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Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

 

Carolyn Newbury, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

 

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Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

 

Carolyn Newbury, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

 

Carolyn Newbury, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

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A 32-year-old woman presents with knee pain on walking and elbow pain. She is 5 ft 6 in tall and weighs 187 lb (BMI 30.2). She was diagnosed with schizophrenia 2 years ago and began treatment with olanzapine at diagnosis; her symptoms currently are controlled, and she has tolerated the medication well. 

The patient says that she has been overweight since her teenage years and weighed 170 lb (BMI ~27) at age 30. However, she remained physically active until development of painful joints over the past 18 months. She works remotely full time and lives alone. She describes her long-standing diet as heavy on meat protein and light on vegetables and snacks and says it hasn't changed; she denies binge eating or other disordered eating. 

Physical exam reveals tender joints at knees and elbows and central obesity (waist circumference, 42 in). Blood pressure is 135/90 mm Hg. Lab results indicate a fasting glucose level of 115 mg/dL and a triglyceride level of 170 mg/dL. She is negative for rheumatoid factor. Radiography shows premature joint erosion at the knees and elbows.

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