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Neuropsychobioiogy 13:111-116 (1985)
©1985 S. Karger AG, Basel
0302-282X/85/0135-0! 11$2.75/0
Periodic Sleep Deprivation in Drug-Refractory Depression
M. Dessauer, U. Goetze, R. Tolle
Clinic of Psychiatry, University of Münster, FRG
Key Words. Depression • Drug-refractory depression • Sleep deprivation • Circadian rhythm
After the antidepressive effect of sleep deprivation
[PJlug and Tolle, 1969, 1971] had been confirmed by a
large number of worldwide investigations, questions
emerged for further research as to the practicability of the
method, the individual indications and the duration of
the effect.
The practicability was improved by way of introduc­
ing partial sleep deprivation in the second half of the
night in lieu of total sleep deprivation [Schilgen and
Tolle, 1980], the former producing at least as good a ther­
apeutic effect, being easier for the patient to carry out
and, in particular, allowing administration on an outpa­
tient basis. In comparison, sleep deprivation in the first
half of the night [Goetze and Tolle, 1981] is less effective
therapeutically, and selective REM sleep deprivation
[Vogel etal., 1968; Vogel, 1981] is impracticable outside
elaborate sleep laboratories. The course of sleep depriva­
tion for 1 night can be made easier for the patient by
various measures [Rudolfand Tolle, 1978a], in particular.
it has been proved useful to allow patients to stay awake
in groups [Richard et al„ 1982],
The indications are meanwhile widely known: pri­
marily endogenous depressions (melancholias) in both
early and late onset forms, monopolar and bipolar de­
pressions, at the onset of the phase and in its later course
[Rudolf et al., 1977; Rudolf and Tolle, 1978b]. The effect
of sleep deprivation on neurotic depressions [Rudolf and
Tolle, 1978b] and on depressive states in schizophrenics
[Fahndrich, 1981] is relatively less pronounced and less
reliable. There are no contraindications to this method,
which is free of side-effects. Sleep disturbance and diur­
nal variations are predictive factors in endogenous de­
pression, particularly the common occurrence of these
features [Rudolf and Tolle, 1978b].
The efficacy of total or partial sleep deprivation for a
single night remains nevertheless limited in time. No
doubt, an extensive remission or even cure occurs (occa­
sionally in the form of a sudden swing to hypomania) in a
small section of the patients. In the majority of patients
partial relapse occurs, however, even after a good initial
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Abstract. For some time it has been known that total and partial sleep deprivation (in the second half of the night)
produces an immediate antidepressive effect and a short-term effect of approximately 1-week duration. A 25-day trial
is discussed here. 18 endogenous depressives who proved to be refractory to tricyclic antidepressive therapy were
treated with periodic sleep deprivation (5 sleep deprivation treatments in the second half of the night at 5-day inter­
vals) under continued drug therapy. The combined treatment led to a better result than would have been expected
from drug therapy alone. Some of the sleep deprivation treatments effected an accelerated remission without the
efficacy of treatment subsiding. In individual cases recovery occurred after one or a few partial sleep deprivation
sessions. Whether in other respects sleep deprivation shortens the course of depressive phases is still unproven.
Methodological Deliberations
A crossover trial is difficult to carry out if one wants to
test combined antidepressants and sleep deprivation
against antidepressants alone. Two treatment periods of
several weeks’ duration often exceed the hospital inpa­
tient stay; autonomous trend, spontaneous remission and
more favorable response to therapy in the later treatment
stage are difficult to supervise; in addition, a ‘drugs only’
period which is preceded by a sleep deprivation period is
not comparable with a drugs period without this precon­
dition. Our pertinent trials (unpublished) showed that
crossover findings with and without sleep deprivation are
difficult to interpret. On the other hand methodological
problems arise in a group statistical procedure. It proved
to be extremely difficult to establish a homogeneous con­
trol group without sleep deprivation. Numerous patients
came to the clinic undoubtedly because of the sleep depri­
vation therapy after a protracted course and numerous
prior treatments (see below). These were to a large extent
so-called therapy-resistant depressives who, because of
the services offered in the region, were admitted here
with preference. In the majority of these patients their
expectations, those of their relatives and referring doctors
and also therapeutical-ethical considerations ruled out
the omission of sleep deprivation therapy, or its neglect,
as a criterion for allocating them to a control group. For
this reason another method for this examination had to
be found.
Numerous investigations [summarized by Woggon,
1983] have shown that in drug-refractory depression the
prognosis becomes more unfavorable with increasing
numbers of phases. The degree of severity is not a predictor
for a refractory therapeutic course. The prevailing duration
of the phase probably correlates with a much more unfa­
vorable course [Rush et al., 1983], In addition, the number
and type of prior treatments in the current phase are
referred to here as criteria for a drug-refractory course. All
the parameters listed do not furnish an absolute scale but
allow a group-statistical comparison (see below).
Does additional sleep deprivation speed up remission
in a drug-refractory course? In order to examine this,
homogeneous groups with and without sleep deprivation
are not compared here (see above) but groups of patients
with varying therapeutic prospects. On continuation of
drug therapy alone it would be expected that the result of
treatment in the group of drug-refractory patients after an
examination period of 25 days would be less favorable
than in the remainder of the patients. The question now
is whether even after additional sleep deprivation therapy
this more unfavorable result is noted. A slightly worse,
almost equivalent treatment result would already speak
for the effectivity of sleep deprivation.
As sleep deprivation is administered here repeatedly
in periodical sequence, the following is examined: Does
sleep deprivation on average retain a constant effectivity
even on repealed application or does an ‘attritive effect'
set in?
The random test comprises 32 endogenous depressives during
inpatient treatment. 3 patients are not taken into account (see below
for reasons).
The diagnostic classification (ICD 9: 296, 1 and 3) was done on
the basis of the characteristic criteria of course and symptomatology
as in our earlier examinations. All patients were under current treat­
ment with tricyclic antidepressants. Table I gives further informa­
tion. The patients were not discriminated with regard to the degree of
severity of depression but according to their response to drug treat­
ment (see above). Table 11 shows that in the group with supplemen­
tary sleep deprivation treatment the number of previous phases was
greater, the duration of the present phase longer and the number of
prior treatments by far greater.
Examination Instruments
Bojanovsky and Chloupkova's [ 1966] rating scale was used to eval­
uate the depression symptomatology. The assessment was undertaken
by one examiner. The items relation to sleep and diurnal variations
were not employed in this trial, nor were the infrequent items 19, 20
and 21 taken into account. The self-assessment of the depth of depres­
sion was undertaken by the patients using Luria's [1975] analogue
mood scale, whose poles were formulated as follows: ‘I have never
been so depressed as I am now’ and ‘I am not depressed now’.
Treatment Measures and Trial Sequence
All patients received tricyclic antidepressants, three quarters of
them amitriptyline. The period of examination was 25 days. One of
the two groups was treated in addition with 5 partial sleep depriva­
tions (second half of the night from 01.30 h) at intervals of 5
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response, often as soon as a day to up to a week later. Two
conclusions were drawn from this: sleep deprivation is
generally combined nowadays with antidepressive medi­
cation; sleep deprivation is repeatedly administered on
the assumption that the therapeutic course of endogenous
depressions can hereby be speeded up. This appears to be
particularly important with regard to drug-refractory de­
Periodic Sleep Deprivation in Drug-Refractory Depression
Table I. Patients: 32 endogenous depressives
Endogenous depressives treated with
Antidepressant drugs
Antidepressant drugs and sleep deprivation
Mean age
Early onset
Late onset
Unipolar Bipolar
Table II. Previous course
Endogenous depressives treated with
Duration of
these phases
Prior treatments
in hospital
in outpatient
Antidepressant drugs
Antidepressant drugs and sleep deprivation
*p < 0.01.
At the end of the 25-day examination period (table III)
a remarkable remission is recorded in the ‘drugs only’
group, which is expressed in a decrease in the depression
index and in a positive self-rating (recognizable by further
figures). In the 'plus sleep deprivation’ group an equally
marked remission occurred (with practically the same or
approximate initial values). This can be evaluated as an
indication of the therapeutic efficacy of additional sleep
deprivation in previous drug-refractory depressions in
accordance with our initial hypothesis.
The individual presentation of therapeutic results
should begin with those patients in whom the trial had to
be stopped prematurely (fig. 1). In 2 patients the depres­
sion had remitted completely after 2 to 3 sleep depriva­
tion treatments, in 1 it had almost remitted, so that
Table III. Treatment results after 25 days
Day 0
Day 25
Treatment with antidepressant drugs (n = 14)
Depression rating
Treatment with antidepressant drugs and sleep deprivation (n = 18)
Depression rating
depression scales could no longer be employed. In 1
patient there was a sudden swing to hypomania. Thus in
4 cases there was an optimum therapeutic result in the
treatment of the depression, while in another patient it
occurred towards the end of the examination period.
In the case of 3 patients whose trial was discontinued
at the outset, 1 exhibited complete remission subsequent
to the first sleep deprivation, another almost complete
remission, in yet another patient there was a sudden
swing to hypomania.
These very favorable treatment courses are contrasted
with 2 extremely unfavorable ones: 1 patient’s condition
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Self-rating and depression rating were carried out in the ‘drugs
only'group on daysO. 5, 10, 20, 25 and in the ‘plus sleep deprivation’
group additionally on days 1,6, 11, 16,21 (fig. 2) in order to include
the depression symptomatology before and after sleep deprivation,
namely, at 08.00 h in the morning. Sleep deprivation was carried out
in the same manner as previously described [Rudolf and Tolle.
1978a; Schilgen and Tolle, 1980],
deteriorated to such an extent at the beginning that the
trial could not be carried out (see above); in 1 patient (E
in fig. 1) deterioration and discontinuation of therapy
occurred in the course of the examination.
To sum up it is established that recovery or almost full
freedom from symptoms occurred in 7 out of 21 drugrefractory depressives. In contrast, deterioration occurred
twice at the outset of the sleep deprivation period.
The results of additional sleep deprivation therapy in
the remainder of the patients who were examined up to
the 25th day are represented as a mean value curve
(fig. 2). The scalariform curve reveals that every sleep
deprivation effects a remission. This trend is no longer
marked in the second half of the trial period on self­
rating, as quantification by means of self-rating [Prusojf
et al., 1972] is more difficult to achieve.
The scalariform remission curve infers that the effects
of sleep deprivation do not wane but remain constant
even on repeated applications. Appropriate statistical cal­
culations (not given here in detail) showed no significant
difference between the second to fourth sleep deprivation
and the first one.
Fig. 2. Course of therapy of endogenous depressives treated with
antidepressive medication and sleep deprivations (t): 5 patients who
finished the examination early: A = Cured; B = cured; C = improved;
D = changed into hypomania, then into mania; E = attempted sui­
cide. a Depression rating; Bojanovsky scale, b Self-rating; analogue
Treatment with periodically administered sleep depri­
vation in combination with antidepressant medication is
of use even in drug-refractory endogenous depressions.
This corresponds to the empirical data of Van Scheyen
[1977], who treated 19 patients with total sleep depriva­
tion for 1 night after unsatisfactory antidepressive ther­
apy and recorded a success in 13 cases. Even in patients
who were refractory to a combination of antidepressants
and electroconvulsive therapy (ECT) a favorable sleep
deprivation effect was achieved by Van Scheyen in 7 out
of 13 cases. Among Bhanji and Roy’s [1975] patients, of
whom more than half had reacted well to repeated total
sleep deprivation at least temporarily, there were depres­
sives with long-standing illness and prior treatment with
various antidepressive agents and ECT (a quarter were
therapy-refractory). On the other hand, it was established
that after unsuccessful sleep deprivation treatment,
though only after a solitary application, subsequent ECT
can be effective [Larsen et al., 1976; Kvist and Kirkegaard, 1980],
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Fig. 1. Course of therapy during 25 days of endogenous depres­
sives (n = 15) treated with antidepressive medication and sleep depri­
vations (T): means of the depression and self-rating.
Periodic Sleep Deprivation in Drug-Refractory Depression
drich [1981] as also Richard et al. [1982] obtained incon­
stant results on repeated sleep deprivation, without the
average efficacy abating. Only Pflug [1978] confirmed
that after a very effective initial treatment (much more
favorable results being recorded than elsewhere in the lit­
erature) the effectivity abated in the 3 subsequent sleep
deprivation treatments.
On the basis of the findings to date it is concluded that
sleep deprivation accelerates remission of drug-treated
endogenous depressions. In individual cases sleep depri­
vation produces asymptomatology, to some extent a sta­
ble recovery. Whether in other respects a phasic shorten­
ing can be achieved through sleep deprivation must be
clarified by further studies.
Bhanji, S.; Roy, G.A.: The treatment of psychotic depression by sleep
deprivation: a replication sludy. Br. J. Psychiat. 127: 222-226
(1975) .
Bojanovsky, J.; Chloupkova, K.: Bewertungsskala der Depressions­
zustände. Psychiatria Neurol. 151: 54-61 (1966).
Elsenga, S.; van den Hoofdakker, R.H.: Sleep deprivation and clom­
ipramine in endogenous depression; in Popoviciu, Asigan, Sleep
1978. Fourth Eur. Congr. Sleep Res., pp. 625-628 (Karger, Basel
Fähndrich, E.: Effects of sleep deprivation on depressed patients of
different nosological groups. Psychiatry Res. 5: 277-285 (1981).
Goetze, U.; Tolle, R.: Antidepressive Wirkung des partiellen Schlaf­
entzuges während der 1. Hälfte der Nacht. Psychiatria clin. 14:
129-149 (1981).
Kvist, J.; Kirkegaard, C : Effect of repeated sleep deprivation on
clinical symptoms and the TRH test in endogenous depression.
Acta psychiat. scand. 62: 494-502 (1980).
Larsen, J.K.; Lindberg, M.L., et al.: Sleep deprivation as treatment
for endogenous depression. Acta psychiat. scand. 54: 167-173
(1976) .
Loosen, P.; Merkel, U., et al.: Kombinierte Schlafentzugs-AnafranilBehandlung endogener Depressionen. Arzneimittel-Forsch. 26:
1177-1178 (1976).
Luria. R.E.: The validity and reliability of the visual analogue mood
scale. J. psychiat. Res. 12: 51-57 (1975).
Pflug, B.: The effect of sleep deprivation on depressed patients. Acta
psychiat. scand. 53: 148-158 (1976).
Pflug, B.: The influence of sleep deprivation on the duration of
endogenous depressive episodes. Arch. Psychiat. NervKrankh.
225: 173-177 (1978).
Pflug, B.; Tolle, R.: Die Behandlung endogener Depressionen durch
Schlafentzug. Zentbl. Neurochir. 196: 7 (1969).
Pflug, B.; Tolle, R.: Therapie endogener Depressionen durch Schlaf­
entzug. Nervenarzt 42: 117-124 (1971).
Philipp. M.: Deprcssionsverlauf nach Schlafentzug. Nervenarzt 49:
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Psychiat. 26: 546-552 (1972).
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It must be emphasized that in a section of the patients
thus treated recovery occurred. This fraction is appar­
ently greater in drug-refractory depressions than in nonselected random tests, for which only a few such favor­
able courses are reported in the literature. Even in an
earlier random test by the authors (patients treated like­
wise with partial sleep deprivation) the extremely posi­
tive as well as extremely negative therapeutic results were
rare, whereas partial improvement (by about 40-60% of
the initial rating of depression symptomatology) was
more frequent than in this group of drug-refractory depressives.
The combination of antidepressives with sleep depri­
vation is universally recommended. Sleep deprivation
treatment on its own is, on the contrary, inferior to antidepressive drug therapy, even in blind trials with concur­
rent placebos instead of antidepressive drugs [Elsenga
and van den Hoofdakker, 1980], This also applies to cure
by sleep deprivation: without further drug therapy [ac­
cording to Kvist and Kirkegaard. 1980] a relapse occurs in
the majority of cases within 2-20 weeks.
Repeated sleep deprivation is a worthwhile therapy.
There are few reliable reports on the frequency of admin­
istration. Several authors recommend sleep deprivation
twice a week [Svendsen, 1976; Larsen et al., 1976; Wasik
and Puchala, 1978; Elsenga and van den Hoofdakker,
1980; Kvist and Kirkegaard, 1980], without this fre­
quency having been compared with the effects of other
The duration of the effectiveness of each sleep depri­
vation can furnish the criterion for determining the opti­
mum frequency. It varies admittedly interindividually,
but the apprised mean values are relatively uniform. In
the case of concurrent treatment with antidepressives the
immediate effect of sleep deprivation is manifest for sev­
eral days up to a week [Loosen et al., 1976; Philipp, 1978;
Goelze and Tolle, 1981]. We therefore chose 5-day inter­
vals for this study. In less severe depressions a greater
interval is justified. Sleep deprivation on a weekly basis is
practicable in outpatient treatment and when staying
awake in groups. Shorter intervals could be indicated in
very severe depressions, which have proved very respon­
sive to sleep deprivation.
The effectivity of sleep deprivation therapy is upheld
on repeated or period applications and does not wane
(fig. 2). It is noted in particular that even if the first (or
second) treatment had little or no effect, the following
treatments can have a marked effect. However, the effec­
tivity of repeated sleep deprivation treatments in individ­
ual patients cannot be predicted with certainty. Fahn-
Vogel. G.: Sleep deprivation; in van Praag. Handbook of biological
psychiatry, vol. VI (Dekker, New York 1981).
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depressed patients. Archs gen. Psychiat. 18: 301-311 (1968).
Wasik. A.; Puchala. G.: Analysis of sleep deprivation as a treatment
method in depressive states (Polish). Psychiat. Pol. 12: 463-468
Woggon, B.: Prognose der Psychopharmakothcrapie (Enke. Stuttgart
Dr. M. Dessauer,
Hoheluftchaussee 56,
D-2000 Hamburg 20
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Richard, J.; Jotterand. E.. el al.: De l'agrypnie dans la mélancolie de
l'âge avancé. Annls méd.-psychol. 140: 321-341 (1982).
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mittels Schlafentzug. Nervenarzt 48: 1-11 (1977).
Rudolf. G.A.E.; Toile. R.: The course of the night with total sleep
deprivation as antidepressant therapy. Waking Sleeping 2: 83-91
Rudolf. G.A.E.; Toile, R.: Sleep deprivation and circadian rhythm in
depression. Psychiatria clin. II: 198-212 (1978b).
Rush, A.J.: Roffwarg. H.P., et al.: Psychobiological predictors of
antidepressant drug response. Pharmakopsychiatr. Neuro-Psychopharmakol. 16: 192-194 (1983).
Scheyen. J.D. van: Slaapdeprivalie bij de behandeling van unipolaire
(endogene) vitale depressies. Ned. Tijdschr. Geneesk. 121: 564—
568 (1977).
Schilgen, B.; Toile, R.: Partial sleep deprivation as therapy for
depression. Archs gen. Psychiat. 37: 267-271 (1980).
Svendscn. K.: Sleep deprivation therapy in depression. Acta psy­
chiat. scand. 54: 184-192 (1976).
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