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.     

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.     

Reversal of antipsychotic-associated weight gain

BACKGROUND: Given growing concern about weight gain associated with treatment with antipsychotic agents, we performed a retrospective chart review of patients who reversed weight gain associated with antipsychotic treatment to determine the prevalence of reversal and both the course and methods used. METHOD: Prevalence of weight gain reversal was determined by surveying clinicians. Of 53 patients who gained >/= 20 lb (9 kg) during antipsychotic treatment, an initial sample of 12 patients (23%) who subsequently lost >/= 10 lb (5 kg) was identified. These 12 patients were combined with additional patients, identified by the authors, who met the same criteria for reversal of antipsychotic-associated weight gain to form a total sample of 35 patients. Course and methods of weight loss were determined by reviewing these patients' charts. Information about interventions and both antipsychotic and other medications was collected. RESULTS: At the point of maximum weight gain, the total sample of 35 patients had gained a mean of 29.36 kg (64.73 lb) over a mean of 33 months. At the point of greatest weight loss (56 months), these patients were a mean of 10.86 kg (23.94 lb) over their baseline weight. The most recent weight for patients (63 months) indicated they were 14.81 kg (32.65 lb) over baseline. The most frequent weight loss interventions were regular dietician visits (42.9% [N = 15]), self-directed diet (28.6% [N = 10]), and weight loss as a treatment goal (25.7% [N = 9]). The least frequent interventions were no intervention (5.7% [N = 2]), psychiatrist addressing weight loss (5.7% [N = 2]), and surgery (2.9% [N = 1]). No significant change in medications prescribed was found. CONCLUSION: Some patients who gain weight while taking antipsychotic medications are able to stop gaining and lose weight over time, largely through behavioral interventions. While patients' weight fluctuated, this group sustained a loss of approximately half their initial gain. Dietary interventions appear promising and should be explored further to prevent and reverse weight gain.     

Switching antipsychotics as a treatment strategy for antipsychotic-induced weight gain and dyslipidemia

Patients taking antipsychotic medications for psychiatric disorders also have many risk factors for medical comorbidities and early death. While these risk factors were present before the arrival of the newer antipsychotic medications, the overall risk factor burden is exacerbated for those high-risk patients whose antipsychotic therapy causes or aggravates obesity or dyslipidemia. Therefore, there is an urgent need for effective interventions to address problems related to the additional iatrogenic burden from weight gain and dyslipidemias caused by antipsychotic medications. For patients with schizophrenia, complete discontinuation of antipsychotic therapy is not advisable and, therefore, pharmacologic options are narrowed to dose adjustments, adding adjunctive agents to induce weight loss, discontinuation of other adjunctive agents associated with weight gain, or changing the antipsychotic medication ("switching"). This article reviews the evidence showing that relative to other possible treatment options, switching to an antipsychotic with a lower propensity to induce weight gain or dyslipidemia can be effective for reversing the weight gain and dyslipidemia caused by previous antipsychotic treatment.     

Double jeopardy: a review of weight gain and weight management strategies for psychotropic medication prescribing during methadone maintenance treatment

Abstract

Methadone maintenance treatment (MMT) is an important treatment tool for the opioid epidemic. One challenge is that many persons who present for MMT also have co-occurring psychiatric disorders. Individually, both methadone and psychiatric medications carry risk of weight gain. Therefore, concurrent prescribing of methadone and psychiatric medications places dual diagnosis patients at even greater risk. As a parallel obesity epidemic grows, results from clinical trials assessing weight gain and weight management strategies among MMT and psychiatric patients can both inform and guide clinical practice. This study reviews findings from a literature search for recent clinical trials that focused on weight gain and weight management strategies during MMT with concurrent psychotropic medication use. While several studies have documented weight gain during MMT and psychotropic medication treatment, this study failed to identify recent work that explored concurrent prescribing. Most weight management strategies involved the use of additional medications and available data suggests that MMT and concurrent use of psychotropic medications increases the risk for obesity. More robust research is needed on weight gain and potential mitigation strategies when these treatment modalities are jointly utilized. Clarification of underlying biological mechanisms and development of non-pharmacological interventions merit further consideration.     

Recognizing Neuroleptic Malignant Syndrome in the Emergency Department: A Case Study

PURPOSE. A case study is presented to discuss the importance of accurate assessment of a patient in the emergency department (ED) who develops neuroleptic malignant syndrome (NMS). CONCLUSIONS. There has been a significant increase in the number of patients with psychiatric emergencies seeking treatment in the ED. The most frequently used medication for treating these patients is a high-potency typical antipsychotic (neuroleptic). Although NMS is a rare condition, it is a potentially fatal complication of neuroleptic medications. PRACTICE IMPLICATIONS. Early identification of this potentially life-threatening syndrome will lead to prompt treatment and improve the care of this vulnerable population.     

A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder

BACKGROUND: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. METHOD: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. RESULTS: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. CONCLUSION: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.     

The adverse effect profile and efficacy of divalproex sodium compared with valproic acid: a pharmacoepidemiology study

BACKGROUND: Divalproex sodium has been reported to be better tolerated than valproic acid. To our knowledge, no study has examined whether significant differences in the tolerability and efficacy exist between these preparations in psychiatric patients. The objective of the present study was to compare the tolerability and efficacy of divalproex sodium with those of valproic acid in psychiatric inpatients. METHOD: Information gathered retrospectively from the medical records of 150 patients treated with divalproex sodium was compared with that of 150 patients treated with valproic acid. These medical records were photocopied, and any mention of divalproex sodium or valproic acid treatment was concealed. A series of demographic and clinical characteristics were compared. RESULTS: Patients treated with divalproex sodium compared with patients treated with valproic acid were less likely to have gastrointestinal side effects (14.7% vs. 28.7%, p = .003), specifically anorexia (6.0% vs. 14.7%, p = .012), nausea or vomiting (6.7% vs. 16.7%, p = .007), and dyspepsia (11.3% vs. 22.0%, p = .013). Divalproex sodium-treated patients compared with valproic acid-treated patients were less likely to have discontinued their medication because of side effects (4.0% vs. 12.7%, p = .0066). Twelve (63.2%) of 19 patients who discontinued valproic acid because of gastrointestinal side effects were subsequently treated with divalproex sodium, of whom only 2 continued to have gastrointestinal side effects. There were no differences in efficacy between the 2 drugs. CONCLUSION: Divalproex sodium was better tolerated than valproic acid in inpatients with a variety of diagnoses and taking concomitant medications. Patients treated with divalproex sodium compared with patients treated with valproic acid were less likely to experience gastrointestinal side effects and to have discontinued their medication because of an adverse event.     

A brief motivational intervention for preventing medication-associated weight gain among youth with bipolar disorder: treatment development and case report

Bipolar disorder (BP) in youth is an impairing psychiatric disorder associated with high rates of relapse and recurrence. High rates of psychiatric and medical co-morbidities account for additional illness burden in pediatric BP. The elevated risk of overweight and obesity in this population is of particular concern. One of the likely etiologies for weight gain in youth with BP is use of mood-stabilizing medications. Although these medications can be effective for mood stabilization, excessive weight gain is a common side effect. Obesity is associated with a host of medical problems and is also correlated with worse psychiatric outcomes in BP, rendering the prevention of weight gain in this population particularly clinically relevant. In this article, we describe the rationale and development of a brief motivational intervention for preventing weight gain among youth with BP initiating mood-stabilizing pharmacological treatment and then present a case example illustrating the principles of the intervention.     

Pharmacologic and nonpharmacologic strategies for weight gain and metabolic disturbance in patients treated with antipsychotic medications.

OBJECTIVES: To provide an overview of pharmacologic and nonpharmacologic strategies for antipsychotic-associated weight gain and metabolic disturbance, to identify important areas for future research, and to make practice recommendations based on current knowledge. METHODS: We undertook a selective review of interventions for weight gain and metabolic disturbance in the general population and in individuals treated with antipsychotic medications, focusing on randomized controlled trials in schizophrenia. RESULTS: Pharmacologic strategies include medication choice, medication dosage and formulation, choice of concomitant psychotropic medications, medication switching, medication addition to effect weight loss or prevent weight gain, and medications to increase insulin sensitivity. Medication choice and medication switching may have the most potent influence on weight and metabolic parameters. Modest short-term weight loss can occur with the addition of selective medications and (or) lifestyle interventions. However, more rigorous and longer-term studies are needed. CONCLUSIONS: Although difficult, the prevention of weight gain and the promotion of weight loss are possible for individuals treated with antipsychotic medications. Further research, including diabetes prevention studies, is required. We suggest a pathway for the management of weight gain and emerging metabolic disturbance.     

'Why getting fat, Doc?' Weight gain and psychotropic medications.

OBJECTIVES: Weight gain associated with the use of psychotropic medications is a common clinical problem that is of particular importance because of its effects on the general health of psychiatric patients and their compliance with treatment. This paper aims to explore this issue and discuss the mechanisms of weight gain and methods of prevention. METHOD: A literature review (Index Medicus/Medline) was carried out as well as a review of other relevant papers and data known to the authors. RESULTS: Significant weight gain may result in considerable morbidity. The majority of psychotropic medications are associated with weight gain, however, the mechanisms of weight gain are often complex and poorly understood. CONCLUSION: Clinically, weight gain can be anticipated and often managed with some success in the majority of psychiatric patients with simple but relatively effective measures. It is important for clinicians to be aware of this common clinical problem and educate patients from the outset, monitoring them regularly and intervening when necessary.     

New-onset type-2 diabetes associated with atypical antipsychotic medications

PURPOSE: This study compared the one-year incidence of new-onset type-2 diabetes mellitus (DM) and changes in weight in patients with a variety of psychiatric diagnoses prescribed olanzapine, risperidone, or quetiapine, compared to a reference group receiving haloperidol and no other antipsychotic medication. RESEARCH DESIGN AND METHODS: Data was abstracted from charts of subjects newly initiated and then maintained for one year on olanzapine (n=112), risperidone (n=100), quetiapine (n=100), and haloperidol (n=100). Baseline and one-year DM status, height, and weight were collected, as well as concurrent psychotropic medications, medical and psychiatric comorbidities. FINDINGS: Using a multivariate model, logistic regression identified a significant association between olanzapine (but not other atypical agents) and the development of diabetes compared to haloperidol over the one-year period (odds ratio 8.4, 95% CI 1.8-38.7). Baseline obesity was independently associated with new-onset DM, but only marginally greater weight gain was found among olanzapine users. CONCLUSIONS: The middle-aged American veterans in this study cohort were highly vulnerable to the diabetogenic effects of olanzapine, but a close correlation with weight change was not found. Patients administered olanzapine should receive careful laboratory monitoring for elevated plasma glucose in addition to weight measurement.     

Using a hypothetical scenario to inform psychiatric advance directives

OBJECTIVES: The study addressed whether a hypothetical psychiatric scenario is a feasible approach for eliciting psychiatric treatment preferences and identified consumer preferences regarding involuntary care. METHODS: Community-residing adults with serious mental illness (N=150) voluntarily completed the Health Care Preferences Questionnaire to determine treatment preferences in response to the use of psychiatric medications, seclusion and restraint, and electroconvulsive therapy (ECT). A vignette was used to determine preferences first with respect to an imaginary patient and then with respect to the respondent. RESULTS: Few participants were distressed by the psychiatric scenario (7%). In regard to their own care, in an emergency most participants supported the use of involuntary treatments (medications, 70%; medication injection, 76%; and seclusion and restraint, 73%), with the exception of ECT (quick treatment, 32%; if life is in danger, 60%). Participants were less likely to support treatments for themselves than for an imaginary patient. The majority (65%) identified specific medication preferences. CONCLUSIONS: Scenarios about the state of medical and psychiatric health are a feasible method of identifying treatment preferences. They are well tolerated and may serve as a model for assisting persons with serious mental illness in considering difficult treatment decisions.     

Beliefs about medications: measurement and relationship to adherence in patients with severe mental disorders

Objective: To determine if the Beliefs about Medicines Questionnaire (BMQ) has satisfactory psychometric properties in patients with severe mental disorders and if their scores differ from those of patients with severe medical disorders. To investigate if the scores are related to medication adherence. Method: Two hundred and eighty psychiatric patients completed the BMQ and reported how much of their medication they had taken the past week. Serum concentrations of medications were analyzed. BMQ scores were compared with those of patients with chronic medical disorders. Results: Cronbach’s alpha was satisfactory for all subscales. The psychiatric group scored lower on the necessity of taking medication than the medical group. Non‐adherent patients felt medication to be less necessary and were more concerned about it than adherent patients. The necessity subscale predicted adherence fairly well. Conclusion: The BMQ has satisfactory psychometric properties for use in patients with severe mental disorders. The constructs measured by the BMQ are related to adherence in these patients.     

Mania in the medically ill

Manic symptoms frequently occur in patients with comorbid medical disorders and present a diagnostic and treatment challenge. Manic symptoms may be due to an independent psychiatric illness, may be induced or precipitated by a medical condition, or may result from medication or substance use. The presence of manic symptoms in medically ill patients can lead to misdiagnosis or complicate the management of comorbid medical illness. It is of paramount importance to identify the etiology of the mania and, in particular, differentiate primary from secondary mania. Management of mania in the medically ill should focus on treating the underlying medical condition, medication management (antipsychotic agents, mood stabilizers, and/or benzodiazepines), and psychotherapy (if needed). Selecting appropriate medication for treatment requires basic knowledge of the pharmacokinetics of the medications, their side effect profile, and drug-drug interaction. The majority of deficits accompanying secondary mania resolve with treatment of the underlying cause, and supportive psychopharmacology may be all that is needed, but if symptoms persist, patients may need medications for a longer duration.     

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.     

Exploring pretreatment weight trajectories in obese patients with binge eating disorder

Treatments for obese patients with binge eating disorder (BED) typically report modest weight losses despite substantial reductions in binge eating. Although the limited weight losses represent a limitation of existing treatments, an improved understanding of weight trajectories before treatment may provide a valuable context for interpreting such findings. The current study examined the weight trajectories of obese patients in the year before enrollment in primary care treatment for BED. Participants were a consecutive series of 68 obese patients with BED recruited from primary care centers. Doctoral-level clinicians administered structured clinical interviews to assess participants' weight history and eating behaviors. Participants also completed a self-report measure assessing eating and weight. Overall, participants reported a mean weight gain of 9.5 lb in the past year, although this overall average comprised remarkable heterogeneity in patterns of weight changes, which ranged from losing 40 lb to gaining 62 lb. Most participants (65%) gained weight, averaging 22.5 lb. Weight gain was associated with more frequent binge eating episodes and overeating at various times. Most obese patients with BED who present to treatment in a primary care setting reported having gained substantial amounts of weight during the previous year. Such weight trajectory findings suggest that the modest amounts of weight losses typically reported by treatment studies for this specific patient group may be more positive than previously thought. Specifically, although the weight losses typically produced by treatments aimed at reducing binge eating seem modest, they could be reinterpreted as potentially positive outcomes given that the treatments might be interrupting the course of recent and large weight gains.     

Reasons for Nonadherence to Psychiatric Medication and Cardiovascular Risk Factors Treatment Among Latino Bipolar Disorder Patients Living in Puerto Rico: A Qualitative Study

Latinos with bipolar disorder (BD) have a high rate of nonadherence to psychiatric medication and treatment for other medical conditions such as cardiovascular disease (CVD) risk factors than non-Latinos with BD. The aim of this study is to identify patients’ perspectives on the reasons for nonadherence to psychiatric medication and for CVD risk factors conditions in outpatients with BD. Three focus group sessions were held for a total of 22 adults ranging from 23 to 60 years old. Participants had BD, Type I/II and CVD risk factors. Audio-recordings of focus groups were transcribed and a content analysis was performed. Reasons identified as barriers to adherence were somewhat different for BD medications in comparison to CVD risk factors suggesting the need for integrated interventions targeting these barriers to adherence for both BD and CVD risk factors.