While waiting to cross a street, a 30-year-old woman was suddenly struck by an oncoming vehicle, which crushed her legs against a parked automobile. She sustained a life-threatening traumatic injury and nearly exsanguinated at the scene. Nearby pedestrians assisted her, including a man who applied his belt to the woman’s left thigh to prevent complete exsanguination following the crush. She was emergently transported to an adult regional trauma center and admitted to the ICU.

The patient was given multiple transfusions of packed red blood cells, platelets, and frozen plasma in attempts to restore hemostasis. She underwent emergent surgery for a complete washout, debridement, and compartment fasciotomy on the right leg. The left leg required an above-knee amputation. Following surgery, full-thickness and split-thickness wounds were present on both extremities.

Before the accident, the woman had a history of hypertension controlled with a single antihypertensive. She was obese, with a BMI of 31.9. She had no surgical history. She denied excessive alcohol consumption, illicit drug use, or smoking. She was unaware of having any food or drug allergies.

The woman was married and had a 6-month-old baby. Until her accident, she was employed full-time as an investment accountant. She expressed contentment regarding her home, family, work, and busy lifestyle.

Once the patient’s condition was stabilized and hemostasis achieved in the trauma ICU, the bilateral lower-extremity wounds were managed by application of foam dressings via negative-pressure therapy. The dressings were changed on the patient’s lower-extremity wounds three times per week for about three weeks. When the wounds’ depth decreased and granulation was achieved, split-thickness skin grafts (STSGs) harvested from the right anterior thigh were applied to the open wounds (see Figure 1) in the operating room.

Following application of the STSGs and hemostasis of the patient’s donor site, silver silicone foam dressings were applied directly over the right lower-extremity graft and the donor site in the operating room. The dressings remained in place for four days (see Figure 2). A nonadherent, petrolatum-based contact layer was then applied to the left lower-extremity amputation graft site, followed by a negative-pressure foam dressing.

The negative-pressure pump was programmed for 75 mm Hg continuous therapy for four days. The silver silicone foam and negative-pressure foam dressings were removed from the respective graft sites on the fourth postpostoperative day. The grafts were viable and intact (see Figures 3 and 4). The silver silicone foam was reapplied to the lower-extremity STSGs and donor site and changed every four days.

When a few pinpoint dehisced areas were noted on the grafts, a silver-coated absorbent antimicrobial dressing was applied. A nonadherent, petrolatum-based contact layer, followed by wide-mesh stretch gauze, was secured as an exterior dressing over the graft sites. Both lower-extremity dressings were layered with elastic wraps to prevent edema. The dressings were changed daily for two weeks.

On postoperative Day 4, the silver silicone foam was removed from the donor site. A nonadherent contact layer of bismuth tribromophenate petrolatum, followed by the silver silicone foam, was selected for placement over the donor site. Gauze and an elastic wrap were secured as an exterior dressing and removed three days later.

The donor site dressing was reduced to a layer of bismuth tribromophenate petrolatum and left open to air. As the edges of the nonadherent contact layer dried, they were trimmed with scissors (see Figure 5). A moisturizing cocoa butter–based lotion was applied daily to the exposed areas of the donor site.

During the patient’s third postoperative week at the trauma center, as she underwent a continuum of aggressive rehabilitation and wound care, the donor and STSG sites were pronounced healed (see Figures 6, 7, and 8). The donor site was left open to air, with daily use of cocoa butter lotion. Maintenance care of the graft sites included daily application of cocoa butter lotion, stretch gauze, and elastic wraps. The patient was discharged from the rehabilitation unit to home, where she awaited a prosthetic fitting.

Throughout the patient’s hospitalization and rehabilitation, surgical, medical, pain, and nutrition management were monitored on a continuum, as were laboratory values. Her vital signs remained within reasonable limits. The patient remained infection free and experienced neither medical nor surgical complications during the course of her hospital stay.

DISCUSSION
Traumatic injuries often result in bodily deformities, amputations, and death. They represent the leading cause of death among people in the US younger than 45.^1,2

Compartment syndrome develops when increased pressure within a bodily cavity minimizes capillary perfusion, resulting in decreased tissue viability.³ Edema and hemorrhage are also precipitating factors for this condition.³ When it goes unrelieved, compromised circulation can lead to muscle devitalization. Amputation of the affected appendage may be necessary unless circulation is restored.

Surgical fasciotomy can help alleviate pressure within the musculofascial compartment to improve circulation.⁴ Typically, such a procedure leaves large open wounds—a challenge for the clinician who cares for the affected patient. Once the wound is stabilized and the tissue becomes viable with granulation, application of an STSG can be considered.^5,6

STSGs provide effective closure for open wounds. The grafting procedure entails removing, processing, and placing a portion of skin, both epidermal and partial dermal layers, on an open wound. Successful grafting requires adequate circulation, but excess bacteria can impede graft viability.⁷ Graft sites must be kept clean and moist without edema.⁵ Immediate application of negative-pressure therapy directly on an STSG has been shown to result in an outstanding graft “take,” as compared with use of traditional dressings.^5,6,8

Nutritional status must be optimal for a successful graft take, with adequate intake of protein, calories, fluids, vitamins, and minerals.^9,10

Treatment
Since days of old when traumatic wounds were treated with goat dung and honey, an array of methods and products has been developed, including numerous agents for cutaneous injuries alone.⁴ Occlusive, semiocclusive, or bacteriostatic topical ointments, foam, silver, or a combination of products can be used to manage and heal surgical wounds, grafts (including STSGs), and donor sites.^11,12

Currently, negative pressure is also used in STSGs to accelerate healing.^7,11 When applied to a wound, negative-pressure therapy enhances granulation, removes excess exudate, and creates a moist environment for healing.^5,13

Silver-coated absorbent antimicrobial dressings appear to reduce bacteria on the surface of the wound surfaces and postoperative surgical sites without inducing bacterial resistance or adversely affecting healthy tissue.^12,14-16 Silver silicone foam reduces bacterial colonization on wound surfaces and absorbs exudate into the foam dressing.^17,18 Wounds with devitalized tissue and excessive drainage are at risk for infection, inflammation, and chronic duration.¹⁹

Nutrition
It has been reported that about half of all persons admitted to US hospitals are malnourished, with increased risk for morbidity and mortality.²⁰ After experiencing hemorrhage, even well-nourished patients require additional protein and iron for successful recovery.¹⁰ Obese patients appear more susceptible to infection and surgical wound dehiscence than are their thinner counterparts, but further research is needed to study the impact of wound development and healing in this population.¹⁴

Tissue regeneration is known to require the amino acids arginine and glutamine for the construction of protein; additional research is also needed to support the theory that supplemental glutamine promotes wound healing.^9,21 Surgical patients and patients with wounds benefit from protein-enhanced diets; zinc and vitamins A and C can also help improve wound healing and clinical outcomes.²² Monitoring protein and prealbumin levels is helpful in evaluating nutritional status, allowing the clinician to modify the medical nutrition plan and optimize the patient’s health and wellness.²²

Rehabilitation
Surgical amputations of the lower extremities impair balance and mobility, necessitating extensive physical therapy and rehabilitation for affected patients.^23,24 Aggressive rehabilitation typically is exhausting for patients. It is important to initiate a supportive team approach (including physical and occupational therapists) soon after surgery, continuing beyond the acute hospitalization into rehabilitation. Individualized, patient-centered goals are targeted and amended as necessary. Physical and occupational therapy increase in intensity and duration to optimize the patient’s functionality. Prosthetic fitting takes place after edema diminishes and the limb is fully healed.²⁴

Patient Outcome
An obese young woman who sustained traumatic lower-extremity injuries and amputation experienced an optimal clinical outcome after 54 days of management. Exceptional surgical and medical strategies were initiated in the adult regional trauma center’s ICU and concluded at the adjoining rehabilitation center.

Strategic selection of products and interventions—negative pressure, silver silicone foam, silver-coated absorbent antimicrobial dressings, nonadherent contact layers, stretch gauze, and elastic wraps—and constant monitoring, including that of the patient’s nutritional status, resulted in expedient resolution of her traumatic wounds, STSGs, and donor site.

CONCLUSION
Despite revolutionary advances and life-sustaining measures in the surgical, medical, and wound care arena, traumatic events remain potentially debilitating and life-threatening for young adults. Triage of the trauma patient for appropriate medical care and collaborative management involving a team of trauma specialists and clinicians of all disciplines can now provide life-sustaining opportunities for these patients.

While waiting to cross a street, a 30-year-old woman was suddenly struck by an oncoming vehicle, which crushed her legs against a parked automobile. She sustained a life-threatening traumatic injury and nearly exsanguinated at the scene. Nearby pedestrians assisted her, including a man who applied his belt to the woman’s left thigh to prevent complete exsanguination following the crush. She was emergently transported to an adult regional trauma center and admitted to the ICU.

The patient was given multiple transfusions of packed red blood cells, platelets, and frozen plasma in attempts to restore hemostasis. She underwent emergent surgery for a complete washout, debridement, and compartment fasciotomy on the right leg. The left leg required an above-knee amputation. Following surgery, full-thickness and split-thickness wounds were present on both extremities.

Before the accident, the woman had a history of hypertension controlled with a single antihypertensive. She was obese, with a BMI of 31.9. She had no surgical history. She denied excessive alcohol consumption, illicit drug use, or smoking. She was unaware of having any food or drug allergies.

The woman was married and had a 6-month-old baby. Until her accident, she was employed full-time as an investment accountant. She expressed contentment regarding her home, family, work, and busy lifestyle.

Once the patient’s condition was stabilized and hemostasis achieved in the trauma ICU, the bilateral lower-extremity wounds were managed by application of foam dressings via negative-pressure therapy. The dressings were changed on the patient’s lower-extremity wounds three times per week for about three weeks. When the wounds’ depth decreased and granulation was achieved, split-thickness skin grafts (STSGs) harvested from the right anterior thigh were applied to the open wounds (see Figure 1) in the operating room.

Following application of the STSGs and hemostasis of the patient’s donor site, silver silicone foam dressings were applied directly over the right lower-extremity graft and the donor site in the operating room. The dressings remained in place for four days (see Figure 2). A nonadherent, petrolatum-based contact layer was then applied to the left lower-extremity amputation graft site, followed by a negative-pressure foam dressing.

The negative-pressure pump was programmed for 75 mm Hg continuous therapy for four days. The silver silicone foam and negative-pressure foam dressings were removed from the respective graft sites on the fourth postpostoperative day. The grafts were viable and intact (see Figures 3 and 4). The silver silicone foam was reapplied to the lower-extremity STSGs and donor site and changed every four days.

When a few pinpoint dehisced areas were noted on the grafts, a silver-coated absorbent antimicrobial dressing was applied. A nonadherent, petrolatum-based contact layer, followed by wide-mesh stretch gauze, was secured as an exterior dressing over the graft sites. Both lower-extremity dressings were layered with elastic wraps to prevent edema. The dressings were changed daily for two weeks.

On postoperative Day 4, the silver silicone foam was removed from the donor site. A nonadherent contact layer of bismuth tribromophenate petrolatum, followed by the silver silicone foam, was selected for placement over the donor site. Gauze and an elastic wrap were secured as an exterior dressing and removed three days later.

The donor site dressing was reduced to a layer of bismuth tribromophenate petrolatum and left open to air. As the edges of the nonadherent contact layer dried, they were trimmed with scissors (see Figure 5). A moisturizing cocoa butter–based lotion was applied daily to the exposed areas of the donor site.

During the patient’s third postoperative week at the trauma center, as she underwent a continuum of aggressive rehabilitation and wound care, the donor and STSG sites were pronounced healed (see Figures 6, 7, and 8). The donor site was left open to air, with daily use of cocoa butter lotion. Maintenance care of the graft sites included daily application of cocoa butter lotion, stretch gauze, and elastic wraps. The patient was discharged from the rehabilitation unit to home, where she awaited a prosthetic fitting.

Throughout the patient’s hospitalization and rehabilitation, surgical, medical, pain, and nutrition management were monitored on a continuum, as were laboratory values. Her vital signs remained within reasonable limits. The patient remained infection free and experienced neither medical nor surgical complications during the course of her hospital stay.

DISCUSSION
Traumatic injuries often result in bodily deformities, amputations, and death. They represent the leading cause of death among people in the US younger than 45.^1,2

Compartment syndrome develops when increased pressure within a bodily cavity minimizes capillary perfusion, resulting in decreased tissue viability.³ Edema and hemorrhage are also precipitating factors for this condition.³ When it goes unrelieved, compromised circulation can lead to muscle devitalization. Amputation of the affected appendage may be necessary unless circulation is restored.

Surgical fasciotomy can help alleviate pressure within the musculofascial compartment to improve circulation.⁴ Typically, such a procedure leaves large open wounds—a challenge for the clinician who cares for the affected patient. Once the wound is stabilized and the tissue becomes viable with granulation, application of an STSG can be considered.^5,6

STSGs provide effective closure for open wounds. The grafting procedure entails removing, processing, and placing a portion of skin, both epidermal and partial dermal layers, on an open wound. Successful grafting requires adequate circulation, but excess bacteria can impede graft viability.⁷ Graft sites must be kept clean and moist without edema.⁵ Immediate application of negative-pressure therapy directly on an STSG has been shown to result in an outstanding graft “take,” as compared with use of traditional dressings.^5,6,8

Nutritional status must be optimal for a successful graft take, with adequate intake of protein, calories, fluids, vitamins, and minerals.^9,10

Treatment
Since days of old when traumatic wounds were treated with goat dung and honey, an array of methods and products has been developed, including numerous agents for cutaneous injuries alone.⁴ Occlusive, semiocclusive, or bacteriostatic topical ointments, foam, silver, or a combination of products can be used to manage and heal surgical wounds, grafts (including STSGs), and donor sites.^11,12

Currently, negative pressure is also used in STSGs to accelerate healing.^7,11 When applied to a wound, negative-pressure therapy enhances granulation, removes excess exudate, and creates a moist environment for healing.^5,13

Silver-coated absorbent antimicrobial dressings appear to reduce bacteria on the surface of the wound surfaces and postoperative surgical sites without inducing bacterial resistance or adversely affecting healthy tissue.^12,14-16 Silver silicone foam reduces bacterial colonization on wound surfaces and absorbs exudate into the foam dressing.^17,18 Wounds with devitalized tissue and excessive drainage are at risk for infection, inflammation, and chronic duration.¹⁹

Nutrition
It has been reported that about half of all persons admitted to US hospitals are malnourished, with increased risk for morbidity and mortality.²⁰ After experiencing hemorrhage, even well-nourished patients require additional protein and iron for successful recovery.¹⁰ Obese patients appear more susceptible to infection and surgical wound dehiscence than are their thinner counterparts, but further research is needed to study the impact of wound development and healing in this population.¹⁴

Tissue regeneration is known to require the amino acids arginine and glutamine for the construction of protein; additional research is also needed to support the theory that supplemental glutamine promotes wound healing.^9,21 Surgical patients and patients with wounds benefit from protein-enhanced diets; zinc and vitamins A and C can also help improve wound healing and clinical outcomes.²² Monitoring protein and prealbumin levels is helpful in evaluating nutritional status, allowing the clinician to modify the medical nutrition plan and optimize the patient’s health and wellness.²²

Rehabilitation
Surgical amputations of the lower extremities impair balance and mobility, necessitating extensive physical therapy and rehabilitation for affected patients.^23,24 Aggressive rehabilitation typically is exhausting for patients. It is important to initiate a supportive team approach (including physical and occupational therapists) soon after surgery, continuing beyond the acute hospitalization into rehabilitation. Individualized, patient-centered goals are targeted and amended as necessary. Physical and occupational therapy increase in intensity and duration to optimize the patient’s functionality. Prosthetic fitting takes place after edema diminishes and the limb is fully healed.²⁴

Patient Outcome
An obese young woman who sustained traumatic lower-extremity injuries and amputation experienced an optimal clinical outcome after 54 days of management. Exceptional surgical and medical strategies were initiated in the adult regional trauma center’s ICU and concluded at the adjoining rehabilitation center.

Strategic selection of products and interventions—negative pressure, silver silicone foam, silver-coated absorbent antimicrobial dressings, nonadherent contact layers, stretch gauze, and elastic wraps—and constant monitoring, including that of the patient’s nutritional status, resulted in expedient resolution of her traumatic wounds, STSGs, and donor site.

CONCLUSION
Despite revolutionary advances and life-sustaining measures in the surgical, medical, and wound care arena, traumatic events remain potentially debilitating and life-threatening for young adults. Triage of the trauma patient for appropriate medical care and collaborative management involving a team of trauma specialists and clinicians of all disciplines can now provide life-sustaining opportunities for these patients.

While waiting to cross a street, a 30-year-old woman was suddenly struck by an oncoming vehicle, which crushed her legs against a parked automobile. She sustained a life-threatening traumatic injury and nearly exsanguinated at the scene. Nearby pedestrians assisted her, including a man who applied his belt to the woman’s left thigh to prevent complete exsanguination following the crush. She was emergently transported to an adult regional trauma center and admitted to the ICU.

The patient was given multiple transfusions of packed red blood cells, platelets, and frozen plasma in attempts to restore hemostasis. She underwent emergent surgery for a complete washout, debridement, and compartment fasciotomy on the right leg. The left leg required an above-knee amputation. Following surgery, full-thickness and split-thickness wounds were present on both extremities.

Before the accident, the woman had a history of hypertension controlled with a single antihypertensive. She was obese, with a BMI of 31.9. She had no surgical history. She denied excessive alcohol consumption, illicit drug use, or smoking. She was unaware of having any food or drug allergies.

The woman was married and had a 6-month-old baby. Until her accident, she was employed full-time as an investment accountant. She expressed contentment regarding her home, family, work, and busy lifestyle.

Once the patient’s condition was stabilized and hemostasis achieved in the trauma ICU, the bilateral lower-extremity wounds were managed by application of foam dressings via negative-pressure therapy. The dressings were changed on the patient’s lower-extremity wounds three times per week for about three weeks. When the wounds’ depth decreased and granulation was achieved, split-thickness skin grafts (STSGs) harvested from the right anterior thigh were applied to the open wounds (see Figure 1) in the operating room.

Following application of the STSGs and hemostasis of the patient’s donor site, silver silicone foam dressings were applied directly over the right lower-extremity graft and the donor site in the operating room. The dressings remained in place for four days (see Figure 2). A nonadherent, petrolatum-based contact layer was then applied to the left lower-extremity amputation graft site, followed by a negative-pressure foam dressing.

The negative-pressure pump was programmed for 75 mm Hg continuous therapy for four days. The silver silicone foam and negative-pressure foam dressings were removed from the respective graft sites on the fourth postpostoperative day. The grafts were viable and intact (see Figures 3 and 4). The silver silicone foam was reapplied to the lower-extremity STSGs and donor site and changed every four days.

When a few pinpoint dehisced areas were noted on the grafts, a silver-coated absorbent antimicrobial dressing was applied. A nonadherent, petrolatum-based contact layer, followed by wide-mesh stretch gauze, was secured as an exterior dressing over the graft sites. Both lower-extremity dressings were layered with elastic wraps to prevent edema. The dressings were changed daily for two weeks.

On postoperative Day 4, the silver silicone foam was removed from the donor site. A nonadherent contact layer of bismuth tribromophenate petrolatum, followed by the silver silicone foam, was selected for placement over the donor site. Gauze and an elastic wrap were secured as an exterior dressing and removed three days later.

The donor site dressing was reduced to a layer of bismuth tribromophenate petrolatum and left open to air. As the edges of the nonadherent contact layer dried, they were trimmed with scissors (see Figure 5). A moisturizing cocoa butter–based lotion was applied daily to the exposed areas of the donor site.

During the patient’s third postoperative week at the trauma center, as she underwent a continuum of aggressive rehabilitation and wound care, the donor and STSG sites were pronounced healed (see Figures 6, 7, and 8). The donor site was left open to air, with daily use of cocoa butter lotion. Maintenance care of the graft sites included daily application of cocoa butter lotion, stretch gauze, and elastic wraps. The patient was discharged from the rehabilitation unit to home, where she awaited a prosthetic fitting.

Throughout the patient’s hospitalization and rehabilitation, surgical, medical, pain, and nutrition management were monitored on a continuum, as were laboratory values. Her vital signs remained within reasonable limits. The patient remained infection free and experienced neither medical nor surgical complications during the course of her hospital stay.

DISCUSSION
Traumatic injuries often result in bodily deformities, amputations, and death. They represent the leading cause of death among people in the US younger than 45.^1,2

Compartment syndrome develops when increased pressure within a bodily cavity minimizes capillary perfusion, resulting in decreased tissue viability.³ Edema and hemorrhage are also precipitating factors for this condition.³ When it goes unrelieved, compromised circulation can lead to muscle devitalization. Amputation of the affected appendage may be necessary unless circulation is restored.

Surgical fasciotomy can help alleviate pressure within the musculofascial compartment to improve circulation.⁴ Typically, such a procedure leaves large open wounds—a challenge for the clinician who cares for the affected patient. Once the wound is stabilized and the tissue becomes viable with granulation, application of an STSG can be considered.^5,6

STSGs provide effective closure for open wounds. The grafting procedure entails removing, processing, and placing a portion of skin, both epidermal and partial dermal layers, on an open wound. Successful grafting requires adequate circulation, but excess bacteria can impede graft viability.⁷ Graft sites must be kept clean and moist without edema.⁵ Immediate application of negative-pressure therapy directly on an STSG has been shown to result in an outstanding graft “take,” as compared with use of traditional dressings.^5,6,8

Nutritional status must be optimal for a successful graft take, with adequate intake of protein, calories, fluids, vitamins, and minerals.^9,10

Treatment
Since days of old when traumatic wounds were treated with goat dung and honey, an array of methods and products has been developed, including numerous agents for cutaneous injuries alone.⁴ Occlusive, semiocclusive, or bacteriostatic topical ointments, foam, silver, or a combination of products can be used to manage and heal surgical wounds, grafts (including STSGs), and donor sites.^11,12

Currently, negative pressure is also used in STSGs to accelerate healing.^7,11 When applied to a wound, negative-pressure therapy enhances granulation, removes excess exudate, and creates a moist environment for healing.^5,13

Silver-coated absorbent antimicrobial dressings appear to reduce bacteria on the surface of the wound surfaces and postoperative surgical sites without inducing bacterial resistance or adversely affecting healthy tissue.^12,14-16 Silver silicone foam reduces bacterial colonization on wound surfaces and absorbs exudate into the foam dressing.^17,18 Wounds with devitalized tissue and excessive drainage are at risk for infection, inflammation, and chronic duration.¹⁹

Nutrition
It has been reported that about half of all persons admitted to US hospitals are malnourished, with increased risk for morbidity and mortality.²⁰ After experiencing hemorrhage, even well-nourished patients require additional protein and iron for successful recovery.¹⁰ Obese patients appear more susceptible to infection and surgical wound dehiscence than are their thinner counterparts, but further research is needed to study the impact of wound development and healing in this population.¹⁴

Tissue regeneration is known to require the amino acids arginine and glutamine for the construction of protein; additional research is also needed to support the theory that supplemental glutamine promotes wound healing.^9,21 Surgical patients and patients with wounds benefit from protein-enhanced diets; zinc and vitamins A and C can also help improve wound healing and clinical outcomes.²² Monitoring protein and prealbumin levels is helpful in evaluating nutritional status, allowing the clinician to modify the medical nutrition plan and optimize the patient’s health and wellness.²²

Rehabilitation
Surgical amputations of the lower extremities impair balance and mobility, necessitating extensive physical therapy and rehabilitation for affected patients.^23,24 Aggressive rehabilitation typically is exhausting for patients. It is important to initiate a supportive team approach (including physical and occupational therapists) soon after surgery, continuing beyond the acute hospitalization into rehabilitation. Individualized, patient-centered goals are targeted and amended as necessary. Physical and occupational therapy increase in intensity and duration to optimize the patient’s functionality. Prosthetic fitting takes place after edema diminishes and the limb is fully healed.²⁴

Patient Outcome
An obese young woman who sustained traumatic lower-extremity injuries and amputation experienced an optimal clinical outcome after 54 days of management. Exceptional surgical and medical strategies were initiated in the adult regional trauma center’s ICU and concluded at the adjoining rehabilitation center.

Strategic selection of products and interventions—negative pressure, silver silicone foam, silver-coated absorbent antimicrobial dressings, nonadherent contact layers, stretch gauze, and elastic wraps—and constant monitoring, including that of the patient’s nutritional status, resulted in expedient resolution of her traumatic wounds, STSGs, and donor site.

CONCLUSION
Despite revolutionary advances and life-sustaining measures in the surgical, medical, and wound care arena, traumatic events remain potentially debilitating and life-threatening for young adults. Triage of the trauma patient for appropriate medical care and collaborative management involving a team of trauma specialists and clinicians of all disciplines can now provide life-sustaining opportunities for these patients.

Mrs. J, age 75, has moderate Alzheimer’s dementia and lives at home with her husband. Since her Alzheimer’s disease (AD) diagnosis 2 years ago, Mrs. J generally has been cooperative and not physically aggressive, but has experienced occasional depressive symptoms. However, Mr. J reports that recently his wife is becoming increasingly confused and agitated and wanders the house at night. His efforts to calm and coax her back to bed often lead to increased agitation and yelling. On 1 occasion Mrs. J pushed her husband. Mr. J is concerned that if these behaviors continue he may not be able to care for her at home. Mr. J read online that antipsychotics might reduce aggressive behavior, but is concerned about the increased risk of mortality and stroke with these medications.

Mrs. J receives donepezil, 10 mg/d, sertra-line, 50 mg/d, and extended-release oxybutynin, 10 mg/d. Her over-the-counter (OTC) medications include acetaminophen, 650 mg as needed for pain, ranitidine, 150 mg/d, and docusate sodium, 100 mg/d. Several nights last week, Mr. J gave his wife an unknown OTC sleep medication, hoping it would stop her nighttime wandering, but it did not help. Physical examination, laboratory testing, and urine culture are all normal.

Most dementia patients experience neuropsychiatric disturbances, especially at later stages, that often lead to caregiver distress and nursing home placement. Although these symptoms may signal progressing dementia, environmental factors, medical conditions, and medications may worsen functioning and should be considered in the assessment.¹

Mrs. J has no medical problems that were identified as possible triggers for her behavior. Mr. J’s interference with his wife’s wandering could have increased her agitation, but he is gentle toward her and she has become agitated with no apparent trigger. “Sundowning” and poor sleep also may be involved, as sleep deprivation can lead to delirium and worsen cognitive deficits and behavioral problems.¹ Depression also should be considered.¹ Finally, Mrs. J is taking several medications with anticholinergic properties—oxybutynin, ranitidine, and an unknown OTC sleep medication, which likely contains diphenhydramine or doxylamine—that might contribute to her agitation.

Patients with dementia are highly sensitive to the cognitive and psychiatric adverse effects of anticholinergic medications. In studies of patients with mild or moderate Alzheimer’s dementia who received the potent anticholinergic scopolamine, adverse effects included:

• memory impairment
• restlessness
• disjointed speech
• motor incoordination
• drowsiness
• euphoria
• agitation
• hallucinations
• hostility.

Many of these effects worsened with increasing doses.^2,3 Age-matched controls experienced less severe memory impairment and no behavioral symptoms, which suggests that dementia-related damage to the cholinergic system leads to increased sensitivity to anticholinergics.

A cross-sectional study of 230 patients with AD identified anticholinergic use as a risk factor for psychosis (odds ratio 2.13, 95% confidence interval, 1.03 to 4.43), after adjusting for age and cognition.⁴ Among patients receiving 2 or 3 anticholinergics, 69% had psychotic symptoms compared with 48% of those receiving 1 anticholinergic and 32% of those receiving no anticholinergics.⁴ Anticholinergic overdoses can cause psychotic symptoms and delirium. A subtle presentation of delirium from prescribed anticholinergics may be confused with worsening dementia.¹ The sum of the evidence suggests that drugs with anticholinergic effects can contribute to agitation and psychosis in dementia.

When to discontinue

When diagnosing dementia it is important to address other potential causes of cognitive impairment, including medications. Approximately one-third of patients with dementia receive anticholinergic drugs, which suggests that providers often do not recognize the potential for harm with these medications.⁵ After patients receive acetylcholinesterase inhibitors (AChEIs)—which are used to enhance cognition in dementia patients—increased anticholinergic use may follow, often to treat adverse effects of AChEIs.⁵ This may negate the benefits of AChEIs and pose risk of further harm from the anticholinergics.^1,5 Although any time is a good time to discontinue an inessential anticholinergic in a patient with dementia, providers might consider screening for these drugs at the initial diagnosis, after initiating a cholinesterase inhibitor or increasing a dose, or if the patient develops psychotic or behavioral symptoms.

For Mrs. J, ranitidine and oxybutynin likely were used to treat gastrointestinal complaints and urinary frequency, which are known adverse effects of AChEIs. Many OTC preparations for insomnia, respiratory symptoms, and allergies contain older, anticholinergic antihistamines. Advise caregivers of dementia patients about possible adverse effects of OTC medications to prevent anticholinergic exposure. The Table provides a partial list of medications thought to have clinically significant anticholinergic effects.

‘Pharmacologic debridement’ refers to tapering and discontinuing medications that are no longer necessary or appropriate. Prescribers often are hesitant to discontinue medications prescribed by other clinicians and may assume that a medication used long term has been tolerated and helpful. However, as patients age—particularly if they develop dementia—their ability to tolerate a medication can change. Patients with dementia also may have difficulty attributing adverse experiences to medications and communicating these effects to providers. Some medical providers may not recognize adverse psychiatric and cognitive effects of the nonpsychiatric medications they prescribe because they do not have sufficient dementia expertise. Consulting with these providers may help determine the risk-benefit considerations of these medications.

Generally, anticholinergics should be discontinued if they are not essential to a patient’s health or if safer non-anticholinergic alternatives are available.⁵ Tapering may be necessary to prevent adverse effects from cholinergic rebound if a potent anticholinergic has been used chronically.⁵ The first step in addressing Mrs. J’s agitation is to discontinue the anticholinergic medications and monitor her symptoms. This pharmacologic debridement may avert the use of antipsychotics, which carry serious risks for dementia patients.¹

Table
Drugs with clinically significant anticholinergic effects*

Related Resources

• Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: a potential risk factor for psychosis onset in Alzheimer’s disease? Expert Opin Drug Saf. 2009;8(5):549-557.
• Meeks TW, Jeste DV. Beyond the black box: what is the role for antipsychotics in dementia? Current Psychiatry. 2008;7(6): 50-65.
• Centers for Education and Research on Therapeutics. Anticholinergic pocket reference card. www.chainonline.org/home/content_images/Anticholinergic%20Pocket%20Card%20CLR%203_12_10.pdf.

Drug Brand Names

• Amitriptyline • Elavil
• Atropine • Sal-Tropine
• Azelastine nasal spray • Astelin
• Belladonna alkaloids • Donnatal
• Benztropine • Cogentin
• Brompheniramine • Dimetane
• Carbamazepine • Carbatrol, Tegretol, others
• Carbinoxamine • Palgic
• Chlorpheniramine • Chlor-Trimeton
• Chlorpromazine • Thorazine
• Cimetidine • Tagamet
• Clemastine • Tavist
• Clidinium • Quarzan
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Cyclobenzaprine • Flexeril
• Cyproheptadine • Periactin
• Darifenacin • Enablex
• Desipramine • Norpramin
• Dexbrompheniramine • Drixoral
• Dexchlorpheniramine • Polaramine
• Dicyclomine • Bentyl
• Dimenhydrinate • Dramamine
• Diphenhydramine • Benadryl, Sominex, others
• Docusate Sodium • Colace
• Donepezil • Aricept
• Doxepin • Adapin
• Doxylamine • Aldex, Unisom, others
• Flavoxate • Urispas
• Glycopyrrolate • Robinul
• Hydroxyzine • Atarax
• Hyoscyamine • Cystospaz, Levbid
• Imipramine • Tofranil
• Ipratropium • Atrovent
• Loxapine • Loxitane
• Meclizine • Antivert
• Meperidine • Demerol
• Mepyramine • Anthisan
• Methscopolamine • Pamine
• Molindone • Moban
• Nortriptyline • Aventyl
• Olanzapine • Zyprexa
• Olopatadine nasal spray • Patanase
• Orphenadrine • Norflex
• Oxybutynin extended-release • Ditropan XL
• Paroxetine • Paxil
• Phenyltoloxamine • Dologesic, Durayin, others
• Pimozide • Orap
• Prochlorperazine • Compazine
• Procyclidine • Kemadrin
• Promethazine • Phenergan
• Propanthelin • Pro-Banthine
• Protriptyline • Vivactil
• Quetiapine • Seroquel
• Ranitidine • Zantac
• Scopolamine • Scopace
• Sertraline • Zoloft
• Solifenacin • VESIcare
• Thioridazine • Mellaril
• Tiotropium • Spiriva
• Tolterodine • Detrol
• Trihexyphenidyl • Artane
• Trimethobenzamide • Tigan
• Trimipramine • Surmontil
• Triprolidine • Actifed
• Trospium • Sanctura

Acknowledgements

This work was supported by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement #5 U18 HSO16094.

Disclosure

Dr. Carnahan receives grant/research support from the Agency for Healthcare Research and Quality.

Mrs. J, age 75, has moderate Alzheimer’s dementia and lives at home with her husband. Since her Alzheimer’s disease (AD) diagnosis 2 years ago, Mrs. J generally has been cooperative and not physically aggressive, but has experienced occasional depressive symptoms. However, Mr. J reports that recently his wife is becoming increasingly confused and agitated and wanders the house at night. His efforts to calm and coax her back to bed often lead to increased agitation and yelling. On 1 occasion Mrs. J pushed her husband. Mr. J is concerned that if these behaviors continue he may not be able to care for her at home. Mr. J read online that antipsychotics might reduce aggressive behavior, but is concerned about the increased risk of mortality and stroke with these medications.

Mrs. J receives donepezil, 10 mg/d, sertra-line, 50 mg/d, and extended-release oxybutynin, 10 mg/d. Her over-the-counter (OTC) medications include acetaminophen, 650 mg as needed for pain, ranitidine, 150 mg/d, and docusate sodium, 100 mg/d. Several nights last week, Mr. J gave his wife an unknown OTC sleep medication, hoping it would stop her nighttime wandering, but it did not help. Physical examination, laboratory testing, and urine culture are all normal.

Most dementia patients experience neuropsychiatric disturbances, especially at later stages, that often lead to caregiver distress and nursing home placement. Although these symptoms may signal progressing dementia, environmental factors, medical conditions, and medications may worsen functioning and should be considered in the assessment.¹

Mrs. J has no medical problems that were identified as possible triggers for her behavior. Mr. J’s interference with his wife’s wandering could have increased her agitation, but he is gentle toward her and she has become agitated with no apparent trigger. “Sundowning” and poor sleep also may be involved, as sleep deprivation can lead to delirium and worsen cognitive deficits and behavioral problems.¹ Depression also should be considered.¹ Finally, Mrs. J is taking several medications with anticholinergic properties—oxybutynin, ranitidine, and an unknown OTC sleep medication, which likely contains diphenhydramine or doxylamine—that might contribute to her agitation.

Patients with dementia are highly sensitive to the cognitive and psychiatric adverse effects of anticholinergic medications. In studies of patients with mild or moderate Alzheimer’s dementia who received the potent anticholinergic scopolamine, adverse effects included:

• memory impairment
• restlessness
• disjointed speech
• motor incoordination
• drowsiness
• euphoria
• agitation
• hallucinations
• hostility.

Many of these effects worsened with increasing doses.^2,3 Age-matched controls experienced less severe memory impairment and no behavioral symptoms, which suggests that dementia-related damage to the cholinergic system leads to increased sensitivity to anticholinergics.

A cross-sectional study of 230 patients with AD identified anticholinergic use as a risk factor for psychosis (odds ratio 2.13, 95% confidence interval, 1.03 to 4.43), after adjusting for age and cognition.⁴ Among patients receiving 2 or 3 anticholinergics, 69% had psychotic symptoms compared with 48% of those receiving 1 anticholinergic and 32% of those receiving no anticholinergics.⁴ Anticholinergic overdoses can cause psychotic symptoms and delirium. A subtle presentation of delirium from prescribed anticholinergics may be confused with worsening dementia.¹ The sum of the evidence suggests that drugs with anticholinergic effects can contribute to agitation and psychosis in dementia.

When to discontinue

When diagnosing dementia it is important to address other potential causes of cognitive impairment, including medications. Approximately one-third of patients with dementia receive anticholinergic drugs, which suggests that providers often do not recognize the potential for harm with these medications.⁵ After patients receive acetylcholinesterase inhibitors (AChEIs)—which are used to enhance cognition in dementia patients—increased anticholinergic use may follow, often to treat adverse effects of AChEIs.⁵ This may negate the benefits of AChEIs and pose risk of further harm from the anticholinergics.^1,5 Although any time is a good time to discontinue an inessential anticholinergic in a patient with dementia, providers might consider screening for these drugs at the initial diagnosis, after initiating a cholinesterase inhibitor or increasing a dose, or if the patient develops psychotic or behavioral symptoms.

For Mrs. J, ranitidine and oxybutynin likely were used to treat gastrointestinal complaints and urinary frequency, which are known adverse effects of AChEIs. Many OTC preparations for insomnia, respiratory symptoms, and allergies contain older, anticholinergic antihistamines. Advise caregivers of dementia patients about possible adverse effects of OTC medications to prevent anticholinergic exposure. The Table provides a partial list of medications thought to have clinically significant anticholinergic effects.

‘Pharmacologic debridement’ refers to tapering and discontinuing medications that are no longer necessary or appropriate. Prescribers often are hesitant to discontinue medications prescribed by other clinicians and may assume that a medication used long term has been tolerated and helpful. However, as patients age—particularly if they develop dementia—their ability to tolerate a medication can change. Patients with dementia also may have difficulty attributing adverse experiences to medications and communicating these effects to providers. Some medical providers may not recognize adverse psychiatric and cognitive effects of the nonpsychiatric medications they prescribe because they do not have sufficient dementia expertise. Consulting with these providers may help determine the risk-benefit considerations of these medications.

Generally, anticholinergics should be discontinued if they are not essential to a patient’s health or if safer non-anticholinergic alternatives are available.⁵ Tapering may be necessary to prevent adverse effects from cholinergic rebound if a potent anticholinergic has been used chronically.⁵ The first step in addressing Mrs. J’s agitation is to discontinue the anticholinergic medications and monitor her symptoms. This pharmacologic debridement may avert the use of antipsychotics, which carry serious risks for dementia patients.¹

Table
Drugs with clinically significant anticholinergic effects*

Related Resources

• Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: a potential risk factor for psychosis onset in Alzheimer’s disease? Expert Opin Drug Saf. 2009;8(5):549-557.
• Meeks TW, Jeste DV. Beyond the black box: what is the role for antipsychotics in dementia? Current Psychiatry. 2008;7(6): 50-65.
• Centers for Education and Research on Therapeutics. Anticholinergic pocket reference card. www.chainonline.org/home/content_images/Anticholinergic%20Pocket%20Card%20CLR%203_12_10.pdf.

Drug Brand Names

• Amitriptyline • Elavil
• Atropine • Sal-Tropine
• Azelastine nasal spray • Astelin
• Belladonna alkaloids • Donnatal
• Benztropine • Cogentin
• Brompheniramine • Dimetane
• Carbamazepine • Carbatrol, Tegretol, others
• Carbinoxamine • Palgic
• Chlorpheniramine • Chlor-Trimeton
• Chlorpromazine • Thorazine
• Cimetidine • Tagamet
• Clemastine • Tavist
• Clidinium • Quarzan
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Cyclobenzaprine • Flexeril
• Cyproheptadine • Periactin
• Darifenacin • Enablex
• Desipramine • Norpramin
• Dexbrompheniramine • Drixoral
• Dexchlorpheniramine • Polaramine
• Dicyclomine • Bentyl
• Dimenhydrinate • Dramamine
• Diphenhydramine • Benadryl, Sominex, others
• Docusate Sodium • Colace
• Donepezil • Aricept
• Doxepin • Adapin
• Doxylamine • Aldex, Unisom, others
• Flavoxate • Urispas
• Glycopyrrolate • Robinul
• Hydroxyzine • Atarax
• Hyoscyamine • Cystospaz, Levbid
• Imipramine • Tofranil
• Ipratropium • Atrovent
• Loxapine • Loxitane
• Meclizine • Antivert
• Meperidine • Demerol
• Mepyramine • Anthisan
• Methscopolamine • Pamine
• Molindone • Moban
• Nortriptyline • Aventyl
• Olanzapine • Zyprexa
• Olopatadine nasal spray • Patanase
• Orphenadrine • Norflex
• Oxybutynin extended-release • Ditropan XL
• Paroxetine • Paxil
• Phenyltoloxamine • Dologesic, Durayin, others
• Pimozide • Orap
• Prochlorperazine • Compazine
• Procyclidine • Kemadrin
• Promethazine • Phenergan
• Propanthelin • Pro-Banthine
• Protriptyline • Vivactil
• Quetiapine • Seroquel
• Ranitidine • Zantac
• Scopolamine • Scopace
• Sertraline • Zoloft
• Solifenacin • VESIcare
• Thioridazine • Mellaril
• Tiotropium • Spiriva
• Tolterodine • Detrol
• Trihexyphenidyl • Artane
• Trimethobenzamide • Tigan
• Trimipramine • Surmontil
• Triprolidine • Actifed
• Trospium • Sanctura

Acknowledgements

This work was supported by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement #5 U18 HSO16094.

Disclosure

Dr. Carnahan receives grant/research support from the Agency for Healthcare Research and Quality.

Mrs. J, age 75, has moderate Alzheimer’s dementia and lives at home with her husband. Since her Alzheimer’s disease (AD) diagnosis 2 years ago, Mrs. J generally has been cooperative and not physically aggressive, but has experienced occasional depressive symptoms. However, Mr. J reports that recently his wife is becoming increasingly confused and agitated and wanders the house at night. His efforts to calm and coax her back to bed often lead to increased agitation and yelling. On 1 occasion Mrs. J pushed her husband. Mr. J is concerned that if these behaviors continue he may not be able to care for her at home. Mr. J read online that antipsychotics might reduce aggressive behavior, but is concerned about the increased risk of mortality and stroke with these medications.

Mrs. J receives donepezil, 10 mg/d, sertra-line, 50 mg/d, and extended-release oxybutynin, 10 mg/d. Her over-the-counter (OTC) medications include acetaminophen, 650 mg as needed for pain, ranitidine, 150 mg/d, and docusate sodium, 100 mg/d. Several nights last week, Mr. J gave his wife an unknown OTC sleep medication, hoping it would stop her nighttime wandering, but it did not help. Physical examination, laboratory testing, and urine culture are all normal.

Most dementia patients experience neuropsychiatric disturbances, especially at later stages, that often lead to caregiver distress and nursing home placement. Although these symptoms may signal progressing dementia, environmental factors, medical conditions, and medications may worsen functioning and should be considered in the assessment.¹

Mrs. J has no medical problems that were identified as possible triggers for her behavior. Mr. J’s interference with his wife’s wandering could have increased her agitation, but he is gentle toward her and she has become agitated with no apparent trigger. “Sundowning” and poor sleep also may be involved, as sleep deprivation can lead to delirium and worsen cognitive deficits and behavioral problems.¹ Depression also should be considered.¹ Finally, Mrs. J is taking several medications with anticholinergic properties—oxybutynin, ranitidine, and an unknown OTC sleep medication, which likely contains diphenhydramine or doxylamine—that might contribute to her agitation.

Patients with dementia are highly sensitive to the cognitive and psychiatric adverse effects of anticholinergic medications. In studies of patients with mild or moderate Alzheimer’s dementia who received the potent anticholinergic scopolamine, adverse effects included:

• memory impairment
• restlessness
• disjointed speech
• motor incoordination
• drowsiness
• euphoria
• agitation
• hallucinations
• hostility.

Many of these effects worsened with increasing doses.^2,3 Age-matched controls experienced less severe memory impairment and no behavioral symptoms, which suggests that dementia-related damage to the cholinergic system leads to increased sensitivity to anticholinergics.

A cross-sectional study of 230 patients with AD identified anticholinergic use as a risk factor for psychosis (odds ratio 2.13, 95% confidence interval, 1.03 to 4.43), after adjusting for age and cognition.⁴ Among patients receiving 2 or 3 anticholinergics, 69% had psychotic symptoms compared with 48% of those receiving 1 anticholinergic and 32% of those receiving no anticholinergics.⁴ Anticholinergic overdoses can cause psychotic symptoms and delirium. A subtle presentation of delirium from prescribed anticholinergics may be confused with worsening dementia.¹ The sum of the evidence suggests that drugs with anticholinergic effects can contribute to agitation and psychosis in dementia.

When to discontinue

When diagnosing dementia it is important to address other potential causes of cognitive impairment, including medications. Approximately one-third of patients with dementia receive anticholinergic drugs, which suggests that providers often do not recognize the potential for harm with these medications.⁵ After patients receive acetylcholinesterase inhibitors (AChEIs)—which are used to enhance cognition in dementia patients—increased anticholinergic use may follow, often to treat adverse effects of AChEIs.⁵ This may negate the benefits of AChEIs and pose risk of further harm from the anticholinergics.^1,5 Although any time is a good time to discontinue an inessential anticholinergic in a patient with dementia, providers might consider screening for these drugs at the initial diagnosis, after initiating a cholinesterase inhibitor or increasing a dose, or if the patient develops psychotic or behavioral symptoms.

For Mrs. J, ranitidine and oxybutynin likely were used to treat gastrointestinal complaints and urinary frequency, which are known adverse effects of AChEIs. Many OTC preparations for insomnia, respiratory symptoms, and allergies contain older, anticholinergic antihistamines. Advise caregivers of dementia patients about possible adverse effects of OTC medications to prevent anticholinergic exposure. The Table provides a partial list of medications thought to have clinically significant anticholinergic effects.

‘Pharmacologic debridement’ refers to tapering and discontinuing medications that are no longer necessary or appropriate. Prescribers often are hesitant to discontinue medications prescribed by other clinicians and may assume that a medication used long term has been tolerated and helpful. However, as patients age—particularly if they develop dementia—their ability to tolerate a medication can change. Patients with dementia also may have difficulty attributing adverse experiences to medications and communicating these effects to providers. Some medical providers may not recognize adverse psychiatric and cognitive effects of the nonpsychiatric medications they prescribe because they do not have sufficient dementia expertise. Consulting with these providers may help determine the risk-benefit considerations of these medications.

Generally, anticholinergics should be discontinued if they are not essential to a patient’s health or if safer non-anticholinergic alternatives are available.⁵ Tapering may be necessary to prevent adverse effects from cholinergic rebound if a potent anticholinergic has been used chronically.⁵ The first step in addressing Mrs. J’s agitation is to discontinue the anticholinergic medications and monitor her symptoms. This pharmacologic debridement may avert the use of antipsychotics, which carry serious risks for dementia patients.¹

Table
Drugs with clinically significant anticholinergic effects*

Related Resources

• Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: a potential risk factor for psychosis onset in Alzheimer’s disease? Expert Opin Drug Saf. 2009;8(5):549-557.
• Meeks TW, Jeste DV. Beyond the black box: what is the role for antipsychotics in dementia? Current Psychiatry. 2008;7(6): 50-65.
• Centers for Education and Research on Therapeutics. Anticholinergic pocket reference card. www.chainonline.org/home/content_images/Anticholinergic%20Pocket%20Card%20CLR%203_12_10.pdf.

Drug Brand Names

• Amitriptyline • Elavil
• Atropine • Sal-Tropine
• Azelastine nasal spray • Astelin
• Belladonna alkaloids • Donnatal
• Benztropine • Cogentin
• Brompheniramine • Dimetane
• Carbamazepine • Carbatrol, Tegretol, others
• Carbinoxamine • Palgic
• Chlorpheniramine • Chlor-Trimeton
• Chlorpromazine • Thorazine
• Cimetidine • Tagamet
• Clemastine • Tavist
• Clidinium • Quarzan
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Cyclobenzaprine • Flexeril
• Cyproheptadine • Periactin
• Darifenacin • Enablex
• Desipramine • Norpramin
• Dexbrompheniramine • Drixoral
• Dexchlorpheniramine • Polaramine
• Dicyclomine • Bentyl
• Dimenhydrinate • Dramamine
• Diphenhydramine • Benadryl, Sominex, others
• Docusate Sodium • Colace
• Donepezil • Aricept
• Doxepin • Adapin
• Doxylamine • Aldex, Unisom, others
• Flavoxate • Urispas
• Glycopyrrolate • Robinul
• Hydroxyzine • Atarax
• Hyoscyamine • Cystospaz, Levbid
• Imipramine • Tofranil
• Ipratropium • Atrovent
• Loxapine • Loxitane
• Meclizine • Antivert
• Meperidine • Demerol
• Mepyramine • Anthisan
• Methscopolamine • Pamine
• Molindone • Moban
• Nortriptyline • Aventyl
• Olanzapine • Zyprexa
• Olopatadine nasal spray • Patanase
• Orphenadrine • Norflex
• Oxybutynin extended-release • Ditropan XL
• Paroxetine • Paxil
• Phenyltoloxamine • Dologesic, Durayin, others
• Pimozide • Orap
• Prochlorperazine • Compazine
• Procyclidine • Kemadrin
• Promethazine • Phenergan
• Propanthelin • Pro-Banthine
• Protriptyline • Vivactil
• Quetiapine • Seroquel
• Ranitidine • Zantac
• Scopolamine • Scopace
• Sertraline • Zoloft
• Solifenacin • VESIcare
• Thioridazine • Mellaril
• Tiotropium • Spiriva
• Tolterodine • Detrol
• Trihexyphenidyl • Artane
• Trimethobenzamide • Tigan
• Trimipramine • Surmontil
• Triprolidine • Actifed
• Trospium • Sanctura

Acknowledgements

This work was supported by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement #5 U18 HSO16094.

Disclosure

Dr. Carnahan receives grant/research support from the Agency for Healthcare Research and Quality.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/07/treating-insomnia-in-women.html#comments

Ms. A, age 44, reports a 3-month history of forgetfulness, difficulty concentrating, and insomnia. She says she can fall asleep but wakes up multiple times during the night and feels tired during the day. She has no history of a mood or anxiety disorder or medications that might be responsible for her symptoms.

Before her current insomnia began, Ms. A could sleep for 7 to 8 hours at night. Her husband suffers from obstructive sleep apnea (OSA), and his snoring occasionally would awaken her, but she slept well overall. Ms. A cannot identify anything that could be causing her sleep complaints. She states “The weird thing is that sometimes I am not sure if I’m cold or hot” and “I sometimes wake up drenched in sweat.” She also reports recent changes in the timing of her otherwise regular menstrual flow.

Ms. A attributes her memory problems to her poor sleep. A recent audit at her company held her responsible for several accounting errors, and Ms. A is worried that she might lose her job. She denies symptoms that would suggest major depression. You are unable to elicit a history of limb movements or excessive snoring.

Compared with men, women have a 1.3- to 1.8-fold greater risk for developing insomnia.^{Improve sleep with group CBT for insomnia,” Current Psychiatry, April 2009.) Pharmacotherapy during pregnancy and for breast-feeding mothers is guided by evaluating the risk/benefit ratio and safety considerations.}

Maintain a high index of suspicion for breathing-related sleep disorders, such as OSA,²¹ and RLS.²² Atypical presentations of OSA are common in pregnant or postpartum women; compared with men, women with OSA are more likely to report fatigue and less likely than to report sleepiness. Refer patients whom you think may have OSA for polysomnography.

If you suspect RLS, check for low ferritin and folate levels. Nutritional supplements may be necessary for women in high-risk groups, including those who are pregnant or have varicose veins, venous reflux, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson’s disease, or certain autoimmune disorders, such as Sjögren’s syndrome, celiac disease, and rheumatoid arthritis.²³ Advise these patients to avoid caffeine.

Although indicated for treating RLS, ropinirole and pramipexole are FDA Pregnancy Category C, which means animal studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks. Opioids, carbamazepine, or gabapentin may be safer for pregnant patients.²⁴

Insomnia during menopause

The prevalence of insomnia increases from 33% to 36% in premenopausal women to 44% to 61% in postmenopausal women.¹⁴ Hot flashes, comorbid mood disturbances, sleep-disordered breathing, and RLS contribute to increased insomnia risk in postmenopausal women (Table 3).^4,14,25,26

Treatment strategy. Always inquire about sleep in perimenopausal/postmenopausal women, even when her presenting complaint is related to menstrual cycle changes or vasomotor symptoms such as hot flashes.¹⁶ Assess patients for OSA, RLS, and mood, anxiety, and cognitive symptoms.²⁶ In addition to pharmacotherapy and behavioral therapy, treatment options include hormone replacement therapy (HRT) and herbal and dietary supplements (Table 4).^27-32

Table 3

Sleep difficulties during menopause: Differential diagnoses

Table 4

Treating insomnia in menopausal women

Comorbid psychiatric disorders

Women have a higher prevalence of psychiatric disorders such as major depressive disorder and anxiety disorders than men.¹ Women have a 10% to 25% lifetime risk of developing major depression. Three quarters of depressed patients experience insomnia.¹ Recent literature suggests insomnia is a risk factor for depression,³³ which emphasizes the need to screen women who present with sleep problems for depression and anxiety.

Five percent to 20% of women experience postpartum depression. Depression and insomnia are correlated to the rapid decline in estrogen and progesterone after delivery.³⁴

Treatment strategy. Insomnia is a common presenting symptom in patients with psychiatric conditions such as mood and anxiety disorders. Treating the underlying psychiatric disorder often alleviates sleeping difficulties. However, if the insomnia is disabling, treat the psychiatric disorder and insomnia concurrently.

CASE CONTINUED: Perimenopausal insomnia

Based on her history, you diagnose Ms. A with insomnia related to general medical condition (perimenopause). There are no indications to refer her for polysomnography. You educate Ms. A about sleep hygiene and recommend that she discuss her menstrual and physical complaints with her primary care physician or gynecologist. Ms. A is not interested in HRT because she has a strong family history of endometrial cancer. You reassure Ms. A and schedule a follow-up visit in 2 months to re-evaluate her insomnia.

Related resource

• Krahn LE. Perimenopausal depression? Ask how she’s sleeping. Current Psychiatry. 2005;4(6):39-53.

Drug brand names

• Carbamazepine • Carbatrol, Tegretol, others
• Escitalopram • Lexapro
• Eszopiclone • Lunesta
• Fluoxetine • Prozac
• Gabapentin • Neurontin, Gabarone
• Paroxetine • Paxil
• Pramipexole • Mirapex
• Ramelteon • Rozerem
• Ropinirole • Requip
• Sertraline • Zoloft
• Trazodone • Desyrel
• Zolpidem • Ambien

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgements

The authors thank Dr. Namita Dhiman and Darrel E. Willoughby for their assistance with this article.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/07/treating-insomnia-in-women.html#comments

Ms. A, age 44, reports a 3-month history of forgetfulness, difficulty concentrating, and insomnia. She says she can fall asleep but wakes up multiple times during the night and feels tired during the day. She has no history of a mood or anxiety disorder or medications that might be responsible for her symptoms.

Before her current insomnia began, Ms. A could sleep for 7 to 8 hours at night. Her husband suffers from obstructive sleep apnea (OSA), and his snoring occasionally would awaken her, but she slept well overall. Ms. A cannot identify anything that could be causing her sleep complaints. She states “The weird thing is that sometimes I am not sure if I’m cold or hot” and “I sometimes wake up drenched in sweat.” She also reports recent changes in the timing of her otherwise regular menstrual flow.

Ms. A attributes her memory problems to her poor sleep. A recent audit at her company held her responsible for several accounting errors, and Ms. A is worried that she might lose her job. She denies symptoms that would suggest major depression. You are unable to elicit a history of limb movements or excessive snoring.

Compared with men, women have a 1.3- to 1.8-fold greater risk for developing insomnia.^{Improve sleep with group CBT for insomnia,” Current Psychiatry, April 2009.) Pharmacotherapy during pregnancy and for breast-feeding mothers is guided by evaluating the risk/benefit ratio and safety considerations.}

Maintain a high index of suspicion for breathing-related sleep disorders, such as OSA,²¹ and RLS.²² Atypical presentations of OSA are common in pregnant or postpartum women; compared with men, women with OSA are more likely to report fatigue and less likely than to report sleepiness. Refer patients whom you think may have OSA for polysomnography.

If you suspect RLS, check for low ferritin and folate levels. Nutritional supplements may be necessary for women in high-risk groups, including those who are pregnant or have varicose veins, venous reflux, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson’s disease, or certain autoimmune disorders, such as Sjögren’s syndrome, celiac disease, and rheumatoid arthritis.²³ Advise these patients to avoid caffeine.

Although indicated for treating RLS, ropinirole and pramipexole are FDA Pregnancy Category C, which means animal studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks. Opioids, carbamazepine, or gabapentin may be safer for pregnant patients.²⁴

Insomnia during menopause

The prevalence of insomnia increases from 33% to 36% in premenopausal women to 44% to 61% in postmenopausal women.¹⁴ Hot flashes, comorbid mood disturbances, sleep-disordered breathing, and RLS contribute to increased insomnia risk in postmenopausal women (Table 3).^4,14,25,26

Treatment strategy. Always inquire about sleep in perimenopausal/postmenopausal women, even when her presenting complaint is related to menstrual cycle changes or vasomotor symptoms such as hot flashes.¹⁶ Assess patients for OSA, RLS, and mood, anxiety, and cognitive symptoms.²⁶ In addition to pharmacotherapy and behavioral therapy, treatment options include hormone replacement therapy (HRT) and herbal and dietary supplements (Table 4).^27-32

Table 3

Sleep difficulties during menopause: Differential diagnoses

Table 4

Treating insomnia in menopausal women

Comorbid psychiatric disorders

Women have a higher prevalence of psychiatric disorders such as major depressive disorder and anxiety disorders than men.¹ Women have a 10% to 25% lifetime risk of developing major depression. Three quarters of depressed patients experience insomnia.¹ Recent literature suggests insomnia is a risk factor for depression,³³ which emphasizes the need to screen women who present with sleep problems for depression and anxiety.

Five percent to 20% of women experience postpartum depression. Depression and insomnia are correlated to the rapid decline in estrogen and progesterone after delivery.³⁴

Treatment strategy. Insomnia is a common presenting symptom in patients with psychiatric conditions such as mood and anxiety disorders. Treating the underlying psychiatric disorder often alleviates sleeping difficulties. However, if the insomnia is disabling, treat the psychiatric disorder and insomnia concurrently.

CASE CONTINUED: Perimenopausal insomnia

Based on her history, you diagnose Ms. A with insomnia related to general medical condition (perimenopause). There are no indications to refer her for polysomnography. You educate Ms. A about sleep hygiene and recommend that she discuss her menstrual and physical complaints with her primary care physician or gynecologist. Ms. A is not interested in HRT because she has a strong family history of endometrial cancer. You reassure Ms. A and schedule a follow-up visit in 2 months to re-evaluate her insomnia.

Related resource

• Krahn LE. Perimenopausal depression? Ask how she’s sleeping. Current Psychiatry. 2005;4(6):39-53.

Drug brand names

• Carbamazepine • Carbatrol, Tegretol, others
• Escitalopram • Lexapro
• Eszopiclone • Lunesta
• Fluoxetine • Prozac
• Gabapentin • Neurontin, Gabarone
• Paroxetine • Paxil
• Pramipexole • Mirapex
• Ramelteon • Rozerem
• Ropinirole • Requip
• Sertraline • Zoloft
• Trazodone • Desyrel
• Zolpidem • Ambien

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgements

The authors thank Dr. Namita Dhiman and Darrel E. Willoughby for their assistance with this article.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/07/treating-insomnia-in-women.html#comments

Ms. A, age 44, reports a 3-month history of forgetfulness, difficulty concentrating, and insomnia. She says she can fall asleep but wakes up multiple times during the night and feels tired during the day. She has no history of a mood or anxiety disorder or medications that might be responsible for her symptoms.

Before her current insomnia began, Ms. A could sleep for 7 to 8 hours at night. Her husband suffers from obstructive sleep apnea (OSA), and his snoring occasionally would awaken her, but she slept well overall. Ms. A cannot identify anything that could be causing her sleep complaints. She states “The weird thing is that sometimes I am not sure if I’m cold or hot” and “I sometimes wake up drenched in sweat.” She also reports recent changes in the timing of her otherwise regular menstrual flow.

Ms. A attributes her memory problems to her poor sleep. A recent audit at her company held her responsible for several accounting errors, and Ms. A is worried that she might lose her job. She denies symptoms that would suggest major depression. You are unable to elicit a history of limb movements or excessive snoring.

Compared with men, women have a 1.3- to 1.8-fold greater risk for developing insomnia.^{Improve sleep with group CBT for insomnia,” Current Psychiatry, April 2009.) Pharmacotherapy during pregnancy and for breast-feeding mothers is guided by evaluating the risk/benefit ratio and safety considerations.}

Maintain a high index of suspicion for breathing-related sleep disorders, such as OSA,²¹ and RLS.²² Atypical presentations of OSA are common in pregnant or postpartum women; compared with men, women with OSA are more likely to report fatigue and less likely than to report sleepiness. Refer patients whom you think may have OSA for polysomnography.

If you suspect RLS, check for low ferritin and folate levels. Nutritional supplements may be necessary for women in high-risk groups, including those who are pregnant or have varicose veins, venous reflux, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson’s disease, or certain autoimmune disorders, such as Sjögren’s syndrome, celiac disease, and rheumatoid arthritis.²³ Advise these patients to avoid caffeine.

Although indicated for treating RLS, ropinirole and pramipexole are FDA Pregnancy Category C, which means animal studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks. Opioids, carbamazepine, or gabapentin may be safer for pregnant patients.²⁴

Insomnia during menopause

The prevalence of insomnia increases from 33% to 36% in premenopausal women to 44% to 61% in postmenopausal women.¹⁴ Hot flashes, comorbid mood disturbances, sleep-disordered breathing, and RLS contribute to increased insomnia risk in postmenopausal women (Table 3).^4,14,25,26

Treatment strategy. Always inquire about sleep in perimenopausal/postmenopausal women, even when her presenting complaint is related to menstrual cycle changes or vasomotor symptoms such as hot flashes.¹⁶ Assess patients for OSA, RLS, and mood, anxiety, and cognitive symptoms.²⁶ In addition to pharmacotherapy and behavioral therapy, treatment options include hormone replacement therapy (HRT) and herbal and dietary supplements (Table 4).^27-32

Table 3

Sleep difficulties during menopause: Differential diagnoses

Table 4

Treating insomnia in menopausal women

Comorbid psychiatric disorders

Women have a higher prevalence of psychiatric disorders such as major depressive disorder and anxiety disorders than men.¹ Women have a 10% to 25% lifetime risk of developing major depression. Three quarters of depressed patients experience insomnia.¹ Recent literature suggests insomnia is a risk factor for depression,³³ which emphasizes the need to screen women who present with sleep problems for depression and anxiety.

Five percent to 20% of women experience postpartum depression. Depression and insomnia are correlated to the rapid decline in estrogen and progesterone after delivery.³⁴

Treatment strategy. Insomnia is a common presenting symptom in patients with psychiatric conditions such as mood and anxiety disorders. Treating the underlying psychiatric disorder often alleviates sleeping difficulties. However, if the insomnia is disabling, treat the psychiatric disorder and insomnia concurrently.

CASE CONTINUED: Perimenopausal insomnia

Based on her history, you diagnose Ms. A with insomnia related to general medical condition (perimenopause). There are no indications to refer her for polysomnography. You educate Ms. A about sleep hygiene and recommend that she discuss her menstrual and physical complaints with her primary care physician or gynecologist. Ms. A is not interested in HRT because she has a strong family history of endometrial cancer. You reassure Ms. A and schedule a follow-up visit in 2 months to re-evaluate her insomnia.

Related resource

• Krahn LE. Perimenopausal depression? Ask how she’s sleeping. Current Psychiatry. 2005;4(6):39-53.

Drug brand names

• Carbamazepine • Carbatrol, Tegretol, others
• Escitalopram • Lexapro
• Eszopiclone • Lunesta
• Fluoxetine • Prozac
• Gabapentin • Neurontin, Gabarone
• Paroxetine • Paxil
• Pramipexole • Mirapex
• Ramelteon • Rozerem
• Ropinirole • Requip
• Sertraline • Zoloft
• Trazodone • Desyrel
• Zolpidem • Ambien

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgements

The authors thank Dr. Namita Dhiman and Darrel E. Willoughby for their assistance with this article.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

TABLE 2
In transition: From PCV7 to PCV13

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

TABLE 2
In transition: From PCV7 to PCV13

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

TABLE 2
In transition: From PCV7 to PCV13

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

How do the authors of “Do beta blockers cause depression?” (Medicine in Brief, Current Psychiatry, May 2010) feel about using propranolol augmentation for patients with anxiety who are already taking a selective serotonin reuptake inhibitor and a benzodiazepine? I often prescribe propranolol because it has a different mechanism of action—but I am curious if others would consider doing more of this, provided the patient is at low risk for suicidal thoughts and attempts.

Corey Yilmaz, MD
Adult and child psychiatrist
Buckeye, AZ

The authors respond

In 1966 Drs. Granville-Grossman and Turner published a seminal article on propranolol for anxiety disorders.¹ Their study included 16 patients who used propranolol, 20 mg/d, which had a beneficial effect on anxiety by alleviating autonomically mediated symptoms. This article also provided evidence for a belief that beta blockers are beneficial in anxiety mainly because they reduce somatic symptoms, a finding that has been supported by review articles.^2,3 We found only 2 studies examining adjunctive use of propranolol.^4,5 In these studies, propranolol combined with alprazolam was found to be well tolerated and effectively reduced somatic anxiety symptoms. Based on available evidence, the addition of a beta blocker could benefit patients who continue to experience physical symptoms of anxiety despite being treated with psychotropics.

Andrew J. Muzyk, PharmD
Assistant professor
Campbell University School of Pharmacy
Clinical specialist in internal medicine/psychiatry
Department of pharmacy
Duke University Hospital

Jane Gagliardi, MD
Assistant professor of psychiatry and behavioral sciences
Assistant clinical professor of medicine
Duke University School of Medicine
Durham, NC

How do the authors of “Do beta blockers cause depression?” (Medicine in Brief, Current Psychiatry, May 2010) feel about using propranolol augmentation for patients with anxiety who are already taking a selective serotonin reuptake inhibitor and a benzodiazepine? I often prescribe propranolol because it has a different mechanism of action—but I am curious if others would consider doing more of this, provided the patient is at low risk for suicidal thoughts and attempts.

Corey Yilmaz, MD
Adult and child psychiatrist
Buckeye, AZ

The authors respond

In 1966 Drs. Granville-Grossman and Turner published a seminal article on propranolol for anxiety disorders.¹ Their study included 16 patients who used propranolol, 20 mg/d, which had a beneficial effect on anxiety by alleviating autonomically mediated symptoms. This article also provided evidence for a belief that beta blockers are beneficial in anxiety mainly because they reduce somatic symptoms, a finding that has been supported by review articles.^2,3 We found only 2 studies examining adjunctive use of propranolol.^4,5 In these studies, propranolol combined with alprazolam was found to be well tolerated and effectively reduced somatic anxiety symptoms. Based on available evidence, the addition of a beta blocker could benefit patients who continue to experience physical symptoms of anxiety despite being treated with psychotropics.

Andrew J. Muzyk, PharmD
Assistant professor
Campbell University School of Pharmacy
Clinical specialist in internal medicine/psychiatry
Department of pharmacy
Duke University Hospital

Jane Gagliardi, MD
Assistant professor of psychiatry and behavioral sciences
Assistant clinical professor of medicine
Duke University School of Medicine
Durham, NC

How do the authors of “Do beta blockers cause depression?” (Medicine in Brief, Current Psychiatry, May 2010) feel about using propranolol augmentation for patients with anxiety who are already taking a selective serotonin reuptake inhibitor and a benzodiazepine? I often prescribe propranolol because it has a different mechanism of action—but I am curious if others would consider doing more of this, provided the patient is at low risk for suicidal thoughts and attempts.

Corey Yilmaz, MD
Adult and child psychiatrist
Buckeye, AZ

The authors respond

In 1966 Drs. Granville-Grossman and Turner published a seminal article on propranolol for anxiety disorders.¹ Their study included 16 patients who used propranolol, 20 mg/d, which had a beneficial effect on anxiety by alleviating autonomically mediated symptoms. This article also provided evidence for a belief that beta blockers are beneficial in anxiety mainly because they reduce somatic symptoms, a finding that has been supported by review articles.^2,3 We found only 2 studies examining adjunctive use of propranolol.^4,5 In these studies, propranolol combined with alprazolam was found to be well tolerated and effectively reduced somatic anxiety symptoms. Based on available evidence, the addition of a beta blocker could benefit patients who continue to experience physical symptoms of anxiety despite being treated with psychotropics.

Andrew J. Muzyk, PharmD
Assistant professor
Campbell University School of Pharmacy
Clinical specialist in internal medicine/psychiatry
Department of pharmacy
Duke University Hospital

Jane Gagliardi, MD
Assistant professor of psychiatry and behavioral sciences
Assistant clinical professor of medicine
Duke University School of Medicine
Durham, NC