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The effect of alcohol and substance abuse on the course of bipolar affective disorder
ELSEVIER
Journal of Affective
Disorders 37
(I 996) 43-49
Research report
The effect of alcohol and substance abuse on the course of bipolar affective disorder Jessica A. Feinman, David L. Dunner Uniumiry
of Wushin~fon
Medical
Received
Center,
Oufpufient
Psychiatry,
4225
I5 June 1995; revised 6 September
Rooscwelt
Way NE,
* Suite 306.
1995; accepted 27 September
Seurrle.
WA 98/O>.
lJ.V
1995
Abstract
It has been found that > 60% of bipolar I and almost 50% of bipolar II patients have a history of substance abuse (Regier et al., 1990). While previous studies have examined comorbidity of bipolar disorder and substance abuse, little has been done to examine the effect of substance abuse on the course of bipolar disorder. There has also been little distinction made between bipolar disorder occurring prior to substance abuse and that occurring after the onset of substance abuse. Given the high prevalence of substance abuse in bipolar patients, it would be useful to determine more about the effect of substance abuse on demographic and clinical features and on the course of illness. We attempted to do this with a retrospective chart review of 188 bipolar patients seen by D.L. Dunner between January 1992 and December 1993. Demographic and clinical information as well as information about course of illness were systematically extracted from the charts. We compared the means and percentages of these variables and analysed them for significance. Preliminary results show differences in demographics, clinical features and course of illness between patient groups. These differences may illustrate the clinical effects of substance abuse on the course of bipolar disorder. Our results also indicate that there are differences between patients whose bipolar disorder began prior to and those whose disorder began after the onset of substance abuse. Key~~ord.c:Substance abuse; Bipolar affective disorder; Alcohol; Course of illness
1. Introduction
The purpose of this paper is to determine the effect of alcohol and substance abuse on the course of bipolar affective disorder. In results from the Epidemiologic Catchment Area Study, bipolar I patients had a substance abuse prevalence rate of 60.7% and bipolar 11 patients had a substance abuse prevalence rate of 48.1% (Regier et al., 1990). Although several studies have examined comorbidity of substance abuse and affective disorders (Brady et al.,
* Corresponding
author. Fax: (I) (206) 543-7565.
0165.0327/96/$15.00 SD/
0165.0327(95)00080-l
0
1996 Elsevier Science B.V. All rights reserved
1991; Russell et al., 1994; Warner et al., 19941, there has been relatively little determined about the effect of substance abuse on the course of bipolar disorder. Given the high prevalence of substance abuse in patients with bipolar disorder, it would be useful to determine the effects of substance abuse on demographic and clinical features and on course of illness. Primary affective disorder (Feighner et al., 1972) refers to a mood disorder occurring prior to the onset of another psychiatric condition. Secondary affective disorders occur after the onset of other psychiatric conditions. To determine the effect of substance abuse on bipolar disorder, we studied 3 groups of patients. The 1st group consisted of patients with a
44
JA. Frinmun, D.L. Dunner/Journul
diagnosis of primary bipolar disorder who had no past or present history of alcohol or substance abuse (primary bipolar). The 2nd group consisted of those patients whose primary bipolar disorder was complicated by substance abuse which began after the onset of the bipolar disorder (complicated bipolar). The 3rd group was composed of patients whose bipolar disorder began after the onset of alcohol or substance abuse or dependence (secondary bipolar). In studies of comorbidity of substance abuse with mental disorders, both Regier et al. (1990) and Russell et al. (1994) found an association between substance abuse and anxiety disorders. Morrison (1974) found that twice as many alcoholic as nonalcoholic bipolar patients attempted suicide. These studies led us to expect that a greater percentage of secondary than primary bipolar patients would have panic attacks and that a greater percentage would have attempted suicide. There has also been speculation that use of cocaine might contribute to a rapid cycling pattern in bipolar disorder (Ananth et al., 1993). If this speculation is correct, we would expect a greater percentage of rapid cyclers in the complicated and secondary groups. Warner et al. (1994) found that 60% of the relatives of patients with moderate to severe substance abuse had a history of substance abuse, in contrast to 30.8% substance abuse for relatives of patients without a substance abuse history. Hensel et al. (1979) found a 4-fold increase in morbid risk for alcoholism among relatives of male patients with bipolar disorder complicated by drinking problems as compared with those male bipolar patients without drinking problems. They also found a decreased morbid risk for unipolar illness in relatives of those male patients with drinking problems. These results led us to expect a higher morbid risk for alcohol (and drug) use and a lower morbid risk for unipolar depression in the relatives of our complicated and secondary patients. Our hypotheses were that the primary and secondary groups would indeed differ and that the complicated group would have a profile intermediate between the 2 groups. We expected that the secondary group would have a later age of onset of bipolar disorder, greater percentage of rapid cyclers, a history of more panic attacks and suicide attempts and higher anxiety ratings. The secondary bipolar
of’Afectiue
Disorders 37 (1996) 43-49
patients were expected to have an increased family history of substance abuse and decreased family history of bipolar illness vs. primary bipolar patients. We were also interested to see how the groups differed with respect to age, sex, age of onset and type of bipolar illness.
2. Methods The authors carried out a retrospective chart review of all physician and self referred (485) outpatients seen by D.L. Dunner at the Center for Anxiety and Depression of the Department of Psychiatry, University of Washington between January 1992 and December 1993. D.L. Dunner evaluated all the patients using a semistructured interview format (Dunner, 1993) and all chart information was extracted by J.A. Feinman. All patients gave informed consent for research review of charts. Patients for whom a complete history could not be obtained (20) were excluded. Of patients with a complete history, all (209) patients with a history of both depression and mania/hypomania were included regardless of duration of mood state. During analysis of the data, those patients (21 patients) whose bipolar illness was secondary to another psychiatric illness, head trauma or MAO inhibitor use, but not to substance abuse, were excluded. The following definitions were used: a bipolar patient is defined as a person experiencing episodes of both major depression and mania or hypomania. Those patients having been hospitalized for mania were considered bipolar I. Those patients having depressions of 2 2 weeks and hypomania for 2 4 days were considered bipolar II (DSM IV) (APA, 1994). Those patients who had a 2-year pattern of depressions of < 2 weeks and hypomania of < 4 days were classified as ‘cyclothymic’. Those patients with depressions of 2 2 weeks but hypomania of < 4 days were considered bipolar NOS (not otherwise specified). Rapid cycling was defined as 2 4 affective episodes (depressions 2 2 weeks; hypomanias 2 4 days) in 1 year. Truncated daily cycling was defined as cycles in which either the depressive or hypomanic or both episodes lasted l-3 days. Truncated hourly cycling was defined as cycles in which either
J.A. Feinmun,
D.L. Dunner/Journal
of Afectiue
hypomania or depression or both lasted < 24 h. Slow-cycling patients were considered as those with < 4 episodes per year. Bipolar I, II and NOS were classified as rapid, slow, truncated daily or truncated hourly; cyclothymic patients, by definition truncated, were classified daily or hourly. Patients were classified according to cycling pattern during the previous year. Alcohol abuse was determined by having 2 3 symptoms of problem drinking according to DSMIII-R criteria (APA, 1987). Marijuana abuse was considered as use 2 2 X a week for at least a month. Abuse of cocaine, amphetamines, hallucinogens, heroin and prescription painkillers was considered if > 10 uses occurred. Any report of intravenous drug use was considered abuse. The following information was systematically obtained during the interview: age; sex; marital status; age of onset of bipolar disorder; history of panic attacks; suicide attempts; family history; and ratings on the Hamilton and Beck scales for anxiety and depression and on the Tridimensional Personality Questionnaire. We calculated means and standard deviations for discrete variables. These data were analysed by F ratios. A x2 test was used for comparison of categorical variables to test for significant group differences. Family history of alcoholism, drug use and primary affective disorder was determined by structured interview of patients during the evaluation by D.L. Dunner. The total number of parents and siblings studied was 763; 395 relatives were female and 368
Table I Demographic
Disorders
37 (1996) 43-49
were male. Morbid risks for unipolar and bipolar illnesses were calculated by using age-adjusted numbers at risk according to data from the Lithium Clinic, New York State Psychiatric Institute (Dunner, 1983). Morbid risks for alcohol and drug use were calculated assuming an equal risk for all age groups. A x2 test was performed to analyse the morbid risk data of both male and female relatives.
3. Results For the 188 cases in the sample, 103 (55%) were primary, 35 (19%) were complicated and 50 (27%) were secondary to substance abuse (Table 11. Overall, 91(48.4%) were women and 97 (5 1.6%) were men. Mean age was 41.6 years (SD = 11.1). The 3 groups did not differ significantly with regards to mean age or marital status. The 3 groups showed nonsignificant differences in distribution of gender. The percentage of female patients in the complicated group (45.7%) was intermediate between that of the primary (57.3%) and secondary (32.0%) groups. The primary group had the highest percentage of BP1 and NOS and the lowest percentage of cyclothymics; the secondary group had the highest percentage of cyclothymics; and the complicated group had the highest percentage of BPII. Of the complicated bipolar patients, 8 (22.9%) abused only alcohol and 3 (8.6%) abused only marijuana (Table 2). Of the secondary bipolar patients, 9 (18.0%) abused only alcohol and 10 (20.0%) abused
characteristics
Features
Primary
Complicated
Secondary
Total
No. patients Mean age (SD) % Female MS:Mar Div Sing Wid. Dx : BP11 BPI cyc. NOS
103 43.1 (12.9) 57.3% 55.3% 23.3% 19.4% I .9% 42.7% 29. I % 3.9% 24.3%
35 38.9 (8.5) 45.7% 48.6% 3 I .4% 20.0% 0.0% 54.3% 14.3% 20.0% 11.4%
50 40.5 (7.8) 32.0% 36.0% 40.0% 22.0% 2.0% 38.0% 14.0% 30.0% 18.0%
188 41.6 (11.1) 48.4% 48.9% 29.3% 20.2% I .6% 43.6% 22.3% 13.8% 20.2%
Dx, diagnosis;
45
MS, marital status; NOS. not otherwise
specified;
Cyc., cyclothymic.
Significance
F = 2.28, NS
,y* = 8.74, df = 2, P < 0.013 xl= 6.65,df=6,NS
x2=26.07,df=6,
P
J.A. Feinmun. D.L. Dunner/Journd
46 Table 2 Patterns of substance
ofA#ectiue Disorders 37 (1996) 43-49
abuse
Substance
Complicated(%)
Secondary(%)
Alcohol only Alcohol Marijuana only Marijuana Hallucinogens Amphet. only Amphet. Cocaine Amphet./Cocaine Heroin Total
20.0 2.9 0.0 8.6 5.7 2.9 25.7 8.6 22.9 2.9 1100.2
16.0 2.0 6.0 14.0 0.0 0.0 20.0 12.0 30.0 0.0 I00.0
Unless listed as ‘only’ all categories
include some other drug use.
only marijuana. 1 complicated patient (2.9%) abused only amphetamines. All other complicated and secondary patients abused at least 2 drugs. Of those, 20 complicated patients (56.3%) and 31 secondary patients (62.1 %o>used cocaine and/or amphetamines. Substance abuse occurring within 1 year of the assessment was documented in 16 secondary and 13 complicated patients.
The 3 groups differed significantly according to clinical features (Table 3). The complicated group had the earliest mean age of onset of symptoms at 13.3 years. The complicated group had the highest percentage of patients who attempted suicide. Considering only female bipolar patients, the secondary group had the highest percentage of patients who made a suicide attempt. Among the male patients, the difference in suicide attempts was nonsignificant. The secondary bipolar patients had the greatest percentage of infrequent (less than once a week) and frequent (greater than once a week) panic attacks, while the primary group had the highest percentage of patients who had never experienced a panic attack. We also analysed the percentage of panic attacks in our female patients alone. The percentages for primary and complicated patients were similar to those for the population as a whole. The females in the secondary group had much higher percentages of both infrequent and frequent panic attacks. Bipolar patients with rapid cycling have been shown to be predominantly female (Dunner and Fieve, 1974; Wehr et al., 1988; Coryell et al., 1992;
Table 3 Clinical features Features
Primary
22.7 (I 2.8) Onset Sx 30.1% %SA + : Total 33.9% Female PA: Total 70.9% None 26.2% Infreq. 2.9% Frequent Females only 69.5% None 27.1% Infreq. 3.4% Frequent Cycling: Total population 36.9% NRC 48.5% RC TD 10.7% TH 3.9% Females only 39.0% NRC 49.2% RC 8.5% TD 3.4% TH Sx, symptoms; hourly.
SA, suicide attempts;
Complicated
Secondary
Total
Significance
13.5 (5.5) 54.3% 62.5%
27.5 (10.1) 46.0% 81.3%
22.1 (12.0) 38.3% 47.3%
F = 16.70, P < 0.001 x2 = 7.91, df = 2, P < 0.019 x2 = 13.13, df = 2, P < 0.001
60.0% 22.9% 17.1%
44.0% 38.0% 18.0%
61.7% 28.7% 9.6%
x2 = 16.68, df = 4, P < 0.002
56.3% 37.5% 6.3%
12.5% 56.3% 31.3%
57.1% 34.1% 8.8%
x2=21.62,df=4,
25.7% 45.7% 22.9% 5.7%
26.0% 24.0% 40.0% 10.0%
30.3% 41.5% 20.7% 5.9%
x2 = 26.34, df = 8, P < 0.001
25.0% 56.3% 18.8% 0.0%
18.8% 3 1.3% 37.5% 6.3%
33.0% 47.3% 15.4% 3.3%
x2=
PA, panic attacks;
NRC, nonrapid
cycling;
15.80,df=8,
RC, rapid cyclin g; TD, truncated
P
P
daily; TH, truncated
JA. F&man,
D.L. Dunner/Journnl
Bauer and Whybrow, 1993). Because our patient groups differed with respect to the male:female ratio, we compared cycling patterns for both groups as a whole and for only female patients. For both the entire population and the women alone, the primary group had the highest percentage of slow-cyclers, while the secondary group had the highest percentage of both truncated daily and truncated hourly cyclers. When analysing the population as a whole, the primary bipolars had the largest group of rapid cyclers. However, when comparing only the women patients, the complicated group had a greater percentage of rapid cyclers. The 3 groups differed significantly on both the Hamilton and Beck anxiety and depression rating scales. On both the anxiety scales, the complicated and secondary groups mean scores were within one point of each other and were significantly greater than those of the primary group. The complicated group’s mean scores on both depression tests were higher than those of both other groups. The difference between groups on the novelty seeking part of the Tridimensional Personality Questionnaire was also significant, with the mean score for the complicated group being higher than the scores of the other 2. The 3 groups mean scores on harm avoidance and reward dependence did not differ significantly. Among patients with substance abuse histories, ratings on these scales were not significantly different comparing those patients who had substance abuse within 1 year of the evaluation with those who had no recent substance abuse. The difference in family history between the 3 groups was significant for both female and male relatives. Of female relatives, those of the complicated bipolar patients had the highest morbid risk for alcohol abuse, while those of secondary bipolar patients had the highest morbid risk for drug abuse. Of the male relatives, the complicated group had the highest morbid risk for alcoholism, while the secondary bipolars had the highest morbid risk for unipolar depression and drug abuse. 4. Discussion As expected, the primary, complicated and secondary bipolar patients differed significantly with regard to several variables. The 3 groups differed
c)j’Aflectioe Disorders 37 (1996) 43-49
47
with regard to demographics, clinical symptoms, behavioral rating scales and family history. The more surprising result was that in many instances the values for the complicated group were not intermediate to those of the other 2 groups. In our study, 55% of the male patients and 35% of the female patients had a history of substance abuse. Hensel et al. (1979) found that 18% of their male patients and 6% of their female patients with affective disorders had drinking problems. The differences in percentages is probably due to the fact that the report of Hensel et al. related to a population from which patients with a history of alcohol or substance abuse had been excluded. The difference in percentage of women between our complicated and secondary bipolar groups agrees with Winokur’s finding that bipolar patients with primary alcoholism were 15% female, while those with secondary alcoholism were 43% female (Winokur et al., 1995). This difference might be explained by Cloninger (1987) finding that women develop alcoholism with a later onset, while alcoholism in men often has an earlier onset. This might mean that men would be more likely to develop alcohol or substance abuse problems prior to the onset of bipolar symptoms and would constitute a greater percentage of the secondary group. The clinical features of our sample are the most striking of our findings. Rather than being intermediate to primary and secondary groups, the complicated group had a significantly earlier age of onset than either group. These results are consistent with those of Winokur et al. (1995) who also found significantly earlier onset for bipolar alcoholics with primary affective disorder. Although the prior data do not always indicate that early onset of bipolar disorder has a worse course of illness (Dunner et al., 19791, they do show a close correlation of early onset with substance abuse as reviewed by Goodwin and Jamison (1990). Our results as well as previous findings indicate a connection between early onset of bipolar disorder and subsequent drug use. This may mean that early onset predisposes bipolar patients toward substance abuse (perhaps, for social or emotional reasons); it may also mean that these complicated patients represent a distinct population of patients who are at risk for early onset of affective illness and substance abuse.
48
JA. Feinman, D.L. Dunner/Journal
As noted before, alcoholic bipolar patients have almost twice the percentage of suicide attempts as nonalcoholic bipolar patients (Morrison, 1974). Our study correlates well with Morrison’s, in that a greater percentage of suicide attempts was found among complicated and secondary as compared with primary bipolar patients. We thought that the higher rate of suicide attempts in the complicated group might be due to the fact that there is a higher percentage of women in that group. For example, Goodwin and Jamison (1990) reviewed findings that bipolar females attempt suicide more often that bipolar men. When females alone were compared, the complicated group was intermediate to the other groups as we hypothesized. These results seem to indicate that substance abuse can worsen the course of bipolar disorder. Our results for panic attacks also seem to support the idea that substance abuse can worsen the course of bipolar illness. The complicated group was again intermediate to the others. Although anxiety disorders are common in the general public, alcohol and drug abuse (especially cocaine) are associated with increased anxiety (Aronson and Craig, 1986; Regier et al., 1990; Russell et al., 1994; Cooke et al., 1994). The greater percentage of truncated daily and truncated hourly cyclers in the secondary and complicated groups may be related to long-term effects of drugs on the duration of cycles. Perhaps, greater mood lability is produced by substance abuse, or perhaps those with rapidly shifting moods are more likely to abuse drugs and alcohol. However, another possible explanation would be that those primary bipolar patients with truncated daily or hourly cycling did not find it necessary to seek treatment. The scores on behavioral ratings scales were also significant. Higher mean ratings on anxiety scales for complicated and secondary than for primary patients were found. The mean scores for the depression scales were highest for the complicated bipolar patients. This may mean an actual difference between the complicated and secondary groups or again may be an effect of the higher percentage of women in the complicated group. The fact that the mean scores are higher for both groups than for primary patients is consistent with the increased depression in patients with substance abuse. The higher scores on the novelty seeking dimen-
of Affective Disorders 37 (1996) 43-49
sion of the TPQ for complicated and secondary groups are consistent with the idea that those using drugs would have a greater tendency toward novelty seeking. No significant difference was found in terms of harm avoidance or reward dependence, suggesting that there is little significant difference between the populations with regard to these personality measures. The differences in family history between the 3 groups were somewhat surprising. As expected, the complicated and secondary patient’s relatives had the highest morbid risk for alcohol and drug abuse. However, the morbid risk for alcohol abuse for relatives of complicated patients was much higher than for relatives of secondary patients. Like the early age of onset, this finding suggests that the complicated group represents a unique population of bipolar patients. These findings disagree with those of Winokur et al. (1995) in which there was no greater risk for the complicated or secondary groups in family history for bipolar disorder, unipolar disorder or alcoholism. The higher morbid risk for unipolar depression in male relatives of secondary patients is confusing and does not agree with other studies (Hensel et al., 1979; Warner et al., 1994). As we postulated, patients with bipolar disorder secondary to substance abuse presented a significantly different picture from primary bipolar patients. We found this difference in demographics, clinical course and family history. However, it was surprising to find that the complicated patients had a much lower mean age of onset of bipolar disorder and a much greater family history of alcoholism. Our results show that substance abuse affects the course of bipolar disorder. However, they also raise questions as to the differences between those whose substance abuse began prior to or after the onset of bipolar disorder. Perhaps, the next step in determining the effects of substance abuse on bipolar disorder would be to do a more thorough investigation of the relationship between onset of bipolar disorder and onset of substance abuse. References American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd Rev. Ed. (DSM-III-R). American Psychiatric Association, Washington, DC.
JA. Feinman, D.L. Dunner/Journd American Psychiatric Association (I 994) Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV). American Psychiatric Association, Washington, DC. Ananth, J., Wohl, M., Ranganath. V. and Beshay, M. (1993) Rapid cycling patients: conceptual and etiological factors. Neuropsychobiology 27, l93- I98 Aronson, T.A. and Craig, T.J. (1986) Cocaine precepitation of panic disorder. Am. J. Psychiatry 143, 643-645. Bauer, MS. and Whybrow, P.C. (1993) Validity of rapid cycling as a modifier for bipolar disorder in DSM-IV. Depression I, I I-19. Brady, K.. Casto, S., Lydiard, R., Malcom, R. and Arana, G. (1991) Substance abuse in an inpatient psychiatric sample. J. Drug Alcohol Abuse 17, 389-397. Cloninger, C.R. (I 987) Neurogenetic adaptive mechanisms in alcoholism. Science 236, 410-416. Cooke, R.. Young, L., Robb, J., Levitt, A. and Joffe, R. (1994) Anxiety symptoms in bipolar disorder. Presented at The First International Conference on Bipolar Disorder. University of Pittsburgh Medical Center, Pittsburgh, PA, June. Coryell. W., Endicott, J. and Keller, M.B. (1992) Rapidly cycling affective disorders: demographics, diagnosis, family history, and course. Arch. Gen. Psychiatry 49, l26- I3 I. Dunner, D.L., Drug treatment of the acute maniac episode. In: Grinspoon, L. (Ed.) (1983) Psychiatry Update. American Psychiatric Press, Washington, DC, Vol. II, pp. 293-302. Dunner, D.L. (1993) Diagnostic Assessment. Psychiatric Clin. N. Am. 16, 431-441. Dunner, D.L. and Fieve, R.R. (1974) Clinical factors in lithium carbonate prophylaxis failure. Arch. Gen. Psychiatry 30. 229331. Dunner. D.L., Murphy, D., Stallone, F. and Fieve, R.R. (1979)
ofA#ective Disorders 37 (1996) 43-49
49
Episode frequency prior to lithium treatment in bipolar manic-depressive patients. Comp. Psychiatry 20, 5 I l-5 IS. Feighner, J., Robins, E., Guze, S., Woodruff, R., Winokur, G. And Munoz, R. (1972) Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiatry 26, 57-63. Goodwin, F.K. and Jamison, K.R. (1990) Manic-Depressive lllness. New York, Oxford University Press. Hensel, B., Dunner. D.L. and Fieve, R.R. (1979) The relationship of family history of alcoholism to primary affective disorder. J. Affect. Disord. I, lO5- 113. Morrison, J.R. (1974) Bipolar affective disorder and alcoholism. Am. J. Psychiatry 131, 1130-i 133. Regier, D.A., Farmer, M.E., Rae, D.S., Locke, B.Z.. Keith, S.J., Judd, L.L. and Goodwin, F. (1990) Comorbidity of mental disorders with alcohol and other drug abuse. JAMA 264, 251 l-2518. Russell, J.M., Newman, S.C. and Bland, R.C. (1994) Drug abuse and dependence. Acta Psychiatr. Stand. (Suppl.) 376, 54-62. Warner, R., Taylor, D., Wright, J., Sloat, A., Springett, G., Arnold, S. and Weinberg, H. (1994) Substance use among the mentally ill: prevalence, reasons for use, and effects on illness. Am. J. Orthopsychiatry 64, 30-39. Wehr, T.A., Sack. D.A., Rosenthal, N.E. and Cowdry, R.W. (1988) Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients. Am. J. Psychiatry 145, l79- 184. Winokur, G., Coryell, W. Akiskal, H.S., Maser, J.D., Keller, M.B., Endicott. J. and Mueller, T. (1995) Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction. Am. J. Psychiatry 152, 3655372.
Journal of Affective
Disorders 37
(I 996) 43-49
Research report
The effect of alcohol and substance abuse on the course of bipolar affective disorder Jessica A. Feinman, David L. Dunner Uniumiry
of Wushin~fon
Medical
Received
Center,
Oufpufient
Psychiatry,
4225
I5 June 1995; revised 6 September
Rooscwelt
Way NE,
* Suite 306.
1995; accepted 27 September
Seurrle.
WA 98/O>.
lJ.V
1995
Abstract
It has been found that > 60% of bipolar I and almost 50% of bipolar II patients have a history of substance abuse (Regier et al., 1990). While previous studies have examined comorbidity of bipolar disorder and substance abuse, little has been done to examine the effect of substance abuse on the course of bipolar disorder. There has also been little distinction made between bipolar disorder occurring prior to substance abuse and that occurring after the onset of substance abuse. Given the high prevalence of substance abuse in bipolar patients, it would be useful to determine more about the effect of substance abuse on demographic and clinical features and on the course of illness. We attempted to do this with a retrospective chart review of 188 bipolar patients seen by D.L. Dunner between January 1992 and December 1993. Demographic and clinical information as well as information about course of illness were systematically extracted from the charts. We compared the means and percentages of these variables and analysed them for significance. Preliminary results show differences in demographics, clinical features and course of illness between patient groups. These differences may illustrate the clinical effects of substance abuse on the course of bipolar disorder. Our results also indicate that there are differences between patients whose bipolar disorder began prior to and those whose disorder began after the onset of substance abuse. Key~~ord.c:Substance abuse; Bipolar affective disorder; Alcohol; Course of illness
1. Introduction
The purpose of this paper is to determine the effect of alcohol and substance abuse on the course of bipolar affective disorder. In results from the Epidemiologic Catchment Area Study, bipolar I patients had a substance abuse prevalence rate of 60.7% and bipolar 11 patients had a substance abuse prevalence rate of 48.1% (Regier et al., 1990). Although several studies have examined comorbidity of substance abuse and affective disorders (Brady et al.,
* Corresponding
author. Fax: (I) (206) 543-7565.
0165.0327/96/$15.00 SD/
0165.0327(95)00080-l
0
1996 Elsevier Science B.V. All rights reserved
1991; Russell et al., 1994; Warner et al., 19941, there has been relatively little determined about the effect of substance abuse on the course of bipolar disorder. Given the high prevalence of substance abuse in patients with bipolar disorder, it would be useful to determine the effects of substance abuse on demographic and clinical features and on course of illness. Primary affective disorder (Feighner et al., 1972) refers to a mood disorder occurring prior to the onset of another psychiatric condition. Secondary affective disorders occur after the onset of other psychiatric conditions. To determine the effect of substance abuse on bipolar disorder, we studied 3 groups of patients. The 1st group consisted of patients with a
44
JA. Frinmun, D.L. Dunner/Journul
diagnosis of primary bipolar disorder who had no past or present history of alcohol or substance abuse (primary bipolar). The 2nd group consisted of those patients whose primary bipolar disorder was complicated by substance abuse which began after the onset of the bipolar disorder (complicated bipolar). The 3rd group was composed of patients whose bipolar disorder began after the onset of alcohol or substance abuse or dependence (secondary bipolar). In studies of comorbidity of substance abuse with mental disorders, both Regier et al. (1990) and Russell et al. (1994) found an association between substance abuse and anxiety disorders. Morrison (1974) found that twice as many alcoholic as nonalcoholic bipolar patients attempted suicide. These studies led us to expect that a greater percentage of secondary than primary bipolar patients would have panic attacks and that a greater percentage would have attempted suicide. There has also been speculation that use of cocaine might contribute to a rapid cycling pattern in bipolar disorder (Ananth et al., 1993). If this speculation is correct, we would expect a greater percentage of rapid cyclers in the complicated and secondary groups. Warner et al. (1994) found that 60% of the relatives of patients with moderate to severe substance abuse had a history of substance abuse, in contrast to 30.8% substance abuse for relatives of patients without a substance abuse history. Hensel et al. (1979) found a 4-fold increase in morbid risk for alcoholism among relatives of male patients with bipolar disorder complicated by drinking problems as compared with those male bipolar patients without drinking problems. They also found a decreased morbid risk for unipolar illness in relatives of those male patients with drinking problems. These results led us to expect a higher morbid risk for alcohol (and drug) use and a lower morbid risk for unipolar depression in the relatives of our complicated and secondary patients. Our hypotheses were that the primary and secondary groups would indeed differ and that the complicated group would have a profile intermediate between the 2 groups. We expected that the secondary group would have a later age of onset of bipolar disorder, greater percentage of rapid cyclers, a history of more panic attacks and suicide attempts and higher anxiety ratings. The secondary bipolar
of’Afectiue
Disorders 37 (1996) 43-49
patients were expected to have an increased family history of substance abuse and decreased family history of bipolar illness vs. primary bipolar patients. We were also interested to see how the groups differed with respect to age, sex, age of onset and type of bipolar illness.
2. Methods The authors carried out a retrospective chart review of all physician and self referred (485) outpatients seen by D.L. Dunner at the Center for Anxiety and Depression of the Department of Psychiatry, University of Washington between January 1992 and December 1993. D.L. Dunner evaluated all the patients using a semistructured interview format (Dunner, 1993) and all chart information was extracted by J.A. Feinman. All patients gave informed consent for research review of charts. Patients for whom a complete history could not be obtained (20) were excluded. Of patients with a complete history, all (209) patients with a history of both depression and mania/hypomania were included regardless of duration of mood state. During analysis of the data, those patients (21 patients) whose bipolar illness was secondary to another psychiatric illness, head trauma or MAO inhibitor use, but not to substance abuse, were excluded. The following definitions were used: a bipolar patient is defined as a person experiencing episodes of both major depression and mania or hypomania. Those patients having been hospitalized for mania were considered bipolar I. Those patients having depressions of 2 2 weeks and hypomania for 2 4 days were considered bipolar II (DSM IV) (APA, 1994). Those patients who had a 2-year pattern of depressions of < 2 weeks and hypomania of < 4 days were classified as ‘cyclothymic’. Those patients with depressions of 2 2 weeks but hypomania of < 4 days were considered bipolar NOS (not otherwise specified). Rapid cycling was defined as 2 4 affective episodes (depressions 2 2 weeks; hypomanias 2 4 days) in 1 year. Truncated daily cycling was defined as cycles in which either the depressive or hypomanic or both episodes lasted l-3 days. Truncated hourly cycling was defined as cycles in which either
J.A. Feinmun,
D.L. Dunner/Journal
of Afectiue
hypomania or depression or both lasted < 24 h. Slow-cycling patients were considered as those with < 4 episodes per year. Bipolar I, II and NOS were classified as rapid, slow, truncated daily or truncated hourly; cyclothymic patients, by definition truncated, were classified daily or hourly. Patients were classified according to cycling pattern during the previous year. Alcohol abuse was determined by having 2 3 symptoms of problem drinking according to DSMIII-R criteria (APA, 1987). Marijuana abuse was considered as use 2 2 X a week for at least a month. Abuse of cocaine, amphetamines, hallucinogens, heroin and prescription painkillers was considered if > 10 uses occurred. Any report of intravenous drug use was considered abuse. The following information was systematically obtained during the interview: age; sex; marital status; age of onset of bipolar disorder; history of panic attacks; suicide attempts; family history; and ratings on the Hamilton and Beck scales for anxiety and depression and on the Tridimensional Personality Questionnaire. We calculated means and standard deviations for discrete variables. These data were analysed by F ratios. A x2 test was used for comparison of categorical variables to test for significant group differences. Family history of alcoholism, drug use and primary affective disorder was determined by structured interview of patients during the evaluation by D.L. Dunner. The total number of parents and siblings studied was 763; 395 relatives were female and 368
Table I Demographic
Disorders
37 (1996) 43-49
were male. Morbid risks for unipolar and bipolar illnesses were calculated by using age-adjusted numbers at risk according to data from the Lithium Clinic, New York State Psychiatric Institute (Dunner, 1983). Morbid risks for alcohol and drug use were calculated assuming an equal risk for all age groups. A x2 test was performed to analyse the morbid risk data of both male and female relatives.
3. Results For the 188 cases in the sample, 103 (55%) were primary, 35 (19%) were complicated and 50 (27%) were secondary to substance abuse (Table 11. Overall, 91(48.4%) were women and 97 (5 1.6%) were men. Mean age was 41.6 years (SD = 11.1). The 3 groups did not differ significantly with regards to mean age or marital status. The 3 groups showed nonsignificant differences in distribution of gender. The percentage of female patients in the complicated group (45.7%) was intermediate between that of the primary (57.3%) and secondary (32.0%) groups. The primary group had the highest percentage of BP1 and NOS and the lowest percentage of cyclothymics; the secondary group had the highest percentage of cyclothymics; and the complicated group had the highest percentage of BPII. Of the complicated bipolar patients, 8 (22.9%) abused only alcohol and 3 (8.6%) abused only marijuana (Table 2). Of the secondary bipolar patients, 9 (18.0%) abused only alcohol and 10 (20.0%) abused
characteristics
Features
Primary
Complicated
Secondary
Total
No. patients Mean age (SD) % Female MS:Mar Div Sing Wid. Dx : BP11 BPI cyc. NOS
103 43.1 (12.9) 57.3% 55.3% 23.3% 19.4% I .9% 42.7% 29. I % 3.9% 24.3%
35 38.9 (8.5) 45.7% 48.6% 3 I .4% 20.0% 0.0% 54.3% 14.3% 20.0% 11.4%
50 40.5 (7.8) 32.0% 36.0% 40.0% 22.0% 2.0% 38.0% 14.0% 30.0% 18.0%
188 41.6 (11.1) 48.4% 48.9% 29.3% 20.2% I .6% 43.6% 22.3% 13.8% 20.2%
Dx, diagnosis;
45
MS, marital status; NOS. not otherwise
specified;
Cyc., cyclothymic.
Significance
F = 2.28, NS
,y* = 8.74, df = 2, P < 0.013 xl= 6.65,df=6,NS
x2=26.07,df=6,
P
J.A. Feinmun. D.L. Dunner/Journd
46 Table 2 Patterns of substance
ofA#ectiue Disorders 37 (1996) 43-49
abuse
Substance
Complicated(%)
Secondary(%)
Alcohol only Alcohol Marijuana only Marijuana Hallucinogens Amphet. only Amphet. Cocaine Amphet./Cocaine Heroin Total
20.0 2.9 0.0 8.6 5.7 2.9 25.7 8.6 22.9 2.9 1100.2
16.0 2.0 6.0 14.0 0.0 0.0 20.0 12.0 30.0 0.0 I00.0
Unless listed as ‘only’ all categories
include some other drug use.
only marijuana. 1 complicated patient (2.9%) abused only amphetamines. All other complicated and secondary patients abused at least 2 drugs. Of those, 20 complicated patients (56.3%) and 31 secondary patients (62.1 %o>used cocaine and/or amphetamines. Substance abuse occurring within 1 year of the assessment was documented in 16 secondary and 13 complicated patients.
The 3 groups differed significantly according to clinical features (Table 3). The complicated group had the earliest mean age of onset of symptoms at 13.3 years. The complicated group had the highest percentage of patients who attempted suicide. Considering only female bipolar patients, the secondary group had the highest percentage of patients who made a suicide attempt. Among the male patients, the difference in suicide attempts was nonsignificant. The secondary bipolar patients had the greatest percentage of infrequent (less than once a week) and frequent (greater than once a week) panic attacks, while the primary group had the highest percentage of patients who had never experienced a panic attack. We also analysed the percentage of panic attacks in our female patients alone. The percentages for primary and complicated patients were similar to those for the population as a whole. The females in the secondary group had much higher percentages of both infrequent and frequent panic attacks. Bipolar patients with rapid cycling have been shown to be predominantly female (Dunner and Fieve, 1974; Wehr et al., 1988; Coryell et al., 1992;
Table 3 Clinical features Features
Primary
22.7 (I 2.8) Onset Sx 30.1% %SA + : Total 33.9% Female PA: Total 70.9% None 26.2% Infreq. 2.9% Frequent Females only 69.5% None 27.1% Infreq. 3.4% Frequent Cycling: Total population 36.9% NRC 48.5% RC TD 10.7% TH 3.9% Females only 39.0% NRC 49.2% RC 8.5% TD 3.4% TH Sx, symptoms; hourly.
SA, suicide attempts;
Complicated
Secondary
Total
Significance
13.5 (5.5) 54.3% 62.5%
27.5 (10.1) 46.0% 81.3%
22.1 (12.0) 38.3% 47.3%
F = 16.70, P < 0.001 x2 = 7.91, df = 2, P < 0.019 x2 = 13.13, df = 2, P < 0.001
60.0% 22.9% 17.1%
44.0% 38.0% 18.0%
61.7% 28.7% 9.6%
x2 = 16.68, df = 4, P < 0.002
56.3% 37.5% 6.3%
12.5% 56.3% 31.3%
57.1% 34.1% 8.8%
x2=21.62,df=4,
25.7% 45.7% 22.9% 5.7%
26.0% 24.0% 40.0% 10.0%
30.3% 41.5% 20.7% 5.9%
x2 = 26.34, df = 8, P < 0.001
25.0% 56.3% 18.8% 0.0%
18.8% 3 1.3% 37.5% 6.3%
33.0% 47.3% 15.4% 3.3%
x2=
PA, panic attacks;
NRC, nonrapid
cycling;
15.80,df=8,
RC, rapid cyclin g; TD, truncated
P
P
daily; TH, truncated
JA. F&man,
D.L. Dunner/Journnl
Bauer and Whybrow, 1993). Because our patient groups differed with respect to the male:female ratio, we compared cycling patterns for both groups as a whole and for only female patients. For both the entire population and the women alone, the primary group had the highest percentage of slow-cyclers, while the secondary group had the highest percentage of both truncated daily and truncated hourly cyclers. When analysing the population as a whole, the primary bipolars had the largest group of rapid cyclers. However, when comparing only the women patients, the complicated group had a greater percentage of rapid cyclers. The 3 groups differed significantly on both the Hamilton and Beck anxiety and depression rating scales. On both the anxiety scales, the complicated and secondary groups mean scores were within one point of each other and were significantly greater than those of the primary group. The complicated group’s mean scores on both depression tests were higher than those of both other groups. The difference between groups on the novelty seeking part of the Tridimensional Personality Questionnaire was also significant, with the mean score for the complicated group being higher than the scores of the other 2. The 3 groups mean scores on harm avoidance and reward dependence did not differ significantly. Among patients with substance abuse histories, ratings on these scales were not significantly different comparing those patients who had substance abuse within 1 year of the evaluation with those who had no recent substance abuse. The difference in family history between the 3 groups was significant for both female and male relatives. Of female relatives, those of the complicated bipolar patients had the highest morbid risk for alcohol abuse, while those of secondary bipolar patients had the highest morbid risk for drug abuse. Of the male relatives, the complicated group had the highest morbid risk for alcoholism, while the secondary bipolars had the highest morbid risk for unipolar depression and drug abuse. 4. Discussion As expected, the primary, complicated and secondary bipolar patients differed significantly with regard to several variables. The 3 groups differed
c)j’Aflectioe Disorders 37 (1996) 43-49
47
with regard to demographics, clinical symptoms, behavioral rating scales and family history. The more surprising result was that in many instances the values for the complicated group were not intermediate to those of the other 2 groups. In our study, 55% of the male patients and 35% of the female patients had a history of substance abuse. Hensel et al. (1979) found that 18% of their male patients and 6% of their female patients with affective disorders had drinking problems. The differences in percentages is probably due to the fact that the report of Hensel et al. related to a population from which patients with a history of alcohol or substance abuse had been excluded. The difference in percentage of women between our complicated and secondary bipolar groups agrees with Winokur’s finding that bipolar patients with primary alcoholism were 15% female, while those with secondary alcoholism were 43% female (Winokur et al., 1995). This difference might be explained by Cloninger (1987) finding that women develop alcoholism with a later onset, while alcoholism in men often has an earlier onset. This might mean that men would be more likely to develop alcohol or substance abuse problems prior to the onset of bipolar symptoms and would constitute a greater percentage of the secondary group. The clinical features of our sample are the most striking of our findings. Rather than being intermediate to primary and secondary groups, the complicated group had a significantly earlier age of onset than either group. These results are consistent with those of Winokur et al. (1995) who also found significantly earlier onset for bipolar alcoholics with primary affective disorder. Although the prior data do not always indicate that early onset of bipolar disorder has a worse course of illness (Dunner et al., 19791, they do show a close correlation of early onset with substance abuse as reviewed by Goodwin and Jamison (1990). Our results as well as previous findings indicate a connection between early onset of bipolar disorder and subsequent drug use. This may mean that early onset predisposes bipolar patients toward substance abuse (perhaps, for social or emotional reasons); it may also mean that these complicated patients represent a distinct population of patients who are at risk for early onset of affective illness and substance abuse.
48
JA. Feinman, D.L. Dunner/Journal
As noted before, alcoholic bipolar patients have almost twice the percentage of suicide attempts as nonalcoholic bipolar patients (Morrison, 1974). Our study correlates well with Morrison’s, in that a greater percentage of suicide attempts was found among complicated and secondary as compared with primary bipolar patients. We thought that the higher rate of suicide attempts in the complicated group might be due to the fact that there is a higher percentage of women in that group. For example, Goodwin and Jamison (1990) reviewed findings that bipolar females attempt suicide more often that bipolar men. When females alone were compared, the complicated group was intermediate to the other groups as we hypothesized. These results seem to indicate that substance abuse can worsen the course of bipolar disorder. Our results for panic attacks also seem to support the idea that substance abuse can worsen the course of bipolar illness. The complicated group was again intermediate to the others. Although anxiety disorders are common in the general public, alcohol and drug abuse (especially cocaine) are associated with increased anxiety (Aronson and Craig, 1986; Regier et al., 1990; Russell et al., 1994; Cooke et al., 1994). The greater percentage of truncated daily and truncated hourly cyclers in the secondary and complicated groups may be related to long-term effects of drugs on the duration of cycles. Perhaps, greater mood lability is produced by substance abuse, or perhaps those with rapidly shifting moods are more likely to abuse drugs and alcohol. However, another possible explanation would be that those primary bipolar patients with truncated daily or hourly cycling did not find it necessary to seek treatment. The scores on behavioral ratings scales were also significant. Higher mean ratings on anxiety scales for complicated and secondary than for primary patients were found. The mean scores for the depression scales were highest for the complicated bipolar patients. This may mean an actual difference between the complicated and secondary groups or again may be an effect of the higher percentage of women in the complicated group. The fact that the mean scores are higher for both groups than for primary patients is consistent with the increased depression in patients with substance abuse. The higher scores on the novelty seeking dimen-
of Affective Disorders 37 (1996) 43-49
sion of the TPQ for complicated and secondary groups are consistent with the idea that those using drugs would have a greater tendency toward novelty seeking. No significant difference was found in terms of harm avoidance or reward dependence, suggesting that there is little significant difference between the populations with regard to these personality measures. The differences in family history between the 3 groups were somewhat surprising. As expected, the complicated and secondary patient’s relatives had the highest morbid risk for alcohol and drug abuse. However, the morbid risk for alcohol abuse for relatives of complicated patients was much higher than for relatives of secondary patients. Like the early age of onset, this finding suggests that the complicated group represents a unique population of bipolar patients. These findings disagree with those of Winokur et al. (1995) in which there was no greater risk for the complicated or secondary groups in family history for bipolar disorder, unipolar disorder or alcoholism. The higher morbid risk for unipolar depression in male relatives of secondary patients is confusing and does not agree with other studies (Hensel et al., 1979; Warner et al., 1994). As we postulated, patients with bipolar disorder secondary to substance abuse presented a significantly different picture from primary bipolar patients. We found this difference in demographics, clinical course and family history. However, it was surprising to find that the complicated patients had a much lower mean age of onset of bipolar disorder and a much greater family history of alcoholism. Our results show that substance abuse affects the course of bipolar disorder. However, they also raise questions as to the differences between those whose substance abuse began prior to or after the onset of bipolar disorder. Perhaps, the next step in determining the effects of substance abuse on bipolar disorder would be to do a more thorough investigation of the relationship between onset of bipolar disorder and onset of substance abuse. References American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd Rev. Ed. (DSM-III-R). American Psychiatric Association, Washington, DC.
JA. Feinman, D.L. Dunner/Journd American Psychiatric Association (I 994) Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV). American Psychiatric Association, Washington, DC. Ananth, J., Wohl, M., Ranganath. V. and Beshay, M. (1993) Rapid cycling patients: conceptual and etiological factors. Neuropsychobiology 27, l93- I98 Aronson, T.A. and Craig, T.J. (1986) Cocaine precepitation of panic disorder. Am. J. Psychiatry 143, 643-645. Bauer, MS. and Whybrow, P.C. (1993) Validity of rapid cycling as a modifier for bipolar disorder in DSM-IV. Depression I, I I-19. Brady, K.. Casto, S., Lydiard, R., Malcom, R. and Arana, G. (1991) Substance abuse in an inpatient psychiatric sample. J. Drug Alcohol Abuse 17, 389-397. Cloninger, C.R. (I 987) Neurogenetic adaptive mechanisms in alcoholism. Science 236, 410-416. Cooke, R.. Young, L., Robb, J., Levitt, A. and Joffe, R. (1994) Anxiety symptoms in bipolar disorder. Presented at The First International Conference on Bipolar Disorder. University of Pittsburgh Medical Center, Pittsburgh, PA, June. Coryell. W., Endicott, J. and Keller, M.B. (1992) Rapidly cycling affective disorders: demographics, diagnosis, family history, and course. Arch. Gen. Psychiatry 49, l26- I3 I. Dunner, D.L., Drug treatment of the acute maniac episode. In: Grinspoon, L. (Ed.) (1983) Psychiatry Update. American Psychiatric Press, Washington, DC, Vol. II, pp. 293-302. Dunner, D.L. (1993) Diagnostic Assessment. Psychiatric Clin. N. Am. 16, 431-441. Dunner, D.L. and Fieve, R.R. (1974) Clinical factors in lithium carbonate prophylaxis failure. Arch. Gen. Psychiatry 30. 229331. Dunner. D.L., Murphy, D., Stallone, F. and Fieve, R.R. (1979)
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Episode frequency prior to lithium treatment in bipolar manic-depressive patients. Comp. Psychiatry 20, 5 I l-5 IS. Feighner, J., Robins, E., Guze, S., Woodruff, R., Winokur, G. And Munoz, R. (1972) Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiatry 26, 57-63. Goodwin, F.K. and Jamison, K.R. (1990) Manic-Depressive lllness. New York, Oxford University Press. Hensel, B., Dunner. D.L. and Fieve, R.R. (1979) The relationship of family history of alcoholism to primary affective disorder. J. Affect. Disord. I, lO5- 113. Morrison, J.R. (1974) Bipolar affective disorder and alcoholism. Am. J. Psychiatry 131, 1130-i 133. Regier, D.A., Farmer, M.E., Rae, D.S., Locke, B.Z.. Keith, S.J., Judd, L.L. and Goodwin, F. (1990) Comorbidity of mental disorders with alcohol and other drug abuse. JAMA 264, 251 l-2518. Russell, J.M., Newman, S.C. and Bland, R.C. (1994) Drug abuse and dependence. Acta Psychiatr. Stand. (Suppl.) 376, 54-62. Warner, R., Taylor, D., Wright, J., Sloat, A., Springett, G., Arnold, S. and Weinberg, H. (1994) Substance use among the mentally ill: prevalence, reasons for use, and effects on illness. Am. J. Orthopsychiatry 64, 30-39. Wehr, T.A., Sack. D.A., Rosenthal, N.E. and Cowdry, R.W. (1988) Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients. Am. J. Psychiatry 145, l79- 184. Winokur, G., Coryell, W. Akiskal, H.S., Maser, J.D., Keller, M.B., Endicott. J. and Mueller, T. (1995) Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction. Am. J. Psychiatry 152, 3655372.