Detecting the Unidentified Victims: Recognized Versus

An Analysis of Clozapine- and Olanzapine-Induced Weight Gain and Associated Psychological Effects
Jason E. Vogler, Petra Kleinlein and William D. Spaulding
University of Nebraska-Lincoln
Following the market entrance of clozapine and olanzapine there has been
an increasing amount of discourse among mental health providers about the
observed weight-gain associated with the use of both medications (Gothelf et
al., 2002; Kinon, Basson, Gilmore, & Tollefson, 2001; Lewis, 2002; Malyuk,
Gibson, Procyshyn, & Kang, 2002).
A total of 32 patients receiving inpatient and outpatient mental health services were enrolled in the study. Participants were recruited from two sites in Lincoln, NE; the Community Transition Program (CTP) at the Lincoln Regional Center (n = 18),
and the Community Mental Health Center in Lincoln (n = 14). Inclusion criteria for the treatment group (n = 16) were current use of clozapine (Clozaril) and/or olanzapine (Zyprexa).
Examining the attitudes and beliefs about weight gain among people with
serious mental illness provides information about the effectiveness and
potential drawbacks to using clozapine and olanzapine as a method of
treatment for psychotic symptoms.
In addition, knowing how people with serious mental illness think and feel
about their medication has implications for their level of treatment
compliance, relative degree of depression, and vulnerability for developing
new-onset diabetes mellitus and obesity (Umbricht, Flury, & Bridler, 2001;
Vanina et al., 2002; Webster, Devarajan, Gallant, Harris, & Kopala, 2001).
It is hypothesized that weight gain experienced by those persons taking
clozapine or olanzapine will be viewed negatively, those who experience
weight gain while taking clozapine and olanzapine will attribute their weight
gain to the medications, and weight gain will contribute to negative beliefs
about the clinical effectiveness of clozapine or olanzapine.
The mean age for all participants is 41 years (SD = 11.48; range 22 to 56 years). Most participants were European-American (87.5%) and 12.5% African-American. More males (75%) than females (25%) participated in the study. Of the patients in
the treatment group, 68.8% were currently taking clozapine and 31.3% were taking olanzapine.
Participants in the treatment group reported eating an average of 3 full meals per day, and an average of 1.8 snacks per day. The majority (56.3%) of patients taking clozapine and/or olanzapine reported to have gained weight over the past six
months. Most patients believed that a person’s weight is related to their eating habits (85%). A moderate effect was found for patients’ beliefs about needing medication (73%) and their attribution of weight gain to their medication (73%). Perceived
effectiveness of medication for experienced symptoms was somewhat smaller (67%).
A mixed groups factorial ANOVA was performed to examine the effects of Time and Study Group regarding weight gain among the control group and the medication group (those people taking clozapine and olanzapine). Table 1 shows the means
for each condition of the design. The interaction of Time and Study Group as they relate to weight gain approached significance (F(3, 54) = 2.683, p = .056, Mse = 160.94). As hypothesized, the pattern of this interaction was that weight increases over
time more for the Medication Group than the Control Group. Despite having an interaction which approached significance, the main effect of Time (F(3, 54) = .219, p = .883) was not significant. In addition, the main effect for Study Group (F(1, 18) =
.242, p = .628) was also not significant.
With respect to those people taking clozapine and those taking olanzapine, there were no significant differences between location, gender, ethnicity, history of obesity, history of diabetes, familial history of obesity, or familial history of diabetes.
Regarding performance on the structured interview, no significant differences were observed between the mean scores of those people taking clozapine and those taking olanzapine (Table 2). Despite the lack of statistical significance, those people
taking clozapine had higher mean scores on the four domains of the interview than those taking olanzapine with the exception of Beliefs About Weight Gain. Table 2 provides the weighted means scores for each group for each domain and the standard
deviation of each group.
The graph below shows change in weight over time for each of the 16 participants in the study (each colored line represents one participant). There are marked co-fluctuations in weights which may reflect the changes in weight over time in which
some data was incomplete, thus the changes look more disparate. The solid line represents the trend line for the medication group and the dashed line represents the trend line for the control group.
Two groups of individuals were used in this research; each group was
comprised of inpatients of the Lincoln Regional Center (LRC) and people
receiving outpatient treatment at the Community Mental Health Center
(CMHC) of Lancaster County in Nebraska.
The participants in the antipsychotic medication group (N = 16) were
receiving either clozapine (Clozaril) or olanzapine (Zyprexa) and those
participants in the control group were not receiving clozapine or olanzapine for
the treatment of their symptoms.
The control group (N = 16) was constructed using a matched-control design
on the basis of date of birth within one year, gender, ethnicity, date of admission
within two months, and weight within 10 pounds at the time the matching
participant began pharmacological treatment.
For those in the antipsychotic medication group, retrospective weights were
collected from the medical charts for one year prior to antipsychotic medication
treatment and retrospectively, for an additional year following initiation of
antipsychotic treatment.
For those in the control group retrospective weights were collected from the
medical chart for two years, with a midpoint that matched the initiation of
antipsychotic treatment in the antipsychotic medication group.
Those participants who are currently admitted were given a structured
interview to access their attitudes and beliefs about the need for medication,
eating habits, weight gain, attributions of weight gain to antipsychotic
medication, clinical effectiveness of antipsychotic medication, family history of
diabetes mellitus, and family history of obesity.
The results of this study should be interpreted with caution due to the small sample size (N = 32). Thus the
findings presented represent “a first look” at the relationship between weight gain due to clozapine and
olanzapine and four domains which may change in relation to the subjective experience of weight gain due to
antipsychotic medications. One barrier encountered in course of this study was the completeness of weight data
included in patients’ medical charts. For participants in the medication group it was difficult to determine
weights prior to the date on which they were first prescribed clozapine and olanzapine, because of this weight
data was aggregated into four 6-month variables for the purpose of analysis.
As indicated in the weight chart, there were differences in weight among those in the medication group and
those in the control group. Although these results did not reach significance, the predicted direction of change is
supported by the authors’ hypotheses and preliminary evidence suggested by Vanina, et al., 2002.
With respect to responses to the structured interview, the results failed to provide a clear explanation for how
those people taking clozapine and olanzapine regarded their medications. Although group differences
approached significance, the results were not powerful enough to make this distinction clear. For this, a larger
sample size is needed to find the effect. The finding that those people taking clozapine had higher scores on the
interview might be a reflection of level of care, as most people prescribed clozapine were outpatients. These
results may also suggest that those people taking clozapine regard their medications more highly, although this
finding would need additional research as previous studies of patient satisfaction with clozapine (e.g., Czobor, et
al., 2002) have revealed some dislike due to the reported side effects.
Table 1.
Means for Time and Study Group.
PreMed/Match 12
to 7 mos.
PreMed/Match 6
to 1 mos.
PostMed/Match 1
to 6 mos.
PostMed/Match 7
to 12 mos.
Table 2.
Scores on structured interview for those taking clozapine and olanzapine.
Structured Interview Domains
Beliefs About
Need for
M = 4.11
SD = 1.24
M = 3.85
SD = 1.35
M = 4.55
SD = 1.49
M = 3.95
SD = 1.11
of Weight
Gain to
M = 4.45
SD = .70
M = 4.20
SD = 1.28
Beliefs About
Weight Gain
M = 5.09
SD = .83
M = 5.13
SD = 1.24
While more research is needed, these results have important implications for the course of treatment for those
people with SMI. It has been suggested that those people who experience an increase in weight as a result of
their medication have the potential to develop depression, diabetes, low self-esteem, obesity, an increase in
suicidal ideation, and may become less compliant with treatment (Sheitman, et al., 1999; Vanina, et al., 2002).
As treatment research and mental healthcare providers strive to find ways of increasing and improving
treatment compliance, the topic of beliefs and attitudes about medication become ever more important.
Additionally, as the pharmaceutical industry continues in its efforts to modify and create new medications it is
important for them to know how the side effects of such medications impact their clients.

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