Abstract
Excess body weight in patients prescribed antipsychotic medication has been documented for over 40 years with 40–80% of such individuals experiencing weight gain [1]. A recent meta-analysis of 81 studies confirmed the relationship between weight gain and antipsychotic agents and illustrated that some medications have a greater weight promoting action than others [2]. For example, the average weight gain of patients taking clozapine and olanzapine over 10 weeks was 4.5 kg and 4.2 kg, respectively, whereas weight gain of 1.1 kg was reported for haloperidol. Clozapine and olanzapine are commonly prescribed in the clinical setting and often over extended periods of time which means that in some individuals the weight-promoting effect of the pharmacologic agent may continue for years [3].
Weight management is a significant problem in the wider population but is a unique challenge in patients with psychiatric disorders and poses a number of substantial clinical dilemmas. For example, how does one strike a balance between the clinical imperatives of management of the psychiatric condition and management of obesity and related comorbid conditions?
Recent research has reported that weight gain with atypical antipsychotic medication occurred despite active weight loss programs involving diet and exercise over a 5-year period [3]. A fundamental concern in relation to such findings is whether best practice guidelines for diet and exercise were utilized. If the approaches employed to date have been suboptimal, how might future interventions be improved? Herein lies the challenge – how can sound nutritional and physical activity practices necessary for weight management (weight-loss and/or weight maintenance) be implemented in this population?
A number of recent papers have reviewed potential weight management strategies for people administered atypical antipsychotic drugs [4–8]. The cornerstone of the treatment and management of obesity [9], including for mental health patients, is consistently identified as behaviour modification to improve diet and increase physical activity. There is widespread agreement that interventions should be proactive and target potential gainers either prior to or at the commencement of atypical administration. Regular monitoring, realistic goal setting and weight control strategies are vital.
Given the propensity for clozapine and olanzapine to promote a higher weight gain than other antipsychotic agents it is important to investigate the efficacy of strategies to reduce weight gain induced by these agents. As few weight loss programs involving psychiatric patients have been successful [10, 11] it is important to recognize the relative strengths and weaknesses of studies in the area. Most studies have been limited to descriptive clinical insights with consistent shortcomings being small subject numbers and lack of a control group.
Our major aim is to review weight management intervention studies related to clozapine and/or olanzapine induced weight gain. A parallel aim is to summarize the challenges facing future research and provide an overview of best practice in the management of weight in mental health patients.
Method
A systematic literature search was conducted using Medline, Cinahl and PsychINFO databases and reference lists from relevant published articles. Five studies related to weight control practices and atypical antipsychotic medications were reviewed.
Results
Dietary restriction: hospital setting
The study by Heimberg et al. [12] was the first to report on the use of dietary restriction to control weight gain associated with the prescription of clozapine. Weight change was monitored in 40 patients with schizophrenia or schizoaffective disorder treated with clozapine for more than 6 months. Gender and diet influenced weight gain over a 6-month period with weight gain most pronounced in non-dieting women (mean gain: 6.1 kg) compared with dieting women (gained <0.5 kg). In contrast, nondieting men gained a mean of 2.0 kg while men who ‘dieted’ lost an average of 7.1 kg while taking clozapine. A selection bias existed as the subjects chosen for dietary management were those with pre-existing physical or metabolic defects so they may have responded better to dietary restriction than patients without these conditions. It is unknown whether the participants experienced any problems with diet adherence or whether this restriction in calorie intake caused distress. All subjects were hospital inpatients so it is unlikely that these results could be generalized to people taking clozapine in community settings. What potential may exist for further improvement with the incorporation of an optimal exercise prescription?
Primary intervention programme: residential setting
Despite the serious and persistent mental illness of subjects, the primary intervention program by Aquila and Emanuel [13] conducted in a residential setting found that the average body weight of 32 subjects did not change over 2 years. The setting enabled control over the nutritional intake of participants. During the intervention subjects were provided with a low-fat, low-calorie diet, averaging 2000 kilocalories per day. With nutrition counselling and dietary changes, patients who gained weight were able to lose it and subsequently maintain the weight loss. Twenty-five subjects were treated with olanzapine, the balance with clozapine.
Nutritional goals of the program were to increase fresh produce and soups, to replace rich desserts with fresh fruit, serve ‘Crystal-lite’ or water with each meal, to restrict sugar and caffeine-laden drinks, and to decrease portion size for all foods except vegetables and salad. ‘Seconds’ were not allowed and nighttime snacks were eliminated except for people with diabetes. Further reinforcement was provided in a ‘healthy eating habits’ group in which a nutritionist educated patients regarding proper eating habits. Subjects were also provided appropriate medical care for comorbid conditions such as diabetes, hypertension and hypercholesterolemia.
Wellness Clinic: community setting
Wirshing et al. [14] reported on the clinical weight management of 122 males with schizophrenia involved in clinical trials of different antipsychotic medication. This community-based program involved a stepwise approach to intervention as weight gain increased. The initial focus of the programme related to awareness of weight and monitoring of food intake. All patients received the same clinical management including regular weighing. Subjects who gained 4.5 kg were instructed to keep a detailed food diary and if weight gain continued patients were referred to a clinical nutritionist. Further weight gain resulted in referral to a ‘Wellness Clinic’ for a more rigorous evaluation of diet and exercise habits, education and exercise classes with group support.
Patients prescribed clozapine were not responsive to weight loss interventions whereas weight gain in patients prescribed olanzapine were more readily reversed with diet and exercise changes instituted at the ‘Wellness Clinic’ despite a similar weight gain of 8.8% above baseline for both groups.
Predisposition to weight gain has important implications for prevention, treatment and management. Despite individual variability in response to pharmacologic agents, it is prudent to recognize that all mental health patients may be vulnerable to weight gain with persistent poor dietary practices and low levels of physical activity. Further, weight gain may be exacerbated for those who are prescribed clozapine. A more proactive approach to weight management should be taken with all patients prescribed antipsychotic medication.
Weight Watchers: community setting
Ball et al. [15] evaluated the effectiveness of a Weight Watchers program for 21 patients with schizophrenia or schizoaffective disorder. All subjects had gained at least 7% of their pretreatment body weight since they commenced on olanzapine a minimum of 6 months prior to the intervention. The programme was delivered on an outpatient basis with ten weekly Weight Watchers meetings during which participants were taught to evaluate food choices. Exercise sessions were scheduled three times a week. Eleven subjects completed the program, seven withdrew before commencement, and three dropped out during the program. Seven of the eight male participants lost a significant amount of weight across the 10-week intervention (range = 0.5–8.2 kg). In contrast, three of the four female participants gained weight and the remaining woman lost 6.0 kg. Exercise duration was minimal at the beginning of the programme (5–10 min of walking over approximately 0.16 km) but extended to 25 min and a distance of 1.6 km by the end of the program.
No adverse events were reported in this study; however, ‘psychiatric symptoms’ prevented two of the women, initially successful in losing weight, from adhering to the programme. It is important to consider the extent to which weight-loss and then weight maintenance is possible through the use of a combined Weight Watchers and exercise programme. More specific strategies may be needed to assist some patients.
Cognitive behavioural therapy: community setting
Umbricht et al. [16] reported promising results of an intervention to promote weight-loss in a small group (n = 6) of people with schizophrenia. Four individuals had experienced weight gain while taking clozapine and two while taking olanzapine. A psychologist and a dietitian delivered group and individual sessions using a cognitive behaviour approach focused on causes of weight gain, healthy lowcalorie nutrition, specific recommendations for weight loss, and instructions about physical exercise and relaxation. The individual treatment spanned 7–9 sessions while ten bi-weekly group sessions focused on weight reduction and a further six sessions on weight maintenance. Weight loss ranged from 0 to 21 kg with a significant drop in BMI from a preintervention mean of 29.6–25.1 kg/m 2. Longer-term success in weight loss or weight maintenance and persistence of lifestyle changes such as regular physical activity and improved nutritional practices is not known and no follow-up was apparent.
Discussion
The variability of results in the studies reviewed may be due to a range of reasons, including the substantial differences in setting, study design and implementation. The authors chose a cross-section of recent papers to highlight both the current knowledge and practices in the area and the challenges facing clinicians. Strengths and weaknesses of these studies may be considered in relation to documented best practice in weight management and also ideal but difficult to implement study designs. The population is very challenging but this should not be used as an excuse for less than optimal studies. There is an urgent need for well designed randomised controlled trials to assess the differential effect of medication and various combinations of diet and exercise on weight gain, weight loss and weight maintenance. Further, greater attention is needed to train clinicians to understand the complications of obesity and the role of nutrition and physical activity in the prevention, treatment and management of weight gain in patients prescribed atypical antipsychotic medication. An active and persistent approach by clinicians to monitor and intervene during weight gain associated with the prescription of medication may be particularly fruitful. For example, a standardized screening tool and clinical pathway would help clinicians to target appropriate interventions for each person taking atypical antipsychotic medication.
The collective findings of the studies reported suggest that the weight gain liability of clozapine and olanzapine can be limited by appropriate lifestyle interventions. Not surprisingly, the ‘best’ results are consistent with a setting where there is at least partial control over eating and physical activity behaviours, for example in the setting used in the study by Aquila and Emanuel [13] that featured low-calorie, nutritious diets and rigorous educational efforts. Mechanisms of weight gain may relate to the compound effects of poor diet and inactive behaviours plus antipsychotic medication. Without evidence from well controlled interventions it is difficult to tease out the respective contributions of each factor. However, improvements in approach to the modification of eating and activity behaviours appear to hold the greatest chance of longer-term success. Consistent with the mainstream literature, men appear to be more successful in weight loss.
As there is a dearth of systematic efficacy and safety data in this population [17] the use of pharmacological strategies is generally discouraged or considered on an individual basis as an adjunct to the promotion of healthy lifestyle practices, not as a substitute. A change to an atypical agent with a lower weight gain liability may be an effective strategy for some individuals [7]; 708 ATYPICAL ANTIPSYCHOTIC WEIGHT GAIN however, the contrasting viewpoint is the risk of relapse if an effective agent is discontinued in favour of a medication with a lower risk of weight gain [18].
Many factors may influence success in weight management (Table 1) including the use of programs with concrete models, simple directions and reinforcement to facilitate the participation of patients with cognitive difficulties and psychosis [6]. The primary emphasis should be long-term weight maintenance through realistic lifestyle changes rather than weight loss per se with subsequent effort on the loss of moderate amounts of body weight (5–10%) [9]. The success rate of long-term weight loss in the general population is commonly low, around 15% [19]; however, many studies (including those reported here) have not included all features of a well designed weight management program (Table 2).
Factors which affect management of atypical antipsychotic induced weight gain
Features of successful weight management programs
The benefits of physical activity should not be underestimated as activity is the strongest environmental determinant of total body fat and abdominal fat accumulation [20]. Physical activity increases energy expenditure, has a positive effect on resting metabolic rate and body composition and independent of weight control improves diseases that are over-represented in this population such as diabetes and cardiovascular disease [21, 22]. Regular physical activity may also help to provide a greater sense of wellbeing [23].
As many people with psychotic disorders are inactive, a graded approach to physical activity and exercise is more likely to be sustained in the long-term. Attempts to increase physical activity should be considered using a three-level approach. An assessment of current physical activity level should be followed by the first level, to provide specific advice on ways to increase habitual physical activity such as using stairs, walking wherever possible and increasing activity levels in the home or institution such as gardening. The second level involves an increase in planned physical activity using general guidelines such as the progressive accumulation of 30 min of moderate intensity exercise on a daily basis. Moderate intensity physical activity causes a slight but noticeable increase in respiratory rate and heart rate such as a brisk walk at a pace where a person can comfortably talk. Very inactive patients need to be assured that in initial phases they do not need to exercise strenuously to gain health benefits. The accumulation of small bouts of exercise may be as effective as single longer bouts if the overall amount of energy expended is the same [24], for example in a walking programme. The third stage, once individuals have become more active in their daily life, is to provide an individualized prescription for exercise. The nature of exercise prescription influences long-term adherence to physical activity [24] and such specific programmes needs to be prescribed by an exercise physiologist.
Conclusion
In summary, the control of obesity associated with atypical antipsychotic medication is clinically important. There is evidence that weight gain can be ameliorated by lifestyle changes such as improved nutritional practices and increased physical activity. Patients need to be actively assisted to acquire the necessary knowledge and skills to practise good nutrition and lead a physically active lifestyle.
Randomised controlled trials are needed to improve understanding of the effect of medication and different interventions on weight gain, weight loss and weight maintenance. Increased training of health professionals in obesity and the role of nutrition and physical activity would greatly assist patients. A standardized screening tool and clinical pathway would help clinicians to identify appropriate interventions for individual patients.
Footnotes
Acknowledgements
Financial support was provided by the Ipswich Hospital Foundation (scholarship) and the School of Human Movement Studies, Queensland University of Technology.