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Patterns of response to repeated total sleep deprivations in depression
Journal of Affective Disorders 64 (2001) 257–260 www.elsevier.com / locate / jad
Brief report
Patterns of response to repeated total sleep deprivations in depression a, b c Michael H. Wiegand *, Christoph J. Lauer , Wolfgang Schreiber a
Department of Psychiatry and Psychotherapy, Technical University, Munich, Germany b ¨ , Deggendorf, Germany Klinik Angermuhle c Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany
Received 25 September 1999; received in revised form 3 March 2000; accepted 29 March 2000
Abstract Background: Patterns of response and nonresponse in repeated sleep deprivation (SD) are of both clinical and scientific interest; as yet, studies have yielded inconsistent results. Methods: Eighteen inpatients suffering from a major depression were subjected to a series of six scheduled total sleep deprivations within 3 weeks; 12 of them completed the whole protocol. All were under a constant antidepressant medication with amitriptyline. SD effects were measured using observer and self rating scales. Results: Each single SD led to a significant improvement. Of the 12 patients who completed the protocol, seven were classified as responders at endpoint (i.e., 1 week after the sixth TSD). The majority of patients exhibited a pattern of responses and nonresponses randomly distributed over time. There was no temporal trend. The initial effect did not predict the average response to the following SDs. Limitations: One third of patients dropped out before completing the protocol which limits the scope of the study. Conclusions: Response to a single SD is not generalizable on a series of following SDs in an individual. The mechanism of action of SD does probably not involve mechanisms subjected to habituation or sensitization. 2001 Elsevier Science B.V. All rights reserved. Keywords: Total sleep deprivation; Repeated sleep deprivations; Major depression; Amitriptyline; Antidepressant therapy
1. Introduction Sleep deprivation (SD) leads to a transient improvement of mood in depressed patients; in general, a relapse occurs after the following night (Wu and Bunney, 1990) or subsequent to daytime naps *Corresponding author. Tel.: 1 49-89-4140-4248; fax: 1 4989-4140-4245. E-mail address: [email protected] (M.H. Wiegand).
(Wiegand et al., 1993; Riemann et al., 1993). In the majority of studies in this field, only a single sleep deprivation in each patient has been examined. In studies on repeated (mostly partial) sleep deprivations, an inconstant pattern of responses has been observed. It remains controversial whether response to the first SD predicts responses to subsequent SDs (supported by Holsboer-Trachsler et al. (1988); not observed by Kuhs et al. (1996)). Temporal trends were generally not observed, except for the studies
0165-0327 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 00 )00210-X
M.H. Wiegand et al. / Journal of Affective Disorders 64 (2001) 257 – 260
258
by Roy-Byrne et al. (1984) and Pflug (1976) who ¨ described a gradual decrease, and Fahndrich (1981) who reported an increase of responses to a series of SDs. It was the aim of the present study to examine the pattern of responses and nonresponses to six total sleep deprivations within 3 weeks in patients under constant medication with a fixed dosage of amitriptyline throughout the study.
the observer-rated depression score (HAMD-6) after vs. before sleep deprivation. Statistical analyses were performed using T-tests for paired measurements, and calculating Pearson’s correlation coefficients. In addition, an analysis of variance for repeated measurements was performed. The level of significance was set at P . 0.05 (twotailed).
3. Results 2. Methods
3.1. Patterns of responses Patients: Eighteen inpatients with a major depression (DSM-IV: 296.23, 296.33 or 296.53) were included (nine male, nine female, mean age 45.7611.0 years, mean baseline HAMD-21 score 29.665.4). All were under a continuous medication with amitriptyline (150 mg daily); no other psychoactive medication was given. During 3 weeks, six total sleep deprivations (SDs) were scheduled at regular intervals. 12 patients completed the protocol; two patients dropped out after the third, two after the fourth and two after the fifth SD due to complete clinical remission or on demand of the patient. Psychopathometry: Depressive symptomatology was assessed by means of the 6-item version of the Hamilton Depression Scale (HAMD-6, Bech et al., 1975) covering depressed mood, guilt feelings, work and interest, psychomotor retardation, anxiety (psychic), and physical symptoms (maximum score 22); ratings took place in the morning before and after each sleep deprivation. Mood was self-rated using the Adjective Mood Scale (AMS, von Zerssen, 1986) in the mornings and evenings daily. ‘Response’ was defined as a reduction of at least 50% in
On average, each of the six total sleep deprivations led to an improvement (Table 1). This is mirrored clearly in the observer ratings which improve significantly during each sleep deprivation; changes in self-ratings do not consistently reach statistical significance. There was a positive correlation between averaged observer and self-rated changes (r 5 0.44, P , 0.05, one-tailed). Before the following SD (after two or three interpolated ‘normal’ nights), mean ratings returned to baseline. Fig. 1 demonstrates the individual patterns of (observer-rated) responses and non-responses. One patient responded six times, another one did never respond and dropped out after the fourth TSD. The majority of patients exhibited a pattern of responses and nonresponses which appears randomly distributed over time. An analysis of variance for repeated measurements (MANOVA) restricted to those 12 patients completing the study protocol with 6 TSDs was performed using two series of time factors (factor 1: before / after SD; factor 2: the six consecutive measurements) resulting in a significant main
Table 1 Mean depression and mood scores before and after each sleep deprivation n
1st TSD 2nd TSD 3rd TSD 4th TSD 5th TSD 6th TSD
18 18 18 16 14 12
Depression scores (HAMD-6)
Mood scores (AMS)
Before TSD
After TSD
P
Bevore TSD
After TSD
P
13.762.9 11.764.4 10.364.8 10.164.5 11.364.5 11.764.4
5.764.4 5.164.7 5.864.5 4.963.6 6.864.5 5.365.1
, 0.01 , 0.01 , 0.01 , 0.01 , 0.05 , 0.01
35.4613.3 33.9613.6 30.1614.8 32.1615.4 33.5613.5 32.8610.2
32.0613.3 27.0613.9 27.6614.7 27.3614.6 25.8611.1 28.8612.8
ns , 0.01 ns ns , 0.05 ns
M.H. Wiegand et al. / Journal of Affective Disorders 64 (2001) 257 – 260
259
Fig. 1. Immediate effects of serial total sleep deprivations (TSD) in 18 patients (R 5 response; N 5 nonresponse).
effect for factor 1 (F 5 84.0, P 5 0.000). No significant effect was observed for factor 2 (F 5 0.6, P 5 .44) and for the interaction between factors (F 5 3.2, P 5 0.10).At endpoint (1 week after the completion of the trial), another depression rating was performed, exhibiting a mean HAMD-6 score of 7.963.7. When comparing initial and endpoint ratings, seven patients were classified as responders and five as nonresponders to the whole TSD series. There were no significant correlations between the observer-rated effect of the first TSD with the average effect of the following TSDs (r 5 0.38, P 5 0.23) and the pooled effects of TSDs 1 and 2 with the average effects of TSDs 3 to 6 (r 5 0.21, P 5 0.52). Responses to TSD were preceded by a more pronounced typical diurnal variation of mood (defined as difference in evening vs. morning AMS ratings) than nonresponses; however, the difference was significant for the sixth TSD only (P 5 0.03).
4. Discussion Each single sleep deprivation had a clear effect, particularly on observer-rated depression and–to a somewhat lesser degree–on self-rated mood. Before the subsequent SD, measures had returned to
baseline. Thus, we did not observe a ‘cumulative’ effect of repeated SDs as did Holsboer-Trachsler and Ernst (1986) and Sack et al. (1988) who repeated partial SDs with only one interpolated ‘normal’ night, as opposed to two or three nights in the present study, applying a total SD regimen. For patients complaining about too large mood swings in the course of serial SDs, (partial) SDs with one interpolated night appear more favourable than the design of the present study. The average response to serial sleep deprivation was not predictable from response to the first SD, or from the pooled responses to the first two SDs. For clinical practice, this indicates that an initial nonresponse should not decourage to continue the series. There is evidence that serial sleep deprivation has favourable antidepressant properties irrespective of the immediate effects (Kuhs et al., 1996; 1998). Responses and nonresponses to TSDs varied in the majority of patients, with no recognizable and consistent pattern. Thus, response to a given sleep deprivation cannot be considered an indicator of a stable trait. This may explain why in the sleep deprivation literature, data on sociodemographic, clinical and biological predictors of SD response are highly inconsistent. The absence of any temporal trend (decrease or increase of SD effects over time)
260
M.H. Wiegand et al. / Journal of Affective Disorders 64 (2001) 257 – 260
indicates that the still unknown mode of action of sleep deprivation does probably not involve mechanisms of habituation or sensitization.
References Bech, P., Gram, L.F., Dein, E., Jacobsen, O., Vitger, J., Bolwig, T.G., 1975. Quantitative rating of depressive states. Acta Psychiat Scand 51, 161–170. ¨ Fahndrich, E., 1981. Effects of sleep deprivation on depressed patients of different nosological groups. Psychiat Res 5, 277– 285. Holsboer-Trachsler, E., Ernst, K., 1986. Sustained antidepressive effect of repeated partial sleep deprivation. Psychopathology 19, 172–176. Holsboer-Trachsler, E., Wiedemann, K., Holsboer, F., 1988. Serial partial sleep deprivation in depression–clinical effects and dexamethasone suppression test results. Neuropsychobiology 19, 73–78. ¨ ¨ S., Mrosek, S., Tolle, ¨ Kuhs, H., Farber, D., Borgstadt, R., 1996. Amitriptyline in combination with repeated late sleep deprivation versus amitriptyline alone in major depression. A randomised study. J Affect. Disord. 37, 31–41. Kuhs, H., Kemper, B., Lippe-Neubauer, U., Meyer-Dunker, J., ¨ Tolle, R., 1998. Repeated sleep deprivation once versus twice a
week in combination with amitriptyline. J Affect. Disord. 47, 97–103. Pflug, B., 1976. The effect of sleep deprivation on depressed patients. Acta Psychiat Scand 53, 148–158. Riemann, D., Wiegand, M., Lauer, Ch., Berger, M., 1993. Naps after total sleep deprivation in depressed patients: are they depressiogenic? Psychiat Res 49, 109–120. Roy-Byrne, P.P., Uhde, T.W., Post, R.M., 1984. Antidepressant effects of one night’s sleep deprivation: clinical and theoretical implications. In: Post, R.M., Ballenger, J.C. (Eds.). Neurobiology of mood disorders. Williams & Wilkins, Baltimore, pp. 817–835. Sack, D.A., Duncan, W., Rosenthal, N.E., Mendelson, W.E., Wehr, T.A., 1988. The timing and duration of sleep in partial sleep deprivation therapy in depression. Acta Psychia Scand 77, 219–224. Wiegand, M., Riemann, D., Schreiber, W., Lauer, C., Berger, M., 1993. Effect of morning and afternoon naps on mood after total sleep deprivation in patients with major depression. Biol Psychiatry 33, 467–476. Wu, J.C., Bunney, W.E., 1990. The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am J Psychiatry 147, 14–21. von Zerssen, D., 1986. Clinical self-rating scales (CSRS) of the Munich Psychiatric Information System (PSYCHISS ¨ Munchen). In: Sartorius, N., Ban, T. (Eds.). Assessment of Depression. Springer, Berlin, pp. 270–303.
Brief report
Patterns of response to repeated total sleep deprivations in depression a, b c Michael H. Wiegand *, Christoph J. Lauer , Wolfgang Schreiber a
Department of Psychiatry and Psychotherapy, Technical University, Munich, Germany b ¨ , Deggendorf, Germany Klinik Angermuhle c Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany
Received 25 September 1999; received in revised form 3 March 2000; accepted 29 March 2000
Abstract Background: Patterns of response and nonresponse in repeated sleep deprivation (SD) are of both clinical and scientific interest; as yet, studies have yielded inconsistent results. Methods: Eighteen inpatients suffering from a major depression were subjected to a series of six scheduled total sleep deprivations within 3 weeks; 12 of them completed the whole protocol. All were under a constant antidepressant medication with amitriptyline. SD effects were measured using observer and self rating scales. Results: Each single SD led to a significant improvement. Of the 12 patients who completed the protocol, seven were classified as responders at endpoint (i.e., 1 week after the sixth TSD). The majority of patients exhibited a pattern of responses and nonresponses randomly distributed over time. There was no temporal trend. The initial effect did not predict the average response to the following SDs. Limitations: One third of patients dropped out before completing the protocol which limits the scope of the study. Conclusions: Response to a single SD is not generalizable on a series of following SDs in an individual. The mechanism of action of SD does probably not involve mechanisms subjected to habituation or sensitization. 2001 Elsevier Science B.V. All rights reserved. Keywords: Total sleep deprivation; Repeated sleep deprivations; Major depression; Amitriptyline; Antidepressant therapy
1. Introduction Sleep deprivation (SD) leads to a transient improvement of mood in depressed patients; in general, a relapse occurs after the following night (Wu and Bunney, 1990) or subsequent to daytime naps *Corresponding author. Tel.: 1 49-89-4140-4248; fax: 1 4989-4140-4245. E-mail address: [email protected] (M.H. Wiegand).
(Wiegand et al., 1993; Riemann et al., 1993). In the majority of studies in this field, only a single sleep deprivation in each patient has been examined. In studies on repeated (mostly partial) sleep deprivations, an inconstant pattern of responses has been observed. It remains controversial whether response to the first SD predicts responses to subsequent SDs (supported by Holsboer-Trachsler et al. (1988); not observed by Kuhs et al. (1996)). Temporal trends were generally not observed, except for the studies
0165-0327 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 00 )00210-X
M.H. Wiegand et al. / Journal of Affective Disorders 64 (2001) 257 – 260
258
by Roy-Byrne et al. (1984) and Pflug (1976) who ¨ described a gradual decrease, and Fahndrich (1981) who reported an increase of responses to a series of SDs. It was the aim of the present study to examine the pattern of responses and nonresponses to six total sleep deprivations within 3 weeks in patients under constant medication with a fixed dosage of amitriptyline throughout the study.
the observer-rated depression score (HAMD-6) after vs. before sleep deprivation. Statistical analyses were performed using T-tests for paired measurements, and calculating Pearson’s correlation coefficients. In addition, an analysis of variance for repeated measurements was performed. The level of significance was set at P . 0.05 (twotailed).
3. Results 2. Methods
3.1. Patterns of responses Patients: Eighteen inpatients with a major depression (DSM-IV: 296.23, 296.33 or 296.53) were included (nine male, nine female, mean age 45.7611.0 years, mean baseline HAMD-21 score 29.665.4). All were under a continuous medication with amitriptyline (150 mg daily); no other psychoactive medication was given. During 3 weeks, six total sleep deprivations (SDs) were scheduled at regular intervals. 12 patients completed the protocol; two patients dropped out after the third, two after the fourth and two after the fifth SD due to complete clinical remission or on demand of the patient. Psychopathometry: Depressive symptomatology was assessed by means of the 6-item version of the Hamilton Depression Scale (HAMD-6, Bech et al., 1975) covering depressed mood, guilt feelings, work and interest, psychomotor retardation, anxiety (psychic), and physical symptoms (maximum score 22); ratings took place in the morning before and after each sleep deprivation. Mood was self-rated using the Adjective Mood Scale (AMS, von Zerssen, 1986) in the mornings and evenings daily. ‘Response’ was defined as a reduction of at least 50% in
On average, each of the six total sleep deprivations led to an improvement (Table 1). This is mirrored clearly in the observer ratings which improve significantly during each sleep deprivation; changes in self-ratings do not consistently reach statistical significance. There was a positive correlation between averaged observer and self-rated changes (r 5 0.44, P , 0.05, one-tailed). Before the following SD (after two or three interpolated ‘normal’ nights), mean ratings returned to baseline. Fig. 1 demonstrates the individual patterns of (observer-rated) responses and non-responses. One patient responded six times, another one did never respond and dropped out after the fourth TSD. The majority of patients exhibited a pattern of responses and nonresponses which appears randomly distributed over time. An analysis of variance for repeated measurements (MANOVA) restricted to those 12 patients completing the study protocol with 6 TSDs was performed using two series of time factors (factor 1: before / after SD; factor 2: the six consecutive measurements) resulting in a significant main
Table 1 Mean depression and mood scores before and after each sleep deprivation n
1st TSD 2nd TSD 3rd TSD 4th TSD 5th TSD 6th TSD
18 18 18 16 14 12
Depression scores (HAMD-6)
Mood scores (AMS)
Before TSD
After TSD
P
Bevore TSD
After TSD
P
13.762.9 11.764.4 10.364.8 10.164.5 11.364.5 11.764.4
5.764.4 5.164.7 5.864.5 4.963.6 6.864.5 5.365.1
, 0.01 , 0.01 , 0.01 , 0.01 , 0.05 , 0.01
35.4613.3 33.9613.6 30.1614.8 32.1615.4 33.5613.5 32.8610.2
32.0613.3 27.0613.9 27.6614.7 27.3614.6 25.8611.1 28.8612.8
ns , 0.01 ns ns , 0.05 ns
M.H. Wiegand et al. / Journal of Affective Disorders 64 (2001) 257 – 260
259
Fig. 1. Immediate effects of serial total sleep deprivations (TSD) in 18 patients (R 5 response; N 5 nonresponse).
effect for factor 1 (F 5 84.0, P 5 0.000). No significant effect was observed for factor 2 (F 5 0.6, P 5 .44) and for the interaction between factors (F 5 3.2, P 5 0.10).At endpoint (1 week after the completion of the trial), another depression rating was performed, exhibiting a mean HAMD-6 score of 7.963.7. When comparing initial and endpoint ratings, seven patients were classified as responders and five as nonresponders to the whole TSD series. There were no significant correlations between the observer-rated effect of the first TSD with the average effect of the following TSDs (r 5 0.38, P 5 0.23) and the pooled effects of TSDs 1 and 2 with the average effects of TSDs 3 to 6 (r 5 0.21, P 5 0.52). Responses to TSD were preceded by a more pronounced typical diurnal variation of mood (defined as difference in evening vs. morning AMS ratings) than nonresponses; however, the difference was significant for the sixth TSD only (P 5 0.03).
4. Discussion Each single sleep deprivation had a clear effect, particularly on observer-rated depression and–to a somewhat lesser degree–on self-rated mood. Before the subsequent SD, measures had returned to
baseline. Thus, we did not observe a ‘cumulative’ effect of repeated SDs as did Holsboer-Trachsler and Ernst (1986) and Sack et al. (1988) who repeated partial SDs with only one interpolated ‘normal’ night, as opposed to two or three nights in the present study, applying a total SD regimen. For patients complaining about too large mood swings in the course of serial SDs, (partial) SDs with one interpolated night appear more favourable than the design of the present study. The average response to serial sleep deprivation was not predictable from response to the first SD, or from the pooled responses to the first two SDs. For clinical practice, this indicates that an initial nonresponse should not decourage to continue the series. There is evidence that serial sleep deprivation has favourable antidepressant properties irrespective of the immediate effects (Kuhs et al., 1996; 1998). Responses and nonresponses to TSDs varied in the majority of patients, with no recognizable and consistent pattern. Thus, response to a given sleep deprivation cannot be considered an indicator of a stable trait. This may explain why in the sleep deprivation literature, data on sociodemographic, clinical and biological predictors of SD response are highly inconsistent. The absence of any temporal trend (decrease or increase of SD effects over time)
260
M.H. Wiegand et al. / Journal of Affective Disorders 64 (2001) 257 – 260
indicates that the still unknown mode of action of sleep deprivation does probably not involve mechanisms of habituation or sensitization.
References Bech, P., Gram, L.F., Dein, E., Jacobsen, O., Vitger, J., Bolwig, T.G., 1975. Quantitative rating of depressive states. Acta Psychiat Scand 51, 161–170. ¨ Fahndrich, E., 1981. Effects of sleep deprivation on depressed patients of different nosological groups. Psychiat Res 5, 277– 285. Holsboer-Trachsler, E., Ernst, K., 1986. Sustained antidepressive effect of repeated partial sleep deprivation. Psychopathology 19, 172–176. Holsboer-Trachsler, E., Wiedemann, K., Holsboer, F., 1988. Serial partial sleep deprivation in depression–clinical effects and dexamethasone suppression test results. Neuropsychobiology 19, 73–78. ¨ ¨ S., Mrosek, S., Tolle, ¨ Kuhs, H., Farber, D., Borgstadt, R., 1996. Amitriptyline in combination with repeated late sleep deprivation versus amitriptyline alone in major depression. A randomised study. J Affect. Disord. 37, 31–41. Kuhs, H., Kemper, B., Lippe-Neubauer, U., Meyer-Dunker, J., ¨ Tolle, R., 1998. Repeated sleep deprivation once versus twice a
week in combination with amitriptyline. J Affect. Disord. 47, 97–103. Pflug, B., 1976. The effect of sleep deprivation on depressed patients. Acta Psychiat Scand 53, 148–158. Riemann, D., Wiegand, M., Lauer, Ch., Berger, M., 1993. Naps after total sleep deprivation in depressed patients: are they depressiogenic? Psychiat Res 49, 109–120. Roy-Byrne, P.P., Uhde, T.W., Post, R.M., 1984. Antidepressant effects of one night’s sleep deprivation: clinical and theoretical implications. In: Post, R.M., Ballenger, J.C. (Eds.). Neurobiology of mood disorders. Williams & Wilkins, Baltimore, pp. 817–835. Sack, D.A., Duncan, W., Rosenthal, N.E., Mendelson, W.E., Wehr, T.A., 1988. The timing and duration of sleep in partial sleep deprivation therapy in depression. Acta Psychia Scand 77, 219–224. Wiegand, M., Riemann, D., Schreiber, W., Lauer, C., Berger, M., 1993. Effect of morning and afternoon naps on mood after total sleep deprivation in patients with major depression. Biol Psychiatry 33, 467–476. Wu, J.C., Bunney, W.E., 1990. The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am J Psychiatry 147, 14–21. von Zerssen, D., 1986. Clinical self-rating scales (CSRS) of the Munich Psychiatric Information System (PSYCHISS ¨ Munchen). In: Sartorius, N., Ban, T. (Eds.). Assessment of Depression. Springer, Berlin, pp. 270–303.