Bilateral wrist pain with associated swelling consistent with synovitis pointed to an inflammatory arthritis confirmed by x-ray imaging. An elevated erythrocyte sedimentation rate (109 mm/hr), rheumatoid factor (314 IU/mL), and cyclic citrullinated peptide (34.5 EU/mL) confirmed the diagnosis of rheumatoid arthritis (RA). Hepatitis and tuberculosis screens were negative and uric acid was normal.

The patient’s radiographic imaging of the wrists revealed mild-to-moderate narrowing of the radiocarpal and midcarpal joints, multiple scattered cyst-like and erosive changes throughout, and mild-to-moderate soft tissue edema. These findings were consistent with a diagnosis of RA. Additionally, the radiographs showed cortical irregularity of the proximal ulnar aspect of the lunate, consistent with ulnar abutment syndrome, a degenerative condition in which the ulnar head abuts the triangular fibrocartilage complex and ulnar-sided carpal bones.

Some of the first changes that can be observed radiographically in RA include soft tissue swelling and periarticular osteopenia.¹ As the disease progresses, bony erosions, especially in the metacarpophalangeal and proximal interphalangeal joints, can be observed. Additional findings with active disease include joint space narrowing and deformities, such as joint subluxation. Erosions of cartilage and bone can also occur in some other forms of inflammatory and gouty arthropathies, so it is important to consider differential diagnoses in the case of ambiguous laboratory findings.

The primary disease-modifying antirheumatic drug (DMARD) used for treatment of RA is methotrexate.² DMARDs take weeks to months before there is noticeable improvement and should be used in combination with anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs or glucocorticoids. Response rates to DMARDs decrease over time. In the case of drug resistance, combination therapy (eg, methotrexate plus sulfasalazine and hydroxychloroquine, or methotrexate plus a tumor necrosis factor inhibitor) can be used. For acute flares, patients can undergo intra-articular glucocorticoid injections if a limited number of joints are affected. Widespread flares can be treated with oral glucocorticoids. Severe flares can be treated with pulse intravenous methylprednisolone.

Our patient was referred to Rheumatology for prompt treatment. He was started on DMARD therapy (methotrexate 12.5 mg weekly) with daily folic acid and a plan to increase the methotrexate to 25 mg after the third week of therapy. He was also prescribed oral prednisone to have on hand for flares, and azithromycin to treat possible future infections. Additionally, the patient underwent bilateral steroid wrist injections at the clinic.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Rachel Ruckman, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Bilateral wrist pain with associated swelling consistent with synovitis pointed to an inflammatory arthritis confirmed by x-ray imaging. An elevated erythrocyte sedimentation rate (109 mm/hr), rheumatoid factor (314 IU/mL), and cyclic citrullinated peptide (34.5 EU/mL) confirmed the diagnosis of rheumatoid arthritis (RA). Hepatitis and tuberculosis screens were negative and uric acid was normal.

The patient’s radiographic imaging of the wrists revealed mild-to-moderate narrowing of the radiocarpal and midcarpal joints, multiple scattered cyst-like and erosive changes throughout, and mild-to-moderate soft tissue edema. These findings were consistent with a diagnosis of RA. Additionally, the radiographs showed cortical irregularity of the proximal ulnar aspect of the lunate, consistent with ulnar abutment syndrome, a degenerative condition in which the ulnar head abuts the triangular fibrocartilage complex and ulnar-sided carpal bones.

Some of the first changes that can be observed radiographically in RA include soft tissue swelling and periarticular osteopenia.¹ As the disease progresses, bony erosions, especially in the metacarpophalangeal and proximal interphalangeal joints, can be observed. Additional findings with active disease include joint space narrowing and deformities, such as joint subluxation. Erosions of cartilage and bone can also occur in some other forms of inflammatory and gouty arthropathies, so it is important to consider differential diagnoses in the case of ambiguous laboratory findings.

The primary disease-modifying antirheumatic drug (DMARD) used for treatment of RA is methotrexate.² DMARDs take weeks to months before there is noticeable improvement and should be used in combination with anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs or glucocorticoids. Response rates to DMARDs decrease over time. In the case of drug resistance, combination therapy (eg, methotrexate plus sulfasalazine and hydroxychloroquine, or methotrexate plus a tumor necrosis factor inhibitor) can be used. For acute flares, patients can undergo intra-articular glucocorticoid injections if a limited number of joints are affected. Widespread flares can be treated with oral glucocorticoids. Severe flares can be treated with pulse intravenous methylprednisolone.

Our patient was referred to Rheumatology for prompt treatment. He was started on DMARD therapy (methotrexate 12.5 mg weekly) with daily folic acid and a plan to increase the methotrexate to 25 mg after the third week of therapy. He was also prescribed oral prednisone to have on hand for flares, and azithromycin to treat possible future infections. Additionally, the patient underwent bilateral steroid wrist injections at the clinic.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Rachel Ruckman, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Bilateral wrist pain with associated swelling consistent with synovitis pointed to an inflammatory arthritis confirmed by x-ray imaging. An elevated erythrocyte sedimentation rate (109 mm/hr), rheumatoid factor (314 IU/mL), and cyclic citrullinated peptide (34.5 EU/mL) confirmed the diagnosis of rheumatoid arthritis (RA). Hepatitis and tuberculosis screens were negative and uric acid was normal.

The patient’s radiographic imaging of the wrists revealed mild-to-moderate narrowing of the radiocarpal and midcarpal joints, multiple scattered cyst-like and erosive changes throughout, and mild-to-moderate soft tissue edema. These findings were consistent with a diagnosis of RA. Additionally, the radiographs showed cortical irregularity of the proximal ulnar aspect of the lunate, consistent with ulnar abutment syndrome, a degenerative condition in which the ulnar head abuts the triangular fibrocartilage complex and ulnar-sided carpal bones.

Some of the first changes that can be observed radiographically in RA include soft tissue swelling and periarticular osteopenia.¹ As the disease progresses, bony erosions, especially in the metacarpophalangeal and proximal interphalangeal joints, can be observed. Additional findings with active disease include joint space narrowing and deformities, such as joint subluxation. Erosions of cartilage and bone can also occur in some other forms of inflammatory and gouty arthropathies, so it is important to consider differential diagnoses in the case of ambiguous laboratory findings.

The primary disease-modifying antirheumatic drug (DMARD) used for treatment of RA is methotrexate.² DMARDs take weeks to months before there is noticeable improvement and should be used in combination with anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs or glucocorticoids. Response rates to DMARDs decrease over time. In the case of drug resistance, combination therapy (eg, methotrexate plus sulfasalazine and hydroxychloroquine, or methotrexate plus a tumor necrosis factor inhibitor) can be used. For acute flares, patients can undergo intra-articular glucocorticoid injections if a limited number of joints are affected. Widespread flares can be treated with oral glucocorticoids. Severe flares can be treated with pulse intravenous methylprednisolone.

Our patient was referred to Rheumatology for prompt treatment. He was started on DMARD therapy (methotrexate 12.5 mg weekly) with daily folic acid and a plan to increase the methotrexate to 25 mg after the third week of therapy. He was also prescribed oral prednisone to have on hand for flares, and azithromycin to treat possible future infections. Additionally, the patient underwent bilateral steroid wrist injections at the clinic.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Rachel Ruckman, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

CASE GI distress while taking clozapine

Mr. F, age 29, has a history of psychiatric hospitalizations for psychotic episodes. It took a herculean effort to get him to agree to try clozapine, to which he has experienced a modest to good response. Unfortunately, recently he has been experiencing significant upper gastrointestinal (GI) distress. He attributes this to clozapine, and asks if he can discontinue this medication.

HISTORY Nausea becomes severe

Mr. F, age 29, resides in a long-term residential setting for patients with serious mental illness who need additional support following acute hospitalization. He has treatment-refractory schizophrenia. He first developed symptoms at age 18, and experienced multiple psychotic episodes requiring psychiatric hospitalizations that lasted for months. He has had numerous antipsychotic trials and a course of electroconvulsive therapy, with limited benefit.

More recently, Mr. F’s symptoms began to stabilize on a medication regimen that includes clozapine, 350 mg/d at bedtime, and haloperidol, 2 mg/d. He has not required psychiatric hospitalization for the past year.

Within months of initiating clozapine, Mr. F starts to complain daily about symptoms of worsening abdominal pain, abdominal bloating, nausea, intermittent episodes of emesis, and heartburn. The symptoms begin when he wakes up, are worse in the morning, and persist throughout the morning. He has experienced occasional mild constipation, but no diarrhea or weight loss. There have been no major changes in his diet, addition of new medications, or significant use of nonsteroidal anti-inflammatory drugs.

Mr. F’s nausea worsens over the next several weeks, to the point he begins to significantly limit how much he eats to cope with it. His GI symptoms are also impacting his mood and daily functioning.

This is not Mr. F’s first experience with significant GI distress. A few months before his first psychotic episode, Mr. F began developing vision problems, joint and abdominal pain, and a general decline in social and academic functioning. At that time, he underwent a significant workup by both GI and integrative medicine, including stool testing, upper endoscopy, and a Cyrex panel (a complementary medicine approach to exploring for specific autoimmune conditions). Results were largely within expected parameters, though a hydrogen breath test was suggestive of possible small intestine bowel overgrowth. More recently, he has been adhering to a gluten-free diet, which his family felt may help prevent some of his physical symptoms as well as mitigate some of his psychotic symptoms. He now asks if he can stop taking clozapine.

[polldaddy:11008393]

EVALUATION Establishing the correct diagnosis

Initially, Mr. F is diagnosed with gastroesophageal reflux disease (GERD) and attempts to manage his symptoms with pharmacologic and diet-based interventions. He significantly cuts down on soda consumption, and undergoes trials of calcium carbonate, antiemetics, and a PPI. Unfortunately, no material improvements are noted, and he continued to experience significant upper GI distress, especially after meals.

The psychiatric treatment team, Mr. F, and his family seek consultation with a GI specialist, who recommends that Mr. F. undergo a nuclear medicine solid gastric emptying scintigraphy study to evaluate for gastroparesis (delayed gastric emptying).¹ Results demonstrate grade 3 gastroparesis, with 56% radiotracer retainment at 4 hours. Mr. F is relieved to finally have an explanation for his persistent GI symptoms, and discusses his treatment options with the GI consultant and psychiatry team.

Continue to: The authors’ observations...

Mr. F and his family are opposed to starting a dopamine antagonist such as metoclopramide or domperidone (the latter is not FDA-approved but is available by special application to the FDA). These are first-line treatments for gastroparesis, but Mr. F and his family do not want them because of the risk of tardive dyskinesia. This is consistent with their previously expressed concerns regarding first-generation antipsychotics, and is why Mr. F has only been treated with a very low dose of haloperidol while the clozapine was titrated. Instead, Mr. F, his family, the psychiatry treatment team, and the GI specialist agree to pursue a combination of a GI hypomotility diet—which includes frequent small meals (4 to 6 per day), ideally with low fiber, low fat, and increased fluid intake—and a trial of the second line agent for gastroparesis, erythromycin, a medication with known hepatic cytochrome P450 (CYP) drug-drug interactions that impacts the clearance of clozapine.

Shared decision making is an evidence-based approach to engaging patients in medical decision making. It allows clinicians to provide education on potential treatment options and includes a discussion of risks and benefits. It also includes an assessment of the patient’s understanding of their condition, explores attitudes towards treatment, and elicits patient values specific to the desired outcome. Even in very ill patients with schizophrenia, shared decision making has been demonstrated to increase patient perception of involvement in their own care and knowledge about their condition.² Using this framework, Mr. F and his family, as well as the GI and psychiatric teams, felt confident that the agreed-upon approach was the best one for Mr. F.

TREATMENT Erythromycin and continued clozapine

Mr. F. is started on erythromycin, 100 mg 3 times a day. Erythromycin is a prokinetic agent that acts as a motilin agonist and increases the rate of gastric emptying. The liquid formulation of the medication is a suspension typically taken in 3- to 4-week courses, with 1 week “off” to prevent tachyphylaxis.³ Compared to the tablet, the liquid suspension has higher bioavailability, allows for easier dose adjustment, and takes less time to reach peak serum concentrations, which make it the preferred formulation for gastroparesis treatment.

Per the GI consultant’s recommendation, Mr. F receives a total of 3 courses of erythromycin, with some improvement in the frequency of his nausea noted only during the third erythromycin course. His clozapine levels are closely monitored during this time, as well as symptoms of clozapine toxicity (ie, sedation, confusion, hypersalivation, seizures, myoclonic jerks), because erythromycin can directly affect clozapine levels.^4,5 Case reports suggest that when these 2 medications are taken concomitantly, erythromycin inhibits the metabolism of hepatic enzyme CYP3A4, causing increased plasma concentrations of clozapine. Before starting erythromycin, Mr. F’s clozapine levels were 809 ng/mL at 350 mg/d. During the erythromycin courses, his levels are 1,043 to 1,074 ng/mL, despite reducing clozapine to 300 mg/d. However, he does not experience any adverse effects of clozapine (including seizures), which were being monitored closely.

The authors’ observations

Clozapine is the most effective medication for treatment-refractory schizophrenia.⁶ Compared to the other second-generation antipsychotics, it is associated with a lower risk of rehospitalization and treatment discontinuation, a significant decrease of positive symptom burden, and a reduction in suicidality.^7,8 Unfortunately, clozapine use is not without significant risk. FDA black box warnings highlight severe neutropenia, myocarditis, seizures, and hypotension as potentially life-threatening adverse effects that require close monitoring.⁹

Recently, clinicians have increasingly focused on the underrecognized but well-established finding that clozapine can cause significant GI adverse effects. While constipation is a known adverse effect of other antipsychotics, a 2016 meta-analysis of 32 studies estimated that the pooled prevalence of clozapine-associated constipation was 31.2%, and showed that patients receiving clozapine were 3 times more likely to be constipated than patients receiving other antipsychotics (odds ratio 3.02, CI 1.91-4.77, P < .001, n = 11 studies).¹⁰ A 2012 review of 16 studies involving potentially lethal adverse effects of clozapine demonstrated that rates of agranulocytosis and GI hypomotility were nearly identical, but that mortality from constipation was 3.6 to 12.5 times higher than mortality from agranulocytosis.¹¹

In 2020, the FDA issued an increased warning regarding severe bowel-related complications in patients receiving clozapine, ranging in severity from mild discomfort to ileus, bowel obstruction, toxic megacolon, and death.⁹

As exemplified by Mr. F’s case, upper GI symptoms associated with clozapine also are distressing and can have a significant impact on quality of life. Dyspepsia is a common complaint in patients with chronic psychiatric illness. A study of 79 psychiatric inpatients hospitalized long-term found that 80% reported at least 1 symptom of dyspepsia.¹² There are few older studies describing the effect of clozapine on the upper GI system. We and others previously reported on significantly increased use of—not only antacids—but also H2 blockers and prokinetic agents after initiating clozapine, but sample sizes are small.^13-15 These older data and newer studies suggest that GERD is a common upper GI disorder diagnosis following clozapine initiation, perhaps reflecting a knowledge gap and infrequent use of the more complex testing required to confirm a diagnosis of GI motility disorders such as gastroparesis.

In a study of 17 patients receiving clozapine, wireless motility capsules were used to measure whole gut motility, including gastric emptying time, small bowel transit time, and colonic transit time. In 82% of patients, there was demonstrated GI hypomotility in at least 1 region, and 41% of participants exhibited delayed gastric emptying, with a cut-off time of >5 hours required for a gastroparesis diagnosis.¹⁶ This is significantly higher than the prevalence of gastroparesis observed in studies of the general community.¹⁷ The Table^18,19 summarizes the differences between GERD and gastroparesis.

OUTCOME Some improvement

Mr. F experiences limited improvement of some of his nausea symptoms during the third erythromycin cycle and returns to the gastroenterologist for a follow-up appointment. The GI specialist decides to discontinue erythromycin in view of potential drug-drug interactions and Mr. F’s elevated clozapine levels and the associated risks that might entail. Mr. F is again offered the D2 dopamine antagonist metoclopramide, but again refuses due to the risk for tardive dyskinesia. He is asked to continue the GI dysmotility diet. Mr. F finds some relief of nausea symptoms from an over-the-counter product for nausea (a nasal inhalant containing essential oils) and is advised to follow up with the GI specialist in 3 months. Shortly thereafter, he is discharged to live in a less restrictive supportive housing environment, and his follow-up psychiatric care is provided by an assertive community treatment team. Over the next several months, the dosage of clozapine is decreased to 250 mg/d. Mr. F initially experiences worsening psychiatric symptoms, but stabilizes thereafter. He then moves out of state to be closer to his family.

Bottom Line

In patients receiving clozapine, frequent nausea along with clustering of heartburn, abdominal pain, bloating, early satiety, and vomiting (especially after meals) may signal gastroparesis rather than gastroesophageal reflux disease. Such patients may require consultation with a gastroenterologist, a scintigraphy-based gastric emptying test, and treatment if gastroparesis is confirmed.
 

CASE GI distress while taking clozapine

Mr. F, age 29, has a history of psychiatric hospitalizations for psychotic episodes. It took a herculean effort to get him to agree to try clozapine, to which he has experienced a modest to good response. Unfortunately, recently he has been experiencing significant upper gastrointestinal (GI) distress. He attributes this to clozapine, and asks if he can discontinue this medication.

HISTORY Nausea becomes severe

Mr. F, age 29, resides in a long-term residential setting for patients with serious mental illness who need additional support following acute hospitalization. He has treatment-refractory schizophrenia. He first developed symptoms at age 18, and experienced multiple psychotic episodes requiring psychiatric hospitalizations that lasted for months. He has had numerous antipsychotic trials and a course of electroconvulsive therapy, with limited benefit.

More recently, Mr. F’s symptoms began to stabilize on a medication regimen that includes clozapine, 350 mg/d at bedtime, and haloperidol, 2 mg/d. He has not required psychiatric hospitalization for the past year.

Within months of initiating clozapine, Mr. F starts to complain daily about symptoms of worsening abdominal pain, abdominal bloating, nausea, intermittent episodes of emesis, and heartburn. The symptoms begin when he wakes up, are worse in the morning, and persist throughout the morning. He has experienced occasional mild constipation, but no diarrhea or weight loss. There have been no major changes in his diet, addition of new medications, or significant use of nonsteroidal anti-inflammatory drugs.

Mr. F’s nausea worsens over the next several weeks, to the point he begins to significantly limit how much he eats to cope with it. His GI symptoms are also impacting his mood and daily functioning.

This is not Mr. F’s first experience with significant GI distress. A few months before his first psychotic episode, Mr. F began developing vision problems, joint and abdominal pain, and a general decline in social and academic functioning. At that time, he underwent a significant workup by both GI and integrative medicine, including stool testing, upper endoscopy, and a Cyrex panel (a complementary medicine approach to exploring for specific autoimmune conditions). Results were largely within expected parameters, though a hydrogen breath test was suggestive of possible small intestine bowel overgrowth. More recently, he has been adhering to a gluten-free diet, which his family felt may help prevent some of his physical symptoms as well as mitigate some of his psychotic symptoms. He now asks if he can stop taking clozapine.

[polldaddy:11008393]

EVALUATION Establishing the correct diagnosis

Initially, Mr. F is diagnosed with gastroesophageal reflux disease (GERD) and attempts to manage his symptoms with pharmacologic and diet-based interventions. He significantly cuts down on soda consumption, and undergoes trials of calcium carbonate, antiemetics, and a PPI. Unfortunately, no material improvements are noted, and he continued to experience significant upper GI distress, especially after meals.

The psychiatric treatment team, Mr. F, and his family seek consultation with a GI specialist, who recommends that Mr. F. undergo a nuclear medicine solid gastric emptying scintigraphy study to evaluate for gastroparesis (delayed gastric emptying).¹ Results demonstrate grade 3 gastroparesis, with 56% radiotracer retainment at 4 hours. Mr. F is relieved to finally have an explanation for his persistent GI symptoms, and discusses his treatment options with the GI consultant and psychiatry team.

Continue to: The authors’ observations...

Mr. F and his family are opposed to starting a dopamine antagonist such as metoclopramide or domperidone (the latter is not FDA-approved but is available by special application to the FDA). These are first-line treatments for gastroparesis, but Mr. F and his family do not want them because of the risk of tardive dyskinesia. This is consistent with their previously expressed concerns regarding first-generation antipsychotics, and is why Mr. F has only been treated with a very low dose of haloperidol while the clozapine was titrated. Instead, Mr. F, his family, the psychiatry treatment team, and the GI specialist agree to pursue a combination of a GI hypomotility diet—which includes frequent small meals (4 to 6 per day), ideally with low fiber, low fat, and increased fluid intake—and a trial of the second line agent for gastroparesis, erythromycin, a medication with known hepatic cytochrome P450 (CYP) drug-drug interactions that impacts the clearance of clozapine.

Shared decision making is an evidence-based approach to engaging patients in medical decision making. It allows clinicians to provide education on potential treatment options and includes a discussion of risks and benefits. It also includes an assessment of the patient’s understanding of their condition, explores attitudes towards treatment, and elicits patient values specific to the desired outcome. Even in very ill patients with schizophrenia, shared decision making has been demonstrated to increase patient perception of involvement in their own care and knowledge about their condition.² Using this framework, Mr. F and his family, as well as the GI and psychiatric teams, felt confident that the agreed-upon approach was the best one for Mr. F.

TREATMENT Erythromycin and continued clozapine

Mr. F. is started on erythromycin, 100 mg 3 times a day. Erythromycin is a prokinetic agent that acts as a motilin agonist and increases the rate of gastric emptying. The liquid formulation of the medication is a suspension typically taken in 3- to 4-week courses, with 1 week “off” to prevent tachyphylaxis.³ Compared to the tablet, the liquid suspension has higher bioavailability, allows for easier dose adjustment, and takes less time to reach peak serum concentrations, which make it the preferred formulation for gastroparesis treatment.

Per the GI consultant’s recommendation, Mr. F receives a total of 3 courses of erythromycin, with some improvement in the frequency of his nausea noted only during the third erythromycin course. His clozapine levels are closely monitored during this time, as well as symptoms of clozapine toxicity (ie, sedation, confusion, hypersalivation, seizures, myoclonic jerks), because erythromycin can directly affect clozapine levels.^4,5 Case reports suggest that when these 2 medications are taken concomitantly, erythromycin inhibits the metabolism of hepatic enzyme CYP3A4, causing increased plasma concentrations of clozapine. Before starting erythromycin, Mr. F’s clozapine levels were 809 ng/mL at 350 mg/d. During the erythromycin courses, his levels are 1,043 to 1,074 ng/mL, despite reducing clozapine to 300 mg/d. However, he does not experience any adverse effects of clozapine (including seizures), which were being monitored closely.

The authors’ observations

Clozapine is the most effective medication for treatment-refractory schizophrenia.⁶ Compared to the other second-generation antipsychotics, it is associated with a lower risk of rehospitalization and treatment discontinuation, a significant decrease of positive symptom burden, and a reduction in suicidality.^7,8 Unfortunately, clozapine use is not without significant risk. FDA black box warnings highlight severe neutropenia, myocarditis, seizures, and hypotension as potentially life-threatening adverse effects that require close monitoring.⁹

Recently, clinicians have increasingly focused on the underrecognized but well-established finding that clozapine can cause significant GI adverse effects. While constipation is a known adverse effect of other antipsychotics, a 2016 meta-analysis of 32 studies estimated that the pooled prevalence of clozapine-associated constipation was 31.2%, and showed that patients receiving clozapine were 3 times more likely to be constipated than patients receiving other antipsychotics (odds ratio 3.02, CI 1.91-4.77, P < .001, n = 11 studies).¹⁰ A 2012 review of 16 studies involving potentially lethal adverse effects of clozapine demonstrated that rates of agranulocytosis and GI hypomotility were nearly identical, but that mortality from constipation was 3.6 to 12.5 times higher than mortality from agranulocytosis.¹¹

In 2020, the FDA issued an increased warning regarding severe bowel-related complications in patients receiving clozapine, ranging in severity from mild discomfort to ileus, bowel obstruction, toxic megacolon, and death.⁹

As exemplified by Mr. F’s case, upper GI symptoms associated with clozapine also are distressing and can have a significant impact on quality of life. Dyspepsia is a common complaint in patients with chronic psychiatric illness. A study of 79 psychiatric inpatients hospitalized long-term found that 80% reported at least 1 symptom of dyspepsia.¹² There are few older studies describing the effect of clozapine on the upper GI system. We and others previously reported on significantly increased use of—not only antacids—but also H2 blockers and prokinetic agents after initiating clozapine, but sample sizes are small.^13-15 These older data and newer studies suggest that GERD is a common upper GI disorder diagnosis following clozapine initiation, perhaps reflecting a knowledge gap and infrequent use of the more complex testing required to confirm a diagnosis of GI motility disorders such as gastroparesis.

In a study of 17 patients receiving clozapine, wireless motility capsules were used to measure whole gut motility, including gastric emptying time, small bowel transit time, and colonic transit time. In 82% of patients, there was demonstrated GI hypomotility in at least 1 region, and 41% of participants exhibited delayed gastric emptying, with a cut-off time of >5 hours required for a gastroparesis diagnosis.¹⁶ This is significantly higher than the prevalence of gastroparesis observed in studies of the general community.¹⁷ The Table^18,19 summarizes the differences between GERD and gastroparesis.

OUTCOME Some improvement

Mr. F experiences limited improvement of some of his nausea symptoms during the third erythromycin cycle and returns to the gastroenterologist for a follow-up appointment. The GI specialist decides to discontinue erythromycin in view of potential drug-drug interactions and Mr. F’s elevated clozapine levels and the associated risks that might entail. Mr. F is again offered the D2 dopamine antagonist metoclopramide, but again refuses due to the risk for tardive dyskinesia. He is asked to continue the GI dysmotility diet. Mr. F finds some relief of nausea symptoms from an over-the-counter product for nausea (a nasal inhalant containing essential oils) and is advised to follow up with the GI specialist in 3 months. Shortly thereafter, he is discharged to live in a less restrictive supportive housing environment, and his follow-up psychiatric care is provided by an assertive community treatment team. Over the next several months, the dosage of clozapine is decreased to 250 mg/d. Mr. F initially experiences worsening psychiatric symptoms, but stabilizes thereafter. He then moves out of state to be closer to his family.

Bottom Line

In patients receiving clozapine, frequent nausea along with clustering of heartburn, abdominal pain, bloating, early satiety, and vomiting (especially after meals) may signal gastroparesis rather than gastroesophageal reflux disease. Such patients may require consultation with a gastroenterologist, a scintigraphy-based gastric emptying test, and treatment if gastroparesis is confirmed.
 

CASE GI distress while taking clozapine

Mr. F, age 29, has a history of psychiatric hospitalizations for psychotic episodes. It took a herculean effort to get him to agree to try clozapine, to which he has experienced a modest to good response. Unfortunately, recently he has been experiencing significant upper gastrointestinal (GI) distress. He attributes this to clozapine, and asks if he can discontinue this medication.

HISTORY Nausea becomes severe

Mr. F, age 29, resides in a long-term residential setting for patients with serious mental illness who need additional support following acute hospitalization. He has treatment-refractory schizophrenia. He first developed symptoms at age 18, and experienced multiple psychotic episodes requiring psychiatric hospitalizations that lasted for months. He has had numerous antipsychotic trials and a course of electroconvulsive therapy, with limited benefit.

More recently, Mr. F’s symptoms began to stabilize on a medication regimen that includes clozapine, 350 mg/d at bedtime, and haloperidol, 2 mg/d. He has not required psychiatric hospitalization for the past year.

Within months of initiating clozapine, Mr. F starts to complain daily about symptoms of worsening abdominal pain, abdominal bloating, nausea, intermittent episodes of emesis, and heartburn. The symptoms begin when he wakes up, are worse in the morning, and persist throughout the morning. He has experienced occasional mild constipation, but no diarrhea or weight loss. There have been no major changes in his diet, addition of new medications, or significant use of nonsteroidal anti-inflammatory drugs.

Mr. F’s nausea worsens over the next several weeks, to the point he begins to significantly limit how much he eats to cope with it. His GI symptoms are also impacting his mood and daily functioning.

This is not Mr. F’s first experience with significant GI distress. A few months before his first psychotic episode, Mr. F began developing vision problems, joint and abdominal pain, and a general decline in social and academic functioning. At that time, he underwent a significant workup by both GI and integrative medicine, including stool testing, upper endoscopy, and a Cyrex panel (a complementary medicine approach to exploring for specific autoimmune conditions). Results were largely within expected parameters, though a hydrogen breath test was suggestive of possible small intestine bowel overgrowth. More recently, he has been adhering to a gluten-free diet, which his family felt may help prevent some of his physical symptoms as well as mitigate some of his psychotic symptoms. He now asks if he can stop taking clozapine.

[polldaddy:11008393]

EVALUATION Establishing the correct diagnosis

Initially, Mr. F is diagnosed with gastroesophageal reflux disease (GERD) and attempts to manage his symptoms with pharmacologic and diet-based interventions. He significantly cuts down on soda consumption, and undergoes trials of calcium carbonate, antiemetics, and a PPI. Unfortunately, no material improvements are noted, and he continued to experience significant upper GI distress, especially after meals.

The psychiatric treatment team, Mr. F, and his family seek consultation with a GI specialist, who recommends that Mr. F. undergo a nuclear medicine solid gastric emptying scintigraphy study to evaluate for gastroparesis (delayed gastric emptying).¹ Results demonstrate grade 3 gastroparesis, with 56% radiotracer retainment at 4 hours. Mr. F is relieved to finally have an explanation for his persistent GI symptoms, and discusses his treatment options with the GI consultant and psychiatry team.

Continue to: The authors’ observations...

Mr. F and his family are opposed to starting a dopamine antagonist such as metoclopramide or domperidone (the latter is not FDA-approved but is available by special application to the FDA). These are first-line treatments for gastroparesis, but Mr. F and his family do not want them because of the risk of tardive dyskinesia. This is consistent with their previously expressed concerns regarding first-generation antipsychotics, and is why Mr. F has only been treated with a very low dose of haloperidol while the clozapine was titrated. Instead, Mr. F, his family, the psychiatry treatment team, and the GI specialist agree to pursue a combination of a GI hypomotility diet—which includes frequent small meals (4 to 6 per day), ideally with low fiber, low fat, and increased fluid intake—and a trial of the second line agent for gastroparesis, erythromycin, a medication with known hepatic cytochrome P450 (CYP) drug-drug interactions that impacts the clearance of clozapine.

Shared decision making is an evidence-based approach to engaging patients in medical decision making. It allows clinicians to provide education on potential treatment options and includes a discussion of risks and benefits. It also includes an assessment of the patient’s understanding of their condition, explores attitudes towards treatment, and elicits patient values specific to the desired outcome. Even in very ill patients with schizophrenia, shared decision making has been demonstrated to increase patient perception of involvement in their own care and knowledge about their condition.² Using this framework, Mr. F and his family, as well as the GI and psychiatric teams, felt confident that the agreed-upon approach was the best one for Mr. F.

TREATMENT Erythromycin and continued clozapine

Mr. F. is started on erythromycin, 100 mg 3 times a day. Erythromycin is a prokinetic agent that acts as a motilin agonist and increases the rate of gastric emptying. The liquid formulation of the medication is a suspension typically taken in 3- to 4-week courses, with 1 week “off” to prevent tachyphylaxis.³ Compared to the tablet, the liquid suspension has higher bioavailability, allows for easier dose adjustment, and takes less time to reach peak serum concentrations, which make it the preferred formulation for gastroparesis treatment.

Per the GI consultant’s recommendation, Mr. F receives a total of 3 courses of erythromycin, with some improvement in the frequency of his nausea noted only during the third erythromycin course. His clozapine levels are closely monitored during this time, as well as symptoms of clozapine toxicity (ie, sedation, confusion, hypersalivation, seizures, myoclonic jerks), because erythromycin can directly affect clozapine levels.^4,5 Case reports suggest that when these 2 medications are taken concomitantly, erythromycin inhibits the metabolism of hepatic enzyme CYP3A4, causing increased plasma concentrations of clozapine. Before starting erythromycin, Mr. F’s clozapine levels were 809 ng/mL at 350 mg/d. During the erythromycin courses, his levels are 1,043 to 1,074 ng/mL, despite reducing clozapine to 300 mg/d. However, he does not experience any adverse effects of clozapine (including seizures), which were being monitored closely.

The authors’ observations

Clozapine is the most effective medication for treatment-refractory schizophrenia.⁶ Compared to the other second-generation antipsychotics, it is associated with a lower risk of rehospitalization and treatment discontinuation, a significant decrease of positive symptom burden, and a reduction in suicidality.^7,8 Unfortunately, clozapine use is not without significant risk. FDA black box warnings highlight severe neutropenia, myocarditis, seizures, and hypotension as potentially life-threatening adverse effects that require close monitoring.⁹

Recently, clinicians have increasingly focused on the underrecognized but well-established finding that clozapine can cause significant GI adverse effects. While constipation is a known adverse effect of other antipsychotics, a 2016 meta-analysis of 32 studies estimated that the pooled prevalence of clozapine-associated constipation was 31.2%, and showed that patients receiving clozapine were 3 times more likely to be constipated than patients receiving other antipsychotics (odds ratio 3.02, CI 1.91-4.77, P < .001, n = 11 studies).¹⁰ A 2012 review of 16 studies involving potentially lethal adverse effects of clozapine demonstrated that rates of agranulocytosis and GI hypomotility were nearly identical, but that mortality from constipation was 3.6 to 12.5 times higher than mortality from agranulocytosis.¹¹

In 2020, the FDA issued an increased warning regarding severe bowel-related complications in patients receiving clozapine, ranging in severity from mild discomfort to ileus, bowel obstruction, toxic megacolon, and death.⁹

As exemplified by Mr. F’s case, upper GI symptoms associated with clozapine also are distressing and can have a significant impact on quality of life. Dyspepsia is a common complaint in patients with chronic psychiatric illness. A study of 79 psychiatric inpatients hospitalized long-term found that 80% reported at least 1 symptom of dyspepsia.¹² There are few older studies describing the effect of clozapine on the upper GI system. We and others previously reported on significantly increased use of—not only antacids—but also H2 blockers and prokinetic agents after initiating clozapine, but sample sizes are small.^13-15 These older data and newer studies suggest that GERD is a common upper GI disorder diagnosis following clozapine initiation, perhaps reflecting a knowledge gap and infrequent use of the more complex testing required to confirm a diagnosis of GI motility disorders such as gastroparesis.

In a study of 17 patients receiving clozapine, wireless motility capsules were used to measure whole gut motility, including gastric emptying time, small bowel transit time, and colonic transit time. In 82% of patients, there was demonstrated GI hypomotility in at least 1 region, and 41% of participants exhibited delayed gastric emptying, with a cut-off time of >5 hours required for a gastroparesis diagnosis.¹⁶ This is significantly higher than the prevalence of gastroparesis observed in studies of the general community.¹⁷ The Table^18,19 summarizes the differences between GERD and gastroparesis.

OUTCOME Some improvement

Mr. F experiences limited improvement of some of his nausea symptoms during the third erythromycin cycle and returns to the gastroenterologist for a follow-up appointment. The GI specialist decides to discontinue erythromycin in view of potential drug-drug interactions and Mr. F’s elevated clozapine levels and the associated risks that might entail. Mr. F is again offered the D2 dopamine antagonist metoclopramide, but again refuses due to the risk for tardive dyskinesia. He is asked to continue the GI dysmotility diet. Mr. F finds some relief of nausea symptoms from an over-the-counter product for nausea (a nasal inhalant containing essential oils) and is advised to follow up with the GI specialist in 3 months. Shortly thereafter, he is discharged to live in a less restrictive supportive housing environment, and his follow-up psychiatric care is provided by an assertive community treatment team. Over the next several months, the dosage of clozapine is decreased to 250 mg/d. Mr. F initially experiences worsening psychiatric symptoms, but stabilizes thereafter. He then moves out of state to be closer to his family.

Bottom Line

In patients receiving clozapine, frequent nausea along with clustering of heartburn, abdominal pain, bloating, early satiety, and vomiting (especially after meals) may signal gastroparesis rather than gastroesophageal reflux disease. Such patients may require consultation with a gastroenterologist, a scintigraphy-based gastric emptying test, and treatment if gastroparesis is confirmed.
 

In non–small cell lung cancer (NSCLC), earlier detection may be an under-appreciated factor in recent trends of declining mortality, according to a new analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registries published in JAMA Network Open. Between 2006 and 2016, a stage shift occurred with an increase in stage 1 and 2 diagnoses and a decrease in stage 3 and 4 diagnoses.

While targeted therapy and immunotherapy have rightfully been credited with improved NSCLC survival, the new results underline the importance of screening, according to study author Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology and the associate director for population science at the Tisch Cancer Institute at Mount Sinai, New York.

She noted that the average survival for stage 1 or stage 2 patients was 57 months, but just 7 months when the stage diagnosis was 3 or 4. “So being diagnosed with stage 1 and 2 is a major driver of better survival,” said Dr. Taioli in an interview.

The study included 312,382 individuals diagnosed with NSCLC (53.4% male; median age, 68). Incidence-based, 5-year mortality declined by 3.7% (95% confidence interval, 3.4%-4.1%). Stage 1 or 2 diagnoses increased from 26.5% to 31.2% of diagnoses between 2006 and 2016 (average annual percentage change, 1.5%; 95% CI, 0.5%-2.5%).

“Immunotherapy is a very exciting field. And it is an important contributor for people who have a disease that can be treated with immunotherapy, so that’s why people focus on that. But if you can diagnose the cancer earlier, that’s the best bet,” Dr. Taioli said.

Unfortunately, many patients and physicians haven’t received that message. Even though computed tomography lung cancer screening is covered by Medicare for current or former smokers, only about 7% of eligible patients undergo annual screening. Dr. Taioli said that a belief persists that lung cancer is so deadly that early detection isn’t effective.

But advances in therapy and surgery have changed that outlook. “It’s not true anymore. People don’t know, and physicians are not educated to the idea that lung cancer can be diagnosed earlier and save lives,” she said.

People who have quit smoking may be relatively easy to convince. “They made a big step, because quitting smoking is incredibly hard. I think they will be amenable to screening because they are in a phase [of life] in which they want to take care of themselves. The physician should really explain the benefits, and I don’t think they do it very clearly now,” Dr. Taioli said.

The study is limited by its retrospective nature, and it did not include information on diagnostic method or many NSCLC risk factors.

Dr. Taioli has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), earlier detection may be an under-appreciated factor in recent trends of declining mortality, according to a new analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registries published in JAMA Network Open. Between 2006 and 2016, a stage shift occurred with an increase in stage 1 and 2 diagnoses and a decrease in stage 3 and 4 diagnoses.

While targeted therapy and immunotherapy have rightfully been credited with improved NSCLC survival, the new results underline the importance of screening, according to study author Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology and the associate director for population science at the Tisch Cancer Institute at Mount Sinai, New York.

She noted that the average survival for stage 1 or stage 2 patients was 57 months, but just 7 months when the stage diagnosis was 3 or 4. “So being diagnosed with stage 1 and 2 is a major driver of better survival,” said Dr. Taioli in an interview.

The study included 312,382 individuals diagnosed with NSCLC (53.4% male; median age, 68). Incidence-based, 5-year mortality declined by 3.7% (95% confidence interval, 3.4%-4.1%). Stage 1 or 2 diagnoses increased from 26.5% to 31.2% of diagnoses between 2006 and 2016 (average annual percentage change, 1.5%; 95% CI, 0.5%-2.5%).

“Immunotherapy is a very exciting field. And it is an important contributor for people who have a disease that can be treated with immunotherapy, so that’s why people focus on that. But if you can diagnose the cancer earlier, that’s the best bet,” Dr. Taioli said.

Unfortunately, many patients and physicians haven’t received that message. Even though computed tomography lung cancer screening is covered by Medicare for current or former smokers, only about 7% of eligible patients undergo annual screening. Dr. Taioli said that a belief persists that lung cancer is so deadly that early detection isn’t effective.

But advances in therapy and surgery have changed that outlook. “It’s not true anymore. People don’t know, and physicians are not educated to the idea that lung cancer can be diagnosed earlier and save lives,” she said.

People who have quit smoking may be relatively easy to convince. “They made a big step, because quitting smoking is incredibly hard. I think they will be amenable to screening because they are in a phase [of life] in which they want to take care of themselves. The physician should really explain the benefits, and I don’t think they do it very clearly now,” Dr. Taioli said.

The study is limited by its retrospective nature, and it did not include information on diagnostic method or many NSCLC risk factors.

Dr. Taioli has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), earlier detection may be an under-appreciated factor in recent trends of declining mortality, according to a new analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registries published in JAMA Network Open. Between 2006 and 2016, a stage shift occurred with an increase in stage 1 and 2 diagnoses and a decrease in stage 3 and 4 diagnoses.

While targeted therapy and immunotherapy have rightfully been credited with improved NSCLC survival, the new results underline the importance of screening, according to study author Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology and the associate director for population science at the Tisch Cancer Institute at Mount Sinai, New York.

She noted that the average survival for stage 1 or stage 2 patients was 57 months, but just 7 months when the stage diagnosis was 3 or 4. “So being diagnosed with stage 1 and 2 is a major driver of better survival,” said Dr. Taioli in an interview.

The study included 312,382 individuals diagnosed with NSCLC (53.4% male; median age, 68). Incidence-based, 5-year mortality declined by 3.7% (95% confidence interval, 3.4%-4.1%). Stage 1 or 2 diagnoses increased from 26.5% to 31.2% of diagnoses between 2006 and 2016 (average annual percentage change, 1.5%; 95% CI, 0.5%-2.5%).

“Immunotherapy is a very exciting field. And it is an important contributor for people who have a disease that can be treated with immunotherapy, so that’s why people focus on that. But if you can diagnose the cancer earlier, that’s the best bet,” Dr. Taioli said.

Unfortunately, many patients and physicians haven’t received that message. Even though computed tomography lung cancer screening is covered by Medicare for current or former smokers, only about 7% of eligible patients undergo annual screening. Dr. Taioli said that a belief persists that lung cancer is so deadly that early detection isn’t effective.

But advances in therapy and surgery have changed that outlook. “It’s not true anymore. People don’t know, and physicians are not educated to the idea that lung cancer can be diagnosed earlier and save lives,” she said.

People who have quit smoking may be relatively easy to convince. “They made a big step, because quitting smoking is incredibly hard. I think they will be amenable to screening because they are in a phase [of life] in which they want to take care of themselves. The physician should really explain the benefits, and I don’t think they do it very clearly now,” Dr. Taioli said.

The study is limited by its retrospective nature, and it did not include information on diagnostic method or many NSCLC risk factors.

Dr. Taioli has no relevant financial disclosures.

As a health care provider, I have always been interested in topics that concern incarcerated citizens, whether the discussion is related to the pursuit of aggressive care or jurisprudence in general. Additionally, I have followed the issue of capital punishment for most of my career, wondering if our democracy would continue this form of punishment for violent crimes.

In the early 2000s, public opinion moved away from capital punishment. The days of executing violent criminals such as Ted Bundy (who was killed in the electric chair in 1989) seemed to be in the rearview mirror. The ability of prison systems to obtain drugs for execution had become arduous, and Americans appeared disinterested in continuing with the process. Slowly, states began opting out of executions. Currently, 27 U.S. states offer the death penalty as an option at prosecution.
 

Botched executions

So far in 2021, 11 prisoners have been put to death by the federal government as well as five states, using either a one-drug or three-drug intravenous protocol. Of those prisoners, one was female.

The length of time from sentencing to date of execution varied from a low of 9 years to a high of 29 years, according to the Death Penalty Information Center. Of the executions performed this year, one was considered “botched.” The victim convulsed and vomited for several minutes before his ultimate demise. In fact, in the history of using the death penalty, from 1890 to 2010, approximately 3% of total executions (276 prisoners) were botched. They involved failed electric shocks, convulsions, labored breathing, and in one particularly horrific incident, a victim who was shot in the hip and abdomen by a firing squad and took several minutes to die.

One of the more difficult tasks for conducting an execution is intravenous access, with acquisition of an intravenous site proving to be a common issue. Another concern involves intravenous efficacy, or failure of the site to remain patent until death is achieved. That is why a few states that still practice capital punishment have returned to an electric chair option for execution (the method is chosen by the prisoner).
 

Majority favor capital punishment

But why do most Americans believe we need the death penalty? According to a 2021 poll by the Pew Research Center, 60% of U.S. citizens favor the use of capital punishment for those convicted of murder, including 27% who strongly favor its use. About 4 in 10 oppose the punishment, but only 15% are strongly opposed. The belief of those who favor retaining execution is that use of the death penalty deters violent crime.

Surprisingly, the American South has both the highest murder rate in the country and the highest percentage of executions. This geographic area encompasses 81% of the nation’s executions. A 2012 National Research Council poll determined that studies claiming the death penalty deters violent crime are “fundamentally flawed.” States that have abolished the death penalty do not show an increase in murder rates; in fact, the opposite is true, the organization concluded.

Since 1990, states without death penalty punishment have had consistently lower murder rates than those that retain capital punishment.
 

Where does that leave us?

Place my attitude in the column labeled “undecided.” I would love to believe capital punishment is a deterrent to violent crime, yet statistics do not prove the hypothesis to be true. We live in one of the more violent times in history, with mass shootings becoming commonplace. Large-scale retail theft has also been on the rise, especially in recent weeks.

The idea of severe punishment for heinous crime appeals to me, yet in 2001 Timothy McVeigh was executed after eating ice cream and gazing at the moon. His treatment before execution and the length of time he served were in opposition to other inmates sentenced to death. This, despite being punished for killing 168 people (including 19 children) in the Oklahoma City bombings.

I know we cannot be complacent. Violent crime needs to be reduced, and Americans need to feel safe. The process for achieving that goal? You tell me.
 

Nurses in prisons

About 1% of employed nurses (i.e., close to 21,000) in the United States work in prisons. This figure does not include the many LPNs and unlicensed assistive personnel who are also working in the field and may underrepresent actual numbers.

Correctional nurses have their own scope and standards of practice. They demonstrate superb assessment skills and organization.

If you can hire a correctional nurse, or even aspire to be one, do not hesitate. Patients will thank you.

A version of this article first appeared on Medscape.com.

As a health care provider, I have always been interested in topics that concern incarcerated citizens, whether the discussion is related to the pursuit of aggressive care or jurisprudence in general. Additionally, I have followed the issue of capital punishment for most of my career, wondering if our democracy would continue this form of punishment for violent crimes.

In the early 2000s, public opinion moved away from capital punishment. The days of executing violent criminals such as Ted Bundy (who was killed in the electric chair in 1989) seemed to be in the rearview mirror. The ability of prison systems to obtain drugs for execution had become arduous, and Americans appeared disinterested in continuing with the process. Slowly, states began opting out of executions. Currently, 27 U.S. states offer the death penalty as an option at prosecution.
 

Botched executions

So far in 2021, 11 prisoners have been put to death by the federal government as well as five states, using either a one-drug or three-drug intravenous protocol. Of those prisoners, one was female.

The length of time from sentencing to date of execution varied from a low of 9 years to a high of 29 years, according to the Death Penalty Information Center. Of the executions performed this year, one was considered “botched.” The victim convulsed and vomited for several minutes before his ultimate demise. In fact, in the history of using the death penalty, from 1890 to 2010, approximately 3% of total executions (276 prisoners) were botched. They involved failed electric shocks, convulsions, labored breathing, and in one particularly horrific incident, a victim who was shot in the hip and abdomen by a firing squad and took several minutes to die.

One of the more difficult tasks for conducting an execution is intravenous access, with acquisition of an intravenous site proving to be a common issue. Another concern involves intravenous efficacy, or failure of the site to remain patent until death is achieved. That is why a few states that still practice capital punishment have returned to an electric chair option for execution (the method is chosen by the prisoner).
 

Majority favor capital punishment

But why do most Americans believe we need the death penalty? According to a 2021 poll by the Pew Research Center, 60% of U.S. citizens favor the use of capital punishment for those convicted of murder, including 27% who strongly favor its use. About 4 in 10 oppose the punishment, but only 15% are strongly opposed. The belief of those who favor retaining execution is that use of the death penalty deters violent crime.

Surprisingly, the American South has both the highest murder rate in the country and the highest percentage of executions. This geographic area encompasses 81% of the nation’s executions. A 2012 National Research Council poll determined that studies claiming the death penalty deters violent crime are “fundamentally flawed.” States that have abolished the death penalty do not show an increase in murder rates; in fact, the opposite is true, the organization concluded.

Since 1990, states without death penalty punishment have had consistently lower murder rates than those that retain capital punishment.
 

Where does that leave us?

Place my attitude in the column labeled “undecided.” I would love to believe capital punishment is a deterrent to violent crime, yet statistics do not prove the hypothesis to be true. We live in one of the more violent times in history, with mass shootings becoming commonplace. Large-scale retail theft has also been on the rise, especially in recent weeks.

The idea of severe punishment for heinous crime appeals to me, yet in 2001 Timothy McVeigh was executed after eating ice cream and gazing at the moon. His treatment before execution and the length of time he served were in opposition to other inmates sentenced to death. This, despite being punished for killing 168 people (including 19 children) in the Oklahoma City bombings.

I know we cannot be complacent. Violent crime needs to be reduced, and Americans need to feel safe. The process for achieving that goal? You tell me.
 

Nurses in prisons

About 1% of employed nurses (i.e., close to 21,000) in the United States work in prisons. This figure does not include the many LPNs and unlicensed assistive personnel who are also working in the field and may underrepresent actual numbers.

Correctional nurses have their own scope and standards of practice. They demonstrate superb assessment skills and organization.

If you can hire a correctional nurse, or even aspire to be one, do not hesitate. Patients will thank you.

A version of this article first appeared on Medscape.com.

As a health care provider, I have always been interested in topics that concern incarcerated citizens, whether the discussion is related to the pursuit of aggressive care or jurisprudence in general. Additionally, I have followed the issue of capital punishment for most of my career, wondering if our democracy would continue this form of punishment for violent crimes.

In the early 2000s, public opinion moved away from capital punishment. The days of executing violent criminals such as Ted Bundy (who was killed in the electric chair in 1989) seemed to be in the rearview mirror. The ability of prison systems to obtain drugs for execution had become arduous, and Americans appeared disinterested in continuing with the process. Slowly, states began opting out of executions. Currently, 27 U.S. states offer the death penalty as an option at prosecution.
 

Botched executions

So far in 2021, 11 prisoners have been put to death by the federal government as well as five states, using either a one-drug or three-drug intravenous protocol. Of those prisoners, one was female.

The length of time from sentencing to date of execution varied from a low of 9 years to a high of 29 years, according to the Death Penalty Information Center. Of the executions performed this year, one was considered “botched.” The victim convulsed and vomited for several minutes before his ultimate demise. In fact, in the history of using the death penalty, from 1890 to 2010, approximately 3% of total executions (276 prisoners) were botched. They involved failed electric shocks, convulsions, labored breathing, and in one particularly horrific incident, a victim who was shot in the hip and abdomen by a firing squad and took several minutes to die.

One of the more difficult tasks for conducting an execution is intravenous access, with acquisition of an intravenous site proving to be a common issue. Another concern involves intravenous efficacy, or failure of the site to remain patent until death is achieved. That is why a few states that still practice capital punishment have returned to an electric chair option for execution (the method is chosen by the prisoner).
 

Majority favor capital punishment

But why do most Americans believe we need the death penalty? According to a 2021 poll by the Pew Research Center, 60% of U.S. citizens favor the use of capital punishment for those convicted of murder, including 27% who strongly favor its use. About 4 in 10 oppose the punishment, but only 15% are strongly opposed. The belief of those who favor retaining execution is that use of the death penalty deters violent crime.

Surprisingly, the American South has both the highest murder rate in the country and the highest percentage of executions. This geographic area encompasses 81% of the nation’s executions. A 2012 National Research Council poll determined that studies claiming the death penalty deters violent crime are “fundamentally flawed.” States that have abolished the death penalty do not show an increase in murder rates; in fact, the opposite is true, the organization concluded.

Since 1990, states without death penalty punishment have had consistently lower murder rates than those that retain capital punishment.
 

Where does that leave us?

Place my attitude in the column labeled “undecided.” I would love to believe capital punishment is a deterrent to violent crime, yet statistics do not prove the hypothesis to be true. We live in one of the more violent times in history, with mass shootings becoming commonplace. Large-scale retail theft has also been on the rise, especially in recent weeks.

The idea of severe punishment for heinous crime appeals to me, yet in 2001 Timothy McVeigh was executed after eating ice cream and gazing at the moon. His treatment before execution and the length of time he served were in opposition to other inmates sentenced to death. This, despite being punished for killing 168 people (including 19 children) in the Oklahoma City bombings.

I know we cannot be complacent. Violent crime needs to be reduced, and Americans need to feel safe. The process for achieving that goal? You tell me.
 

Nurses in prisons

About 1% of employed nurses (i.e., close to 21,000) in the United States work in prisons. This figure does not include the many LPNs and unlicensed assistive personnel who are also working in the field and may underrepresent actual numbers.

Correctional nurses have their own scope and standards of practice. They demonstrate superb assessment skills and organization.

If you can hire a correctional nurse, or even aspire to be one, do not hesitate. Patients will thank you.

A version of this article first appeared on Medscape.com.

As new COVID-19 cases mount in New York City, Mayor Bill de Blasio began his final week in office watching a sweeping vaccine mandate for private employers take effect.

Business owners were supposed to require all workers to have at least one dose of vaccine by Monday, Dec. 27. Workers won’t be able to opt out of vaccinations, as a proposed federal mandate for private sector employees would allow. Municipal workers were already under a vaccine mandate.

Mayor De Blasio called it the strongest private sector vaccine mandate in the world – and insists it’s absolutely necessary.

“I am 110 percent convinced this was the right thing to do, remains the right thing to do, particularly with the ferocity of Omicron,” the mayor told reporters on Dec. 27. “I don’t know if there’s going to be another variant behind it, but I do know our best defense is to get everyone vaccinated and mandates have worked.”

It’s unclear if Mayor de Blasio’s successor, Mayor-Elect Eric Adams, will continue the vaccine mandate. The New York Times reported that Mr. Adams’ spokesman, Evan Thies, said in a text: “The mayor-elect will make announcements on his administration’s Covid policy this week.”

Mayor De Blasio said enforcement would be light in the first week. Not every business owner is following the law.

The New York Post said Stratis Morfogen, owner of the Brooklyn Dumpling Shop and executive managing director of Brooklyn Chop House, went on Instagram and dared the mayor and Gov. Kathy Hochul to come and arrest him.

“Not going to follow your mandate on threatening my family of employees to get the jab or lose your job!” he said.

Mr. Morfogen said he’s not against vaccines but thinks the mandate violates his employees’ constitutional rights. He said he’s taking more steps toward safety, such as frequent testing of employees.

Union Square Hospitality Group CEO Danny Meyer, who oversees restaurants such as Union Square Cafe and Blue Smoke, requires employees not only to get vaccinated, but to get the booster, too.

“Hospitality is a team sport – it’s kind of like putting on a play on Broadway or playing a basketball game,” Mr. Meyer told CNBC. “If you can’t field a full healthy team, you’re going to have to hit pause.”

Customers at Union Square Hospitality Group restaurants will soon be required to show proof of having received a booster shot.

Also starting Dec. 27, all New Yorkers 12 and up must show they’ve received two doses of vaccine to enter indoor dining, fitness, entertainment, and performance venues unless they’ve gotten the one-dose Johnson & Johnson vaccine.

A version of this article first appeared on WebMD.com.

As new COVID-19 cases mount in New York City, Mayor Bill de Blasio began his final week in office watching a sweeping vaccine mandate for private employers take effect.

Business owners were supposed to require all workers to have at least one dose of vaccine by Monday, Dec. 27. Workers won’t be able to opt out of vaccinations, as a proposed federal mandate for private sector employees would allow. Municipal workers were already under a vaccine mandate.

Mayor De Blasio called it the strongest private sector vaccine mandate in the world – and insists it’s absolutely necessary.

“I am 110 percent convinced this was the right thing to do, remains the right thing to do, particularly with the ferocity of Omicron,” the mayor told reporters on Dec. 27. “I don’t know if there’s going to be another variant behind it, but I do know our best defense is to get everyone vaccinated and mandates have worked.”

It’s unclear if Mayor de Blasio’s successor, Mayor-Elect Eric Adams, will continue the vaccine mandate. The New York Times reported that Mr. Adams’ spokesman, Evan Thies, said in a text: “The mayor-elect will make announcements on his administration’s Covid policy this week.”

Mayor De Blasio said enforcement would be light in the first week. Not every business owner is following the law.

The New York Post said Stratis Morfogen, owner of the Brooklyn Dumpling Shop and executive managing director of Brooklyn Chop House, went on Instagram and dared the mayor and Gov. Kathy Hochul to come and arrest him.

“Not going to follow your mandate on threatening my family of employees to get the jab or lose your job!” he said.

Mr. Morfogen said he’s not against vaccines but thinks the mandate violates his employees’ constitutional rights. He said he’s taking more steps toward safety, such as frequent testing of employees.

Union Square Hospitality Group CEO Danny Meyer, who oversees restaurants such as Union Square Cafe and Blue Smoke, requires employees not only to get vaccinated, but to get the booster, too.

“Hospitality is a team sport – it’s kind of like putting on a play on Broadway or playing a basketball game,” Mr. Meyer told CNBC. “If you can’t field a full healthy team, you’re going to have to hit pause.”

Customers at Union Square Hospitality Group restaurants will soon be required to show proof of having received a booster shot.

Also starting Dec. 27, all New Yorkers 12 and up must show they’ve received two doses of vaccine to enter indoor dining, fitness, entertainment, and performance venues unless they’ve gotten the one-dose Johnson & Johnson vaccine.

A version of this article first appeared on WebMD.com.

As new COVID-19 cases mount in New York City, Mayor Bill de Blasio began his final week in office watching a sweeping vaccine mandate for private employers take effect.

Business owners were supposed to require all workers to have at least one dose of vaccine by Monday, Dec. 27. Workers won’t be able to opt out of vaccinations, as a proposed federal mandate for private sector employees would allow. Municipal workers were already under a vaccine mandate.

Mayor De Blasio called it the strongest private sector vaccine mandate in the world – and insists it’s absolutely necessary.

“I am 110 percent convinced this was the right thing to do, remains the right thing to do, particularly with the ferocity of Omicron,” the mayor told reporters on Dec. 27. “I don’t know if there’s going to be another variant behind it, but I do know our best defense is to get everyone vaccinated and mandates have worked.”

It’s unclear if Mayor de Blasio’s successor, Mayor-Elect Eric Adams, will continue the vaccine mandate. The New York Times reported that Mr. Adams’ spokesman, Evan Thies, said in a text: “The mayor-elect will make announcements on his administration’s Covid policy this week.”

Mayor De Blasio said enforcement would be light in the first week. Not every business owner is following the law.

The New York Post said Stratis Morfogen, owner of the Brooklyn Dumpling Shop and executive managing director of Brooklyn Chop House, went on Instagram and dared the mayor and Gov. Kathy Hochul to come and arrest him.

“Not going to follow your mandate on threatening my family of employees to get the jab or lose your job!” he said.

Mr. Morfogen said he’s not against vaccines but thinks the mandate violates his employees’ constitutional rights. He said he’s taking more steps toward safety, such as frequent testing of employees.

Union Square Hospitality Group CEO Danny Meyer, who oversees restaurants such as Union Square Cafe and Blue Smoke, requires employees not only to get vaccinated, but to get the booster, too.

“Hospitality is a team sport – it’s kind of like putting on a play on Broadway or playing a basketball game,” Mr. Meyer told CNBC. “If you can’t field a full healthy team, you’re going to have to hit pause.”

Customers at Union Square Hospitality Group restaurants will soon be required to show proof of having received a booster shot.

Also starting Dec. 27, all New Yorkers 12 and up must show they’ve received two doses of vaccine to enter indoor dining, fitness, entertainment, and performance venues unless they’ve gotten the one-dose Johnson & Johnson vaccine.

A version of this article first appeared on WebMD.com.

The coronavirus that causes COVID-19 can spread to the heart and brain within days of infection and can survive for months in organs, according to a new study by the National Institutes of Health.

The virus can spread to almost every organ system in the body, which could contribute to the ongoing symptoms seen in “long COVID” patients, the study authors wrote. The study is considered one of the most comprehensive reviews of how the virus replicates in human cells and persists in the human body. It is under review for publication in the journal Nature.

“This is remarkably important work,” Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, told Bloomberg News. Dr. Al-Aly wasn’t involved with the NIH study but has researched the long-term effects of COVID-19.

“For a long time now, we have been scratching our heads and asking why long COVID seems to affect so many organ systems,” he said. “This paper sheds some light and may help explain why long COVID can occur even in people who had mild or asymptomatic acute disease.”

The NIH researchers sampled and analyzed tissues from autopsies on 44 patients who died after contracting the coronavirus during the first year of the pandemic. They found persistent virus particles in multiple parts of the body, including the heart and brain, for as long as 230 days after symptoms began. This could represent infection with defective virus particles, they said, which has also been seen in persistent infections among measles patients.

“We don’t yet know what burden of chronic illness will result in years to come,” Raina MacIntyre, PhD, a professor of global biosecurity at the University of New South Wales, Sydney, told Bloomberg News.

“Will we see young-onset cardiac failure in survivors or early-onset dementia?” she asked. “These are unanswered questions which call for a precautionary public health approach to mitigation of the spread of this virus.”

Unlike other COVID-19 autopsy research, the NIH team had a more comprehensive postmortem tissue collection process, which typically occurred within a day of the patient’s death, Bloomberg News reported. The researchers also used a variety of ways to preserve tissue to figure out viral levels. They were able to grow the virus collected from several tissues, including the heart, lungs, small intestine, and adrenal glands.

“Our results collectively show that, while the highest burden of SARS-CoV-2 is in the airways and lung, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain,” the study authors wrote.

A version of this article first appeared on WebMD.com.

The coronavirus that causes COVID-19 can spread to the heart and brain within days of infection and can survive for months in organs, according to a new study by the National Institutes of Health.

The virus can spread to almost every organ system in the body, which could contribute to the ongoing symptoms seen in “long COVID” patients, the study authors wrote. The study is considered one of the most comprehensive reviews of how the virus replicates in human cells and persists in the human body. It is under review for publication in the journal Nature.

“This is remarkably important work,” Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, told Bloomberg News. Dr. Al-Aly wasn’t involved with the NIH study but has researched the long-term effects of COVID-19.

“For a long time now, we have been scratching our heads and asking why long COVID seems to affect so many organ systems,” he said. “This paper sheds some light and may help explain why long COVID can occur even in people who had mild or asymptomatic acute disease.”

The NIH researchers sampled and analyzed tissues from autopsies on 44 patients who died after contracting the coronavirus during the first year of the pandemic. They found persistent virus particles in multiple parts of the body, including the heart and brain, for as long as 230 days after symptoms began. This could represent infection with defective virus particles, they said, which has also been seen in persistent infections among measles patients.

“We don’t yet know what burden of chronic illness will result in years to come,” Raina MacIntyre, PhD, a professor of global biosecurity at the University of New South Wales, Sydney, told Bloomberg News.

“Will we see young-onset cardiac failure in survivors or early-onset dementia?” she asked. “These are unanswered questions which call for a precautionary public health approach to mitigation of the spread of this virus.”

Unlike other COVID-19 autopsy research, the NIH team had a more comprehensive postmortem tissue collection process, which typically occurred within a day of the patient’s death, Bloomberg News reported. The researchers also used a variety of ways to preserve tissue to figure out viral levels. They were able to grow the virus collected from several tissues, including the heart, lungs, small intestine, and adrenal glands.

“Our results collectively show that, while the highest burden of SARS-CoV-2 is in the airways and lung, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain,” the study authors wrote.

A version of this article first appeared on WebMD.com.

The coronavirus that causes COVID-19 can spread to the heart and brain within days of infection and can survive for months in organs, according to a new study by the National Institutes of Health.

The virus can spread to almost every organ system in the body, which could contribute to the ongoing symptoms seen in “long COVID” patients, the study authors wrote. The study is considered one of the most comprehensive reviews of how the virus replicates in human cells and persists in the human body. It is under review for publication in the journal Nature.

“This is remarkably important work,” Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, told Bloomberg News. Dr. Al-Aly wasn’t involved with the NIH study but has researched the long-term effects of COVID-19.

“For a long time now, we have been scratching our heads and asking why long COVID seems to affect so many organ systems,” he said. “This paper sheds some light and may help explain why long COVID can occur even in people who had mild or asymptomatic acute disease.”

The NIH researchers sampled and analyzed tissues from autopsies on 44 patients who died after contracting the coronavirus during the first year of the pandemic. They found persistent virus particles in multiple parts of the body, including the heart and brain, for as long as 230 days after symptoms began. This could represent infection with defective virus particles, they said, which has also been seen in persistent infections among measles patients.

“We don’t yet know what burden of chronic illness will result in years to come,” Raina MacIntyre, PhD, a professor of global biosecurity at the University of New South Wales, Sydney, told Bloomberg News.

“Will we see young-onset cardiac failure in survivors or early-onset dementia?” she asked. “These are unanswered questions which call for a precautionary public health approach to mitigation of the spread of this virus.”

Unlike other COVID-19 autopsy research, the NIH team had a more comprehensive postmortem tissue collection process, which typically occurred within a day of the patient’s death, Bloomberg News reported. The researchers also used a variety of ways to preserve tissue to figure out viral levels. They were able to grow the virus collected from several tissues, including the heart, lungs, small intestine, and adrenal glands.

“Our results collectively show that, while the highest burden of SARS-CoV-2 is in the airways and lung, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain,” the study authors wrote.

A version of this article first appeared on WebMD.com.

Hormone therapy in breast cancer patients can lead to mood and sleep disorders. A new randomized, controlled trial shows that omega-3 supplementation improves these symptoms. After 4 weeks of treatment, patients who received omega-3 reported better sleep, depression, and mood outcomes than those who received placebo.

Estrogen-receptor inhibitors are used to treat breast cancer with positive hormone receptors in combination with other therapies. However, the drugs can lead to long-term side effects, including hot flashes, night sweats, and changes to mood and sleep.

These side effects are often treated with selective serotonin reuptake inhibitors and some anticonvulsant drugs. Omega-3 supplements contain various polyunsaturated fatty acids, which influence cell signaling and contribute to the production of bioactive fat mediators that counter inflammation. They are widely used in cardiovascular disease, breast cancer, rheumatoid arthritis, depression, and other cognitive disorders. They also appear to amplify the antitumor efficacy of tamoxifen through the inhibition of proliferative and antiapoptotic pathways that that are influenced by estrogen-receptor signaling.

“This study showed that omega-3 supplementation can improve mood and sleep disorder in women suffering from breast cancer while they (are) managing with antihormone drugs. … this supplement can be proposed for the treatment of these patients,” wrote researchers led by Azadeh Moghaddas, MD, PhD, who is an associate professor of clinical pharmacy and pharmacy practice at Isfahan (Iran) University of Medical Sciences.

The study was made available as a preprint on ResearchSquare and has not yet been peer reviewed. It included 60 patients who were screened for baseline mood disorders using the hospital anxiety and depression scale (HADS), then randomized to 2 mg omega-3 per day for 4 weeks, or placebo.

Studies have shown that omega-3 supplementation improves menopause and mood symptoms in postmenopausal women without cancer.

Omega-3 supplementation has neuroprotective effects and improved brain function and mood in rats, and a 2019 review suggested that the evidence is strong enough to warrant clinical studies.

To determine if the supplement was also safe and effective in women with breast cancer undergoing hormone therapy, the researchers analyzed data from 32 patients in the intervention group and 28 patients in the placebo group.

At 4 weeks of follow-up, patients in the intervention group had significantly lower values on the Center for Epidemiological Studies-Depression scale (mean, 22.8 vs. 30.8; P < .001), Profile of Mood State (mean, 30.8 versus 39.5; P<.001), and Pittsburgh Sleep Quality Index (mean, 4.6 vs. 5.9; P = .04). There were no statistically significant changes in these values in the placebo group.

At 4 weeks, paired samples t-test comparisons between the intervention and the placebo groups revealed lower scores in the intervention group for mean scores in the PSQI subscales subjective sleep quality (0.8 vs. 1.4; P = .002), delay in falling asleep (1.1 vs. 1.6; P = .02), and sleep disturbances (0.8 vs. 1.1; P = .005).

There were no significant adverse reactions in either group.

The study is limited by its small sample size and the short follow-up period.

The study was funded by Isfahan University of Medical Sciences. The authors declare no other conflicts of interest.

Hormone therapy in breast cancer patients can lead to mood and sleep disorders. A new randomized, controlled trial shows that omega-3 supplementation improves these symptoms. After 4 weeks of treatment, patients who received omega-3 reported better sleep, depression, and mood outcomes than those who received placebo.

Estrogen-receptor inhibitors are used to treat breast cancer with positive hormone receptors in combination with other therapies. However, the drugs can lead to long-term side effects, including hot flashes, night sweats, and changes to mood and sleep.

These side effects are often treated with selective serotonin reuptake inhibitors and some anticonvulsant drugs. Omega-3 supplements contain various polyunsaturated fatty acids, which influence cell signaling and contribute to the production of bioactive fat mediators that counter inflammation. They are widely used in cardiovascular disease, breast cancer, rheumatoid arthritis, depression, and other cognitive disorders. They also appear to amplify the antitumor efficacy of tamoxifen through the inhibition of proliferative and antiapoptotic pathways that that are influenced by estrogen-receptor signaling.

“This study showed that omega-3 supplementation can improve mood and sleep disorder in women suffering from breast cancer while they (are) managing with antihormone drugs. … this supplement can be proposed for the treatment of these patients,” wrote researchers led by Azadeh Moghaddas, MD, PhD, who is an associate professor of clinical pharmacy and pharmacy practice at Isfahan (Iran) University of Medical Sciences.

The study was made available as a preprint on ResearchSquare and has not yet been peer reviewed. It included 60 patients who were screened for baseline mood disorders using the hospital anxiety and depression scale (HADS), then randomized to 2 mg omega-3 per day for 4 weeks, or placebo.

Studies have shown that omega-3 supplementation improves menopause and mood symptoms in postmenopausal women without cancer.

Omega-3 supplementation has neuroprotective effects and improved brain function and mood in rats, and a 2019 review suggested that the evidence is strong enough to warrant clinical studies.

To determine if the supplement was also safe and effective in women with breast cancer undergoing hormone therapy, the researchers analyzed data from 32 patients in the intervention group and 28 patients in the placebo group.

At 4 weeks of follow-up, patients in the intervention group had significantly lower values on the Center for Epidemiological Studies-Depression scale (mean, 22.8 vs. 30.8; P < .001), Profile of Mood State (mean, 30.8 versus 39.5; P<.001), and Pittsburgh Sleep Quality Index (mean, 4.6 vs. 5.9; P = .04). There were no statistically significant changes in these values in the placebo group.

At 4 weeks, paired samples t-test comparisons between the intervention and the placebo groups revealed lower scores in the intervention group for mean scores in the PSQI subscales subjective sleep quality (0.8 vs. 1.4; P = .002), delay in falling asleep (1.1 vs. 1.6; P = .02), and sleep disturbances (0.8 vs. 1.1; P = .005).

There were no significant adverse reactions in either group.

The study is limited by its small sample size and the short follow-up period.

The study was funded by Isfahan University of Medical Sciences. The authors declare no other conflicts of interest.

Hormone therapy in breast cancer patients can lead to mood and sleep disorders. A new randomized, controlled trial shows that omega-3 supplementation improves these symptoms. After 4 weeks of treatment, patients who received omega-3 reported better sleep, depression, and mood outcomes than those who received placebo.

Estrogen-receptor inhibitors are used to treat breast cancer with positive hormone receptors in combination with other therapies. However, the drugs can lead to long-term side effects, including hot flashes, night sweats, and changes to mood and sleep.

These side effects are often treated with selective serotonin reuptake inhibitors and some anticonvulsant drugs. Omega-3 supplements contain various polyunsaturated fatty acids, which influence cell signaling and contribute to the production of bioactive fat mediators that counter inflammation. They are widely used in cardiovascular disease, breast cancer, rheumatoid arthritis, depression, and other cognitive disorders. They also appear to amplify the antitumor efficacy of tamoxifen through the inhibition of proliferative and antiapoptotic pathways that that are influenced by estrogen-receptor signaling.

“This study showed that omega-3 supplementation can improve mood and sleep disorder in women suffering from breast cancer while they (are) managing with antihormone drugs. … this supplement can be proposed for the treatment of these patients,” wrote researchers led by Azadeh Moghaddas, MD, PhD, who is an associate professor of clinical pharmacy and pharmacy practice at Isfahan (Iran) University of Medical Sciences.

The study was made available as a preprint on ResearchSquare and has not yet been peer reviewed. It included 60 patients who were screened for baseline mood disorders using the hospital anxiety and depression scale (HADS), then randomized to 2 mg omega-3 per day for 4 weeks, or placebo.

Studies have shown that omega-3 supplementation improves menopause and mood symptoms in postmenopausal women without cancer.

Omega-3 supplementation has neuroprotective effects and improved brain function and mood in rats, and a 2019 review suggested that the evidence is strong enough to warrant clinical studies.

To determine if the supplement was also safe and effective in women with breast cancer undergoing hormone therapy, the researchers analyzed data from 32 patients in the intervention group and 28 patients in the placebo group.

At 4 weeks of follow-up, patients in the intervention group had significantly lower values on the Center for Epidemiological Studies-Depression scale (mean, 22.8 vs. 30.8; P < .001), Profile of Mood State (mean, 30.8 versus 39.5; P<.001), and Pittsburgh Sleep Quality Index (mean, 4.6 vs. 5.9; P = .04). There were no statistically significant changes in these values in the placebo group.

At 4 weeks, paired samples t-test comparisons between the intervention and the placebo groups revealed lower scores in the intervention group for mean scores in the PSQI subscales subjective sleep quality (0.8 vs. 1.4; P = .002), delay in falling asleep (1.1 vs. 1.6; P = .02), and sleep disturbances (0.8 vs. 1.1; P = .005).

There were no significant adverse reactions in either group.

The study is limited by its small sample size and the short follow-up period.

The study was funded by Isfahan University of Medical Sciences. The authors declare no other conflicts of interest.