Contents
Scroll to:
Drug‑induced weight gain: pathophysiological mechanisms, clinically relevant drug classes, and management strategies
https://doi.org/10.37489/2949-1924-0139
EDN: KNVGYW
Abstract
Background. Drug-induced weight gain (DIWG) is a common and often overlooked adverse effect of many widely prescribed medications, representing a significant interdisciplinary challenge. Despite its high prevalence, DIWG remains underrecognized in clinical practice, contributing to poor treatment adherence, worsening of cardiometabolic risk factors, and diminished quality of life.
Objective. This review provides a comprehensive analysis of the pathophysiological mechanisms underlying medication-associated weight gain, including modulation of central neurotransmitter systems (serotonin, histamine, dopamine), endocrine alterations (hyperinsulinemia, leptin resistance), changes in energy expenditure, as well as the emerging roles of gut microbiota and genetic susceptibility.
Key drug classes. The article details the major drug classes implicated in weight gain: antipsychotics (particularly atypical agents), antidepressants, antihypertensives, corticosteroids, and antihyperglycemic drugs (insulin, sulfonylureas). For each class, the magnitude of weight change, underlying mechanisms, and metabolic consequences are discussed.
Management strategies. Current approaches to the prevention and treatment of DIWG are presented, emphasizing the selection of medications with a favorable metabolic profile (e. g., metformin, topiramate, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors), the use of adjunctive therapies, and non-pharmacological interventions. The importance of early screening (body mass index, waist circumference, glucose, lipids) and a multidisciplinary approach involving psychiatrists, endocrinologists, and cardiologists is underscored.
Conclusion. A personalized strategy that balances therapeutic efficacy with metabolic safety is essential to minimize iatrogenic risks and improve long-term patient outcomes.
Keywords
drug-induced obesity,
iatrogenic obesity,
antipsychotics,
corticosteroids,
metabolic disorders,
metformin,
topiramate,
GLP-1 agonists,
SGLT2 inhibitors,
adverse drug reaction
For citations:
Pleshchevа T.N., Savgacheva M.Yu., Karakchiev D.A. Drug‑induced weight gain: pathophysiological mechanisms, clinically relevant drug classes, and management strategies. Patient-Oriented Medicine and Pharmacy. 2026;4(2):35-45. (In Russ.) https://doi.org/10.37489/2949-1924-0139. EDN: KNVGYW
Introduction
In recent decades, obesity has assumed the character of a non‑communicable pandemic. According to the World Health Organization, in 2016, more than 1.9 billion adults were overweight, of whom over 650 million had obesity [1]. In the Russian Federation, the proportion of individuals with overweight was 62.0%, and with obesity — 26.2% [1]. Projections indicate that by 2030, up to 60% of the world’s population may be overweight or obese if current trends continue [1]. The prevalence of obesity among men in Russia reaches 30%, and among women — 39.5%, with abdominal obesity registered in 30.9% of men and 55.1% of women [2].
Alongside well‑known factors (physical inactivity, hypercaloric nutrition, genetic predisposition), iatrogenic factors contribute substantially to the increasing prevalence of overweight. According to meta‑analyses, up to 20–25% of newly diagnosed obesity cases in adults may be associated with the use of medications prescribed for chronic diseases [3, 4]. In the United States, about 50% of adults take at least one medication over a 30‑day period, and many of these have the potential to induce weight gain [5].
Drug‑induced weight gain (DIWG) is often regarded as a "silent" adverse effect that is either underestimated by clinicians or accepted as a trade‑off for controlling the primary disease (e.g., managing psychotic symptoms or achieving target glucose levels). However, weight gain during pharmacotherapy leads to poor adherence, increased risk of cardiovascular complications, progression of hepatic steatosis, and reduced quality of life [5]. In the clinical guidelines of the Ministry of Health of the Russian Federation (2024), iatrogenic obesity is classified as a distinct category (ICD‑10 code E66.1) [1], underscoring the relevance of this issue.
Pathophysiological mechanisms
The mechanisms of DIWG are complex and multifactorial. The key pathogenetic links include [6, 7]:
1. Central effects. Many drugs act on hypothalamic centers regulating hunger and satiety.
Serotonin (5-HT2C) and histamine (H1) receptor antagonism: leads to increased appetite and reduced satiety. This is the primary mechanism for atypical antipsychotics [8]. It has been established that differences in H1 receptor affinity largely explain the variability in weight gain within the antipsychotic class: clozapine and olanzapine exhibit the highest H1 affinity, whereas aripiprazole and ziprasidone show minimal affinity [9].
Modulation of the dopaminergic system: changes in dopamine tone in the mesolimbic pathway may influence hedonic evaluation of food, promoting craving for high‑calorie foods.
Effects on neuropeptides: some drugs alter the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus, directly regulating appetite and energy homeostasis [10].
2. Endocrine disturbances.
Hyperinsulinemia and insulin resistance: many drugs (glucocorticoids, insulin, secretagogues) directly stimulate lipogenesis and suppress lipolysis, and also promote pancreatic insulin secretion, creating an anabolic milieu. Glucocorticoids induce insulin resistance by stimulating 11β‑hydroxysteroid dehydrogenase type 1 (11β‑HSD‑1) in the liver and adipose tissue, increasing local active cortisol concentrations [11, 12].
Leptin resistance: chronic inflammation induced by some agents (e.g., antipsychotics) impairs leptin signaling, creating a vicious cycle of hyperphagia [13]. In patients receiving valproates, elevated leptin levels without adequate appetite suppression have been described [14].
3. Alterations in energy balance.
Reduced basal metabolic rate: β‑adrenergic blockers lower basal metabolic rate by 12% compared with other antihypertensives and reduce the thermogenic response to food by 25% [15, 16].
Suppression of brown adipose tissue thermogenesis: experimental studies have shown that antipsychotics (olanzapine, risperidone) inhibit brown adipocyte differentiation, reducing energy expenditure [17].
Peripheral insulin resistance and fat redistribution: glucocorticoids and protease inhibitors promote preferential visceral fat accumulation, associated with higher cardiometabolic risk [18].
4. Role of microbiota and genetic predisposition.
In recent years, it has been established that antipsychotics (risperidone) alter the gut microbiota composition, reducing diversity and increasing the Firmicutes / Bacteroidetes ratio, which may contribute to weight gain by enhancing energy extraction from food [19, 20].
Genetic polymorphisms play an important role in the variability of weight gain. Associations have been shown between polymorphisms in the genes for the melanocortin‑4 receptor (MC4R), serotonin 2C receptor (HTR2C), leptin receptor, and neuropeptide Y (11Β‑HSD‑1) and the severity of antipsychotic‑induced metabolic adverse effects [21, 22].
5. Impact on eating behavior and thirst.
Many psychotropic drugs cause dry mouth (anticholinergic effect), which may lead to increased consumption of sugar‑sweetened beverages high in fructose, contributing to visceral obesity and insulin resistance [23].
Changes in taste preferences toward more fatty and sweet foods ("food craving") have also been described during antipsychotic and antidepressant therapy [24].
The main classes of drugs that induce weight gain
Antipsychotics. The most extensively studied group is atypical antipsychotics (second‑generation). The risk of weight gain varies by agent: highest for clozapine and olanzapine (gain of 4–10 kg over the first 6–12 months, with 80% of patients gaining more than 20% of baseline weight) [8, 25]; moderate for risperidone and quetiapine (gain of 2–4 kg) [26]; minimal for aripiprazole, ziprasidone, amisulpride, asenapine, iloperidone, lurasidone, and paliperidone, which are associated with the lowest metabolic risk [27, 28].
Pathogenesis: potent H1 and 5‑HT2C receptor antagonism, along with effects on AMP‑activated protein kinase in adipocytes. Notably, in antipsychotic‑naïve patients, weight gain may be more pronounced, especially in children and adolescents [29]. Weight gain during the first month of treatment is a strong predictor of long‑term weight gain, enabling timely intervention [30].
Furthermore, antipsychotics are associated with the development of type 2 diabetes mellitus (T2DM) and metabolic syndrome even without significant weight gain, indicating direct effects on pancreatic β‑cells and peripheral insulin sensitivity [31, 32]. The prevalence of metabolic syndrome in patients with schizophrenia reaches 32%, and the risk of T2DM is 2–3 times higher than in the general population [33].
Antidepressants and mood stabilizers. Tricyclic antidepressants (amitriptyline, nortriptyline) and monoamine oxidase inhibitors are associated with significant weight gain — on average 2–4 kg, and in some patients up to 9 kg [34, 35]. Among selective serotonin reuptake inhibitors (SSRIs), paroxetine is the most unfavorable (gain of 1.7–3.6 kg); citalopram is also associated with weight gain, while fluoxetine and sertraline are relatively neutral in the long term [36, 37]. Bupropion, conversely, consistently demonstrates weight loss (0.4–2.4 kg) and may be considered a metabolically favorable alternative, particularly in patients with obesity [38, 39]. In combination with naltrexone, bupropion is registered as an anti‑obesity medication [40].
Lithium and valproic acid also promote weight gain. In 60% of patients on lithium, a weight gain of more than 5% of baseline is observed [41]. Valproate is characterized by the development of insulin resistance and hyperinsulinemia, related to direct action on pancreatic β‑cells (GABA‑mediated enhancement of insulin secretion), increased leptin levels, and decreased adiponectin [14, 42]. Non‑alcoholic fatty liver disease develops in 60% of patients receiving valproate [43].
Antihyperglycemic agents. Paradoxically, drugs designed to control diabetes often exacerbate obesity. Insulin causes dose‑dependent weight gain via several mechanisms: appetite stimulation, especially during hypoglycemic episodes, reduced glucosuria, and anabolic action (increasing muscle and fat mass) [44, 45]. Weight gain with insulin may range from 0.4 to 4.8 kg, and is more pronounced with rapid‑acting insulins compared with basal insulins [46]. Insulin detemir has a relative weight‑reducing effect, the mechanism of which is not fully understood [47].
Sulfonylureas (glibenclamide, glimepiride) also cause hyperinsulinemia and weight gain: in the UKPDS and ADOPT trials, the gain was approximately 4 kg in the first year of treatment [48, 49]. Gliclazide and glimepiride are associated with less weight gain than older sulfonylureas [50].
Thiazolidinediones (pioglitazone, rosiglitazone) increase subcutaneous fat mass due to preadipocyte differentiation, but may reduce visceral fat content and improve hepatic steatosis [51, 52]. Weight gain is 1.5–4 kg in the first year.
In contrast to these classes, metformin is associated with weight loss (1–2.9 kg) [3, 53]. Dipeptidyl peptidase‑4 (DPP‑4) inhibitors (sitagliptin, saxagliptin, linagliptin) are neutral or associated with slight weight loss [54]. GLP‑1 receptor agonists (exenatide, liraglutide, semaglutide) and SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) provide sustained weight loss, making them preferred in patients with obesity and T2DM [3, 55, 56].
Glucocorticoids. Systemic (and, to a lesser extent, inhaled) glucocorticoid use leads to iatrogenic Cushing’s syndrome. According to population‑based studies, 70% of patients on long‑term glucocorticoid therapy experience significant weight gain, and 20% gain more than 10 kg in the first year of treatment [57, 58]. Prednisolone is associated with a gain of 1.7–5.8 kg, prednisone — 1.5–4.4 kg, cortisone — 1.5–8.4 kg [59, 60].
The mechanism includes appetite stimulation through altered AMP‑activated protein kinase activity in the hypothalamus, increased preference for fatty foods, activation of the endocannabinoid system in the liver and adipose tissue (via cannabinoid receptor type 1), and induction of insulin resistance [11, 61, 62]. Notably, even low doses of prednisone (5–10 mg/day) can cause significant metabolic disturbances [63].
Antihypertensive agents. β‑blockers (especially non‑selective ones such as propranolol and atenolol) reduce basal metabolic rate (by 4–9%), decrease exercise tolerance, and suppress lipolysis, leading to an average weight gain of 1–2 kg [15, 64, 65]. In the GEMINI trial, patients on metoprolol gained 0.6 kg over 6 months, whereas weight did not change with carvedilol [66]. Selective β‑blockers with vasodilating properties (carvedilol, nebivolol) have a more favorable metabolic profile and do not worsen insulin sensitivity [67].
Diuretics (hydrochlorothiazide, chlorthalidone) and calcium channel blockers (amlodipine) are considered neutral or associated with slight weight loss (0.4–2.7 kg) [68, 69]. Angiotensin‑converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) do not affect weight or promote modest weight loss, while improving insulin sensitivity [70, 71]. Direct renin inhibitors (aliskiren) are also metabolically neutral [72].
Antiepileptic drugs and other groups. DIWG is also predisposed by antiepileptic drugs. Valproate causes weight gain in 71% of patients, carbamazepine in 43%, and gabapentin and pregabalin also contribute to weight gain, especially with long‑term use [73, 74]. Valproate is associated with the development of insulin resistance independent of the degree of weight gain and with a high risk of non‑alcoholic fatty liver disease [14, 43]. Topiramate and zonisamide, in contrast, are associated with weight loss, which is used in combination therapy for obesity (phentermine/topiramate) [75, 76].
Among other groups: first‑generation antihistamines (diphenhydramine, hydroxyzine) may cause weight gain via H1 receptor blockade; protease inhibitors (antiretroviral therapy) induce lipodystrophy and visceral obesity [77].
Clinical significance and patient management strategies
A major problem is that clinicians often delay intervention until the patient's body mass index reaches critical values (class II–III obesity). According to Russian clinical guidelines, the diagnosis of obesity (code E66) should be based on measurement of body mass index (BMI) and waist circumference (WC) [1]. Abdominal obesity (WC ≥94 cm in men and ≥80 cm in women) is an independent risk factor for cardiovascular disease and requires active intervention [1, 2]. In the Russian population, the combination of obesity with hypertension and carbohydrate metabolism disorders significantly worsens prognosis [2].
The weight management strategy in the context of DIWG should include three stages:
1. Prevention (primary and secondary)
Screening: assessment of BMI, waist circumference, and metabolic parameters (glucose, lipid profile) before therapy initiation and at 1, 3, and 6 months. The ADA/APA consensus (2004) recommends monitoring weight and metabolic parameters in all patients receiving antipsychotics [78]. Russian clinical guidelines also emphasize the need for evaluation to exclude endocrine causes of obesity (measurement of thyroid‑stimulating hormone, cortisol, prolactin) [1].
Drug selection: when efficacy is equal, preference is given to agents with the lowest metabolic risk [5, 79].
Antipsychotics: aripiprazole, ziprasidone, lurasidone [27, 28].
Antidepressants: bupropion, fluoxetine, sertraline [37, 39].
Antihypertensives: ACE inhibitors, ARBs, calcium channel blockers [70, 71].
Antihyperglycemics: metformin, DPP‑4 inhibitors, GLP‑1 receptor agonists, SGLT2 inhibitors [3, 55].
Antiepileptics: topiramate, zonisamide (instead of valproate in obesity) [75].
2. Therapy modification. When significant weight gain occurs (more than 5–7% from baseline), pharmacotherapy revision is appropriate [78, 80]:
Switching within the class. For example, switching from olanzapine to aripiprazole or from citalopram to sertraline [36, 81].
Adjunctive therapy:
Metformin (500–2000 mg/day) — the most studied agent for preventing and treating antipsychotic‑induced weight gain; meta‑analyses show weight reduction of 2–3 kg and improved metabolic parameters [82, 83].
Topiramate (50–200 mg/day) — effective in valproate‑induced obesity and in combination with antipsychotics [75, 84].
GLP‑1 receptor agonists (liraglutide 3.0 mg/day, semaglutide 2.4 mg/week) — have shown high efficacy in reducing body weight, including antipsychotic‑induced weight gain, with improved glycemic control and reduced cardiovascular risk [85, 86, 87]. In a randomized clinical trial in patients with schizophrenia receiving clozapine or olanzapine, the addition of liraglutide resulted in a weight loss of 5.3 kg compared with placebo [88].
Orlistat (120 mg three times daily) — an intestinal lipase inhibitor that reduces fat absorption by 30%, but its use is limited by gastrointestinal side effects [89].
Promising directions: PKC‑β inhibitors (ruboxistaurin), selective peripheral cannabinoid receptor antagonists, 11β‑HSD‑1 inhibitors, which are undergoing preclinical and clinical studies [90, 91].
3. Non‑pharmacological interventions. Lifestyle modification remains a cornerstone; however, the effectiveness of dietary restrictions and physical activity during treatment with centrally acting drugs may be reduced. Structured programs involving dietitians and physiotherapists are needed. According to clinical guidelines, a 5–10% weight loss over 3–6 months reduces health risks and improves the course of comorbid diseases [1]. In patients with BMI ≥35 kg/m² and severe complications (T2DM, obstructive sleep apnea syndrome), bariatric surgery may be considered [1, 92]. In patients with psychotic disorders and obesity, combined programs (diet + physical activity) provide an average weight loss of up to 3.3 kg [93].
Principles of a patient‑centered approach to drug‑induced weight gain
Effective management of drug‑induced weight gain (DIWG) is impossible without implementing patient‑centered principles, which transform the traditional "doctor‑patient" model into a partnership. This approach is based on the following key elements:
Shared decision‑making. The choice of therapeutic strategy, especially when several equally effective options exist, should be based on dialogue. The physician provides evidence‑based information on the risks and benefits of each approach (including metabolic risks), while the patient shares their priorities, fears, and treatment expectations. For example, when choosing an antipsychotic or antidepressant, it is necessary to discuss with the patient how critical potential weight gain is compared to other side effects or the speed of therapeutic response. This promotes realistic expectations and improves treatment adherence.
Consideration of individual values and preferences. It is important to recognize that the subjective significance of body weight varies among patients. For one patient, a gain of 2 kg may be psychologically insignificant in the context of disease control, while for another, it may be a reason for treatment discontinuation. The physician should explore these nuances during the conversation, avoiding judgment. Validated quality‑of‑life questionnaires (e.g., SF‑36 or specific scales for assessing the impact of weight on well‑being) and eating behavior scales can be used to objectively evaluate the impact of DIWG on the patient's life.
Patient education and information. The patient must understand why weight gain may occur during therapy, what mechanisms are involved, and what can be done to minimize this effect. Simple, non‑alarming information, with an emphasis on the possibility of control, significantly reduces anxiety and increases willingness to cooperate. Explaining that DIWG is not the patient's "fault" but an objective pharmacological effect is an important psychotherapeutic point and the basis for constructive dialogue.
Realistic planning and monitoring. Non‑pharmacological correction strategies (diet, physical activity) must be tailored to the patient's lifestyle and capabilities. Unattainable goals lead to disappointment and loss of motivation. Regular monitoring should be perceived by the patient not as control, but as a joint review of progress, allowing timely adjustments to the action plan.
Integrating these principles into clinical practice not only enables more effective weight management but also strengthens the therapeutic alliance, which is critically important for the treatment of chronic diseases.
Conclusion
Drug‑induced weight gain is an inevitable consequence of therapy for many chronic diseases and requires a systematic approach. Ignoring this adverse effect negates the long‑term benefits of treatment, contributing to the cardiometabolic continuum. Personalized drug selection considering metabolic profile, early monitoring (BMI, waist circumference, glucose, lipids), and multidisciplinary collaboration (psychiatrist, endocrinologist, cardiologist) are the foundations for minimizing iatrogenic risks and improving patient adherence to therapy. The introduction into clinical practice of modern metabolically neutral and weight‑reducing drugs (GLP‑1 receptor agonists, SGLT2 inhibitors, metformin) opens new possibilities for weight management in patients who must take medications with weight‑gain potential.
References
1. Dedov I.I., Mokrysheva N.G., Melnichenko G.A., et al. Clinical recommendations «Gestational diabetes mellitus» of the Russian Ministry of Health. Version of the year 2024. Bulletin of Reproductive Health. 2025;4(2):14-30. (In Russ.)].
2. Balanova Yu.A., Shalnova S.A., Imaeva A.E., et al. Obesity in the Russian population: contribution to survival and cardiovascular events. Data from ESSE-RF and ESSE-RF2. Cardiovascular Therapy and Prevention. 2025;24(6):4336. (In Russ.)].
3. Domecq JP, Prutsky G, Leppin A, et al. Drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(2):363-370. doi: 10.1210/jc.2014-3421
4. Leslie WS, Hankey CR, Lean MEJ. Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review. QJM. 2007;100(7):395-404. doi: 10.1093/qjmed/hcm044
5. Wharton S, Raiber L, Serodio KJ, et al. Medications that cause weight gain and alternatives in Canada: a narrative review. Diabetes Metab Syndr Obes. 2018;11:427-438. doi: 10.2147/DMSO.S171365
6. Verhaegen AA, Van Gaal LF. Drug-induced obesity and its metabolic consequences: a review with a focus on mechanisms and possible therapeutic options. J Endocrinol Invest. 2017;40(11):1165-1174. doi: 10.1007/s40618-017-0719-6
7. Himmerich H, Minkwitz J, Kirkby KC. Weight gain and metabolic changes during treatment with antipsychotics and antidepressants. Endocr Metab Immune Disord Drug Targets. 2015;15(4):252-260. doi: 10.2174/1871530315666150623092031
8. Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156(11):1686-1696. doi: 10.1176/ajp.156.11.1686
9. Allison DB, Casey DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psy-chiatry. 2001;62(Suppl 7):22-31. PMID: 11346194
10. Zimmermann U, Kraus T, Himmerich H, et al. Epidemiology, implications and mechanisms underlying drug induced weight gain in psychiatric patients. J Psychiatr Res. 2003;37(3):193-220. doi: 10.1016/s0022-3956(03)00007-4
11. Bowles NP, Karatsoreos IN, Li X, et al. A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome. Proc Natl Acad Sci USA. 2015;112(1):285-290. doi: 10.1073/pnas.1421420112
12. Dube S, Slama MQ, Basu A, et al. Glucocorticoid excess increases hepatic 11β-HSD-1 activity in humans: implications in steroid-induced diabetes. J Clin Endocrinol Metab. 2015;100(11):4155-4162. doi: 10.1210/jc.2015-2607
13. Capuron L, Lasselin J, Castanon N. Role of adiposity-driven inflammation in depressive morbidity. Neuropsychopharmacology. 2017;42(1):115-128. doi: 10.1038/npp.2016.123
14. Verrotti A, D'Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev. 2011;12(5):e32-e43. doi: 10.1111/j.1467-789X.2010.00802.x
15. Sharma AM, Pischon T, Hardt S, et al. β-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension. 2001;37(2):250-254. doi: 10.1161/01.hyp.37.2.250
16. Welle S, Schwartz RG, Statt M. Reduced metabolic rate during beta-adrenergic blockade in humans. Metabolism. 1991;40(6):619-622. doi: 10.1016/0026-0495(91)90053-3
17. Oh JE, Cho YM, Kwak SN, et al. Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics. Exp Mol Med. 2012;44(9):545-553. doi: 10.3858/emm.2012.44.9.062
18. Medici V, McClave SA, Miller KR. Common medications which lead to unintended alterations in weight gain or organ lipotoxicity. Curr Gastroenter-ol Rep. 2016;18(1):2-12. doi: 10.1007/s11894-015-0482-0
19. Bahra SM, Weidemann BJ, Castro AN, et al. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure. EBioMedicine. 2015;2(11):1725-1734. doi: 10.1016/j.ebiom.2015.10.018
20. Flowers SA, Evans SJ, Ward KM, et al. Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort. Pharmacotherapy. 2017;37(3):261-267. doi: 10.1002/phar.1890
21. Shams TA, Müller DJ. Antipsychotic induced weight gain: genetics, epigenetics, and biomarkers re-viewed. Curr Psychiatry Rep. 2014;16(10):473. doi: 10.1007/s11920-014-0473-9
22. Lett TA, Wallace TJ, Chowdhury NI, et al. Pharma-cogenetics of antipsychotic-induced weight gain: review and clinical implications. Mol Psychiatry. 2012;17(3):242-266. doi: 10.1038/mp.2011.109
23. Stanhope KL, Havel PJ. Fructose consumption: recent results and their potential implications. Ann N Y Acad Sci. 2010;1190:15-24. doi: 10.1111/j.1749-6632.2009.05266.x
24. Bernstein JG. Induction of obesity by psychotropic drugs. Ann N Y Acad Sci. 1987;499:203-215. doi: 10.1111/j.1749-6632.1987.tb36212.x
25. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382(9896):951-962. doi: 10.1016/S0140-6736(13)60733-3
26. Brecher M, Leong RW, Stening G, et al. Quetiapine and long-term weight change: a comprehensive data review of patients with schizophrenia. J Clin Psychiatry. 2007;68(4):597-603. doi: 10.4088/jcp.v68n0415
27. de Hert M, Yu W, Detraux J, et al. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012;26(9):733-759. doi: 10.2165/11634520-000000000-00000
28. Orsolini L, Tomasetti C, Valchera A, et al. An update of safety of clinically used atypical antipsychotics. Expert Opin Drug Saf. 2016;15(10):1329-1347. doi: 10.1080/14740338.2016.1201475
29. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302(16):1765-1773. doi: 10.1001/jama.2009.1549
30. Vandenberghe F, Gholam-Rezaee M, Saigí-Morgui N, et al. Importance of early weight changes to predict long-term weight gain during psychotropic drug treatment. J Clin Psychiatry. 2015;76(11):e1417-e1423. doi: 10.4088/JCP.14m09358
31. Ballon JS, Pajvani U, Freyberg Z, et al. Molecular pathophysiology of metabolic effects of antipsychotic medications. Trends Endocrinol Metab. 2014;25(11):593-600. doi: 10.1016/j.tem.2014.07.001
32. Holt RI, Peveler RC. Association between antipsychotic drugs and diabetes. Diabetes Obes Metab. 2006;8(2):125-135. doi: 10.1111/j.1463-1326.2005.00511.x
33. Mitchell AJ, Vancampfort D, Sweers K, et al. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis. Schizophr Bull. 2013;39(2):306-318. doi: 10.1093/schbul/sbr148
34. Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71(10):1259-1272. doi: 10.4088/JCP.09r05346blu
35. Cantú TG, Korek JS. Monoamine oxidase inhibitors and weight gain. Drug Intell Clin Pharm. 1988; 22(10):755-759. doi: 10.1177/106002808802201003
36. Blumenthal SR, Castro VM, Clements CC, et al. An electronic health records study of long-term weight gain following antidepressant use. JAMA Psychiatry. 2014;71(8):889-896. doi: 10.1001/jama-psychiatry.2014.414
37. Maina G, Albert U, Salvi V, Bogetto F. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry. 2004;65(10):1365-1371. doi: 10.4088/jcp.v65n1011
38. Gadde KM, Xiong GL. Bupropion for weight reduction. Expert Rev Neurother. 2007;7(1):17-24. doi: 10.1586/14737175.7.1.17
39. Croft H, Settle E, Houser T, et al. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther. 1999;21(4):643-658. doi: 10.1016/S0149-2918(00)88317-4
40. Billes SK, Sinnayah P, Cowley MA. Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss. Pharmacol Res. 2014;84:1-11. doi: 10.1016/j.phrs.2014.04.004
41. Livingstone C, Rampes H. Lithium: a review of its metabolic adverse effects. J Psychopharmacol. 2006;20(3):347-355. doi: 10.1177/0269881105057515
42. Belcastro V, D'Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res. 2013;107(1-2):1-8. doi: 10.1016/j.eplepsyres.2013.08.016
43. Farinelli E, Giampaoli D, Cenciarini A, et al. Valproic acid and nonalcoholic fatty liver disease: a possible association? World J Hepatol. 2015;7(9):1251-1257. doi: 10.4254/wjh.v7.i9.1251
44. Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes—causes, effects and coping strategies. Diabetes Obes Metab. 2007;9(6):799-812. doi: 10.1111/j.1463-1326.2006.00686.x
45. Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Diabetes Obes Metab. 2011;13(11): 1008-1019. doi: 10.1111/j.1463-1326.2011.01433.x
46. Montañana CF, Herrero CH, Fernández MR. Less weight gain and hypoglycaemia with once-daily insulin detemir than NPH insulin in intensification of insulin therapy in overweight type 2 diabetes patients - the PREDICTIVE™ BMI clinical trial. Diabet Med. 2008;25(8):916-923. doi: 10.1111/j.1464-5491.2008.02478.x
47. Hermansen K, Davies M. Does insulin detemir have a role in reducing risk of insulin-associated weight gain? Diabetes Obes Metab. 2007;9(3):209-217. doi: 10.1111/j.1463-1326.2006.00608.x
48. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.
49. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427-2443. doi: 10.1056/NEJMoa066224
50. Tan MH, Baksi A, Krahulec B, et al. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care. 2005;28(3):544-550. doi: 10.2337/diacare.28.3.544
51. Wilding J. Thiazolidinediones, insulin resistance and obesity: finding a balance. Int J Clin Pract. 2006;60(10):1272-1280. doi: 10.1111/j.1742-1241.2006.01077.x
52. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675-1685. doi: 10.1056/NEJMoa0907929
53. Tessier D, Maheux P, Khalil A, Fülöp T. Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Metabolism. 1999;48(7):897-903. doi: 10.1016/s0026-0495(99)90227-9
54. Aroda VR, Henry RR, Han J, et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther. 2012;34(6):1247-1258.e22. doi: 10.1016/j.clinthera.2012.04.013
55. Van Gaal L, Scheen A. Weight management in type 2 diabetes: current and emerging approaches to treatment. Diabetes Care. 2015;38(6):1161-1172. doi: 10.2337/dc14-1630
56. Stenlöf K, Cefalu WT, Kim KA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately con-trolled with diet and exercise. Diabetes Obes Me-tab. 2013;15(4):372-382. doi: 10.1111/dom.12054
57. Curtis JR, Westfall AO, Allison J, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006;55(3):420-426. doi: 10.1002/art.21984
58. Wung PK, Anderson T, Fontaine KR, et al. Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis. Arthritis Rheum. 2008;59(5):746-753. doi: 10.1002/art.23561
59. Dessein PH, Joffe BI, Stanwix AE, et al. Glucocorticoids and insulin sensitivity in rheumatoid arthritis. J Rheumatol. 2004;31(5):867-874.
60. Sheehan HL, Summers VK. Oral cortisone treatment of hypopituitarism. Br Med J. 1954;1(4864):723-726. doi: 10.1136/bmj.1.4864.723
61. Christ-Crain M, Kola B, Lolli F, et al. AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. FASEB J. 2008;22(6):1672-1683. doi: 10.1096/fj.07-094144
62. Berthon BS, Macdonald-Wicks LK, Wood LG. A systematic review of the effect of oral glucocorticoids on energy intake, appetite, and body weight in humans. Nutr Res. 2014;34(3):179-190. doi: 10.1016/j.nutres.2013.12.006
63. Petersons CJ, Mangelsdorf BL, Jenkins AB, et al. Effects of low-dose prednisolone on hepatic and peripheral insulin sensitivity, insulin secretion, and abdominal adiposity in patients with inflammatory rheumatologic disease. Diabetes Care. 2013;36(9): 2822-2829. doi: 10.2337/dc12-2527
64. Messerli FH, Bell DS, Fonseca V, et al. Body weight changes with beta-blocker use: results from GEMINI. Am J Med. 2007;120(7):610-615. doi: 10.1016/j.amjmed.2006.10.017
65. Astrup A, Simonsen L, Bülow J, et al. Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle. Am J Physiol. 1989;257(3 Pt 1):E340-E345. doi: 10.1152/ajpendo.1989.257.3.E340
66. Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292(18):2227-2236. doi: 10.1001/jama.292.18.2227
67. Ripley TL, Saseen JJ. β-blockers: a review of their pharmacological and physiological diversity in hypertension. Ann Pharmacother. 2014;48(6):723-733. doi: 10.1177/1060028013514942
68. Reisin E, Weir MR, Falkner B, et al. Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Hypertension. 1997;30(1):140-145. doi: 10.1161/01.hyp.30.1.140
69. Finnerty FA, Maxwell MH, Lunn J, Moser M. Long-term effects of furosemide and hydrochlorothiazide in patients with essential hypertension: a two-year comparison of efficacy and safety. Angiology. 1977; 28(2):125-133. doi: 10.1177/000331977702800210
70. Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369(9557):201-207. doi: 10.1016/S0140-6736(07)60108-1
71. Yusuf S, Gerstein H, Hoogwerf B, et al. Ramipril and the development of diabetes. JAMA. 2001; 286(15):1882-1885. doi: 10.1001/jama.286.15.1882
72. Jordan J, Engeli S, Boye SW, et al. Direct renin inhibition with aliskiren in obese patients with arterial hypertension. Hypertension. 2007;49(5):1047-1055. doi: 10.1161/HYPERTENSIONAHA.106.084962
73. Ben-Menachem E. Weight issues for people with epilepsy—a review. Epilepsia. 2007;48(Suppl 9):42-45. doi: 10.1111/j.1528-1167.2007.01400.x
74. Pickrell WO, Lacey AS, Thomas RH, et al. Weight change associated with antiepileptic drugs. J Neurol Neurosurg Psychiatry. 2013;84(7):796-799. doi: 10.1136/jnnp-2012-303353
75. Antel J, Hebebrand J. Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide. Handb Exp Pharmacol. 2012;209:433-466. doi: 10.1007/978-3-642-24716-3_20
76. Smith SM, Meyer M, Trinkley KE. Phentermine/ topiramate for the treatment of obesity. Ann Pharmacother. 2013;47(3):340-349. doi: 10.1345/aph.1R501
77. Elster EA, Leeser DB, Morrisette C, et al. Obesity following kidney transplantation and steroid avoidance immunosuppression. Clin Transplant. 2008;22(3):354-359. doi: 10.1111/j.1399-0012.2008.00798.x
78. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. doi: 10.2337/diacare.27.2.596
79. Newcomer JW, Weiden PJ, Buchanan RW. Switching antipsychotic medications to reduce adverse event burden in schizophrenia: establishing evidence-based practice. J Clin Psychiatry. 2013;74(11):1108-1120. doi: 10.4088/JCP.12002co1c
80. Hasnain M, Vieweg WV. Weight considerations in psychotropic drug prescribing and switching. Postgrad Med. 2013;125(5):117-129. doi: 10.3810/pgm.2013.09.2706
81. Mukundan A, Faulkner G, Cohn T, Remington G. Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems. Cochrane Database Syst Rev. 2010;(12):CD006629. doi: 10.1002/14651858.CD006629.pub2
82. Zheng W, Li XB, Tang YL, et al. Metformin for weight gain and metabolic abnormalities associated with antipsychotic treatment: meta-analysis of randomized placebo-controlled trials. J Clin Psychopharmacol. 2015;35(5):499-509. doi: 10.1097/JCP.0000000000000382
83. Mizuno Y, Suzuki T, Nakagawa A, et al. Pharma-cological strategies to counteract antipsychotic-in-duced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2014;40(6):1385-1403. doi: 10.1093/schbul/sbu030
84. Gierisch JM, Nieuwssma JA, Bradford DW, et al. Interventions to improve cardiovascular risk factors in people with serious mental illness. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013. Report No.: 13-EHC063-EF.
85. Ebdrup BH, Knop FK, Ishøy PL, et al. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits. BMC Med. 2012;10:92. doi: 10.1186/1741-7015-10-92
86. Lykkegaard K, Larsen PJ, Vrang N, et al. The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance. Schizophr Res. 2008;103(1-3):94-103. doi: 10.1016/j.schres.2008.03.019
87. Sharma AN, Ligade SS, Sharma JN, et al. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats. Metab Brain Dis. 2015;30(2):519-527. doi: 10.1007/s11011-014-9610-y
88. Larsen JR, Vedtofte L, Jakobsen MSL, et al. Effect of liraglutide treatment on prediabetes and overweight or obesity in clozapine- or olanzapine-treated patients with schizophrenia spectrum disorder: a randomized clinical trial. JAMA Psychiatry. 2017;74(7):719-728. doi: 10.1001/jamapsychiatry.2017.1220
89. Drent ML, van der Veen EA. Lipase inhibition: a novel concept in the treatment of obesity. Int J Obes Relat Metab Disord. 1993;17(4):241-244. PMID: 8387979
90. Rimessi A, Pavan C, Ioannidi E, et al. Protein kinase C β: a new target therapy to prevent the longterm atypical antipsychotic-induced weight gain. Neuropsychopharmacology. 2017;42(7):1491-1501. doi: 10.1038/npp.2016.290
91. Gross C, Blasey CM, Roe RL, Belanoff JK. Mifepristone reduces weight gain and improves metabolic abnormalities associated with risperidone treatment in normal men. Obesity (Silver Spring). 2010;18(12):2295-2300. doi: 10.1038/oby.2010.67
92. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362. doi: 10.1210/jc.2014-3415
93. Alvarez-Jiménez M, Hetrick SE, González-Blanch C, et al. Non-pharmacological management of antipsychotic-induced weight gain: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2008;193(2):101-107. doi: 10.1192/bjp.bp.107.042853
About the Authors
T. N. Pleshchevа
Yaroslavl State Medical University
Russian Federation
Competing Interests:
Russian Federation
Tatyana N. Pleshchevа - Senior Lecturer of the Department of General Hygiene with Ecology
Yaroslavl
Competing Interests:
The authors state that there is no conflict of interest.
M. Yu. Savgacheva
Yaroslavl State Medical University
Russian Federation
Competing Interests:
Russian Federation
Maria Yu. Savgacheva - Lecturer at the Department of Public Health and Public Health
Yaroslavl
Competing Interests:
The authors state that there is no conflict of interest.
D. A. Karakchiev
Yaroslavl State Medical University
Russian Federation
Competing Interests:
Russian Federation
Dmitry A. Karakchiev - 4th year student of the Institute of Pediatrics and Reproductive Health
Yaroslavl
Competing Interests:
The authors state that there is no conflict of interest.
Review
For citations:
Pleshchevа T.N., Savgacheva M.Yu., Karakchiev D.A. Drug‑induced weight gain: pathophysiological mechanisms, clinically relevant drug classes, and management strategies. Patient-Oriented Medicine and Pharmacy. 2026;4(2):35-45. (In Russ.) https://doi.org/10.37489/2949-1924-0139. EDN: KNVGYW
Views:
256
JATS XML
.png)
Email this article 