SEARCH

SEARCH BY CITATION

Keywords:

  • antipsychotics;
  • quality of life;
  • weight gain

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENT
  7. REFERENCES

Aims:  Weight gain secondary to antipsychotic medication is associated with many serious conditions, including type II diabetes mellitus, hypertension, and coronary heart disease, and also with poor medication compliance. Weight control programs may be of benefit to outpatients with schizophrenia, but also raise an issue of cost-effectiveness. We aimed to evaluate the effectiveness of a 10-week weight control program for outpatients taking atypical antipsychotics for treatment of schizophrenia, and to follow up the effects of this weight control program in controlling weight gain after termination of the program.

Methods:  A total of 33 patients with schizophrenia and antipsychotic-related obesity were enrolled in a 10-week multimodal weight control program. The patients' weights were recorded at baseline, week 4, week 8, week 10 (end of the intervention), week 12, week 24, and week 48. Secondary measures included blood sugar levels, cholesterol levels, triglyceride levels, quality of life and mental health.

Results:  For those who completed the weight control program, there was a mean weight loss of 2.1 kg by the end of the intervention, 3.7 kg over 6 months, and 2.7 kg over 12 months. The mean body mass index decreased by 0.8, 1.5 and 1.1 at week 10, week 24 and week 48, respectively, all with statistical significance.

Conclusions:  The 10-week weight control program was effective in terms of weight reduction among obese patients with schizophrenia or schizoaffective disorder, and the weight reduction effect lasted for up to 6 months, and up to 12 months in some cases.

ANTIPSYCHOTIC MEDICATIONS ARE essential for many individuals with schizophrenia and other psychotic disorders. However, both conventional and atypical antipsychotic drugs are associated with weight gain.1,2 In addition, people with schizophrenia tend to have an unhealthy lifestyle, often taking little exercise and eating a diet higher in fat than the general population.3 Consequently, patients with schizophrenia are, on average, significantly heavier than the general population.4–6 We have recently shown that the prevalence of obesity among male and female patients with schizophrenia is 2.7 and 2.5 times greater than the Taiwanese reference population, and the prevalence of severe obesity among the male and female patients was 4.7 times and 3.5 times greater than that in the Taiwanese reference population, respectively.6

Obesity and excess weight are clearly associated with many serious conditions, including type II diabetes mellitus, hypertension, obstructive sleep apnea and coronary heart disease, and are also associated with increased mortality risk.7 Besides its adverse effects on disease outcomes, excessive weight also impairs physical functioning, reduces quality of life, and is associated with poor mental health. These psychological and mental health consequences of excessive weight represent an additional burden for patients with schizophrenia and other mental disorders.8 In addition, it is well recognized that weight gain secondary to antipsychotic medication reduces medication compliance, leading to the return of psychotic symptoms.9,10 Strategies for weight gain management that have been proven effective in clinical trials include regular check-ups, lifestyle and medication counseling, medication assessments, behavioral control programs, and pharmacological intervention.11 In a very recent review of pharmacological and non-pharmacological strategies for reducing or preventing weight gain in individuals with schizophrenia, Faulkner et al. concluded that no single pharmacological agent emerges as consistently superior in terms of weight loss efficacy, and that non-pharmacological interventions incorporating dietary and physical activity modifications demonstrate promise in terms of preventing weight gain.12 Furthermore, clinical weight management programs focusing on behavioral change are reported to improve several factors of health-related quality of life.13

Patients undergoing a weight control program from the time they commence antipsychotics, via group education14 or individual intervention,15 have less weight gain than controls. Ball et al. reported the effects of a 10-week Weight Watchers Program with exercise sessions three times a week on patients with weight gain during olanzapine therapy.16 This small study found significant weight loss in male patients (n = 7), but not in the female patients (n = 4). Kwon et al. reported that a 12-week weight management program is effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine.17 In addition, such a weight management program may improve the quality of life of patients with schizophrenia, specifically with respect to physical well-being.17 One of the limitations of these studies is the short duration of study and lack of follow up of the effects of the weight management programs. Menza et al. conducted a 12-month weight control program involving patients with weight gain while on atypical antipsychotics.18 After 12 months, the intervention group had lost 3 kg compared to a gain of 3.5 kg in the usual care group. These studies suggest generally that weight control programs may be of benefit to outpatients with schizophrenia, but also raise the issue of cost-effectiveness. The aims of this study were (i) to evaluate the effectiveness of a 10-week weight control program for outpatients taking atypical antipsychotics for treatment of schizophrenia or schizoaffective disorder; (ii) to evaluate the effects of this weight control program on symptom profiles and quality of life; (iii) to follow up the effects of this weight control program in controlling weight gain after termination of the program.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENT
  7. REFERENCES

Participants

Thirty-three subjects from the Department of Psychiatry, Chang Gung Memorial Hospital, Taiwan, were enrolled in a 10-week multimodal weight control program, termed ‘A Meaningful Day’. Study approval was obtained from the Institutional Review Boards of Chang Gung Memorial Hospital, Taiwan. Written informed consent was obtained from the subjects following an explanation of the study. The inclusion criteria were: (i) a diagnosis of schizophrenia or schizoaffective disorder using the Diagnostic and Statistical Manual of Mental Disorders; (ii) age between 20 and 50 years old; (iii) taking an atypical antipsychotic for at least 3 months; (iv) with a body mass index >25. Exclusion criteria were as follows: pregnant or breast-feeding, severe medical disease, drug or alcohol abuse within the last 3 months, and an acute psychotic state in need of intensive management. There was no change of antipsychotic medication or use of medication for weight control for the subjects during the weight control program and follow-up period. The subjects who needed changes of antipsychotic medication, either due to symptoms instability or intolerance to adverse effects, were withdrawn from the study.

Intervention

The ‘A Meaningful Day’ weight control program incorporated nutrition counseling, exercise, and behavioral interventions designed to help patients with schizophrenia, particularly those with obesity in addition to schizophrenia. There were some similarities between the ‘A Meaningful Day’ program and ‘Solutions for Wellness’ initiated by Eli Lilly and Co or weight control programs applied in other studies.16,17 This program emphasized a healthy lifestyle and structured life schedule. Motivational counseling techniques were also utilized. The patient number for each group was set to be around 12. The subjects of this study consisted of patients from three groups, with patient numbers of 11, 12 and 10, respectively. The weight control program consisted of 10 sessions of 90-minute group activities. The content of the sessions included drug adherence and relapse prevention (three sessions), a structured life schedule (one session), healthy eating (six sessions) and exercise. Forty-five minutes of aerobic exercise was incorporated into each session except the first and the last sessions which were spared for introduction and wrap up. The subjects were urged to keep a food diary and an exercise diary. The participants were asked to do additional aerobic exercise for more than 45 min three times per week, at home. The sessions were carried out by a psychiatrist, a psychiatric nurse, a dietitian and a fitness coach.

Measurements

The primary outcome measures were weight and BMI. The patients' weights were recorded at baseline, week 4, week 8, week 10 (end of the intervention), week 12, week 24 and week 48. Subject body weight and height were assessed in a standardized fashion to calculate body mass indices (BMI: weight for squared height, kg/m2). Height was measured to the nearest millimeter, with subjects' barefoot and standing upright. Body weight was measured with an electronic scale calibrated to ±0.1 kg. Subjects were weighed in light indoor clothing. The secondary measures included blood sugar levels, cholesterol levels, triglyceride levels, quality of life and mental health. Quality of life was measured using the 36-Item Short-Form Health Survey (SF-36)19 and the World Health Organization–Quality of Life–Brief version (WHO–QOL–BREF).20 The inventories for assessing psychiatric health were the Positive and Negative Symptom Scale (PANSS),21 the Beck Depression Inventory (BDI),22 the Beck Anxiety Inventory (BAI),23 and the Epworth Sleepiness Scale (ESS).24

Analysis

Data regarding weight change, BMI, cholesterol, triglyceride, blood sugar, SF-36, WHO–QOL–BREF, PANSS, BDI, BAI, and ESS were analyzed from baseline to the end-point of the intervention using a paired t-test. In cases in which some subjects did not complete the program, the ‘last observation carried forward’ method was used in comparing the weight before and after intervention. While comparing those who completed the intervention program with those who did not, continuous variables were analyzed using the Student's t-test, and categorical variables were calculated using χ2 tests. All tests were two-tailed, and P values less than or equal to 0.05 were considered significant.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENT
  7. REFERENCES

The participants consisted of 6 men and 27 women. The mean age of the participants was 31.9 years (SD = 6.4). Their mean weight and BMI were 77.9 kg (SD = 15.5 kg) and 30.3 (SD = 4.6), respectively. The antipsychotics that the subjects were taking were risperidone (n = 12), olanzapine (n = 11), quetiapine (n = 6), and clozapine (n = 4). Seven (21.2%) participants withdrew before the end of the program, and 26 completed the program. The overall session attendance rate of those who completed this study was 90.1%. Of these, 73.1% attended at least eight of the 10 sessions. Of the 26 subjects who completed the weight control program, 20 subjects (76.9%) were rated to be above 75% compliant, and six (23.1%) were 50% to 75% compliant with diet management and exercise homework.

After the 10-week program, there was a significant reduction of weight for all subjects (mean weight from 77.9 kg to 76.6 kg, t = 2.6, d.f. = 32, P = 0.014). Bodyweight and BMI changes in the participants who completed the weight control program from baseline to the endpoint of the intervention (week 10) and to 12 months are presented in Table 1. For those who completed the weight control program, there was a mean weight loss of 2.1 kg by the end of the intervention, 3.7 kg over 6 months, and 2.7 kg over 12 months. The mean BMI decreased by 0.8, 1.5, and 1.1 at week 10, week 24, and week 48, respectively, all with statistical significance compared to baseline. The weight data of the non-completers at week 24 was obtained, although other data were incomplete. The non-completers had a mean weight gain of 2.8 kg (SD = 3.5) and a mean increase in BMI of 1.1 (SD = 1.3) at week 24. There were significant differences in weight changes (t = 5.1, d.f. = 31, P < 0.001) and BMI changes (t = 5.2, d.f. = 31, P < 0.001) between the completers and non-completers at week 24. At the week 48 follow up, the mean weight of those who remained on the same antipsychotic regimen (n = 16) was 76.1 kg (SD = 16.9), which was significantly lower than the mean weight at baseline.

Table 1.  Weight and body mass index of patients who completed the weight control program
 Weight (n = 26) Mean (SD), kgChange of weight from baseline (n = 26) Mean (SD), kgBMI (n = 26) Mean (SD)Change of BMI from baseline Mean (SD)P
  • n = 16 for the data of week 48.

  • BMI, body mass index.

Baseline78.8 (16.5) 30.5 (4.9)  
Week 478.2 (16.3)−0.5 (1.6)30.3 (4.8)−0.2 (0.6)0.124
Week 877.5 (16.0)−1.3 (2.4)30.0 (4.7)−0.5 (1.0)0.019
Week 1076.7 (16.3)−2.1 (2.8)29.7 (4.8)−0.8 (1.1)0.001
Week 1275.7 (16.5)−3.0 (2.9)29.3 (4.9)−1.2 (1.1)<0.001
Week 2475.0 (16.7)−3.7 (2.9)29.0 (4.9)−1.5 (1.1)<0.001
Week 4876.1 (16.9)−2.7 (2.2)29.4 (4.9)−1.1 (1.0)<0.001

Changes in the secondary measures, such as blood sugar levels, cholesterol levels, triglyceride levels, quality of life, and mental health are shown in Table 2. The completers had a significantly lower level of triglyceride, but not blood sugar or total cholesterol, than at baseline. These participants also had significant improvement in WHO–QOL–BREF, PANSS, BDI, BAI, and ESS scores at the completion of the weight control program. In terms of the composite measures of the SF-36, the completers had significant improvements in the bodily pain, general health and emotional role subscales.

Table 2.  Secondary outcome measures of patients who completed the weight control program
 Pre-intervention Mean (SD)Post-intervention Mean (SD)P
  1. BAI, beck anxiety inventory; BDI, Beck depression inventory; ESS, Epworth sleepiness scale; PANSS, positive and negative symptom scale; SF-36, 36-item shot-form health survey; WHOQOLBREF, World Health OrganizationQuality of LifeBrief version.

Blood sugar88.15 (5.74)86.35 (8.03)0.327
Cholesterol188.23 (27.27)187.35 (34.15)0.800
Triglyceride163.46 (94.27)141.04 (74.02)0.037
WHOQOLBREF76.38 (13.33)84.65 (18.55)0.003
SF-36   
 Physical Functioning80.38 (19.59)80.96 (16.43)0.891
 Role Physical50.00 (41.83)57.69 (42.29)0.342
 Bodily Pain60.31 (25.67)71.00 (24.06)0.007
 General Health42.92 (21.27)50.54 (20.44)0.009
 Vitality46.54 (23.82)53.46 (19.99)0.072
 Social Functioning53.85 (20.85)60.10 (25.99)0.183
 Role Emotional46.15 (42.24)70.51 (39.25)0.015
 Mental Health48.92 (20.06)54.00 (20.87)0.095
PANSS72.15 (14.72)50.19 (13.03)<0.001
BDI20.19 (14.49)14.11 (11.81)0.004
BAI18.46 (14.58)12.38 (11.78)0.003
ESS10.08 (6.24)7.62 (6.51)0.016

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENT
  7. REFERENCES

The results of this study showed that the 10-week weight control program was effective in terms of weight reduction among obese patients with schizophrenia or schizoaffective disorder, and that the effects of weight reduction lasted for up to 6 months, and even 12 months in some cases. The subjects who completed the program also had significant improvement in the blood level of triglyceride, and in psychiatric health rating scores, including PANSS, BDI, BAI, ESS, and quality of life. However, particular caution is needed in extrapolating the effects that the weight control program had on the improvement of various psychiatric symptoms and quality of life.

The effects in weight reduction of this 10-week weight control program at endpoint were in general compatible with those of the brief weight control programs reported previously.17,25–27 In a 52-week weight control program for atypical antipsychotic-associated weight gain, Menza et al. found that those with intervention had a mean weight loss of 3.0 kg over 1 year.18 The weight loss occurred mainly in the first months. However, in the first 3 months of their program, the patients were seen three times (two group meetings and one individual session) a week. This kind of intensive program is difficult to use with psychiatric outpatients due to cost-effectiveness. A notable point is that our study showed that a brief weight control program (10 weekly sessions) was effective in weight control and more cost-effective overall.

Allison et al. concluded that antipsychotic-induced weight gain was likely responsible for excess weight among schizophrenic individuals.2 Numerous psychotropic drugs can cause weight gain.9 Notably, investigations have confirmed that atypical antipsychotics are more closely associated with weight gain in patients than typical antipsychotics, but not all.28 Therefore, in this study, we recruited only those patients who were taking atypical antipsychotics, but not those on conventional antipsychotics. Whether or not the results of this study can be generalized to those with conventional antipsychotics-related weight gain is in need of further investigation.

The high dropout rate of patients in weight management programs has been of concern. In the present study, seven out of 33 participants did not complete the program. The subjects generally had significant weight reduction at the endpoint. Nevertheless, it is notable that the non-completers had a mean weight gain of 2.8 kg while the completers had a mean weight reduction of 3.7 kg at week 24. This may suggest that careful case selection or motivation enhancement for program completion is important in conducting such a weight control program.

The results of this program also showed that the patients who completed the weight control program had significant improvements in the measures of various domains of mental health, such as psychosis, depression, anxiety, and daytime sleepiness. These subjects also reported a better quality of life. A weight control program for adults without major psychiatric disorders demonstrated that at the completion of a weight loss intervention, there were increases in the physical functioning, general health, vitality, and mental health subscales of the SF-36.13 In this study, there were significant improvements in the bodily pain, general health and emotional role subscales of the SF-36, and trends of increases in the vitality and mental health subscales, which was in general compatible with the findings of Blissmer et al.13 The differential effects of the weight control program on the various aspects of health-related quality of life need further investigation. There is also a need to develop a better understanding of what factors in the weight control program lead to improvements in health-related quality of life among obese patients with schizophrenia or schizoaffective disorder. It is possible that behavioral factors such as exercising, changing diet, or a structured life schedule can explain the improvement, and it is also possible that the social interaction or other support of this program was responsible for the improvements in health-related quality of life.

One of the main limitations of this study was the lack of randomized controls. The findings that those who completed the intervention had significant improvement in psychiatric health rating scoring, such as the PANSS, BDI, BAI, ESS, and quality of life, need to be interpreted with caution. Since this study was not a blind one, placebo effects and rating bias cannot be ruled out. The body weight and blood triglyceride level measurements were objective, and less likely to be influenced by these biases. Therefore, we concluded that a brief structured weight control program was effective in terms of weight reduction among obese patients with schizophrenia or schizoaffective disorder, and that the effects of weight reduction could last for up to 6 months, and even 12 months in some cases.

ACKNOWLEDGEMENT

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENT
  7. REFERENCES

This study was supported by an investigator-initiated grant from Eli Lilly and Co, Taiwan.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENT
  7. REFERENCES