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PubMed2026

Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics: A Systematic Review and Network Meta-Analysis.

IMPORTANCE: Significant weight gain is a concerning adverse effect of antipsychotic medications experienced by patients with schizophrenia spectrum disorders (SSDs). Its high prevalence and significant contribution to cardiometabolic morbidity in this population warrant better consensus on the management of antipsychotic-induced weight gain and related comorbidity. OBJECTIVES: To evaluate the association between pharmacological interventions and changes in body weight among antipsychotic-treated patients with SSDs. DATA SOURCES: Ovid MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) Search Portal were searched up to December 5, 2025. STUDY SELECTION: Randomized clinical trials examining any pharmacological intervention for weight reduction in antipsychotic-treated patients with SSDs were included. No restrictions to study duration were applied. DATA EXTRACTION AND SYNTHESIS: A systematic review and frequentist random-effects network meta-analysis was conducted. Certainty in the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. The first round of data analysis took place between May 2025 to November 2025 and was updated in December 2025. MAIN OUTCOMES AND MEASURES: The primary outcome was change in body weight following treatment with pharmacological agent vs placebo or standard care. Secondary outcomes included other anthropometric and metabolic parameters. RESULTS: A total of 95 studies examining 39 individual pharmacological interventions were included in this review (pooled N = 5898). The network meta-analysis found that semaglutide (mean difference [MD], -10.98 kg; 95% CI, -13.33 to -8.62; k = 3; moderate certainty), liraglutide (MD, -5.43 kg; 95% CI, -8.54 to -2.33; k = 2; moderate certainty), topiramate (MD, -3.95 kg; 95% CI, -5.89 to -2.02; k = 5; moderate certainty), metformin (MD, -3.86 kg; 95% CI, -5.02 to -2.70; k = 16; moderate certainty), and exenatide (MD, -2.97 kg; 95% CI, -5.83 to -0.11; k = 3; moderate certainty) were associated with the most significant reductions in body weight compared to placebo. Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. Clinically meaningful weight change of 5% or greater was observed with semaglutide and metformin. Beneficial effects on other metabolic outcomes were also noted with several of the medications, and there were no major concerns with gastrointestinal adverse effects or leaving the study early (ie, dropouts) between interventions. CONCLUSIONS AND RELEVANCE: This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain.

Humans↗

PubMed1978

[Weight changes and risk factors during a 10-year period. Observations on subjects in the Basel study].

The change in body mass index (MI) over a 10 year period was compared to different risk factors for cardiovascular disease in 1663 men (aged 15-64) of the Basle Study. Blood pressure and betalipoproteins correlated significantly (alpha less than 0,01) with changes in MI as well as triglycerides (alpha less than 0,05). No correlation was observed between MI and cholesterol or smoking habits. Our results confirme that the age dependent increase in blood pressure, beta-lipoproteins and triglycerides is largely due to the increment of obesity in the adult.

Adolescent↗

PubMed1979

Increased weight gain as a morphine withdrawal response in rats.

Adult male Wistar rats injected daily with 20 or 200 mg/kg morphine-SO4 for 35 days suffered a dose-dependent weight loss over the first 3 days of morphine withdrawal. However, during the next 28 days they gained weight more rapidly than controls, the rates being related to the previous morphine dosage. These findings were replicated in Sprague-Dawley rats treated for 26 days with 60 mg/kg morphine. Food-restricted controls suffering weight losses equal to those of the morphine-treated or morphine-withdrawn groups did not subsequently gain weight as rapidly as the latter groups. Therefore the rapid post-withdrawal weight gain may be a true adaptive response to the weight suppressing effects of morphine. Also, comparisons of weight changes during treatment in the two experiments indicated possible strain differences for tolerance to morphine's direct weight-reducing effect.

Animals↗

PubMed1977

The applicability of inescapable shock as a source of animal depression.

Male rats (N = 27) were given initial experience with escapable shock, equivalent amounts of inescapable shock, or no shock. Measures were then obtained in the ensuing 15 hours on food intake, water intake, number of cage crossings, and weight change for all groups. Following this, animals were tested on an escape task. Inescapably shocked animals showed significant decreases in food and water consumption in comparison to both nonshocked and escapably shocked control rats. Weight gains were significantly decreased by exposure to shock irrespective of the availability of a coping response. Consistency of these findings with proposals suggesting that exposure to inescapable shock leads to a state of animal depression (learned helplessness) is discussed and compared to alternative stress explanations.

Animals↗

PubMed1977

The relationship between dietary intake, weight change, nitrogen balance, and protein turnover in man.

We have examined the relationships between protein turnover, protein synthesis, and protein breakdown and dietary intake, weight change, and nitrogen balance in children who were recovering and had recovered from severe protein-energy-malnutrition. Protein metabolism was measured by giving [15N]glycine and measuring the enrichment of urinary urea. The level of dietary protein did not affect protein metabolism. There were highly significant correlations between both protein flux and protein synthesis and the ad libitum dietary intake, nitrogen balance, and weight change. Over the range of dietary intake, 60 to 270 cal/kg per day, the protein synthesis rate increased 5-fold. Large changes in dietary intake resulted in small changes in protein breakdown, with breakdown being least on an inadequate intake. Changes in the rate of protein breakdown did not contribute to changes in nitrogen balance or body weight.

Body Weight↗

PubMed1978

Protein deprivation in primates. XI. Determinants of weight change during and after pregnancy.

Individual differences in weight gain of rhesus monkeys during pregnancy far exceed the variation in infant weight. Weight gain thus reflects maternal adjustment to her physiological state in relation to her environment rather than growth of the infant. Diets high in protein lead to great weight gain. Skeletal length is positively correlated and conception weight negatively correlated with weight gain. Season of pregnancy, length of gestation and sex of the infant are unrelated to weight gain. None of the monkeys exhibited edema during gestation. Postpartum changes in body weight were small during the first 6 weeks.

Animals↗

PubMed1979

Changes in weight during treatment for depression.

Changes in appetite and weight were examined in a group of 47 carefully diagnosed primary depressives who were treated in a random design with either placebo (N = 17) or amitryptyline (N = 30) over a 35-day protocol. While the amitriptyline treated group as a whole showed a greater gain in weight than did the placebo group (4.5 vs. 0.5 lb, p less than 0.05), no differential effects could be demonstrated between drug responders and nonresponders. Likewise, while a consistent relationship between the self-report of decreased appetite and final weight change was noted in the placebo group, no simple relationship between final weight change and self-reported changes in appetite were apparent in the drug-treated patients. There was, however, a relationship between the report of decreased appetite and clinical severity of depression in the drug nonresponder subgroup despite significant weight gain during the protocol. Thus, weight change during this study period did not appear to show a simple relationship to corresponding clinical change. The clinical lore that has supported the notion that increased appetite and weight gain in patients being treated with tricyclic antidepressants are "good" signs cannot be confirmed by our findings.

Adult↗

PubMed1979

Weight changes with depot neuroleptic maintenance therapy.

A prospective study of schizophrenic patients prescribed injectable depot neuroleptic drugs as maintenance therapy showed a clinically significant weight gain in 55% of patients. No significant difference was shown between flupenthixol decanoate and fluphenazine decanoate, nor was a clinically meaningful relationship shown with dose, or the use of anti-parkinsonian drugs. The weight gain continued for at least 2 years following a mental state relapse. It is suggested that the monitoring of weight and giving of appropriate advice on diet are two essential in maintenance therapy of chronic schizophrenia.

Body Weight↗

PubMed1977

Plasma fenfluramine levels, weight loss, and side effects.

Fifty women with refractory obesity received fenfluramine for 20 weeks. Every two weeks details of weight change, drug dose, degree of anorexia, and any side effects were recorded and plasma was obtained for fenfluramine and norfenfluramine measurements. Of the 41 patients available for final analysis 26 achieved a maximum plateau dose of 160 mg/day. Plasma fenfluramine concentrations did not correlate with the degree of anorexia or with the incidence of side effects other than the severity of dream disturbance. There was a highly significant relation between weight loss and plasma fenfluramine and norfenfluramine concentrations and also between weight loss and the presence of sustained anorexia. Women who achieved mean plateau concentrations over 200 ng/ml lost a mean 8.8 kg while those with concentrations less than 100 ng/ml lost a mean of only 2.1 kg. When fenfluramine is prescribed in refractory obesity the dose should be increased stepwise until either satisfactory weight loss is achieved or troublesome side effects appear.

Adult↗

PubMed1979

[Effectiveness of a preventive mass examination for cardiac risk factors (author's transl)].

18 months after a mass examination for coronary heart disease risk factors in employees of a large industrial firm, 75% of the subjects examined at that time were re-interviewed and measurements of blood pressure and weight repeated. Despite an altogether inadequate longterm control of the risk factors detected, a part of the subjects examined had drawn consequences regarding their way of life by reducing weight, changing smoking habits and increasing physical activity, thus proving the effectiveness of information and advice received in a screening investigation. In about 40% of the overweight subjects a reduction in weight and in half of the hypertensives a lowering of blood pressure to values below 160/95 mmHg was noted.

Adult↗

PubMed1979

Determination of the caloric requirement of patients with cancer.

The weight change of 16 adult patients with cancer receiving total parenteral nutrition for an average period of 12 days was evaluated. The nitrogen to calorie ratio of the hyperalimentation fluid ranged from 1:144 to 1:235. The amount of nonprotein calories delivered was expressed as a multiple of the resting metabolic expenditure, and patients were divided according to the following different rates of calories delivered/resting metabolic expenditure into three groups: group 1, 1.11 to 1.48, mean 1.33; group 2, 1.55 to 1.76, mean 1.67, and group 3, 1.78 to 2.10, mean 1.87. The weight change in group 2 patients, +0.32 kilograms per day, was statistically different from that of group 1 patients, p less than 0.01, but not from that of group 3 patients. We conclude that the optimal hyperalimentation infusion rate to achieve weight gain in patients with cancer includes 50 nonprotein calories per kilogram per day as well as 1.5 grams of amino acids per kilogram per day with a nitrogen to calorie ratio of 1:208.

Adenocarcinoma↗

PubMed1976

[A study of toxic substances in pertussis cultures].

For the purpose of studying the toxic properties of pertussis strains with different agglutination composition and to ascertain the interrelationship between the action of the toxic substances and the serological type of the strains the author used a test of the weight change in albino mice to which crude and heated (at 56 degrees C for 10 minutes) suspensions of the strains of various serological types were injected intraperitoneally. The toxic properties were checked in 17 strains. The test of the change of the animal body weight with the determination of the regression coefficient permitted to determine roughly the presence of the toxic substances in the strains; the action of the thermostable dermonecrotic toxin and thermostable endotoxin was expressed with greater constancy than that of the lymphocytosis stimulating factor. There was no interrelationship between the manifestation of the action of toxic substances in the pertussis strains and their serological type. The toxic activity peristed in the strains stored in dried condition.

Agglutination Tests↗

PubMed1977

[Relations between weight changes and various biological parameters. Results of a longitudinal epidemiological survey].

Weight changes over a three year period were measured on a group of about 1400 working men aged 46 to 52 years and related to several biological parameters (cholesterolemia, triglyceridemia, uricemia, glycemia and blood pressure). We observed: a) a slight increase in mean weight over the three year period; b) significant correlations between weight change and changes in these biological parameters. These results are compared to those found in cross sectional studies. Their implications for public health and prevention of ischemic heart disease are discussed.

Blood Glucose↗

PubMed1978

Some effects of uninfected laboratory-reared tsetses (Glossina morsitans morsitans westw.) (diptera: glossinidae) on host-rabbits.

Rabbits (Flemish giant x French lop-eared) exposed to 300 to 500 tsetses (Glossina morsitans morsitans Westw.) a day, 2 or 3 days a week, did not show significant differences from littermates receiving no exposure, with respect to weight changes, haematocrits, red and white blood cell counts or whole blood clotting times. In other rabbits, the same daily exposure, 6 days a week, resulted in sharp decreases in haematocrit levels and in some, changes in weights, but no change in citrated plasma thrombin times. Rabbit haematocrit levels correlated negatively with estimated weekly blood loss. Weights and haematocrits of most rabbits exposed to 1,200 to 1,500 flies on a single occasion were not affected. However, following heavy exposure, ears were cold and blood letting difficult, indicating the possibility of arteriolar vasoconstriction.

Animals↗

PubMed1979

Effects of social and environmental change on institutionalized mentally retarded persons: the relocation syndrome reconsidered.

The "relocation syndrome" in multiply-handicapped, institutionalized mentally retarded residents was examined in an observational study. Weight change and the initiation and duration of constructive and nonconstructive behavior was observed, as well as resident-staff interactions before and after relocation to a new living unit. The hypothesis that there would be an increase in behavior deleterious to the health of clients after relocation, when compared to two premove baseline periods of crowding, was not totally supported. Although relocation did cause significant changes in a variety of behaviors, not all were deleterious (i.e., no mortalities, weight gains). Results were discussed in terms of a social-situational model.

Adolescent↗

PubMed1979

Ingestive behavior and composition of weight change during cyproheptadine administration.

The effect of cyproheptadine on spontaneous energy intake was studied by means of an automated (liquid diet) food-dispensing apparatus in two nonobese adults confined to a metabolic ward. The experimental design included both single and double-blind periods. Throughout, the composition of daily weight change was determined by the energy-nitrogen balance method. While on cyproheptadine, both subjects exhibited increases in energy intake with the following average composition of weight gain: protein 16%, fat 14% and water 70% (first subject), and protein 5%, fat 49% and water 46% (second subject). The cyproheptadine-induced increase in energy intake was statistically significant in one of the subjects, who was at his desirable weight level at the outset. The other subject was underweight initially and tended to gain throughout the experiment, although rate of weight gain appeared to be more rapid during the periods of cyproheptadine administration. Energy output in both subjects remained fairly constant throughout. We conclude that cyproheptadine induces weight gain of 'normal' composition by stimulating increased energy intake.

Adult↗

PubMed1979

Plasma corticosterone level of rats after bilateral lesion of the globus pallidus and elimination of the sex-dependence of the body weight loss following pallidal lesion by bilateral adrenalectomy.

Plasma corticosterone (CST) level and body weight were studied in male and female rats after bilateral pallidal lesion (GPL). The effect of high dose of glycocorticoids on body weight of food and water deprived, non-lesioned rats was also studied since high CST levels due to the stress caused by the aphagia and adipsia could be anticipated. Weight changes in lesioned-adrenalectomized animals were in investigated as well. A weight loss, higher in males than females, developed after the pallidal lesion and the CST level was higher in lesioned females than in lesioned males. This sex-difference was present in non-lesioned, food and water deprived animals as well. The weight loss was higher in lesioned males than in food and water deprived male/female controls. Adrenalectomy eliminated weight loss differences between the sexes after lesion, by reducing the weight loss in males. CST administration reduced body weight loss in food and water deprived males but not in familes, and cortisol facilitated it in both sexes.

Adrenal Cortex↗

PubMed1977

The perinatal rat: body weight, hematocrit and regional changes in heart weight and lactate dehydrogenase isozyme composition and activity.

Body weight (BW), hematocrit (Hct), heart weight (HW) and cardiac lactate dehydrogenase (LDH) activity and isozyme pattern were studied in the perinatal rat. BW increased linearly, from 5 days before birth till 10 days after birth, while Hct increased from 30 to 34% within 1 day of birth. HW increased in step with BW. However, the relative contribution to total HW of right ventricle (RV), interventricular septum (S) and atria declined relative to the left ventricle free wall (LVW) beginning 2 to 3 days before birth. RV/LVW declined steadily throughout the study period. LDH specific activity in LVW, RV, S and atria increased greatly prior to birth and less so afterwards, with atria showing the lowest values throughout the study. Total LDH activity in each portion of the heart paralleled the respective regional weight changes. LDH isozyme composition (percent M subunit) declined at the time of birth in LVW, RV and S from 63 to 43%; change in atrial M subunit was smaller. The change in LDH isozyme composition could be accounted for in LVW, RV and S by increasing H subunit activity alone. In atria, both M and H subunit activity increased.

Animals↗