Hindawi Publishing Corporation
Journal of Obesity
Volume 2011, Article ID 893629, 9 pages
Nikhil Nihalani,1Thomas L.Schwartz,2Umar A.Siddiqui,3and James L. Megna4
1SUNY Upstate Medical University, Syracuse, NY 13210, USA
2Department of Psychiatry, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
3Depression and Anxiety Disorders Research Program, Department of Psychiatry, SUNY Upstate Medical University, Syracuse,
NY 13210, USA
4Departments of Psychiatry and Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA
Correspondence should be addressed to Thomas L. Schwartz, email@example.com
Received 15 June 2010; Revised 25 November 2010; Accepted 9 December 2010
Academic Editor: S. B. Heymsfield
Copyright © 2011 Nikhil Nihalani et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much
speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these
agents. There is newer literature looking at the etiology of this weight gain and the potential treatments being used to alleviate this
side effect. The authors undertook a comprehensive literature review in order to present epidemiology, etiology, and treatment
options of weight gain associated with antipsychotics, mood stabilizers, and antidepressants.
Weight gain is a major health problem in the United
States and is a common adverse effect associated with
many psychiatric drugs used to treat depression, anxiety,
bipolar disorder, and schizophrenia. Clearly the new, second
generation antipsychotics have gathered much press and
development of metabolic disorders. Class action law suits
have been filed and settled against drug manufacturers, and
the FDA has issued cautions about these serious side effects
aware of this side effect profile of antipsychotics but also
note weight gain to be associated with a majority of other
commonly used psychiatric medications.
Induction of weight gain and obesity often contributes
towards psychotropic medication nonadherence. This can
lead to relapse and hospitalization. Weight gain clearly con-
tributes to medical comorbidity [1, 2]. Currently prescribed
psychotropics (antipsychotics, antidepressants, and mood
stabilizers) may cause 2–17kg of weight gain over the course
of clinical treatment [3–6]. Unfortunately, there are only a
very few psychotropics associated with weight loss [7–9].
This paper will briefly review the epidemiology, possible
etiology, and available treatment options for psychotropic-
induced weight changes. In a novel format, the authors will
present brief clinical cases to help convey information about
typical patient scenarios and management strategies.
2.Weight Gaindueto Psychotropics
Case 1. HA is a 22-year-old female suffering from depressive
disorder and social anxiety disorder. She had failed to
respond to an initial SSRI antidepressant (paroxetine) and
was subsequently placed on an SNRI. She had a partial
response to this agent and developed a minimal 1-2kg
weight gain. An approved second generation antipsychotic
(aripiprazole) was added for her resistant symptoms and
The above case is a typical and common example of
iatrogenically induced weight gain. With the introduction
of the newer, atypical second generation antipsychotics
(SGAs), the potential to cause remarkable weight gain
has been recognized. Nearly every antipsychotic has been
reported to cause weight gain. Although comparison is
limited by the different designs and recruitment procedures
of reviewed studies , a MEDLINE search from 1966
2 Journal of Obesity
to 2009 showed that the amount of body weight gain
was highest in patients treated with olanzapine (average
body weight gain 2.3kg/month), quetiapine (1.8kg/month),
and clozapine (1.7kg/month). Treatment with risperidone
showed moderate changes in body weight (average body
weight gain 1.0kg/month), where ziprasidone seemed to
induce only slight body weight changes (0.8kg/month).
Asenapine causes up to 0.9kg weight gain in the first three
weeks of treatment  and its FDA Package Insert discusses
. Nineteen percent of patients treated with asenapine
have weight gain as compared to 31% who were treated with
olanzapine . The other recently FDA approved second
generation antipsychotic is iloperidone. It has shown mild
to moderate weight gain (1.5–2.1kg). This appears to be
more than that produced by ziprasidone, but more similar to
that seen with risperidone . The above two antipsychotic
medications may not have enough postmarketing data
available as of now to clearly delineate weight gain potential.
Paliperidone was approved a few years back, and both short-
and long-term (52 weeks) studies have shown no significant
metabolic side effects including weight gain [15, 16]. The
weight gain associated with paliperidone could, in theory, be
similar to risperidone as it is an active risperidone metabo-
lite, unless the parent drug contains the weight-inducing
components which are now omitted from the paliperidone
pharmacodynamic profile after liver first-pass metabolism.
A common comparative finding in the literature suggests
that risperdone causes weight gain between 0.3–2.6kg while
ziprasidone often causes weight loss [17–26]. Olanzapine
may be the most significant second generation agent causing
weight gain from 4.2–7.4kg, and even up to an average gain
of 12kg in 45–90% of patients [27–32]. Quetiapine (regular
release and extended release) also has been implicated in
causing a more remarkable weight gain of 4.1 to 5.6kg
[33, 34]. Clozapine may ultimately be the most likely
agent to cause weight gain of all psychotropics producing
increases of 2.4 to 31.3kg, which is often a 10 percent
gain over baseline [35–39]. Finally, a short-term study using
aripiprazole showed a limited, 0.5–0.9kg weight gain as
compared to placebo .
Case 2. SK is a 43-year-old female with depressive disorder
and posttraumatic stress disorder. She failed to respond
to an approved SSRI (sertraline) but experienced minimal
weight gain. She was placed next on a combination of
an SNRI (venlafaxineER) and a dopamine-norepinephrine
reupake inhibitor (bupropionSR) also without symptomatic
improvement. She did not gain weight. Given her treatment
resistant symptoms, she was placed on tricyclic antidepres-
sants(imipramine, nortriptyline) withaminimum ofweight
gain but experienced cardiac side effects. Finally, she was
social anxiety and agoraphobia, almost refusing to go out of
her house due to the excessive weight gain.
The prevalence of weight gain due to antidepressants
such as imipramine (causing a 3-4kg weight gain) is
more chronic and more common, yet underrecognized as
epidemiologically as compared to psychotic disorders .
Tricyclic antidepressants (TCAs) and perhaps mono-
amine oxidase inhibitors (MAOIs) may be more likely to
cause weight gain than the selective serotonin reuptake
inhibitors (SSRIs), while mirtazapine may be placed between
the SSRIs and the TCAs in terms of relative risk of weight
gain [42, 43]. Bupropion may be the only modern agent
that lowers weight . There is a 1–3kg average weight
gain on antidepressants in 10–20% of the population treated
with them (likely a mixture of serotonergic facilitation
(excess synaptic serotonin, may downregulate and desensi-
tize serotonin-2c receptors causing increased appetite) and
anticholinergic properties). This is further complicated by
the fact that antipsychotic medication use is escalating after
FDA approval for bipolar and major depressive disorders,
which may most likely increase the incidence of metabolic
effects. MAOI’s use results in moderate weight gain .
Trazodone studies show 0.5 to 1.1kg weight gain over time
[8, 44], while five percent of baseline weight loss or 3–4.4kg
of weight loss has been reported with bupropion [45–47].
Although initial studies showed weight loss with fluoxetine,
long-term followup reveals that its weight reducing effect is
associated with a gain in body weight developing over time
. Acute losses of 0.35kg may be noted, but an average
of 2–2.5kg of weight may be gained . Citalopram may
cause 1 to 1.5kg weight gain over a year’s time [50, 51].
Fluvoxamine [5, 52] has two studies showing no weight gain
and no weight loss. Sertraline studies suggest more weight
gain than control groups . Paroxetine is the most likely
of the SSRIs to cause weight gain. Tohen et al. showed that
paroxetine promoted more weight gain when compared to
fluoxetine and sertraline . These findings suggest a lesser
iatrogenic weight gain side effect profile compared to the
SGAs mentioned above.
Mirtazapine has consistently shown greater weight gain
when compared to SSRIs (fluoxetine, paroxetine, and citalo-
pram) [54–56]. In clinical practice it seems to react like
an SGA in this regard. However, aripiprazole which has
recently been approved for adjunctive treatment of major
depressive disorder, differs as it tends to have a lower risk
of association with metabolic abnormalities . In some
patients though, the use of aripirpazole as an adjunct may
the newer SNRI duloxetine is concerned, in a recent 8 month
double blind randomized prospective trial with subjects
initially on duloxetine, escitalopram or placebo, the mean
change in weight was significantly higher for escitalopram
compared with duloxetine (+0.61kg, duloxetine; +1.83kg,
escitalopram; P < .05). However, the incidence of treatment-
emergent abnormal weight gain (FDA definition suggests
greater than or equal to a 7% increase in weight from
baseline) was similar between drugs and was significantly
greater for both duloxetine and escitalopram compared
with placebo. Mood stabilizing agents are used for bipolar
disorder and schizoaffective disorder. As with the antipsy-
chotics and antidepressants, weight gain is a common side
Journal of Obesity3
Seventy-one percent of divalproex treated patients may
gain more than 4kg . Nine tenths of a kilogram to
fourteen kilogram of divalproex-induced weight gain has
been reported in other studies [59, 60] with an incidence
of 8–59%. Lamotrigine has a more favorable, weight neutral
profile and may cause weight loss (of 2kg) or a gain (up to
0.6kg) . Carbamazapine may show a weight change up
to 15kg based on limited studies [62, 63]. Lithium reviews
suggest that weight gain is also a common side effect. Twenty
percent of patients on lithium gained 10kg or more in one
study and a 6.3kg weight gain in a second .
This section will attempt to briefly review the possible causes
of iatrogenic weight gain. Gothelf et al.  studied weight
gain mechanisms and energy balance in olanzapine-treated
adolescent male patients and found that an increase in body
mass index was due to an increase in calorie intake, but
also revealed effects on the resting energy expenditure or
slowing of metabolism. Psychotropics have broad pharma-
codynamic profiles, and it is likely that multiple neuro-
transmitters, receptors, and neurocircuits are responsible for
drug-induced weight gain. Olanzapine has activity at several
different receptor sites . Others, like clozapine, may act
at even different receptors (i.e., δ-opiod receptors) . In
rats, activating 5-HT2Creceptors decreases eating behavior
of the antipsychotics (olanzapine, quetiapine, and clozapine)
and some antidepressants (mirtazapine) have this 5-HT2C
Beta-3 adrenergic receptors found in adipose tissue play
an active role in weight control by converting fat into energy
especially in response to norepinepherine . Clinically
adrenoceptor antagonists but it is known that psychotropics
with higher affinities (i.e., TCAs) for these receptors are
associated with weight gain, whereas those with lower
affinities (e.g., SSRI) are not . Psychotropics with greater
ability to block H-1 receptors often show greater weight gain
potential , possibly through deactivating brain satiety
centers. Another mechanism may be related to blockage
of anticholinergic sites, which is associated with appetite
Potential weight loss strategies are outlined in Table 1. Early
intervention is the key to preventing significant drug-related
weight gain. Patients should be educated about weight gain
as a potential adverse effect before they begin treatment and
their weight should be monitored routinely as a standard
of care, as long as they continue taking drugs that may
increase weight. Informed consent about this risk should be
Metabolic syndrome is now a well-documented effect
of second-generation antipsychotic use. Ideally, a diet and
exercise plan should be initiated to prevent or treat weight
gain before medically significant weight gain occurs . A
successful weight loss program is one which can produce a
loss of 0.5to 1lb of thepatient’s initial body weightper week,
a rate of loss considered safe and acceptable . Diet and
exercise produces maximal benefit, but requires considerable
commitment and motivation on the part of the patient. This
is often difficult or impossible in the mentally ill.
Case 1: Part 2. HA had been given informed consent prior to
starting her serotonergic antidepressants about the potential
for weight gain and was advised to consider prophylactically
increasing her current low level exercise regimen, to watch
caloric intake, and to weigh herself with directions to notify
the clinician if she experienced a consistent gain of 2.5
or more kilograms. After mild initial weight gain, dieting
by portion control methods was discussed. After a more
remarkable weight gain was noted with the second genera-
tion antipsychotic, shewasofferedoff-labeluseof chromium
picolinate, or metformin, or approved use of orlistat. The
patient felt chromium picolinate had the most favorable risk
profile and tried 1000mcg daily without weight improve-
ment. At a subsequent visit she was placed on metformin.
(These interventions are discussed later in this paper).
Case 3. AB is a 30-year-old female with depression, anxiety,
and substance use disorder. Despite gaining sobriety, she still
suffered depressive symptoms and failed to respond to initial
SSRI (fluoxetine) and SNRI (duloxetine) therapy. She was
placed on the second generation antipsychotic, quetiapine,
with moderate symptom reduction but began to gain weight
(3–5kg) and asked for other treatment options. She was
cross-titrated onto aripiprazole with an acceptable weight
loss as a result and continued symptom reduction.
Besides diet and exercise, formal behavior modification
techniques involve changing eating habits and reinforcing
desired weight controlling behavior. It is the gradual but
consistent change in behavior that leads to healthier eating
habits. Simple use of portion control behaviors can teach
patients to eat less at every meal without the complexity
of counting fat versus carbohydrate calories, and does not
sugar diet . Behavior modification alone can generate
a weight loss of 0.5kg to 0.7kg per week . Through
formal, manualized cognitive-behavioral therapy patients
can achieve satisfaction with body image and acceptance of
modest weight loss. In one study, the effects of cognitive-
behavioral therapy on weight gain due to psychotropics was
studied in 6 schizophrenia patients (mean age 37.3 years).
The mean BMI (kg/m2) decreased from 29.6kg to 25.1kg
in the posttreatment group . Cognitive therapy has been
helpful in reducing weight for children and adolescents .
Furthermore, the addition of cognitive therapy to a diet-
controlled method produces better results .
consent, active monitoring of weight and early intervention,
4Journal of Obesity
or even prophlyaxis with diet and exercise are the first
treatment options. If this fails, or the patient is too ill to
comply, then clinical practice suggests that antiobesity drugs
may be appropriate. Risks and benefits should be evaluated
for each antiobesity agent. Sometimes, prior to trying an
and benefits of changing an effective medication should be
adequately considered before making changes.
Chromium compounds were utilized in a case above and
have been used over the counter to facilitate weight loss,
although the evidence for its efficacy is lacking so far [80,
81]. However, chromium picolinate has reasonable data in
regards to improving insulin sensitivity in diabetics and has
been shown to help curb carbohydrate cravings in depressed
patients despite continued depressive symptoms when dosed
600mcg/d [82, 83].
Drugs that reduce caloric intake or suppress hunger, are
commonly known as anorectic agents or appetite suppres-
sants. They act centrally by decreasing appetite or increasing
satiety. Sympathomimetic agents include phendimetrazine,
phentermine, mazindol, diethylpropion (many are con-
trolled substances), amphetamine and related compounds,
and phenylpropanolamine. The amphetamine products are
used on-label for the treatment of sleep apnea, narcolepsy,
and attention deficit/hyperactivity disorders. When these
conditions are comorbid with other primary psychiatric
disorders a weight loss advantage is often clinically noted.
Of note, however, the serotonergic agents, fenfluramine and
dexfenfluramine were withdrawn from the US market in
September 1997 over concerns about valvular heart disease
The three most currently prescribed drugs that are FDA
approved to treat obesity are phentermine, sibutramine,
and orlistat. Drugs approved for treating obesity usually
result in an additional weight loss of approximately 2–
5kg over placebo. At least four other types of single-agent
weight loss drugs are in possible late stage development:
(1) selective central cannabinoid-1 receptor blockers, (2)
selective central 5-hydroxytryptamine 2C serotonin receptor
agonists, (3) an intestinal lipase blocker, and (4) central-
acting incretin mimetic drugs . Furthermore, other
agents under development that may produce beneficial
like peptide-1 analogs such as liraglutide, an amylin analog
davalintide, the 5-HT(2C) receptor agonist lorcaserin, the
monoamine re-uptake inhibitor tesofensine, and a num-
ber of combination therapies such as pramlintide and
metreleptin, bupropion and naltrexone, phentermine and
topiramate, and bupropion and zonisamide . For exam-
ple, lorcaserin is a selective agonist of the 5-HT2C serotonin
receptor. Its shared mechanism of action with fenfluramine
suggests that a lorcaserin-phentermine combination therapy
may be particularly effective for treatment of obesity. The
combination of naltrexone and bupropion has recently been
examined in a large phase 3 trial for the treatment of obesity.
This study demonstrated that one year of treatment with
this two-drug combination produced an approximate 4%
weight loss beyond that seen with placebo therapy, similar
to that seen with other pharmacologic therapies. Because of
the distinct mechanism of action of these two medications,
naltrexone-bupropion may prove to be an attractive option
for patients who are resistant to other agents. Several
clinicians have noted that the combination of phentermine
and topiramate can generate substantial weight loss in at
least a subset of patients who exhibit little weight loss when
treated with phentermine alone. These observations led to
the development of fixed dose combinations of phentermine
and topiramate. A large, phase 3 clinical trial has shown that
one year of treatment with this combination led to weight
loss of up to 9% beyond that seen with placebo therapy.
There have been no head-to-head comparisons, however,
and further studies will be needed to determine the relative
effectiveness of these various treatments. It is noteworthy
that the doses of each agent used in the phentermine topira-
mate combination studied were lower than the typical doses
used for monotherapy with each drug . In one study,
following a 1-week placebo lead-in, 244 obese or overweight,
nondiabetic subjects received placebo subcutaneously (sc)
t.i.d., pramlintide sc (120μg t.i.d.), pramlintide sc (120μg
t.i.d.) + oral sibutramine (10mg q.a.m.), or pramlintide
sc (120μg t.i.d.) + oral phentermine (37.5mg q.a.m.) for
24 weeks. Weight loss achieved at week 24 with either
combination treatment was greater than with pramlintide
alone or placebo . As weight gain is often substantial
with psychotropics, combined antiobesity therapy in clinical
savvy using rational polypharmacy to achieve remission of
the psychiatric disorder at hand, and perhaps may consider
polypharmacy in severe cases of psychotropic drug-induced
obesity. Although risk benefits ratio for the use of single
or multiple antiobesity agents needs to be determined on
a case by case basis before the initiation of these therapies.
Sometimes clinicians can “chase their tails” by adding anti-
anti-side-effect medications have side effects themselves that
must be treated, and so on. Clinicians must make critical,
Hippocratic decisions when it comes to this complex clinical
Single sympathomimetic amphetamine agents, because
of their high potential for abuse, cardiac, and psychiatric
side effects (anxiety induction, insomnia), are generally not
often recommended for treating obesity . Sibutramine
is however relatively safer, as it is a mixed serotonergic and
noradrenergic reuptake inhibitor. It helps patients achieve
a 10% to 15% loss of body weight [89–92]. The safety
and effectiveness beyond 1 year of use have not been
determined. The mechanism by which sibutramine acts is
increased satiety. It decreases the levels of triglycerides, total
cholesterol, and LDL cholesterol, while also increasing the
levels of HDL cholesterol (seen in people who lose >5% of
body weight). Sibutramine can increase blood pressure and
heart rate. Other common adverse effects of sibutramine are
These studies were conducted in obese individuals who
were not taking psychotropics, so the outcome may not be
generalizable to the mentally ill. This agent when combined
Journal of Obesity5
Table 1: Weight gain treatment options.
Mode or medication
Naltreoxone and buropion
Phentermine and topiramate
Weight loss produced
0.5–0.7kg per week
4.5 drop in BMI
Gained 3kg less than patients who did not take Nizatidine
15/19 patients lost weight
Duration of treatment
with other antidepressants may lead to serotonin syndrome
and is often avoided.
Case 2: Part 2. SK had only a partial improvement on the
MAOI treatment, and subsequently, it was stopped but her
weight gain was not alleviated. She was ultimately treated
with a complex polypharmacy antidepressant regimen with
near remission of her symptoms. Similar to Case 1, she was
given metformin and orlistat with gradual, but not complete
weight loss. To gain final remission of depression symptoms
she was placed on a stimulant (methylphenidate) medication
which was titrated to a moderate dose. Her depression
resolved and she continued to lose weight to her baseline
Orlistat, a fat or lipase blocker, has safety and efficacy
data for use, up to two years. Orlistat may be a better option
than sibutramine for patients already taking other drugs
because it does not act systemically, so there is less risk of
interaction with centrally acting medications. Specifically, it
inhibits gastric and pancreatic lipases by binding covalently
to the serine residue at the active site of these enzymes .
This allows fat not to be absorbed by the GI system when
taken with meals [90–92]. It decreases triglycerides, total
cholesterol, and low-density lipoprotein cholesterol while
increasing high-density lipoprotein cholesterol . The
drug also improves glycemic control . The most com-
mon adverse effects are gastrointestinal, including increased
defecation, soft stools, anal leakage, fatty or oily stools, and
vitamin A and E deficiencies [95, 96]. Patients take orlistat
120mg three times daily and must take a multivitamin to
avoid deficiencies and eat a low-fat diet.
Two large placebo-controlled trials [97, 98] document
the efficacy of orlistat use for up to two years. After one year,
the orlistat group lost 10.2% of body weight in one study
and 8.8% in the second study. After 2 years, twice as many
10%. Patients must take other medications one hour before
or after orlistat to avoid change in absorption . One
study in the mentally ill reported that 13 consecutive patients
with psychotropic-induced weight gain lost 34.6% of side
effect weight gained . Nine of the 13 subjects suffered
from major depressive disorder and were taking serotonergic
antidepressants. Patients were deemed obese with a body
mass index (BMI) of >30kg/m2. The average weight gain
from psychotropics prior to orlistat initiation was 16.4kg.
The average weight loss within this relatively short time
period was 5.6kg or 34.6% of the weight gained as a result
of psychotropic drug use.
Amantadine was studied  in twelve patients who
had already gained a mean of 7.3kg during olanzapine
treatment. Subjects were started on amantadine at 300mg
per day. Results of the study showed an average weight loss
of 3.5kg over 3–6 months. No adverse effects were reported.
Implementation of nizatidine (histamine-2 receptor antag-
onist) was studied in a 16-week, randomized, double-blind,
placebo-controlled study in schizophrenia patients. Dosed at
300mg twice per day, it allowed patients to gain an average
of 2.5kg compared with the 5.5kg gained by patients treated
without nizatidine . Naltrexone, an opioid antagonist,
at a dosage of 50mg/day, has been shown to decrease weight
by reversing the observed hunger and craving for sweet,
fatty foods caused by tricyclic antidepressants and lithium.
Subjects reported decreased enjoyment ratings of food and
also diminished subjective feelings of hunger. No adverse
effects of opioid antagonism were seen regarding depressive
symptoms. In another study, naltrexone was coadministered
with antidepressants to eight female patients who had
already gained more than 6kg. After eight weeks, weight
gain was reversed in five patients, stopped in two patients,
and attenuated in another. However, weight increased by
1.5 ± 2.7kg within 14 weeks after the drug was stopped. Of
note, the mean weight loss was small compared to previous
drug-induced weight gain.
Preliminary findings suggest that topiramate may serve
as a dual purpose agent in the treatment of obese patients
with affective disorders. In one case report , topiramate
who had gained weight due to clozapine. Results showed
6Journal of Obesity
a sustained weight loss for the first time with an improve-
ment of psychotic symptoms. Additionally, topiramate
add-on studies for bipolar disorder have shown 33%–55%
of patients losing weight (10–15lbs) [104, 105]. Side effects
of fatigue, cognitive dulling, ataxia, glaucoma, oligohydrosis,
and acidosis are reported at doses of 100–400mg/day. A
recent review of studies using metformin and topiramate has
shown more efficacy and fewer side effects with metformin
Metformin holds promise as a treatment for weight gain
in pediatric patients taking psychotropic medications. In a
12-week open label study  conducted on 19 patients
(aged 10–18 years) who had gained over 10% of their
baseline weight while on antipsychotics, 500mg three times
a day of metformin was given for 12 weeks in addition to
psychotropics. The results of the study showed 15 patients
lost weight, 3 gained weight, and one remained unchanged
in weight. Sporadic diarrhea was noted in some patients that
resolved with time. The results of the safety tests for lactic
acidosis were unremarkable. A recent controlled study by the
same group confirmed this open label finding .
This paper has reviewed the risks of and possible causes
of psychotropic-induced obesity and concluded with some
potential treatment options designed to help manage this
side effect, while ideally maintaining patients on effective,
psychotropic regimens. There are no FDA approved agents
for reversing or preventing this iatrogenic weight gain, and
all options reported above are therefore considered off-label
at this time. Many studies are uncontrolled and of small
scale, limiting our conclusions in the mentally ill population.
A combination of diet, exercise, and medications would
be the ideal approach for combating the weight gain seen
in the mentally ill population, but we often find these
patients unable to comply with rigorous diet and exercise
regimens due to their psychiatric symptoms. Other strategies
which may be useful, but need further randomized placebo-
controlled studies include switching the psychotropic medi-
cation to one less likely to cause metabolic changes as well as
addition of medications such as topiramate and metformin
to note that, although the use of psychotropic medication
has contributed to the increased incidence of metabolic
effects in the mentally ill population, certain studies have
shown that, at baseline, patients with severe and persistent
illness have a higher prevalence of metabolic disorders.
Another concern is the high likelihood that metabolic
disorders are untreated in patients with schizophrenia, with
particularly high rates of nontreatment for hypertension
and dyslipidemia. There is a need for increased attention to
basic monitoring and treatment of metabolic risk factors in
The authors would welcome future psychotropics devoid
of weight gain potential and strongly suggest future, larger
controlled studies focusing on weight reduction in this
population using pharmacologic, nonpharmacologic, and
 D. B. Allison, J. L. Mentore, M. Heo et al., “Antipsychotic-
induced weight gain: a comprehensive research synthesis,”
American Journal of Psychiatry, vol. 156, no. 11, pp. 1686–
 P. S. Masand, “Weight gain associated with psychotropic
drugs,” Expert Opinion on Pharmacotherapy, vol. 1, no. 3, pp.
effect of drug treatment: mechanisms and management,”
Drug Safety, vol. 14, no. 5, pp. 329–342, 1996.
on weight,” Psychoneuroendocrinology, vol. 28, no. 1, pp. 83–
 M. Fava, “Weight gain and antidepressants,” Journal of
Clinical Psychiatry, vol. 61, no. 11, pp. 37–41, 2000.
 C. L. Carman, N. M. Leung, and A. H. Gnberman, “Weight
gain in epileptic patients during treatment with valproic
acid: a retrospective study,” Canadian Journal of Neurological
Sciences, vol. 24, no. 3, pp. 240–244, 1997.
 T. G. Cantu and J. S. Korek, “Monoamine oxidase inhibitors
and weight gain,” Drug Intelligence and Clinical Pharmacy,
vol. 22, no. 10, pp. 755–759, 1988.
 R. H. Weisler, J. A. Johnston, C. G. Lineberry, B. Samara, R. J.
Branconnier, and A. A. Billow, “Comparison of bupropion
and trazodone for the treatment of major depression,”
Journal of Clinical Psychopharmacology, vol. 14, no. 3, pp.
R. Atzert, “Long-term effects of topiramate on bipolar mood
European Psychiatry, vol. 16, no. 3, pp. 186–190, 2001.
 T. Wetterling, “Bodyweight gain with atypical antipsychotics:
a comparative review,” Drug Safety, vol. 24, no. 1, pp. 59–73,
 R. S. McIntyre, M. Cohen, J. Zhao, L. Alphs, T. A. Macek,
and J. Panagides, “Asenapine in the treatment of acute mania
in bipolar I disorder: a randomized, double-blind, placebo-
controlled trial,” Journal of Affective Disorders, vol. 122, no.
1-2, pp. 27–38, 2010.
 D. Bishara and D. Taylor, “Asenapine monotherapy in
the acute treatment of both schizophrenia and bipolar I
disorder,” Neuropsychiatric Disease and Treatment, vol. 5, no.
1, pp. 483–490, 2009.
 R. S. McIntyre, M. Cohen, J. Zhao, L. Alphs, T. A. Macek, and
J. Panagides, “Asenapine versus olanzapine in acute mania: a
double-blind extension study,” Bipolar Disorders, vol. 11, no.
8, pp. 815–826, 2009.
 P. J. Weiden, A. J. Cutler, M. H. Polymeropoulos, and C. D.
Wolfgang, “Safety profile of iloperidone: a pooled analysis
of 6-week acute-phase pivotal trials,” Journal of Clinical
Psychopharmacology, vol. 28, no. 7, pp. S12–S19, 2008.
 E. Spina and R. Cavallaro, “The pharmacology and
safety of paliperidone extended-release in the treatment of
schizophrenia,” Expert Opinion on Drug Safety, vol. 6, no. 6,
pp. 651–662, 2007.
 H. Y. Meltzer, W. V. Bobo, I. F. Nuamah et al., “Efficacy
and tolerability of oral paliperidone extended-release tablets
in the treatment of acute schizophrenia: pooled data from
Journal of Obesity7
three 6-week, placebo-controlled studies,” Journal of Clinical
Psychiatry, vol. 69, no. 5, pp. 817–829, 2008.
 S. Cohen, R. Glazewski, S. Khan, and A. Khan, “Weight gain
with risperidone among patients with mental retardation:
62, no. 2, pp. 114–116, 2001.
 J. M. Russell and J. A. Mackell, “Bodyweight gain associated
with atypical antipsychotics: epidemiology and therapeutic
implications,” CNS Drugs, vol. 15, no. 7, pp. 537–551, 2001.
 R. Ganguli, J. S. Brar, and Z. Ayrton, “Weight gain over 4
months in schizophrenia patients: a comparison of olanza-
pine and risperidone,” Schizophrenia Research, vol. 49, no. 3,
pp. 261–267, 2001.
 Y. Barak, “No weight gain among elderly schizophrenia
patients after 1 year of risperidone treatment,” Journal of
Clinical Psychiatry, vol. 63, no. 2, pp. 117–119, 2002.
 D. M. Taylor and R. McAskill, “Atypical antipsychotics
and weight gain—a systematic review,” Acta Psychiatrica
Scandinavica, vol. 101, no. 6, pp. 416–432, 2000.
 Y. Vanina, A. Podolskaya, K. Sedky et al., “Body weight
changes associated with psycopharmacology,” Psychiatric
Services, vol. 53, no. 7, pp. 842–847, 2002.
 S. J. Kingsbury, M. Fayek, D. Trufasiu, J. Zada, and G. M.
Simpson, “The apparent effects of ziprasidone on plasma
lipids and glucose,” Journal of Clinical Psychiatry, vol. 62, no.
5, pp. 347–349, 2001.
 P. E. Keck, M. Versiani, S. Potkin, S. A. West, E. Giller, and
K. Ice, “Ziprasidone in the treatment of acute bipolar mania:
a three-week, placebo-controlled, double-blind, randomized
trial,” AmericanJournal of Psychiatry, vol. 160, no. 4, pp. 741–
 S. Cohen, B. Fitzgerald, A. Okos, S. Khan, and A. Khan,
“Weight, lipids, glucose, and behavioral measures with
ziprasidone treatment in a population with mental retarda-
tion,” Journal of Clinical Psychiatry, vol. 64, no. 1, pp. 60–62,
 M. Arato, R. O’Connor, and H. Y. Meltzer, “A 1-year, double-
blind, placebo-controlled trial of ziprasidone 40, 80 and 160
mg/day in chronic schizophrenia: the Ziprasidone Extended
Use in Schizophrenia (ZEUS) study,” International Clinical
Psychopharmacology, vol. 17, no. 5, pp. 207–215, 2002.
 J. A. Frazier, J. Biederman, M. Tohen et al., “A prospective
open-label treatment trial of olanzapine monotherapy in
children and adolescents with bipolar disorder,” Journal of
Child and Adolescent Psychopharmacology, vol. 11, no. 3, pp.
 K. H. Littrell, R. G. Petty, N. M. Hilligoss, C. D. Peabody,
and C. G. Johnson, “Weight loss associated with olanzapine
treatment,” Journal of Clinical Psychopharmacology, vol. 22,
no. 4, pp. 436–437, 2002.
 B. Søholm and H. Lublin, “Long-term effectiveness of
risperidone and olanzapine in resistant or intolerant
schizophrenic patients. A mirror study,” Acta Psychiatrica
Scandinavica, vol. 107, no. 5, pp. 344–350, 2003.
 J. A. Lieberman, G. Tollefson, M. Tohen et al., “Comparative
efficacy and safety of atypical and conventional antipsychotic
drugs in first-episode psychosis: a randomized, double-blind
trial of olanzapine versus haloperidol,” American Journal of
Psychiatry, vol. 160, no. 8, pp. 1396–1404, 2003.
 G. Ratzoni, D. Gothelf, A. Brand-Gothelf et al., “Weight gain
associated with olanzapine and risperidone in adolescent
patients: a comparative prospective study,” Journal of the
no. 3, pp. 337–343, 2002.
 D. Gothelf, B. Falk, P. Singer et al., “Weight gain associated
with increased food intake and low habitual activity levels
in male adolescent schizophrenic inpatients treated with
olanzapine,” American Journal of Psychiatry, vol. 159, no. 6,
pp. 1055–1057, 2002.
 J. A. Shaw, J. E. Lewis, S. Pascal et al., “A study of quetiapine:
efficacy and tolerability in psychotic adolescents,” Journal of
Child and Adolescent Psychopharmacology, vol. 11, no. 4, pp.
 M. Brecher, I. W. Rak, K. Melvin, and A. M. Jones, “The
weight in patients with schizophrenia,” International Journal
of Psychiatry in Clinical Practice, vol. 4, no. 4, pp. 287–291,
 D. Briffa and T. Meehan, “Weight changes during clozapine
vol. 32, no. 5, pp. 718–721, 1998.
 C. J. Hong, C. H. Lin, W. Y. Yu Younger, K. H. Yang, and S.
J. Tsai, “Genetic variants of the serotonin system and weight
change during clozapine treatment,” Pharmacogenetics, vol.
11, no. 3, pp. 265–268, 2001.
 G. Masi, M. Mucci, and S. Millepiedi, “Clozapine in ado-
lescent inpatients with acute mania,” Journal of Child and
Adolescent Psychopharmacology, vol. 12, no. 2, pp. 93–99,
 D. B. Allison, J. L. Mentore, M. Heo et al., “Antipsychotic-
induced weight gain: a comprehensive research synthesis,”
American Journal of Psychiatry, vol. 156, no. 11, pp. 1686–
 J. S. Lamberti, T. Bellnier, and S. B. Schwarzkopf, “Weight
gain among schizophrenic patients treated with clozapine,”
American Journal of Psychiatry, vol. 149, no. 5, pp. 689–690,
 S. G. Potkin, A. R. Saha, M. J. Kujawa et al., “Aripiprazole,
an antipsychotic with a novel mechanism of action, and
risperidone vs placebo in patients with schizophrenia and
schizoaffective disorder,” Archives of General Psychiatry, vol.
60, no. 7, pp. 681–690, 2003.
& Wilkins, Baltimore, Md, USA, 8th edition, 1998.
 E. Frank, D. J. Kupfer, C. M. Bulik, and J. A. Levenson,
“Imipramine and weight gain during the treatment of
recurrent depression,” Journal of Affective Disorders, vol. 20,
no. 3, pp. 165–172, 1990.
 J. B. Prince, T. E. Wilens, J. Biederman et al., “A controlled
study of nortriptyline in children and adolescents with
attention deficit hyperactivity disorder,” Journal of Child and
Adolescent Psychopharmacology, vol. 10, no. 3, pp. 193–204,
 C. F. Paradis, J. A. Stack, C. J. George et al., “Nortriptyline
and weight change in depressed patients over 60,” Journal
of Clinical Psychopharmacology, vol. 12, no. 4, pp. 246–250,
 M. Trivedi and A. Rush, “A review of randomized controlled
medication trials in major depression,” Biological Psychiatry,
vol. 31, pp. 188–189, 1992.
 G. Chouinard, “Bupropion and amitriptyline in the treat-
ment of depressed patients,” Journal of Clinical Psychiatry,
vol. 44, no. 5, pp. 121–129, 1983.
 J. W. Anderson, F. L. Greenway, K. Fujioka, K. M. Gadde,
J. McKenney, and P. M. O’Neil, “Bupropion SR enhances
weight loss: a 48-week double-blind, placebo-controlled
trial,” Obesity Research, vol. 10, no. 7, pp. 633–641, 2002.
8Journal of Obesity
 E. Leinonen, J. Skarstein, K. Behnke, H. ˚ Agren, and J. Th.
Helsdingen, “Efficacy and tolerability of mirtazapine versus
citalopram: a double-blind, randomized study in patients
with major depressive disorder,” International Clinical Psy-
chopharmacology, vol. 14, no. 6, pp. 329–337, 1999.
in weight during a 1-year trial of fluoxetine,” American
Journal of Psychiatry, vol. 156, no. 8, pp. 1170–1176, 1999.
 C. D. Bouwer and B. H. Harvey, “Phasic craving for car-
bohydrate observed with citalopram,” International Clinical
Psychopharmacology, vol. 11, no. 4, pp. 273–278, 1996.
 C. A. Abell, D. L. Farquhar, S. M. Galloway, F. Steven,
A. E. Philip, and J. F. Munro, “Placebo controlled double-
blind trial of fluvoxamine maleate in the obese,” Journal of
Psychosomatic Research, vol. 30, no. 2, pp. 143–146, 1986.
 C. A. L. Moon and D. K. Jesinger, “The effects of psy-
chomotor performance of fluvoxamine versus mianserin in
depressed patients in general practice,” British Journal of
Clinical Practice, vol. 45, no. 4, pp. 259–262, 1991.
 M. Tohen, R. W. Baker, L. L. Altshuler et al., “Olanzapine
versus divalproex in the treatment of acute mania,” American
Journal of Psychiatry, vol. 159, no. 6, pp. 1011–1017, 2002.
 B. H. Harvey and C. D. Bouwer, “Neuropharmacology of
paradoxic weight gain with selective serotonin reuptake
inhibitors,” Clinical Neuropharmacology, vol. 23, no. 2, pp.
 L. Ribeiro, J. V. Busnello, M. Kauer-Sant’Anna et al., “Mir-
Brazilian Journal of Medical and Biological Research, vol. 34,
no. 10, pp. 1303–1307, 2001.
 O. Benkert, A. Szegedi, and R. Kohnen, “Mirtazapine
compared with paroxetine in major depression,” Journal of
Clinical Psychiatry, vol. 61, no. 9, pp. 656–663, 2000.
 E. Stip and V. Tourjman, “Aripiprazole in schizophrenia and
schizoaffective disorder: a review,” Clinical Therapeutics, vol.
32, no. 1, pp. S3–S20, 2010.
 T. A. Pigott, A. Prakash, L. M. Arnold, S. T. Aaronson, C.
H. Mallinckrodt, and M. M. Wohlreich, “Duloxetine versus
escitalopram and placebo: an 8-month, double-blind trial
in patients with major depressive disorder,” Current Medical
Research and Opinion, vol. 23, no. 6, pp. 1303–1318, 2007.
 K. N. R. Chengappa, L. Chalasani, J. S. Brar, H. Parepally, P.
Houck, and J. Levine, “Changes in body weight and body
mass index among psychiatric patients receiving lithium,
valproate, or topiramate: an open-label, nonrandomized
chart review,” Clinical Therapeutics, vol. 24, no. 10, pp. 1576–
 V. Biton, W. Mirza, G. Montouris, A. Vuong, A. E. Hammer,
and P. S. Barrett, “Weight change associated with valproate
and lamotrigine monotherapy in patients with epilepsy,”
Neurology, vol. 56, no. 2, pp. 172–177, 2001.
 Ginsberg et al., in Proceedings of the 156th Annual Meeting
of the American Psychiatric Association, San Francisco, Calif,
USA, May 2003.
 Y. Lampl, Y. Eshel, A. Rapaport, and I. Sarova-Pinhas,
“Weight gain, increased appetite, and excessive food intake
induced by carbamazepine,” Clinical Neuropharmacology,
vol. 14, no. 3, pp. 251–255, 1991.
 G. Luef, I. Abraham, M. Haslinger et al., “Polycystic ovaries,
obesity and insulin resistance in women with epilepsy: a
women,” Journal of Neurology, vol. 249, no. 7, pp. 835–841,
weight gain,” Pharmacopsychiatry, vol. 28, no. 2, pp. 35–44,
 D. Gothelf, B. Falk, P. Singer et al., “Weight gain associated
with increased food intake and low habitual activity levels
in male adolescent schizophrenic inpatients treated with
olanzapine,” American Journal of Psychiatry, vol. 159, no. 6,
pp. 1055–1057, 2002.
 D. B. Allison and D. E. Casey, “Antipsychotic-induced weight
gain: a review of the literature,” Journal of Clinical Psychiatry,
vol. 62, no. 7, pp. 22–31, 2001.
 T. Kobayashi, K. Ikeda, and T. Kumanishi, “Effects of
clozapine on the δ- and κ-opioid receptors and the G-
protein-activated K+ (GIRK) channel expressed in Xenopus
oocytes,” British Journal of Pharmacology, vol. 123, no. 3, pp.
 G. Curzon, E. L. Gibson, and A. O. Oluyomi, “Appetite
suppression by commonly used drugs depends on 5-HT
receptors but not on 5-HT availability,” Trends in Pharma-
cological Sciences, vol. 18, no. 1, pp. 21–25, 1997.
 A. D. Strosberg and F. Pietri-Rouxel, “Function and reg-
ulation of the β3-adrenoceptor,” Trends in Pharmacological
Sciences, vol. 17, no. 10, pp. 373–381, 1996.
 G. M. Goodwin, “How do antidepressants affect serotonin
receptors? The role of serotonin receptors in the therapeutic
and side effect profile of the SSRIs,” Journal of Clinical
Psychiatry, vol. 57, no. 4, pp. 9–13, 1996.
 S. H. Stahl, Essential Psychopharmacology, Cambridge Uni-
versity Press, New York, NY, USA, 1996.
no. 2, pp. 596–601, 2004.
 D. Weiss, “How to help your patients lose weight: current
therapy for obesity,” ClevelandClinicJournalofMedicine,vol.
67, no. 10, pp. 739–754, 2000.
 P. R. Thomas, Ed., Weighing the Options: Criteria for Evaluat-
ing Weight Management Programs, National Academy Press,
Washington, DC, USA, 1995.
controlled entrees enhances weight loss in women,” Obesity
Research, vol. 12, no. 3, pp. 538–546, 2004.
 D. Umbricht, H. Flury, and R. Bridler, “Cognitive behavior
therapy for weight gain,” American Journal of Psychiatry, vol.
158, no. 6, pp. 971–972, 2001.
 H. M. Connolly, J. L. Crary, M. D. McGoon et al., “Valvular
heart disease associated with fenfluramine phentermine,”
New England Journal of Medicine, vol. 337, no. 9, pp. 581–
 K. P. Kelly and D. S. Kirschenbaum, “Immersion treatment
of childhood and adolescent obesity: the first review of a
promising intervention,” Obesity Reviews, vol. 12, no. 1, pp.
 M. Q. Werrij, A. Jansen, S. Mulkens, H. J. Elgersma, A. J. H.
A. Ament, and H. J. Hospers, “Adding cognitive therapy to
dietetic treatment is associated with less relapse in obesity,”
Journal of Psychosomatic Research, vol. 67, no. 4, pp. 315–324,
 R. B. Saper, D. M. Eisenberg, and R. S. Phillips, “Common
dietary supplements for weight loss,” American Family Physi-
cian, vol. 70, no. 9, pp. 1731–1738, 2004.
 M. H. Pittler and E. Ernst, “Dietary supplements for body-
weight reduction: a systematic review,” American Journal of
Clinical Nutrition, vol. 79, no. 4, pp. 529–536, 2004.
Journal of Obesity9 Download full-text
 J. R. T. Davidson, K. Abraham, K. M. Connor, and M. N.
McLeod, “Effectiveness of chromium in atypical depression:
a placebo-controlled trial,” Biological Psychiatry, vol. 53, no.
3, pp. 261–264, 2003.
 J. P. Docherty, D. A. Sack, M. Roffman, M. Finch, and
J. R. Komorowski, “A double-blind, placebo-controlled,
exploratory trial of chromium picolinate in atypical depres-
sion: effect on carbohydrate craving,” Journal of Psychiatric
Practice, vol. 11, no. 5, pp. 302–314, 2005.
 G. A. Bray, “Use and abuse of appetite-suppressant drugs in
the treatment of obesity,” Annals of Internal Medicine, vol.
119, no. 7, pp. 707–713, 1993.
 D. C. Klonoff and F. Greenway, “Drugs in the pipeline for the
obesity market,” Journal of Diabetes Science and Technology,
vol. 2, no. 5, pp. 913–918, 2008.
 J. C. G. Halford, E. J. Boyland, J. E. Blundell, T. C. Kirkham,
and J. A. Harrold, “Pharmacological management of appetite
expression in obesity,” Nature Reviews Endocrinology, vol. 6,
no. 5, pp. 255–269, 2010.
 L. M. Kaplan, “Pharmacologic therapies for obesity,” Gas-
troenterology Clinics of North America, vol. 39, no. 1, pp. 69–
 L. J. Aronne, A. E. Halseth, C. M. Burns, S. Miller, and L. Z.
Shen, “Enhanced weight loss following coadministration of
pramlintide with sibutramine or phentermine in a multicen-
ter trial,” Obesity, vol. 18, no. 9, pp. 1739–1746, 2010.
 G. A. Bray, D. H. Ryan, D. Gordon, S. Heidingsfelder, F.
Cerise, and K. Wilson, “A double-blind randomized placebo-
controlled trial of sibutramine,” Obesity Research, vol. 4, no.
3, pp. 263–270, 1996.
 M. E. J. Lean, “Sibutramine—a review of clinical efficacy,”
International Journal of Obesity, vol. 21, no. 1, pp. S30–S36,
 M. Weintraub, A. Rubio, A. Golik, L. Byrne, and M.
L. Scheinbaum, “Sibutramine in weight control: a dose-
tics, vol. 50, no. 3, pp. 330–337, 1991.
 M. J. Stock, “Sibutramine: a review of the pharmacology of
a novel anti-obesity agent,” International Journal of Obesity,
vol. 21, supplement 1, pp. S25–S29, 1997.
 R. Guerciolini, “Mode of action of orlistat,” International
Journal of Obesity, vol. 21, supplement 3, pp. S12–S23, 1997.
 L. F. van Gaal, J. I. Broom, G. Enzi, and H. Toplak, “Efficacy
and tolerability of orlistat in the treatment of obesity: a
6-month dose-ranging study,” European Journal of Clinical
Pharmacology, vol. 54, no. 2, pp. 125–132, 1998.
 L. Sj¨ ostr¨ om, A. Rissanen, T. Andersen et al., “Randomised
placebo-controlled trial of orlistat for weight loss and
prevention of weight regain in obese patients,” Lancet, vol.
352, no. 9123, pp. 167–172, 1998.
 W. McNeely, P. Benfield, L. Drent, and F. X. Pi-Sunyer,
“Orlistat,” Drugs, vol. 56, no. 2, pp. 241–250, 1998.
 P. A. Hollander, S. C. Elbein, I. B. Hirsch et al., “Role
of orlistat in the treatment of obese patients with type 2
diabetes: a 1-year randomized double-blind study,” Diabetes
Care, vol. 21, no. 8, pp. 1288–1294, 1998.
 J. Zhi, A. T. Melia, S. G. Koss-Twardy, S. Arora, and I.
H. Patel, “The effect of orlistat, an inhibitor of dietary fat
volunteers,” Journal of Clinical Pharmacology, vol. 36, no. 2,
pp. 152–159, 1996.
 A. T. Melia, S. G. Koss-Twardy, and J. Zhi, “The effect
of orlistat, an inhibitor of dietary fat absorption, on the
absorption of vitamins A and E in healthy volunteers,”
Journal of Clinical Pharmacology, vol. 36, no. 7, pp. 647–653,
 T. L. Schwartz and M. Beale, “Psychotropic induced weight
gain alleviated with orlistat,” Psychopharm Bulletin, vol. 37,
no. 1, pp. 5–8, 2003.
 M. Floris, J. Lejeune, and W. Deberdt, “Effect of amantadine
on weight gain during olanzapine treatment,” European
Neuropsychopharmacology, vol. 11, no. 2, pp. 181–182, 2001.
 A. Breier, Y. Tanaka, and S. Roychowdhury, “Nizatidine for
double-blind study,” in Proceedings of the Meeting of the Col-
leges of Psychiatric and Neurologic Pharmacists, San Antonio,
Tex, USA, March 2001.
 M. C. Lessig, N. A. Shapira, and T. K. Murphy, “Topiramate
for reversing atypical antipsychotic weight gain,” Journal of
40, no. 12, article 1364, 2001.
 S. N. Ghaemi, S. G. Manwani, J. J. Katzow, J. Y. Ko, and
F. K. Goodwin, “Topiramate treatment of bipolar spectrum
disorders: a retrospective chart review,” Annals of Clinical
Psychiatry, vol. 13, no. 4, pp. 185–189, 2001.
in treatment-resistant bipolar spectrum disorders,” Journal
of Clinical Psychopharmacology, vol. 22, no. 4, pp. 431–435,
 L. K. Ellinger, H. J. Ipema, and J. M. Stachnik, “Efficacy
of metformin and topiramate in prevention and treatment
of second-generation antipsychotic-induced weight gain,”
Annals of Pharmacotherapy, vol. 44, no. 4, pp. 668–679, 2010.
 J. A. Morrison, E. M. Cottingham, and B. A. Barton,
“Metformin for weight loss in pediatric patients taking
psychotropic drugs,” American Journal of Psychiatry, vol. 159,
no. 4, pp. 655–657, 2002.
 D. J. Klein, E. M. Cottingham, M. Sorter, B. A. Barton,
and J. A. Morrison, “A randomized, double-blind, placebo-
controlled trial of metformin treatment of weight gain
associated with initiation of atypical antipsychotic therapy
in children and adolescents,” American Journal of Psychiatry,
vol. 163, no. 12, pp. 2072–2079, 2006.
 H. A. Nasrallah, J. M. Meyer, D. C. Goff et al., “Low rates
of treatment for hypertension, dyslipidemia and diabetes
in schizophrenia: data from the CATIE schizophrenia trial
sample at baseline,” Schizophrenia Research, vol. 86, no. 1–3,
pp. 15–22, 2006.