Table 1.

Clinical study highlights examining weight gain and adiposity changes associated with antipsychotics in patients with serious mental illness.

A. Weight Gain Associated with Antipsychotics
AUTHORS	PARTICIPANTS	AP TREATMENT	METABOLIC OUTCOME
Lau et al. (2016) [17]	• Retrospective Study • Males (n = 67) + Females (n = 50) • Mean age: 34.5	• Clozapine use for at least 1 year (Compared 3 month to 12 month treatment time points) • Average clozapine dose of ~300 mg (3 months) and ~316 mg (12 months)	• Females gained significantly more body weight during 9 month clozapine treatment (5.5% weight increase in females vs 1.2% increase in males)
Covell et al. (2004) [18]	• Patients with schizophrenia • Non-responsive to treatment with 2 other APs • Males (n = 43) + females (n = 60)	• Switched to clozapine and monitored for 2 year treatment • Control patients remained on “usual care”	• Significantly more women (28%) become obese compared to men (3%) treated with clozapine • Significantly more women (29%) gained more than 20% baseline weight compared to men (13%) over 2 year clozapine treatment period
Xiang et al. (2011) [19]	• Retrospective survey • Inpatients with schizophrenia • Males (3734) + females (2707) • Mean age: 44.0	• 3 months of AP treatment	• Significantly more female patients recorded complaints of weight gain compared to males
Hakko et al. (2006) [21]	• Longitudinal study • Males + females • Age: Birth-31 years • Males (2947) + Females (3026)	• BMI measured at 14 and 31 years of age • Lifestyle and health questionnaire administered at 31 years of age to assess variables that included medication use and diagnoses, but ultimately there was not enough data to include antipsychotic use information in model	• Females with a psychiatric disorder were significantly more likely than men to transition from under or normal weight to overweight or obese (3.6 fold risk females vs 2.1 fold risk in males)
Verma et al. (2009) [22]	• Prospective and naturalistic study • First-episode psychiatric disorders with no prior AP exposure • Males (n = 29) + females (n = 27) • Mean age: 29.8	• 6 month AP treatment • Included mono and dual therapy (60.7% received an FGA, 62.5% received an SGA)	• BMI was significantly increased following 6 month treatment • Female sex was a significant predictor of weight gain
Lee et al. (2004) [23]	• In-patients diagnosed with schizophrenia • Males (n = 24) + females (n = 48) • Mean age (olanzapine): 33.9 • Mean age (risperidone): 36.3	• Olanzapine treatment average 103.5 weeks, average dose 12.4 mg/day • Risperidone treatment, average 93.2 weeks, average dose 4.5 mg/day	• Olanzapine and risperidone treatment resulted in weight gain • No effect of gender on weight gain risk
Lipkovich et al. (2009) [24]	• Patients diagnosed with schizophrenia, schizophrenia spectrum disorders, bipolar mania, bipolar depression, or borderline personality disorder (n = 3826) • Mean age: 38.8	• 30 week olanzapine treatment	• Female sex was significantly associated with probability of severe weight gain
Attux et al. (2007) [25]	• First episode psychotic outpatients • Males (n = 26) + females (n = 18) • Mean age:26.3 • (females significantly older than males; mean age 32.8 vs 21.9)	6 month antipsychotic treatment	• Both males and females exhibited increased BMI and weight gain • Only females showed increased waist circumference
Taylor et al. (2018) [26]	• Youths with schizophrenia or schizoaffective disorder • Males (n = 47) + females (n = 22) • Mean age: 14.15	8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine	Sex did not predict or moderate weight change or percent weight change
Susilova et al. (2017) [27]	• Retrospective study • Inpatients with a diagnosis of schizophrenia or schizoaffective disorder • Males (n = 466) + females (n = 271) • Mean age: 30 (males), 38.3 (females)	• Average length of hospital stay range 29.4 days-41.8 days • Received AP monotherapy and polytherapy	• Greater increase in BMI and weight gain in response to polytherapy in men but not women • No significant difference in weight changes between males and females in response to some atypical APs • Significant increase in BMI in men but not women in response to multi-receptor APs and aripiprazole
Lane et al. (2006) [28]	• AP naïve patients with schizophrenia • Male (n = 68) + female (n = 55) • Mean age: 34.0	• 42 day risperidone monotherapy	• Male patients gained more weight than females (by an average of 0.650 kg)
B. Adiposity Changes Associated with Antipsychotics
AUTHORS	PARTICIPANTS	AP TREATMENT AND ADIPOSITY MEASUREMENT APPROACH	METABOLIC OUTCOME
Konarzewska et al. (2014) [29]	• Normal weight patients diagnosed with schizophrenia and BMI-matched controls • Patients with schizophrenia: males (n = 33) + females (n = 19) • Healthy controls: males (23) + females (22) • Mean age: 42.13	• At least 3 months of continuous treatment with an AP prior to beginning the study, and total use of at least 1 year, for patients with schizophrenia • BIA	• Males and females with schizophrenia had significantly increased visceral adipose tissue mass compared to healthy controls • Men with schizophrenia had significantly greater visceral adipose tissue compared to females with schizophrenia (~5-fold)
AUTHORS	PARTICIPANTS	AP TREATMENT	METABOLIC OUTCOME
Sugawara et al. (2012) [30]	• Outpatients diagnosed with schizophrenia • Males (n = 74) + females (n = 130) • Mean age: 41.3	• AP use was defined by chlorpromazine equivalents, but type and duration of AP was not defined • BIA	• BMI was increased in males and females with schizophrenia compared to healthy controls • Females with schizophrenia had greater body weight, body fat, fat-free mass, muscle mass, and body water compared to healthy females • Males with schizophrenia body fat, and % body fat were significantly higher (while lean mass, and body water content were higher in health males)
Zhang et al. (2004) [31]	• AP-naïve patients with schizophrenia • Male (n = 27) + women (n = 19) • Mean age: 26.9	• 10 week AP treatment • MRI	• 10 week treatment with risperidone, chlorpromazine, or quetiapine increased visceral and SQ fat in males • Adipose tissue gain was attenuated in females compared to males
Satoh et al. (2007) [32]	• Males with schizophrenia • n = 80 (+ 64 healthy controls)	• All patients with schizophrenia were on an AP (duration not defined) • BIA	• Significantly increased body fat and lower intracellular fluid in men with schizophrenia • Total body fluid decreased in men with schizophrenia

AP: antipsychotic, BIA: bioelectrical impedance analysis, MRI: magnetic resonance imaging.