melatonin metabolite 6-
sulphatoxymelatonin (aMT6s) over a 24 hour cycle:
comparison of baseline vs. post acupuncture
treatment. The line graph indicates a statistically
significant elevation (p ⴔ .002) of the metabolite in
urine at night (Midnight-8am) and a significant
decrease (p ⴔ .037) during the day (8am–3pm).
U
r
i
n
a
r
y
a
M
T
6
s
i
n
N
m
o
l
.
T
i
m
e
o
f
D
a
y
40
30
20
10
0
9pm–
Midnight
Midnight–
8am
8am–
3pm
3pm
–
9pm
After treatment
Before treatment
ZOGIM-A test. As discussed below the apparent incon-
sistency of reduced alertness following improvements
in sleep quality may possibly have been the result of a
transition into a more adaptive and qualitatively differ-
ent type of alertness. Self assessed feelings of anxiety
and depression decreased following acupuncture. These
findings are fairly consistent with the results of previous
investigations showing that acupuncture has a gener-
alized anxiolytic effect,
71–73
and with other polysomno-
graphic studies of acupuncture effects in insomnia.
22–24
The findings of nocturnal elevations in urinary
aMT6s, indicating increased melatonin secretion, par-
alleled these changes. Melatonin regulates the rhythm
of many functions and alterations in its secretory pattern
have been found in a number of psychiatric disorders.
These have included seasonal affective disorder, bipolar
disorder, unipolar depression, bulimia, anorexia, schizo-
phrenia, panic disorder, and obsessive-compulsive dis-
order,
74
but at present it has not been confirmed if these
changes are causal to or simply a marker of other neu-
rochemical dysfunctionalities. Further, it is not known
if melatonin is equally involved in the development of
the pathophysiology of each of these disorders. Due to
practical limitations we were able to investigate changes
in only one neurally active agent, but clearly it would
have been desirable to study acupuncture’s effects on a
range of neurotransmitters which are known to be
closely linked to the etiology of anxiety or insomnia.
Dysregulation of catecholamine secretion for instance
has circadian variations which correlate closely with
pathological anxiety states
75
and moreover have been
shown to be regulated by melatonin injections.
76
Our
findings thus raise intriguing questions about the nature
and course of acupuncture effects at the neurochemical
level. Studies are needed to further elucidate the role of
norepinephrine as well as that of serotonin, dopamine,
GABA in the changes we observed in melatonin secre-
tion.
The results for the sleep architecture measurements
showed no increases in the percentage of time spent in
stages one or two, findings which have doubtful rele-
vance for this clinical sample. Large improvements were
seen however in the subjects’ transition to stage three or
slow wave sleep, reflective of significant gains in the
quality of their sleep. A wide variability of responses in
this observation reduced the significance level to p ⳱
0.023. The percent of stage three sleep increased from a
mean of 4.2% before treatment to a mean of 6.1% follow-
ing treatment, closely approximating the normal mean
of 7%. There was considerable variability in the amount
of time spent in stage four sleep, with a number of sub-
jects showing no improvement at all, thus accounting
for the lack of statistical significance. The variability in
responsiveness to acupuncture seen in, for instance, acu-
puncture analgesia treatment
77
has been known clini-
cally and in scientific studies for some time. Although
this variability has not been satisfactorily accounted for,
one hypothesis is that psychological factors may be an
impediment to treatment effectiveness. This is consistent
with the findings of Widerstrom-Noga
78
and Creamer
79
showing that trait anxiety (measured by the STAI) can
interfere with the effectiveness of acupuncture analgesia
treatment. In this context our findings that, despite the
variability of response, acupuncture improved overall
sleep quality and had significant effects on anxiety are
therefore noteworthy. The possibility that extreme scor-
ers on trait anxiety are poor treatment candidates, or
perhaps require additional treatment to show measur-
able changes, needs to be explored further with a sample
that is larger than the one used in the present study.
In the present study subjects were screened to exclude
those with clinical levels of psychopathology, including
26 J Neuropsychiatry Clin Neurosci 16:1, Winter 2004
ACUPUNCTURE, INSOMNIA, AND ANXIETY
depression. Nevertheless a number of subjects showed
elevated scores on the CES-D (depression) scale. This is
in accordance with other findings showing that patients
with insomnia may have symptoms of anxiety or de-
pression which do not meet criteria for a specific mental
disorder (DSM-IV, 4th Edition).
9
In fact, symptom co-
occurrence of anxiety and depression frequently exists
in non-clinical samples which do not show serious sleep
disturbance.
80
These symptoms were nevertheless re-
duced by acupuncture and are consistent with previous
reports of acupuncture’s effectiveness in treating mood
disorders.
81–82
A finding that merits closer examination is the appar-
ent lack of consistency implied in the failure of improve-
ments in sleep quality to be accompanied by increasing
alertness during the day. In our sample daytime alert-
ness, as evaluated by self assessments or indirectly
through measures of performance accuracy, either be-
came worse or showed no improvement even though
sleep quality was enhanced. Generally there is a positive
correlation between tests of sleepiness (such as the Mul-
tiple Sleep Latency Test or MSLT) and daytime alertness
(e.g., the Maintenance of Wakefulness Test, the MWT)
(i.e., the better the nighttime sleep the greater the alert-
ness during the day). In depressed patients however a
negative relationship between the two tests is some-
times found.
83
Kayumov et al.
84
investigated this phe-
nomenon in clinically depressed patients who also
scored high on anxiety measures. In the depressed
group the sleep latency on the MWT showed paradox-
ical increases (i.e., was reflective of alertness) in concor-
dance with the severity of sleep disturbance, whereas in
the non-depressed group this did not occur. Our own
findings are consistent with these previous studies and
support the view
84
that in depressed or anxious subjects
the underlying factors which cause sleep disturbance
will also produce heightened alertness during the day.
This view emphasizes that qualitative differences exist
in the “adaptive” alertness of non-anxious subjects,
which is mobilized by relevant environmental stressors,
and the accentuated or “vigilant” alertness of individ-
uals suffering from excess emotional tension. In this
group alertness is chronic and preferentially driven by
internal rather than environmental demands, thus con-
ferring to it a more invariant and non-discriminatory
quality. Our finding therefore that alertness actually de-
creased following acupuncture may imply the substi-
tution of one type of alertness for another rather than
representing a decrement in cognitive efficiency. This
possibility needs to be explored with testing instruments
which are sensitive to these differences.
In this preliminary study acupuncture was shown to
be of value as a therapeutic intervention for insomnia in
anxious subjects and may therefore represent an alter-
native to pharmaceutical therapy for some categories of
patients. Further, the central role attributed by classical
and modern theories of personality to anxiety as the ba-
sis of most psychological defense mechanisms,
85,86
as
well as the evidence that abnormalities in melatonin se-
cretion are involved in a number of psychiatric condi-
tions,
74
suggest that acupuncture may have broad ap-
plicability to other types of psychopathology in which
quality of sleep is impaired. An important shortcoming
of this study however was its lack of a control group
with a placebo acupuncture condition. The findings
therefore need to be confirmed with a study employing
a more rigorous design.
The authors gratefully acknowledge the help of Dr. Raed J.
Hawa of the Department of Psychiatry, University Health
Network, Toronto, Ontario, in interviewing and screening pa-
tients and for his thoughtful suggestions in reviewing the
manuscript.
This investigation was supported by REST Foundation,
Scotland
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