Am J Psychiatry 159:4, April 2002
Metformin for Weight Loss in Pediatric Patients
Taking Psychotropic Drugs
John A. Morrison, Ph.D.
Elizabeth M. Cottingham, M.D.
Bruce A. Barton, Ph.D.
Objective: Metformin was assessed as a treatment for weight
gain in children taking olanzapine, risperidone, quetiapine, or
Method: The subjects were 19 patients aged 10–18 years; 15
were white and four were black, and there were 12 boys and
seven girls. In a 12-week open-label study, each patient received
metformin, 500 mg t.i.d. Changes in weight and body mass in-
dex were evaluated by using repeated measures analysis of
Results: Of the 19 patients, 15 lost weight, three gained 1.6 kg
or less, and one had no change. The mean changes in weight
and body mass index at 12 weeks were highly significant.
Conclusions: Metformin merits further study as a treatment
for weight gain in patients taking psychotropic medications.
(Am J Psychiatry 2002; 159:655–657)
Olanzapine, risperidone, quetiapine, and valproate
provide effective treatment of bipolar disorder and psy-
chosis (1). Their use, however, is associated with weight
gain in as many as 50% of patients (1–5). Metformin,
which is prescribed for patients with non-insulin-depen-
dent diabetes to control blood sugar levels, has been re-
ported to effect weight loss in several groups of patients
characterized by insulin resistance. These include women
with polycystic ovary disease (6, 7) and obese hyperlipi-
demic men and women with and without non-insulin-de-
pendent diabetes (8). Metformin has recently been ap-
proved for use in children. Within this framework, we
conducted an open-label study of metformin and weight
loss in pediatric patients who had gained weight while tak-
ing target drugs. We hypothesized that metformin would
manage weight gain and lead to weight loss.
Patients taking olanzapine, risperidone, quetiapine, or valpro-
ate at Children’s Hospital Medical Center, Cincinnati, with weight
gain over 10% of baseline were given metformin, 500 mg t.i.d. De-
termination of weight gain was based on hospital records and the
patient’s weight at enrollment. Weight and height were measured
to the nearest 0.1 kg and 0.1 cm, respectively, according to a Na-
tional Institutes of Health protocol (9). The first two patients were
seen under an 8-week protocol; subsequent patients were seen
under a 12-week protocol. The patients were instructed not to
change diet or physical activity during the study. Safety monitor-
ing tests for lactic acidosis and liver function were conducted at
all visits. Postmenarchal girls took urine pregnancy tests monthly.
The study’s primary outcome measures were change in weight
and body mass index at 12 weeks of metformin treatment. For
these outcomes, we used paired t tests to assess whether the
mean changes were significantly different from zero. To control
for multiple comparisons, we adjusted the critical alpha level by
using Bonferroni adjustment, testing each outcome at an alpha of
0.025. We tested changes in weight and body mass index at 4 and
8 weeks as secondary outcomes, using a more conservative alpha
of 0.01. All analyses were performed by using SAS version 8.0 (10).
The Children’s Hospital Medical Center institutional review
board approved the protocol. Written informed assent/consent
was obtained. The participants were told that we wanted to see
whether metformin affected weight loss independently of dietary
changes or physical activity.
Nineteen patients, aged 10–18 years (mean=14.1, SD=
2.5), were treated. They included 15 white and four black
subjects; 12 were male, and seven were female. Two pa-
tients were taking valproate only, four were taking valpro-
ate plus olanzapine, eight were taking olanzapine only,
one was taking valproate plus risperidone, three were tak-
ing risperidone only, and one was taking quetiapine only.
The length of treatment with these drugs ranged from 1 to
36 months (mean=10.4, SD=9.5), and weight gain ranged
from 6.0 to 59.1 kg (mean=28.6, SD=15.3). Follow-up data
were available for 19 patients at 4 weeks, 16 patients at 8
weeks, and 12 patients at 12 weeks. Seven patients had less
than 12 weeks of data. Two patients were seen under an 8-
week protocol. One patient stopped taking olanzapine af-
ter 8 weeks of weight loss and was lost to follow-up, al-
though later admitted to the hospital. One patient moved
away. One patient, who gained 0.6 kg in 4 weeks, dropped
out to try a different, dietary approach and was counted as
gaining weight. Two patients did not complete the 12-
week protocol before funding and institutional review
board approval expired. The weight change outcomes
were based on patients’ results at 4, 8, and 12 weeks, and
the weight change classification was based on each pa-
tient’s final visit, whether that was at 4, 8, or 12 weeks.
Of the 19 patients, 15 lost weight, the weight of one re-
mained unchanged, and three gained weight. Weight
gains in these three patients were 0.2 kg (over 3 months),
0.6 kg (over 1 month), and 1.6 kg (over 3 months). The
mean changes in weight and body mass index by length of
follow-up are summarized in Table 1. At 12 weeks, the