CLINICAL
Weight
Gain Among Schizophrenic Treated With Clozapine J.
Steven
Lamberti, and Steven
M.D., Terrance B. Schwarzkopf,
patients weight
(Am
gained
at least
I 0 lb.
The
results
confirm
previous
RESEARCH
REPORTS
Patients
Bellnier, M.D.
A retrospective chart review was used to assess weight changes inpatients who were treated with clozapine after being treated The average weight gain during 6 months of clozapine treatment
AND
R.Ph.,
in 36 chronic schizophrenic with standard neuroleptics. was I 6. 9 Ib; 75.0% of the
findings
of clozapine-associated
gain.
J
Psychiatry 1992; 149:689-690)
C
bozapine is the first antipsychotic medication that has been proven superior to standard neuroleptics for treatment-refractory schizophrenia. Depending on how treatment resistance is defined, potential candidates for cbozapine therapy in the United States may number in the hundreds of thousands. Cbozapine causes fewer extmapymamidab side effects than neumoleptics but has a variety of other side effects, including weight gain. While obesity is a known health risk and has been documented as a side effect of neuroleptics (1, 2), the degree of weight gain associated with cbozapine is unclean. In a review of more than I 3,000 patients treated with dozapine worldwide, Liebenman et al. (3) reported weight
significant weight gain in seven schizophrenic patients treated with cbozapine. Six of these patients gained an average of 24.7 bb, and the authors concluded that dozapine may be associated with the same degree of weight gain seen with typical neuroleptics. The purpose of the present study was to examine the frequency and magnitude of weight gain in cbozapinetreated chronic schizophrenic patients. This study involved a retrospective review of hospital charts for a group of patients treated with both neuroleptics and clozapine.
gain
METHOD
in 0.73%.
In a retrospective
review
of the
medical
charts of 503 inpatients, Nabem and Hippius (4) noted weight gain in only three patients. However, Povlsen et al. (5) noted a frequency of I 1.6% in a retrospective study of 216 inpatients treated with a mean daily dose of 317 mg for up to 12 years. Taken together, these reports have suggested that weight gain occurs infrequently during clozapine treatment. In contrast, Leadbettem et ab. (6) recently reported that 38% of their group of 21 chronically mentally ill patients gained over 10% of their body weight during dozapine treatment. Also, Cohen et al. (7) have described
Abstract presented at the International Congress of Schizophrenia Research, Tucson, Aniz., April 21-25, 1991. Received May 21, 1991; revision received Oct. 9, 1991; accepted Nov. 8, 1991. From the Rochester Psychiatric Center and the Department of Psychiatry, University of Rochester School of Medicine and Dentistry. Address reprint requests to Dr. Lamberti, Department of Psychiatry, University of Rochester Medical Center, 1650 Elmwood Ave., Rochester, NY 14620. Supported in part by NIMH grant MH-40381 to Dr. Lamberti. The authors thank Ulnika Timvik, MS., John F. Cnilly, A.C.S.W.,
John
Venenon,
Pharm.D.,
Kashinath
staff at Rochester Psychiatric lection. Copyright U I 992 American
Am
]
Psychiatry
i49:5,
Center
B. Patil,
M.D.,
for
assistance
Psychiatric
May
1992
their
Association.
and
the dietary in data
col-
Our subjects were 36 inpatients in a state hospital who were consecutively treated with cbozapine oven 33 months. All patients had clinical diagnoses of chronic schizophrenia, according to DSM-III-R criteria, with a variety of subtypes. The mean length of the current hospitalization was 8.2 years (SD=7.6), and the mean number of previous hospitalizations was 5.8 (SD=3.1). Twenty-seven (75.0%) of the subjects were male, and the mean age of the total group was 34.8 years (SD= 9.3). The patients were selected for clozapine treatment by their attending psychiatrists because they had shown little on no clinical improvement during adequate trials of at least three different neurobeptics in the previous S years. The mean total duration of neuroleptic treatment during the current hospitalization was 6.8 years (SD= 4.8). The neurobeptic treatment received by the group during the 6 months before cbozapine treatment is summanized in table 1 . Neuroleptics were discontinued, and the patients’ mean cbozapine dose was 380 mg/day (SD=13S). The transition from neuroleptics to cbozapine was made without a washout period and was gencrabby completed within 4-6 weeks. Each patient was weighed monthly during the last 6
689
CLINICAL
TABLE
phrenic
AND
RESEARCH
REPORTS
1. Standar d Neuroleptics Received by 36 Chronic SchizoInpatients During 6 Months Before Clozapine Treatment Dose (chlorpromazine
Neunoleptic’
N
Halopenidol
Mean
SD
Thiothixene Tnifluopenazine
Perphenazine
I
100.0
Loxapine
I S
800.0 820.0
465.4
4
558.3
252.4
up to three
different
neunoleptics
Chlorpnomazine Thionidazine ‘Patients
received
1519.5 1375.0 1083.4 944.4
(days)
I 1 8 11 9
Fluphenazine
This study demonstrates significant weight gain in a group of schizophrenic patients during cbozapine treatment. Weight gain associated with standard neurolep-
Duration
equivalents/day)
781.0 860.0 285.2 481.0
Mean 1 10.2 106.6 114.2 98.1
SD 57.7 65.4 57.9 63.08
91.0 118.0 134.0
90.5
46.51
30.5
each.
months of neuroleptic treatment and the first 6 months of cbozapine treatment. Cbozapine treatment was initiated during fall and winter months for 15 (41.7%) of the patients, and for 21 (58.3%) it began during spring and summer months. Patients were weighed in street clothes before breakfast and had unrestricted access to food and physical activity throughout the study. An ideal weight mange, including minimum and maximum ideal weights, was calculated for each patient by a registered dietitian. Weight change was assessed by comparing the patient weights before and after each 6month treatment period. The score on the Brief Psychiatnic Rating Scale (BPRS) was also determined by each patient’s attending psychiatrist every 6 weeks during clozapine treatment.
RESULTS The group showed stable weight during the 6 months of standard neunoleptic treatment (mean weight change= -0.2 lb, SD=11.0). When cbozapine treatment began, seven (1 9.4%) ofthe patients weighed less than their minimum ideal weights and 23 (63.9%) weighed more than their maximum ideal weights. As a group they weighed an average of 15.3 lb (SD=35.3) more than their maximum ideal weights. The group subsequently gained an average of 16.9 lb (SD=10.9) during the 6 months of dozapine treatment (t=9.33, df=3S, p
Weight
Gain Among Schizophrenic Treated With Clozapine J.
Steven
Lamberti, and Steven
M.D., Terrance B. Schwarzkopf,
patients weight
(Am
gained
at least
I 0 lb.
The
results
confirm
previous
RESEARCH
REPORTS
Patients
Bellnier, M.D.
A retrospective chart review was used to assess weight changes inpatients who were treated with clozapine after being treated The average weight gain during 6 months of clozapine treatment
AND
R.Ph.,
in 36 chronic schizophrenic with standard neuroleptics. was I 6. 9 Ib; 75.0% of the
findings
of clozapine-associated
gain.
J
Psychiatry 1992; 149:689-690)
C
bozapine is the first antipsychotic medication that has been proven superior to standard neuroleptics for treatment-refractory schizophrenia. Depending on how treatment resistance is defined, potential candidates for cbozapine therapy in the United States may number in the hundreds of thousands. Cbozapine causes fewer extmapymamidab side effects than neumoleptics but has a variety of other side effects, including weight gain. While obesity is a known health risk and has been documented as a side effect of neuroleptics (1, 2), the degree of weight gain associated with cbozapine is unclean. In a review of more than I 3,000 patients treated with dozapine worldwide, Liebenman et al. (3) reported weight
significant weight gain in seven schizophrenic patients treated with cbozapine. Six of these patients gained an average of 24.7 bb, and the authors concluded that dozapine may be associated with the same degree of weight gain seen with typical neuroleptics. The purpose of the present study was to examine the frequency and magnitude of weight gain in cbozapinetreated chronic schizophrenic patients. This study involved a retrospective review of hospital charts for a group of patients treated with both neuroleptics and clozapine.
gain
METHOD
in 0.73%.
In a retrospective
review
of the
medical
charts of 503 inpatients, Nabem and Hippius (4) noted weight gain in only three patients. However, Povlsen et al. (5) noted a frequency of I 1.6% in a retrospective study of 216 inpatients treated with a mean daily dose of 317 mg for up to 12 years. Taken together, these reports have suggested that weight gain occurs infrequently during clozapine treatment. In contrast, Leadbettem et ab. (6) recently reported that 38% of their group of 21 chronically mentally ill patients gained over 10% of their body weight during dozapine treatment. Also, Cohen et al. (7) have described
Abstract presented at the International Congress of Schizophrenia Research, Tucson, Aniz., April 21-25, 1991. Received May 21, 1991; revision received Oct. 9, 1991; accepted Nov. 8, 1991. From the Rochester Psychiatric Center and the Department of Psychiatry, University of Rochester School of Medicine and Dentistry. Address reprint requests to Dr. Lamberti, Department of Psychiatry, University of Rochester Medical Center, 1650 Elmwood Ave., Rochester, NY 14620. Supported in part by NIMH grant MH-40381 to Dr. Lamberti. The authors thank Ulnika Timvik, MS., John F. Cnilly, A.C.S.W.,
John
Venenon,
Pharm.D.,
Kashinath
staff at Rochester Psychiatric lection. Copyright U I 992 American
Am
]
Psychiatry
i49:5,
Center
B. Patil,
M.D.,
for
assistance
Psychiatric
May
1992
their
Association.
and
the dietary in data
col-
Our subjects were 36 inpatients in a state hospital who were consecutively treated with cbozapine oven 33 months. All patients had clinical diagnoses of chronic schizophrenia, according to DSM-III-R criteria, with a variety of subtypes. The mean length of the current hospitalization was 8.2 years (SD=7.6), and the mean number of previous hospitalizations was 5.8 (SD=3.1). Twenty-seven (75.0%) of the subjects were male, and the mean age of the total group was 34.8 years (SD= 9.3). The patients were selected for clozapine treatment by their attending psychiatrists because they had shown little on no clinical improvement during adequate trials of at least three different neurobeptics in the previous S years. The mean total duration of neuroleptic treatment during the current hospitalization was 6.8 years (SD= 4.8). The neurobeptic treatment received by the group during the 6 months before cbozapine treatment is summanized in table 1 . Neuroleptics were discontinued, and the patients’ mean cbozapine dose was 380 mg/day (SD=13S). The transition from neuroleptics to cbozapine was made without a washout period and was gencrabby completed within 4-6 weeks. Each patient was weighed monthly during the last 6
689
CLINICAL
TABLE
phrenic
AND
RESEARCH
REPORTS
1. Standar d Neuroleptics Received by 36 Chronic SchizoInpatients During 6 Months Before Clozapine Treatment Dose (chlorpromazine
Neunoleptic’
N
Halopenidol
Mean
SD
Thiothixene Tnifluopenazine
Perphenazine
I
100.0
Loxapine
I S
800.0 820.0
465.4
4
558.3
252.4
up to three
different
neunoleptics
Chlorpnomazine Thionidazine ‘Patients
received
1519.5 1375.0 1083.4 944.4
(days)
I 1 8 11 9
Fluphenazine
This study demonstrates significant weight gain in a group of schizophrenic patients during cbozapine treatment. Weight gain associated with standard neurolep-
Duration
equivalents/day)
781.0 860.0 285.2 481.0
Mean 1 10.2 106.6 114.2 98.1
SD 57.7 65.4 57.9 63.08
91.0 118.0 134.0
90.5
46.51
30.5
each.
months of neuroleptic treatment and the first 6 months of cbozapine treatment. Cbozapine treatment was initiated during fall and winter months for 15 (41.7%) of the patients, and for 21 (58.3%) it began during spring and summer months. Patients were weighed in street clothes before breakfast and had unrestricted access to food and physical activity throughout the study. An ideal weight mange, including minimum and maximum ideal weights, was calculated for each patient by a registered dietitian. Weight change was assessed by comparing the patient weights before and after each 6month treatment period. The score on the Brief Psychiatnic Rating Scale (BPRS) was also determined by each patient’s attending psychiatrist every 6 weeks during clozapine treatment.
RESULTS The group showed stable weight during the 6 months of standard neunoleptic treatment (mean weight change= -0.2 lb, SD=11.0). When cbozapine treatment began, seven (1 9.4%) ofthe patients weighed less than their minimum ideal weights and 23 (63.9%) weighed more than their maximum ideal weights. As a group they weighed an average of 15.3 lb (SD=35.3) more than their maximum ideal weights. The group subsequently gained an average of 16.9 lb (SD=10.9) during the 6 months of dozapine treatment (t=9.33, df=3S, p
