Sleep phase advance and lithium to sustain the antidepressant effect
of total sleep deprivation in bipolar depression: new findings
supporting the internal coincidence model?
Francesco Benedetti*, Barbara Barbini, Euridice Campori, Mara Cigala Fulgosi,
Adriana Pontiggia, Cristina Colombo
Universita
`
Vita-Salute San Raffaele, School of Medicine, Department of Neuropsychiatric Sciences, Via Stamira d’Ancona 20 20127 Milano, Italy
Received 6 March 2001; received in revised form 2 July 2001; accepted 25 July 2001
Abstract
Recent European studies suggested that sleep phase advance (SPA) could sustain the effects of total sleep deprivation (TSD) both
with or without a combined antidepressant drug treatment. Previous studies by our group showed that an ongoing lithium treat-
ment could enhance and sustain the effect of repeated TSD. In the present study we studied the effect of a single TSD followed by 3
days SPA (beginning with sleep allowed from 17:00 until 24:00, with daily shiftbacks of 2 h) in consecutively admitted bipolar
depressed inpatients who were taking a chronic lithium salts treatment (n=16) or who were devoid of psychotropic medications
(n=14). Changes in mood during treatment were recorded with self administered visual analogue scales and with Hamilton rating
scale for depression. Results showed that SPA could sustain the acute antidepressant effect of TSD, and that lithium enhanced the
effect of the chronobiological treatment. According to the internal coincidence model, the better clinical effects observed in lithium-
treated patients could be due to the phase delaying effect of lithium on biological rhythms, leading to a better synchronization of
biological rhythms with the sleep-wake cycle. # 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Sleep deprivation; Sleep phase advance; Bipolar disorder; Major depression; Lithium
1. Introduction
A growing number of clinical studies supports the
usefulness of total sleep deprivation (TSD) in the treat-
ment of major depression (Leibenluft and Wehr, 1992;
Wirz-Justice and Van den Hoofdakker, 1999). Since a
single TSD night is able to restore euthymia in more
than a half of treated patients, but 80% of TSD
responders relapse short after recovery sleep (Wu and
Bunney, 1990), recent studies focused on the possibility
to sustain the rapid but transient effects of TSD over
time.
High proportions (50–70%) of sustained response to
TSD have been attained by combining TSD with other
antidepressant or mood stabilizing treatments: both
serotonergic (Benedetti et al. 1997; Smeraldi et al.,
1999), noradrenergic (Shelton and Loosen, 1993), mixed
noradrenergic/serotonergic drugs (Kuhs et al., 1996),
light therapy (Neumeister et al., 1996; Colombo et al.,
2000), and lithium salts (Baxter et al., 1986), could suc-
cessfully maintain the acute antidepressant effect of
sleep deprivation. An ongoing long-term treatment with
lithium salts, in particular, was shown to sustain the
effects of repeated TSD, leading to sustained sympto-
matological remission in about 60% of patients (Bene-
detti et al., 1999; Colombo et al., 2000). This finding is
of particular clinical relevance because of an observed
better effect of TSD in bipolar vs. unipolar depressed
patients (Barbini et al., 1998), and because patients
affected by bipolar disorder are often being prescribed a
long-term treatment with lithium salts at the time of
depressive recurrence. We then proposed a three-cycle
repeated TSD as a possible first-choice intervention in
lithium-treated bipolar depression.
Consistent data from European studies suggested
that prolonged manipulations of the sleep-wake cycle
could sustain the effects of TSD both with or without a
0022-3956/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved.
PII: S0022-3956(01)00034-6
Journal of Psychiatric Research 35 (2001) 323–329
www.elsevier.com/locate/jpsychires
* Corresponding author. Tel.: +39-2-2643-3229; fax +39-2-2643-
3265.
E-mail address: benedetti.francesco@hsr.it (F. Benedetti).