CLINICAL
Lithium With
An open trial of lithium carbonate showed little effi cacy for I 0 cocaine abusers with bipolar spectrum disorders. It may be that the bipolar subgroup of cocaine abusers is heterogeneous and that only a fraction are lithium responsive. (Am J Psychiatry 1990; 147:655-657)
A
lthough hypothesized to have cocaine antagonist properties (1, 2), lithium proved no different from placebo and inferior to desipramine as a treatment for unselected cocaine abusers in a recent controlled trial (3). Nevertheless, the results of one small open trial (N=9) suggest that lithium might be effective in the subgroup of cocaine abusers with putative bipolar spectrum disorders, who may be self-medicating (4). We report a second open trial of lithium for 10 cocaine abusers with bipolar spectrum disorders.
METHOD
The subjects were 10 consecutive patients seeking treatment for cocaine dependence at our universitybased outpatient clinic who also met the DSM-III-R criteria for a bipolar disorder. The patients were evaluated by experienced research psychiatrists using a DSM-III-R checklist. Affective disorder was diagnosed only if its onset preceded the onset of all substance dependence disorders during the patient’s lifetime. The bipolar disorders were characterized by hypomania (bipolar disorder not otherwise specified) (patients 3-
Received March 29, 1989; revision received Oct. 3, 1989; accepted Oct. 31, 1989. From the Depression Evaluation Service and the Department of Therapeutics, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University Cotlege of Physicians and Surgeons, New York. Address reprint requests to Dr. Nunes, Depression Evaluation Service, New York State Psychiatric Institute, Box 35, 722 West 168th St., New York, NY 10032.
Supported from grant MH-15144 The authors samples and Copyright
Am
J
by a research grant from New York State, grant DAthe National Institute on Drug Abuse, and training from NIMH. thank Nicholas Willson, M.D., for screening urine Terrie Post, R.N., for research assistance. © 1990 American Psychiatric Association.
Psychiatry
147:5,
May
1990
RESEARCH
REPORTS
Treatment for Cocaine Abusers Bipolar Spectrum Disorders
Edward V. Nunes, M.D., Steven Wager, M.D., and
03836
AND
Patrick Frederic
J. McGrath, M.
Quitkin,
M.D., M.D.
6, 9, 10) or cyclothymia (patients 1, 2, 7, 8). There were no histories of full mania. Five patients met the lifetime criteria for major depression (patients 3, 4, 8, 9) or dysthymic disorder (patient 2), and seven had lifetime histories of alcohol dependence (patient 7), other drug dependence (patients 5, 10), on both (patients 1, 4, 6, 9). Five of the 10 (patients 1-4, 10) each had at least one first-degree relative with alcoholism. There were no clear-cut family histories of affective disorder, although the mothers of two patients (patients 6, 7) were described as “moody,” and the mother of a third (patient 1) had had a “nervous breakdown” of unknown type. The sample included eight men and two women. Five were white, three were black, and two were Hispanic. Four were unemployed. The mean±SD age was 34±4 years. The mean±SD age at onset of cocaine dependence was 27±7 years, and the age at onset of first substance dependence was 21 ±5 years. Four used cocaine intranasally, one injected it intravenously, and five used freebase cocaine or crack. The average amount of cocaine used oven the past year was 4. 1 ± 3 .7 g/week (nange= 1 .0-13 .0). The mean baseline scone on the Hamilton Rating Scale for Depression was in the mildly depressed range (7.7±5.4). Only three patients (patients 3, 8, 9) had baseline scores higher than 10. Each patient met weekly with a research psychiatrist and a drug counselor. Participation in Cocaine Anonymous or Narcotics Anonymous was urged. After giving informed consent, the patients received placebo for 1 week on a single-blind basis and were then openly given lithium carbonate. The trial was intended to last 12 weeks, but before that time six patients dropped out and one was removed because of nonresponse. However, eight patients received lithium for 6 on more weeks and had blood levels between 0.4 and 1.0 meq/ liter. Each week the patients were asked to report cocaine use, to complete the Cocaine Craving Scale (4) and the Cocaine High Scale (20 points each, based on 100-mm line), and to provide urine samples for determination of cocaine use. The Hamilton scale and the 28 hypomania and biphasic items of the General Behavior Inventory (5) were administered biweekly. The General
655
CLINICAL
TABLE
AND
RESEARCH
1. Response
REPORTS
to Lithium
of 10 Consecutive
(years)
Nonrespondersa 1
Abusers With Bipolar Spectrum
Route of Adminis-
Age
Patient
Cocaine
Race
34
Sex
tration
2
33
White White
M M
Intravenous Free-base
3
32
White
F
4
S
33 40
White Black
6
31
7
Dose
(mg/day)
Lithium
Trial
Blood
Level
(meqfliter)
Disorders
Length
(weeks)
600 600
0.1
Intranasal
1500
1.0
12
M M
Free-base Free-base
900 600
0.7 0.4
8 6
Hispanic
M
Free-base
900
0.8
8
30
White
M
Intranasal
1200
0.7
7
8
32
Black
F
Intranasal
600
0.6
12
9
41
Black
M
Free-base
1200
0.8
9
10
32
Hispanic
M
Intranasal
1500
0.7
12
-
Comments
3 3
Craving and mood unchanged Craving and mood unchanged; cornplaints of sedation Craving and hypomania better; depression worse’ Craving better; mood unchanged Craving unchanged; mood better; complaints of sedation Craving unchanged; mood better; complaints of sedation Craving unchanged; mood depressed, “too even,” “miss the highsC
Responders”
“Response defined as 3 con secutive coc aine-fr cc weeks, bSubsequentty improved with imipramine. cSubsequentty
improved
with
confi rmed
and
mood
better;
better; depression unchanged better; hyperthymia stopped taking
sustained and
alcohol
unlithium
and
by ur inc screening.
fluoxetine.
Behavior
(patients
raw
Inventory is rated by the patient; the possible range from 28 to 112. A favorable clinical response was defined as 3 consecutive weeks of abstinence from cocaine, confirmed by urine screening, at any time during the trial. Mean changes from baseline to endpoint for cocaine use, craving, Hamilton score, and General Behavior Inventory hypomania scone were tested with two-tailed paired t tests.
2, 5, and
scores
RESULTS Most patients showed some reduction in cocaine use, but the mean decrease (0.74± 1.63 g/week) was not statistically significant (t= 1.32, df=8). As shown in table 1, only three of the 10 patients (patients 8-10) were cocaine free for 3 consecutive weeks. One of these (patient 9) had persistent depression and alcohol abuse and dropped out at week 9, and another (patient 10) stopped taking lithium and relapsed just after week 12. Only one (patient 8) achieved sustained cocaine abstinence. Five patients (patients 3, 4, 8-10) had some reduction in craving, although the mean decrease (2.6±5.2) was not significant (t=1.58, df=9). Only one patient showed a decrease in cocaine euphoria (patient 8). Mood, particularly hypomania, was improved in five patients (patients 3, 5-8). The mean reduction in the scores on the General Behavior Inventory hypomania items neared significance (13.7± 19.3; t=2.13, df=8, p
Lithium With
An open trial of lithium carbonate showed little effi cacy for I 0 cocaine abusers with bipolar spectrum disorders. It may be that the bipolar subgroup of cocaine abusers is heterogeneous and that only a fraction are lithium responsive. (Am J Psychiatry 1990; 147:655-657)
A
lthough hypothesized to have cocaine antagonist properties (1, 2), lithium proved no different from placebo and inferior to desipramine as a treatment for unselected cocaine abusers in a recent controlled trial (3). Nevertheless, the results of one small open trial (N=9) suggest that lithium might be effective in the subgroup of cocaine abusers with putative bipolar spectrum disorders, who may be self-medicating (4). We report a second open trial of lithium for 10 cocaine abusers with bipolar spectrum disorders.
METHOD
The subjects were 10 consecutive patients seeking treatment for cocaine dependence at our universitybased outpatient clinic who also met the DSM-III-R criteria for a bipolar disorder. The patients were evaluated by experienced research psychiatrists using a DSM-III-R checklist. Affective disorder was diagnosed only if its onset preceded the onset of all substance dependence disorders during the patient’s lifetime. The bipolar disorders were characterized by hypomania (bipolar disorder not otherwise specified) (patients 3-
Received March 29, 1989; revision received Oct. 3, 1989; accepted Oct. 31, 1989. From the Depression Evaluation Service and the Department of Therapeutics, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University Cotlege of Physicians and Surgeons, New York. Address reprint requests to Dr. Nunes, Depression Evaluation Service, New York State Psychiatric Institute, Box 35, 722 West 168th St., New York, NY 10032.
Supported from grant MH-15144 The authors samples and Copyright
Am
J
by a research grant from New York State, grant DAthe National Institute on Drug Abuse, and training from NIMH. thank Nicholas Willson, M.D., for screening urine Terrie Post, R.N., for research assistance. © 1990 American Psychiatric Association.
Psychiatry
147:5,
May
1990
RESEARCH
REPORTS
Treatment for Cocaine Abusers Bipolar Spectrum Disorders
Edward V. Nunes, M.D., Steven Wager, M.D., and
03836
AND
Patrick Frederic
J. McGrath, M.
Quitkin,
M.D., M.D.
6, 9, 10) or cyclothymia (patients 1, 2, 7, 8). There were no histories of full mania. Five patients met the lifetime criteria for major depression (patients 3, 4, 8, 9) or dysthymic disorder (patient 2), and seven had lifetime histories of alcohol dependence (patient 7), other drug dependence (patients 5, 10), on both (patients 1, 4, 6, 9). Five of the 10 (patients 1-4, 10) each had at least one first-degree relative with alcoholism. There were no clear-cut family histories of affective disorder, although the mothers of two patients (patients 6, 7) were described as “moody,” and the mother of a third (patient 1) had had a “nervous breakdown” of unknown type. The sample included eight men and two women. Five were white, three were black, and two were Hispanic. Four were unemployed. The mean±SD age was 34±4 years. The mean±SD age at onset of cocaine dependence was 27±7 years, and the age at onset of first substance dependence was 21 ±5 years. Four used cocaine intranasally, one injected it intravenously, and five used freebase cocaine or crack. The average amount of cocaine used oven the past year was 4. 1 ± 3 .7 g/week (nange= 1 .0-13 .0). The mean baseline scone on the Hamilton Rating Scale for Depression was in the mildly depressed range (7.7±5.4). Only three patients (patients 3, 8, 9) had baseline scores higher than 10. Each patient met weekly with a research psychiatrist and a drug counselor. Participation in Cocaine Anonymous or Narcotics Anonymous was urged. After giving informed consent, the patients received placebo for 1 week on a single-blind basis and were then openly given lithium carbonate. The trial was intended to last 12 weeks, but before that time six patients dropped out and one was removed because of nonresponse. However, eight patients received lithium for 6 on more weeks and had blood levels between 0.4 and 1.0 meq/ liter. Each week the patients were asked to report cocaine use, to complete the Cocaine Craving Scale (4) and the Cocaine High Scale (20 points each, based on 100-mm line), and to provide urine samples for determination of cocaine use. The Hamilton scale and the 28 hypomania and biphasic items of the General Behavior Inventory (5) were administered biweekly. The General
655
CLINICAL
TABLE
AND
RESEARCH
1. Response
REPORTS
to Lithium
of 10 Consecutive
(years)
Nonrespondersa 1
Abusers With Bipolar Spectrum
Route of Adminis-
Age
Patient
Cocaine
Race
34
Sex
tration
2
33
White White
M M
Intravenous Free-base
3
32
White
F
4
S
33 40
White Black
6
31
7
Dose
(mg/day)
Lithium
Trial
Blood
Level
(meqfliter)
Disorders
Length
(weeks)
600 600
0.1
Intranasal
1500
1.0
12
M M
Free-base Free-base
900 600
0.7 0.4
8 6
Hispanic
M
Free-base
900
0.8
8
30
White
M
Intranasal
1200
0.7
7
8
32
Black
F
Intranasal
600
0.6
12
9
41
Black
M
Free-base
1200
0.8
9
10
32
Hispanic
M
Intranasal
1500
0.7
12
-
Comments
3 3
Craving and mood unchanged Craving and mood unchanged; cornplaints of sedation Craving and hypomania better; depression worse’ Craving better; mood unchanged Craving unchanged; mood better; complaints of sedation Craving unchanged; mood better; complaints of sedation Craving unchanged; mood depressed, “too even,” “miss the highsC
Responders”
“Response defined as 3 con secutive coc aine-fr cc weeks, bSubsequentty improved with imipramine. cSubsequentty
improved
with
confi rmed
and
mood
better;
better; depression unchanged better; hyperthymia stopped taking
sustained and
alcohol
unlithium
and
by ur inc screening.
fluoxetine.
Behavior
(patients
raw
Inventory is rated by the patient; the possible range from 28 to 112. A favorable clinical response was defined as 3 consecutive weeks of abstinence from cocaine, confirmed by urine screening, at any time during the trial. Mean changes from baseline to endpoint for cocaine use, craving, Hamilton score, and General Behavior Inventory hypomania scone were tested with two-tailed paired t tests.
2, 5, and
scores
RESULTS Most patients showed some reduction in cocaine use, but the mean decrease (0.74± 1.63 g/week) was not statistically significant (t= 1.32, df=8). As shown in table 1, only three of the 10 patients (patients 8-10) were cocaine free for 3 consecutive weeks. One of these (patient 9) had persistent depression and alcohol abuse and dropped out at week 9, and another (patient 10) stopped taking lithium and relapsed just after week 12. Only one (patient 8) achieved sustained cocaine abstinence. Five patients (patients 3, 4, 8-10) had some reduction in craving, although the mean decrease (2.6±5.2) was not significant (t=1.58, df=9). Only one patient showed a decrease in cocaine euphoria (patient 8). Mood, particularly hypomania, was improved in five patients (patients 3, 5-8). The mean reduction in the scores on the General Behavior Inventory hypomania items neared significance (13.7± 19.3; t=2.13, df=8, p
