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Mood effects of alternate-day corticosteroid therapy in patients with systemic lupus erythematosus
Mood Effects of Alternate-Day Corticosteroid Therapy in Patients with Systemic Lupus Erythematosus Russell T. Joffe, M.D. Department of Psychiatry, St. Michael’s Hospital and the University of Toronto
Kirk D. Denicoff, M.D. David R. Rubinow, M.D. Psychiatry Consultation-Liason Service, National Institute of Mental Health
George Tsokos, M.D. Department of Medicine, Uniformed Services University of the Health Sciences.
James E. Balow, M.D. Stanley E. Pillemer, M.D. Kidney Section, NIDDK, National Institutes of Health
Abstract: Moodand cognitionwere assessed on consecutive days in 18 female patients with systemic lupus eythematosus on alternate-day corticosteroid therapy. No overall differences in mood and cognition were observed between the on- and offmedication days. However, 10 patients showed marked worsening or improvement of either depression or anxiety on their off-medication day. Two weeks ofprospective behavioral ratings confirmed the observed mood changes in several patients. The clinical and theoretical implications of these findings are discussed.
Corticosteroids are important in the treatment of inflammatory and immunologically mediated disorders such as systemic lupus erythematosus (SLE) [l]. Despite widespread use, corticosteroid treatment is associated with a wide range of physical and mental adverse effects [24]. In particular, a variety of psychiatric syndromes, including depression, mania, and psychosis, significantly complicate the management of patients on steroid treatment [24]. Several studies have shown that
alternate-day dosage of steroids may substantially decrease the occurrence of physical side effects [5, 61. An early study supported the assumption that alternate-day dosage regimens may also lead to reductions in the frequency and severity of psychiatric disturbance [7l. However, several clinical reports have described marked changes in mood with alternate-day corticosteroid therapy [8]. In this study we have systematically assessed the effects of alternate-day corticosteroid therapy on mood and cognition in patients with SLE.
Methods Eighteen subjects, all female, mean age 36.7 2 11.3 years, who were outpatients in the Rheumatology Clinic of the NIADDK, consented to participate in the study. All patients met the revised criteria of the Arthritis and Rheumatism Association (ARA) for the diagnosis of SLE and were currently taking altemateday prednisone treatment. Since the prevalence of General Hospital Psychiatry 10, 56-60,1988
56 1SSN 016~8343/&31$0.00
Alternate Day Corticosteroid Therapy
SLE is 9 times higher in women than in men, the study was confined to women. Subjects were evaluated at 12 noon on 2 consecutive days, 3 hours after the time of prednisone administration, by a research psychiatrist (R.J. or K.D.) who was blind to which day the patient took her prednisone. Eight patients were seen on their off-medication day first, and the remaining 10 patients were seen on their on-medication day for their first assessment. At the time of the first assessment, lifetime psychiatric diagnosis was determined using a modified version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version [9], which allows one to make diagnosis of depression mania, anxiety, and psychosis by Research Diagnostic Criteria [lo]. The patients completed the same evaluation on both days. This included: 1) Beck Depression Inventory, a self-rated measure of depression [ll]; 2) Spielberger State Anxiety Inventory, a self-rated measure of anxiety [12]; 3) Symptom Checklist-90R, which provides measures along nine dimensions of psychopathology including depression, euphoria, and psychosis [13]; 4) Digit Symbol Subtest of the Wechsler Adult Intelligence Scale [14], a measure of visual-motor performance, attention, and concentration that is also a good indicator of cerebral function; and 5) Cancellation Test [15], a measure of visual-motor and visual-spatial performance. A series of visual analog scales measuring depression, irritability, fatigue, anxiety, physical discomfort, confusion, sexual arousal, joint and muscle pain, and general well-being were completed by the patient on each test day and for the following 2 weeks. These scales have been shown to provide a sensitive measure of symptomatic change over time [16], At the time of psychiatric assessment, the rheumatologists (S.P. and G.T.) evaluated each patient by clinical examination and chart review for the presence of current and past ARA criteria for SLE. A global clinical assessment was made of whether the patient currently had active or inactive disease. Differences in mood and cognition between onand off-medication days were evaluated by Student t-tests.
Results The mean dosage of qod prednisone taken was 13.9 & 9.4 mg (mean + SD.). With regard to the rheumatological assessment, five patients were considered to have active disease, and 13 patients were
considered to have inactive disease. At the time of evaluation the mean number of current ARA criteria for systemic lupus erythematosus met was 2.8 + 3.4 and the mean number of past ARA criteria met was 5.8 + 2.0. All but one patient had no history of seizures or psychosis. There was no significant difference in mean scores on each of the mood and cognitive tests for the on-and off-medication days. In particular, there was no significant difference between on- and offmedication days on the Beck Depression Inventory (7.8 ? 6.3 versus 8.7 & 6.4, p = NS) and Spielberger State Anxiety Inventory (38.7 ? 10.4 versus 40.4 +- 10.0, p = NS). However five of the 18 subjects showed a substantial change in scores on the Beck Depression Inventory between their on- and off-medication days. Three patients had an increase and two patients had a decrease of between nine and eleven points on the Beck Depression Inventory, indicating a marked increase in depressive symptoms. In the remaining 13 patients there was minimal change in depression scores. Six of the 18 patients had a change in 10 or more points in their score on the Spielberger State Anxiety Inventory between the 2 days. Four of the patients had an increase in anxiety scores of between 12 and 21 points indicating a marked worsening of their anxiety, whereas two patients had reductions of 11 and 15 points indicating a marked alleviation of anxiety symptoms. There was a significant positive relationship between changes in Beck Depression Inventory and Spielberger Anxiety Inventory Scores for the whole group (Pearson correlation coefficient r = 0.51, df = 17, p < 0.05) as well as for the patients who showed significant mood changes (r = 0.58, df = 9, p < 0.05). There was no relationship between mood ratings and prednisone dose. When patients were grouped according to whether their Beck OYSpielberger Inventory Scores indicated improvement, worsening or no change on drug, then six patients were noted to markedly improve, four patients were noted to get worse, and the remainder showed no change in either depression or anxiety scores on their on-medication day (Table 1). Patients with active and inactive SLE were evenly distributed among the three groups (Table 1). In addition, several of the patients, in their 2-week prospective self-ratings, using visual analog scales, reported marked differences in mood between onmedication and off-medication day confirming the finding on the two day evaluation (Fig. 1). Moreover, those who had either their off- or on-medication day 57
R.
J. Joffe et al.
Table 1. Comparison of patients who improved, worsened, or showed no change when the on medication was compared to the off-medication day Improved
Worsened
No change
6 2
4
8 2
Number Active SLE Mean prednisone dose (mg)
11.2
+- 5.7”
11.8
+ 4.3
16.5
5
Change
in Beck Score
-5.8
5 4.7
+7.3
*
2.2
-0.8
f
3.2
Change
in Spielberger
5
+6.5
+ 7.7
-0.7
”
3.4
“Improvement,
worsening,
Score
-12.3
1
8.8
12.5
and no change defined by changes in Beck or Spielberger scores (see text).
bValues equal mean r+_S.D.
first were evenly distributed between the improved, worsened, and no-change groups. Two patients had a lifetime psychiatric diagnosis. One had a past history of acute mania related to high-dose steroid treatment and showed improvement in depression scores between on- and off-medication days. The other had a past history of major depression and showed no change in behavioral scores. No patient had current evidence of mania or hypomania.
Discussion Our data show that substantial alterations in mood, particularly depression and anxiety, may occur between the day-on and the day-off medication in a subgroup of patients with systemic lupus erythematosus who are treated with alternate-day prednisone. Although the overall mean scores for the various mood and cognitive tests were not significantly different between the on-medication and off-medication days, 10 of the 18 patients were noted to have a sub stantial alteration in their levels of depression or anxiety. Six of the subjects had a marked improvement in depression or anxiety on the day that they received medication, whereas four subjects had substantial worsening of depression or anxiety on the day on which they received medication. Therefore, both daily and alternate-day exogenous steroids are associated with improvement or worsening of mood. AIthough the mechanisms of these mood effects are unknown, further study of this phenomenon may clarify neuroendocrine factors involved in the regulation of mood. Our data confirm the clinical findings of Sharfstein and colleagues [S] who described three patients who showed mood cycling when treated
with 50-60 mg of prednisone on an alternate-day schedule. However, the doses used by our patients were substantially lower than those used in the cases reported by Sharfstein et al. [S]. Although a dose-response effect of prednisone in the induction of psychiatric symptoms has been demonstrated in several studies (31, our data would suggest that low-dose prednisone treatment, on an alternateday basis, may lead to significant changes in depression and anxiety and, therefore, significant psychiatric morbidity. Contrary to other reports 171, we observed significant changes in mood and cognition with alternate-day steroids. Cordess and colleagues [7] suggested that alternate-day steroids were associated with less psychiatric morbidity than daily treatment schedules. However, they compared baseline psychopathology in alternate-day steroid patients with normal controls and did not prospectively examine mood and cognitive symptoms that may have occurred as a function of treatment. Our findings are not due to an effect of order of treatment, as patients who had their on- or offmedication day first were equally distributed between the improved, worsened, and no-change groups. Furthermore, our results are unlikely to be due to chance as they were confirmed in the 2week prospective ratings, although unspecified factors also appear to modulate this process and contribute to the variance in mood. In conclusion, our data show that altemateday treatment with low doses of prednisone can be associated with substantial fluctuations in levels of depression and anxiety. Our findings have several implications. First, it would be important to establish whether the daily mood fluctuation is due to the steroids or to the SLE. We examined three patients with SLE on no steroids in the same manner and found no significant daily fluctuation in
Alternate Day Corticosteroid
Therapy
w No Change U Improved -Worsened
80 4 9 70ul $60 7 a= 505 ; 40 .’ 3020 10 -
0
1
2
3
4
5
6
7 8 Days
9
10 11 12 13 14
Figure 1. Two-week visual analog scale ratings for patients who improved, worsened, and showed no change in mood on alternate-day corticosteroid therapy. These data are consistent with the findings on the 2-day assessment, although it is apparent that steroid treatment does not account for all the variance in mood.
mood. This suggests that SLE need not be associated with mood alterations, although the effects of prednisone on mood may be specifically related to patients with SLE 141. Second,therefore, it would be important to evaluate the mood effects of alternate-day steroids in other illnesses in which they are commonly used. Last, clinicians should be aware of and carefully observe patients for mood changes on alternate-day steroids as it is possible that alterations in mood, particularly worsening, may have an impact on medication compliance. Additionally, it is appropriate for physicians to advise patients that alterations in mood may be a complication of alternate-day and daily steroid administration.
References 1. Kaplan D: Systemic lupus erythematosus-corticosteroids. Clin Rheum Dis 9:601-616, 1983 2. Ling MHM, Perry PJ, Tsuang MT: Side effects of corticosteroid therapy. Arch Gen Psychiatry 38:471477, 1981 psychiatric 3. Lewis DA, Smith RE: Steroid-induced syndromes. J Affective Discord 5:319-332, 1983 4. Hall RCW, Popkin MK, Stickney SK, Gardner ER: Presentation of the steroid psychoses. J Nerv Ment Dis 167:229-236, 1979 5. Fauci AS: Alternate-day corticosteroid therapy. Am J Med 64:729-731, 1978 6. Fauci AS, Dale DC, Balow JE: Glucocorticosteroid therapy: Mechanisms of action and clinical considerations. Ann Intern Med 84:304-315, 1976 7. Cordess C, Folstein M, Drachman D: Psychiatric effects of alternate-day steroid therapy. Br J Psychiatry 138:504-506, 1981 8. Sharfstein SS, Sack DS, Fauci AS: Relationship between alternate-day corticosteroid therapy and behavioural abnormalities. JAMA 248:2987-2989, 1982 9. Spitzer RL, Endicott J: Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADSL), Ed. 3. New York, Psychiatric Institute, 1978 10. Spitzer RL, Endicott J, Robins E: Research diagnostic criteria: Rationale and reliability. Arch Gen Psychiatry 35:773-782, 1978 11. Beck AH, Ward CH, Mendelson M: An inventory for measuring depression. Arch Gen Psychiatry 31:561-571, 1961
59
R. J. Joffe et al.
12. Spielberger CB, Gorsuch RL, Luschene RE: STAI Manual for the State-Trait Anxiety Inventory. Palo Alto, Ca., Consulting Psychologist Press Inc., 1970 13. Derogatis S: SCL-90-R Manual. Towson, Md., Clinical Psychometric Research, 1984 14. Wechsler D: Wechsler Adult Intelligence Scale Revised. New York, The Psychological Corporation, 1981 15. Talland G: Deranged Memory. New York, Academic Press, 1985. 16. Rubinow, DR, Roy-Byrne PI’, Hoban MC, Gold PW,
60
Post RM: Prospective assessment of menstrually related mood disorders. Am J Psychiatry 1413684-686, 1984 Direct reprint requeststo: David Rubinow, M.D. National Institute of Mental Health Bldg 10, Room 3N238 9000 Rockville Pike Bethesda, MD 20892
Kirk D. Denicoff, M.D. David R. Rubinow, M.D. Psychiatry Consultation-Liason Service, National Institute of Mental Health
George Tsokos, M.D. Department of Medicine, Uniformed Services University of the Health Sciences.
James E. Balow, M.D. Stanley E. Pillemer, M.D. Kidney Section, NIDDK, National Institutes of Health
Abstract: Moodand cognitionwere assessed on consecutive days in 18 female patients with systemic lupus eythematosus on alternate-day corticosteroid therapy. No overall differences in mood and cognition were observed between the on- and offmedication days. However, 10 patients showed marked worsening or improvement of either depression or anxiety on their off-medication day. Two weeks ofprospective behavioral ratings confirmed the observed mood changes in several patients. The clinical and theoretical implications of these findings are discussed.
Corticosteroids are important in the treatment of inflammatory and immunologically mediated disorders such as systemic lupus erythematosus (SLE) [l]. Despite widespread use, corticosteroid treatment is associated with a wide range of physical and mental adverse effects [24]. In particular, a variety of psychiatric syndromes, including depression, mania, and psychosis, significantly complicate the management of patients on steroid treatment [24]. Several studies have shown that
alternate-day dosage of steroids may substantially decrease the occurrence of physical side effects [5, 61. An early study supported the assumption that alternate-day dosage regimens may also lead to reductions in the frequency and severity of psychiatric disturbance [7l. However, several clinical reports have described marked changes in mood with alternate-day corticosteroid therapy [8]. In this study we have systematically assessed the effects of alternate-day corticosteroid therapy on mood and cognition in patients with SLE.
Methods Eighteen subjects, all female, mean age 36.7 2 11.3 years, who were outpatients in the Rheumatology Clinic of the NIADDK, consented to participate in the study. All patients met the revised criteria of the Arthritis and Rheumatism Association (ARA) for the diagnosis of SLE and were currently taking altemateday prednisone treatment. Since the prevalence of General Hospital Psychiatry 10, 56-60,1988
56 1SSN 016~8343/&31$0.00
Alternate Day Corticosteroid Therapy
SLE is 9 times higher in women than in men, the study was confined to women. Subjects were evaluated at 12 noon on 2 consecutive days, 3 hours after the time of prednisone administration, by a research psychiatrist (R.J. or K.D.) who was blind to which day the patient took her prednisone. Eight patients were seen on their off-medication day first, and the remaining 10 patients were seen on their on-medication day for their first assessment. At the time of the first assessment, lifetime psychiatric diagnosis was determined using a modified version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version [9], which allows one to make diagnosis of depression mania, anxiety, and psychosis by Research Diagnostic Criteria [lo]. The patients completed the same evaluation on both days. This included: 1) Beck Depression Inventory, a self-rated measure of depression [ll]; 2) Spielberger State Anxiety Inventory, a self-rated measure of anxiety [12]; 3) Symptom Checklist-90R, which provides measures along nine dimensions of psychopathology including depression, euphoria, and psychosis [13]; 4) Digit Symbol Subtest of the Wechsler Adult Intelligence Scale [14], a measure of visual-motor performance, attention, and concentration that is also a good indicator of cerebral function; and 5) Cancellation Test [15], a measure of visual-motor and visual-spatial performance. A series of visual analog scales measuring depression, irritability, fatigue, anxiety, physical discomfort, confusion, sexual arousal, joint and muscle pain, and general well-being were completed by the patient on each test day and for the following 2 weeks. These scales have been shown to provide a sensitive measure of symptomatic change over time [16], At the time of psychiatric assessment, the rheumatologists (S.P. and G.T.) evaluated each patient by clinical examination and chart review for the presence of current and past ARA criteria for SLE. A global clinical assessment was made of whether the patient currently had active or inactive disease. Differences in mood and cognition between onand off-medication days were evaluated by Student t-tests.
Results The mean dosage of qod prednisone taken was 13.9 & 9.4 mg (mean + SD.). With regard to the rheumatological assessment, five patients were considered to have active disease, and 13 patients were
considered to have inactive disease. At the time of evaluation the mean number of current ARA criteria for systemic lupus erythematosus met was 2.8 + 3.4 and the mean number of past ARA criteria met was 5.8 + 2.0. All but one patient had no history of seizures or psychosis. There was no significant difference in mean scores on each of the mood and cognitive tests for the on-and off-medication days. In particular, there was no significant difference between on- and offmedication days on the Beck Depression Inventory (7.8 ? 6.3 versus 8.7 & 6.4, p = NS) and Spielberger State Anxiety Inventory (38.7 ? 10.4 versus 40.4 +- 10.0, p = NS). However five of the 18 subjects showed a substantial change in scores on the Beck Depression Inventory between their on- and off-medication days. Three patients had an increase and two patients had a decrease of between nine and eleven points on the Beck Depression Inventory, indicating a marked increase in depressive symptoms. In the remaining 13 patients there was minimal change in depression scores. Six of the 18 patients had a change in 10 or more points in their score on the Spielberger State Anxiety Inventory between the 2 days. Four of the patients had an increase in anxiety scores of between 12 and 21 points indicating a marked worsening of their anxiety, whereas two patients had reductions of 11 and 15 points indicating a marked alleviation of anxiety symptoms. There was a significant positive relationship between changes in Beck Depression Inventory and Spielberger Anxiety Inventory Scores for the whole group (Pearson correlation coefficient r = 0.51, df = 17, p < 0.05) as well as for the patients who showed significant mood changes (r = 0.58, df = 9, p < 0.05). There was no relationship between mood ratings and prednisone dose. When patients were grouped according to whether their Beck OYSpielberger Inventory Scores indicated improvement, worsening or no change on drug, then six patients were noted to markedly improve, four patients were noted to get worse, and the remainder showed no change in either depression or anxiety scores on their on-medication day (Table 1). Patients with active and inactive SLE were evenly distributed among the three groups (Table 1). In addition, several of the patients, in their 2-week prospective self-ratings, using visual analog scales, reported marked differences in mood between onmedication and off-medication day confirming the finding on the two day evaluation (Fig. 1). Moreover, those who had either their off- or on-medication day 57
R.
J. Joffe et al.
Table 1. Comparison of patients who improved, worsened, or showed no change when the on medication was compared to the off-medication day Improved
Worsened
No change
6 2
4
8 2
Number Active SLE Mean prednisone dose (mg)
11.2
+- 5.7”
11.8
+ 4.3
16.5
5
Change
in Beck Score
-5.8
5 4.7
+7.3
*
2.2
-0.8
f
3.2
Change
in Spielberger
5
+6.5
+ 7.7
-0.7
”
3.4
“Improvement,
worsening,
Score
-12.3
1
8.8
12.5
and no change defined by changes in Beck or Spielberger scores (see text).
bValues equal mean r+_S.D.
first were evenly distributed between the improved, worsened, and no-change groups. Two patients had a lifetime psychiatric diagnosis. One had a past history of acute mania related to high-dose steroid treatment and showed improvement in depression scores between on- and off-medication days. The other had a past history of major depression and showed no change in behavioral scores. No patient had current evidence of mania or hypomania.
Discussion Our data show that substantial alterations in mood, particularly depression and anxiety, may occur between the day-on and the day-off medication in a subgroup of patients with systemic lupus erythematosus who are treated with alternate-day prednisone. Although the overall mean scores for the various mood and cognitive tests were not significantly different between the on-medication and off-medication days, 10 of the 18 patients were noted to have a sub stantial alteration in their levels of depression or anxiety. Six of the subjects had a marked improvement in depression or anxiety on the day that they received medication, whereas four subjects had substantial worsening of depression or anxiety on the day on which they received medication. Therefore, both daily and alternate-day exogenous steroids are associated with improvement or worsening of mood. AIthough the mechanisms of these mood effects are unknown, further study of this phenomenon may clarify neuroendocrine factors involved in the regulation of mood. Our data confirm the clinical findings of Sharfstein and colleagues [S] who described three patients who showed mood cycling when treated
with 50-60 mg of prednisone on an alternate-day schedule. However, the doses used by our patients were substantially lower than those used in the cases reported by Sharfstein et al. [S]. Although a dose-response effect of prednisone in the induction of psychiatric symptoms has been demonstrated in several studies (31, our data would suggest that low-dose prednisone treatment, on an alternateday basis, may lead to significant changes in depression and anxiety and, therefore, significant psychiatric morbidity. Contrary to other reports 171, we observed significant changes in mood and cognition with alternate-day steroids. Cordess and colleagues [7] suggested that alternate-day steroids were associated with less psychiatric morbidity than daily treatment schedules. However, they compared baseline psychopathology in alternate-day steroid patients with normal controls and did not prospectively examine mood and cognitive symptoms that may have occurred as a function of treatment. Our findings are not due to an effect of order of treatment, as patients who had their on- or offmedication day first were equally distributed between the improved, worsened, and no-change groups. Furthermore, our results are unlikely to be due to chance as they were confirmed in the 2week prospective ratings, although unspecified factors also appear to modulate this process and contribute to the variance in mood. In conclusion, our data show that altemateday treatment with low doses of prednisone can be associated with substantial fluctuations in levels of depression and anxiety. Our findings have several implications. First, it would be important to establish whether the daily mood fluctuation is due to the steroids or to the SLE. We examined three patients with SLE on no steroids in the same manner and found no significant daily fluctuation in
Alternate Day Corticosteroid
Therapy
w No Change U Improved -Worsened
80 4 9 70ul $60 7 a= 505 ; 40 .’ 3020 10 -
0
1
2
3
4
5
6
7 8 Days
9
10 11 12 13 14
Figure 1. Two-week visual analog scale ratings for patients who improved, worsened, and showed no change in mood on alternate-day corticosteroid therapy. These data are consistent with the findings on the 2-day assessment, although it is apparent that steroid treatment does not account for all the variance in mood.
mood. This suggests that SLE need not be associated with mood alterations, although the effects of prednisone on mood may be specifically related to patients with SLE 141. Second,therefore, it would be important to evaluate the mood effects of alternate-day steroids in other illnesses in which they are commonly used. Last, clinicians should be aware of and carefully observe patients for mood changes on alternate-day steroids as it is possible that alterations in mood, particularly worsening, may have an impact on medication compliance. Additionally, it is appropriate for physicians to advise patients that alterations in mood may be a complication of alternate-day and daily steroid administration.
References 1. Kaplan D: Systemic lupus erythematosus-corticosteroids. Clin Rheum Dis 9:601-616, 1983 2. Ling MHM, Perry PJ, Tsuang MT: Side effects of corticosteroid therapy. Arch Gen Psychiatry 38:471477, 1981 psychiatric 3. Lewis DA, Smith RE: Steroid-induced syndromes. J Affective Discord 5:319-332, 1983 4. Hall RCW, Popkin MK, Stickney SK, Gardner ER: Presentation of the steroid psychoses. J Nerv Ment Dis 167:229-236, 1979 5. Fauci AS: Alternate-day corticosteroid therapy. Am J Med 64:729-731, 1978 6. Fauci AS, Dale DC, Balow JE: Glucocorticosteroid therapy: Mechanisms of action and clinical considerations. Ann Intern Med 84:304-315, 1976 7. Cordess C, Folstein M, Drachman D: Psychiatric effects of alternate-day steroid therapy. Br J Psychiatry 138:504-506, 1981 8. Sharfstein SS, Sack DS, Fauci AS: Relationship between alternate-day corticosteroid therapy and behavioural abnormalities. JAMA 248:2987-2989, 1982 9. Spitzer RL, Endicott J: Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADSL), Ed. 3. New York, Psychiatric Institute, 1978 10. Spitzer RL, Endicott J, Robins E: Research diagnostic criteria: Rationale and reliability. Arch Gen Psychiatry 35:773-782, 1978 11. Beck AH, Ward CH, Mendelson M: An inventory for measuring depression. Arch Gen Psychiatry 31:561-571, 1961
59
R. J. Joffe et al.
12. Spielberger CB, Gorsuch RL, Luschene RE: STAI Manual for the State-Trait Anxiety Inventory. Palo Alto, Ca., Consulting Psychologist Press Inc., 1970 13. Derogatis S: SCL-90-R Manual. Towson, Md., Clinical Psychometric Research, 1984 14. Wechsler D: Wechsler Adult Intelligence Scale Revised. New York, The Psychological Corporation, 1981 15. Talland G: Deranged Memory. New York, Academic Press, 1985. 16. Rubinow, DR, Roy-Byrne PI’, Hoban MC, Gold PW,
60
Post RM: Prospective assessment of menstrually related mood disorders. Am J Psychiatry 1413684-686, 1984 Direct reprint requeststo: David Rubinow, M.D. National Institute of Mental Health Bldg 10, Room 3N238 9000 Rockville Pike Bethesda, MD 20892