Epidemiology,implications and mechanisms underlying drug-induced weight gain in psychiatric patients

Body weight gain frequently occurs during drug treatment of psychiatric disorders and is often accompanied by increased appetite or food craving. While occurrence and time course of this side effect are difficult to predict, it ultimately results in obesity and the morbidity associated therewith in a substantial part of patients, often causing them to discontinue treatment even if it is effective. This paper reviews the available epidemiological data on the frequency and extent of weight gain associated with antidepressant, mood-stabilizing, and antipsychotic treatment. Possible underlying pathomechanisms are discussed with special attention to central nervous control of appetite including the role of leptin and the tumor necrosis factor system. Metabolic alterations induced by drug treatment such as type 2 diabetes mellitus and the metabolic syndrome are also considered. Weight gain appears to be most prominent in patients treated with some of the second generation antipsychotic drugs and with some mood stabilizers. Marked weight gain also frequently occurs during treatment with most tricyclic antidepressants, while conventional antipsychotics typically induce only slight to moderate weight gain. Serotonin reuptake inhibitors may induce weight loss during the first few weeks, but some of them induce weight gain during long-term treatment. Several antidepressant and antipsychotic drugs are identified which reliably do not cause weight gain or even reduce weight. Based on these insights, countermeasures to manage drug-induced weight gain are suggested.     

Newer antipsychotic drugs and obesity in children and adolescents. How should we assess drug‐associated weight gain?

OBJECTIVE: Antipsychotic drugs may contribute to weight gain in children and adolescents. METHOD: We used Medline's PubMed in the pediatric age using key words 'weight gain' and 'obesity', for each newer antipsychotic drug. RESULTS: We found 21 articles linking weight gain and obesity with newer antipsychotic drugs among youths. Risperidone was the most commonly cited agent. Weight gain from olanzapine was the largest among the more commonly prescribed newer agents. All studies reported absolute weight gain. Only a few studies used the better measure of body mass index (BMI). None incorporated growth charts to allow for changes in weight and height over time because of growth. CONCLUSION: Weight gain may be a major problem when prescribing newer antipsychotic drugs in the pediatric population. Risperidone is associated with less weight gain than olanzapine. Published reports and studies have not utilized state-of-the-art techniques using BMI with readily available growth charts.     

Ghrelin plasma levels during psychopharmacological treatment

The mechanisms underlying weight gain induced by psychopharmacological agents are poorly understood. Because the recently discovered enteric hormone, ghrelin, stimulates food intake, we hypothesized that increases in circulating ghrelin levels might mediate the weight gain caused by certain antidepressants and atypical antipsychotic drugs. Fifty-two patients receiving psychopharmacological treatments were included in the study: 16 patients received antidepressants that are not known to induce weight gain, and 13 patients received mirtazapine or trimipramine, which are antidepressants known to lead to weight gain; 6 patients received clozapine and olanzapine, which have the highest liability among the antipsychotics to cause weight gain, and 17 patients received other antipsychotics. Fasting venous blood samples for the measurement of ghrelin were drawn in the morning between 06:00 and 08:00 a.m. in the second week of treatment. Although psychopharmacological treatment induced significant weight changes in the expected directions (most prominent in the clozapine or olanzapine treatment group), ghrelin levels did not differ significantly between groups. Psychotropic drugs with different propensities to induce body weight gain are associated with similar concentrations of plasma ghrelin in psychiatric patients after a short period of treatment.     

Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review

We performed an updated review of the available literature on weight gain and increase of body mass index (BMI) among children and adolescents treated with antipsychotic medications. A PubMed search was conducted specifying the following MeSH terms: (antipsychotic agents) hedged with (weight gain) or (body mass index). We selected 127 reports, including 71 intervention trials, 42 observational studies and 14 literature reviews. Second-generation antipsychotics (SGAs), in comparison with first-generation antipsychotics, are associated with a greater risk for antipsychotic-induced weight gain although this oversimplification should be clarified by distinguishing across different antipsychotic drugs. Among SGAs, olanzapine appears to cause the most significant weight gain, while ziprasidone seems to cause the least. Antipsychotic-induced BMI increase appears to remain regardless of the specific psychotropic co-treatment. Children and adolescents seem to be at a greater risk than adults for antipsychotic-induced weight gain; and the younger the child, the higher the risk. Genetic or environmental factors related to antipsychotic-induced weight gain among children and adolescents are mostly unknown, although certain genetic factors related to serotonin receptors or hormones such as leptin, adiponectin or melanocortin may be involved. Strategies to reduce this antipsychotic side effect include switching to another antipsychotic drug, lowering the dosage or initiating treatment with metformin or topiramate, as well as non-pharmacological interventions. Future research should avoid some methodological limitations such as not accounting for age- and sex-adjusted BMI (zBMI), small sample size, short period of treatment, great heterogeneity of diagnoses and confounding by indication.     

抗精神病药物对精神分裂症患者血脂、血糖和体重影响的研究

目的比较精神分裂症患者服用抗精神病药物后血脂、血糖及体重的变化,评价不同药物的安全性。方法选择109例单一应用抗精神病药物治疗满8周的精神分裂症患者,分别于第4周、第8周测量血脂(胆固醇、甘油三脂)、血糖和体重。结果服用抗精神病药物后女性、高龄患者甘油三脂增高显著,差异有统计学意义(t=-2.34,P<0.05;r=0.256,P=0.007);氯氮平对胆固醇升高影响显著高于利培酮、奎硫平、氯丙嗪、奋乃静等(P<0.05);氯氮平、氯丙嗪对甘油三脂升高影响显著高于利培酮(P<0·05);所有纳入研究的药物对血糖、体重有不同程度影响,差异无显著性(P>0.05)。结论大多数抗精神病药物可增加高血脂、肥胖的风险,选择药物应考虑性别及年龄因素。     

Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods.

BACKGROUND: We performed a retrospective analysis of data involving 121 inpatients to examine the rate of weight gain during antipsychotic-free periods and during treatment with various antipsychotic drugs. METHOD: Data were analyzed to determine differences in weekly weight change during antipsychotic-free (N = 65), typical antipsychotic (N = 51), or atypical antipsychotic (N = 130) treatment periods. Atypical antipsychotic treatment periods were further subdivided into olanzapine (N = 45), clozapine (N = 47), or risperidone (N = 36) treatment periods. A paired comparison was conducted on 65 patients who had an antipsychotic-free treatment period preceding or following a neuroleptic drug treatment period. In addition, patients were classified as either non-obese (with a body mass index [BMI] < or = 29.9 kg/ml) or obese (BMI > or = 30.0 kg/m2) to test whether the rate of weight gain during treatment periods was related to initial BMI. RESULTS: Across all treatment periods, weekly weight gain was as follows: 0.89 lb/wk (0.40 kg/wk) on atypical antipsychotic medication, 0.61 lb/wk (0.27 kg/wk) on typical antipsychotic medication, and 0.21 lb/wk (0.09 kg/wk) on no antipsychotic medications. The atypical antipsychotic versus antipsychotic-free comparison was significant (F = 3.51; df = 2,231; p = .031), while the typical antipsychotic versus antipsychotic-free comparison was not. Among the individual atypical antipsychotic medications, significantly more weight gain occurred during olanzapine treatment (1.70 lb/wk) (0.76 kg/wk) than with either clozapine (0.50 lb/wk) (0.22 kg/wk) or risperidone (0.34 lb/wk) (0.15 kg/wk) treatments (F = 7.77; df = 2,117; p = .001). In the paired analysis with patients serving as their own controls, the difference between weekly weight gain during atypical antipsychotic treatment and antipsychotic-free treatment was significant (t = -3.91; df = 44; p = .001), while the difference between weight gain during typical antipsychotic treatment and antipsychotic-free treatment was not significant. With the individual drugs. treatment with both olanzapine and clozapine caused significantly higher weekly weight gain than antipsychotic-free treatment (p = .001 and p = .036, respectively). while treatment with risperidone did not. Non-obese patients (BMI < 29.9 kg/m2) and obese patients (BMI > 30.0 kg/m2) did not differ significantly in their weight gain during typical or atypical antipsychotic treatment. CONCLUSION: Treatment with atypical antipsychotics was associated with more weight gain than treatment with typical antipsychotics. Among the atypical drugs, olanzapine was associated with more weight gain than either clozapine or risperidone. The patient's admission BMI was not associated with the amount of weight gained during subsequent antipsychotic treatment.     

Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin

BACKGROUND: Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment. METHODS: A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin. RESULTS: The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and nonweight metabolic changes. Leptin changes were directly related to a medication's weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities. CONCLUSIONS: Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics.     

Long-term topiramate treatment of psychotropic drug-induced weight gain: a retrospective chart review

OBJECTIVE: The objective of this study was to determine the efficacy and tolerability of long-term topiramate treatment of psychotropic drug-induced weight gain. METHOD: We conducted a retrospective review of the charts of patients treated with add-on topiramate in order to control weight gain induced by psychotropic drugs (antipsychotic drugs, lithium or valproate). RESULTS: The case series consisted of 100 patients. The mean final dose of topiramate was 186.8+/-138.3 mg/day, whereas the median dose was 200 mg/day for a total treatment duration of 41+/-38 weeks. Adverse events led to topiramate discontinuation in 22% of the sample. A significant reduction in body mass index was observed between the first and last measures, from 29.7+/-3.6 to 28+/-3.3 (t=5.82, P<.0005). The reduction in body mass index was greater in patients treated with antipsychotic drugs than in those treated with lithium or valproate alone. No difference was found between subjects with and those without comorbid active substance abuse or dependence. CONCLUSIONS: In this retrospective case series, topiramate was found to be effective in reversing weight gain associated with antipsychotic drugs, lithium or valproate. Tolerability of topiramate was an issue in some patients.     

Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone

OBJECTIVE: Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine, risperidone, and haloperidol were sought through retrospective analyses. METHOD: Six-week body-weight data from 2 trials, study 1 comparing olanzapine and haloperidol (N = 1,369) and study 2 olanzapine and risperidone (N = 268), were analyzed. Effects of 8 clinically relevant covariates--therapy, clinical outcome (Brief Psychiatric Rating Scale), baseline body mass index (BBMI), increased appetite, age, gender, race, and dose--on weight were compared. RESULTS: In study 1, olanzapine (vs. haloperidol) therapy, better clinical outcome, lower BBMI, and nonwhite race significantly affected weight gain. Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol. In study 2, better clinical outcome, lower BBMI, and younger age significantly affected weight gain. Increased appetite was more frequent during olanzapine treatment than during haloperidol, but not significantly different from risperidone. Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone. No evidence was found that lower antipsychotic drug doses were associated with lower weight gain. CONCLUSION: This report identifies predictive factors of acute weight change in patients with schizophrenia. Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome, low BBMI, and nonwhite race. Factors differing between conventional (haloperidol) and atypical (olanzapine) agents included increased appetite and gender. Choice of atypical antipsychotic drug (olanzapine vs. risperidone) was of minor importance with regard to influence on acute weight gain.     

Risperidone-associated new-onset diabetes.

BACKGROUND: Weight gain, and its associated complications such as the development of diabetes, is becoming increasingly recognized as an important potential side effect of the novel antipsychotic drugs. METHODS: Two retrospective cases are described in which patients with schizophrenia developed diabetes while taking the antipsychotic medication risperidone. RESULTS: Both patients had preexisting risk factors for diabetes and developed insulin resistance in the context of weight gain. Both cases necessitated medical intervention and one patient requires ongoing treatment with insulin. CONCLUSIONS: Although the exact mechanism of antipsychotic induced diabetes remains obscure, weight gain appears to be a significant risk factor. Careful monitoring of weight and fasting glucoses is recommended for any patient taking novel antipsychotic medications.     

Psychotic disorders, eating habits, and physical activity: who is ready for lifestyle changes?

OBJECTIVES: Significant weight gain is a serious side effect of many antipsychotic medications, yet successful strategies for significant weight loss are lacking. The transtheoretical model for weight management can be used to identify people who are ready to change (contemplation-preparation group) their eating habits and physical activity. This study compared characteristics of patients in Canada who had a psychotic disorder and were ready to make lifestyle changes with characteristics of patients who were not considering lifestyle changes. METHODS: Participants were surveyed to determine their stages of change for eating habits and physical activity, and various characteristics were measured, including body mass index, body image, nutritional intake, and level of physical activity. RESULTS: A total of 101 participants (64 men) (mean+/-SD age 35+/-11 years) were taking antipsychotic medications. Seventy-one percent had schizophrenia spectrum disorders, and 15% had affective psychosis. The prevalence of patients identified as being ready for change was higher than expected: 68% for eating habits and 54% for physical activity. Participants who were ready to change eating habits were also ready to change physical activity habits (p<.04). Stages of change for eating habits were associated with body mass index (p<.004), whereas stages of change for physical activity were associated with self-reported vigorous (p<.001) and moderate (p<.005) physical activity but not mild physical activity. CONCLUSIONS: Clinicians may help patients develop healthier eating and physical activity habits by using the transtheoretical model, because it identifies patients who are ready to change to healthier lifestyle strategies and may help patients with antipsychotic-induced weight gain.     

Interventions for Weight Gain in Adults Treated With Novel Antipsychotics

BACKGROUND: Weight gain is a significant side effect associated with typical and atypical antipsychotic agents. It has the potential to add to the increased morbidity and mortality associated with schizophrenia and schizoaffective disorder. Because the newer antipsychotic medications have proved to be superior to traditional agents in controlling the positive and negative symptoms of schizophrenia, it is additionally critical to address the relationship of these newer agents to weight gain. METHOD: Prior to the availability of novel antipsychotic medication, we looked at a group of 17 residents, of whom 71% had significant weight gain on treatment with traditional antipsychotic medications between 1991 and 1994. This prompted our interest in weight gain, especially after the introduction of novel antipsychotic medications, and our decision to look closely at their diets and help them make changes that would minimize their weight gain. We monitored the effect of a comprehensive primary intervention strategy on controlling obesity in a retrospective study of 32 patients with DSM-IV schizophrenia or schizoaffective disorders. All patients were residents in an adult care facility for formerly homeless persons with serious mental illness. Intervention consisted of complete medical and psychiatric care; switch to a patient-optimal atypical drug; low-calorie, monitored diet; nutritional education; and supportive care. RESULTS: There was no significant change in mean body weight at 12 and 18 months after initiation of intervention. Weight gain was observed in only 30% of study patients after the intervention as opposed to 71% at the start of the study. In general, as the negative symptoms of schizophrenia improved, patients were found to become more receptive to education and to become proactive in their health care. The lack of weight gain was consistently seen with all 3 agents tested-clozapine, olanzapine, and risperidone. CONCLUSION: A patient's diet appears to be a better predictor of weight gain than the choice of novel antipsychotic medication. Clinicians might prescribe nutritional and lifestyle changes alongside medication with weight gain potential.     

Innsiktsorientert terapi med studenter-grupper: Noen klient-sentrerte synspunkter

Breum L. Psykofarmaka og appetitregulation. Psykofarmakologisk inducerede aendringer i appetitregulationen: patogenese og profylakse.

Psychotropic drugs are often associated with alterations in appetite and body weight. During treatment with antidepressants, lithium or neuroleptics, more than 50% of patients show a drug-related increase in appetite and body weight. The weight gain often leads to obesity, but even smaller weight alterations will decrease the patient's compliance to treatment. The mechanism' behind this appetite change is very complex. Down-regulation of the serotoninergic S2 receptor is believed to play a major role through an increase in carbohydrate intake. Also anticholinergic and sedative properties are important. Careful dietetic instructions and restrictive use of these drugs are necessary if weight gain is to be prevented. A new promising class of antidepressant is described.     

Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain

OBJECTIVE: Weight gain, leading to further morbidity and poor treatment adherence, is a common consequence of treatment with antipsychotic drugs. A recent study showed that a polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene is associated with antipsychotic-induced weight gain. The authors determined whether this association held true for weight gain after clozapine treatment. METHOD: Thirty-two Chinese Han patients with first-episode schizophrenia were genotyped for the -759C/T polymorphism and had weight changes monitored after 6 weeks of clozapine treatment. RESULTS: The authors found that the 10 patients with the -759T variant allele showed significantly less weight gain than those without this allele. The effect was strongest in the male patients and not apparent in the female patients. CONCLUSIONS: These findings identify an important genetic factor associated with clozapine-induced weight increases in schizophrenia.     

Are atypical antipsychotic drugs also atypical antidepressants?

OBJECTIVE: To report a case series and review the psychopharmacology of the neuroleptic drugs to suggest that the atypical antipsychotic drugs may have an antidepressant action, at least for those patients with the melancholic subtype. METHOD: We note the literature suggesting that the older (or typical) antipsychotic drugs were established as having antidepressant activity, describe an open study of some two dozen patients with a treatment-resistant melancholic depression, describe rapid resolution of depression and augmentation benefits associated with commencing an atypical antipsychotic drug in a percentage of subjects, and then review relevant psychopharmacological studies to consider whether there is a rationale for use of antipsychotic drugs to treat depression. RESULTS: Of some two dozen patients treated with an atypical antipsychotic drug, almost immediate improvement was noted in four patients, and evidence of augmentation benefit obtained in another three patients. CONCLUSIONS: Impressions from this case series are encouraging. However, as open clinical observational studies are problematic, controlled studies are required to establish whether the atypical antipsychotic drugs have a role in the management of certain expressions of depression, and, in particular, treatment-resistant melancholic depression.     

Mort subite, antipsychotiques et schizophrénie

Sudden death is a multidimensional notion that can be defined in several ways. Epidemiologically, sudden death affects from 15 to 30% of the population and 30% of the schizophrenics. Since antipsychotic drugs appeared in 1954, the death rate of the schizophrenic population has decreased but has still remained higher than the death rate of the entire population (standardized mortality rate from 1 to 4). However, there is no proof of a decrease in the number of sudden deaths because of a lack of statistical data about the first period of time. Several factors may explain the excessively high death rate of the schizophrenics but mainly cardiovascular risk factors and an insufficient diagnosis of somatic comorbid conditions. Stress is also a well-known aetiology of sudden death: Ventricular tachycardia can occur in situations of anxiety; the Tako Tsubo syndrome is a coronarian syndrome occurring in a context of emotional stress. Death due to cardiovascular factors is probably the main aetiology of the schizophrenics’ sudden deaths, which are often associated with a prolonged QT interval (it is considered today that the QT interval is prolonged beyond 450 MS). Schizophrenia is partly the cause of these sudden deaths with regard to the stress generated by the disease. The influence of drugs on these deaths, and especially antipsychotic drugs, has also been considered. So, the use of thioridazine and sertindole was suspended after a dose-effect and sudden deaths were observed. Other antipsychotic drugs, such as haloperidol and risperidone are associated with some cases of a prolonged QT interval, with a high dosage. Another aetiology of sudden death is epilepsy: Before the rise of antipsychotic drugs, the comitial crises rate was already higher among the schizophrenics and crises occur today with or without a subjacent treatment; but antipsychotic drugs have also been incriminated in some sudden deaths. In the case of sudden deaths caused by pulmonary embolism, schizophrenia is a predisposition, especially catatonic schizophrenia. Obesity, physical restraints in case of agitated state are also the causes of a restrained mobility that can favour pulmonary embolism. As for antipsychotic drugs, and especially clozapine, they favour a gain of weight and a sedation with a high dosage, which result in a reduced mobility. As for sudden deaths caused by choking, schizophrenia contributes to these deaths through a poor mastication, a poor dentition or poor hygienic and dietetic habits. Phenothiazines can favour these deaths insofar as they favour deglutition impairment; the use of haloperidol can result in a respiratory dyskinesia that leads to asphyxia; the clozapine-benzodiazepine combination must be avoided. In the case of sudden deaths through intestinal obstruction, constipation is often poorly diagnosed for schizophrenics for whom the pain threshold is higher and because of their negative symptoms. These factors already explained the excessive death rate among the schizophrenics before the antipsychotic drugs era. But antipsychotic drugs have an analgesic effect that delays the diagnosis of constipation and an anticholinergic effect that favours constipation. The combination with a tricyclic antidepressant increases the risk. The incrimination of antipsychotic drugs in the sudden deaths of the schizophrenics remains debatable and epidemiology provides no conclusion. An autopsy is sometimes not enough to put the blame or not on antipsychotic drugs. Prevention measures about morbidity and mortality associated with antipsychotic drugs that prolonged QT, and with schizophrenia itself are proposed. The connection between sudden death and antipsychotic drugs remains poorly understood: in psychiatry, the high sudden deaths rate is due to several factors and antipsychotic drugs remain the most commonly used treatment for psychosis.     

Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism

BACKGROUND: Preliminary evidence suggests that use of antipsychotic drugs is associated with an increased risk of venous thromboembolism. OBJECTIVE: To evaluate the relationship between antipsychotic or antidepressant drug use and venous thromboembolism among adults aged 65 years and older. DESIGN: Retrospective cohort study using linked health care administrative databases over a nine year period. SETTING: The entire province of Ontario, Canada. PARTICIPANTS: Individuals aged 65 years and over exclusively prescribed either antipsychotic drugs (n = 22,514), antidepressant drugs (n = 75,649) or thyroid replacement hormones (33,033), the referent control group. We excluded those with an antecedent history of cardiovascular disease, venous thromboembolism or cancer, as well as those dispensed warfarin before study entry. MEASUREMENTS: Diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Relative to those prescribed thyroid hormones, neither antidepressant (adjusted hazard ratio 1.02, 95% CI 0.91-1.14) nor antipsychotic (adjusted hazard ratio 1.13, 95% CI 0.96-1.32) drug use was associated with an increased risk for deep vein thrombosis. Similar risk estimates were found for deep vein thrombosis or pulmonary embolism. In a sub-group analysis, only butyrophenone use was found to be associated with a slightly increased risk of deep vein thrombosis (adjusted HR 1.51, 95% CI 1.23-1.86) as well as deep vein thrombosis or pulmonary embolism (adjusted HR 1.43, 95% CI 1.18-1.74). CONCLUSIONS: In a large cohort of adults aged 65 years and older, neither antipsychotic or antidepressant drug use was associated with an increased risk of venous thromboembolism, with the exception of a slightly increased risk among those prescribed butyrophenones. Further data are required before use of these psychoactive drugs can be considered a risk factor for venous thromboembolism.     

Weight gain and glucose and lipid metabolism disturbances during antipsychotic medication: a review

Antipsychotic medication is the mainstay of treatment for functional psychotic illnesses. However, for some patients weight gain and the disturbances in blood-lipid levels and glucose balance associated with their use are significant disadvantages, and pose health risks that may affect prognosis. A substantial body of evidence suggests that weight gain is at least partly related to the blocking effects of antipsychotic medication on serotonin- and histamine-mediated neurotransmission. The disadvantages associated with weight gain can be reduced by an appropriate choice of antipsychotic and avoidance of polypharmacy, by regular monitoring of the patient's weight, and, if necessary, by the patient's participation in a dieting programme. Received: 28 June 2002 / Accepted: 18 November 2002 Correspondence to Prof. Hannu Koponen