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In 30 depressed patients who had responded to total sleep deprivation therapy, morning naps led more frequently to relapses into depression than did afternoon ...

BIOL PSYCHIATRY 1993;33:467-476


Effect of Morning and Afternoon Naps on Mood After Total Sleep Deprivation in Patients with Major Depression Michael Wiegand,* Dieter Riemann, Wolfgang Schreiber, Christoph J. Lauer, and Mathias Berger"

In 30 depressed patients who had responded to total sleep deprivation therapy, morning naps led more frequently to relapses into depression than did afternoon naps. Longer naps were less detrimental than shorter ones, and there was no significant relationship between the effect of a nap on mood and its content of slow-wave-sleep. The amount of the rapid eye-movement sleep, too, was unrelated to clinical nap effects. Thus, some of the current theories on the re!ati~nsh;.p between sleep and depressive symptomatology are not supported by the data. Our results demonstrate the importance of nap timing, suggesting a circadian variation of propensiC¢ to relapae into depression.

Key Words: depression, total sleep deprivation, naps

Introduction Total sleep deprivation (TSD) is an effective treatment for major depression (for review, see Gerner et al 1979; Gillin 1983; Wu and Bunney 1990). According to Wu and Bunney, who reviewed 61 articles on the topic, including over 1700 individual patients, the overall response rate reported in the literature is 59%. In contrast to other antidepressant treatments, the therapeutic effect develops rapidly, but a relapse into depression usually occurs after the following nocturnal sleep; 83% of patients not receiving medication and 59% of patients receiving medication are reported to relapse after the first night of sleep (Wu and Bunney 1990). From the Max Planck Institute of Psychiatry, (MW, WS, CJL) Munich, and Central Institute of Mental Health (DR, MB), Mannheim, Germany. Address reprint requests to M. Wicgand, M.D., Psychia_nicClinic of the Technical University of Munich, Ismaninger Strasse 22, W-8000 Miinchen 80, Germany. *Current address: Psychiatric Clinic, Technical University of Munich, Germany. tCurrent address: Psychiatric Clinic, University of Freiburg, Germany. Received March ! 1, 1992; December 4, 1992. © 1993 Society of Biological Psychiatry

Although limited in its clinical usefulness, TSD has become an important paradigm in research on affective disorders. To elucidate its mechanism of action, previous sPddies have tamed to identify predictors of response to TSD (Gillin 1983; Roy-Byrne et al 1984). Accordiag to Duncan et al (1980), response to TSD is predicted by a baseline sleep electroencephalographic (EEG) pattern with features typical for depression [increased intermittent and early morning awakening, reduced rapid eye-movement (REM) latency, reduced sleep efficiency]. In a study with a larger sample, Riemann et al (1991) confirmed the predictive value of a shortened REM latency for response to TSD. Other reliable neurobiological predictors, especially neurochemical ones, have not yet been identified. Among clinical va_dables, diurnal variation in mood is clearly related to response to sleep deprivation (Reinink et al 1990; Riemann et al 1991). In the present study, an alternative experimental approach to investigate the antidepressant properties of sleep 0006-3223/93/$06.00


M. Wiegand et al

BIOL PSYCHIATRY 1993;33:467-476

deprivation is presented. It is based on clinical observations that point to the reversibility of a favorable sleep deprivation effect by a short daytime nap. In an early report by Pflug and T611e (1971), it was mentioned for the first time that in some responders to TSD, a daytime nap after successful sleep deprivation provoked a worsening of mood. In a single case study, Knowles et al ~¢I OTO~,,.,described_ a relapse into depression caused by a short nap (15 min of non-REM sleep) in the early morning (5:00 AM), and RoyByrne et al (1984) observed a severe mood worsening subsequent to as little as 90 sec of polysomnographically recorded sleep at 3:30 PM. In a single case study of 48-hr sleep deprivation, Southmayd et al (1987) observed a relapse in a TSD responder after several very short episodes of sleep during the second deprivation night, with a cumulated total of 11.1 min of stage 2 sleep, revealed by continuous EEG monitoring. The observations from these anecdotal re~ tn~ts and case studies could be confirmed by some systematic investigations. In the first study on this topic (Wiegand et al 1987b), we observed effects ranging from improvement to dramatic worsening in drug-free depressed patients who, after TSD, took a nap at 1:00 PM. In 6 of 12 responders to TSD, the nap led to a clear relapse into depression. The results of this pilot study did not allow definite conclusions as to the respective determinants of relapse but pointed to the role of longer nap sleep duration and the occurrence of REM sleep as crucial factors. In a separate analysis of hourly mood r,:tings before and after the naps, we found a delayed mooa setback in those TSD responders who had not worsened immediately after the nap (Wiegand et al 1987a). Other systematic studies yielded inconsistent results. Kraft et al (1984) described a relapse in one of seven depressed patients after a 10-min afternoon nap following response to sleep deprivation. Gillin et al (1989), however, did not observe such relapses following 10-min naps at 8:30 A M or 3:00 r,M In a ~ h l d v i n n a t i ~ n t e r,~t,,~i,,in,-, ,-~,~d ication, Giedke (1988) observed no consistent effect of naps at 1:30 PM on mood. Wu and Bunney (1990) ment;oned unpublished data from their group showing relapses in five of seven TSD responders after a 60-min nap. The antidepressant effect of sleep deprivation and its v y oa~,,,,l.~ ~ u a y u i u ~ , ii&pS as w r i i d~ liOi.,tl.tilldl


supports the hypothesis that sleep can be depressiogenic in depression. This assumption is further supported by the frequent clinical phenomenon of positive diurnal variation in mood, with a maximal depressed mood in the morning and a gradual improvement during the course of the day (Haug and F/ihndrich 1990). Several hypotheses have been proposed to explain the antidepressant eur.t:t ".... of sleep deprivation and, conversely, the "depressiogenic" properties of sleep in depression. Among these, the following are presently the most dis-

cussed (van der Hoofdakker and Beersma 1988; Wu and Bunney 1990): 1. Several theories emphasize the involvement of circadian processes in these phenomena. Under a chronobiological perspective, major depression can be characterized by an alteration of the "internal clock". Sleep deprivatioa is presumed to exert its antidepressant action by either resynchronizing disturbed rhythms or by preventing sleep during a so-called critical phase in the early morning hours (Wehr and Wirz-Justice 1981; Kripke 1984). In light of these theories, the timing of a daytime nap following sleep deprivation can be expected to be crucial to its effect on mood and depressive symptomatology. 2. The "two-process model" of sleep (Borb61y, 1987; Borb61y and Wirz-Justice, 1982) postulates a deficiency in a homeostatic "process S" (associated with EEG slowwave activity) in depression that may account for the im'~irm,~nt in mood. Sleep depfivatien is pi~umed to increase the level of"process S" by lengthening the duration of wakefulness, thus leading to improvement in mood. This model allows the prediction that the depressiogenic impact of sleep is related to the degree of "process S" reduction. Correspondingly, the EEG slow-wave activity during a nap can be expected to be essential to its "depressiogenic" action. 3. Wu and Bunney (1990) proposed the hypothesis of a sleep-associated depressiogenic process, possibly represented by a substance that is released during sleep and is metabolized during wakefulness. In many respects, this theory resembles the Borb61y and Wirz-Justice model; the latter differs from the former in implying a "euphorogenic" substance released in wakefulness rather than a "depressiogenic" substance released during sleep. Both theories allow the hypothesis that longer naps are more detrimental than shorter ones and that longer prior wakefulness protects against the mood worsening caused by daytime naps. 4. With regard to the antidepressant effect of selective REM sleep deprivation observed by Vogel et al (1980), it has been hypothesized that REM sleep suppression is essential to the beneficial effects of several antidepressant treatment modalities, including sleep deprivation (Berger et al 1990). This view is in line with the cholinergicadrenergic imbalance model of depression (Janowsky et al 19';-'2)and the reciprocal interaction model of REM sleep regulation (McCarley ! 982). In light of this approach, the occurrence of REM sleep during a daytime nap, as a correlate of elevated cholinergic neuronal activity, should be accompanied by a greater propensity of relapse into depression. The induction of depressive symptomatology by short sleep episodes can be regarded as a cmcia! experiment to test these hypotheses. The study presented here was designed to examine this phenomenon systematically to elu-

Naps After Sleep Deprivation in Depression

cidate the nature of the depressiogenic properties of sleep in depression. The main purpose was to examine the relationship between the clinical effects of daytime naps following sleep deprivation and the timing of the nap (morning versus afternoon). Other factors were also considered: the length of a nap as well as the occurrence and the amount of both slow-wave sleep and REM sleep. Special emphasis was placed on the possible interaction of these variables with nap timing.


Subjects The study was performed simultaneously at the Max Planck Institute of Psychiatry, Munich, and the Central Institute of Mental Health, Mannheim, Germany (part of the data have been published previously by Wiegand et al 1989). Thirty inpatients [10 male, 20 female, 9 single episode, 21 recurrent episodes; mean age 48.7 ___ 11.5 (SD) years] suffering from a major depression according to DSM-IIIR (296.2 x , 296.3 x , 296.5 x , rated by experienced psychiatrist), with a mean baseline depression score ( _ SD) on the Hamilton Depression Rating Scale, 2 l-item version (HAMD-21) of 26.9 +__ 5.3 (minimum 18 points) were included in the study. Informed, written consent was obtained from all patients.

Design After a drug washout period of at least 7 days and an adaptation night in the sleep laboratory, followed by one night of polysomnography, patients were subjected to a TSD. On the following day, patients took a nap in the sleep laboratory (with polysomnographic recording) either at 9:00 AM or 3:00 PM, they were assigned randomly to the morning versus afternoon nap condition. Sleep recordings were terminated when the patient woke up spontaneously without falling asleep again within 5 min. In the morning nap group, two patients did not fall asleep at the scheduled nap ume and were excluded from the present analysis. Gender ratio, mean age, and baseline psychopathology of the resuhmg sample are characterized in Table 1. With regard to these variables, there were no significant differences between the morning and afternoon nap groups nor between responders and nonresponders to TSD.

Polysomnography The recordings were performed using a 17-channel Nihon Kohden 4417 EEG machine that measured the following parameters: EEG (C3-A2/C4-AI), electro-ocuaog~am ~norizontai), and electromyogram (submental). The sleep polygraphs were rated visually according to standard criteria




(Rechtschaffen and Kales 1968). The following definitions of sleep parameters were used:

1. Total sleep time: time spent asleep less any awake time.

2. Sleep onset latency: time from lights out until the appearance of stage 2 sleep. 3. Sleep efficiency: ratio of total sleep time to time in bed. 4. REM latency: time from sleep onset until the first occurrence of REM sleep. 5. REM density: number of 3-sec "miniepochs" of REM sleep containing eye movements as a percentage of the total number of "miniepochs" of REM sleep.

Depression Ratings Depressive symptomatology was observer rated by means of the six-item version of the Hamilton Depression Scale (HAMD-6) (Bech et al 1975) covering depressed mood, guilt feelings, woik and haterest, psychomotor retardation, anxiety (psychic), and physical symptoms (maximum score 22); ratings took place on the day before TSD at approximately 9:00 AM and 3:00 PM and on the day following TSD approximately 9:00 AM and 11:00 AM (or 30 min after termination of a morning nap, respectively) and 3:00 PM and 5:00 PM (or 30 min after termination of an afternoon nap, respectively). Raters were unaware of the experimental conditions. Response to total sle~:p deprivation was defined as a reduction of at least 30% in the HAMD-6 score, based on both 9:00 AM ratings. A nap effect (difference in HAMD-6 ratings after versus before the nap) of four points or more was defined as a relapse; changes between one and three points were termed a slight worsening. The difference in HAMD-6 ratings between 9:00 AM and 3:00 PM on the day before TSD is referred to as

morning/afternoon variation of mood. Statistical Analyses Comparisons between subgroups were mainly performed by means of two-way analyses of variance, with "nap timing" and "response to TSD" as factors. The variations in HAMD-6 scores were analyzed by means of Wilcoxon's test. Correlational analyses were performed by computing product-moment correlation coefficients. The level of significance was set at p < 0.05 (two-tailed).


Characteristics of Nap Sleep aot~ 2 u~,.,,u~.s morning and afternoon nap sleep. Naps at 9:00 AM and 3:00 PM did not differ in any of the sleep parameters. Responders to TSD exhibited significantly less



M. Wiegand et al


Table I. Clinical Description of the Study Samplea Total

Male/female ratio Meanage(_+SD)(yr) Mean HAMD-21 baseline score ( ± SD)

Respoaders to TSD

Nonresponders to TSD

Naps at 9:00 AM (n = 13)

Naps at 3:00 PM (n = 15)

Naps at 9:00 AM (n = 8)

Naps at 3:00 PM (n = 11)

Naps ai 9:00 AM (n = 5)

Naps at 3:00 PM (n = 4)


2/I ! 51.1 ± 10.6 28.5 ± 5.6

8/7 46.5 __ 12.9 25.7 +- 5.3

1/7 52.5 -- 12.3 28.5 -- 4.8

4/7 48.5 -+ 11.8 26.5 -- 5.6

I/4 48.8 _+ 7.9 28.6 +- 7.3

4/0 4 1 . 0 - + t5.9 23.8 -- 4.3


~TSD. total sleep deprivation; HAMD-21, Hamilton Depression Scale, 21-item version. bANOVA, analysis of variation results (with factors "nap timing" and "response to TSD"); NS, not significant.

REM sleep and a lower REM density than nonresponders. Results did not change when analyzing the relative instead of the absolute amounts of sleep stages.

Influence of Nap Timing and Preceding Response to TSD on Mood Changes Figure 1 describes the distribution of nap effects in the morning and afternoon nap groups, separately for responders and nonresponders to TSD. Five of the responders who took a nap at 9:00 AM exhibited severe relapse into depression. In contrast, afternoon naps induced only slight (if any) worsening in re,ponders to TSD, with the exception of one patient who showed a dramatic deterioration in mood. A significant difference in the relapse rate between morning and afternoon naps occurred in responders to TSD [Fisher's exact test comparing rate of r~'lapse (nap effect ->4) with rate of nonrelapse (nap effect

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