BIOl, i~SYCHIATRY
257
Phototherapy in Nonseasonal Depression Arthur Mackert, Hans-Peter Volz, Rolf-Dieter Stieglitz, and B no Miiller-Oerlinghausen
Previous reports have shown that bright light exposure max, benefit patients with seaso~l depression. In the present study, the possible therapeutic effect of bright light in nonseasonal major depressive disorder was examined. Forts,-two depressed patients not receivb~g additional antidepressant medication were exposed to bright white light of 25bO iux or dim red light of 50 hoe over one week for m,o hr daily in the morning. The change in depressive symptoms was assessed by rating scales (Hamilton Depression Rating Scale, CGI) and by self-rating scales (Depression Scale, Complaint List, Visual Analogae Scale). Consistent for all ratings, the decrease in depressive sb.'mptoms after bright white light was only slight and not different from dim red-light exposure. Contrary. to the findings in seasonal affective disorder, phototherapy administered over one week for two hr daily is not effective in nonseasonal major depressive disorder. Introduction Seasonal affective disorder (SAD) is characterized by recumng cycles of depression in the fall and winter with hypomania or euthymia in the spring and summer. Lewy et al (1982) first reported on a patient with seasonal mood cycles, whose winter depression retorted when daylight was lengthened with bright artificial light. Subsequent studies have shown that patients with SAD improve on exposure to bright light of approx~ately 2500 lux in intensity, whereas dim light (300 lux or less) has only a negligible therapeutic effect (Rosenthal et al 1984, 1985; James et al 1985; Wehr et al 1987; Isaacs et al 1988). The antidepressant effect produced by bright artificial light appears within one week, w;th r~lanc~ nc..alh,
There have been only a few investigations to determine whether bright light may also induce remission in patients with nonseasonal depression. Kripke et al (1983a) found a significantly greater effect after a single hour of bright light than after dim light exposure from 5 AM to 6 AM in 12 patients suffering from major depressive disorder. Dietzel et al (1986) reported a significant improvement in mood and sleep of 10 female patients with major depressive disorder after a single day of light therapy of 3 hr duration in the morning and 4 hr in the evening. In contrast, Yerevanian et al (1986) found a beneficial effect of a i- to 2-week phototherapy only in seasonal, but not in nonseasonal depressives, although most of the nonseasonal depressives had concurrently received psychotropic
From the Department of Psychiatry. Free University of Berlin. Germany. Address reprint requests to Dr. A. Mackert. Psychiatrische Klinik und Polildinik der Freien Univers~t Berlin, Eschenallee 3, D-1000 Berlin 19 FRG. Received September 2. 1990; revised February 27, 1991. 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
38
BIOL PSYCHIATRY 1991;~:257~268
A. Mackert et al
agents during light treatment. Kripke et al (1987) reported only a minimal reduction in the symptoms of 14 patients with major depression in response to bright light given for 5 days, either for one ~ ia the morning or for one hr both in the morning and in the evening. In a subsequent study, nonseasonal depressed patients neared with bright light over one week for 3 hr daily in the evening showed an approximate 20% decrease in depression ratings when compared to the group receiving dim light in the stone design, which had not improved (Kripke et al 1989). The available literature on the benefits of phototherapy in nonseasonal depression is rather contradictory. This is mainly attributable to the small number of subjects involved and to differences in the experimental design, in particular to (a) the number of days, (b) the time of day, (c) the daily duration of exposure to light, and (d) the concomitant use or nonuse of antidepressants. The aim of the present study was to evaluate a sufficiently large number of patients and determine whether bright light as opposed to dim light is suitable for clinical treatment of patients suffering from major depression without recurrent fall/winter depression. Preliminary reports of some on these data in a siaaller group of patients were recently published (Mackert et al 1990; Volz et al 1990).
Methods
Subjects From January 1987 to November 1988, 50 inpatients consecutively admitted and meeting Research Diagnostic Criteria (RDC) for major depressive disorder (Spitzer et al 1977) consented to participate in the study. Patients with seasonal depression were excluded according to the criteria of seasonality based on DSM-III-R: three episodes, at least two of which were consecutive, with manifestation within a seasonal 90-day period between the beginning of September and the end of November (the seasonal pattern according to DSM-III-R is restricted to a 60-day window). Because 2 patients had a first manifestation of depressive illness between September and November (see Table 2), a seasonal depression occurring during the further course of illness could not be ruled out. Other exclusion criteria were ophthalmologic disorders, alcohol or drug abuse, brain injury and neurological disorders, and acute suicidal tendencies. Patients with an IQ lower than 90 as measured by a multiple choice vocabulary test (Lehrl 1978) were also not included. Before beginning the study, each patient underwent a medical examination including both routine laboratory analysis and electrocardiogram (l~CCi). unne specimens were obtained to detect the use of illicit drugs. The 50 patients were randomly exposed to either bright white or dim red light. The patients were informed that they were to participate in a study, in which two different kinds of exposure to light would be investigated. They were not told that dim red light was expected to be ineffective. Eight patients discontinued the study either because drug treatment was mandatory on clinical grounds (6 patients), or because urine specimens revealed the use of illicit drugs (2 patients). Of the remaining 42 patients, 36 with major depressive disorder and 6 with bipolar depression, 22 were exposed to bright white light and 20 patients to dim red light. As may be seen from Table 1, there were no statistical differences in age, sex, and initial HDRS-scores between these two subgroups. Based on documentation of previous hospitalizations, reports from psychiatrists, who had treated these patients as outpatients, as well as information from relatives and the patients themselves, a drug history was established for each patient with special regard to prior man-
BIOL.PSY(~I~TRY
Phototherapy in Nonseasonal Depression
259
Table I. Age, Sex, and Initial HDRS of Patients Treated with Bright and Dim Light Patients ~ All patients Gender re_Me
female Age (years) Hamilton Depression Rating Scale (HDRS) before treatment
8 33 54.2 ± 13.2 19.3 ± 4.2
Bright white light (n = 22)
to D ~ red ~ght (n = 20)
5
3
17
17
51.5 ± 14.7 19.5 ± 4.1
57.2 ± II.7 |9.1 -*- 4.2
NS (X ~ tesO NS NS
ifestations and an up-to-date history of medication (see Table 2). Thirteen patients were without antidepressant treatment or had taken the last medication at least six weeks prior to the study, two had been treated with tricyclic antidepressants up to three days before light exposure, and the remaining patients were without medication in ~ last 6 - ! 2 days (see Table 2). The mean wash-out period was 8.7 _+. 3.4 days. Thirteen patients presented with the first manifestation of illness (second manifestation: n = 8, third ~ f e s t a t i o n : n - 11, four or more manifestations: n = 10).
Procedure To minimize therapy-independent changes in psychopathology occuning shortly after admission, phototherapy was given from the 4th to 7th day after patients had been admitted to the hospital. During a seven-day period, the patients were rando~y e x p o ~ to either bright white light of 2500 lux or dim red light of 50 lux from 7:20 AM tO 9:20 AM. The patients were sitting alone in a room otherwise shut off from light. Phototherapy was administered under supervision of the ward staff. To guarantee absolute compliance d u n g treatment, a nurse ascertained at lO-min intervals that the patient was s i n g properly in front of the light box and not sleeping. To exclude additional effects of natural su~ght, especially on clear sunny summer days, patients were requested not to leave the hospital during the course of exposure to light. During the seven days of exposure to fight, patients ~id not receive psycbou'-opic medication except a maximum of ! ~ mg chJ.o.~1_hhyd_~Jte per day, when required. On the day before and after light therapy (days 0 and 8), patients were rated on the 21-item Hamilton Depression Rating scale (HDRS, Hamilton 1967) by an experienced and trained rater, blind to the type of exposure to light. The scale of C ~ c a l Global Impressions [(CGI), NIMH 1970, 1976] was completed by the ward physician, who attended to the patients before and after light therapy, and who was also blind to the treatment condition. Additionally, patients completed self-rating scales including the Depression Scale [(parallel form D-S and D-S') yon Zerssen 1986], the Complaint List (C-L, yon 7_erssen 1986) and a visual analogue scale [(VAS) Ai~en 1969] twice ~ l y at 7 AM and 7 PM. To measure subject expectation of the therapeutic method, we assessed the "subjective initial response" (Priebe 1987), which means the patients' statements after the first exposure to bright white or dim red light. The patients were asked whether they believed they receive the fight treatment. There was no difference in expectation
Age
60 35 57 54 67 04 47 43 43 40 60 3! 38 57 42 42 49 24 46
66
48 63 61
Subject
I 2 3 4 5 6 7 8 9 10 II 12 i3 14 15 16 i7 18 19
20
2! 22 23
m f f
f
m f f f f f m f f m f f f f f f m f f
Sex
II i !
I
| ! l I ii i ! I i ll ! !
I
i I1 ! !1 ! I
Diagnosis*
4/64 2/70 5/62
8/79
9/86 4/78 2/87 6/81 5/70 I/86 3/68 10/74 10/86 4/78 12/86 12/85 9/83 4/87 6/73 10/73 2/80 5/87 2/71
m.i.
I st
I 3 2
3
0 3 0 2 I 2 2 4 0 2 0 I ! 0 2 3 5 0 6
p.m.
N ° of
O.
i !/87 ! 1/87 !/88
9•87
9/86 11/86 12/86 1/87 10/86 2/87 3/87 4/87 10/86 3/87 12/86 9,/86 5/87 4/87 3/87 4/87 ! !/87 5/87 4/87 y y y
y
y y y y y y y y y y y y
n
y y y n y y
day 0
S.d.
y y y
y
y y y y n y y n y y y y y y y y y n y
day 8
Clomipramine ( I I ) L-Tryptophan (8) Oxazepam (9), Dibenzepine (9)
0
Maprotiline ( I I ) 0 Clomipramine (3), Ludiomil (3) 0 0 Dibenzepine (3) 0 0 Triflupromazine (2 !) 0 0 Perazine (6) Maprotiline (I 0) Fluspirilene (9) Dibenzepine (10) Maprotiline (14) 0 Amitriptyline (7) lmipramine (10)
Medication
Response to Bright and Dim Light Exposure
m.r.m,
Table 2. Individual Clinical Characteristics and h e i r
b d
1/88 !/88 ~88
1/88
1/87 ~J87 ~87 2/87 ~J87 3/87 3/87 4:87 5/87 5/87 5/87 5~87 5/87 6/87 7/87 7:87 ! I/87 11/87 !/88
b b d d b d b b b d d d b b b b b b d d d
Time of treatment
Type of light exp.
+
+
+
Responder
IP,.t
~t
>
e~,k
51 64 61 66 60 72 53 72 64 65 77 4! 29 66 57 52 78 41 67
f f f f f f f f m f f m f f f f f f m
I I 1 I i I ! ! | i I I I I I il I I !
5/67 10/80 ~88 6/67 3/87 12/87 4/75 7t87 3/86 5/85 7/83 3/88 3/88 2/75 !/88 8173 2/63 1/88 5/49
2 I 0 13 ! 0 2 0 2 ! i 0 0 2 0 7 2 0 5
7187 5/77 2/88 3/88 1188 12/87 !/88 7•87 2/88 4/88 3/88 3/88 3/88 7/88 !/88 4/88 7/88 !/88 8/88
y y y y y y y y y y y y y y y y y y y
y y y y y y y y y y y y y y y y y y y
*, major depressive disorder = !, bipolar depression = !!. Ist m.i,, first manifestation of illness (month/year). N° of p, m , , number of prior manifestations. O, m r , m , , onsel of most recent manifestation (month/year). S,d., sleep disturbances (HDRS, items 4-6) yes,/no -- y/n. Medication, subs~nce and number of days after' the last intake ( ) preceding light therapy. Type of light exposure, bright light (b) ! dim light (d). Time of treatment (month/year) Responder ! + ), decrease of HDRS-score
257
Phototherapy in Nonseasonal Depression Arthur Mackert, Hans-Peter Volz, Rolf-Dieter Stieglitz, and B no Miiller-Oerlinghausen
Previous reports have shown that bright light exposure max, benefit patients with seaso~l depression. In the present study, the possible therapeutic effect of bright light in nonseasonal major depressive disorder was examined. Forts,-two depressed patients not receivb~g additional antidepressant medication were exposed to bright white light of 25bO iux or dim red light of 50 hoe over one week for m,o hr daily in the morning. The change in depressive symptoms was assessed by rating scales (Hamilton Depression Rating Scale, CGI) and by self-rating scales (Depression Scale, Complaint List, Visual Analogae Scale). Consistent for all ratings, the decrease in depressive sb.'mptoms after bright white light was only slight and not different from dim red-light exposure. Contrary. to the findings in seasonal affective disorder, phototherapy administered over one week for two hr daily is not effective in nonseasonal major depressive disorder. Introduction Seasonal affective disorder (SAD) is characterized by recumng cycles of depression in the fall and winter with hypomania or euthymia in the spring and summer. Lewy et al (1982) first reported on a patient with seasonal mood cycles, whose winter depression retorted when daylight was lengthened with bright artificial light. Subsequent studies have shown that patients with SAD improve on exposure to bright light of approx~ately 2500 lux in intensity, whereas dim light (300 lux or less) has only a negligible therapeutic effect (Rosenthal et al 1984, 1985; James et al 1985; Wehr et al 1987; Isaacs et al 1988). The antidepressant effect produced by bright artificial light appears within one week, w;th r~lanc~ nc..alh,
There have been only a few investigations to determine whether bright light may also induce remission in patients with nonseasonal depression. Kripke et al (1983a) found a significantly greater effect after a single hour of bright light than after dim light exposure from 5 AM to 6 AM in 12 patients suffering from major depressive disorder. Dietzel et al (1986) reported a significant improvement in mood and sleep of 10 female patients with major depressive disorder after a single day of light therapy of 3 hr duration in the morning and 4 hr in the evening. In contrast, Yerevanian et al (1986) found a beneficial effect of a i- to 2-week phototherapy only in seasonal, but not in nonseasonal depressives, although most of the nonseasonal depressives had concurrently received psychotropic
From the Department of Psychiatry. Free University of Berlin. Germany. Address reprint requests to Dr. A. Mackert. Psychiatrische Klinik und Polildinik der Freien Univers~t Berlin, Eschenallee 3, D-1000 Berlin 19 FRG. Received September 2. 1990; revised February 27, 1991. 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
38
BIOL PSYCHIATRY 1991;~:257~268
A. Mackert et al
agents during light treatment. Kripke et al (1987) reported only a minimal reduction in the symptoms of 14 patients with major depression in response to bright light given for 5 days, either for one ~ ia the morning or for one hr both in the morning and in the evening. In a subsequent study, nonseasonal depressed patients neared with bright light over one week for 3 hr daily in the evening showed an approximate 20% decrease in depression ratings when compared to the group receiving dim light in the stone design, which had not improved (Kripke et al 1989). The available literature on the benefits of phototherapy in nonseasonal depression is rather contradictory. This is mainly attributable to the small number of subjects involved and to differences in the experimental design, in particular to (a) the number of days, (b) the time of day, (c) the daily duration of exposure to light, and (d) the concomitant use or nonuse of antidepressants. The aim of the present study was to evaluate a sufficiently large number of patients and determine whether bright light as opposed to dim light is suitable for clinical treatment of patients suffering from major depression without recurrent fall/winter depression. Preliminary reports of some on these data in a siaaller group of patients were recently published (Mackert et al 1990; Volz et al 1990).
Methods
Subjects From January 1987 to November 1988, 50 inpatients consecutively admitted and meeting Research Diagnostic Criteria (RDC) for major depressive disorder (Spitzer et al 1977) consented to participate in the study. Patients with seasonal depression were excluded according to the criteria of seasonality based on DSM-III-R: three episodes, at least two of which were consecutive, with manifestation within a seasonal 90-day period between the beginning of September and the end of November (the seasonal pattern according to DSM-III-R is restricted to a 60-day window). Because 2 patients had a first manifestation of depressive illness between September and November (see Table 2), a seasonal depression occurring during the further course of illness could not be ruled out. Other exclusion criteria were ophthalmologic disorders, alcohol or drug abuse, brain injury and neurological disorders, and acute suicidal tendencies. Patients with an IQ lower than 90 as measured by a multiple choice vocabulary test (Lehrl 1978) were also not included. Before beginning the study, each patient underwent a medical examination including both routine laboratory analysis and electrocardiogram (l~CCi). unne specimens were obtained to detect the use of illicit drugs. The 50 patients were randomly exposed to either bright white or dim red light. The patients were informed that they were to participate in a study, in which two different kinds of exposure to light would be investigated. They were not told that dim red light was expected to be ineffective. Eight patients discontinued the study either because drug treatment was mandatory on clinical grounds (6 patients), or because urine specimens revealed the use of illicit drugs (2 patients). Of the remaining 42 patients, 36 with major depressive disorder and 6 with bipolar depression, 22 were exposed to bright white light and 20 patients to dim red light. As may be seen from Table 1, there were no statistical differences in age, sex, and initial HDRS-scores between these two subgroups. Based on documentation of previous hospitalizations, reports from psychiatrists, who had treated these patients as outpatients, as well as information from relatives and the patients themselves, a drug history was established for each patient with special regard to prior man-
BIOL.PSY(~I~TRY
Phototherapy in Nonseasonal Depression
259
Table I. Age, Sex, and Initial HDRS of Patients Treated with Bright and Dim Light Patients ~ All patients Gender re_Me
female Age (years) Hamilton Depression Rating Scale (HDRS) before treatment
8 33 54.2 ± 13.2 19.3 ± 4.2
Bright white light (n = 22)
to D ~ red ~ght (n = 20)
5
3
17
17
51.5 ± 14.7 19.5 ± 4.1
57.2 ± II.7 |9.1 -*- 4.2
NS (X ~ tesO NS NS
ifestations and an up-to-date history of medication (see Table 2). Thirteen patients were without antidepressant treatment or had taken the last medication at least six weeks prior to the study, two had been treated with tricyclic antidepressants up to three days before light exposure, and the remaining patients were without medication in ~ last 6 - ! 2 days (see Table 2). The mean wash-out period was 8.7 _+. 3.4 days. Thirteen patients presented with the first manifestation of illness (second manifestation: n = 8, third ~ f e s t a t i o n : n - 11, four or more manifestations: n = 10).
Procedure To minimize therapy-independent changes in psychopathology occuning shortly after admission, phototherapy was given from the 4th to 7th day after patients had been admitted to the hospital. During a seven-day period, the patients were rando~y e x p o ~ to either bright white light of 2500 lux or dim red light of 50 lux from 7:20 AM tO 9:20 AM. The patients were sitting alone in a room otherwise shut off from light. Phototherapy was administered under supervision of the ward staff. To guarantee absolute compliance d u n g treatment, a nurse ascertained at lO-min intervals that the patient was s i n g properly in front of the light box and not sleeping. To exclude additional effects of natural su~ght, especially on clear sunny summer days, patients were requested not to leave the hospital during the course of exposure to light. During the seven days of exposure to fight, patients ~id not receive psycbou'-opic medication except a maximum of ! ~ mg chJ.o.~1_hhyd_~Jte per day, when required. On the day before and after light therapy (days 0 and 8), patients were rated on the 21-item Hamilton Depression Rating scale (HDRS, Hamilton 1967) by an experienced and trained rater, blind to the type of exposure to light. The scale of C ~ c a l Global Impressions [(CGI), NIMH 1970, 1976] was completed by the ward physician, who attended to the patients before and after light therapy, and who was also blind to the treatment condition. Additionally, patients completed self-rating scales including the Depression Scale [(parallel form D-S and D-S') yon Zerssen 1986], the Complaint List (C-L, yon 7_erssen 1986) and a visual analogue scale [(VAS) Ai~en 1969] twice ~ l y at 7 AM and 7 PM. To measure subject expectation of the therapeutic method, we assessed the "subjective initial response" (Priebe 1987), which means the patients' statements after the first exposure to bright white or dim red light. The patients were asked whether they believed they receive the fight treatment. There was no difference in expectation
Age
60 35 57 54 67 04 47 43 43 40 60 3! 38 57 42 42 49 24 46
66
48 63 61
Subject
I 2 3 4 5 6 7 8 9 10 II 12 i3 14 15 16 i7 18 19
20
2! 22 23
m f f
f
m f f f f f m f f m f f f f f f m f f
Sex
II i !
I
| ! l I ii i ! I i ll ! !
I
i I1 ! !1 ! I
Diagnosis*
4/64 2/70 5/62
8/79
9/86 4/78 2/87 6/81 5/70 I/86 3/68 10/74 10/86 4/78 12/86 12/85 9/83 4/87 6/73 10/73 2/80 5/87 2/71
m.i.
I st
I 3 2
3
0 3 0 2 I 2 2 4 0 2 0 I ! 0 2 3 5 0 6
p.m.
N ° of
O.
i !/87 ! 1/87 !/88
9•87
9/86 11/86 12/86 1/87 10/86 2/87 3/87 4/87 10/86 3/87 12/86 9,/86 5/87 4/87 3/87 4/87 ! !/87 5/87 4/87 y y y
y
y y y y y y y y y y y y
n
y y y n y y
day 0
S.d.
y y y
y
y y y y n y y n y y y y y y y y y n y
day 8
Clomipramine ( I I ) L-Tryptophan (8) Oxazepam (9), Dibenzepine (9)
0
Maprotiline ( I I ) 0 Clomipramine (3), Ludiomil (3) 0 0 Dibenzepine (3) 0 0 Triflupromazine (2 !) 0 0 Perazine (6) Maprotiline (I 0) Fluspirilene (9) Dibenzepine (10) Maprotiline (14) 0 Amitriptyline (7) lmipramine (10)
Medication
Response to Bright and Dim Light Exposure
m.r.m,
Table 2. Individual Clinical Characteristics and h e i r
b d
1/88 !/88 ~88
1/88
1/87 ~J87 ~87 2/87 ~J87 3/87 3/87 4:87 5/87 5/87 5/87 5~87 5/87 6/87 7/87 7:87 ! I/87 11/87 !/88
b b d d b d b b b d d d b b b b b b d d d
Time of treatment
Type of light exp.
+
+
+
Responder
IP,.t
~t
>
e~,k
51 64 61 66 60 72 53 72 64 65 77 4! 29 66 57 52 78 41 67
f f f f f f f f m f f m f f f f f f m
I I 1 I i I ! ! | i I I I I I il I I !
5/67 10/80 ~88 6/67 3/87 12/87 4/75 7t87 3/86 5/85 7/83 3/88 3/88 2/75 !/88 8173 2/63 1/88 5/49
2 I 0 13 ! 0 2 0 2 ! i 0 0 2 0 7 2 0 5
7187 5/77 2/88 3/88 1188 12/87 !/88 7•87 2/88 4/88 3/88 3/88 3/88 7/88 !/88 4/88 7/88 !/88 8/88
y y y y y y y y y y y y y y y y y y y
y y y y y y y y y y y y y y y y y y y
*, major depressive disorder = !, bipolar depression = !!. Ist m.i,, first manifestation of illness (month/year). N° of p, m , , number of prior manifestations. O, m r , m , , onsel of most recent manifestation (month/year). S,d., sleep disturbances (HDRS, items 4-6) yes,/no -- y/n. Medication, subs~nce and number of days after' the last intake ( ) preceding light therapy. Type of light exposure, bright light (b) ! dim light (d). Time of treatment (month/year) Responder ! + ), decrease of HDRS-score
