Clinical Review

CASE: Is vacuum extraction right for this delivery?
A 41-year-old woman (G2P2002) is at term in her third pregnancy, and the fetus exhibits prolonged deceleration that does not resolve while the mother pushes from a +3 station. The fetus, estimated to weigh 8 lb, is in the occiput anterior (OA) position. The mother is willing to consider vaginal extraction, and you must weigh the factors that may influence successful delivery.

Vacuum extraction (VE) is an effective method to facilitate delivery. From 2007 to 2013, VE was used to facilitate about 3% of vaginal deliveries in the United States.¹ By contrast, cesarean delivery rates over the same period averaged about 30%.²

Controversy exists on the pros and cons of operative vaginal deliveries versus cesarean delivery, as well as on the instruments and operational approaches used. While opinion tends to be resolute and influential, evidence remains inconclusive.

Multiple factors influence a decision on whether to choose VE. The clinician’s own bias regarding delivery routes and comfort level with performing VE are important. The patient, too, may have preconceived opinions about VE. Knowing the indications for VE and its benefits and risks (TABLE 1) can help the patient make an informed choice and the counseling on which will be needed in obtaining the patient’s informed consent. The expectations and desires of the patient in concert with the experience and skill of the clinician will serve to achieve the optimal decision.

Indications for VE
Maternal indications for the use of VE include prolongation or arrest of the second stage of labor. Another indication is the need to shorten the second stage due to a maternal cardiac or cardiovascular disorder or due to maternal exhaustion.

Fetal indications include nonreassuring fetal status or a need to correct for minor degrees of malposition (asynclitism, deflexion) that historically have been addressed with the use of obstetric forceps. VE delivery in these circumstances requires a very experienced and skilled operator.

Further selection criteria
Birthweight influences the consideration of VE. Low birthweight or prematurity are contraindications to the use of VE due to concerns about fetal/neonatal bleeding. Large fetuses will have issues with cephalopelvic disproportion, thus increasing the risk for 2 disorders: shoulder dystocia and fetal cranial bleeding.

Cranial bleeding, both intracranial and extracranial, can result in serious neonatal morbidity and mortality. Bleeding may occur spontaneously or with the use of VE. In using VE, force is transmitted to the fetal scalp. The scalp then has the tendency to pull on its contents and attachments—skull bones, brain, fluids, etc. The scalp attachments include vessels at right angles to the scalp, which may be traumatized or torn by the pulling force. This may lead to subgaleal hemorrhage, a collection of blood in the large potential space below the scalp and above the aponeurosis. Enough force may be generated to deform the intracranial contents and cause intracranial bleeding.

The likelihood of success with VE varies depending on maternal anatomy, the position of the fetal head, gestational age, and the presence or absence of gestational diabetes (TABLE 2).

Delivery by VE: Main considerations
After determining that a candidate is suitable for VE and obtaining informed consent, consider key operative factors:

Two major cup types are available: rigid and flexible.

Rigid plastic cup. This design is similar to the metal cup used by Malmström and attaches to the scalp via chignon formation. A variation of the rigid cup is the mityvac “M” that mimics the Malmström design but incorporates a semiflexible handle to facilitate proper cup placement and aid in the direction of pulling force.

Flexible cup. This type of cup flattens against the scalp with vacuum and may result in less minor scalp trauma than the rigid cup.

Greater force can be employed with rigid cup designs than with flexible cups, which can increase the chances of a successful delivery when the fetus is in the occiput posterior (OP) position. Flexible designs tend to cause less damage to the scalp than the rigid cup but are reported to have a higher failure rate.

Cardinal rule of any procedure. Prior to cup placement, remember this rule: abandon the procedure if it proves too difficult. Most deliveries will occur with 3 or 4 pulls.³ Difficulties include:

Less than optimal placement of the vacuum extractor will increase the risk of scalp trauma, particularly in nulliparous women.³

If the procedure is unsuccessful, the resulting options include cesarean delivery and expectant management.

Tip. Use both hands during the pull to more reliably detect a problem with cup attachment, thereby minimizing the possibility of detachment and subsequent scalp trauma (FIGURE).

Key points of technique
Perform a careful and thorough pelvic examination to determine fetal station, position, attitude, and synclitism.

The optimal cup placement is 2- to 3-cm proximal to the posterior fontanel or, alternatively, 5- to 6-cm distal to the anterior fontanel, assuming the fetal head is properly flexed.⁴ The correct point of flexion will result in the smallest diameter of the fetal head presenting to the birth canal and should minimize the force necessary to achieve delivery.

Use minimal vacuum to attach the cup to the fetal head. As the subsequent contraction develops, apply full vacuum with the hand device. Encourage maternal expulsive effort and use traction only in concert with pushing efforts. Three pushes facilitated with pulling may be achieved during a single contraction. Failure to bring about descent with the initial pull indicates potential failure with this approach and, in the absence of technical reasons for the failure, merits serious consideration of abandoning the procedure (TABLE 3).

In the event of failed delivery with VE, it is important to recognize that you should not make a second attempt with another instrument; the chance of success is low and the risk of injury is significantly increased.⁵

Carefully document the decision for VE and its implementation
The medical record is the most important witness to the event. Clearly record the following items, preferably as close in time to the decision/event as possible:

Closing reminders and advice
In preparing to discuss the patient’s preferences for delivery, understand clearly the risks and benefits of VE and develop a comfortable approach to sharing this information with your patient and her family. Also, if VE is selected, consider performing the procedure in the cesarean delivery room. This will serve to remind you to be mindful to abandon the procedure, if need be, at an appropriate point.

CASE: Resolved
You apply the vacuum extractor, and a small amount of vacuum demonstrates satisfactory attachment. On the second pull, the fetus easily delivers, and the Apgar scores are 8 and 8. The birthweight is 3,725 g. The vacuum-assisted delivery has resulted in the shortest delay in delivery and without adverse consequences for neonate or mother.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE: Is vacuum extraction right for this delivery?
A 41-year-old woman (G2P2002) is at term in her third pregnancy, and the fetus exhibits prolonged deceleration that does not resolve while the mother pushes from a +3 station. The fetus, estimated to weigh 8 lb, is in the occiput anterior (OA) position. The mother is willing to consider vaginal extraction, and you must weigh the factors that may influence successful delivery.

Vacuum extraction (VE) is an effective method to facilitate delivery. From 2007 to 2013, VE was used to facilitate about 3% of vaginal deliveries in the United States.¹ By contrast, cesarean delivery rates over the same period averaged about 30%.²

Controversy exists on the pros and cons of operative vaginal deliveries versus cesarean delivery, as well as on the instruments and operational approaches used. While opinion tends to be resolute and influential, evidence remains inconclusive.

Multiple factors influence a decision on whether to choose VE. The clinician’s own bias regarding delivery routes and comfort level with performing VE are important. The patient, too, may have preconceived opinions about VE. Knowing the indications for VE and its benefits and risks (TABLE 1) can help the patient make an informed choice and the counseling on which will be needed in obtaining the patient’s informed consent. The expectations and desires of the patient in concert with the experience and skill of the clinician will serve to achieve the optimal decision.

Indications for VE
Maternal indications for the use of VE include prolongation or arrest of the second stage of labor. Another indication is the need to shorten the second stage due to a maternal cardiac or cardiovascular disorder or due to maternal exhaustion.

Fetal indications include nonreassuring fetal status or a need to correct for minor degrees of malposition (asynclitism, deflexion) that historically have been addressed with the use of obstetric forceps. VE delivery in these circumstances requires a very experienced and skilled operator.

Further selection criteria
Birthweight influences the consideration of VE. Low birthweight or prematurity are contraindications to the use of VE due to concerns about fetal/neonatal bleeding. Large fetuses will have issues with cephalopelvic disproportion, thus increasing the risk for 2 disorders: shoulder dystocia and fetal cranial bleeding.

Cranial bleeding, both intracranial and extracranial, can result in serious neonatal morbidity and mortality. Bleeding may occur spontaneously or with the use of VE. In using VE, force is transmitted to the fetal scalp. The scalp then has the tendency to pull on its contents and attachments—skull bones, brain, fluids, etc. The scalp attachments include vessels at right angles to the scalp, which may be traumatized or torn by the pulling force. This may lead to subgaleal hemorrhage, a collection of blood in the large potential space below the scalp and above the aponeurosis. Enough force may be generated to deform the intracranial contents and cause intracranial bleeding.

The likelihood of success with VE varies depending on maternal anatomy, the position of the fetal head, gestational age, and the presence or absence of gestational diabetes (TABLE 2).

Delivery by VE: Main considerations
After determining that a candidate is suitable for VE and obtaining informed consent, consider key operative factors:

Two major cup types are available: rigid and flexible.

Rigid plastic cup. This design is similar to the metal cup used by Malmström and attaches to the scalp via chignon formation. A variation of the rigid cup is the mityvac “M” that mimics the Malmström design but incorporates a semiflexible handle to facilitate proper cup placement and aid in the direction of pulling force.

Flexible cup. This type of cup flattens against the scalp with vacuum and may result in less minor scalp trauma than the rigid cup.

Greater force can be employed with rigid cup designs than with flexible cups, which can increase the chances of a successful delivery when the fetus is in the occiput posterior (OP) position. Flexible designs tend to cause less damage to the scalp than the rigid cup but are reported to have a higher failure rate.

Cardinal rule of any procedure. Prior to cup placement, remember this rule: abandon the procedure if it proves too difficult. Most deliveries will occur with 3 or 4 pulls.³ Difficulties include:

Less than optimal placement of the vacuum extractor will increase the risk of scalp trauma, particularly in nulliparous women.³

If the procedure is unsuccessful, the resulting options include cesarean delivery and expectant management.

Tip. Use both hands during the pull to more reliably detect a problem with cup attachment, thereby minimizing the possibility of detachment and subsequent scalp trauma (FIGURE).

Key points of technique
Perform a careful and thorough pelvic examination to determine fetal station, position, attitude, and synclitism.

The optimal cup placement is 2- to 3-cm proximal to the posterior fontanel or, alternatively, 5- to 6-cm distal to the anterior fontanel, assuming the fetal head is properly flexed.⁴ The correct point of flexion will result in the smallest diameter of the fetal head presenting to the birth canal and should minimize the force necessary to achieve delivery.

Use minimal vacuum to attach the cup to the fetal head. As the subsequent contraction develops, apply full vacuum with the hand device. Encourage maternal expulsive effort and use traction only in concert with pushing efforts. Three pushes facilitated with pulling may be achieved during a single contraction. Failure to bring about descent with the initial pull indicates potential failure with this approach and, in the absence of technical reasons for the failure, merits serious consideration of abandoning the procedure (TABLE 3).

In the event of failed delivery with VE, it is important to recognize that you should not make a second attempt with another instrument; the chance of success is low and the risk of injury is significantly increased.⁵

Carefully document the decision for VE and its implementation
The medical record is the most important witness to the event. Clearly record the following items, preferably as close in time to the decision/event as possible:

Closing reminders and advice
In preparing to discuss the patient’s preferences for delivery, understand clearly the risks and benefits of VE and develop a comfortable approach to sharing this information with your patient and her family. Also, if VE is selected, consider performing the procedure in the cesarean delivery room. This will serve to remind you to be mindful to abandon the procedure, if need be, at an appropriate point.

CASE: Resolved
You apply the vacuum extractor, and a small amount of vacuum demonstrates satisfactory attachment. On the second pull, the fetus easily delivers, and the Apgar scores are 8 and 8. The birthweight is 3,725 g. The vacuum-assisted delivery has resulted in the shortest delay in delivery and without adverse consequences for neonate or mother.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE: Is vacuum extraction right for this delivery?
A 41-year-old woman (G2P2002) is at term in her third pregnancy, and the fetus exhibits prolonged deceleration that does not resolve while the mother pushes from a +3 station. The fetus, estimated to weigh 8 lb, is in the occiput anterior (OA) position. The mother is willing to consider vaginal extraction, and you must weigh the factors that may influence successful delivery.

Vacuum extraction (VE) is an effective method to facilitate delivery. From 2007 to 2013, VE was used to facilitate about 3% of vaginal deliveries in the United States.¹ By contrast, cesarean delivery rates over the same period averaged about 30%.²

Controversy exists on the pros and cons of operative vaginal deliveries versus cesarean delivery, as well as on the instruments and operational approaches used. While opinion tends to be resolute and influential, evidence remains inconclusive.

Multiple factors influence a decision on whether to choose VE. The clinician’s own bias regarding delivery routes and comfort level with performing VE are important. The patient, too, may have preconceived opinions about VE. Knowing the indications for VE and its benefits and risks (TABLE 1) can help the patient make an informed choice and the counseling on which will be needed in obtaining the patient’s informed consent. The expectations and desires of the patient in concert with the experience and skill of the clinician will serve to achieve the optimal decision.

Indications for VE
Maternal indications for the use of VE include prolongation or arrest of the second stage of labor. Another indication is the need to shorten the second stage due to a maternal cardiac or cardiovascular disorder or due to maternal exhaustion.

Fetal indications include nonreassuring fetal status or a need to correct for minor degrees of malposition (asynclitism, deflexion) that historically have been addressed with the use of obstetric forceps. VE delivery in these circumstances requires a very experienced and skilled operator.

Further selection criteria
Birthweight influences the consideration of VE. Low birthweight or prematurity are contraindications to the use of VE due to concerns about fetal/neonatal bleeding. Large fetuses will have issues with cephalopelvic disproportion, thus increasing the risk for 2 disorders: shoulder dystocia and fetal cranial bleeding.

Cranial bleeding, both intracranial and extracranial, can result in serious neonatal morbidity and mortality. Bleeding may occur spontaneously or with the use of VE. In using VE, force is transmitted to the fetal scalp. The scalp then has the tendency to pull on its contents and attachments—skull bones, brain, fluids, etc. The scalp attachments include vessels at right angles to the scalp, which may be traumatized or torn by the pulling force. This may lead to subgaleal hemorrhage, a collection of blood in the large potential space below the scalp and above the aponeurosis. Enough force may be generated to deform the intracranial contents and cause intracranial bleeding.

The likelihood of success with VE varies depending on maternal anatomy, the position of the fetal head, gestational age, and the presence or absence of gestational diabetes (TABLE 2).

Delivery by VE: Main considerations
After determining that a candidate is suitable for VE and obtaining informed consent, consider key operative factors:

Two major cup types are available: rigid and flexible.

Rigid plastic cup. This design is similar to the metal cup used by Malmström and attaches to the scalp via chignon formation. A variation of the rigid cup is the mityvac “M” that mimics the Malmström design but incorporates a semiflexible handle to facilitate proper cup placement and aid in the direction of pulling force.

Flexible cup. This type of cup flattens against the scalp with vacuum and may result in less minor scalp trauma than the rigid cup.

Greater force can be employed with rigid cup designs than with flexible cups, which can increase the chances of a successful delivery when the fetus is in the occiput posterior (OP) position. Flexible designs tend to cause less damage to the scalp than the rigid cup but are reported to have a higher failure rate.

Cardinal rule of any procedure. Prior to cup placement, remember this rule: abandon the procedure if it proves too difficult. Most deliveries will occur with 3 or 4 pulls.³ Difficulties include:

Less than optimal placement of the vacuum extractor will increase the risk of scalp trauma, particularly in nulliparous women.³

If the procedure is unsuccessful, the resulting options include cesarean delivery and expectant management.

Tip. Use both hands during the pull to more reliably detect a problem with cup attachment, thereby minimizing the possibility of detachment and subsequent scalp trauma (FIGURE).

Key points of technique
Perform a careful and thorough pelvic examination to determine fetal station, position, attitude, and synclitism.

The optimal cup placement is 2- to 3-cm proximal to the posterior fontanel or, alternatively, 5- to 6-cm distal to the anterior fontanel, assuming the fetal head is properly flexed.⁴ The correct point of flexion will result in the smallest diameter of the fetal head presenting to the birth canal and should minimize the force necessary to achieve delivery.

Use minimal vacuum to attach the cup to the fetal head. As the subsequent contraction develops, apply full vacuum with the hand device. Encourage maternal expulsive effort and use traction only in concert with pushing efforts. Three pushes facilitated with pulling may be achieved during a single contraction. Failure to bring about descent with the initial pull indicates potential failure with this approach and, in the absence of technical reasons for the failure, merits serious consideration of abandoning the procedure (TABLE 3).

In the event of failed delivery with VE, it is important to recognize that you should not make a second attempt with another instrument; the chance of success is low and the risk of injury is significantly increased.⁵

Carefully document the decision for VE and its implementation
The medical record is the most important witness to the event. Clearly record the following items, preferably as close in time to the decision/event as possible:

Closing reminders and advice
In preparing to discuss the patient’s preferences for delivery, understand clearly the risks and benefits of VE and develop a comfortable approach to sharing this information with your patient and her family. Also, if VE is selected, consider performing the procedure in the cesarean delivery room. This will serve to remind you to be mindful to abandon the procedure, if need be, at an appropriate point.

CASE: Resolved
You apply the vacuum extractor, and a small amount of vacuum demonstrates satisfactory attachment. On the second pull, the fetus easily delivers, and the Apgar scores are 8 and 8. The birthweight is 3,725 g. The vacuum-assisted delivery has resulted in the shortest delay in delivery and without adverse consequences for neonate or mother.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Introduction

Between 2006 and 2013, over 9,000 continuous flow left ventricular assist devices (LVADs) were implanted in patients with end-stage heart failure; nearly 2,500 of these devices were placed in 2013 alone.¹ As the number of patients with an LVAD continues to grow, so too does the likelihood of a patient with an LVAD presenting to the ED—even if the hospital is not a designated VAD center. An earlier article appearing in the February 2014 issue of Emergency Medicine addressed the management of the unique medical complications faced by patients with LVADs.² This article focuses on troubleshooting the device when a patient with a LVAD presents to the ED.

Device Indications and Types

Left ventricular assist devices are mechanical implantable devices that provide circulatory support to patients with refractory advanced heart failure. A few of these devices are approved by the US Food and Drug Administration for use as either a bridge to heart transplant or as destination therapy if the patient is not a candidate for heart transplant.

Nearly all of the LVADs currently on the market are designed to provide continuous flow.^3-6 The most commonly employed LVADs include the HeartMate II (Thoratec Corporation, Pleasanton, California), HeartWare Ventricular Assist System (HeartWare, Framingham, Massachusetts), and the Jarvik 2000 VAS (Jarvik Heart, New York, New York) (Table). These devices differ somewhat in configuration, but the initial management of LVAD patients with a device malfunction is essentially the same.

Even though the type of device is clearly marked on the patient’s controller, to ensure appropriate management and facilitate troubleshooting for malfunction, patients should always carry an information card identifying the type of device implanted, as well as the complete contact information for each of their health care providers, including their LVAD coordinator.^3,7

Device Components

Left ventricular assist devices consist of several different components. All LVADs consist of a pump, controller, driveline, and batteries/battery pack that work together to augment function of the native heart.

Pump
     The LVAD pump is surgically implanted into the patient’s abdominal or chest cavity, with an inflow cannula positioned in the left ventricle and an outflow cannula inserted into the ascending aorta. The pump is designed to have a single internal moving part called the impeller. The pump draws blood from the left ventricle and directs it to the aorta.

Controller and Driveline
     The actions of the pump are directed by a controller, a mini-processor contained in a small box located outside the patient’s body. This processor is connected to the pump by a driveline inside the body. The driveline exits the body through the patient’s abdominal wall and connects to the controller. The controller regulates the pump speed and provides information about pump speed, flow, pulsatility index, and power of the LVAD.^3,4 
     Speed Monitor. The LVAD speed on the controller is usually set at the time of discharge from the hospital; most devices cannot be changed manually.
     Power Monitor. On the monitor, the "power" indictor reflects the voltage and current of the pump motor, whereas the "flow" indicator is a reflection of both power and speed (ie, the higher the power, the higher the flow and vice versa).
     Batteries/Battery Pack. The LVAD is powered by two batteries attached to the controller or, in some models, to a power base unit that can be plugged into an electrical outlet. Each battery is connected to the controller by a separate connector wire. When battery power in the device becomes low, the batteries should be replaced with fully charged backup batteries, one battery at a time. If the controller is disconnected from both batteries at the same time, the LVAD will lose power and stop working. It is critical to patient health that the LVAD be powered at all times.^3,5,7,8
     Pulsatility Index. Changes in a patient’s blood pressure (BP) can affect flow, with higher BP causing a decrease in flow. The pulsatility index reflects the heart’s contractility and stretch, as well as the patient’s volume status. As the preload decreases (ie, due to a decrease in blood volume) the device will indicate a decreased pulsatility index. If the patient is volume overloaded, the pulsatility index will be increased. Pump speed and pulsatility index are inversely related. In some devices, if the controller detects a significant change in pulsatility index from the prior 15-second average, it will reduce the pump speed to low and then gradually accelerate to the set fixed speed.^3,8 Significant changes in pulsatility index often indicate an event has occurred, such as an obstruction of the inflow cannula, a decrease in the patient’s volume status, an arrhythmia, or increased pulmonary artery pressure suggestive of right heart failure.^3,4

Patient Responsibility

Following LVAD placement, patients are discharged from the hospital with extra batteries (usually four to six), a battery-charger station, a spare controller, and in certain models, a power base unit that can power the LVAD when they are at home and/or asleep. When patients are away from home, they should always have extra fully charged batteries, the spare controller, information about their device, and the complete names and contact information for their health care providers (ie, cardiologist, cardiothoracic surgeon, VAD coordinator) with them at all times.^3,7,8

Patient Evaluation and Troubleshooting the Device

Perfusion and Mean Arterial Pressure
     At presentation, the EP should evaluate the patient for signs of poor perfusion (eg, decreased mental status, pallor, cool skin) and, when indicated, provide a fluid bolus. Patients with an LVAD typically do not have palpable pulses due to the continuous flow of their devices.^3-7 Therefore, a mean arterial pressure (MAP) using a Doppler and a manual BP cuff should be taken. The pressure at which the first sound is heard is used as the estimate of the MAP. The MAP for an LVAD patient generally should be between 70 and 90 mm Hg.^3,4,7
     Patients with an LVAD are afterload sensitive, and high BP must be addressed immediately to avoid morbidity. Elevated BP increases the work of the pump against increased peripheral resistance, which can lead to thrombus and stroke.⁷

Power and Connections
     The EP should always check the controller to make sure the power light is on. Once this has been confirmed, she or he should auscultate over the patient’s chest and abdomen to detect the humming sound of the pump. If the pump is not powered or does not appear to be functioning, the controller should be replaced with the patient’s backup controller. Next, all connections to the power source and the connection between the driveline and the controller should be checked to confirm they are intact. After this has been completed, the connections should be disconnected and reconnected. Then the driveline should be evaluated for defects or damage.

Battery Assessment
     While troubleshooting the LVAD for malfunction, the batteries on the device should be replaced with backup batteries or connected to the hospital’s power base unit (if one exists) or to the patient’s power base unit if it is present. If a battery replacement is required, before doing so, the patient should first be positioned flat on the stretcher or bed.⁷

Low-Flow Indicator
     The EP should always check the controller to determine which alarms, if any, are flashing. Although the alarm buttons vary among the various LVAD devices, all types have a “low-flow” indicator. If the controller indicates low flow, the patient first should be given a fluid bolus. Patients with LVADs are preload dependent, and given their history of heart failure and fluid restriction, are often reluctant to maintain good fluid intake once an LVAD has been implanted.^3,7
     Another important etiology for a low-flow reading on the LVAD controller is pump thrombosis. Pump thrombosis should be considered when the MAP is low and the controller indicates a decreased pulsatility index and decreased flow. Often the RPMs (the speed) are increased as the controller attempts to adjust to the thrombosis with an increase in power. A bedside echocardiogram showing dilated right and left ventricles is consistent with a pump thrombosis. Treatment for pump thrombosis is anticoagulation with heparin or thrombolytics, and cardiothoracic surgery should be consulted.³

Suction Events
     In addition to hypovolemia, another cause of hypotension is a “suction event” in which the left ventricle is not filling but the pump continues to attempt to pull blood from it and the walls of the ventricle suck in on themselves. Suction events can also be caused by cannula malposition, increased peripheral vascular resistance, and tamponade. A small left ventricle on bedside echocardiogram is consistent with a suction event. Often, the controller can sense this and will respond by slowing the pump speed and slowly bringing it back up to allow the ventricles to reaccumulate blood. Initial treatment consists of a fluid bolus and cardiothoracic surgery consultation.^3,4

Low Battery
     If an LVAD patient presents to the ED with a low battery, no backup batteries, and the hospital does not have a power base unit or other way to power the LVAD, the EP should call the patient’s VAD coordinator to assist. Often, the coordinator can identify a local LVAD patient who is willing to transport extra batteries to the ED.
     To conserve power, the controller in some LVAD models is programmed to automatically reduce the pump speed when the battery power becomes low. This feature can be a cause of syncope or lightheadedness in in some patients. While some older LVAD models had the capability of being powered by a hand pump in the event of loss of function, the newer devices do not.^4,7,8

Cardiac Assessment and Protocols

The presence of an LVAD should not have any effect on electrocardiography studies. When evaluating patients, standard advanced cardiac life support protocols should be followed, but extreme caution should be used before starting chest compressions as this can dislodge the cannula and lead to death. Prior to initiating chest compressions, the patient’s VAD coordinator should be contacted to ensure that any problems with the device itself have been considered, addressed, and ruled out. Defibrillation, cardioversion, and pacing are all acceptable in LVAD patients, but defibrillator or pacer pads should not be placed directly over the patient’s pump.⁷

Summary

As the number of patients with an implantable cardiac device continues to grow, EPs are likely to encounter an LVAD patient in the ED. An understanding of device function and knowledge of the basic trouble-shooting skills can prove life-saving in many instances. In addition, a familiarity with available LVAD resources, both online and within the health care community, is also essential to ensure the appropriate management and care of these patients.

Introduction

Between 2006 and 2013, over 9,000 continuous flow left ventricular assist devices (LVADs) were implanted in patients with end-stage heart failure; nearly 2,500 of these devices were placed in 2013 alone.¹ As the number of patients with an LVAD continues to grow, so too does the likelihood of a patient with an LVAD presenting to the ED—even if the hospital is not a designated VAD center. An earlier article appearing in the February 2014 issue of Emergency Medicine addressed the management of the unique medical complications faced by patients with LVADs.² This article focuses on troubleshooting the device when a patient with a LVAD presents to the ED.

Device Indications and Types

Left ventricular assist devices are mechanical implantable devices that provide circulatory support to patients with refractory advanced heart failure. A few of these devices are approved by the US Food and Drug Administration for use as either a bridge to heart transplant or as destination therapy if the patient is not a candidate for heart transplant.

Nearly all of the LVADs currently on the market are designed to provide continuous flow.^3-6 The most commonly employed LVADs include the HeartMate II (Thoratec Corporation, Pleasanton, California), HeartWare Ventricular Assist System (HeartWare, Framingham, Massachusetts), and the Jarvik 2000 VAS (Jarvik Heart, New York, New York) (Table). These devices differ somewhat in configuration, but the initial management of LVAD patients with a device malfunction is essentially the same.

Even though the type of device is clearly marked on the patient’s controller, to ensure appropriate management and facilitate troubleshooting for malfunction, patients should always carry an information card identifying the type of device implanted, as well as the complete contact information for each of their health care providers, including their LVAD coordinator.^3,7

Device Components

Left ventricular assist devices consist of several different components. All LVADs consist of a pump, controller, driveline, and batteries/battery pack that work together to augment function of the native heart.

Pump
     The LVAD pump is surgically implanted into the patient’s abdominal or chest cavity, with an inflow cannula positioned in the left ventricle and an outflow cannula inserted into the ascending aorta. The pump is designed to have a single internal moving part called the impeller. The pump draws blood from the left ventricle and directs it to the aorta.

Controller and Driveline
     The actions of the pump are directed by a controller, a mini-processor contained in a small box located outside the patient’s body. This processor is connected to the pump by a driveline inside the body. The driveline exits the body through the patient’s abdominal wall and connects to the controller. The controller regulates the pump speed and provides information about pump speed, flow, pulsatility index, and power of the LVAD.^3,4 
     Speed Monitor. The LVAD speed on the controller is usually set at the time of discharge from the hospital; most devices cannot be changed manually.
     Power Monitor. On the monitor, the "power" indictor reflects the voltage and current of the pump motor, whereas the "flow" indicator is a reflection of both power and speed (ie, the higher the power, the higher the flow and vice versa).
     Batteries/Battery Pack. The LVAD is powered by two batteries attached to the controller or, in some models, to a power base unit that can be plugged into an electrical outlet. Each battery is connected to the controller by a separate connector wire. When battery power in the device becomes low, the batteries should be replaced with fully charged backup batteries, one battery at a time. If the controller is disconnected from both batteries at the same time, the LVAD will lose power and stop working. It is critical to patient health that the LVAD be powered at all times.^3,5,7,8
     Pulsatility Index. Changes in a patient’s blood pressure (BP) can affect flow, with higher BP causing a decrease in flow. The pulsatility index reflects the heart’s contractility and stretch, as well as the patient’s volume status. As the preload decreases (ie, due to a decrease in blood volume) the device will indicate a decreased pulsatility index. If the patient is volume overloaded, the pulsatility index will be increased. Pump speed and pulsatility index are inversely related. In some devices, if the controller detects a significant change in pulsatility index from the prior 15-second average, it will reduce the pump speed to low and then gradually accelerate to the set fixed speed.^3,8 Significant changes in pulsatility index often indicate an event has occurred, such as an obstruction of the inflow cannula, a decrease in the patient’s volume status, an arrhythmia, or increased pulmonary artery pressure suggestive of right heart failure.^3,4

Patient Responsibility

Following LVAD placement, patients are discharged from the hospital with extra batteries (usually four to six), a battery-charger station, a spare controller, and in certain models, a power base unit that can power the LVAD when they are at home and/or asleep. When patients are away from home, they should always have extra fully charged batteries, the spare controller, information about their device, and the complete names and contact information for their health care providers (ie, cardiologist, cardiothoracic surgeon, VAD coordinator) with them at all times.^3,7,8

Patient Evaluation and Troubleshooting the Device

Perfusion and Mean Arterial Pressure
     At presentation, the EP should evaluate the patient for signs of poor perfusion (eg, decreased mental status, pallor, cool skin) and, when indicated, provide a fluid bolus. Patients with an LVAD typically do not have palpable pulses due to the continuous flow of their devices.^3-7 Therefore, a mean arterial pressure (MAP) using a Doppler and a manual BP cuff should be taken. The pressure at which the first sound is heard is used as the estimate of the MAP. The MAP for an LVAD patient generally should be between 70 and 90 mm Hg.^3,4,7
     Patients with an LVAD are afterload sensitive, and high BP must be addressed immediately to avoid morbidity. Elevated BP increases the work of the pump against increased peripheral resistance, which can lead to thrombus and stroke.⁷

Power and Connections
     The EP should always check the controller to make sure the power light is on. Once this has been confirmed, she or he should auscultate over the patient’s chest and abdomen to detect the humming sound of the pump. If the pump is not powered or does not appear to be functioning, the controller should be replaced with the patient’s backup controller. Next, all connections to the power source and the connection between the driveline and the controller should be checked to confirm they are intact. After this has been completed, the connections should be disconnected and reconnected. Then the driveline should be evaluated for defects or damage.

Battery Assessment
     While troubleshooting the LVAD for malfunction, the batteries on the device should be replaced with backup batteries or connected to the hospital’s power base unit (if one exists) or to the patient’s power base unit if it is present. If a battery replacement is required, before doing so, the patient should first be positioned flat on the stretcher or bed.⁷

Low-Flow Indicator
     The EP should always check the controller to determine which alarms, if any, are flashing. Although the alarm buttons vary among the various LVAD devices, all types have a “low-flow” indicator. If the controller indicates low flow, the patient first should be given a fluid bolus. Patients with LVADs are preload dependent, and given their history of heart failure and fluid restriction, are often reluctant to maintain good fluid intake once an LVAD has been implanted.^3,7
     Another important etiology for a low-flow reading on the LVAD controller is pump thrombosis. Pump thrombosis should be considered when the MAP is low and the controller indicates a decreased pulsatility index and decreased flow. Often the RPMs (the speed) are increased as the controller attempts to adjust to the thrombosis with an increase in power. A bedside echocardiogram showing dilated right and left ventricles is consistent with a pump thrombosis. Treatment for pump thrombosis is anticoagulation with heparin or thrombolytics, and cardiothoracic surgery should be consulted.³

Suction Events
     In addition to hypovolemia, another cause of hypotension is a “suction event” in which the left ventricle is not filling but the pump continues to attempt to pull blood from it and the walls of the ventricle suck in on themselves. Suction events can also be caused by cannula malposition, increased peripheral vascular resistance, and tamponade. A small left ventricle on bedside echocardiogram is consistent with a suction event. Often, the controller can sense this and will respond by slowing the pump speed and slowly bringing it back up to allow the ventricles to reaccumulate blood. Initial treatment consists of a fluid bolus and cardiothoracic surgery consultation.^3,4

Low Battery
     If an LVAD patient presents to the ED with a low battery, no backup batteries, and the hospital does not have a power base unit or other way to power the LVAD, the EP should call the patient’s VAD coordinator to assist. Often, the coordinator can identify a local LVAD patient who is willing to transport extra batteries to the ED.
     To conserve power, the controller in some LVAD models is programmed to automatically reduce the pump speed when the battery power becomes low. This feature can be a cause of syncope or lightheadedness in in some patients. While some older LVAD models had the capability of being powered by a hand pump in the event of loss of function, the newer devices do not.^4,7,8

Cardiac Assessment and Protocols

The presence of an LVAD should not have any effect on electrocardiography studies. When evaluating patients, standard advanced cardiac life support protocols should be followed, but extreme caution should be used before starting chest compressions as this can dislodge the cannula and lead to death. Prior to initiating chest compressions, the patient’s VAD coordinator should be contacted to ensure that any problems with the device itself have been considered, addressed, and ruled out. Defibrillation, cardioversion, and pacing are all acceptable in LVAD patients, but defibrillator or pacer pads should not be placed directly over the patient’s pump.⁷

Summary

As the number of patients with an implantable cardiac device continues to grow, EPs are likely to encounter an LVAD patient in the ED. An understanding of device function and knowledge of the basic trouble-shooting skills can prove life-saving in many instances. In addition, a familiarity with available LVAD resources, both online and within the health care community, is also essential to ensure the appropriate management and care of these patients.

Introduction

Between 2006 and 2013, over 9,000 continuous flow left ventricular assist devices (LVADs) were implanted in patients with end-stage heart failure; nearly 2,500 of these devices were placed in 2013 alone.¹ As the number of patients with an LVAD continues to grow, so too does the likelihood of a patient with an LVAD presenting to the ED—even if the hospital is not a designated VAD center. An earlier article appearing in the February 2014 issue of Emergency Medicine addressed the management of the unique medical complications faced by patients with LVADs.² This article focuses on troubleshooting the device when a patient with a LVAD presents to the ED.

Device Indications and Types

Left ventricular assist devices are mechanical implantable devices that provide circulatory support to patients with refractory advanced heart failure. A few of these devices are approved by the US Food and Drug Administration for use as either a bridge to heart transplant or as destination therapy if the patient is not a candidate for heart transplant.

Nearly all of the LVADs currently on the market are designed to provide continuous flow.^3-6 The most commonly employed LVADs include the HeartMate II (Thoratec Corporation, Pleasanton, California), HeartWare Ventricular Assist System (HeartWare, Framingham, Massachusetts), and the Jarvik 2000 VAS (Jarvik Heart, New York, New York) (Table). These devices differ somewhat in configuration, but the initial management of LVAD patients with a device malfunction is essentially the same.

Even though the type of device is clearly marked on the patient’s controller, to ensure appropriate management and facilitate troubleshooting for malfunction, patients should always carry an information card identifying the type of device implanted, as well as the complete contact information for each of their health care providers, including their LVAD coordinator.^3,7

Device Components

Left ventricular assist devices consist of several different components. All LVADs consist of a pump, controller, driveline, and batteries/battery pack that work together to augment function of the native heart.

Pump
     The LVAD pump is surgically implanted into the patient’s abdominal or chest cavity, with an inflow cannula positioned in the left ventricle and an outflow cannula inserted into the ascending aorta. The pump is designed to have a single internal moving part called the impeller. The pump draws blood from the left ventricle and directs it to the aorta.

Controller and Driveline
     The actions of the pump are directed by a controller, a mini-processor contained in a small box located outside the patient’s body. This processor is connected to the pump by a driveline inside the body. The driveline exits the body through the patient’s abdominal wall and connects to the controller. The controller regulates the pump speed and provides information about pump speed, flow, pulsatility index, and power of the LVAD.^3,4 
     Speed Monitor. The LVAD speed on the controller is usually set at the time of discharge from the hospital; most devices cannot be changed manually.
     Power Monitor. On the monitor, the "power" indictor reflects the voltage and current of the pump motor, whereas the "flow" indicator is a reflection of both power and speed (ie, the higher the power, the higher the flow and vice versa).
     Batteries/Battery Pack. The LVAD is powered by two batteries attached to the controller or, in some models, to a power base unit that can be plugged into an electrical outlet. Each battery is connected to the controller by a separate connector wire. When battery power in the device becomes low, the batteries should be replaced with fully charged backup batteries, one battery at a time. If the controller is disconnected from both batteries at the same time, the LVAD will lose power and stop working. It is critical to patient health that the LVAD be powered at all times.^3,5,7,8
     Pulsatility Index. Changes in a patient’s blood pressure (BP) can affect flow, with higher BP causing a decrease in flow. The pulsatility index reflects the heart’s contractility and stretch, as well as the patient’s volume status. As the preload decreases (ie, due to a decrease in blood volume) the device will indicate a decreased pulsatility index. If the patient is volume overloaded, the pulsatility index will be increased. Pump speed and pulsatility index are inversely related. In some devices, if the controller detects a significant change in pulsatility index from the prior 15-second average, it will reduce the pump speed to low and then gradually accelerate to the set fixed speed.^3,8 Significant changes in pulsatility index often indicate an event has occurred, such as an obstruction of the inflow cannula, a decrease in the patient’s volume status, an arrhythmia, or increased pulmonary artery pressure suggestive of right heart failure.^3,4

Patient Responsibility

Following LVAD placement, patients are discharged from the hospital with extra batteries (usually four to six), a battery-charger station, a spare controller, and in certain models, a power base unit that can power the LVAD when they are at home and/or asleep. When patients are away from home, they should always have extra fully charged batteries, the spare controller, information about their device, and the complete names and contact information for their health care providers (ie, cardiologist, cardiothoracic surgeon, VAD coordinator) with them at all times.^3,7,8

Patient Evaluation and Troubleshooting the Device

Perfusion and Mean Arterial Pressure
     At presentation, the EP should evaluate the patient for signs of poor perfusion (eg, decreased mental status, pallor, cool skin) and, when indicated, provide a fluid bolus. Patients with an LVAD typically do not have palpable pulses due to the continuous flow of their devices.^3-7 Therefore, a mean arterial pressure (MAP) using a Doppler and a manual BP cuff should be taken. The pressure at which the first sound is heard is used as the estimate of the MAP. The MAP for an LVAD patient generally should be between 70 and 90 mm Hg.^3,4,7
     Patients with an LVAD are afterload sensitive, and high BP must be addressed immediately to avoid morbidity. Elevated BP increases the work of the pump against increased peripheral resistance, which can lead to thrombus and stroke.⁷

Power and Connections
     The EP should always check the controller to make sure the power light is on. Once this has been confirmed, she or he should auscultate over the patient’s chest and abdomen to detect the humming sound of the pump. If the pump is not powered or does not appear to be functioning, the controller should be replaced with the patient’s backup controller. Next, all connections to the power source and the connection between the driveline and the controller should be checked to confirm they are intact. After this has been completed, the connections should be disconnected and reconnected. Then the driveline should be evaluated for defects or damage.

Battery Assessment
     While troubleshooting the LVAD for malfunction, the batteries on the device should be replaced with backup batteries or connected to the hospital’s power base unit (if one exists) or to the patient’s power base unit if it is present. If a battery replacement is required, before doing so, the patient should first be positioned flat on the stretcher or bed.⁷

Low-Flow Indicator
     The EP should always check the controller to determine which alarms, if any, are flashing. Although the alarm buttons vary among the various LVAD devices, all types have a “low-flow” indicator. If the controller indicates low flow, the patient first should be given a fluid bolus. Patients with LVADs are preload dependent, and given their history of heart failure and fluid restriction, are often reluctant to maintain good fluid intake once an LVAD has been implanted.^3,7
     Another important etiology for a low-flow reading on the LVAD controller is pump thrombosis. Pump thrombosis should be considered when the MAP is low and the controller indicates a decreased pulsatility index and decreased flow. Often the RPMs (the speed) are increased as the controller attempts to adjust to the thrombosis with an increase in power. A bedside echocardiogram showing dilated right and left ventricles is consistent with a pump thrombosis. Treatment for pump thrombosis is anticoagulation with heparin or thrombolytics, and cardiothoracic surgery should be consulted.³

Suction Events
     In addition to hypovolemia, another cause of hypotension is a “suction event” in which the left ventricle is not filling but the pump continues to attempt to pull blood from it and the walls of the ventricle suck in on themselves. Suction events can also be caused by cannula malposition, increased peripheral vascular resistance, and tamponade. A small left ventricle on bedside echocardiogram is consistent with a suction event. Often, the controller can sense this and will respond by slowing the pump speed and slowly bringing it back up to allow the ventricles to reaccumulate blood. Initial treatment consists of a fluid bolus and cardiothoracic surgery consultation.^3,4

Low Battery
     If an LVAD patient presents to the ED with a low battery, no backup batteries, and the hospital does not have a power base unit or other way to power the LVAD, the EP should call the patient’s VAD coordinator to assist. Often, the coordinator can identify a local LVAD patient who is willing to transport extra batteries to the ED.
     To conserve power, the controller in some LVAD models is programmed to automatically reduce the pump speed when the battery power becomes low. This feature can be a cause of syncope or lightheadedness in in some patients. While some older LVAD models had the capability of being powered by a hand pump in the event of loss of function, the newer devices do not.^4,7,8

Cardiac Assessment and Protocols

The presence of an LVAD should not have any effect on electrocardiography studies. When evaluating patients, standard advanced cardiac life support protocols should be followed, but extreme caution should be used before starting chest compressions as this can dislodge the cannula and lead to death. Prior to initiating chest compressions, the patient’s VAD coordinator should be contacted to ensure that any problems with the device itself have been considered, addressed, and ruled out. Defibrillation, cardioversion, and pacing are all acceptable in LVAD patients, but defibrillator or pacer pads should not be placed directly over the patient’s pump.⁷

Summary

As the number of patients with an implantable cardiac device continues to grow, EPs are likely to encounter an LVAD patient in the ED. An understanding of device function and knowledge of the basic trouble-shooting skills can prove life-saving in many instances. In addition, a familiarity with available LVAD resources, both online and within the health care community, is also essential to ensure the appropriate management and care of these patients.

Introduction

Coarctation of the aorta comprises approximately 5% to 8% of congenital heart defects and is often associated with valvular malformations.¹ These defects are typically diagnosed early and are managed with surgical repair, balloon angioplasty, or endovascular stent placement. However, as the following case illustrates, complications can occur in this population despite early intervention.

Case

A 15-year-old male adolescent presented to the pediatric ED after repeated blood pressure (BP) checks by the school nurse revealed consistently elevated systolic and diastolic pressures. The patient’s hypertension was associated with symptoms of intermittent headache and light-headedness. His medical history was remarkable for a congenital aortic coarctation and a bicuspid aortic valve. The patient had undergone a subclavian flap repair prior to 1 month of age, followed by a balloon dilatation 1 year later for recurrent coarctation. The rest of the patient’s medical history was unremarkable, including normal renal function. He denied illicit drug or alcohol use, sexual activity, or trauma.

On evaluation, the patient’s cardiac examination revealed a regular rate and rhythm with normally split S2; there were no rubs, murmurs, or gallops on auscultation. He had normal and equal pulses of the upper and lower extremities bilaterally. The patient presented without cyanosis. He was alert and oriented with normal upper and lower extremity reflexes. The neurological examination, including cranial nerve, strength, and gait testing, was unremarkable. The gastrointestinal examination showed a soft, nondistended abdomen, with no pulsatile masses. There was no abnormal swelling of his extremities. Although the physical examination findings were unremarkable, the patient’s vital signs were concerning as BP in his right upper extremity was as high as 208/110 mm Hg, while BP in his right leg was 130/68 mm Hg.

The patient followed up with his cardiologist, who ordered cardiac magnetic resonance imaging (MRI). The MRI showed mild narrowing of the distal aortic arch with a minimal and clinically insignificant pressure gradient. Based on the MRI findings, the patient was referred to a pediatric nephrologist, who performed a 24-hour ambulatory BP evaluation. The results of this study showed the patient to have systolic hypertension at the 95th percentile for his age and height. Based on the patient’s athletic predilection, β-blockers were avoided, and he was instead started on the angiotensin-converting enzyme (ACE) inhibitor lisinopril, along with annual follow-up cardiac evaluation.

Discussion

The authors’ initial concern for this patient was the possibility of a recurrent coarctation causing a significant pressure gradient between the upper and lower extremities with associated symptoms. A review of the literature demonstrates such an occurrence is not uncommon in this patient population, especially in patients with a history of early intervention (ie, within the first year of life).²

Causes and Incidence

One of the factors believed to contribute to recurrent coarctation is insufficient growth versus retraction of the manipulated tissues over time. The rates of recurrence vary based on the initial technique used for repair. These recurrences have been found to be approximately 6% in patients who had subclavian flap repairs; 31% for those who had balloon angioplasty alone; and approximately 20% in patients who had aortic stenting.^3-5 As seen in this case, balloon angioplasty is usually performed in patients requiring revascularization. However, up to 32% of these patients will require further intervention due to subsequent recurrence.⁶

Evaluation

Although emergency physicians (EPs) have numerous diagnostic modalities available to evaluate patients with suspected aortic coarctation, as long as the patient is in no acute distress, much of the work-up can be performed on an outpatient basis—in conjunction with the primary- and subspecialty-care team. Regarding appropriate imaging modalities, echocardiography with Doppler or 3D reconstruction of MR angiogram can be useful in detecting both anatomical abnormalities as well as the associated gradient dysfunction; computed tomography can be used for assessing the anatomy.⁷ All of these modalities can also be used to evaluate late-term complications of aortic coarctation pathology, including aortic aneurysms. To help ensure good outcome, the EP should always keep the possibility of recurrence in the differential when evaluating these patients, regardless of the number of previous interventions attempted.

Hypertension

As this case illustrates, patients with a history of coarctation repair often develop high BP. Unfortunately, up to 23% of these patients will go on to have BP above the 95th percentile.⁵ Moreover, a significant number of patients in this population will also suffer from exercise-induced hypertension, even when at-rest BP is controlled with antihypertensive medications.⁸

β-blockers, angiotensin-receptor blockers, and ACE inhibitors are considered the first-line medications for hypertension in adults and adult-sized patients with this condition.⁹

Since a high proportion of patients as young as age 7 years may develop high BP postrepair,¹⁰ the EP should discuss the initiation of an antihypertensive agent with the patient’s care team prior to discharge. It is also important to keep in mind that elevated BP is present to a significant degree even in patients without recurrent obstruction. The negative sequelae associated with uncontrolled hypertension is well known, and patients with congenital anatomical anomalies are at higher risk for such negative outcomes.

Conclusion

This case illustrates a common presentation of a teenaged patient with a chronic medical condition due to a corrected congenital cardiac defect. It also demonstrates the unique and early opportunity the EP has to evaluate and provide appropriate intervention for patients with potentially life-threatening diseases.

Patients with a history of corrective vascular surgery due to congenital heart malformations are an at-risk population. Therefore, during evaluation, the EP should always keep in mind that that these patients have a higher prevalence of related abnormalities at earlier ages than the general population. Steps initiated in the ED prior to discharge, in collaboration with the patient’s primary- and specialty-care team, can assist in expediting appropriate outpatient management of any sequelae. If a patient does not have a cardiologist, a referral to one should always be made prior to discharge.

Dr Smith is a postgraduate year 3 resident in the department of emergency medicine at Alpert Medical School of Brown University, Providence, Rhode Island. Dr Merritt is an assistant professor and pediatric emergency medicine attending in the department of emergency medicine, Brown Alpert Medical School, Providence, Rhode Island. 

Introduction

Coarctation of the aorta comprises approximately 5% to 8% of congenital heart defects and is often associated with valvular malformations.¹ These defects are typically diagnosed early and are managed with surgical repair, balloon angioplasty, or endovascular stent placement. However, as the following case illustrates, complications can occur in this population despite early intervention.

Case

A 15-year-old male adolescent presented to the pediatric ED after repeated blood pressure (BP) checks by the school nurse revealed consistently elevated systolic and diastolic pressures. The patient’s hypertension was associated with symptoms of intermittent headache and light-headedness. His medical history was remarkable for a congenital aortic coarctation and a bicuspid aortic valve. The patient had undergone a subclavian flap repair prior to 1 month of age, followed by a balloon dilatation 1 year later for recurrent coarctation. The rest of the patient’s medical history was unremarkable, including normal renal function. He denied illicit drug or alcohol use, sexual activity, or trauma.

On evaluation, the patient’s cardiac examination revealed a regular rate and rhythm with normally split S2; there were no rubs, murmurs, or gallops on auscultation. He had normal and equal pulses of the upper and lower extremities bilaterally. The patient presented without cyanosis. He was alert and oriented with normal upper and lower extremity reflexes. The neurological examination, including cranial nerve, strength, and gait testing, was unremarkable. The gastrointestinal examination showed a soft, nondistended abdomen, with no pulsatile masses. There was no abnormal swelling of his extremities. Although the physical examination findings were unremarkable, the patient’s vital signs were concerning as BP in his right upper extremity was as high as 208/110 mm Hg, while BP in his right leg was 130/68 mm Hg.

The patient followed up with his cardiologist, who ordered cardiac magnetic resonance imaging (MRI). The MRI showed mild narrowing of the distal aortic arch with a minimal and clinically insignificant pressure gradient. Based on the MRI findings, the patient was referred to a pediatric nephrologist, who performed a 24-hour ambulatory BP evaluation. The results of this study showed the patient to have systolic hypertension at the 95th percentile for his age and height. Based on the patient’s athletic predilection, β-blockers were avoided, and he was instead started on the angiotensin-converting enzyme (ACE) inhibitor lisinopril, along with annual follow-up cardiac evaluation.

Discussion

The authors’ initial concern for this patient was the possibility of a recurrent coarctation causing a significant pressure gradient between the upper and lower extremities with associated symptoms. A review of the literature demonstrates such an occurrence is not uncommon in this patient population, especially in patients with a history of early intervention (ie, within the first year of life).²

Causes and Incidence

One of the factors believed to contribute to recurrent coarctation is insufficient growth versus retraction of the manipulated tissues over time. The rates of recurrence vary based on the initial technique used for repair. These recurrences have been found to be approximately 6% in patients who had subclavian flap repairs; 31% for those who had balloon angioplasty alone; and approximately 20% in patients who had aortic stenting.^3-5 As seen in this case, balloon angioplasty is usually performed in patients requiring revascularization. However, up to 32% of these patients will require further intervention due to subsequent recurrence.⁶

Evaluation

Although emergency physicians (EPs) have numerous diagnostic modalities available to evaluate patients with suspected aortic coarctation, as long as the patient is in no acute distress, much of the work-up can be performed on an outpatient basis—in conjunction with the primary- and subspecialty-care team. Regarding appropriate imaging modalities, echocardiography with Doppler or 3D reconstruction of MR angiogram can be useful in detecting both anatomical abnormalities as well as the associated gradient dysfunction; computed tomography can be used for assessing the anatomy.⁷ All of these modalities can also be used to evaluate late-term complications of aortic coarctation pathology, including aortic aneurysms. To help ensure good outcome, the EP should always keep the possibility of recurrence in the differential when evaluating these patients, regardless of the number of previous interventions attempted.

Hypertension

As this case illustrates, patients with a history of coarctation repair often develop high BP. Unfortunately, up to 23% of these patients will go on to have BP above the 95th percentile.⁵ Moreover, a significant number of patients in this population will also suffer from exercise-induced hypertension, even when at-rest BP is controlled with antihypertensive medications.⁸

β-blockers, angiotensin-receptor blockers, and ACE inhibitors are considered the first-line medications for hypertension in adults and adult-sized patients with this condition.⁹

Since a high proportion of patients as young as age 7 years may develop high BP postrepair,¹⁰ the EP should discuss the initiation of an antihypertensive agent with the patient’s care team prior to discharge. It is also important to keep in mind that elevated BP is present to a significant degree even in patients without recurrent obstruction. The negative sequelae associated with uncontrolled hypertension is well known, and patients with congenital anatomical anomalies are at higher risk for such negative outcomes.

Conclusion

This case illustrates a common presentation of a teenaged patient with a chronic medical condition due to a corrected congenital cardiac defect. It also demonstrates the unique and early opportunity the EP has to evaluate and provide appropriate intervention for patients with potentially life-threatening diseases.

Patients with a history of corrective vascular surgery due to congenital heart malformations are an at-risk population. Therefore, during evaluation, the EP should always keep in mind that that these patients have a higher prevalence of related abnormalities at earlier ages than the general population. Steps initiated in the ED prior to discharge, in collaboration with the patient’s primary- and specialty-care team, can assist in expediting appropriate outpatient management of any sequelae. If a patient does not have a cardiologist, a referral to one should always be made prior to discharge.

Dr Smith is a postgraduate year 3 resident in the department of emergency medicine at Alpert Medical School of Brown University, Providence, Rhode Island. Dr Merritt is an assistant professor and pediatric emergency medicine attending in the department of emergency medicine, Brown Alpert Medical School, Providence, Rhode Island. 

Introduction

Coarctation of the aorta comprises approximately 5% to 8% of congenital heart defects and is often associated with valvular malformations.¹ These defects are typically diagnosed early and are managed with surgical repair, balloon angioplasty, or endovascular stent placement. However, as the following case illustrates, complications can occur in this population despite early intervention.

Case

A 15-year-old male adolescent presented to the pediatric ED after repeated blood pressure (BP) checks by the school nurse revealed consistently elevated systolic and diastolic pressures. The patient’s hypertension was associated with symptoms of intermittent headache and light-headedness. His medical history was remarkable for a congenital aortic coarctation and a bicuspid aortic valve. The patient had undergone a subclavian flap repair prior to 1 month of age, followed by a balloon dilatation 1 year later for recurrent coarctation. The rest of the patient’s medical history was unremarkable, including normal renal function. He denied illicit drug or alcohol use, sexual activity, or trauma.

On evaluation, the patient’s cardiac examination revealed a regular rate and rhythm with normally split S2; there were no rubs, murmurs, or gallops on auscultation. He had normal and equal pulses of the upper and lower extremities bilaterally. The patient presented without cyanosis. He was alert and oriented with normal upper and lower extremity reflexes. The neurological examination, including cranial nerve, strength, and gait testing, was unremarkable. The gastrointestinal examination showed a soft, nondistended abdomen, with no pulsatile masses. There was no abnormal swelling of his extremities. Although the physical examination findings were unremarkable, the patient’s vital signs were concerning as BP in his right upper extremity was as high as 208/110 mm Hg, while BP in his right leg was 130/68 mm Hg.

The patient followed up with his cardiologist, who ordered cardiac magnetic resonance imaging (MRI). The MRI showed mild narrowing of the distal aortic arch with a minimal and clinically insignificant pressure gradient. Based on the MRI findings, the patient was referred to a pediatric nephrologist, who performed a 24-hour ambulatory BP evaluation. The results of this study showed the patient to have systolic hypertension at the 95th percentile for his age and height. Based on the patient’s athletic predilection, β-blockers were avoided, and he was instead started on the angiotensin-converting enzyme (ACE) inhibitor lisinopril, along with annual follow-up cardiac evaluation.

Discussion

The authors’ initial concern for this patient was the possibility of a recurrent coarctation causing a significant pressure gradient between the upper and lower extremities with associated symptoms. A review of the literature demonstrates such an occurrence is not uncommon in this patient population, especially in patients with a history of early intervention (ie, within the first year of life).²

Causes and Incidence

One of the factors believed to contribute to recurrent coarctation is insufficient growth versus retraction of the manipulated tissues over time. The rates of recurrence vary based on the initial technique used for repair. These recurrences have been found to be approximately 6% in patients who had subclavian flap repairs; 31% for those who had balloon angioplasty alone; and approximately 20% in patients who had aortic stenting.^3-5 As seen in this case, balloon angioplasty is usually performed in patients requiring revascularization. However, up to 32% of these patients will require further intervention due to subsequent recurrence.⁶

Evaluation

Although emergency physicians (EPs) have numerous diagnostic modalities available to evaluate patients with suspected aortic coarctation, as long as the patient is in no acute distress, much of the work-up can be performed on an outpatient basis—in conjunction with the primary- and subspecialty-care team. Regarding appropriate imaging modalities, echocardiography with Doppler or 3D reconstruction of MR angiogram can be useful in detecting both anatomical abnormalities as well as the associated gradient dysfunction; computed tomography can be used for assessing the anatomy.⁷ All of these modalities can also be used to evaluate late-term complications of aortic coarctation pathology, including aortic aneurysms. To help ensure good outcome, the EP should always keep the possibility of recurrence in the differential when evaluating these patients, regardless of the number of previous interventions attempted.

Hypertension

As this case illustrates, patients with a history of coarctation repair often develop high BP. Unfortunately, up to 23% of these patients will go on to have BP above the 95th percentile.⁵ Moreover, a significant number of patients in this population will also suffer from exercise-induced hypertension, even when at-rest BP is controlled with antihypertensive medications.⁸

β-blockers, angiotensin-receptor blockers, and ACE inhibitors are considered the first-line medications for hypertension in adults and adult-sized patients with this condition.⁹

Since a high proportion of patients as young as age 7 years may develop high BP postrepair,¹⁰ the EP should discuss the initiation of an antihypertensive agent with the patient’s care team prior to discharge. It is also important to keep in mind that elevated BP is present to a significant degree even in patients without recurrent obstruction. The negative sequelae associated with uncontrolled hypertension is well known, and patients with congenital anatomical anomalies are at higher risk for such negative outcomes.

Conclusion

This case illustrates a common presentation of a teenaged patient with a chronic medical condition due to a corrected congenital cardiac defect. It also demonstrates the unique and early opportunity the EP has to evaluate and provide appropriate intervention for patients with potentially life-threatening diseases.

Patients with a history of corrective vascular surgery due to congenital heart malformations are an at-risk population. Therefore, during evaluation, the EP should always keep in mind that that these patients have a higher prevalence of related abnormalities at earlier ages than the general population. Steps initiated in the ED prior to discharge, in collaboration with the patient’s primary- and specialty-care team, can assist in expediting appropriate outpatient management of any sequelae. If a patient does not have a cardiologist, a referral to one should always be made prior to discharge.

Dr Smith is a postgraduate year 3 resident in the department of emergency medicine at Alpert Medical School of Brown University, Providence, Rhode Island. Dr Merritt is an assistant professor and pediatric emergency medicine attending in the department of emergency medicine, Brown Alpert Medical School, Providence, Rhode Island. 

The "Standards of Medical Care in Diabetes" guidelines published in 2015 by the American Diabetes Association (ADA) state that metformin is the preferred initial pharmacotherapy for managing type 2 diabetes.¹ Metformin, a biguanide, enhances insulin sensitivity in muscle and fat tissue and inhibits hepatic glucose production. Advantages of metformin include the longstanding research supporting its efficacy and safety, an expected decrease in the glycated hemoglobin (HbA1c) level of 1% to 1.5%, low cost, minimal hypoglycemic risk, and potential reductions in cardiovascular (CV) events due to decreased low-density lipoprotein (LDL) cholesterol.^1,2

To minimize adverse gastrointestinal effects, start metformin at 500 mg once or twice a day and titrate upward every one to 2 weeks to the target dose.³ To help guide dosing decisions, use the estimated glomerular filtration rate (eGFR) instead of the serum creatinine (SCr) level, because the SCr can translate into a variable range of eGFRs (TABLE 1).^4,5

What if metformin alone isn't enough?

CASE › Richard C, age 50, has type 2 diabetes, hypertension, hyperlipidemia, and obesity. He takes metformin 1 g twice a day for his diabetes. After 3 months on this regimen, his HbA1c is 8.8%. How would you manage Mr. C's diabetes going forward?

If metformin at a maximum tolerated dose does not achieve the HbA1c target after 3 months, add a second oral agent (a sulfonylurea [SU], thiazolidinedione [TZD], dipeptidyl peptidase 4 [DPP-4] inhibitor, or sodium-glucose cotransporter-2 [SGLT2] inhibitor), a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal insulin (TABLE 2).¹

Factors that will affect the choice of the second agent include patient preference, cost, potential adverse effects, impact on weight, efficacy, and risk of hypoglycemia.

Based on cost, familiarity, and longstanding safety data, you decide to give Mr. C an SU, while cautioning him about hypoglycemia.

CASE › Mr. C has now been taking metformin and an SU at maximum doses for 2 years and continues with lifestyle modifications. Though his HbA1c level dropped after adding the SU, over 2 years it has crept up to 8.6% and his mean blood glucose is 186 mg/dL. What are your treatment options now?

If the target HbA1c level is not achieved on dual therapy, consider triple therapy combinations (TABLE 3).¹

In Mr. C's case, a third oral agent could be added, but DPP-4 and SGLT2 are unlikely to get his HbA1c below 7%. TZD may get his HbA1c into the desired range but is associated with adverse effects such as heart failure, edema, and weight gain. Mr. C agrees instead to start a basal insulin in conjunction with metformin. You could continue the SU, but you decide to stop it because the additive effect of these medications increases the risk of hypoglycemia.

CASE › Six months later Mr. C is taking metformin and insulin glargine, a basal insulin, adjusted to a fasting blood glucose of 80 to 130 mg/dL. His HbA1c is still above target at 8.4%, and the mean postprandial blood glucose is 232 mg/dL.

Mr. C is still above target for HbA1c and for postprandial blood glucose (goal: <180 mg/dL), so he needs pharmacotherapy that targets postprandial glucose elevations.¹ His fasting blood glucose readings are at goal, so increasing his insulin glargine is not recommended because it could cause hypoglycemia. An oral agent other than SU could be added, but none is potent enough to lower the HbA1c to goal (TABLE 2).¹ There are 3 other options:

• add a mealtime bolus of insulin
• add a GLP-1 receptor agonist
• switch to premixed (biphasic) insulin.

What to do when basal insulin isn’t enough—with or without oral meds

For type 2 diabetes poorly controlled on basal insulin with or without oral agents, the 2015 ADA treatment guidelines recommend adding a GLP-1 receptor agonist or mealtime insulin.¹ A less desirable alternative is to switch from basal insulin to a twice-daily premixed (biphasic) insulin analog (70/30 aspart mix or 75/25 or 50/50 lispro mix). The human NPH-Regular premixed formulations (70/30) are less costly alternatives. The disadvantage with all premixed insulins is they only cover 2 postprandial glucose elevations a day.^1,6,7

When prescribing medication for T2DM, consider efficacy, cost, tolerability, impact on body weight, comorbidities, risk of hypoglycemia, and patient preference.

Insulin requires multiple daily injections, can lead to weight gain, and carries the risk of hypoglycemia, which causes significant morbidity.^8,9 Daily or weekly administration of a GLP-1 receptor agonist combined with basal insulin can offer a more convenient alternative to mealtime boluses of insulin.

What are GLP-1 receptor agonists?

GLP-1 receptor agonists exert their maximum influence on blood glucose levels during the postprandial period by mimicking the body’s natural incretin hormonal response to oral glucose ingestion.¹⁰ They delay gastric emptying, promote satiety, decrease glucagon secretion, and increase insulin secretion.^10,11 This mechanism blunts the spiking of postprandial blood glucose after a meal and improves blood glucose control and weight reduction.^1,6,7

A systematic review and meta-analysis by Eng and colleagues compared the safety and efficacy of combined GLP-1 agonist and basal insulin with other treatment regimens.⁷ Fifteen randomized controlled trials were included involving 4348 participants with a mean trial duration of 25 weeks.

Compared with all other treatment regimens, the GLP-1 receptor agonist and basal insulin combination not only significantly reduced HbA1c by 0.44% (95% confidence interval [CI], -0.60 to -0.29) and increased the likelihood of attaining an HbA1c of <7.0% (relative risk [RR]=1.92; 95% CI, 1.43 to 2.56) but also reduced weight by 3.22 kg (-4.90 to -1.54) with no increased risk of hypoglycemia (RR=0.99; 0.76 to 1.29).⁷

GLP-1 agonist vs bolus insulin

Compared with basal-bolus insulin regimens, the combination of a GLP-1 receptor agonist with basal insulin has led to a significantly lowered risk of hypoglycemia (RR=0.67; 95% CI, 0.56 to 0.80), greater weight loss (-5.66 kg; 95% CI, -9.8 to -1.51) and an average reduction in HbA1c of 0.1% (95% CI, -0.17 to -0.02).⁷

There are 5 GLP-1 receptor agonists that have US Food and Drug Administration approval for the treatment of type 2 diabetes: albiglutide, dulaglutide, exenatide, exenatide XR, and liraglutide (TABLE 4).^3,12

All 5 agents are administered subcutaneously and packaged in pen-injector form. Adverse effects include nausea, which is transient and diminishes within the first few weeks of therapy, and less commonly, pancreatitis.^3,12

All of the GLP-1 receptor agonists, except short-acting exenatide, carry a warning about the risk of worsening renal function and a possible association with medullary thyroid carcinomas, which were identified in rats, but have not been observed in humans.^3,12 Medications in this drug class have a low risk for precipitating hypoglycemia.¹¹ Cost is their chief disadvantage, although copay reduction cards are available online for most of the products. Evaluate efficacy, ease of use, tolerability, and cost when selecting a GLP-1 receptor agonist.^3,12

CASE › Mr. C prefers a more convenient option than adding another daily injection. Given his obesity, a GLP-1 receptor agonist can help with weight loss and lower his risk for hypoglycemia. To further increase the convenience in dosing, you lean toward either weekly exenatide XR or dulaglutide over basal-bolus combination insulin. Weekly albiglutide is less potent than exenatide XR and dulaglutide in decreasing HbA1c.¹² Mr. C’s insurance plan provides preferred coverage for exenatide XR and he is eligible for a copay savings card, meaning he will pay no more than $25 per month for this new prescription. You prescribe exenatide XR and ask him to record his postprandial blood glucose levels. You follow up in one month to assess his response.

CORRESPONDENCE
Anne Mounsey, MD, University of North Carolina School of Medicine, Department of Family Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599; [email protected].

The "Standards of Medical Care in Diabetes" guidelines published in 2015 by the American Diabetes Association (ADA) state that metformin is the preferred initial pharmacotherapy for managing type 2 diabetes.¹ Metformin, a biguanide, enhances insulin sensitivity in muscle and fat tissue and inhibits hepatic glucose production. Advantages of metformin include the longstanding research supporting its efficacy and safety, an expected decrease in the glycated hemoglobin (HbA1c) level of 1% to 1.5%, low cost, minimal hypoglycemic risk, and potential reductions in cardiovascular (CV) events due to decreased low-density lipoprotein (LDL) cholesterol.^1,2

To minimize adverse gastrointestinal effects, start metformin at 500 mg once or twice a day and titrate upward every one to 2 weeks to the target dose.³ To help guide dosing decisions, use the estimated glomerular filtration rate (eGFR) instead of the serum creatinine (SCr) level, because the SCr can translate into a variable range of eGFRs (TABLE 1).^4,5

What if metformin alone isn't enough?

CASE › Richard C, age 50, has type 2 diabetes, hypertension, hyperlipidemia, and obesity. He takes metformin 1 g twice a day for his diabetes. After 3 months on this regimen, his HbA1c is 8.8%. How would you manage Mr. C's diabetes going forward?

If metformin at a maximum tolerated dose does not achieve the HbA1c target after 3 months, add a second oral agent (a sulfonylurea [SU], thiazolidinedione [TZD], dipeptidyl peptidase 4 [DPP-4] inhibitor, or sodium-glucose cotransporter-2 [SGLT2] inhibitor), a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal insulin (TABLE 2).¹

Factors that will affect the choice of the second agent include patient preference, cost, potential adverse effects, impact on weight, efficacy, and risk of hypoglycemia.

Based on cost, familiarity, and longstanding safety data, you decide to give Mr. C an SU, while cautioning him about hypoglycemia.

CASE › Mr. C has now been taking metformin and an SU at maximum doses for 2 years and continues with lifestyle modifications. Though his HbA1c level dropped after adding the SU, over 2 years it has crept up to 8.6% and his mean blood glucose is 186 mg/dL. What are your treatment options now?

If the target HbA1c level is not achieved on dual therapy, consider triple therapy combinations (TABLE 3).¹

In Mr. C's case, a third oral agent could be added, but DPP-4 and SGLT2 are unlikely to get his HbA1c below 7%. TZD may get his HbA1c into the desired range but is associated with adverse effects such as heart failure, edema, and weight gain. Mr. C agrees instead to start a basal insulin in conjunction with metformin. You could continue the SU, but you decide to stop it because the additive effect of these medications increases the risk of hypoglycemia.

CASE › Six months later Mr. C is taking metformin and insulin glargine, a basal insulin, adjusted to a fasting blood glucose of 80 to 130 mg/dL. His HbA1c is still above target at 8.4%, and the mean postprandial blood glucose is 232 mg/dL.

Mr. C is still above target for HbA1c and for postprandial blood glucose (goal: <180 mg/dL), so he needs pharmacotherapy that targets postprandial glucose elevations.¹ His fasting blood glucose readings are at goal, so increasing his insulin glargine is not recommended because it could cause hypoglycemia. An oral agent other than SU could be added, but none is potent enough to lower the HbA1c to goal (TABLE 2).¹ There are 3 other options:

• add a mealtime bolus of insulin
• add a GLP-1 receptor agonist
• switch to premixed (biphasic) insulin.

What to do when basal insulin isn’t enough—with or without oral meds

For type 2 diabetes poorly controlled on basal insulin with or without oral agents, the 2015 ADA treatment guidelines recommend adding a GLP-1 receptor agonist or mealtime insulin.¹ A less desirable alternative is to switch from basal insulin to a twice-daily premixed (biphasic) insulin analog (70/30 aspart mix or 75/25 or 50/50 lispro mix). The human NPH-Regular premixed formulations (70/30) are less costly alternatives. The disadvantage with all premixed insulins is they only cover 2 postprandial glucose elevations a day.^1,6,7

When prescribing medication for T2DM, consider efficacy, cost, tolerability, impact on body weight, comorbidities, risk of hypoglycemia, and patient preference.

Insulin requires multiple daily injections, can lead to weight gain, and carries the risk of hypoglycemia, which causes significant morbidity.^8,9 Daily or weekly administration of a GLP-1 receptor agonist combined with basal insulin can offer a more convenient alternative to mealtime boluses of insulin.

What are GLP-1 receptor agonists?

GLP-1 receptor agonists exert their maximum influence on blood glucose levels during the postprandial period by mimicking the body’s natural incretin hormonal response to oral glucose ingestion.¹⁰ They delay gastric emptying, promote satiety, decrease glucagon secretion, and increase insulin secretion.^10,11 This mechanism blunts the spiking of postprandial blood glucose after a meal and improves blood glucose control and weight reduction.^1,6,7

A systematic review and meta-analysis by Eng and colleagues compared the safety and efficacy of combined GLP-1 agonist and basal insulin with other treatment regimens.⁷ Fifteen randomized controlled trials were included involving 4348 participants with a mean trial duration of 25 weeks.

Compared with all other treatment regimens, the GLP-1 receptor agonist and basal insulin combination not only significantly reduced HbA1c by 0.44% (95% confidence interval [CI], -0.60 to -0.29) and increased the likelihood of attaining an HbA1c of <7.0% (relative risk [RR]=1.92; 95% CI, 1.43 to 2.56) but also reduced weight by 3.22 kg (-4.90 to -1.54) with no increased risk of hypoglycemia (RR=0.99; 0.76 to 1.29).⁷

GLP-1 agonist vs bolus insulin

Compared with basal-bolus insulin regimens, the combination of a GLP-1 receptor agonist with basal insulin has led to a significantly lowered risk of hypoglycemia (RR=0.67; 95% CI, 0.56 to 0.80), greater weight loss (-5.66 kg; 95% CI, -9.8 to -1.51) and an average reduction in HbA1c of 0.1% (95% CI, -0.17 to -0.02).⁷

There are 5 GLP-1 receptor agonists that have US Food and Drug Administration approval for the treatment of type 2 diabetes: albiglutide, dulaglutide, exenatide, exenatide XR, and liraglutide (TABLE 4).^3,12

All 5 agents are administered subcutaneously and packaged in pen-injector form. Adverse effects include nausea, which is transient and diminishes within the first few weeks of therapy, and less commonly, pancreatitis.^3,12

All of the GLP-1 receptor agonists, except short-acting exenatide, carry a warning about the risk of worsening renal function and a possible association with medullary thyroid carcinomas, which were identified in rats, but have not been observed in humans.^3,12 Medications in this drug class have a low risk for precipitating hypoglycemia.¹¹ Cost is their chief disadvantage, although copay reduction cards are available online for most of the products. Evaluate efficacy, ease of use, tolerability, and cost when selecting a GLP-1 receptor agonist.^3,12

CASE › Mr. C prefers a more convenient option than adding another daily injection. Given his obesity, a GLP-1 receptor agonist can help with weight loss and lower his risk for hypoglycemia. To further increase the convenience in dosing, you lean toward either weekly exenatide XR or dulaglutide over basal-bolus combination insulin. Weekly albiglutide is less potent than exenatide XR and dulaglutide in decreasing HbA1c.¹² Mr. C’s insurance plan provides preferred coverage for exenatide XR and he is eligible for a copay savings card, meaning he will pay no more than $25 per month for this new prescription. You prescribe exenatide XR and ask him to record his postprandial blood glucose levels. You follow up in one month to assess his response.

CORRESPONDENCE
Anne Mounsey, MD, University of North Carolina School of Medicine, Department of Family Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599; [email protected].

The "Standards of Medical Care in Diabetes" guidelines published in 2015 by the American Diabetes Association (ADA) state that metformin is the preferred initial pharmacotherapy for managing type 2 diabetes.¹ Metformin, a biguanide, enhances insulin sensitivity in muscle and fat tissue and inhibits hepatic glucose production. Advantages of metformin include the longstanding research supporting its efficacy and safety, an expected decrease in the glycated hemoglobin (HbA1c) level of 1% to 1.5%, low cost, minimal hypoglycemic risk, and potential reductions in cardiovascular (CV) events due to decreased low-density lipoprotein (LDL) cholesterol.^1,2

To minimize adverse gastrointestinal effects, start metformin at 500 mg once or twice a day and titrate upward every one to 2 weeks to the target dose.³ To help guide dosing decisions, use the estimated glomerular filtration rate (eGFR) instead of the serum creatinine (SCr) level, because the SCr can translate into a variable range of eGFRs (TABLE 1).^4,5

What if metformin alone isn't enough?

CASE › Richard C, age 50, has type 2 diabetes, hypertension, hyperlipidemia, and obesity. He takes metformin 1 g twice a day for his diabetes. After 3 months on this regimen, his HbA1c is 8.8%. How would you manage Mr. C's diabetes going forward?

If metformin at a maximum tolerated dose does not achieve the HbA1c target after 3 months, add a second oral agent (a sulfonylurea [SU], thiazolidinedione [TZD], dipeptidyl peptidase 4 [DPP-4] inhibitor, or sodium-glucose cotransporter-2 [SGLT2] inhibitor), a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal insulin (TABLE 2).¹

Factors that will affect the choice of the second agent include patient preference, cost, potential adverse effects, impact on weight, efficacy, and risk of hypoglycemia.

Based on cost, familiarity, and longstanding safety data, you decide to give Mr. C an SU, while cautioning him about hypoglycemia.

CASE › Mr. C has now been taking metformin and an SU at maximum doses for 2 years and continues with lifestyle modifications. Though his HbA1c level dropped after adding the SU, over 2 years it has crept up to 8.6% and his mean blood glucose is 186 mg/dL. What are your treatment options now?

If the target HbA1c level is not achieved on dual therapy, consider triple therapy combinations (TABLE 3).¹

In Mr. C's case, a third oral agent could be added, but DPP-4 and SGLT2 are unlikely to get his HbA1c below 7%. TZD may get his HbA1c into the desired range but is associated with adverse effects such as heart failure, edema, and weight gain. Mr. C agrees instead to start a basal insulin in conjunction with metformin. You could continue the SU, but you decide to stop it because the additive effect of these medications increases the risk of hypoglycemia.

CASE › Six months later Mr. C is taking metformin and insulin glargine, a basal insulin, adjusted to a fasting blood glucose of 80 to 130 mg/dL. His HbA1c is still above target at 8.4%, and the mean postprandial blood glucose is 232 mg/dL.

Mr. C is still above target for HbA1c and for postprandial blood glucose (goal: <180 mg/dL), so he needs pharmacotherapy that targets postprandial glucose elevations.¹ His fasting blood glucose readings are at goal, so increasing his insulin glargine is not recommended because it could cause hypoglycemia. An oral agent other than SU could be added, but none is potent enough to lower the HbA1c to goal (TABLE 2).¹ There are 3 other options:

• add a mealtime bolus of insulin
• add a GLP-1 receptor agonist
• switch to premixed (biphasic) insulin.

What to do when basal insulin isn’t enough—with or without oral meds

For type 2 diabetes poorly controlled on basal insulin with or without oral agents, the 2015 ADA treatment guidelines recommend adding a GLP-1 receptor agonist or mealtime insulin.¹ A less desirable alternative is to switch from basal insulin to a twice-daily premixed (biphasic) insulin analog (70/30 aspart mix or 75/25 or 50/50 lispro mix). The human NPH-Regular premixed formulations (70/30) are less costly alternatives. The disadvantage with all premixed insulins is they only cover 2 postprandial glucose elevations a day.^1,6,7

When prescribing medication for T2DM, consider efficacy, cost, tolerability, impact on body weight, comorbidities, risk of hypoglycemia, and patient preference.

Insulin requires multiple daily injections, can lead to weight gain, and carries the risk of hypoglycemia, which causes significant morbidity.^8,9 Daily or weekly administration of a GLP-1 receptor agonist combined with basal insulin can offer a more convenient alternative to mealtime boluses of insulin.

What are GLP-1 receptor agonists?

GLP-1 receptor agonists exert their maximum influence on blood glucose levels during the postprandial period by mimicking the body’s natural incretin hormonal response to oral glucose ingestion.¹⁰ They delay gastric emptying, promote satiety, decrease glucagon secretion, and increase insulin secretion.^10,11 This mechanism blunts the spiking of postprandial blood glucose after a meal and improves blood glucose control and weight reduction.^1,6,7

A systematic review and meta-analysis by Eng and colleagues compared the safety and efficacy of combined GLP-1 agonist and basal insulin with other treatment regimens.⁷ Fifteen randomized controlled trials were included involving 4348 participants with a mean trial duration of 25 weeks.

Compared with all other treatment regimens, the GLP-1 receptor agonist and basal insulin combination not only significantly reduced HbA1c by 0.44% (95% confidence interval [CI], -0.60 to -0.29) and increased the likelihood of attaining an HbA1c of <7.0% (relative risk [RR]=1.92; 95% CI, 1.43 to 2.56) but also reduced weight by 3.22 kg (-4.90 to -1.54) with no increased risk of hypoglycemia (RR=0.99; 0.76 to 1.29).⁷

GLP-1 agonist vs bolus insulin

Compared with basal-bolus insulin regimens, the combination of a GLP-1 receptor agonist with basal insulin has led to a significantly lowered risk of hypoglycemia (RR=0.67; 95% CI, 0.56 to 0.80), greater weight loss (-5.66 kg; 95% CI, -9.8 to -1.51) and an average reduction in HbA1c of 0.1% (95% CI, -0.17 to -0.02).⁷

There are 5 GLP-1 receptor agonists that have US Food and Drug Administration approval for the treatment of type 2 diabetes: albiglutide, dulaglutide, exenatide, exenatide XR, and liraglutide (TABLE 4).^3,12

All 5 agents are administered subcutaneously and packaged in pen-injector form. Adverse effects include nausea, which is transient and diminishes within the first few weeks of therapy, and less commonly, pancreatitis.^3,12

All of the GLP-1 receptor agonists, except short-acting exenatide, carry a warning about the risk of worsening renal function and a possible association with medullary thyroid carcinomas, which were identified in rats, but have not been observed in humans.^3,12 Medications in this drug class have a low risk for precipitating hypoglycemia.¹¹ Cost is their chief disadvantage, although copay reduction cards are available online for most of the products. Evaluate efficacy, ease of use, tolerability, and cost when selecting a GLP-1 receptor agonist.^3,12

CASE › Mr. C prefers a more convenient option than adding another daily injection. Given his obesity, a GLP-1 receptor agonist can help with weight loss and lower his risk for hypoglycemia. To further increase the convenience in dosing, you lean toward either weekly exenatide XR or dulaglutide over basal-bolus combination insulin. Weekly albiglutide is less potent than exenatide XR and dulaglutide in decreasing HbA1c.¹² Mr. C’s insurance plan provides preferred coverage for exenatide XR and he is eligible for a copay savings card, meaning he will pay no more than $25 per month for this new prescription. You prescribe exenatide XR and ask him to record his postprandial blood glucose levels. You follow up in one month to assess his response.

CORRESPONDENCE
Anne Mounsey, MD, University of North Carolina School of Medicine, Department of Family Medicine, 590 Manning Drive, Campus Box 7595, Chapel Hill, NC 27599; [email protected].

Personality disorders (PDs) are common, affecting up to 15% of US adults, and are associated with comorbid medical and psychiatric conditions and increased utilization of health care resources.^1,2 Having a basic understanding of these patterns of thinking and behaving can help family physicians (FPs) identify specific PD diagnoses, ensure appropriate treatment, and reduce the frustration that arises when an individual is viewed as a “difficult patient.”

Here we describe the diagnostic features of the disorders in the 3 major clusters of PDs and review an effective approach to the management of the most common disorder in each cluster, using a case study patient.

Defense mechanisms offer clues that your patient may have a PD

Personality is an enduring pattern of inner experience and behaviors that is relatively stable across time and in different situations. Such traits comprise an individual’s inherent makeup.¹ PDs are diagnosed when an individual’s personality traits create significant distress or impairment in daily functioning. Specifically, PDs have a negative impact on cognition, affect, interpersonal relationships, and/or impulse control.¹

One of the ways people alleviate distress is by using defense mechanisms. Defense mechanisms are unconscious mental processes that individuals use to resolve conflicts, and thereby reduce anxiety and depression on a conscious level. Taken alone, defense mechanisms are not pathologic, but they may become maladaptive in certain stressful circumstances, such as when receiving medical treatment. Recognizing patterns of chronic use of certain defense mechanisms may be a clue that your patient has a PD. TABLE 1^3,4 and TABLE 2^3,4 provide an overview of common defense mechanisms used by patients with PDs.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) organizes PDs into 3 clusters based on similar and often overlapping symptoms.¹TABLE 3¹ provides a brief summary of the characteristic features of each disorder in these clusters.

Cluster A: Odd, eccentric

Patients with one of these disorders are odd, eccentric, or bizarre in their behavior and thinking. There appears to be a genetic link between cluster A PDs (especially schizotypal) and schizophrenia.⁵ These patients rarely seek treatment for their disorder because they have limited insight into their maladaptive traits.^5,6

CASE 1 › Daniel A, age 57, has hypertension and hyperlipidemia and comes in to see his FP for a 6-month follow-up appointment. He never misses appointments, but has a history of poor adherence with prescribed medications. He enjoys his discussions with you in the office, although he often perseverates on conspiracy theories. He lives alone and has never been married. He believes that some of the previously prescribed medications, including a statin and a thiazide diuretic, were interfering with the absorption of “positive nutrients” in his diet. He also refuses to take the generic form of a statin, which he believes was adulterated by the government to be sold at lower cost.

Mr. A demonstrates the odd and eccentric beliefs that characterize schizotypal personality disorder. How can his FP best help him adhere to his medication regimen? (For the answer, click here.)

Schizotypal personality disorder shares certain disturbances of thought with schizophrenia, and is believed to exist on a spectrum with other primary psychotic disorders. Support for this theory comes from the higher rates of schizotypal PD among family members of patients with schizophrenia. There is a genetic component to the disorder.^3,5,6

Clinically, these patients appear odd and eccentric with unusual beliefs. They may have a fascination with magic, clairvoyance, telepathy, or other such notions.^1,5 Although the perceptual disturbances are unusual and often bizarre, they are not frank delusions: patients with schizotypal PD are willing to consider alternative explanations for their beliefs and can engage in rational discussion. Cognitive deficits, particularly of memory and attention, are common and distressing to patients. Frequently, the presenting complaint is depression and anxiety due to the emotional discord and isolation from others.^1,3,5,6

Continue to cluster B >>

Cluster B: Dramatic, erratic

Does your patient complain that you don't understand him "the way his other doctor did"? Or does he frequently lose his temper? Perhaps it's time to consider a personality disorder.

Patients with cluster B PDs are dramatic, excessively emotional, confrontational, erratic, and impulsive in their behaviors.¹ They often have comorbid mood and anxiety disorders, as well as a disproportionately high co-occurrence of functional disorders.^3,7 Their rates of health care utilization can be substantial. Because individuals with one of these PDs sometimes exhibit reckless and impulsive behavior, physicians should be aware these patients have a high risk of physical injuries (fights, accidents, self-injurious behavior), suicide attempts, risky sexual behaviors, and unplanned pregnancy.^8,9

CASE 2 › Sheryl B is a 34-year-old new patient with a history of irritable bowel syndrome, fibromyalgia, depression, and anxiety who shows up for her appointment an hour late. She is upset and blames the office scheduler for not reminding her of the appointment. She brings a list of medications from her previous physician that includes sertraline, clonazepam, gabapentin, oxycodone, and as-needed alprazolam. She insists that her physician increase the dose of the benzodiazepines.

A review of her medical history reveals diagnoses of anxiety, bipolar disorder, and posttraumatic stress disorder. Ms. B has also engaged in superficial cutting since adolescence, often triggered by arguments with her boyfriend. Currently, she attributes her anxiety and pain to not receiving the “correct medications” because of her transition from a previous physician who “knew her better than any other doctor.” After the FP explains to Ms. B that he would have to carefully review her case before continuing to prescribe benzodiazepines, she becomes tearful and argumentative, proclaiming, “You won’t give me the only thing that will help me because you want me to be miserable!”

Ms. B exhibits many cluster B personality traits consistent with borderline PD. How should the FP respond to her claims? (For the answer, click here.)

Borderline PD is the most studied of the PDs. It can be a stigmatizing diagnosis, and even experienced psychiatrists may hesitate to inform patients of this diagnosis.¹⁰ Patients with borderline PD may be erroneously diagnosed with bipolar disorder, treatment-resistant depression, or posttraumatic stress disorder because of a complicated clinical presentation, physician unfamiliarity with diagnostic criteria, or the presence of genuine comorbid conditions.^3,11

The etiology of this disorder appears to be multifactorial, and includes genetic predisposition, disruptive parent-child relationships (especially separation), and, often, past sexual or physical trauma.^9,12

Predominant clinical features include emotional lability, efforts to avoid abandonment, extremes of idealization and devaluation, unstable and intense interpersonal relationships, and impulsivity.¹ Characteristically, these patients also engage in self-injurious behaviors.^13,14 Common defense mechanisms used by patients with borderline PD include splitting (viewing others as either all good or all bad), acting out (yelling, agitation, or violence), and passive aggression (TABLE 1^3,4).

Cluster C: Anxious, fearful

Individuals with cluster C PDs appear anxious, fearful, and worried. They have features that overlap with anxiety disorders.¹⁵

CASE 3 › Judy C is a 40-year-old lawyer with a history of gastroesophageal reflux disorder, hypertension, and anxiety who presents for a 3-week follow-up visit after starting sertraline. The patient describes herself as a perfectionist who has increased work-related stress recently because she has to “do extra work for my colleagues who don’t know how to get things done right.” She recently fired her assistant for “not understanding my filing system.” She appears formal and serious, often looking at her watch during the evaluation.

Ms. C demonstrates a pattern of perfectionism, formality, and rigidity in thought and behavior characteristic of obsessive-compulsive PD. What treatment should her physician recommend? (For the answer, click here.)

Unlike patients with frank delusions, patients with schizotypal personality disorder are willing to consider alternative explanations for their odd beliefs.

Obsessive-compulsive PD. Although this disorder is associated with significant anxiety, patients often view the specific traits of obsessive-compulsive PD, such as perfectionism, as desirable. Neurotic defense mechanisms are common, especially rationalization, intellectualization, and isolation of affect (TABLE 2^3,4). These patients appear formal, rigid, and serious, and are preoccupied with rules and orderliness to achieve perfection.¹ Significant anxiety often arises from fear of making mistakes and ruminating on decision-making.^1,11,15

Although some overlap exists between obsessive-compulsive disorder (OCD) and obsessive-compulsive PD, patients with OCD exhibit distinct obsessions and associated compulsive behavior, whereas those with obsessive-compulsive PD do not.¹

In terms of treatment, it is generally appropriate to recognize the 2 conditions as distinct entities.¹⁵ OCD responds well to cognitive behavioral therapies and high-dose selective serotonin reuptake inhibitors (SSRIs).¹⁶ In contrast, there is little data that suggests antidepressants are effective for obsessive-compulsive PD, and treatment is aimed at addressing comorbid anxiety with psychotherapy and pharmacotherapy, if needed.^11,15

Continue to psychotherapy for PD is the first-line treatment >>

Psychotherapy for PD is the first-line treatment

Psychotherapy is the most effective treatment for PDs.^11,17,18 Several psychotherapies are used to treat these disorders, including dialectical behavioral therapy, schema therapy, and cognitive behavioral therapy (CBT). A recent study demonstrated the superiority of several evidence-based psychotherapies for PD compared to treatment-as-usual.¹⁷ Even more promising is that certain benefits have been demonstrated when psychotherapy is provided by clinicians without advanced mental health training.^19-21 However, the benefits of therapies for specific disorders are often limited by lack of available data, patient preference, and accessibility of resources.

Limited evidence supports pharmacotherapy

The use of pharmacotherapy for treating PDs is common, although there’s limited evidence to support the practice.^11,22 Certain circumstances may allow for the judicious use of medication, although prescribing strategies are based largely on clinical experience and expert opinion.

Prescribers should emphasize a realistic perspective on treatment response, because research suggests at best a mild-moderate response of some personality traits to pharmacotherapy.^11,22-25 There is no evidence for polypharmacy in treating PDs, and FPs should allow for sufficient treatment duration, switch medications rather than augment ineffective treatments, and resist the urge to prescribe for every psychological crisis.^11,22,25,26

Patient safety should always be a consideration when prescribing medication. Because use of second-generation antipsychotics is associated with the metabolic syndrome, the patient’s baseline weight and fasting glucose, lipids, and hemoglobin A1c levels should be obtained and monitored regularly. Weight gain can be particularly distressing to patients, increase stress and anxiety, and hinder the doctor-patient relationship.²⁵ Finally, medications with abuse potential or that can be lethal in overdose (eg, tricyclic antidepressants and benzodiazepines) are best avoided in patients with emotional lability and impulsivity.^25,26

Tailor treatment to the specific PD

Patients often view the specific traits of obsessive-compulsive personality disorder, such as perfectionism, as desirable.

Tx for cluster A disorders. Few studies have examined the effectiveness of psychotherapies for cluster A disorders. Cognitive therapy may have benefit in addressing cognitive distortions and social impairment in schizotypal PD.^11,12,22 There is little evidence supporting psychotherapy for paranoid PD, because challenging patients’ beliefs in this form is likely to exacerbate paranoia. Low-dose risperidone has demonstrated some beneficial effects on perceptual disturbances; however, the adverse metabolic effects of this medication may outweigh any potential benefit, as these symptoms are often not distressing to patients.^6,27 In comparison, patients often find deficits in memory and attention to be more bothersome, and some data suggest that the alpha-2 agonist guanfacine may help treat these symptoms.²⁸

Tx for cluster B disorders. Several forms of psychotherapy have proven effective in managing symptoms and improving overall functioning in patients with borderline PD, including dialectical behavioral therapy, mentalization-based therapy, transference-focused therapy, and schema therapy.²⁹ Dialectical behavioral therapy is often the initial treatment because it emphasizes reducing self-harm behaviors and emotion regulation.^11,17,26

Gunderson¹⁹ developed a more basic approach to treating borderline PD that is intended to be used by all clinicians who treat the disorder, and not just mental health professionals with advanced training in psychotherapy. A large, multisite randomized controlled trial found that the clinical efficacy of the technique, known as good psychiatric management, rivaled that of dialectical behavioral therapy.^20,21

The general premise is that clinicians foster a therapeutic relationship that is supportive, engaging, and flexible. Physicians are encouraged to educate patients about the disorder and emphasize improvement in daily functioning. Clinicians should share the diagnosis with patients, which may give patients a sense of relief in having an accurate diagnosis and allow them to fully invest in diagnosis-specific treatments.¹⁹

Systematic reviews and meta-analyses of studies that evaluated pharmacotherapy for borderline PD often have had conflicting conclusions as a result of analyzing data from underpowered studies with varying study designs.^{23,24,26,30,31} In targeting specific symptoms of the disorder, the most consistent evidence has supported the use of antipsychotics for cognitive perceptual disturbances; patients commonly experience depersonalization or out-of-body experiences.²⁵ Additionally, the use of antipsychotics and mood stabilizers (lamotrigine and topiramate) appears to be somewhat effective for managing emotional lability and impulsivity.^26,32,33 Despite the widespread use of SSRIs, a recent systematic review found the least support for these and other antidepressants for management of borderline PD.²⁵

Tx for cluster C disorders. Some evidence supports using cognitive and interpersonal psychotherapies to treat cluster C PDs.³⁴ In contrast, there is little evidence to support the use of pharmacotherapy.³⁵ However, given the significant overlap among these disorders (especially avoidant PD) and social phobia and generalized anxiety disorder, effective pharmacologic strategies can be inferred based on data for those conditions.¹¹ SSRIs, serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), and gabapentin have demonstrated efficacy in anxiety disorders and are reasonable and safe initial treatments for patients with a cluster C PD.^11,34

Continue for the answers >>

CASE 1 › Mr. A’s schizotypal PD symptoms interfere with medication adherence because of his unusual belief system. Importantly, unlike patients with frank delusions, patients with schizotypal PD are willing to consider alternative explanations for their unusual beliefs. Mr. A’s intense suspiciousness may indicate some degree of overlap between paranoid and schizotypal PDs.

The FP is patient and willing to listen to Mr. A’s beliefs without devaluing them. To improve medication adherence, the FP offers him reasonable alternatives with clear explanations. (“I understand you have concerns about previous medications. At the same time, it seems that managing your blood pressure and cholesterol is important to you. Can we discuss alternative treatments?”)

CASE 2 › In response to Ms. B’s borderline PD, the FP must be cautious to avoid reacting out of frustration, which may upset the patient and validate her mistrust. The FP first reflects her anger (“I can tell you are upset because you don’t think I want to help you”), which may allow her to calmly engage in a discussion. He wants to recognize Ms. B’s dramatic behavior, but not reward it with added attention and unreasonable concessions. To help establish rapport, he provides a statement to legitimize Ms. B’s concerns (“Many patients would be frustrated during the process of changing physicians”).

The FP listens empathically to Ms. B, sets clear limits, and provides consistent and evidence-based treatments. He also provides early referral to psychotherapy, but to mitigate any perceived abandonment, he assures Ms. B he will remain involved with her treatment. (“It sounds like managing your anxiety is important to you, and often psychiatrists or therapists can help give additional options for treatment. I want you to know that I am still your doctor and we can review their recommendations together at our next visit.”)

Psychotherapy can be beneficial for patients with personality disorders, even when it is provided by clinicians without advanced mental health training.

CASE 3 › The FP recognizes that Ms. C’s pattern of perfectionism, formality, and rigidity in thought and behavior are likely a manifestation of obsessive-compulsive PD, and that the maladaptive psychological traits underlying her anxiety are distinct from a primary anxiety disorder.

An SSRI may be a reasonable option to treat Ms. B’s anxiety, and the FP also refers her for CBT. (“I can tell you are feeling really anxious and many people feel that way, especially with work. I think the medication is a good start, but I wonder if we could discuss other forms of therapy to maximize your symptom improvement.”) Because of their exacting nature, many patients with cluster C personality traits are willing to engage in treatments, especially if they are supported by data and recommended by a knowledgeable physician.

CORRESPONDENCE
Nicholas Morcos, Department of Psychiatry, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109; [email protected].

Personality disorders (PDs) are common, affecting up to 15% of US adults, and are associated with comorbid medical and psychiatric conditions and increased utilization of health care resources.^1,2 Having a basic understanding of these patterns of thinking and behaving can help family physicians (FPs) identify specific PD diagnoses, ensure appropriate treatment, and reduce the frustration that arises when an individual is viewed as a “difficult patient.”

Here we describe the diagnostic features of the disorders in the 3 major clusters of PDs and review an effective approach to the management of the most common disorder in each cluster, using a case study patient.

Defense mechanisms offer clues that your patient may have a PD

Personality is an enduring pattern of inner experience and behaviors that is relatively stable across time and in different situations. Such traits comprise an individual’s inherent makeup.¹ PDs are diagnosed when an individual’s personality traits create significant distress or impairment in daily functioning. Specifically, PDs have a negative impact on cognition, affect, interpersonal relationships, and/or impulse control.¹

One of the ways people alleviate distress is by using defense mechanisms. Defense mechanisms are unconscious mental processes that individuals use to resolve conflicts, and thereby reduce anxiety and depression on a conscious level. Taken alone, defense mechanisms are not pathologic, but they may become maladaptive in certain stressful circumstances, such as when receiving medical treatment. Recognizing patterns of chronic use of certain defense mechanisms may be a clue that your patient has a PD. TABLE 1^3,4 and TABLE 2^3,4 provide an overview of common defense mechanisms used by patients with PDs.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) organizes PDs into 3 clusters based on similar and often overlapping symptoms.¹TABLE 3¹ provides a brief summary of the characteristic features of each disorder in these clusters.

Cluster A: Odd, eccentric

Patients with one of these disorders are odd, eccentric, or bizarre in their behavior and thinking. There appears to be a genetic link between cluster A PDs (especially schizotypal) and schizophrenia.⁵ These patients rarely seek treatment for their disorder because they have limited insight into their maladaptive traits.^5,6

CASE 1 › Daniel A, age 57, has hypertension and hyperlipidemia and comes in to see his FP for a 6-month follow-up appointment. He never misses appointments, but has a history of poor adherence with prescribed medications. He enjoys his discussions with you in the office, although he often perseverates on conspiracy theories. He lives alone and has never been married. He believes that some of the previously prescribed medications, including a statin and a thiazide diuretic, were interfering with the absorption of “positive nutrients” in his diet. He also refuses to take the generic form of a statin, which he believes was adulterated by the government to be sold at lower cost.

Mr. A demonstrates the odd and eccentric beliefs that characterize schizotypal personality disorder. How can his FP best help him adhere to his medication regimen? (For the answer, click here.)

Schizotypal personality disorder shares certain disturbances of thought with schizophrenia, and is believed to exist on a spectrum with other primary psychotic disorders. Support for this theory comes from the higher rates of schizotypal PD among family members of patients with schizophrenia. There is a genetic component to the disorder.^3,5,6

Clinically, these patients appear odd and eccentric with unusual beliefs. They may have a fascination with magic, clairvoyance, telepathy, or other such notions.^1,5 Although the perceptual disturbances are unusual and often bizarre, they are not frank delusions: patients with schizotypal PD are willing to consider alternative explanations for their beliefs and can engage in rational discussion. Cognitive deficits, particularly of memory and attention, are common and distressing to patients. Frequently, the presenting complaint is depression and anxiety due to the emotional discord and isolation from others.^1,3,5,6

Continue to cluster B >>

Cluster B: Dramatic, erratic

Does your patient complain that you don't understand him "the way his other doctor did"? Or does he frequently lose his temper? Perhaps it's time to consider a personality disorder.

Patients with cluster B PDs are dramatic, excessively emotional, confrontational, erratic, and impulsive in their behaviors.¹ They often have comorbid mood and anxiety disorders, as well as a disproportionately high co-occurrence of functional disorders.^3,7 Their rates of health care utilization can be substantial. Because individuals with one of these PDs sometimes exhibit reckless and impulsive behavior, physicians should be aware these patients have a high risk of physical injuries (fights, accidents, self-injurious behavior), suicide attempts, risky sexual behaviors, and unplanned pregnancy.^8,9

CASE 2 › Sheryl B is a 34-year-old new patient with a history of irritable bowel syndrome, fibromyalgia, depression, and anxiety who shows up for her appointment an hour late. She is upset and blames the office scheduler for not reminding her of the appointment. She brings a list of medications from her previous physician that includes sertraline, clonazepam, gabapentin, oxycodone, and as-needed alprazolam. She insists that her physician increase the dose of the benzodiazepines.

A review of her medical history reveals diagnoses of anxiety, bipolar disorder, and posttraumatic stress disorder. Ms. B has also engaged in superficial cutting since adolescence, often triggered by arguments with her boyfriend. Currently, she attributes her anxiety and pain to not receiving the “correct medications” because of her transition from a previous physician who “knew her better than any other doctor.” After the FP explains to Ms. B that he would have to carefully review her case before continuing to prescribe benzodiazepines, she becomes tearful and argumentative, proclaiming, “You won’t give me the only thing that will help me because you want me to be miserable!”

Ms. B exhibits many cluster B personality traits consistent with borderline PD. How should the FP respond to her claims? (For the answer, click here.)

Borderline PD is the most studied of the PDs. It can be a stigmatizing diagnosis, and even experienced psychiatrists may hesitate to inform patients of this diagnosis.¹⁰ Patients with borderline PD may be erroneously diagnosed with bipolar disorder, treatment-resistant depression, or posttraumatic stress disorder because of a complicated clinical presentation, physician unfamiliarity with diagnostic criteria, or the presence of genuine comorbid conditions.^3,11

The etiology of this disorder appears to be multifactorial, and includes genetic predisposition, disruptive parent-child relationships (especially separation), and, often, past sexual or physical trauma.^9,12

Predominant clinical features include emotional lability, efforts to avoid abandonment, extremes of idealization and devaluation, unstable and intense interpersonal relationships, and impulsivity.¹ Characteristically, these patients also engage in self-injurious behaviors.^13,14 Common defense mechanisms used by patients with borderline PD include splitting (viewing others as either all good or all bad), acting out (yelling, agitation, or violence), and passive aggression (TABLE 1^3,4).

Cluster C: Anxious, fearful

Individuals with cluster C PDs appear anxious, fearful, and worried. They have features that overlap with anxiety disorders.¹⁵

CASE 3 › Judy C is a 40-year-old lawyer with a history of gastroesophageal reflux disorder, hypertension, and anxiety who presents for a 3-week follow-up visit after starting sertraline. The patient describes herself as a perfectionist who has increased work-related stress recently because she has to “do extra work for my colleagues who don’t know how to get things done right.” She recently fired her assistant for “not understanding my filing system.” She appears formal and serious, often looking at her watch during the evaluation.

Ms. C demonstrates a pattern of perfectionism, formality, and rigidity in thought and behavior characteristic of obsessive-compulsive PD. What treatment should her physician recommend? (For the answer, click here.)

Unlike patients with frank delusions, patients with schizotypal personality disorder are willing to consider alternative explanations for their odd beliefs.

Obsessive-compulsive PD. Although this disorder is associated with significant anxiety, patients often view the specific traits of obsessive-compulsive PD, such as perfectionism, as desirable. Neurotic defense mechanisms are common, especially rationalization, intellectualization, and isolation of affect (TABLE 2^3,4). These patients appear formal, rigid, and serious, and are preoccupied with rules and orderliness to achieve perfection.¹ Significant anxiety often arises from fear of making mistakes and ruminating on decision-making.^1,11,15

Although some overlap exists between obsessive-compulsive disorder (OCD) and obsessive-compulsive PD, patients with OCD exhibit distinct obsessions and associated compulsive behavior, whereas those with obsessive-compulsive PD do not.¹

In terms of treatment, it is generally appropriate to recognize the 2 conditions as distinct entities.¹⁵ OCD responds well to cognitive behavioral therapies and high-dose selective serotonin reuptake inhibitors (SSRIs).¹⁶ In contrast, there is little data that suggests antidepressants are effective for obsessive-compulsive PD, and treatment is aimed at addressing comorbid anxiety with psychotherapy and pharmacotherapy, if needed.^11,15

Continue to psychotherapy for PD is the first-line treatment >>

Psychotherapy for PD is the first-line treatment

Psychotherapy is the most effective treatment for PDs.^11,17,18 Several psychotherapies are used to treat these disorders, including dialectical behavioral therapy, schema therapy, and cognitive behavioral therapy (CBT). A recent study demonstrated the superiority of several evidence-based psychotherapies for PD compared to treatment-as-usual.¹⁷ Even more promising is that certain benefits have been demonstrated when psychotherapy is provided by clinicians without advanced mental health training.^19-21 However, the benefits of therapies for specific disorders are often limited by lack of available data, patient preference, and accessibility of resources.

Limited evidence supports pharmacotherapy

The use of pharmacotherapy for treating PDs is common, although there’s limited evidence to support the practice.^11,22 Certain circumstances may allow for the judicious use of medication, although prescribing strategies are based largely on clinical experience and expert opinion.

Prescribers should emphasize a realistic perspective on treatment response, because research suggests at best a mild-moderate response of some personality traits to pharmacotherapy.^11,22-25 There is no evidence for polypharmacy in treating PDs, and FPs should allow for sufficient treatment duration, switch medications rather than augment ineffective treatments, and resist the urge to prescribe for every psychological crisis.^11,22,25,26

Patient safety should always be a consideration when prescribing medication. Because use of second-generation antipsychotics is associated with the metabolic syndrome, the patient’s baseline weight and fasting glucose, lipids, and hemoglobin A1c levels should be obtained and monitored regularly. Weight gain can be particularly distressing to patients, increase stress and anxiety, and hinder the doctor-patient relationship.²⁵ Finally, medications with abuse potential or that can be lethal in overdose (eg, tricyclic antidepressants and benzodiazepines) are best avoided in patients with emotional lability and impulsivity.^25,26

Tailor treatment to the specific PD

Patients often view the specific traits of obsessive-compulsive personality disorder, such as perfectionism, as desirable.

Tx for cluster A disorders. Few studies have examined the effectiveness of psychotherapies for cluster A disorders. Cognitive therapy may have benefit in addressing cognitive distortions and social impairment in schizotypal PD.^11,12,22 There is little evidence supporting psychotherapy for paranoid PD, because challenging patients’ beliefs in this form is likely to exacerbate paranoia. Low-dose risperidone has demonstrated some beneficial effects on perceptual disturbances; however, the adverse metabolic effects of this medication may outweigh any potential benefit, as these symptoms are often not distressing to patients.^6,27 In comparison, patients often find deficits in memory and attention to be more bothersome, and some data suggest that the alpha-2 agonist guanfacine may help treat these symptoms.²⁸

Tx for cluster B disorders. Several forms of psychotherapy have proven effective in managing symptoms and improving overall functioning in patients with borderline PD, including dialectical behavioral therapy, mentalization-based therapy, transference-focused therapy, and schema therapy.²⁹ Dialectical behavioral therapy is often the initial treatment because it emphasizes reducing self-harm behaviors and emotion regulation.^11,17,26

Gunderson¹⁹ developed a more basic approach to treating borderline PD that is intended to be used by all clinicians who treat the disorder, and not just mental health professionals with advanced training in psychotherapy. A large, multisite randomized controlled trial found that the clinical efficacy of the technique, known as good psychiatric management, rivaled that of dialectical behavioral therapy.^20,21

The general premise is that clinicians foster a therapeutic relationship that is supportive, engaging, and flexible. Physicians are encouraged to educate patients about the disorder and emphasize improvement in daily functioning. Clinicians should share the diagnosis with patients, which may give patients a sense of relief in having an accurate diagnosis and allow them to fully invest in diagnosis-specific treatments.¹⁹

Systematic reviews and meta-analyses of studies that evaluated pharmacotherapy for borderline PD often have had conflicting conclusions as a result of analyzing data from underpowered studies with varying study designs.^{23,24,26,30,31} In targeting specific symptoms of the disorder, the most consistent evidence has supported the use of antipsychotics for cognitive perceptual disturbances; patients commonly experience depersonalization or out-of-body experiences.²⁵ Additionally, the use of antipsychotics and mood stabilizers (lamotrigine and topiramate) appears to be somewhat effective for managing emotional lability and impulsivity.^26,32,33 Despite the widespread use of SSRIs, a recent systematic review found the least support for these and other antidepressants for management of borderline PD.²⁵

Tx for cluster C disorders. Some evidence supports using cognitive and interpersonal psychotherapies to treat cluster C PDs.³⁴ In contrast, there is little evidence to support the use of pharmacotherapy.³⁵ However, given the significant overlap among these disorders (especially avoidant PD) and social phobia and generalized anxiety disorder, effective pharmacologic strategies can be inferred based on data for those conditions.¹¹ SSRIs, serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), and gabapentin have demonstrated efficacy in anxiety disorders and are reasonable and safe initial treatments for patients with a cluster C PD.^11,34

Continue for the answers >>

CASE 1 › Mr. A’s schizotypal PD symptoms interfere with medication adherence because of his unusual belief system. Importantly, unlike patients with frank delusions, patients with schizotypal PD are willing to consider alternative explanations for their unusual beliefs. Mr. A’s intense suspiciousness may indicate some degree of overlap between paranoid and schizotypal PDs.

The FP is patient and willing to listen to Mr. A’s beliefs without devaluing them. To improve medication adherence, the FP offers him reasonable alternatives with clear explanations. (“I understand you have concerns about previous medications. At the same time, it seems that managing your blood pressure and cholesterol is important to you. Can we discuss alternative treatments?”)

CASE 2 › In response to Ms. B’s borderline PD, the FP must be cautious to avoid reacting out of frustration, which may upset the patient and validate her mistrust. The FP first reflects her anger (“I can tell you are upset because you don’t think I want to help you”), which may allow her to calmly engage in a discussion. He wants to recognize Ms. B’s dramatic behavior, but not reward it with added attention and unreasonable concessions. To help establish rapport, he provides a statement to legitimize Ms. B’s concerns (“Many patients would be frustrated during the process of changing physicians”).

The FP listens empathically to Ms. B, sets clear limits, and provides consistent and evidence-based treatments. He also provides early referral to psychotherapy, but to mitigate any perceived abandonment, he assures Ms. B he will remain involved with her treatment. (“It sounds like managing your anxiety is important to you, and often psychiatrists or therapists can help give additional options for treatment. I want you to know that I am still your doctor and we can review their recommendations together at our next visit.”)

Psychotherapy can be beneficial for patients with personality disorders, even when it is provided by clinicians without advanced mental health training.

CASE 3 › The FP recognizes that Ms. C’s pattern of perfectionism, formality, and rigidity in thought and behavior are likely a manifestation of obsessive-compulsive PD, and that the maladaptive psychological traits underlying her anxiety are distinct from a primary anxiety disorder.

An SSRI may be a reasonable option to treat Ms. B’s anxiety, and the FP also refers her for CBT. (“I can tell you are feeling really anxious and many people feel that way, especially with work. I think the medication is a good start, but I wonder if we could discuss other forms of therapy to maximize your symptom improvement.”) Because of their exacting nature, many patients with cluster C personality traits are willing to engage in treatments, especially if they are supported by data and recommended by a knowledgeable physician.

CORRESPONDENCE
Nicholas Morcos, Department of Psychiatry, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109; [email protected].

Personality disorders (PDs) are common, affecting up to 15% of US adults, and are associated with comorbid medical and psychiatric conditions and increased utilization of health care resources.^1,2 Having a basic understanding of these patterns of thinking and behaving can help family physicians (FPs) identify specific PD diagnoses, ensure appropriate treatment, and reduce the frustration that arises when an individual is viewed as a “difficult patient.”

Here we describe the diagnostic features of the disorders in the 3 major clusters of PDs and review an effective approach to the management of the most common disorder in each cluster, using a case study patient.

Defense mechanisms offer clues that your patient may have a PD

Personality is an enduring pattern of inner experience and behaviors that is relatively stable across time and in different situations. Such traits comprise an individual’s inherent makeup.¹ PDs are diagnosed when an individual’s personality traits create significant distress or impairment in daily functioning. Specifically, PDs have a negative impact on cognition, affect, interpersonal relationships, and/or impulse control.¹

One of the ways people alleviate distress is by using defense mechanisms. Defense mechanisms are unconscious mental processes that individuals use to resolve conflicts, and thereby reduce anxiety and depression on a conscious level. Taken alone, defense mechanisms are not pathologic, but they may become maladaptive in certain stressful circumstances, such as when receiving medical treatment. Recognizing patterns of chronic use of certain defense mechanisms may be a clue that your patient has a PD. TABLE 1^3,4 and TABLE 2^3,4 provide an overview of common defense mechanisms used by patients with PDs.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) organizes PDs into 3 clusters based on similar and often overlapping symptoms.¹TABLE 3¹ provides a brief summary of the characteristic features of each disorder in these clusters.

Cluster A: Odd, eccentric

Patients with one of these disorders are odd, eccentric, or bizarre in their behavior and thinking. There appears to be a genetic link between cluster A PDs (especially schizotypal) and schizophrenia.⁵ These patients rarely seek treatment for their disorder because they have limited insight into their maladaptive traits.^5,6

CASE 1 › Daniel A, age 57, has hypertension and hyperlipidemia and comes in to see his FP for a 6-month follow-up appointment. He never misses appointments, but has a history of poor adherence with prescribed medications. He enjoys his discussions with you in the office, although he often perseverates on conspiracy theories. He lives alone and has never been married. He believes that some of the previously prescribed medications, including a statin and a thiazide diuretic, were interfering with the absorption of “positive nutrients” in his diet. He also refuses to take the generic form of a statin, which he believes was adulterated by the government to be sold at lower cost.

Mr. A demonstrates the odd and eccentric beliefs that characterize schizotypal personality disorder. How can his FP best help him adhere to his medication regimen? (For the answer, click here.)

Schizotypal personality disorder shares certain disturbances of thought with schizophrenia, and is believed to exist on a spectrum with other primary psychotic disorders. Support for this theory comes from the higher rates of schizotypal PD among family members of patients with schizophrenia. There is a genetic component to the disorder.^3,5,6

Clinically, these patients appear odd and eccentric with unusual beliefs. They may have a fascination with magic, clairvoyance, telepathy, or other such notions.^1,5 Although the perceptual disturbances are unusual and often bizarre, they are not frank delusions: patients with schizotypal PD are willing to consider alternative explanations for their beliefs and can engage in rational discussion. Cognitive deficits, particularly of memory and attention, are common and distressing to patients. Frequently, the presenting complaint is depression and anxiety due to the emotional discord and isolation from others.^1,3,5,6

Continue to cluster B >>

Cluster B: Dramatic, erratic

Does your patient complain that you don't understand him "the way his other doctor did"? Or does he frequently lose his temper? Perhaps it's time to consider a personality disorder.

Patients with cluster B PDs are dramatic, excessively emotional, confrontational, erratic, and impulsive in their behaviors.¹ They often have comorbid mood and anxiety disorders, as well as a disproportionately high co-occurrence of functional disorders.^3,7 Their rates of health care utilization can be substantial. Because individuals with one of these PDs sometimes exhibit reckless and impulsive behavior, physicians should be aware these patients have a high risk of physical injuries (fights, accidents, self-injurious behavior), suicide attempts, risky sexual behaviors, and unplanned pregnancy.^8,9

CASE 2 › Sheryl B is a 34-year-old new patient with a history of irritable bowel syndrome, fibromyalgia, depression, and anxiety who shows up for her appointment an hour late. She is upset and blames the office scheduler for not reminding her of the appointment. She brings a list of medications from her previous physician that includes sertraline, clonazepam, gabapentin, oxycodone, and as-needed alprazolam. She insists that her physician increase the dose of the benzodiazepines.

A review of her medical history reveals diagnoses of anxiety, bipolar disorder, and posttraumatic stress disorder. Ms. B has also engaged in superficial cutting since adolescence, often triggered by arguments with her boyfriend. Currently, she attributes her anxiety and pain to not receiving the “correct medications” because of her transition from a previous physician who “knew her better than any other doctor.” After the FP explains to Ms. B that he would have to carefully review her case before continuing to prescribe benzodiazepines, she becomes tearful and argumentative, proclaiming, “You won’t give me the only thing that will help me because you want me to be miserable!”

Ms. B exhibits many cluster B personality traits consistent with borderline PD. How should the FP respond to her claims? (For the answer, click here.)

Borderline PD is the most studied of the PDs. It can be a stigmatizing diagnosis, and even experienced psychiatrists may hesitate to inform patients of this diagnosis.¹⁰ Patients with borderline PD may be erroneously diagnosed with bipolar disorder, treatment-resistant depression, or posttraumatic stress disorder because of a complicated clinical presentation, physician unfamiliarity with diagnostic criteria, or the presence of genuine comorbid conditions.^3,11

The etiology of this disorder appears to be multifactorial, and includes genetic predisposition, disruptive parent-child relationships (especially separation), and, often, past sexual or physical trauma.^9,12

Predominant clinical features include emotional lability, efforts to avoid abandonment, extremes of idealization and devaluation, unstable and intense interpersonal relationships, and impulsivity.¹ Characteristically, these patients also engage in self-injurious behaviors.^13,14 Common defense mechanisms used by patients with borderline PD include splitting (viewing others as either all good or all bad), acting out (yelling, agitation, or violence), and passive aggression (TABLE 1^3,4).

Cluster C: Anxious, fearful

Individuals with cluster C PDs appear anxious, fearful, and worried. They have features that overlap with anxiety disorders.¹⁵

CASE 3 › Judy C is a 40-year-old lawyer with a history of gastroesophageal reflux disorder, hypertension, and anxiety who presents for a 3-week follow-up visit after starting sertraline. The patient describes herself as a perfectionist who has increased work-related stress recently because she has to “do extra work for my colleagues who don’t know how to get things done right.” She recently fired her assistant for “not understanding my filing system.” She appears formal and serious, often looking at her watch during the evaluation.

Ms. C demonstrates a pattern of perfectionism, formality, and rigidity in thought and behavior characteristic of obsessive-compulsive PD. What treatment should her physician recommend? (For the answer, click here.)

Unlike patients with frank delusions, patients with schizotypal personality disorder are willing to consider alternative explanations for their odd beliefs.

Obsessive-compulsive PD. Although this disorder is associated with significant anxiety, patients often view the specific traits of obsessive-compulsive PD, such as perfectionism, as desirable. Neurotic defense mechanisms are common, especially rationalization, intellectualization, and isolation of affect (TABLE 2^3,4). These patients appear formal, rigid, and serious, and are preoccupied with rules and orderliness to achieve perfection.¹ Significant anxiety often arises from fear of making mistakes and ruminating on decision-making.^1,11,15

Although some overlap exists between obsessive-compulsive disorder (OCD) and obsessive-compulsive PD, patients with OCD exhibit distinct obsessions and associated compulsive behavior, whereas those with obsessive-compulsive PD do not.¹

In terms of treatment, it is generally appropriate to recognize the 2 conditions as distinct entities.¹⁵ OCD responds well to cognitive behavioral therapies and high-dose selective serotonin reuptake inhibitors (SSRIs).¹⁶ In contrast, there is little data that suggests antidepressants are effective for obsessive-compulsive PD, and treatment is aimed at addressing comorbid anxiety with psychotherapy and pharmacotherapy, if needed.^11,15

Continue to psychotherapy for PD is the first-line treatment >>

Psychotherapy for PD is the first-line treatment

Psychotherapy is the most effective treatment for PDs.^11,17,18 Several psychotherapies are used to treat these disorders, including dialectical behavioral therapy, schema therapy, and cognitive behavioral therapy (CBT). A recent study demonstrated the superiority of several evidence-based psychotherapies for PD compared to treatment-as-usual.¹⁷ Even more promising is that certain benefits have been demonstrated when psychotherapy is provided by clinicians without advanced mental health training.^19-21 However, the benefits of therapies for specific disorders are often limited by lack of available data, patient preference, and accessibility of resources.

Limited evidence supports pharmacotherapy

The use of pharmacotherapy for treating PDs is common, although there’s limited evidence to support the practice.^11,22 Certain circumstances may allow for the judicious use of medication, although prescribing strategies are based largely on clinical experience and expert opinion.

Prescribers should emphasize a realistic perspective on treatment response, because research suggests at best a mild-moderate response of some personality traits to pharmacotherapy.^11,22-25 There is no evidence for polypharmacy in treating PDs, and FPs should allow for sufficient treatment duration, switch medications rather than augment ineffective treatments, and resist the urge to prescribe for every psychological crisis.^11,22,25,26

Patient safety should always be a consideration when prescribing medication. Because use of second-generation antipsychotics is associated with the metabolic syndrome, the patient’s baseline weight and fasting glucose, lipids, and hemoglobin A1c levels should be obtained and monitored regularly. Weight gain can be particularly distressing to patients, increase stress and anxiety, and hinder the doctor-patient relationship.²⁵ Finally, medications with abuse potential or that can be lethal in overdose (eg, tricyclic antidepressants and benzodiazepines) are best avoided in patients with emotional lability and impulsivity.^25,26

Tailor treatment to the specific PD

Patients often view the specific traits of obsessive-compulsive personality disorder, such as perfectionism, as desirable.

Tx for cluster A disorders. Few studies have examined the effectiveness of psychotherapies for cluster A disorders. Cognitive therapy may have benefit in addressing cognitive distortions and social impairment in schizotypal PD.^11,12,22 There is little evidence supporting psychotherapy for paranoid PD, because challenging patients’ beliefs in this form is likely to exacerbate paranoia. Low-dose risperidone has demonstrated some beneficial effects on perceptual disturbances; however, the adverse metabolic effects of this medication may outweigh any potential benefit, as these symptoms are often not distressing to patients.^6,27 In comparison, patients often find deficits in memory and attention to be more bothersome, and some data suggest that the alpha-2 agonist guanfacine may help treat these symptoms.²⁸

Tx for cluster B disorders. Several forms of psychotherapy have proven effective in managing symptoms and improving overall functioning in patients with borderline PD, including dialectical behavioral therapy, mentalization-based therapy, transference-focused therapy, and schema therapy.²⁹ Dialectical behavioral therapy is often the initial treatment because it emphasizes reducing self-harm behaviors and emotion regulation.^11,17,26

Gunderson¹⁹ developed a more basic approach to treating borderline PD that is intended to be used by all clinicians who treat the disorder, and not just mental health professionals with advanced training in psychotherapy. A large, multisite randomized controlled trial found that the clinical efficacy of the technique, known as good psychiatric management, rivaled that of dialectical behavioral therapy.^20,21

The general premise is that clinicians foster a therapeutic relationship that is supportive, engaging, and flexible. Physicians are encouraged to educate patients about the disorder and emphasize improvement in daily functioning. Clinicians should share the diagnosis with patients, which may give patients a sense of relief in having an accurate diagnosis and allow them to fully invest in diagnosis-specific treatments.¹⁹

Systematic reviews and meta-analyses of studies that evaluated pharmacotherapy for borderline PD often have had conflicting conclusions as a result of analyzing data from underpowered studies with varying study designs.^{23,24,26,30,31} In targeting specific symptoms of the disorder, the most consistent evidence has supported the use of antipsychotics for cognitive perceptual disturbances; patients commonly experience depersonalization or out-of-body experiences.²⁵ Additionally, the use of antipsychotics and mood stabilizers (lamotrigine and topiramate) appears to be somewhat effective for managing emotional lability and impulsivity.^26,32,33 Despite the widespread use of SSRIs, a recent systematic review found the least support for these and other antidepressants for management of borderline PD.²⁵

Tx for cluster C disorders. Some evidence supports using cognitive and interpersonal psychotherapies to treat cluster C PDs.³⁴ In contrast, there is little evidence to support the use of pharmacotherapy.³⁵ However, given the significant overlap among these disorders (especially avoidant PD) and social phobia and generalized anxiety disorder, effective pharmacologic strategies can be inferred based on data for those conditions.¹¹ SSRIs, serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), and gabapentin have demonstrated efficacy in anxiety disorders and are reasonable and safe initial treatments for patients with a cluster C PD.^11,34

Continue for the answers >>

CASE 1 › Mr. A’s schizotypal PD symptoms interfere with medication adherence because of his unusual belief system. Importantly, unlike patients with frank delusions, patients with schizotypal PD are willing to consider alternative explanations for their unusual beliefs. Mr. A’s intense suspiciousness may indicate some degree of overlap between paranoid and schizotypal PDs.

The FP is patient and willing to listen to Mr. A’s beliefs without devaluing them. To improve medication adherence, the FP offers him reasonable alternatives with clear explanations. (“I understand you have concerns about previous medications. At the same time, it seems that managing your blood pressure and cholesterol is important to you. Can we discuss alternative treatments?”)

CASE 2 › In response to Ms. B’s borderline PD, the FP must be cautious to avoid reacting out of frustration, which may upset the patient and validate her mistrust. The FP first reflects her anger (“I can tell you are upset because you don’t think I want to help you”), which may allow her to calmly engage in a discussion. He wants to recognize Ms. B’s dramatic behavior, but not reward it with added attention and unreasonable concessions. To help establish rapport, he provides a statement to legitimize Ms. B’s concerns (“Many patients would be frustrated during the process of changing physicians”).

The FP listens empathically to Ms. B, sets clear limits, and provides consistent and evidence-based treatments. He also provides early referral to psychotherapy, but to mitigate any perceived abandonment, he assures Ms. B he will remain involved with her treatment. (“It sounds like managing your anxiety is important to you, and often psychiatrists or therapists can help give additional options for treatment. I want you to know that I am still your doctor and we can review their recommendations together at our next visit.”)

Psychotherapy can be beneficial for patients with personality disorders, even when it is provided by clinicians without advanced mental health training.

CASE 3 › The FP recognizes that Ms. C’s pattern of perfectionism, formality, and rigidity in thought and behavior are likely a manifestation of obsessive-compulsive PD, and that the maladaptive psychological traits underlying her anxiety are distinct from a primary anxiety disorder.

An SSRI may be a reasonable option to treat Ms. B’s anxiety, and the FP also refers her for CBT. (“I can tell you are feeling really anxious and many people feel that way, especially with work. I think the medication is a good start, but I wonder if we could discuss other forms of therapy to maximize your symptom improvement.”) Because of their exacting nature, many patients with cluster C personality traits are willing to engage in treatments, especially if they are supported by data and recommended by a knowledgeable physician.

CORRESPONDENCE
Nicholas Morcos, Department of Psychiatry, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI 48109; [email protected].

IN THIS ARTICLE

• The 2008 USPHS guideline: 10 key recommendations
• USPHS smoking cessation guideline: An evidence summary
• Medications for smoking cessation: Dosing, advantages, and adverse effects

In its 2014 report, The Health Consequences of Smoking—50 Years of Progress,¹ the US Surgeon General concluded that, while significant improvements have been made since the publication of its landmark 1964 report, cigarette smoking remains a major public health problem. It is the leading cause of preventable death, increasing the risk for such common causes of mortality as cardiovascular disease, pulmonary disease, and malignancy. Cigarette smoking is responsible for an estimated 443,000 deaths annually.²

Overall, 42 million US adults and about 3 million middle and high school students smoke, despite the availability of an array of pharmacologic interventions to help them quit.¹ Half of those who continue to smoke will die from a tobacco-related cause. Stopping before the age of 50 cuts the risk in half, and quitting before age 30 almost completely negates it.³

The most recent comprehensive smoking cessation guideline, sponsored by the US Public Health Service, was published in 2008.⁴ The US Preventive Services Task Force (USPSTF) recommendation that “clinicians ask all adults about tobacco use and provide tobacco cessation interventions” for those who smoke was issued one year later.⁵ Since then, multiple studies have assessed the merits of the various medications, forms of nicotine replacement therapy (NRT), and counseling aimed at helping smokers maintain abstinence from tobacco.

This article reviews the guideline and provides family practice providers with an evidence-based update.

Continue for treating tobacco use and dependence >>

The guideline: Treating tobacco use and dependence
Prescribing a firstline medication (bupropion SR, varenicline, nicotine gum, nicotine inhaler, nicotine lozenge, nicotine nasal spray, or nicotine patch) for every patient who seeks to quit smoking is a key component of the 2008 guideline (see Table 1).⁴ The only exceptions: patients for whom such agents are medically contraindicated and groups for which there is insufficient evidence of effectiveness, such as pregnant women and adolescents.

The use of any of these medications as a single agent nearly doubles the likelihood of success compared with placebo, with an average cessation rate of 25% (see Table 2).⁴ Combination therapy (pairing a nicotine patch and an additional agent) was found to be even more effective, with some combinations attaining success rates as high as 65%.⁴

Second-line therapies, including clonidine and nortriptyline, were also cited as effective, with an average cessation rate of 24%.⁴ Although the meta-analyses that these averages were based on did not include head-to-head comparisons, subsequent studies that also showed efficacy did include such comparisons.

Continue for counseling is an essential component >>

Counseling is an essential component
In one of the meta-analyses on which the guideline was based, the combination of counseling and medication proved to be more effective than either intervention alone. Individual, group, and telephone counseling were all effective (odds ratios [ORs], 1.7, 1.3, and 1.2, respectively), provided they included practical help that emphasized problem solving and skills training, as well as social support. The benefits of a team-based approach were evident from the finding that counseling provided by more than one type of clinician had higher effect sizes (OR, 2.5 when two different clinical disciplines were involved and 2.4 for three or more disciplines).⁴

The guideline also found state-sponsored quit lines, accessible at no charge via 800-QUIT-NOW, are an effective option. (For more information about this and other resources, see Table W1.) For patients who aren’t ready to stop smoking, the guideline recommends motivational interviewing⁴—a direct, patient-centered technique used to explore and work through ambivalence. Further information about this method is available at www.motivational interviewing.org.

In counseling patients who are considering a quit attempt, it is important to present all options. A smoking history is needed, too, because factors such as the number of cigarettes smoked per day, how long a patient is typically awake before smoking the first cigarette of the day, and level of dependence are important factors in determining medication and dosage. Consider the advantages and disadvantages of the various medications (see Table 3) or methods used for prior quit attempts and reasons for relapse, if appropriate, as well as patient preference.^4,6,7

Continue for evidence update >>

Evidence update: What’s best?
Since 2009, many clinical trials have examined the best way to help smokers quit. Here’s a closer look at the latest evidence.

NRT boosts long-term cessation
A 2012 Cochrane review examined 150 trials and found that every type of NRT—gum, lozenge, patch, inhaler, and nasal spray—was associated with long-term cessation (relative risk [RR], 1.60).⁸ This effect was essentially unchanged regardless of the duration, setting, or intensity of supportive therapy offered, and no single type of NRT was more effective than any other. However, combining a short-acting form, such as a lozenge, with a long-acting patch was found to be more effective than either one alone (RR, 1.34).

Starting the NRT before the patient quit did not improve cessation rates over traditional start times (RR, 1.18). Neither was there an added benefit to using NRT beyond the recommended 24-week prescription period,⁹ although doing so was found to be safe. Another 2012 Cochrane review looked specifically at the use of pharmacologic smoking cessation interventions during pregnancy and concluded that there was still not sufficient data to document efficacy for this patient population.¹⁰

Adherence. In deciding on which type of NRT to prescribe, it is important to consider not only patient preference and previous efforts but also the latest evidence. A study comparing various NRT formulations found patient adherence to be highest with the patch, followed by nicotine gum, which had a higher compliance rate than either the nicotine inhaler or nasal spray.¹¹

Varenicline is still a firstline agent
Since the 2008 guideline recommended this partial nicotinic receptor agonist/antagonist as a firstline pharmacologic agent, additional meta-analyses have confirmed its long-term efficacy in smokers who are ready to quit.^12,13 A 2012 Cochrane review found varenicline to increase long-term cessation compared with placebo (RR, 2.27).¹³ It also showed varenicline to be more effective than bupropion SR (RR, 1.52), but about as effective as NRT (RR, 1.13).

Newer data suggest that varenicline may also be effective for those who are willing to cut down on smoking but not yet ready to give up cigarettes completely. Used for 24 weeks by those who were initially resistant to quitting, researchers found varenicline nearly tripled the cessation rate at 52 weeks compared with placebo (RR, 2.7).¹⁴

Latest evidence on safety. Additional concerns about the safety of varenicline have been raised, however, since the 2008 guideline was published. In 2009, the FDA required that black box warnings be added to the labels of both varenicline and bupropion SR based on postmarketing safety reports showing risk for neuropsychiatric symptoms, including suicidality.¹⁵ In 2011, a large case-control study by the FDA Adverse Event Reporting System also showed an increased risk for suicidality in patients taking these drugs.¹⁶

Follow-up studies, however, including a large prospective cohort study and a large meta-analysis, failed to show an increased association with neuropsychiatric adverse effects.^17,18 A smaller randomized controlled trial (RCT) showed that in smokers diagnosed with schizophrenia and bipolar disorder, maintenance therapy with varenicline was effective in preventing smoking relapse for up to 52 weeks. Abstinence rates were 60% for those in the varenicline group versus 19% for those in the placebo group (OR, 6.2). Although no increased risk for adverse psychiatric events was found in this study, it was not powered to detect them.¹⁹ Also of note: A meta-analysis of 14 RCTs showed an increased rate of cardiovascular events associated with varenicline.²⁰ There are concerns about methodologic flaws in this meta-analysis, however, and two subsequent meta-analyses failed to find a cardiovascular risk.^21,22

The higher quality studies that have been published since the original concerns about varenicline’s safety are reassuring, but it is still essential to carefully weigh the risks and benefits of varenicline. Review cardiac and psychiatric history and conduct a suicidality assessment before prescribing it as a smoking cessation aid, and provide close follow-up.

Continue for a closer look at antidepressants >>

A closer look at antidepressants
Bupropion SR, an atypical antidepressant, was also listed as a firstline treatment in the 2008 guideline. A 2014 Cochrane review of 90 studies confirmed the evidence for this recommendation.⁶ Monotherapy with this agent was found to significantly increase rates of long-term cessation (RR, 1.62). No increased risk for serious adverse events was identified compared with placebo. As already noted, associations with neuropsychiatric symptoms were found, but this risk must be considered with any antidepressant.

Bupropion’s efficacy was not significantly different from that of NRT, but moderate evidence suggests that it is less effective than varenicline (RR, 0.68). Other classes of antidepressants, including selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors, were found to be ineffective for smoking cessation.⁶

Nortriptyline, a tricyclic antidepressant, was not significantly different from bupropion SR (RR, 1.30) in efficacy for smoking cessation, but it lacks FDA approval for this purpose and is not considered a firstline agent.⁶

Second-line agents
Clonidine is an alpha-2 adrenergic receptor agonist that was originally used to treat hypertension but found to be effective for smoking cessation in a meta-analysis performed for the 2008 guideline.⁴ Like nortriptyline, however, clonidine is not FDA-approved for this purpose and is not considered a firstline agent.⁵ A 2013 Cochrane meta-analysis further showed that clonidine is effective for smoking cessation versus placebo (RR, 1.63)⁷ but suggested that its significant dose-related adverse effects, including postural hypotension and sedation, could limit its usefulness.

Combination therapies are highly effective
Evidence for various combinations of smoking cessation pharmacotherapy continues to mount.^23-26 Perhaps the most compelling evidence comes from a comparative effectiveness trial that randomized 1,346 patients in 12 primary care clinics to nicotine patches, nicotine lozenges, bupropion SR, a combination of patch plus lozenge, and bupropion SR plus lozenge. The six-month abstinence rate was 30% for the bupropion SR plus lozenge combination, the most effective option. The combination was superior to either patch or bupropion SR monotherapy (ORs, 0.56 and 0.54, respectively).²³ Based on data from the 2008 guideline, similar combinations (eg, nicotine patch plus nicotine gum or bupropion SR plus the patch) are likely to be equally effective. The 2008 guideline also supports a nicotine patch and nicotine inhaler combination.

Another study found varenicline combined with the patch to be highly effective, with a 65% abstinence rate at 24 weeks compared with 47% for varenicline alone (number needed to treat [NNT], 6).²⁴

In heavy smokers—defined as those who smoke 20 or more cigarettes daily—a varenicline and bupropion SR combination was more effective than varenicline alone (NNT, 9), but the combination can lead to increased anxiety and depression.²⁵ A smaller study found triple therapy using nicotine patch plus inhaler plus bupropion SR to be more effective than the nicotine patch alone (35% abstinence vs 19% abstinence at 26 weeks; NNT, 6).²⁶ Consider using these combinations in patients who have high nicotine dependency levels or who have been unable to quit using a single firstline agent.

Continue to the role e-cigarettes play >>

What role do e-cigarettes play?
The use of electronic cigarettes or “vapes”—battery-operated devices that deliver nicotine to the user through vapor—has increased significantly since their US introduction in 2007. A recent study found that “ever use” of e-cigarettes increased from 1.8% in 2010 to 13% in 2013; current use increased from 0.3% to 6.8% in the same time frame.²⁷ Vaping, as inhaling on an e-cigarette is sometimes known, causes a sensor to detect airflow and initiate the heating element to vaporize the liquid solution within the cartridge, which contains propylene glycol, flavoring, and nicotine.

There is limited evidence of the efficacy of e-cigarettes for smoking cessation, but there is support for their role in reducing the quantity of conventional cigarettes smoked. A 2014 Cochrane review of two RCTs evaluating e-cigarette efficacy for smoking cessation or reduction found evidence of increased abstinence at six months in users of e-cigarettes containing nicotine, compared with placebo e-cigarettes (9% vs 4%; RR, 2.29). Additionally, e-cigarette use was associated with a more than 50% decrease in cigarette smoking versus placebo (36% vs 27%; RR,1.31) or patch (61% vs 44%; RR, 1.41).²⁸

A survey published after the review also showed a correlation between cigarette reduction (but not cessation) after one year of e-cigarette use.²⁹ A subsequent RCT conducted in a controlled laboratory setting found that e-cigarettes were highly effective in reducing cessation-related cravings.³⁰ And at eight-month follow-up, 44% of those using e-cigarettes were found to have at least a 50% reduction in the use of conventional cigarettes—and complete cessation in some cases.

Concerns about health effects
E-cigarettes have generally been thought to be safer than conventional cigarettes, given that they mainly deliver nicotine and propylene glycol instead of the more toxic chemicals—eg, benzene, carbon monoxide, and formaldehyde—released by conventional cigarettes.³¹ Carcinogens have also been found in e-cigarettes, but at significantly lower levels.³¹ However, a systematic review found wide variation in the toxin content of e-cigarettes.³² In addition, recent reports have detailed incidents in which e-cigarette devices were alleged to have exploded, causing severe bodily harm.³³

Adverse effects of e-cigarettes include minor irritation of the throat, mouth, and lungs. Among cigarette-naive patients, lightheadedness, throat irritation, dizziness, and cough were most commonly reported. No serious adverse events have been reported, but the lack of long-term safety data is a source of concern.³²

Additionally, minimal regulatory oversight of the e-cigarette industry exists. Currently, the FDA only has authority to regulate e-cigarettes that are marketed for therapeutic purposes, although the agency is seeking to extend its oversight to all e-cigarettes.

The bottom line: More data on safety and regulatory oversight are needed before recommendations on the use of e-cigarettes as a smoking cessation tool can be made.

Continue for looking ahead >>

Looking ahead
Several novel pharmacotherapies have been evaluated for smoking cessation in recent years. Among them is a nicotine vaccine that several drug companies have been pursuing. In theory, such a vaccine would create an immunologic reaction to nicotine in a smoker, thereby preventing the substance from reaching the brain and providing rewarding stimuli. A 2008 Cochrane review of four trials assessing the efficacy of nicotine vaccines for tobacco cessation found that none showed efficacy.³⁴

Naltrexone, an opioid antagonist, has shown efficacy in helping those with opioid or alcohol dependence achieve abstinence from these substances, raising the possibility that it might aid in smoking cessation as well. A 2013 Cochrane review of eight trials found that this was not the case: Compared with placebo, naltrexone was not beneficial when used alone (RR, 1.00) or as an adjunct to NRT compared with NRT alone (RR, 0.95).³⁵

Cytisine, an extract from plants in the Faboideae family, has been used in Eastern Europe for decades for smoking cessation. It appears to work as a nicotine receptor partial agonist similar to varenicline. The extract does not have FDA approval, but the National Institutes of Health’s Center for Complementary and Integrative Health is sponsoring early-stage safety trials that could lead to its approval in the US.³⁶

A 2012 Cochrane review identified two recent RCTs evaluating cytisine and found it to be effective in increasing smoking cessation rates, compared with placebo (RR, 3.98).¹³

The authors thank Matt Orr, PhD, and Kathryn E. Bornemann for their help with this manuscript.

References
1. National Center for Chronic Disease Prevention and Health Promotion Office on Smoking and Health. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. www.ncbi.nlm.nih.gov/pubmed/24455788. Accessed January 21, 2016.
2. Smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008;57:1226-1228.
3. Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ. 2004;328:1519.
4. US Public Health Service. A clinical practice guideline for treating tobacco use and dependence: 2008 update. Am J Prev Med. 2008;35:158-176.
5. US Preventive Services Task Force. Tobacco use in adults and pregnant women: counseling and interventions. April 2009. www.uspreventiveservicestaskforce.org/Page/Topic/recommendation-summary/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions. Accessed January 21, 2016.
6. Hughes JR, Stead LF, Hartmann-Boyce J, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031.
7. Cahill K, Stevens S, Perera R, et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013;(5):CD009329.
8. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;(11):CD000146.
9. Schnoll RA, Goelz PM, Veluz-Wilkins A, et al. Long-term nicotine replacement therapy: a randomized clinical trial. JAMA Intern Med. 2015;175: 504-511.
10. Coleman T, Chamberlain C, Davey MA, et al. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2012;(9):CD010078.
11. Hajek P, West R, Foulds J, et al. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med. 1999;159:2033-2038.
12. Eisenberg MJ, Filion KB, Yavin D, et al. Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials. CMAJ. 2008;179:135-144.
13. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2012;(4):CD006103.
14. Ebbert JO, Hughes JR, West RJ, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015;313:687-694.
15. FDA. Reports of suicidality associated with use of varenicline (marketed as CHANTIX) and bupropion (marketed as ZYBAN and GENERICS). FDA Drug Safety News. 2009.
16. Moore TJ, Furberg CD, Glenmullen J, et al. Suicidal behavior and depression in smoking cessation treatments. PLoS One. 2011;6:e27016.
17. Thomas KH, Martin RM, Davies NM, et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study. BMJ. 2013;347:f5704.
18. Thomas KH, Martin RM, Knipe DW, et al. Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ. 2015;350:h1109.
19. Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014;311:145-154.
20. Singh S, Loke YK, Spangler JG, et al. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011;183:1359-1366.
21. Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ. 2012;344:e2856.
22. Svanström H, Pasternak B, Hviid A. Use of varenicline for smoking cessation and risk of serious cardiovascular events: nationwide cohort study. BMJ. 2012;345:e7176.
23. Smith SS, McCarthy DE, Japuntich SJ, et al. Comparative effectiveness of five smoking cessation pharmacotherapies in primary care clinics. Arch Intern Med. 2009;169:2148-2155.
24. Koegelenberg CFN, Noor F, Bateman ED, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation. JAMA. 2014;312:155-161.
25. Ebbert JO, Hatsukami DK, Croghan IT, et al. Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA. 2014;311:155-163.
26. Steinberg MB, Greenhaus S, Schmelzer AC, et al. Triple-combination pharmacotherapy for medically ill smokers: a randomized trial. Ann Intern Med. 2009;150:447-454.
27. McMillen RC, Gottlieb MA, Shaefer RMW, et al. Trends in electronic cigarette use among US adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 2015;17:1195-1202.
28. McRobbie H, Bullen C, Hartmann-Boyce J, et al. Electronic cigarettes for smoking cessation and reduction. Cochrane Database Syst Rev. 2014;(12):CD010216.
29. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110:1160-1168.
30. Adriaens K, Van Gucht D, Declerck P, et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11:11220-11248.
31. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133-139.
32. Pisinger C, Døssing M. A systematic review of health effects of electronic cigarettes. Prev Med (Baltim). 2014;69C:248-260.
33. Bowerman M. Fla man hospitalized after e-cigarette explodes in face. USA Today Network. October 29, 2015. www.usatoday.com/story/news/nation-now/2015/10/29/fla-man-hospitalized-e-cigarette-explodes-face/74791722/. Accessed January 21, 2016.
34. Hatsukami D, Cahill K, Stead LF. Nicotine vaccines for smoking cessation. Cochrane Database Syst Rev. 2008;(2):CD007072.
35. David SP, Lancaster T, Stead LF, et al. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2013;(6):CD003086.
36. Frankel T. Pill that quashes tobacco urge found in plain sight. Washington Post. May 15, 2015. www.washingtonpost.com/business/economy/pill-promises-a-safercheaper-way-than-chantix-to-quit-smoking/2015/05/15/8ce5590c-f830-11e4-9030-b4732caefe81_story.html. Accessed January 21, 2016.

IN THIS ARTICLE

• The 2008 USPHS guideline: 10 key recommendations
• USPHS smoking cessation guideline: An evidence summary
• Medications for smoking cessation: Dosing, advantages, and adverse effects

In its 2014 report, The Health Consequences of Smoking—50 Years of Progress,¹ the US Surgeon General concluded that, while significant improvements have been made since the publication of its landmark 1964 report, cigarette smoking remains a major public health problem. It is the leading cause of preventable death, increasing the risk for such common causes of mortality as cardiovascular disease, pulmonary disease, and malignancy. Cigarette smoking is responsible for an estimated 443,000 deaths annually.²

Overall, 42 million US adults and about 3 million middle and high school students smoke, despite the availability of an array of pharmacologic interventions to help them quit.¹ Half of those who continue to smoke will die from a tobacco-related cause. Stopping before the age of 50 cuts the risk in half, and quitting before age 30 almost completely negates it.³

The most recent comprehensive smoking cessation guideline, sponsored by the US Public Health Service, was published in 2008.⁴ The US Preventive Services Task Force (USPSTF) recommendation that “clinicians ask all adults about tobacco use and provide tobacco cessation interventions” for those who smoke was issued one year later.⁵ Since then, multiple studies have assessed the merits of the various medications, forms of nicotine replacement therapy (NRT), and counseling aimed at helping smokers maintain abstinence from tobacco.

This article reviews the guideline and provides family practice providers with an evidence-based update.

Continue for treating tobacco use and dependence >>

The guideline: Treating tobacco use and dependence
Prescribing a firstline medication (bupropion SR, varenicline, nicotine gum, nicotine inhaler, nicotine lozenge, nicotine nasal spray, or nicotine patch) for every patient who seeks to quit smoking is a key component of the 2008 guideline (see Table 1).⁴ The only exceptions: patients for whom such agents are medically contraindicated and groups for which there is insufficient evidence of effectiveness, such as pregnant women and adolescents.

The use of any of these medications as a single agent nearly doubles the likelihood of success compared with placebo, with an average cessation rate of 25% (see Table 2).⁴ Combination therapy (pairing a nicotine patch and an additional agent) was found to be even more effective, with some combinations attaining success rates as high as 65%.⁴

Second-line therapies, including clonidine and nortriptyline, were also cited as effective, with an average cessation rate of 24%.⁴ Although the meta-analyses that these averages were based on did not include head-to-head comparisons, subsequent studies that also showed efficacy did include such comparisons.

Continue for counseling is an essential component >>

Counseling is an essential component
In one of the meta-analyses on which the guideline was based, the combination of counseling and medication proved to be more effective than either intervention alone. Individual, group, and telephone counseling were all effective (odds ratios [ORs], 1.7, 1.3, and 1.2, respectively), provided they included practical help that emphasized problem solving and skills training, as well as social support. The benefits of a team-based approach were evident from the finding that counseling provided by more than one type of clinician had higher effect sizes (OR, 2.5 when two different clinical disciplines were involved and 2.4 for three or more disciplines).⁴

The guideline also found state-sponsored quit lines, accessible at no charge via 800-QUIT-NOW, are an effective option. (For more information about this and other resources, see Table W1.) For patients who aren’t ready to stop smoking, the guideline recommends motivational interviewing⁴—a direct, patient-centered technique used to explore and work through ambivalence. Further information about this method is available at www.motivational interviewing.org.

In counseling patients who are considering a quit attempt, it is important to present all options. A smoking history is needed, too, because factors such as the number of cigarettes smoked per day, how long a patient is typically awake before smoking the first cigarette of the day, and level of dependence are important factors in determining medication and dosage. Consider the advantages and disadvantages of the various medications (see Table 3) or methods used for prior quit attempts and reasons for relapse, if appropriate, as well as patient preference.^4,6,7

Continue for evidence update >>

Evidence update: What’s best?
Since 2009, many clinical trials have examined the best way to help smokers quit. Here’s a closer look at the latest evidence.

NRT boosts long-term cessation
A 2012 Cochrane review examined 150 trials and found that every type of NRT—gum, lozenge, patch, inhaler, and nasal spray—was associated with long-term cessation (relative risk [RR], 1.60).⁸ This effect was essentially unchanged regardless of the duration, setting, or intensity of supportive therapy offered, and no single type of NRT was more effective than any other. However, combining a short-acting form, such as a lozenge, with a long-acting patch was found to be more effective than either one alone (RR, 1.34).

Starting the NRT before the patient quit did not improve cessation rates over traditional start times (RR, 1.18). Neither was there an added benefit to using NRT beyond the recommended 24-week prescription period,⁹ although doing so was found to be safe. Another 2012 Cochrane review looked specifically at the use of pharmacologic smoking cessation interventions during pregnancy and concluded that there was still not sufficient data to document efficacy for this patient population.¹⁰

Adherence. In deciding on which type of NRT to prescribe, it is important to consider not only patient preference and previous efforts but also the latest evidence. A study comparing various NRT formulations found patient adherence to be highest with the patch, followed by nicotine gum, which had a higher compliance rate than either the nicotine inhaler or nasal spray.¹¹

Varenicline is still a firstline agent
Since the 2008 guideline recommended this partial nicotinic receptor agonist/antagonist as a firstline pharmacologic agent, additional meta-analyses have confirmed its long-term efficacy in smokers who are ready to quit.^12,13 A 2012 Cochrane review found varenicline to increase long-term cessation compared with placebo (RR, 2.27).¹³ It also showed varenicline to be more effective than bupropion SR (RR, 1.52), but about as effective as NRT (RR, 1.13).

Newer data suggest that varenicline may also be effective for those who are willing to cut down on smoking but not yet ready to give up cigarettes completely. Used for 24 weeks by those who were initially resistant to quitting, researchers found varenicline nearly tripled the cessation rate at 52 weeks compared with placebo (RR, 2.7).¹⁴

Latest evidence on safety. Additional concerns about the safety of varenicline have been raised, however, since the 2008 guideline was published. In 2009, the FDA required that black box warnings be added to the labels of both varenicline and bupropion SR based on postmarketing safety reports showing risk for neuropsychiatric symptoms, including suicidality.¹⁵ In 2011, a large case-control study by the FDA Adverse Event Reporting System also showed an increased risk for suicidality in patients taking these drugs.¹⁶

Follow-up studies, however, including a large prospective cohort study and a large meta-analysis, failed to show an increased association with neuropsychiatric adverse effects.^17,18 A smaller randomized controlled trial (RCT) showed that in smokers diagnosed with schizophrenia and bipolar disorder, maintenance therapy with varenicline was effective in preventing smoking relapse for up to 52 weeks. Abstinence rates were 60% for those in the varenicline group versus 19% for those in the placebo group (OR, 6.2). Although no increased risk for adverse psychiatric events was found in this study, it was not powered to detect them.¹⁹ Also of note: A meta-analysis of 14 RCTs showed an increased rate of cardiovascular events associated with varenicline.²⁰ There are concerns about methodologic flaws in this meta-analysis, however, and two subsequent meta-analyses failed to find a cardiovascular risk.^21,22

The higher quality studies that have been published since the original concerns about varenicline’s safety are reassuring, but it is still essential to carefully weigh the risks and benefits of varenicline. Review cardiac and psychiatric history and conduct a suicidality assessment before prescribing it as a smoking cessation aid, and provide close follow-up.

Continue for a closer look at antidepressants >>

A closer look at antidepressants
Bupropion SR, an atypical antidepressant, was also listed as a firstline treatment in the 2008 guideline. A 2014 Cochrane review of 90 studies confirmed the evidence for this recommendation.⁶ Monotherapy with this agent was found to significantly increase rates of long-term cessation (RR, 1.62). No increased risk for serious adverse events was identified compared with placebo. As already noted, associations with neuropsychiatric symptoms were found, but this risk must be considered with any antidepressant.

Bupropion’s efficacy was not significantly different from that of NRT, but moderate evidence suggests that it is less effective than varenicline (RR, 0.68). Other classes of antidepressants, including selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors, were found to be ineffective for smoking cessation.⁶

Nortriptyline, a tricyclic antidepressant, was not significantly different from bupropion SR (RR, 1.30) in efficacy for smoking cessation, but it lacks FDA approval for this purpose and is not considered a firstline agent.⁶

Second-line agents
Clonidine is an alpha-2 adrenergic receptor agonist that was originally used to treat hypertension but found to be effective for smoking cessation in a meta-analysis performed for the 2008 guideline.⁴ Like nortriptyline, however, clonidine is not FDA-approved for this purpose and is not considered a firstline agent.⁵ A 2013 Cochrane meta-analysis further showed that clonidine is effective for smoking cessation versus placebo (RR, 1.63)⁷ but suggested that its significant dose-related adverse effects, including postural hypotension and sedation, could limit its usefulness.

Combination therapies are highly effective
Evidence for various combinations of smoking cessation pharmacotherapy continues to mount.^23-26 Perhaps the most compelling evidence comes from a comparative effectiveness trial that randomized 1,346 patients in 12 primary care clinics to nicotine patches, nicotine lozenges, bupropion SR, a combination of patch plus lozenge, and bupropion SR plus lozenge. The six-month abstinence rate was 30% for the bupropion SR plus lozenge combination, the most effective option. The combination was superior to either patch or bupropion SR monotherapy (ORs, 0.56 and 0.54, respectively).²³ Based on data from the 2008 guideline, similar combinations (eg, nicotine patch plus nicotine gum or bupropion SR plus the patch) are likely to be equally effective. The 2008 guideline also supports a nicotine patch and nicotine inhaler combination.

Another study found varenicline combined with the patch to be highly effective, with a 65% abstinence rate at 24 weeks compared with 47% for varenicline alone (number needed to treat [NNT], 6).²⁴

In heavy smokers—defined as those who smoke 20 or more cigarettes daily—a varenicline and bupropion SR combination was more effective than varenicline alone (NNT, 9), but the combination can lead to increased anxiety and depression.²⁵ A smaller study found triple therapy using nicotine patch plus inhaler plus bupropion SR to be more effective than the nicotine patch alone (35% abstinence vs 19% abstinence at 26 weeks; NNT, 6).²⁶ Consider using these combinations in patients who have high nicotine dependency levels or who have been unable to quit using a single firstline agent.

Continue to the role e-cigarettes play >>

What role do e-cigarettes play?
The use of electronic cigarettes or “vapes”—battery-operated devices that deliver nicotine to the user through vapor—has increased significantly since their US introduction in 2007. A recent study found that “ever use” of e-cigarettes increased from 1.8% in 2010 to 13% in 2013; current use increased from 0.3% to 6.8% in the same time frame.²⁷ Vaping, as inhaling on an e-cigarette is sometimes known, causes a sensor to detect airflow and initiate the heating element to vaporize the liquid solution within the cartridge, which contains propylene glycol, flavoring, and nicotine.

There is limited evidence of the efficacy of e-cigarettes for smoking cessation, but there is support for their role in reducing the quantity of conventional cigarettes smoked. A 2014 Cochrane review of two RCTs evaluating e-cigarette efficacy for smoking cessation or reduction found evidence of increased abstinence at six months in users of e-cigarettes containing nicotine, compared with placebo e-cigarettes (9% vs 4%; RR, 2.29). Additionally, e-cigarette use was associated with a more than 50% decrease in cigarette smoking versus placebo (36% vs 27%; RR,1.31) or patch (61% vs 44%; RR, 1.41).²⁸

A survey published after the review also showed a correlation between cigarette reduction (but not cessation) after one year of e-cigarette use.²⁹ A subsequent RCT conducted in a controlled laboratory setting found that e-cigarettes were highly effective in reducing cessation-related cravings.³⁰ And at eight-month follow-up, 44% of those using e-cigarettes were found to have at least a 50% reduction in the use of conventional cigarettes—and complete cessation in some cases.

Concerns about health effects
E-cigarettes have generally been thought to be safer than conventional cigarettes, given that they mainly deliver nicotine and propylene glycol instead of the more toxic chemicals—eg, benzene, carbon monoxide, and formaldehyde—released by conventional cigarettes.³¹ Carcinogens have also been found in e-cigarettes, but at significantly lower levels.³¹ However, a systematic review found wide variation in the toxin content of e-cigarettes.³² In addition, recent reports have detailed incidents in which e-cigarette devices were alleged to have exploded, causing severe bodily harm.³³

Adverse effects of e-cigarettes include minor irritation of the throat, mouth, and lungs. Among cigarette-naive patients, lightheadedness, throat irritation, dizziness, and cough were most commonly reported. No serious adverse events have been reported, but the lack of long-term safety data is a source of concern.³²

Additionally, minimal regulatory oversight of the e-cigarette industry exists. Currently, the FDA only has authority to regulate e-cigarettes that are marketed for therapeutic purposes, although the agency is seeking to extend its oversight to all e-cigarettes.

The bottom line: More data on safety and regulatory oversight are needed before recommendations on the use of e-cigarettes as a smoking cessation tool can be made.

Continue for looking ahead >>

Looking ahead
Several novel pharmacotherapies have been evaluated for smoking cessation in recent years. Among them is a nicotine vaccine that several drug companies have been pursuing. In theory, such a vaccine would create an immunologic reaction to nicotine in a smoker, thereby preventing the substance from reaching the brain and providing rewarding stimuli. A 2008 Cochrane review of four trials assessing the efficacy of nicotine vaccines for tobacco cessation found that none showed efficacy.³⁴

Naltrexone, an opioid antagonist, has shown efficacy in helping those with opioid or alcohol dependence achieve abstinence from these substances, raising the possibility that it might aid in smoking cessation as well. A 2013 Cochrane review of eight trials found that this was not the case: Compared with placebo, naltrexone was not beneficial when used alone (RR, 1.00) or as an adjunct to NRT compared with NRT alone (RR, 0.95).³⁵

Cytisine, an extract from plants in the Faboideae family, has been used in Eastern Europe for decades for smoking cessation. It appears to work as a nicotine receptor partial agonist similar to varenicline. The extract does not have FDA approval, but the National Institutes of Health’s Center for Complementary and Integrative Health is sponsoring early-stage safety trials that could lead to its approval in the US.³⁶

A 2012 Cochrane review identified two recent RCTs evaluating cytisine and found it to be effective in increasing smoking cessation rates, compared with placebo (RR, 3.98).¹³

The authors thank Matt Orr, PhD, and Kathryn E. Bornemann for their help with this manuscript.

References
1. National Center for Chronic Disease Prevention and Health Promotion Office on Smoking and Health. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. www.ncbi.nlm.nih.gov/pubmed/24455788. Accessed January 21, 2016.
2. Smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008;57:1226-1228.
3. Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ. 2004;328:1519.
4. US Public Health Service. A clinical practice guideline for treating tobacco use and dependence: 2008 update. Am J Prev Med. 2008;35:158-176.
5. US Preventive Services Task Force. Tobacco use in adults and pregnant women: counseling and interventions. April 2009. www.uspreventiveservicestaskforce.org/Page/Topic/recommendation-summary/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions. Accessed January 21, 2016.
6. Hughes JR, Stead LF, Hartmann-Boyce J, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031.
7. Cahill K, Stevens S, Perera R, et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013;(5):CD009329.
8. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;(11):CD000146.
9. Schnoll RA, Goelz PM, Veluz-Wilkins A, et al. Long-term nicotine replacement therapy: a randomized clinical trial. JAMA Intern Med. 2015;175: 504-511.
10. Coleman T, Chamberlain C, Davey MA, et al. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2012;(9):CD010078.
11. Hajek P, West R, Foulds J, et al. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med. 1999;159:2033-2038.
12. Eisenberg MJ, Filion KB, Yavin D, et al. Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials. CMAJ. 2008;179:135-144.
13. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2012;(4):CD006103.
14. Ebbert JO, Hughes JR, West RJ, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015;313:687-694.
15. FDA. Reports of suicidality associated with use of varenicline (marketed as CHANTIX) and bupropion (marketed as ZYBAN and GENERICS). FDA Drug Safety News. 2009.
16. Moore TJ, Furberg CD, Glenmullen J, et al. Suicidal behavior and depression in smoking cessation treatments. PLoS One. 2011;6:e27016.
17. Thomas KH, Martin RM, Davies NM, et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study. BMJ. 2013;347:f5704.
18. Thomas KH, Martin RM, Knipe DW, et al. Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ. 2015;350:h1109.
19. Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014;311:145-154.
20. Singh S, Loke YK, Spangler JG, et al. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011;183:1359-1366.
21. Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ. 2012;344:e2856.
22. Svanström H, Pasternak B, Hviid A. Use of varenicline for smoking cessation and risk of serious cardiovascular events: nationwide cohort study. BMJ. 2012;345:e7176.
23. Smith SS, McCarthy DE, Japuntich SJ, et al. Comparative effectiveness of five smoking cessation pharmacotherapies in primary care clinics. Arch Intern Med. 2009;169:2148-2155.
24. Koegelenberg CFN, Noor F, Bateman ED, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation. JAMA. 2014;312:155-161.
25. Ebbert JO, Hatsukami DK, Croghan IT, et al. Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA. 2014;311:155-163.
26. Steinberg MB, Greenhaus S, Schmelzer AC, et al. Triple-combination pharmacotherapy for medically ill smokers: a randomized trial. Ann Intern Med. 2009;150:447-454.
27. McMillen RC, Gottlieb MA, Shaefer RMW, et al. Trends in electronic cigarette use among US adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 2015;17:1195-1202.
28. McRobbie H, Bullen C, Hartmann-Boyce J, et al. Electronic cigarettes for smoking cessation and reduction. Cochrane Database Syst Rev. 2014;(12):CD010216.
29. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110:1160-1168.
30. Adriaens K, Van Gucht D, Declerck P, et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11:11220-11248.
31. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133-139.
32. Pisinger C, Døssing M. A systematic review of health effects of electronic cigarettes. Prev Med (Baltim). 2014;69C:248-260.
33. Bowerman M. Fla man hospitalized after e-cigarette explodes in face. USA Today Network. October 29, 2015. www.usatoday.com/story/news/nation-now/2015/10/29/fla-man-hospitalized-e-cigarette-explodes-face/74791722/. Accessed January 21, 2016.
34. Hatsukami D, Cahill K, Stead LF. Nicotine vaccines for smoking cessation. Cochrane Database Syst Rev. 2008;(2):CD007072.
35. David SP, Lancaster T, Stead LF, et al. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2013;(6):CD003086.
36. Frankel T. Pill that quashes tobacco urge found in plain sight. Washington Post. May 15, 2015. www.washingtonpost.com/business/economy/pill-promises-a-safercheaper-way-than-chantix-to-quit-smoking/2015/05/15/8ce5590c-f830-11e4-9030-b4732caefe81_story.html. Accessed January 21, 2016.

IN THIS ARTICLE

• The 2008 USPHS guideline: 10 key recommendations
• USPHS smoking cessation guideline: An evidence summary
• Medications for smoking cessation: Dosing, advantages, and adverse effects

In its 2014 report, The Health Consequences of Smoking—50 Years of Progress,¹ the US Surgeon General concluded that, while significant improvements have been made since the publication of its landmark 1964 report, cigarette smoking remains a major public health problem. It is the leading cause of preventable death, increasing the risk for such common causes of mortality as cardiovascular disease, pulmonary disease, and malignancy. Cigarette smoking is responsible for an estimated 443,000 deaths annually.²

Overall, 42 million US adults and about 3 million middle and high school students smoke, despite the availability of an array of pharmacologic interventions to help them quit.¹ Half of those who continue to smoke will die from a tobacco-related cause. Stopping before the age of 50 cuts the risk in half, and quitting before age 30 almost completely negates it.³

The most recent comprehensive smoking cessation guideline, sponsored by the US Public Health Service, was published in 2008.⁴ The US Preventive Services Task Force (USPSTF) recommendation that “clinicians ask all adults about tobacco use and provide tobacco cessation interventions” for those who smoke was issued one year later.⁵ Since then, multiple studies have assessed the merits of the various medications, forms of nicotine replacement therapy (NRT), and counseling aimed at helping smokers maintain abstinence from tobacco.

This article reviews the guideline and provides family practice providers with an evidence-based update.

Continue for treating tobacco use and dependence >>

The guideline: Treating tobacco use and dependence
Prescribing a firstline medication (bupropion SR, varenicline, nicotine gum, nicotine inhaler, nicotine lozenge, nicotine nasal spray, or nicotine patch) for every patient who seeks to quit smoking is a key component of the 2008 guideline (see Table 1).⁴ The only exceptions: patients for whom such agents are medically contraindicated and groups for which there is insufficient evidence of effectiveness, such as pregnant women and adolescents.

The use of any of these medications as a single agent nearly doubles the likelihood of success compared with placebo, with an average cessation rate of 25% (see Table 2).⁴ Combination therapy (pairing a nicotine patch and an additional agent) was found to be even more effective, with some combinations attaining success rates as high as 65%.⁴

Second-line therapies, including clonidine and nortriptyline, were also cited as effective, with an average cessation rate of 24%.⁴ Although the meta-analyses that these averages were based on did not include head-to-head comparisons, subsequent studies that also showed efficacy did include such comparisons.

Continue for counseling is an essential component >>

Counseling is an essential component
In one of the meta-analyses on which the guideline was based, the combination of counseling and medication proved to be more effective than either intervention alone. Individual, group, and telephone counseling were all effective (odds ratios [ORs], 1.7, 1.3, and 1.2, respectively), provided they included practical help that emphasized problem solving and skills training, as well as social support. The benefits of a team-based approach were evident from the finding that counseling provided by more than one type of clinician had higher effect sizes (OR, 2.5 when two different clinical disciplines were involved and 2.4 for three or more disciplines).⁴

The guideline also found state-sponsored quit lines, accessible at no charge via 800-QUIT-NOW, are an effective option. (For more information about this and other resources, see Table W1.) For patients who aren’t ready to stop smoking, the guideline recommends motivational interviewing⁴—a direct, patient-centered technique used to explore and work through ambivalence. Further information about this method is available at www.motivational interviewing.org.

In counseling patients who are considering a quit attempt, it is important to present all options. A smoking history is needed, too, because factors such as the number of cigarettes smoked per day, how long a patient is typically awake before smoking the first cigarette of the day, and level of dependence are important factors in determining medication and dosage. Consider the advantages and disadvantages of the various medications (see Table 3) or methods used for prior quit attempts and reasons for relapse, if appropriate, as well as patient preference.^4,6,7

Continue for evidence update >>

Evidence update: What’s best?
Since 2009, many clinical trials have examined the best way to help smokers quit. Here’s a closer look at the latest evidence.

NRT boosts long-term cessation
A 2012 Cochrane review examined 150 trials and found that every type of NRT—gum, lozenge, patch, inhaler, and nasal spray—was associated with long-term cessation (relative risk [RR], 1.60).⁸ This effect was essentially unchanged regardless of the duration, setting, or intensity of supportive therapy offered, and no single type of NRT was more effective than any other. However, combining a short-acting form, such as a lozenge, with a long-acting patch was found to be more effective than either one alone (RR, 1.34).

Starting the NRT before the patient quit did not improve cessation rates over traditional start times (RR, 1.18). Neither was there an added benefit to using NRT beyond the recommended 24-week prescription period,⁹ although doing so was found to be safe. Another 2012 Cochrane review looked specifically at the use of pharmacologic smoking cessation interventions during pregnancy and concluded that there was still not sufficient data to document efficacy for this patient population.¹⁰

Adherence. In deciding on which type of NRT to prescribe, it is important to consider not only patient preference and previous efforts but also the latest evidence. A study comparing various NRT formulations found patient adherence to be highest with the patch, followed by nicotine gum, which had a higher compliance rate than either the nicotine inhaler or nasal spray.¹¹

Varenicline is still a firstline agent
Since the 2008 guideline recommended this partial nicotinic receptor agonist/antagonist as a firstline pharmacologic agent, additional meta-analyses have confirmed its long-term efficacy in smokers who are ready to quit.^12,13 A 2012 Cochrane review found varenicline to increase long-term cessation compared with placebo (RR, 2.27).¹³ It also showed varenicline to be more effective than bupropion SR (RR, 1.52), but about as effective as NRT (RR, 1.13).

Newer data suggest that varenicline may also be effective for those who are willing to cut down on smoking but not yet ready to give up cigarettes completely. Used for 24 weeks by those who were initially resistant to quitting, researchers found varenicline nearly tripled the cessation rate at 52 weeks compared with placebo (RR, 2.7).¹⁴

Latest evidence on safety. Additional concerns about the safety of varenicline have been raised, however, since the 2008 guideline was published. In 2009, the FDA required that black box warnings be added to the labels of both varenicline and bupropion SR based on postmarketing safety reports showing risk for neuropsychiatric symptoms, including suicidality.¹⁵ In 2011, a large case-control study by the FDA Adverse Event Reporting System also showed an increased risk for suicidality in patients taking these drugs.¹⁶

Follow-up studies, however, including a large prospective cohort study and a large meta-analysis, failed to show an increased association with neuropsychiatric adverse effects.^17,18 A smaller randomized controlled trial (RCT) showed that in smokers diagnosed with schizophrenia and bipolar disorder, maintenance therapy with varenicline was effective in preventing smoking relapse for up to 52 weeks. Abstinence rates were 60% for those in the varenicline group versus 19% for those in the placebo group (OR, 6.2). Although no increased risk for adverse psychiatric events was found in this study, it was not powered to detect them.¹⁹ Also of note: A meta-analysis of 14 RCTs showed an increased rate of cardiovascular events associated with varenicline.²⁰ There are concerns about methodologic flaws in this meta-analysis, however, and two subsequent meta-analyses failed to find a cardiovascular risk.^21,22

The higher quality studies that have been published since the original concerns about varenicline’s safety are reassuring, but it is still essential to carefully weigh the risks and benefits of varenicline. Review cardiac and psychiatric history and conduct a suicidality assessment before prescribing it as a smoking cessation aid, and provide close follow-up.

Continue for a closer look at antidepressants >>

A closer look at antidepressants
Bupropion SR, an atypical antidepressant, was also listed as a firstline treatment in the 2008 guideline. A 2014 Cochrane review of 90 studies confirmed the evidence for this recommendation.⁶ Monotherapy with this agent was found to significantly increase rates of long-term cessation (RR, 1.62). No increased risk for serious adverse events was identified compared with placebo. As already noted, associations with neuropsychiatric symptoms were found, but this risk must be considered with any antidepressant.

Bupropion’s efficacy was not significantly different from that of NRT, but moderate evidence suggests that it is less effective than varenicline (RR, 0.68). Other classes of antidepressants, including selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors, were found to be ineffective for smoking cessation.⁶

Nortriptyline, a tricyclic antidepressant, was not significantly different from bupropion SR (RR, 1.30) in efficacy for smoking cessation, but it lacks FDA approval for this purpose and is not considered a firstline agent.⁶

Second-line agents
Clonidine is an alpha-2 adrenergic receptor agonist that was originally used to treat hypertension but found to be effective for smoking cessation in a meta-analysis performed for the 2008 guideline.⁴ Like nortriptyline, however, clonidine is not FDA-approved for this purpose and is not considered a firstline agent.⁵ A 2013 Cochrane meta-analysis further showed that clonidine is effective for smoking cessation versus placebo (RR, 1.63)⁷ but suggested that its significant dose-related adverse effects, including postural hypotension and sedation, could limit its usefulness.

Combination therapies are highly effective
Evidence for various combinations of smoking cessation pharmacotherapy continues to mount.^23-26 Perhaps the most compelling evidence comes from a comparative effectiveness trial that randomized 1,346 patients in 12 primary care clinics to nicotine patches, nicotine lozenges, bupropion SR, a combination of patch plus lozenge, and bupropion SR plus lozenge. The six-month abstinence rate was 30% for the bupropion SR plus lozenge combination, the most effective option. The combination was superior to either patch or bupropion SR monotherapy (ORs, 0.56 and 0.54, respectively).²³ Based on data from the 2008 guideline, similar combinations (eg, nicotine patch plus nicotine gum or bupropion SR plus the patch) are likely to be equally effective. The 2008 guideline also supports a nicotine patch and nicotine inhaler combination.

Another study found varenicline combined with the patch to be highly effective, with a 65% abstinence rate at 24 weeks compared with 47% for varenicline alone (number needed to treat [NNT], 6).²⁴

In heavy smokers—defined as those who smoke 20 or more cigarettes daily—a varenicline and bupropion SR combination was more effective than varenicline alone (NNT, 9), but the combination can lead to increased anxiety and depression.²⁵ A smaller study found triple therapy using nicotine patch plus inhaler plus bupropion SR to be more effective than the nicotine patch alone (35% abstinence vs 19% abstinence at 26 weeks; NNT, 6).²⁶ Consider using these combinations in patients who have high nicotine dependency levels or who have been unable to quit using a single firstline agent.

Continue to the role e-cigarettes play >>

What role do e-cigarettes play?
The use of electronic cigarettes or “vapes”—battery-operated devices that deliver nicotine to the user through vapor—has increased significantly since their US introduction in 2007. A recent study found that “ever use” of e-cigarettes increased from 1.8% in 2010 to 13% in 2013; current use increased from 0.3% to 6.8% in the same time frame.²⁷ Vaping, as inhaling on an e-cigarette is sometimes known, causes a sensor to detect airflow and initiate the heating element to vaporize the liquid solution within the cartridge, which contains propylene glycol, flavoring, and nicotine.

There is limited evidence of the efficacy of e-cigarettes for smoking cessation, but there is support for their role in reducing the quantity of conventional cigarettes smoked. A 2014 Cochrane review of two RCTs evaluating e-cigarette efficacy for smoking cessation or reduction found evidence of increased abstinence at six months in users of e-cigarettes containing nicotine, compared with placebo e-cigarettes (9% vs 4%; RR, 2.29). Additionally, e-cigarette use was associated with a more than 50% decrease in cigarette smoking versus placebo (36% vs 27%; RR,1.31) or patch (61% vs 44%; RR, 1.41).²⁸

A survey published after the review also showed a correlation between cigarette reduction (but not cessation) after one year of e-cigarette use.²⁹ A subsequent RCT conducted in a controlled laboratory setting found that e-cigarettes were highly effective in reducing cessation-related cravings.³⁰ And at eight-month follow-up, 44% of those using e-cigarettes were found to have at least a 50% reduction in the use of conventional cigarettes—and complete cessation in some cases.

Concerns about health effects
E-cigarettes have generally been thought to be safer than conventional cigarettes, given that they mainly deliver nicotine and propylene glycol instead of the more toxic chemicals—eg, benzene, carbon monoxide, and formaldehyde—released by conventional cigarettes.³¹ Carcinogens have also been found in e-cigarettes, but at significantly lower levels.³¹ However, a systematic review found wide variation in the toxin content of e-cigarettes.³² In addition, recent reports have detailed incidents in which e-cigarette devices were alleged to have exploded, causing severe bodily harm.³³

Adverse effects of e-cigarettes include minor irritation of the throat, mouth, and lungs. Among cigarette-naive patients, lightheadedness, throat irritation, dizziness, and cough were most commonly reported. No serious adverse events have been reported, but the lack of long-term safety data is a source of concern.³²

Additionally, minimal regulatory oversight of the e-cigarette industry exists. Currently, the FDA only has authority to regulate e-cigarettes that are marketed for therapeutic purposes, although the agency is seeking to extend its oversight to all e-cigarettes.

The bottom line: More data on safety and regulatory oversight are needed before recommendations on the use of e-cigarettes as a smoking cessation tool can be made.

Continue for looking ahead >>

Looking ahead
Several novel pharmacotherapies have been evaluated for smoking cessation in recent years. Among them is a nicotine vaccine that several drug companies have been pursuing. In theory, such a vaccine would create an immunologic reaction to nicotine in a smoker, thereby preventing the substance from reaching the brain and providing rewarding stimuli. A 2008 Cochrane review of four trials assessing the efficacy of nicotine vaccines for tobacco cessation found that none showed efficacy.³⁴

Naltrexone, an opioid antagonist, has shown efficacy in helping those with opioid or alcohol dependence achieve abstinence from these substances, raising the possibility that it might aid in smoking cessation as well. A 2013 Cochrane review of eight trials found that this was not the case: Compared with placebo, naltrexone was not beneficial when used alone (RR, 1.00) or as an adjunct to NRT compared with NRT alone (RR, 0.95).³⁵

Cytisine, an extract from plants in the Faboideae family, has been used in Eastern Europe for decades for smoking cessation. It appears to work as a nicotine receptor partial agonist similar to varenicline. The extract does not have FDA approval, but the National Institutes of Health’s Center for Complementary and Integrative Health is sponsoring early-stage safety trials that could lead to its approval in the US.³⁶

A 2012 Cochrane review identified two recent RCTs evaluating cytisine and found it to be effective in increasing smoking cessation rates, compared with placebo (RR, 3.98).¹³

The authors thank Matt Orr, PhD, and Kathryn E. Bornemann for their help with this manuscript.

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