Anoop Narahari, MD

When a patient who smokes enters a tobacco-free medical facility and has access to caffeinated beverages, he (she) might experience toxicity to many pharmaceuticals and caffeine. Similarly, if a patient is discharged from a smoke-free envi­ronment with a newly adjusted medication regimen and resumes smoking or caffeine consumption, alterations in enzyme activ­ity might reduce therapeutic efficacy of pre­scribed medicines. These effects are a result of alterations in the hepatic cytochrome P450 (CYP) enzyme system.

Taking a careful history of tobacco and caffeine use, and knowing the effects that these substances will have on specific medi­cations, will help guide treatment and man­agement decisions.

The role of CYP enzymes
CYP hepatic enzymes detoxify a variety of environmental agents into water-soluble compounds that are excreted in urine. CYP1A2 metabolizes 20% of drugs handled by the CYP system and comprises 13% of all the CYP enzymes expressed in the liver. The wide interindividual variation in CYP1A2 enzyme activity is influenced by a combina­tion of genetic, epigenetic, ethnic, and envi­ronmental variables.¹

Influence of tobacco on CYP
The polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2 and CYP2B6 hepatic enzymes.² Smokers exhibit increased activity of these enzymes, which results in faster clearance of many drugs, lower con­centrations in blood, and diminished clinical response. The Table lists psycho­tropic medicines that are metabolized by CYP1A2 and CYP2B6. Co-administration of these substrates could decrease the elimina­tion rate of other drugs also metabolized by CYP1A2. Nicotine in tobacco or in nicotine replacement therapies does not play a role in inducing CYP enzymes.

Psychiatric patients smoke at a higher rate than the general population.² One study found that approximately 70% of patients with schizophrenia and as many as 45% of those with bipolar disorder smoke enough cigarettes (7 to 20 a day) to induce CYP1A2 and CYP2B6 activity.² Patients who smoke and are given clozapine, haloperidol, or olanzapine show a lower serum concen­tration than non-smokers; in fact, the clo­zapine level can be reduced as much as 2.4-fold.2-5 Subsequently, patients can expe­rience diminished clinical response to these 3 psychotropics.³

The turnover time for CYP1A2 is rapid— approximately 3 days—and a new CYP1A2 steady state activity is reached after approxi­mately 1 week,⁴ which is important to remember when managing inpatients in a smoke-free facility. During acute hospitaliza­tion, patients could experience drug toxic­ity if the outpatient dosage is maintained.⁵

When they resume smoking after being discharged on a stabilized dosage of any of the medications listed in the Table, previous enzyme activity rebounds and might reduce the drug level, potentially leading to inad­equate clinical response.

Caffeine and other substances
Asking about the patient’s caffeine intake is necessary because consumption of coffee is prevalent among smokers, and caffeine is metabolized by CYP1A2. Smokers need to consume as much as 4 times the amount of caffeine as non-smokers to achieve a similar caffeine serum concentration.² Caffeine can form an insoluble precipitate with antipsychotic medication in the gut, which decreases absorption. The interac­tion between smoking-related induction of CYP1A2 enzymes and forced smoking ces­sation during hospitalization, with ongo­ing caffeine consumption, could lead to caffeine toxicity.^4,5

Other common inducers of CYP1A2 are insulin, cabbage, cauliflower, broccoli, and charcoal-grilled meat. Also, cumin and tur­meric inhibit CYP1A2 activity, which might explain an ethnic difference in drug toler­ance across population groups. Additionally, certain genetic polymorphisms, in specific ethnic distributions, alter the potential for tobacco smoke to induce CYP1A2.⁶

Some of these polymorphisms can be genotyped for clinical application.³

Asking about a patient’s tobacco and caffeine use and understanding their inter­actions with specific medications provides guidance when prescribing antipsychotic medications and adjusting dosage for inpatients and during clinical follow-up care.

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

When a patient who smokes enters a tobacco-free medical facility and has access to caffeinated beverages, he (she) might experience toxicity to many pharmaceuticals and caffeine. Similarly, if a patient is discharged from a smoke-free envi­ronment with a newly adjusted medication regimen and resumes smoking or caffeine consumption, alterations in enzyme activ­ity might reduce therapeutic efficacy of pre­scribed medicines. These effects are a result of alterations in the hepatic cytochrome P450 (CYP) enzyme system.

Taking a careful history of tobacco and caffeine use, and knowing the effects that these substances will have on specific medi­cations, will help guide treatment and man­agement decisions.

The role of CYP enzymes
CYP hepatic enzymes detoxify a variety of environmental agents into water-soluble compounds that are excreted in urine. CYP1A2 metabolizes 20% of drugs handled by the CYP system and comprises 13% of all the CYP enzymes expressed in the liver. The wide interindividual variation in CYP1A2 enzyme activity is influenced by a combina­tion of genetic, epigenetic, ethnic, and envi­ronmental variables.¹

Influence of tobacco on CYP
The polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2 and CYP2B6 hepatic enzymes.² Smokers exhibit increased activity of these enzymes, which results in faster clearance of many drugs, lower con­centrations in blood, and diminished clinical response. The Table lists psycho­tropic medicines that are metabolized by CYP1A2 and CYP2B6. Co-administration of these substrates could decrease the elimina­tion rate of other drugs also metabolized by CYP1A2. Nicotine in tobacco or in nicotine replacement therapies does not play a role in inducing CYP enzymes.

Psychiatric patients smoke at a higher rate than the general population.² One study found that approximately 70% of patients with schizophrenia and as many as 45% of those with bipolar disorder smoke enough cigarettes (7 to 20 a day) to induce CYP1A2 and CYP2B6 activity.² Patients who smoke and are given clozapine, haloperidol, or olanzapine show a lower serum concen­tration than non-smokers; in fact, the clo­zapine level can be reduced as much as 2.4-fold.2-5 Subsequently, patients can expe­rience diminished clinical response to these 3 psychotropics.³

The turnover time for CYP1A2 is rapid— approximately 3 days—and a new CYP1A2 steady state activity is reached after approxi­mately 1 week,⁴ which is important to remember when managing inpatients in a smoke-free facility. During acute hospitaliza­tion, patients could experience drug toxic­ity if the outpatient dosage is maintained.⁵

When they resume smoking after being discharged on a stabilized dosage of any of the medications listed in the Table, previous enzyme activity rebounds and might reduce the drug level, potentially leading to inad­equate clinical response.

Caffeine and other substances
Asking about the patient’s caffeine intake is necessary because consumption of coffee is prevalent among smokers, and caffeine is metabolized by CYP1A2. Smokers need to consume as much as 4 times the amount of caffeine as non-smokers to achieve a similar caffeine serum concentration.² Caffeine can form an insoluble precipitate with antipsychotic medication in the gut, which decreases absorption. The interac­tion between smoking-related induction of CYP1A2 enzymes and forced smoking ces­sation during hospitalization, with ongo­ing caffeine consumption, could lead to caffeine toxicity.^4,5

Other common inducers of CYP1A2 are insulin, cabbage, cauliflower, broccoli, and charcoal-grilled meat. Also, cumin and tur­meric inhibit CYP1A2 activity, which might explain an ethnic difference in drug toler­ance across population groups. Additionally, certain genetic polymorphisms, in specific ethnic distributions, alter the potential for tobacco smoke to induce CYP1A2.⁶

Some of these polymorphisms can be genotyped for clinical application.³

Asking about a patient’s tobacco and caffeine use and understanding their inter­actions with specific medications provides guidance when prescribing antipsychotic medications and adjusting dosage for inpatients and during clinical follow-up care.

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

When a patient who smokes enters a tobacco-free medical facility and has access to caffeinated beverages, he (she) might experience toxicity to many pharmaceuticals and caffeine. Similarly, if a patient is discharged from a smoke-free envi­ronment with a newly adjusted medication regimen and resumes smoking or caffeine consumption, alterations in enzyme activ­ity might reduce therapeutic efficacy of pre­scribed medicines. These effects are a result of alterations in the hepatic cytochrome P450 (CYP) enzyme system.

Taking a careful history of tobacco and caffeine use, and knowing the effects that these substances will have on specific medi­cations, will help guide treatment and man­agement decisions.

The role of CYP enzymes
CYP hepatic enzymes detoxify a variety of environmental agents into water-soluble compounds that are excreted in urine. CYP1A2 metabolizes 20% of drugs handled by the CYP system and comprises 13% of all the CYP enzymes expressed in the liver. The wide interindividual variation in CYP1A2 enzyme activity is influenced by a combina­tion of genetic, epigenetic, ethnic, and envi­ronmental variables.¹

Influence of tobacco on CYP
The polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2 and CYP2B6 hepatic enzymes.² Smokers exhibit increased activity of these enzymes, which results in faster clearance of many drugs, lower con­centrations in blood, and diminished clinical response. The Table lists psycho­tropic medicines that are metabolized by CYP1A2 and CYP2B6. Co-administration of these substrates could decrease the elimina­tion rate of other drugs also metabolized by CYP1A2. Nicotine in tobacco or in nicotine replacement therapies does not play a role in inducing CYP enzymes.

Psychiatric patients smoke at a higher rate than the general population.² One study found that approximately 70% of patients with schizophrenia and as many as 45% of those with bipolar disorder smoke enough cigarettes (7 to 20 a day) to induce CYP1A2 and CYP2B6 activity.² Patients who smoke and are given clozapine, haloperidol, or olanzapine show a lower serum concen­tration than non-smokers; in fact, the clo­zapine level can be reduced as much as 2.4-fold.2-5 Subsequently, patients can expe­rience diminished clinical response to these 3 psychotropics.³

The turnover time for CYP1A2 is rapid— approximately 3 days—and a new CYP1A2 steady state activity is reached after approxi­mately 1 week,⁴ which is important to remember when managing inpatients in a smoke-free facility. During acute hospitaliza­tion, patients could experience drug toxic­ity if the outpatient dosage is maintained.⁵

When they resume smoking after being discharged on a stabilized dosage of any of the medications listed in the Table, previous enzyme activity rebounds and might reduce the drug level, potentially leading to inad­equate clinical response.

Caffeine and other substances
Asking about the patient’s caffeine intake is necessary because consumption of coffee is prevalent among smokers, and caffeine is metabolized by CYP1A2. Smokers need to consume as much as 4 times the amount of caffeine as non-smokers to achieve a similar caffeine serum concentration.² Caffeine can form an insoluble precipitate with antipsychotic medication in the gut, which decreases absorption. The interac­tion between smoking-related induction of CYP1A2 enzymes and forced smoking ces­sation during hospitalization, with ongo­ing caffeine consumption, could lead to caffeine toxicity.^4,5

Other common inducers of CYP1A2 are insulin, cabbage, cauliflower, broccoli, and charcoal-grilled meat. Also, cumin and tur­meric inhibit CYP1A2 activity, which might explain an ethnic difference in drug toler­ance across population groups. Additionally, certain genetic polymorphisms, in specific ethnic distributions, alter the potential for tobacco smoke to induce CYP1A2.⁶

Some of these polymorphisms can be genotyped for clinical application.³

Asking about a patient’s tobacco and caffeine use and understanding their inter­actions with specific medications provides guidance when prescribing antipsychotic medications and adjusting dosage for inpatients and during clinical follow-up care.

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

In some patients, symptoms of depres­sion, psychosis, delirium, or dementia exist concomitantly with, or as a result of, an abnormal (elevated or low) serum cal­cium concentration that has been precipi­tated by an unrecognized endocrinopathy. The apparent psychiatric presentations of such patients might reflect parathyroid pathology—not psychopathology.

Hypercalcemia and hypocalcemia often are related to a distinct spectrum of condi­tions, such as diseases of the parathyroid glands, kidneys, and various neoplasms including malignancies. Be alert to the pos­sibility of parathyroid disease in patients whose presentation suggests mental ill­ness concurrent with, or as a direct conse­quence of, an abnormal calcium level, and investigate appropriately.

The Table^1-9 illustrates how 3 clini­cal laboratory tests—serum calcium, serum parathyroid hormone (PTH), and phosphate—can narrow the differen­tial diagnosis when the clinical impres­sion is parathyroid-related illness. Seek endocrinology consultation whenever a parathyroid-associated ailment is discov­ered or suspected. Serum calcium is rou­tinely assayed in hospitalized patients; when managing a patient with treatment-refractory psychiatric illness, (1) always check the reported result of that test and (2) consider measuring PTH.

Case reports¹
Case 1: Woman with chronic depression. The patient was hospitalized while suicidal. Serial serum calcium levels were 12.5 mg/dL and 15.8 mg/dL (reference range, 8.2–10.2 mg/dL). The PTH level was elevated at 287 pg/mL (refer­ence range, 10–65 pg/mL).

After thyroid imaging, surgery revealed a parathyroid mass, which was resected. Histologic examination confirmed an adenoma.

The calcium concentration declined to 8.6 mg/dL postoperatively and stabilized at 9.2 mg/dL. Psychiatric symptoms resolved fully; she experienced a complete recovery.

Case 2: Man on long-term lithium mainte­nance. The patient was admitted in a delusional psychotic state. The serum calcium level was 14.3 mg/dL initially, decreasing to 11.5 mg/dL after lithium was discontinued. The PTH level was elevated at 97 pg/mL at admission, consis­tent with hyperparathyroidism.

A parathyroid adenoma was resected. Serum calcium level normalized at 10.7 mg/dL; psycho­sis resolved with striking, sustained improve­ment in mental status.

Full return to mental, physical health

The diagnosis of parathyroid adenoma in these 2 patients, which began with a psy­chiatric presentation, was properly made after an abnormal serum calcium level was documented. Surgical treatment of the endocrinopathy produced full remission and a return to normal mental and physi­cal health.

Although psychiatric manifestations are associated with an abnormal serum calcium concentration, the severity of those presen­tations does not correlate with the degree of abnormality of the calcium level.¹⁰

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

In some patients, symptoms of depres­sion, psychosis, delirium, or dementia exist concomitantly with, or as a result of, an abnormal (elevated or low) serum cal­cium concentration that has been precipi­tated by an unrecognized endocrinopathy. The apparent psychiatric presentations of such patients might reflect parathyroid pathology—not psychopathology.

Hypercalcemia and hypocalcemia often are related to a distinct spectrum of condi­tions, such as diseases of the parathyroid glands, kidneys, and various neoplasms including malignancies. Be alert to the pos­sibility of parathyroid disease in patients whose presentation suggests mental ill­ness concurrent with, or as a direct conse­quence of, an abnormal calcium level, and investigate appropriately.

The Table^1-9 illustrates how 3 clini­cal laboratory tests—serum calcium, serum parathyroid hormone (PTH), and phosphate—can narrow the differen­tial diagnosis when the clinical impres­sion is parathyroid-related illness. Seek endocrinology consultation whenever a parathyroid-associated ailment is discov­ered or suspected. Serum calcium is rou­tinely assayed in hospitalized patients; when managing a patient with treatment-refractory psychiatric illness, (1) always check the reported result of that test and (2) consider measuring PTH.

Case reports¹
Case 1: Woman with chronic depression. The patient was hospitalized while suicidal. Serial serum calcium levels were 12.5 mg/dL and 15.8 mg/dL (reference range, 8.2–10.2 mg/dL). The PTH level was elevated at 287 pg/mL (refer­ence range, 10–65 pg/mL).

After thyroid imaging, surgery revealed a parathyroid mass, which was resected. Histologic examination confirmed an adenoma.

The calcium concentration declined to 8.6 mg/dL postoperatively and stabilized at 9.2 mg/dL. Psychiatric symptoms resolved fully; she experienced a complete recovery.

Case 2: Man on long-term lithium mainte­nance. The patient was admitted in a delusional psychotic state. The serum calcium level was 14.3 mg/dL initially, decreasing to 11.5 mg/dL after lithium was discontinued. The PTH level was elevated at 97 pg/mL at admission, consis­tent with hyperparathyroidism.

A parathyroid adenoma was resected. Serum calcium level normalized at 10.7 mg/dL; psycho­sis resolved with striking, sustained improve­ment in mental status.

Full return to mental, physical health

The diagnosis of parathyroid adenoma in these 2 patients, which began with a psy­chiatric presentation, was properly made after an abnormal serum calcium level was documented. Surgical treatment of the endocrinopathy produced full remission and a return to normal mental and physi­cal health.

Although psychiatric manifestations are associated with an abnormal serum calcium concentration, the severity of those presen­tations does not correlate with the degree of abnormality of the calcium level.¹⁰

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

In some patients, symptoms of depres­sion, psychosis, delirium, or dementia exist concomitantly with, or as a result of, an abnormal (elevated or low) serum cal­cium concentration that has been precipi­tated by an unrecognized endocrinopathy. The apparent psychiatric presentations of such patients might reflect parathyroid pathology—not psychopathology.

Hypercalcemia and hypocalcemia often are related to a distinct spectrum of condi­tions, such as diseases of the parathyroid glands, kidneys, and various neoplasms including malignancies. Be alert to the pos­sibility of parathyroid disease in patients whose presentation suggests mental ill­ness concurrent with, or as a direct conse­quence of, an abnormal calcium level, and investigate appropriately.

The Table^1-9 illustrates how 3 clini­cal laboratory tests—serum calcium, serum parathyroid hormone (PTH), and phosphate—can narrow the differen­tial diagnosis when the clinical impres­sion is parathyroid-related illness. Seek endocrinology consultation whenever a parathyroid-associated ailment is discov­ered or suspected. Serum calcium is rou­tinely assayed in hospitalized patients; when managing a patient with treatment-refractory psychiatric illness, (1) always check the reported result of that test and (2) consider measuring PTH.

Case reports¹
Case 1: Woman with chronic depression. The patient was hospitalized while suicidal. Serial serum calcium levels were 12.5 mg/dL and 15.8 mg/dL (reference range, 8.2–10.2 mg/dL). The PTH level was elevated at 287 pg/mL (refer­ence range, 10–65 pg/mL).

After thyroid imaging, surgery revealed a parathyroid mass, which was resected. Histologic examination confirmed an adenoma.

The calcium concentration declined to 8.6 mg/dL postoperatively and stabilized at 9.2 mg/dL. Psychiatric symptoms resolved fully; she experienced a complete recovery.

Case 2: Man on long-term lithium mainte­nance. The patient was admitted in a delusional psychotic state. The serum calcium level was 14.3 mg/dL initially, decreasing to 11.5 mg/dL after lithium was discontinued. The PTH level was elevated at 97 pg/mL at admission, consis­tent with hyperparathyroidism.

A parathyroid adenoma was resected. Serum calcium level normalized at 10.7 mg/dL; psycho­sis resolved with striking, sustained improve­ment in mental status.

Full return to mental, physical health

The diagnosis of parathyroid adenoma in these 2 patients, which began with a psy­chiatric presentation, was properly made after an abnormal serum calcium level was documented. Surgical treatment of the endocrinopathy produced full remission and a return to normal mental and physi­cal health.

Although psychiatric manifestations are associated with an abnormal serum calcium concentration, the severity of those presen­tations does not correlate with the degree of abnormality of the calcium level.¹⁰

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

Snoring, snorting, gasping, and obstruc­tive sleep apnea are caused by col­lapse of the pharyngeal airway during sleep.¹ Pathophysiology includes a combi­nation of anatomical and physiological vari­ables.¹ Common anatomical predisposing conditions include abnormalities of pharyn­geal, lingual, and dental arches; physiologi­cal concerns are advancing age, male sex, obesity, use of sedatives, body positioning, and reduced muscle tone during rapid eye movement sleep. Coexistence of anatomic and physiological elements can produce significant narrowing of the upper airway.

Comorbidities include vascular, meta­bolic, and psychiatric conditions. As many as one-third of people with symptoms of sleep apnea report depressed mood; approx­imately 10% of these patients meet criteria for moderate or severe depression.²

In short, sleep-disordered breathing has a globally negative effect on mental health.

When should you consider obtaining a sleep apnea study?
Refer patients for a sleep study when snor­ing, snorting, gasping, or pauses in breathing occur during sleep, or in the case of daytime sleepiness, fatigue, or unrefreshing sleep that cannot be explained by another medical or psychiatric illness.² A sleep specialist can determine the most appropriate intervention for sleep-disordered breathing.

An apneic event is characterized by complete cessation of airflow; hypopnea is a partially compromised airway. In either event, at least a 3% decrease in oxygen saturation occurs for at least 10 seconds.³ A diagnosis of obstructive sleep apnea or hypopnea is required when polysomnography reveals either of:
   • ≥5 episodes of apnea or hypopnea, or both, per hour of sleep, with symptoms of a rhythmic breathing disturbance or daytime sleepiness or fatigue
   • ≥15 episodes of apnea or hypopnea, or both, per hour of sleep, regardless of accom­panying symptoms.²

What are the treatment options? 
   • Continuous positive airway pressure (CPAP) machines.
   • Surgical procedures include adeno-tonsillectomy in children and surgical maxilla-mandibular advancement or pala­tal implants for adults.
   • A novel implantable electrical stimu­lation device stimulates the hypoglossal nerve, which activates the genioglossus muscle, thus moving the tongue forward to open the airway.
   • An anterior mandibular positioning (AMP) device increases the diameter of the retroglossal space by preventing posterior movement of the mandible and tongue, thereby limiting encroachment on the air­way diameter and reducing the potential for collapse.^1-4

When should you recommend an AMP device?
Consider recommending an AMP device to treat sleep-disordered breathing when (1) lifestyle changes, such as sleep hygiene, weight loss, and stopping sedatives, do not work and (2) a CPAP machine or a surgical procedure is contraindicated or has been ineffective.¹ An AMP device can minimize snoring and relieve airway obstruction, especially in patients with supine position-related apnea.⁴ To keep the airway open in non-supine position-related cases, an AMP device might be indicated in addition to CPAP delivered nasally.¹

This plastic oral appliance is either a 1- or 2-piece design, and looks and is sized simi­larly to an athletic mouth-protection guard or an oral anti-bruxism tooth-protection appliance. It is affixed to the mandible and maxillary arches by clasps (Figure).

An AMP device often is most beneficial for supine-dependent sleep apnea patients and those with loud snoring, without sleep apnea.⁴ Response is best in young adults and in patients who have a low body mass index, are free of sedatives, and have appropriate cephalometrics of the oral, dental, or pha­ryngeal anatomy. Improved sleep architec­ture, continuous sleep with less snoring, and increased daytime alertness are observed in patients who respond to an AMP device.

An AMP device is contraindicated when the device cannot be affixed to the dental arches and in some patients with an anatom­ical or pain-related temporomandibular joint disorder.⁵ The device is easy to use, nonin­vasive, readily accessible, and less expensive than alternatives.³

How can you help maintain treatment adherence?
AMP devices can induce adverse effects, including dental pain or discomfort through orthodontic alterations; patient reports and follow-up can yield detection and device adjustments can alleviate such problems. Adherence generally is good, with complaints usually limited to minor tooth discomfort, occlusive changes, and increased or decreased salivation.⁵ In our clinical experience, many patients find these devices comfortable and easy to use, but might complain of feeling awkward when wearing them.

Changes in occlusion can occur during long-term treatment with an AMP device. Proper fitting is essential to facilitate a more open airway and the ability to speak and drink fluids, and to maintain safety, even if vomiting occurs while the device is in place.

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

Snoring, snorting, gasping, and obstruc­tive sleep apnea are caused by col­lapse of the pharyngeal airway during sleep.¹ Pathophysiology includes a combi­nation of anatomical and physiological vari­ables.¹ Common anatomical predisposing conditions include abnormalities of pharyn­geal, lingual, and dental arches; physiologi­cal concerns are advancing age, male sex, obesity, use of sedatives, body positioning, and reduced muscle tone during rapid eye movement sleep. Coexistence of anatomic and physiological elements can produce significant narrowing of the upper airway.

Comorbidities include vascular, meta­bolic, and psychiatric conditions. As many as one-third of people with symptoms of sleep apnea report depressed mood; approx­imately 10% of these patients meet criteria for moderate or severe depression.²

In short, sleep-disordered breathing has a globally negative effect on mental health.

When should you consider obtaining a sleep apnea study?
Refer patients for a sleep study when snor­ing, snorting, gasping, or pauses in breathing occur during sleep, or in the case of daytime sleepiness, fatigue, or unrefreshing sleep that cannot be explained by another medical or psychiatric illness.² A sleep specialist can determine the most appropriate intervention for sleep-disordered breathing.

An apneic event is characterized by complete cessation of airflow; hypopnea is a partially compromised airway. In either event, at least a 3% decrease in oxygen saturation occurs for at least 10 seconds.³ A diagnosis of obstructive sleep apnea or hypopnea is required when polysomnography reveals either of:
   • ≥5 episodes of apnea or hypopnea, or both, per hour of sleep, with symptoms of a rhythmic breathing disturbance or daytime sleepiness or fatigue
   • ≥15 episodes of apnea or hypopnea, or both, per hour of sleep, regardless of accom­panying symptoms.²

What are the treatment options? 
   • Continuous positive airway pressure (CPAP) machines.
   • Surgical procedures include adeno-tonsillectomy in children and surgical maxilla-mandibular advancement or pala­tal implants for adults.
   • A novel implantable electrical stimu­lation device stimulates the hypoglossal nerve, which activates the genioglossus muscle, thus moving the tongue forward to open the airway.
   • An anterior mandibular positioning (AMP) device increases the diameter of the retroglossal space by preventing posterior movement of the mandible and tongue, thereby limiting encroachment on the air­way diameter and reducing the potential for collapse.^1-4

When should you recommend an AMP device?
Consider recommending an AMP device to treat sleep-disordered breathing when (1) lifestyle changes, such as sleep hygiene, weight loss, and stopping sedatives, do not work and (2) a CPAP machine or a surgical procedure is contraindicated or has been ineffective.¹ An AMP device can minimize snoring and relieve airway obstruction, especially in patients with supine position-related apnea.⁴ To keep the airway open in non-supine position-related cases, an AMP device might be indicated in addition to CPAP delivered nasally.¹

This plastic oral appliance is either a 1- or 2-piece design, and looks and is sized simi­larly to an athletic mouth-protection guard or an oral anti-bruxism tooth-protection appliance. It is affixed to the mandible and maxillary arches by clasps (Figure).

An AMP device often is most beneficial for supine-dependent sleep apnea patients and those with loud snoring, without sleep apnea.⁴ Response is best in young adults and in patients who have a low body mass index, are free of sedatives, and have appropriate cephalometrics of the oral, dental, or pha­ryngeal anatomy. Improved sleep architec­ture, continuous sleep with less snoring, and increased daytime alertness are observed in patients who respond to an AMP device.

An AMP device is contraindicated when the device cannot be affixed to the dental arches and in some patients with an anatom­ical or pain-related temporomandibular joint disorder.⁵ The device is easy to use, nonin­vasive, readily accessible, and less expensive than alternatives.³

How can you help maintain treatment adherence?
AMP devices can induce adverse effects, including dental pain or discomfort through orthodontic alterations; patient reports and follow-up can yield detection and device adjustments can alleviate such problems. Adherence generally is good, with complaints usually limited to minor tooth discomfort, occlusive changes, and increased or decreased salivation.⁵ In our clinical experience, many patients find these devices comfortable and easy to use, but might complain of feeling awkward when wearing them.

Changes in occlusion can occur during long-term treatment with an AMP device. Proper fitting is essential to facilitate a more open airway and the ability to speak and drink fluids, and to maintain safety, even if vomiting occurs while the device is in place.

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

Snoring, snorting, gasping, and obstruc­tive sleep apnea are caused by col­lapse of the pharyngeal airway during sleep.¹ Pathophysiology includes a combi­nation of anatomical and physiological vari­ables.¹ Common anatomical predisposing conditions include abnormalities of pharyn­geal, lingual, and dental arches; physiologi­cal concerns are advancing age, male sex, obesity, use of sedatives, body positioning, and reduced muscle tone during rapid eye movement sleep. Coexistence of anatomic and physiological elements can produce significant narrowing of the upper airway.

Comorbidities include vascular, meta­bolic, and psychiatric conditions. As many as one-third of people with symptoms of sleep apnea report depressed mood; approx­imately 10% of these patients meet criteria for moderate or severe depression.²

In short, sleep-disordered breathing has a globally negative effect on mental health.

When should you consider obtaining a sleep apnea study?
Refer patients for a sleep study when snor­ing, snorting, gasping, or pauses in breathing occur during sleep, or in the case of daytime sleepiness, fatigue, or unrefreshing sleep that cannot be explained by another medical or psychiatric illness.² A sleep specialist can determine the most appropriate intervention for sleep-disordered breathing.

An apneic event is characterized by complete cessation of airflow; hypopnea is a partially compromised airway. In either event, at least a 3% decrease in oxygen saturation occurs for at least 10 seconds.³ A diagnosis of obstructive sleep apnea or hypopnea is required when polysomnography reveals either of:
   • ≥5 episodes of apnea or hypopnea, or both, per hour of sleep, with symptoms of a rhythmic breathing disturbance or daytime sleepiness or fatigue
   • ≥15 episodes of apnea or hypopnea, or both, per hour of sleep, regardless of accom­panying symptoms.²

What are the treatment options? 
   • Continuous positive airway pressure (CPAP) machines.
   • Surgical procedures include adeno-tonsillectomy in children and surgical maxilla-mandibular advancement or pala­tal implants for adults.
   • A novel implantable electrical stimu­lation device stimulates the hypoglossal nerve, which activates the genioglossus muscle, thus moving the tongue forward to open the airway.
   • An anterior mandibular positioning (AMP) device increases the diameter of the retroglossal space by preventing posterior movement of the mandible and tongue, thereby limiting encroachment on the air­way diameter and reducing the potential for collapse.^1-4

When should you recommend an AMP device?
Consider recommending an AMP device to treat sleep-disordered breathing when (1) lifestyle changes, such as sleep hygiene, weight loss, and stopping sedatives, do not work and (2) a CPAP machine or a surgical procedure is contraindicated or has been ineffective.¹ An AMP device can minimize snoring and relieve airway obstruction, especially in patients with supine position-related apnea.⁴ To keep the airway open in non-supine position-related cases, an AMP device might be indicated in addition to CPAP delivered nasally.¹

This plastic oral appliance is either a 1- or 2-piece design, and looks and is sized simi­larly to an athletic mouth-protection guard or an oral anti-bruxism tooth-protection appliance. It is affixed to the mandible and maxillary arches by clasps (Figure).

An AMP device often is most beneficial for supine-dependent sleep apnea patients and those with loud snoring, without sleep apnea.⁴ Response is best in young adults and in patients who have a low body mass index, are free of sedatives, and have appropriate cephalometrics of the oral, dental, or pha­ryngeal anatomy. Improved sleep architec­ture, continuous sleep with less snoring, and increased daytime alertness are observed in patients who respond to an AMP device.

An AMP device is contraindicated when the device cannot be affixed to the dental arches and in some patients with an anatom­ical or pain-related temporomandibular joint disorder.⁵ The device is easy to use, nonin­vasive, readily accessible, and less expensive than alternatives.³

How can you help maintain treatment adherence?
AMP devices can induce adverse effects, including dental pain or discomfort through orthodontic alterations; patient reports and follow-up can yield detection and device adjustments can alleviate such problems. Adherence generally is good, with complaints usually limited to minor tooth discomfort, occlusive changes, and increased or decreased salivation.⁵ In our clinical experience, many patients find these devices comfortable and easy to use, but might complain of feeling awkward when wearing them.

Changes in occlusion can occur during long-term treatment with an AMP device. Proper fitting is essential to facilitate a more open airway and the ability to speak and drink fluids, and to maintain safety, even if vomiting occurs while the device is in place.

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

Frontotemporal dementia (FTD) is a neu­rologic disease that affects the frontal and the temporal lobes of the cerebral cortex.¹ This disorder is observed most often in people between age 45 to 65, but also can manifest in younger or older persons.¹ The cause varies among a range of pathologies affecting the anterior portions of the brain.²

Presentations
FTD presents with changes in personality, social skills, ability to concentrate, motiva­tion, reasoning, and language abnormal­ity.³ Memory loss is less prominent in this condition compared with other dementias; therefore, identification may be a diagnos­tic challenge. FTD can be misdiagnosed as a psychiatric illness or not recognized because social symptoms dominate over cognitive dysfunction. As the disease progresses, patients may become increasingly unable to plan or organize activities of daily living, behave appropriately, and react normally in social interactions.¹

FTD has 3 diagnostic variants^1-4:

Behavioral variant. Known as Pick dis­ease or the “frontal variant,”^1,2 this type of FTD manifests as changes in personality, improper behavior in social settings, per­sonal neglect, or impulsivity, such as shop­lifting or hypersexuality.

Primary progressive aphasia. Two types of language dysfunction are observed in FTD:
   • Semantic dementia (SD)³: Left-sided SD presents with “meaningless speech” or “word substitutions” (eg, “chair” instead of “table”). Right-sided SD, however, is char­acterized by forgetting the faces of familiar people or objects.
   • Primary nonfluent aphasia³: Language fluency is compromised. Persons with such language dysfunction cannot produce words easily, and their speech is stumbling and nonfluent.

FTD with motor neuron disease.⁴ The most common type of motor neuron dis­ease associated with FTD is amyotrophic lateral sclerosis. Afflicted patients exhibit muscle weakness, spasms, and rigidity. This leads to difficulty in swallowing or breathing because the diaphragm and pharynx are paralyzed. Other diseases associated with FTD include corticobasal degeneration and progressive supranu­clear palsy.

Diagnosis
In DSM-5, FTD has been renamed “fronto­temporal lobar degeneration” under the cat­egory of “Major and Mild Neurocognitive Disorders.”⁵ The workup begins with a his­tory, physical examination, and mental sta­tus assessment. Physical signs can include frontal-release, primitive reflexes. Early in the disease course, a palmomental reflex often is observed; later, as disease progress, the rooting reflex or palmar grasp may become apparent.^1,5

Diagnosing FTD requires recognizing its symptoms and ruling out conditions such as Alzheimer’s disease, depression, and schizophrenia.⁶ Laboratory studies may help identify other conditions. Brain imaging, such as MRI, can depict fronto­temporal pathology and rule in or exclude other diseases.^3,5

Psychometric testing can evaluate mem­ory or cognitive ability, which might be unremarkable during the initial phases of FTD.⁴ Further psychological assessments may provide objective verification of frontal lobe deficiencies in social skills or activities of daily living.³ Positron emission tomogra­phy and single-photon emission computed tomography may demonstrate areas of decreased activity or hypoperfusion in fron­tal and temporal lobes.⁷

Interventions
Treatment of FTD is limited to symp­tomatic therapy⁸; there are no specific, approved countermeasures available. Comorbid conditions, such as diabetes mellitus or hypertension, should be treated medically. Social interventions such as day care, increased supervision, and emotional support from the family can be effective adjuvants.²

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

Frontotemporal dementia (FTD) is a neu­rologic disease that affects the frontal and the temporal lobes of the cerebral cortex.¹ This disorder is observed most often in people between age 45 to 65, but also can manifest in younger or older persons.¹ The cause varies among a range of pathologies affecting the anterior portions of the brain.²

Presentations
FTD presents with changes in personality, social skills, ability to concentrate, motiva­tion, reasoning, and language abnormal­ity.³ Memory loss is less prominent in this condition compared with other dementias; therefore, identification may be a diagnos­tic challenge. FTD can be misdiagnosed as a psychiatric illness or not recognized because social symptoms dominate over cognitive dysfunction. As the disease progresses, patients may become increasingly unable to plan or organize activities of daily living, behave appropriately, and react normally in social interactions.¹

FTD has 3 diagnostic variants^1-4:

Behavioral variant. Known as Pick dis­ease or the “frontal variant,”^1,2 this type of FTD manifests as changes in personality, improper behavior in social settings, per­sonal neglect, or impulsivity, such as shop­lifting or hypersexuality.

Primary progressive aphasia. Two types of language dysfunction are observed in FTD:
   • Semantic dementia (SD)³: Left-sided SD presents with “meaningless speech” or “word substitutions” (eg, “chair” instead of “table”). Right-sided SD, however, is char­acterized by forgetting the faces of familiar people or objects.
   • Primary nonfluent aphasia³: Language fluency is compromised. Persons with such language dysfunction cannot produce words easily, and their speech is stumbling and nonfluent.

FTD with motor neuron disease.⁴ The most common type of motor neuron dis­ease associated with FTD is amyotrophic lateral sclerosis. Afflicted patients exhibit muscle weakness, spasms, and rigidity. This leads to difficulty in swallowing or breathing because the diaphragm and pharynx are paralyzed. Other diseases associated with FTD include corticobasal degeneration and progressive supranu­clear palsy.

Diagnosis
In DSM-5, FTD has been renamed “fronto­temporal lobar degeneration” under the cat­egory of “Major and Mild Neurocognitive Disorders.”⁵ The workup begins with a his­tory, physical examination, and mental sta­tus assessment. Physical signs can include frontal-release, primitive reflexes. Early in the disease course, a palmomental reflex often is observed; later, as disease progress, the rooting reflex or palmar grasp may become apparent.^1,5

Diagnosing FTD requires recognizing its symptoms and ruling out conditions such as Alzheimer’s disease, depression, and schizophrenia.⁶ Laboratory studies may help identify other conditions. Brain imaging, such as MRI, can depict fronto­temporal pathology and rule in or exclude other diseases.^3,5

Psychometric testing can evaluate mem­ory or cognitive ability, which might be unremarkable during the initial phases of FTD.⁴ Further psychological assessments may provide objective verification of frontal lobe deficiencies in social skills or activities of daily living.³ Positron emission tomogra­phy and single-photon emission computed tomography may demonstrate areas of decreased activity or hypoperfusion in fron­tal and temporal lobes.⁷

Interventions
Treatment of FTD is limited to symp­tomatic therapy⁸; there are no specific, approved countermeasures available. Comorbid conditions, such as diabetes mellitus or hypertension, should be treated medically. Social interventions such as day care, increased supervision, and emotional support from the family can be effective adjuvants.²

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

Frontotemporal dementia (FTD) is a neu­rologic disease that affects the frontal and the temporal lobes of the cerebral cortex.¹ This disorder is observed most often in people between age 45 to 65, but also can manifest in younger or older persons.¹ The cause varies among a range of pathologies affecting the anterior portions of the brain.²

Presentations
FTD presents with changes in personality, social skills, ability to concentrate, motiva­tion, reasoning, and language abnormal­ity.³ Memory loss is less prominent in this condition compared with other dementias; therefore, identification may be a diagnos­tic challenge. FTD can be misdiagnosed as a psychiatric illness or not recognized because social symptoms dominate over cognitive dysfunction. As the disease progresses, patients may become increasingly unable to plan or organize activities of daily living, behave appropriately, and react normally in social interactions.¹

FTD has 3 diagnostic variants^1-4:

Behavioral variant. Known as Pick dis­ease or the “frontal variant,”^1,2 this type of FTD manifests as changes in personality, improper behavior in social settings, per­sonal neglect, or impulsivity, such as shop­lifting or hypersexuality.

Primary progressive aphasia. Two types of language dysfunction are observed in FTD:
   • Semantic dementia (SD)³: Left-sided SD presents with “meaningless speech” or “word substitutions” (eg, “chair” instead of “table”). Right-sided SD, however, is char­acterized by forgetting the faces of familiar people or objects.
   • Primary nonfluent aphasia³: Language fluency is compromised. Persons with such language dysfunction cannot produce words easily, and their speech is stumbling and nonfluent.

FTD with motor neuron disease.⁴ The most common type of motor neuron dis­ease associated with FTD is amyotrophic lateral sclerosis. Afflicted patients exhibit muscle weakness, spasms, and rigidity. This leads to difficulty in swallowing or breathing because the diaphragm and pharynx are paralyzed. Other diseases associated with FTD include corticobasal degeneration and progressive supranu­clear palsy.

Diagnosis
In DSM-5, FTD has been renamed “fronto­temporal lobar degeneration” under the cat­egory of “Major and Mild Neurocognitive Disorders.”⁵ The workup begins with a his­tory, physical examination, and mental sta­tus assessment. Physical signs can include frontal-release, primitive reflexes. Early in the disease course, a palmomental reflex often is observed; later, as disease progress, the rooting reflex or palmar grasp may become apparent.^1,5

Diagnosing FTD requires recognizing its symptoms and ruling out conditions such as Alzheimer’s disease, depression, and schizophrenia.⁶ Laboratory studies may help identify other conditions. Brain imaging, such as MRI, can depict fronto­temporal pathology and rule in or exclude other diseases.^3,5

Psychometric testing can evaluate mem­ory or cognitive ability, which might be unremarkable during the initial phases of FTD.⁴ Further psychological assessments may provide objective verification of frontal lobe deficiencies in social skills or activities of daily living.³ Positron emission tomogra­phy and single-photon emission computed tomography may demonstrate areas of decreased activity or hypoperfusion in fron­tal and temporal lobes.⁷

Interventions
Treatment of FTD is limited to symp­tomatic therapy⁸; there are no specific, approved countermeasures available. Comorbid conditions, such as diabetes mellitus or hypertension, should be treated medically. Social interventions such as day care, increased supervision, and emotional support from the family can be effective adjuvants.²

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