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.     

Antipsychotic induced weight gain in schizophrenia:mechanisms and management

The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible individual or team; and (iii) the adoption of clear structured protocols for clinicians to follow in case of clinically significant weight gain and metabolic issues, which should incorporate greater collaboration between various health professionals from psychiatric and medical specialist services.     

The heart of the matter: cardiometabolic care in youth with psychosis

Aim: Weight gain, obesity and metabolic disturbances in youth with psychosis are significant contributors to the health burden of people with psychosis, with a two‐ to threefold increase in rates compared with the general population and a 20% reduction in life expectancy. Several studies have now described cardiometabolic benefits of a range of interventions, including a structured diet and exercise programmes and metformin for patients receiving antipsychotic medications. Despite the development of Australian consensus guidelines and screening algorithms to detect such metabolic abnormalities, there is a lack of guidelines for clinicians to determine appropriate, timely, targeted prevention and intervention to manage these complications in the youth population. Methods: The Bondi Early Psychosis Programme targets young people (aged 15–25 years) experiencing their first episode of psychosis. This service has developed a model of metabolic screening and a treatment algorithm to provide clinicians with recommendations for targeted interventions. Results: Positive Cardiometabolic Health: an early intervention framework for patients on psychotropic medication describes a method for early detection, prevention and intervention strategies targeting antipsychotic‐induced metabolic abnormalities and cardiovascular risk factors. Conclusion: Although further research is required, there is sufficient evidence to support early intervention and prevention strategies to improve physical health outcomes in young people with first‐episode psychosis.     

Strategies for dosing and switching antipsychotics for optimal clinical management

Optimal clinical management of schizophrenia and bipolar disorder can be achieved through careful antipsychotic dosing and, if necessary, switching to another well-chosen antipsychotic using suitable switching strategies. For severely ill patients treated in clinical practice, adequate dosing may not result from following the relatively low dosing levels and abrupt titration schedules typically used in clinical registration trials. Data from recent effectiveness trials, naturalistic studies, and the Roadmap Expert Consensus Survey provide evidence of specific dose levels and titration schedules for antipsychotic agents that may be appropriate in clinical practice. Discontinuation and frequent switching of medication are common among patients treated with antipsychotics, but data suggest that an adequate trial of the first antipsychotic medication should be undertaken before switching to another antipsychotic medication. Making a decision to switch from a typical to an atypical antipsychotic or between atypical antipsychotics should involve consideration of variables relating to the patient, illness, medication, and the patient's environment. Switching can improve efficacy and tolerability but may also result in predictable side effects or withdrawal symptoms, including weight gain and metabolic effects as well as effects associated with prolactin changes. Many side effects that occur during switching are attributable to receptor profiles and antimuscarinic or antihistaminic blockade. Individualized switching strategies that include careful choice of medication, dose, and titration and tapering schedules; management of symptoms; and patient psychoeducation can reduce or treat side effects, increasing the likelihood of a successful switch and greater adherence and efficacy.     

Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives

Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.     

Metabolic monitoring for patients treated with antipsychotic medications.

OBJECTIVES: Metabolic side effects of antipsychotic treatment include weight gain, dyslipidemia and increased susceptibility to diabetes. Patients with schizophrenia have increased coronary heart disease mortality and reduced life expectancy. There is an urgent clinical need to monitor antipsychotic-treated patients for metabolic disturbance. Our objectives were to review published international monitoring guidelines, establish goals for metabolic monitoring, and make recommendations for practice. METHOD: We reviewed the major published consensus guidelines for metabolic monitoring of patients treated with antipsychotic medications and selectively reviewed practice guidelines for the management of diabetes, dyslipidemia, and hypertension. RESULTS: Patients with serious mental illness have markedly elevated rates of metabolic disturbance and limited access to general medical care. Monitoring, but not necessarily medical treatment of metabolic disorder, falls within the scope of psychiatric practice and should include screening for metabolic disturbance as well as tracking the effects of antipsychotic treatment. In addition, psychiatrists and psychiatric services should work toward facilitating patients' access to medical care. There is considerable consensus in the published guidelines. Areas of dissent include which patients to monitor, the utility of glucose tolerance testing, and the point at which to consider switching antipsychotics. CONCLUSION: We encourage clinicians to adopt a structured system for conducting and recording metabolic monitoring and to develop collaborations with family physicians, diabetes specialists, dieticians, and recreation therapists to facilitate appropriate medical care for antipsychotic-treated patients.     

The Risks and Benefits of Switching Antipsychotics: A Case Study Approach

PURPOSE.  Progression of metabolic illness in a patient with schizophrenia who was stabilized on an atypical antipsychotic is described using a case study framework. Risks and benefits of staying on current treatment versus switching to another agent and switching strategies are described.
CONCLUSIONS.  Switching an antipsychotic with more favorable side effects may improve metabolic parameters if other weight loss strategies have failed. Switching or stopping medications too quickly may exacerbate psychiatric symptoms. There is little evidence to support which is the best switching strategy.
PRACTICE IMPLICATIONS.  The psychiatric mental health nurse practitioner carries a significant responsibility of discussing risks and benefits of switching and closely monitoring the patient during a switch of medications. Ensuring that the patient decides and agrees upon the treatment plan will improve the overall outcome.     

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.     

Pharmacological Strategies to Counteract Antipsychotic-Induced Weight Gain and Metabolic Adverse Effects in Schizophrenia: A Systematic Review and Meta-analysis

Background: Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. Objective: To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Data Sources: Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Study Selection: Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Data Extraction: Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Data Synthesis: Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to −3.17 kg (95% CI: −4.44 to −1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.Key words: antipsychotic, meta-analysis, metabolic, concomitant, PRISMA, schizophrenia     

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.     

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.     

Behavioral treatment of obesity in patients taking antipsychotic medications

OBJECTIVE: Antipsychotic medications are associated with weight gain and metabolic dysregulation, yet little is known about the management of obesity among individuals with severe and persistent mental illness. Thus we sought to evaluate the potential utility of a behavioral weight control program for this population. METHOD: Outpatients receiving psychiatric care at a university medical center who had a body mass index (BMI; weight in kg/[height in m](2)) >or= 30 and were currently taking antipsychotic medication participated in a 12-week group behavioral weight control program. A medical chart review was conducted for each participant's body weight over the 10 months prior to beginning the program. A multiple baseline design was used to determine the impact of the intervention on BMI through 12-month posttreatment follow-up. We also assessed self-reported eating behavior, physical activity, and health-related quality of life. Data were collected from October 2000 to July 2003. RESULTS: Among 35 patients who began the program, 29 (83%) completed treatment, with mean (+/- SD) weight loss of 5.04 (+/- 7.52) pounds (p = .001) and improvements in eating, activity, and quality of life. At 3-month posttreatment follow-up (N = 27; 77%), total mean weight loss was 7.14 (+/- 11.47) pounds (p = .003). Results of a longitudinal model based on general estimating equations indicated that, relative to the pretreatment period, BMI decreased significantly during treatment and remained stable through 12-month posttreatment follow-up. CONCLUSION: Behavioral weight control is a promising approach to the treatment of obesity among outpatients taking antipsychotic medications, but longer and more robust interventions are needed.     

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.     

Schizophrenia and weight management: a systematic review of interventions to control weight

OBJECTIVE: Weight gain is a frequent side effect of antipsychotic medication which has serious implications for a patient's health and well being. This study systematically reviews the literature on the effectiveness of interventions designed to control weight gain in schizophrenia. METHOD: A systematic search strategy was conducted of major databases in addition to citation searches. Study quality was rated. RESULTS: Sixteen studies met the inclusion criteria. Five of eight pharmacological intervention studies reported small reductions in weight (<5% baseline body weight). All behavioural (including diet and/or exercise) interventions reported small reductions in, or maintenance of, weight. CONCLUSION: Weight loss may be difficult but it is not impossible. Given the inconsistent results, the widespread use of pharmacological interventions cannot be recommended. Both dietary and exercise counselling set within a behavioural modification programme is necessary for sustained weight control.     

Behavioural management of antipsychotic-induced weight gain: a review

OBJECTIVE: Although psychiatrists are aware of weight gain induced by atypical antipsychotics, only few studies on behavioural interventions in this patient group are published. This review aims to summarize the evidence on effectiveness of behavioural interventions for weight gain in the general population and in-patients treated with atypical antipsychotics. METHOD: Medline and Cochrane databases search for evidence on effectiveness of behavioural interventions. RESULTS: In general, behavioural approaches including, diet, exercise and drug treatments may be effective. There were only 13 studies of behavioural interventions for patients taking antipsychotic medication. No study met the criteria for a RCT. Calorie restriction in a controlled ward environment, structured counselling combined with cognitive behavioural therapy and counselling on life style and provision of rewards may potentially lead to weight loss. CONCLUSION: Currently only limited, methodologically flawed, evidence is available that behavioural interventions in overweight patients treated with antipsychotics, although intuitively appealing, actually work.     

Management of Weight Gain Associated with Antipsychotics

The prevalence of overweight and obesity in untreated patients with severe mental illness mimicks the trends seen in the general population. Furthermore, weight gain is likely to occur with the addition of pharmacotherapy with an antipsychotic. The literature does indicate that despite fundamental cognitive and psychosocial deficits seen in patients with severe and persistent mental disorders such as schizophrenia and bipolar disorder, it is possible to effectively manage weight gain in this population. In particular, behavioral interventions have been shown to be effective in the prevention and treatment of weight gain associated with antipsychotic therapy. Some success has also been seen with the use of adjunctive medication such as amantadine, histamine (H₂) antagonists, metformin, topiramate, and orlistat. Additional, prospective, controlled studies of long-term antipsychotic drug associated weight gain and its clinical consequences are needed in order to identify the most effective therapy for the reduction and maintenance of body weight in patients taking antipsychotic therapy.     

Obesity as a risk factor for antipsychotic noncompliance

OBJECTIVE: Weight gain is a common side effect of antipsychotic medications and is of particular concern with most of the newer "atypical" antipsychotics. It is, therefore, increasingly important to understand the impact of obesity and perceived weight problems on compliance with these medications. METHODS: A survey of treatment and health issues was mailed to local chapters of the National Alliance for the Mentally Ill (NAMI) and National Mental Health Association (NMHA), who distributed them to people with schizophrenia. Noncompliance was defined as a self-report of missing any antipsychotic medication in the previous month. The primary independent variables were (1) body mass index (BMI; weight [kg]/height [m2])-categorized as normal (< 25, n = 73), overweight (25-30, n = 104), or obese (> 30, n = 100)-and (2) subjective distress over weight gain. Other independent variables included demographics, medication attitudes, and treatment satisfaction. RESULT: BMI status and subjective distress from weight gain were predictors of noncompliance. Obese individuals were more than twice as likely as those with a normal BMI to report missing their medication (OR = 2.5; CI 1.1-5.5). A comprehensive model suggested that the primary mediator of noncompliance was distress over weight gain. CONCLUSIONS: There appears to be a significant, positive association between obesity and subjective distress from weight gain and medication noncompliance, even when accounting for other possible confounding factors.     

Comparing safety and tolerability of antipsychotic treatment

Certain modifiable risk factors for diabetes and cardiovascular disease need to be considered when prescribing antipsychotic medications. Antipsychotics may change a patient's weight, glucose, cholesterol, and triglycerides. These changes may lead to changes in cardiopulmonary health. If switching medications is not a viable option, the metabolic and cardiopulmonary risks may be minimized by monitoring certain behaviors such as smoking, exercise, diet, and medication adherence. The principals of primary prevention suggest the importance of lowering risk for disease by using monitoring and intervention approaches.