Kristen Rundell, MD

As many as 240,000 people per year in the United States experience a transient ischemic attack (TIA),^1,2 which is now defined by the American Heart Association and American Stroke Association as a “transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.”³ An older definition of TIA was based on the duration of the event (ie, resolution of symptoms at 24 hours); in the updated (2009) definition, the diagnostic criterion is the extent of focal tissue damage.³ Using the 2009 definition might mean a decrease in the number of patients who have a diagnosis of a TIA and an increase in the number who are determined to have had a stroke because an infarction is found on initial imaging.

Guided by the 2009 revised definition of a TIA, we review here the work-up and treatment of TIA, emphasizing immediacy of management to (1) prevent further tissue damage and (2) decrease the risk of a second event.

Copyright Scott Bodell

CASE

Martin L, 69 years old, retired, a nonsmoker, and with a history of peripheral arterial disease and hypercholesterolemia, presents to the emergency department (ED) of a rural hospital complaining of slurred speech and left-side facial numbness. He had an episode of facial numbness that lasted 30 minutes, then resolved, each of the 2 previous evenings; he did not seek care at those times. Now, in the ED, Mr. L is normotensive.

The patient’s medication history includes a selective serotonin reuptake inhibitor and melatonin to improve sleep. He reports having discontinued a statin because he could not tolerate its adverse effects.

What immediate steps are recommended for Mr. L’s care?

Common event callsfor quick action

A TIA is the strongest predictor of subsequent stroke and stroke-related death; the highest period of risk of these devastating outcomes is immediately following a TIA.^1,2,4,5 It is essential, therefore, for the physician who sees a patient with a current complaint or recent history of suspected focal neurologic deficits to direct that patient to an ED for an accurate diagnosis and, as appropriate, early treatment for the best possible outcome.

A TIA is the strongest predictor of subsequent stroke and stroke-related death; the highest period of risk of these devastating outcomes is immediately following a TIA.

Imaging—preferably, diffusion-­weighted magnetic resonance imaging (DW-MRI), the gold standard for diagnosing stroke (see “Diagnosis includes ruling out mimics”)^2,3—should be performed as soon as the patient with a suspected TIA arrives in the ED. Imaging should not be held while waiting for a stroke to declare itself—ie, by allowing symptoms to persist for longer than 24 hours. ⁶

Continue to: Late presentation

Late presentation. Some patients present ≥ 48 hours after onset of early symptoms of a TIA; for them, the work-up is the same as for prompt presentation but can be completed in the outpatient clinic—as long as the patient is stable clinically and imaging is accessible there. DW-MRI should be completed within 48 hours after late presentation. In such cases, the patient should be cautioned regarding risks and any recurrence of symptoms.^7,8

Diagnosis includes ruling out mimics

All patients in whom a stroke is suspected should be evaluated on an emergency basis with brain imaging upon arrival at the hospital, before any therapy is initiated. As noted, DW-MRI is the preferred modality; noncontrast computed tomography (CT) or CT angiography can be used if MRI is unavailable.^2,3

Mimics. Stroke has many mimics; quickly eliminating them from the differential diagnosis is important so that appropriate therapy can be initiated. Mimics usually have a prolonged presentation of symptoms, whereas the presentation of a TIA is usually abrupt. The 3 more common diagnoses that mimic a TIA are migraine with aura, seizure, and syncope.^9,10 Symptoms that generally are not associated with a TIA are chest pain, generalized weakness, and confusion.¹¹ A complete history and physical exam provide the path to the imaging, laboratory, and cardiac testing that is needed to differentiate these diagnoses from a TIA.

A thorough history is best obtained from the patient and a witness, if available, and should include identification of any focal neurologic deficits and the duration and time to resolution of symptoms. Obtain a history of risk factors for ischemia—tobacco use, diabetes, obesity, dyslipidemia, hypertension, previous TIA or stroke, atrial fibrillation, and any coagulopathy. Ask questions about a family history of TIA, stroke, and coagulopathy.¹¹

A comprehensive physical exam, including vital signs, cardiac exam, a check for carotid bruits, and complete neurologic exam, should be performed. Most patients present with concerns for unilateral weakness and changes in speech, which are usually associated with infarction on DW-MRI.¹² The most common findings on physical exam include cranial nerve abnormalities, such as diplopia, hemianopia, monocular blindness, disconjugate gaze, facial drooping, lateral tongue movement, dysphagia, and vestibular dysfunction. Cerebellar abnormalities are also often noted, including past pointing, dystaxia, ataxia, nystagmus, and motor abnormalities (eg, spasticity, clonus, or unilateral weakness in the face or extremities).¹¹

Electrocardiography at the bedside can confirm atrial fibrillation or another arrhythmia quickly.

Essential laboratory testing includes measurement of blood glucose and serum electrolytes to determine if these particular imbalances are the cause of symptoms. The presence of a hypercoaguable state is determined by a complete blood count and coagulation studies.^3,13 Urine toxicology should also be obtained to rule out other causes of symptoms. A lipid profile is beneficial for making long-term treatment decisions.

Continue to: ABCD2 score

ABCD2 score. Patients who have had a TIA and present within 72 hours after symptoms have resolved should be hospitalized if they have an ABCD2 (Age, Blood pressure [BP], Clinical presentation, Diabetes mellitus [type 1 or 2], Duration of symptoms) prediction system score > 3.¹⁴ ABCD2 criteria can be used to help identify patients who are at higher risk of stroke or need further therapy (TABLE 1).^14,15

Send a patient with a current complaint or recent history of suspected focal neurologic deficits to an ED for accurate diagnosis of a possible TIA and, as appropriate, early treatment.

The ABCD2 score is also used to determine whether a patient needs dual antiplatelet therapy. Patients who score at the higher end of the ABCD2 system usually have an increased risk of stroke, longer hospitalization, and greater disability.

CASE

In the ED, Mr. L is immediately assessed and airlifted to a larger regional medical center, where MRI confirms a stroke.

Management

Initial management of a TIA is aimed at reducing the risk of recurrent TIA or stroke. Early medical and possibly surgical treatment are key for preventing stroke and improving outcomes. The first 48 hours after a TIA are the most critical because the incidence of recurrent TIA or stroke is highest during this period.^16-18

What is the accepted strategy for early treatment?

Initial treatment must include antiplatelet therapy, BP management, anticoagulation, statin therapy, and carotid endarterectomy as indicated.^2,19,20 Control of hypertension and anticoagulation decrease the risk of recurrent stroke by the largest margin²⁰; both are “A”-level Strength of Recommendation Taxonomy interventions.^2,3

Step 1: Antiplatelet therapy. After initial imaging is complete and if there are no contraindications, antiplatelet agents are recommended for patients who have had a noncardioembolic TIA. The American Heart Association and American Stroke Association recommend either aspirin, clopidogrel, dipyridamole + aspirin (available in a single capsule [Aggrenox]), or clopidogrel + aspirin as first-line therapy.^2,20 The choice of agent needs to be individualized, based on tolerability and adverse effects (TABLE 2^2,20,21).

A meta-analysis of antiplatelet therapy reviewed the optimum dosing of each medication.^21,22 Reduction of the risk of ischemic stroke with aspirin is 21% to 22% at the optimal dosing of 75 to 150 mg/d, which also reduces the risk of gastrointestinal bleeding.

Continue to: For a patient who has...

For a patient who has an ABCD2 score ≥ 4, has had a prior TIA, or has large-vessel disease, dual antiplatelet therapy is recommended for the first 21 days, with a subsequent return to monotherapy. Dual antiplatelet therapy of clopidogrel + aspirin increases the risk of adverse reactions and has not been shown to have greater long-term benefit^23-25 (TABLE 2^2,20,21).

Step 2: BP management. This is the next immediate step. As many as 80% of patients who present with a TIA have elevated BP upon admission. BP needs to be treated and carefully monitored during this early treatment phase. The recommendation is for a systolic BP < 185 mm Hg and a diastolic BP < 110 mm Hg.²⁴

Step 3: Anticoagulation. Treatment with warfarin or a direct oral anticoagulant (DOAC) is recommended for patients who have the potential for forming emboli—eg, in the setting of atrial fibrillation, ventricular thrombus, mechanical heart valve, or venous thromboembolism.

Step 4. High-intensity statin. A statin agent is recommended as part of immediate and long-term medical management, regardless of the low-density lipoprotein cholesterol (LDL-C) level, to reduce the risk of stroke.^2,24

Carotid artery management. Surgical intervention is not always considered a component of immediate medical management. However, guidelines recommend that carotid endarterectomy or stenting be considered in patients who have stenosis > 70%.²

CASE

Mr. L is admitted to the hospital and undergoes neurosurgical intervention. Medical management is instituted.

Long-term management and secondary prevention

The main risk factors for stroke can be divided into modifiable, vascular, and unmodifiable. Addressing both modifiable and vascular risks is important for secondary prevention.

Continue to: Modifiable and vascular risk factors

Modifiable risk factors for stroke include hypertension, diabetes, dyslipidemia, smoking, and physical activity; the most important of these, for preventing subsequent stroke after an initial TIA, is hypertension.²⁶

The 2 more significant vascular risk factors for stroke are carotid artery stenosis and atrial fibrillation.

Hypertension. Improving control of hypertension can improve secondary risk reduction for recurrent stroke. Control of both systolic and diastolic BP is important in this regard, with larger systolic BP reductions having a greater impact on decreasing the risk of recurrent stroke.²⁴ Evidence supports lowering BP to improve secondary risk reduction in people with and without diagnosed hypertension: The goal is to lower systolic BP by ≥ 10 mm Hg and diastolic BP by 5 mm Hg.²⁴ No particular class of antihypertensive is recommended in the first line, although preliminary evidence shows that a diuretic, with or without an angiotensin-converting enzyme inhibitor, might be more beneficial than other options.²⁴

Diabetes. The risk of cardiovascular disease, including stroke, is higher in people with diabetes. Evidence shows that various (but not all) agents in 2 pharmaceutical classes—glucagon-like peptide-1 (GLP-1) receptor agonists and the sodium glucose-2 cotransporter (SGLT2) inhibitors—reduce the risk of major cardiovascular events and improve secondary prevention of recurrent stroke:

• EMPA-REG OUTCOME (ClinicalTrials.gov Identifier: NCT01131676) was the first trial to show cardiovascular benefit from an SGLT2 inhibitor (empagliflozin); subsequent studies confirmed the cardiovascular benefits found in EMPA-REG OUTCOME.^27,28
• The ELIXA trial (ClinicalTrials.gov Identifier: NCT01147250) was the first to show cardiovascular benefit from a GLP-1 receptor agonist (lixisenatide); subsequent studies supported this finding.^29,30

Appropriate agents in these 2 classes should be considered as first-line or adjunctive in patients with both diabetes and known cardiovascular disease, as long as there are no contraindications.^27,28

Pioglitazone, a thiazolidinedione-class antidiabetic agent, was once considered a potential option to improve secondary prevention of stroke. However, the thiazolidinediones are generally no longer considered; instead, the SGLT2 inhibitors and GLP-1 receptor agonists are favored.³¹

Evidence demonstrates the effect of hyperglycemia on cardiovascular events; however, it is important to note that hypoglycemia can result in symptoms and focal changes that mimic a stroke. In addition, some evidence suggests that hypoglycemia can increase cardiovascular risk—thereby supporting the importance of strict control of diabetes and maintenance of euglycemia in reducing overall cardiovascular risk.³²

Continue to: Lipids

Lipids. The SPARCL trial (ClinicalTrials.gov Identifier: NCT00147602) was the first study to demonstrate the benefit of high-­intensity statin therapy—specifically, atorvastatin 80 mg/d—for secondary prevention for recurrent stroke.³³ The recommendation is to use high-intensity statin therapy to decrease the risk of recurrent stroke by reducing the level of LDL-C—by ≥ 50% or to < 70 mg/dL, for maximum risk reduction.^24,34

Common conditions that mimic a TIA are migraine with aura, seizure, and syncope; a TIA is generally not associated with chest pain, generalized weakness, or confusion.

The IMPROVE-IT trial (ClinicalTrials.gov Identifier: NCT00202878) demonstrated the benefit of adding ezetimibe, 10 mg/d, to a moderate-to-high-intensity statin (simvastatin, 40-80 mg/d) to reduce the risk of recurrent stroke.³⁵

Results of recent studies support the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for regulating levels of LDL-C, as an additional option to consider—if needed to further reduce the LDL-C level or if statins are contraindicated in a particular patient.³⁴

Smoking cessation. Cigarette smoking is known to increase the risk of ischemic stroke; newer evidence shows that second-hand exposure to smoke also increases the risk of ischemic stroke.^36,37 Although these studies focused on primary prevention of ischemic stroke, the data can reasonably be applied to secondary prevention.³⁸ The recommendation for secondary prevention is to quit smoking and avoid secondhand smoke.²⁴

Alcohol. Evidence demonstrates that heavy alcohol consumption and alcoholism increase the risk of stroke; similar to what is known about smoking, most available data relate to primary prevention.³⁸ The recommendation for providing secondary stroke prevention is to stop or decrease alcohol intake.²⁴

Weight reduction. Obesity (body mass index > 30) increases the risk of ischemic stroke. However, there is, as yet, no evidence that weight loss diminishes the risk of subsequent stroke for secondary prevention.²⁴

Physical activity. Aerobic exercise and strength-training programs after a stroke improve cardiovascular health and mobility. There is no evidence that exercise leads to a reduction in the risk of subsequent stroke.²⁴

Continue to: Nutrition

Nutrition. No current randomized controlled trials are focused on the relationship between diet and recurrent stroke for purposes of prevention; however, evidence for both BP and lipid control incorporate dietary guidance. Recommendations include reducing intake of saturated fats and of sodium (the latter, to < 2.3 g/d) and increasing intake of fruits and vegetables, both of which are beneficial for controlling BP and lipid levels and promoting overall cardiovascular health.³⁸

Carotid artery stenosis. Several randomized controlled trials have demonstrated benefit from treating carotid stenosis (> 70% stenosis but not < 50%) with carotid endarterectomy to reduce the risk of recurrent stroke after TIA.² The ideal timing of carotid endarterectomy is still being studied; however, available evidence supports intervention within 2 to 6 weeks after TIA or stroke.²⁵ Studies are ongoing that compare carotid angioplasty and stenting against carotid endarterectomy. Medical therapy, with antiplatelet agents and statins, is recommended after carotid endarterectomy.²⁵

Atrial fibrillation increases the risk of recurrent stroke after a TIA, and is the most important indication for secondary stroke prevention with anticoagulation therapy:

• Warfarin. Several studies have shown that warfarin provides a 68% relative risk reduction and a 1.4% absolute risk reduction in the annual stroke rate.²⁴ To achieve this reduction in risk, the optimal international normalized ratio is 2.5 (range, 2-3).²⁴
• Aspirin provides a 13% relative risk reduction for recurrent stroke, although there is evidence that long-term anticoagulation provides more benefit than aspirin after a TIA.^39-41 Optimal dosing of aspirin ranges from 75-100 mg/d; greatest benefit is likely in the 12 weeks after stroke, when the risk of recurrent stroke is highest.^31,41,42
• DOACs have similar efficacy to warfarin but more rapid onset, lower risk of bleeding, fewer drug interactions, and no requirement for monitoring—often making them a more tolerable long-term choice. Options are rivaroxaban 20 mg/d, dabigatran 150 mg twice daily, apixaban 5 mg twice daily, and edoxaban 60 mg/d.³⁹

Initial treatment of a TIA must include antiplatelet therapy, BP management, anticoagulation, and statin therapy; carotid endarterectomy might also be indicated.

When to start anticoagulation and the choice of agent should be weighed against a risk of bleeding, which is highest after the initial stroke. Cost is also a consideration: DOACs are more expensive than warfarin.

CASE

Mr. L is discharged 3 days after carotid endarterectomy and free of residual deficits. He is started on dual antiplatelet therapy (aspirin + clopidogrel) for 21 days, to be followed by a return to monotherapy. He is restarted on a high-intensity statin. He is instructed to resume taking the selective serotonin reuptake inhibitor and melatonin for sleep, as needed. Last, he is told to schedule follow-up with his primary care physician in 7 to 10 days to begin post-stroke care.

Final thoughts

Primary care physicians are often the first point of contact for patients with current or remote TIA symptoms. Based on that ­provider–patient relationship, evidence supports several recommendations for diagnosing and treating a TIA and for reducing the risk of recurrent stroke after TIA. Addressing each of these areas, in this order, is imperative to reduce the risk of recurrent stroke and improve overall cardiovascular outcomes:

• Obtain an accurate diagnosis of a TIA, using DW-MRI or comparable brain imaging, to allow for prompt intervention.
• Initiate BP management promptly in the acute setting and establish optimal BP control over the long term.
• Begin appropriate antiplatelet therapy.
• When indicated (eg, atrial fibrillation), begin anticoagulation therapy with a DOAC or warfarin.
• Begin high-intensity statin therapy.
• Consider treating patients with diabetes using an SGLT2 inhibitor or GLP-1 receptor agonist.
• Encourage smoking cessation, prescribe quit-smoking medications, or refer a smoker for behavioral support.

Education. Last, it is important to educate patients—especially those who have risk factors for a TIA or stroke—about the presentation of events, so that they know to seek immediate medical attention.

CORRESPONDENCE
Kristen Rundell, MD, Department of Family and Community Medicine, University of Arizona College of Medicine, 655 North Alvernon Way, Suite 228, Tucson, AZ 85711; [email protected]

As many as 240,000 people per year in the United States experience a transient ischemic attack (TIA),^1,2 which is now defined by the American Heart Association and American Stroke Association as a “transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.”³ An older definition of TIA was based on the duration of the event (ie, resolution of symptoms at 24 hours); in the updated (2009) definition, the diagnostic criterion is the extent of focal tissue damage.³ Using the 2009 definition might mean a decrease in the number of patients who have a diagnosis of a TIA and an increase in the number who are determined to have had a stroke because an infarction is found on initial imaging.

Guided by the 2009 revised definition of a TIA, we review here the work-up and treatment of TIA, emphasizing immediacy of management to (1) prevent further tissue damage and (2) decrease the risk of a second event.

Copyright Scott Bodell

CASE

Martin L, 69 years old, retired, a nonsmoker, and with a history of peripheral arterial disease and hypercholesterolemia, presents to the emergency department (ED) of a rural hospital complaining of slurred speech and left-side facial numbness. He had an episode of facial numbness that lasted 30 minutes, then resolved, each of the 2 previous evenings; he did not seek care at those times. Now, in the ED, Mr. L is normotensive.

The patient’s medication history includes a selective serotonin reuptake inhibitor and melatonin to improve sleep. He reports having discontinued a statin because he could not tolerate its adverse effects.

What immediate steps are recommended for Mr. L’s care?

Common event callsfor quick action

A TIA is the strongest predictor of subsequent stroke and stroke-related death; the highest period of risk of these devastating outcomes is immediately following a TIA.^1,2,4,5 It is essential, therefore, for the physician who sees a patient with a current complaint or recent history of suspected focal neurologic deficits to direct that patient to an ED for an accurate diagnosis and, as appropriate, early treatment for the best possible outcome.

A TIA is the strongest predictor of subsequent stroke and stroke-related death; the highest period of risk of these devastating outcomes is immediately following a TIA.

Imaging—preferably, diffusion-­weighted magnetic resonance imaging (DW-MRI), the gold standard for diagnosing stroke (see “Diagnosis includes ruling out mimics”)^2,3—should be performed as soon as the patient with a suspected TIA arrives in the ED. Imaging should not be held while waiting for a stroke to declare itself—ie, by allowing symptoms to persist for longer than 24 hours. ⁶

Continue to: Late presentation

Late presentation. Some patients present ≥ 48 hours after onset of early symptoms of a TIA; for them, the work-up is the same as for prompt presentation but can be completed in the outpatient clinic—as long as the patient is stable clinically and imaging is accessible there. DW-MRI should be completed within 48 hours after late presentation. In such cases, the patient should be cautioned regarding risks and any recurrence of symptoms.^7,8

Diagnosis includes ruling out mimics

All patients in whom a stroke is suspected should be evaluated on an emergency basis with brain imaging upon arrival at the hospital, before any therapy is initiated. As noted, DW-MRI is the preferred modality; noncontrast computed tomography (CT) or CT angiography can be used if MRI is unavailable.^2,3

Mimics. Stroke has many mimics; quickly eliminating them from the differential diagnosis is important so that appropriate therapy can be initiated. Mimics usually have a prolonged presentation of symptoms, whereas the presentation of a TIA is usually abrupt. The 3 more common diagnoses that mimic a TIA are migraine with aura, seizure, and syncope.^9,10 Symptoms that generally are not associated with a TIA are chest pain, generalized weakness, and confusion.¹¹ A complete history and physical exam provide the path to the imaging, laboratory, and cardiac testing that is needed to differentiate these diagnoses from a TIA.

A thorough history is best obtained from the patient and a witness, if available, and should include identification of any focal neurologic deficits and the duration and time to resolution of symptoms. Obtain a history of risk factors for ischemia—tobacco use, diabetes, obesity, dyslipidemia, hypertension, previous TIA or stroke, atrial fibrillation, and any coagulopathy. Ask questions about a family history of TIA, stroke, and coagulopathy.¹¹

A comprehensive physical exam, including vital signs, cardiac exam, a check for carotid bruits, and complete neurologic exam, should be performed. Most patients present with concerns for unilateral weakness and changes in speech, which are usually associated with infarction on DW-MRI.¹² The most common findings on physical exam include cranial nerve abnormalities, such as diplopia, hemianopia, monocular blindness, disconjugate gaze, facial drooping, lateral tongue movement, dysphagia, and vestibular dysfunction. Cerebellar abnormalities are also often noted, including past pointing, dystaxia, ataxia, nystagmus, and motor abnormalities (eg, spasticity, clonus, or unilateral weakness in the face or extremities).¹¹

Electrocardiography at the bedside can confirm atrial fibrillation or another arrhythmia quickly.

Essential laboratory testing includes measurement of blood glucose and serum electrolytes to determine if these particular imbalances are the cause of symptoms. The presence of a hypercoaguable state is determined by a complete blood count and coagulation studies.^3,13 Urine toxicology should also be obtained to rule out other causes of symptoms. A lipid profile is beneficial for making long-term treatment decisions.

Continue to: ABCD2 score

ABCD2 score. Patients who have had a TIA and present within 72 hours after symptoms have resolved should be hospitalized if they have an ABCD2 (Age, Blood pressure [BP], Clinical presentation, Diabetes mellitus [type 1 or 2], Duration of symptoms) prediction system score > 3.¹⁴ ABCD2 criteria can be used to help identify patients who are at higher risk of stroke or need further therapy (TABLE 1).^14,15

Send a patient with a current complaint or recent history of suspected focal neurologic deficits to an ED for accurate diagnosis of a possible TIA and, as appropriate, early treatment.

The ABCD2 score is also used to determine whether a patient needs dual antiplatelet therapy. Patients who score at the higher end of the ABCD2 system usually have an increased risk of stroke, longer hospitalization, and greater disability.

CASE

In the ED, Mr. L is immediately assessed and airlifted to a larger regional medical center, where MRI confirms a stroke.

Management

Initial management of a TIA is aimed at reducing the risk of recurrent TIA or stroke. Early medical and possibly surgical treatment are key for preventing stroke and improving outcomes. The first 48 hours after a TIA are the most critical because the incidence of recurrent TIA or stroke is highest during this period.^16-18

What is the accepted strategy for early treatment?

Initial treatment must include antiplatelet therapy, BP management, anticoagulation, statin therapy, and carotid endarterectomy as indicated.^2,19,20 Control of hypertension and anticoagulation decrease the risk of recurrent stroke by the largest margin²⁰; both are “A”-level Strength of Recommendation Taxonomy interventions.^2,3

Step 1: Antiplatelet therapy. After initial imaging is complete and if there are no contraindications, antiplatelet agents are recommended for patients who have had a noncardioembolic TIA. The American Heart Association and American Stroke Association recommend either aspirin, clopidogrel, dipyridamole + aspirin (available in a single capsule [Aggrenox]), or clopidogrel + aspirin as first-line therapy.^2,20 The choice of agent needs to be individualized, based on tolerability and adverse effects (TABLE 2^2,20,21).

A meta-analysis of antiplatelet therapy reviewed the optimum dosing of each medication.^21,22 Reduction of the risk of ischemic stroke with aspirin is 21% to 22% at the optimal dosing of 75 to 150 mg/d, which also reduces the risk of gastrointestinal bleeding.

Continue to: For a patient who has...

For a patient who has an ABCD2 score ≥ 4, has had a prior TIA, or has large-vessel disease, dual antiplatelet therapy is recommended for the first 21 days, with a subsequent return to monotherapy. Dual antiplatelet therapy of clopidogrel + aspirin increases the risk of adverse reactions and has not been shown to have greater long-term benefit^23-25 (TABLE 2^2,20,21).

Step 2: BP management. This is the next immediate step. As many as 80% of patients who present with a TIA have elevated BP upon admission. BP needs to be treated and carefully monitored during this early treatment phase. The recommendation is for a systolic BP < 185 mm Hg and a diastolic BP < 110 mm Hg.²⁴

Step 3: Anticoagulation. Treatment with warfarin or a direct oral anticoagulant (DOAC) is recommended for patients who have the potential for forming emboli—eg, in the setting of atrial fibrillation, ventricular thrombus, mechanical heart valve, or venous thromboembolism.

Step 4. High-intensity statin. A statin agent is recommended as part of immediate and long-term medical management, regardless of the low-density lipoprotein cholesterol (LDL-C) level, to reduce the risk of stroke.^2,24

Carotid artery management. Surgical intervention is not always considered a component of immediate medical management. However, guidelines recommend that carotid endarterectomy or stenting be considered in patients who have stenosis > 70%.²

CASE

Mr. L is admitted to the hospital and undergoes neurosurgical intervention. Medical management is instituted.

Long-term management and secondary prevention

The main risk factors for stroke can be divided into modifiable, vascular, and unmodifiable. Addressing both modifiable and vascular risks is important for secondary prevention.

Continue to: Modifiable and vascular risk factors

Modifiable risk factors for stroke include hypertension, diabetes, dyslipidemia, smoking, and physical activity; the most important of these, for preventing subsequent stroke after an initial TIA, is hypertension.²⁶

The 2 more significant vascular risk factors for stroke are carotid artery stenosis and atrial fibrillation.

Hypertension. Improving control of hypertension can improve secondary risk reduction for recurrent stroke. Control of both systolic and diastolic BP is important in this regard, with larger systolic BP reductions having a greater impact on decreasing the risk of recurrent stroke.²⁴ Evidence supports lowering BP to improve secondary risk reduction in people with and without diagnosed hypertension: The goal is to lower systolic BP by ≥ 10 mm Hg and diastolic BP by 5 mm Hg.²⁴ No particular class of antihypertensive is recommended in the first line, although preliminary evidence shows that a diuretic, with or without an angiotensin-converting enzyme inhibitor, might be more beneficial than other options.²⁴

Diabetes. The risk of cardiovascular disease, including stroke, is higher in people with diabetes. Evidence shows that various (but not all) agents in 2 pharmaceutical classes—glucagon-like peptide-1 (GLP-1) receptor agonists and the sodium glucose-2 cotransporter (SGLT2) inhibitors—reduce the risk of major cardiovascular events and improve secondary prevention of recurrent stroke:

• EMPA-REG OUTCOME (ClinicalTrials.gov Identifier: NCT01131676) was the first trial to show cardiovascular benefit from an SGLT2 inhibitor (empagliflozin); subsequent studies confirmed the cardiovascular benefits found in EMPA-REG OUTCOME.^27,28
• The ELIXA trial (ClinicalTrials.gov Identifier: NCT01147250) was the first to show cardiovascular benefit from a GLP-1 receptor agonist (lixisenatide); subsequent studies supported this finding.^29,30

Appropriate agents in these 2 classes should be considered as first-line or adjunctive in patients with both diabetes and known cardiovascular disease, as long as there are no contraindications.^27,28

Pioglitazone, a thiazolidinedione-class antidiabetic agent, was once considered a potential option to improve secondary prevention of stroke. However, the thiazolidinediones are generally no longer considered; instead, the SGLT2 inhibitors and GLP-1 receptor agonists are favored.³¹

Evidence demonstrates the effect of hyperglycemia on cardiovascular events; however, it is important to note that hypoglycemia can result in symptoms and focal changes that mimic a stroke. In addition, some evidence suggests that hypoglycemia can increase cardiovascular risk—thereby supporting the importance of strict control of diabetes and maintenance of euglycemia in reducing overall cardiovascular risk.³²

Continue to: Lipids

Lipids. The SPARCL trial (ClinicalTrials.gov Identifier: NCT00147602) was the first study to demonstrate the benefit of high-­intensity statin therapy—specifically, atorvastatin 80 mg/d—for secondary prevention for recurrent stroke.³³ The recommendation is to use high-intensity statin therapy to decrease the risk of recurrent stroke by reducing the level of LDL-C—by ≥ 50% or to < 70 mg/dL, for maximum risk reduction.^24,34

Common conditions that mimic a TIA are migraine with aura, seizure, and syncope; a TIA is generally not associated with chest pain, generalized weakness, or confusion.

The IMPROVE-IT trial (ClinicalTrials.gov Identifier: NCT00202878) demonstrated the benefit of adding ezetimibe, 10 mg/d, to a moderate-to-high-intensity statin (simvastatin, 40-80 mg/d) to reduce the risk of recurrent stroke.³⁵

Results of recent studies support the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for regulating levels of LDL-C, as an additional option to consider—if needed to further reduce the LDL-C level or if statins are contraindicated in a particular patient.³⁴

Smoking cessation. Cigarette smoking is known to increase the risk of ischemic stroke; newer evidence shows that second-hand exposure to smoke also increases the risk of ischemic stroke.^36,37 Although these studies focused on primary prevention of ischemic stroke, the data can reasonably be applied to secondary prevention.³⁸ The recommendation for secondary prevention is to quit smoking and avoid secondhand smoke.²⁴

Alcohol. Evidence demonstrates that heavy alcohol consumption and alcoholism increase the risk of stroke; similar to what is known about smoking, most available data relate to primary prevention.³⁸ The recommendation for providing secondary stroke prevention is to stop or decrease alcohol intake.²⁴

Weight reduction. Obesity (body mass index > 30) increases the risk of ischemic stroke. However, there is, as yet, no evidence that weight loss diminishes the risk of subsequent stroke for secondary prevention.²⁴

Physical activity. Aerobic exercise and strength-training programs after a stroke improve cardiovascular health and mobility. There is no evidence that exercise leads to a reduction in the risk of subsequent stroke.²⁴

Continue to: Nutrition

Nutrition. No current randomized controlled trials are focused on the relationship between diet and recurrent stroke for purposes of prevention; however, evidence for both BP and lipid control incorporate dietary guidance. Recommendations include reducing intake of saturated fats and of sodium (the latter, to < 2.3 g/d) and increasing intake of fruits and vegetables, both of which are beneficial for controlling BP and lipid levels and promoting overall cardiovascular health.³⁸

Carotid artery stenosis. Several randomized controlled trials have demonstrated benefit from treating carotid stenosis (> 70% stenosis but not < 50%) with carotid endarterectomy to reduce the risk of recurrent stroke after TIA.² The ideal timing of carotid endarterectomy is still being studied; however, available evidence supports intervention within 2 to 6 weeks after TIA or stroke.²⁵ Studies are ongoing that compare carotid angioplasty and stenting against carotid endarterectomy. Medical therapy, with antiplatelet agents and statins, is recommended after carotid endarterectomy.²⁵

Atrial fibrillation increases the risk of recurrent stroke after a TIA, and is the most important indication for secondary stroke prevention with anticoagulation therapy:

• Warfarin. Several studies have shown that warfarin provides a 68% relative risk reduction and a 1.4% absolute risk reduction in the annual stroke rate.²⁴ To achieve this reduction in risk, the optimal international normalized ratio is 2.5 (range, 2-3).²⁴
• Aspirin provides a 13% relative risk reduction for recurrent stroke, although there is evidence that long-term anticoagulation provides more benefit than aspirin after a TIA.^39-41 Optimal dosing of aspirin ranges from 75-100 mg/d; greatest benefit is likely in the 12 weeks after stroke, when the risk of recurrent stroke is highest.^31,41,42
• DOACs have similar efficacy to warfarin but more rapid onset, lower risk of bleeding, fewer drug interactions, and no requirement for monitoring—often making them a more tolerable long-term choice. Options are rivaroxaban 20 mg/d, dabigatran 150 mg twice daily, apixaban 5 mg twice daily, and edoxaban 60 mg/d.³⁹

Initial treatment of a TIA must include antiplatelet therapy, BP management, anticoagulation, and statin therapy; carotid endarterectomy might also be indicated.

When to start anticoagulation and the choice of agent should be weighed against a risk of bleeding, which is highest after the initial stroke. Cost is also a consideration: DOACs are more expensive than warfarin.

CASE

Mr. L is discharged 3 days after carotid endarterectomy and free of residual deficits. He is started on dual antiplatelet therapy (aspirin + clopidogrel) for 21 days, to be followed by a return to monotherapy. He is restarted on a high-intensity statin. He is instructed to resume taking the selective serotonin reuptake inhibitor and melatonin for sleep, as needed. Last, he is told to schedule follow-up with his primary care physician in 7 to 10 days to begin post-stroke care.

Final thoughts

Primary care physicians are often the first point of contact for patients with current or remote TIA symptoms. Based on that ­provider–patient relationship, evidence supports several recommendations for diagnosing and treating a TIA and for reducing the risk of recurrent stroke after TIA. Addressing each of these areas, in this order, is imperative to reduce the risk of recurrent stroke and improve overall cardiovascular outcomes:

• Obtain an accurate diagnosis of a TIA, using DW-MRI or comparable brain imaging, to allow for prompt intervention.
• Initiate BP management promptly in the acute setting and establish optimal BP control over the long term.
• Begin appropriate antiplatelet therapy.
• When indicated (eg, atrial fibrillation), begin anticoagulation therapy with a DOAC or warfarin.
• Begin high-intensity statin therapy.
• Consider treating patients with diabetes using an SGLT2 inhibitor or GLP-1 receptor agonist.
• Encourage smoking cessation, prescribe quit-smoking medications, or refer a smoker for behavioral support.

Education. Last, it is important to educate patients—especially those who have risk factors for a TIA or stroke—about the presentation of events, so that they know to seek immediate medical attention.

CORRESPONDENCE
Kristen Rundell, MD, Department of Family and Community Medicine, University of Arizona College of Medicine, 655 North Alvernon Way, Suite 228, Tucson, AZ 85711; [email protected]

As many as 240,000 people per year in the United States experience a transient ischemic attack (TIA),^1,2 which is now defined by the American Heart Association and American Stroke Association as a “transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.”³ An older definition of TIA was based on the duration of the event (ie, resolution of symptoms at 24 hours); in the updated (2009) definition, the diagnostic criterion is the extent of focal tissue damage.³ Using the 2009 definition might mean a decrease in the number of patients who have a diagnosis of a TIA and an increase in the number who are determined to have had a stroke because an infarction is found on initial imaging.

Guided by the 2009 revised definition of a TIA, we review here the work-up and treatment of TIA, emphasizing immediacy of management to (1) prevent further tissue damage and (2) decrease the risk of a second event.

Copyright Scott Bodell

CASE

Martin L, 69 years old, retired, a nonsmoker, and with a history of peripheral arterial disease and hypercholesterolemia, presents to the emergency department (ED) of a rural hospital complaining of slurred speech and left-side facial numbness. He had an episode of facial numbness that lasted 30 minutes, then resolved, each of the 2 previous evenings; he did not seek care at those times. Now, in the ED, Mr. L is normotensive.

The patient’s medication history includes a selective serotonin reuptake inhibitor and melatonin to improve sleep. He reports having discontinued a statin because he could not tolerate its adverse effects.

What immediate steps are recommended for Mr. L’s care?

Common event callsfor quick action

A TIA is the strongest predictor of subsequent stroke and stroke-related death; the highest period of risk of these devastating outcomes is immediately following a TIA.^1,2,4,5 It is essential, therefore, for the physician who sees a patient with a current complaint or recent history of suspected focal neurologic deficits to direct that patient to an ED for an accurate diagnosis and, as appropriate, early treatment for the best possible outcome.

A TIA is the strongest predictor of subsequent stroke and stroke-related death; the highest period of risk of these devastating outcomes is immediately following a TIA.

Imaging—preferably, diffusion-­weighted magnetic resonance imaging (DW-MRI), the gold standard for diagnosing stroke (see “Diagnosis includes ruling out mimics”)^2,3—should be performed as soon as the patient with a suspected TIA arrives in the ED. Imaging should not be held while waiting for a stroke to declare itself—ie, by allowing symptoms to persist for longer than 24 hours. ⁶

Continue to: Late presentation

Late presentation. Some patients present ≥ 48 hours after onset of early symptoms of a TIA; for them, the work-up is the same as for prompt presentation but can be completed in the outpatient clinic—as long as the patient is stable clinically and imaging is accessible there. DW-MRI should be completed within 48 hours after late presentation. In such cases, the patient should be cautioned regarding risks and any recurrence of symptoms.^7,8

Diagnosis includes ruling out mimics

All patients in whom a stroke is suspected should be evaluated on an emergency basis with brain imaging upon arrival at the hospital, before any therapy is initiated. As noted, DW-MRI is the preferred modality; noncontrast computed tomography (CT) or CT angiography can be used if MRI is unavailable.^2,3

Mimics. Stroke has many mimics; quickly eliminating them from the differential diagnosis is important so that appropriate therapy can be initiated. Mimics usually have a prolonged presentation of symptoms, whereas the presentation of a TIA is usually abrupt. The 3 more common diagnoses that mimic a TIA are migraine with aura, seizure, and syncope.^9,10 Symptoms that generally are not associated with a TIA are chest pain, generalized weakness, and confusion.¹¹ A complete history and physical exam provide the path to the imaging, laboratory, and cardiac testing that is needed to differentiate these diagnoses from a TIA.

A thorough history is best obtained from the patient and a witness, if available, and should include identification of any focal neurologic deficits and the duration and time to resolution of symptoms. Obtain a history of risk factors for ischemia—tobacco use, diabetes, obesity, dyslipidemia, hypertension, previous TIA or stroke, atrial fibrillation, and any coagulopathy. Ask questions about a family history of TIA, stroke, and coagulopathy.¹¹

A comprehensive physical exam, including vital signs, cardiac exam, a check for carotid bruits, and complete neurologic exam, should be performed. Most patients present with concerns for unilateral weakness and changes in speech, which are usually associated with infarction on DW-MRI.¹² The most common findings on physical exam include cranial nerve abnormalities, such as diplopia, hemianopia, monocular blindness, disconjugate gaze, facial drooping, lateral tongue movement, dysphagia, and vestibular dysfunction. Cerebellar abnormalities are also often noted, including past pointing, dystaxia, ataxia, nystagmus, and motor abnormalities (eg, spasticity, clonus, or unilateral weakness in the face or extremities).¹¹

Electrocardiography at the bedside can confirm atrial fibrillation or another arrhythmia quickly.

Essential laboratory testing includes measurement of blood glucose and serum electrolytes to determine if these particular imbalances are the cause of symptoms. The presence of a hypercoaguable state is determined by a complete blood count and coagulation studies.^3,13 Urine toxicology should also be obtained to rule out other causes of symptoms. A lipid profile is beneficial for making long-term treatment decisions.

Continue to: ABCD2 score

ABCD2 score. Patients who have had a TIA and present within 72 hours after symptoms have resolved should be hospitalized if they have an ABCD2 (Age, Blood pressure [BP], Clinical presentation, Diabetes mellitus [type 1 or 2], Duration of symptoms) prediction system score > 3.¹⁴ ABCD2 criteria can be used to help identify patients who are at higher risk of stroke or need further therapy (TABLE 1).^14,15

Send a patient with a current complaint or recent history of suspected focal neurologic deficits to an ED for accurate diagnosis of a possible TIA and, as appropriate, early treatment.

The ABCD2 score is also used to determine whether a patient needs dual antiplatelet therapy. Patients who score at the higher end of the ABCD2 system usually have an increased risk of stroke, longer hospitalization, and greater disability.

CASE

In the ED, Mr. L is immediately assessed and airlifted to a larger regional medical center, where MRI confirms a stroke.

Management

Initial management of a TIA is aimed at reducing the risk of recurrent TIA or stroke. Early medical and possibly surgical treatment are key for preventing stroke and improving outcomes. The first 48 hours after a TIA are the most critical because the incidence of recurrent TIA or stroke is highest during this period.^16-18

What is the accepted strategy for early treatment?

Initial treatment must include antiplatelet therapy, BP management, anticoagulation, statin therapy, and carotid endarterectomy as indicated.^2,19,20 Control of hypertension and anticoagulation decrease the risk of recurrent stroke by the largest margin²⁰; both are “A”-level Strength of Recommendation Taxonomy interventions.^2,3

Step 1: Antiplatelet therapy. After initial imaging is complete and if there are no contraindications, antiplatelet agents are recommended for patients who have had a noncardioembolic TIA. The American Heart Association and American Stroke Association recommend either aspirin, clopidogrel, dipyridamole + aspirin (available in a single capsule [Aggrenox]), or clopidogrel + aspirin as first-line therapy.^2,20 The choice of agent needs to be individualized, based on tolerability and adverse effects (TABLE 2^2,20,21).

A meta-analysis of antiplatelet therapy reviewed the optimum dosing of each medication.^21,22 Reduction of the risk of ischemic stroke with aspirin is 21% to 22% at the optimal dosing of 75 to 150 mg/d, which also reduces the risk of gastrointestinal bleeding.

Continue to: For a patient who has...

For a patient who has an ABCD2 score ≥ 4, has had a prior TIA, or has large-vessel disease, dual antiplatelet therapy is recommended for the first 21 days, with a subsequent return to monotherapy. Dual antiplatelet therapy of clopidogrel + aspirin increases the risk of adverse reactions and has not been shown to have greater long-term benefit^23-25 (TABLE 2^2,20,21).

Step 2: BP management. This is the next immediate step. As many as 80% of patients who present with a TIA have elevated BP upon admission. BP needs to be treated and carefully monitored during this early treatment phase. The recommendation is for a systolic BP < 185 mm Hg and a diastolic BP < 110 mm Hg.²⁴

Step 3: Anticoagulation. Treatment with warfarin or a direct oral anticoagulant (DOAC) is recommended for patients who have the potential for forming emboli—eg, in the setting of atrial fibrillation, ventricular thrombus, mechanical heart valve, or venous thromboembolism.

Step 4. High-intensity statin. A statin agent is recommended as part of immediate and long-term medical management, regardless of the low-density lipoprotein cholesterol (LDL-C) level, to reduce the risk of stroke.^2,24

Carotid artery management. Surgical intervention is not always considered a component of immediate medical management. However, guidelines recommend that carotid endarterectomy or stenting be considered in patients who have stenosis > 70%.²

CASE

Mr. L is admitted to the hospital and undergoes neurosurgical intervention. Medical management is instituted.

Long-term management and secondary prevention

The main risk factors for stroke can be divided into modifiable, vascular, and unmodifiable. Addressing both modifiable and vascular risks is important for secondary prevention.

Continue to: Modifiable and vascular risk factors

Modifiable risk factors for stroke include hypertension, diabetes, dyslipidemia, smoking, and physical activity; the most important of these, for preventing subsequent stroke after an initial TIA, is hypertension.²⁶

The 2 more significant vascular risk factors for stroke are carotid artery stenosis and atrial fibrillation.

Hypertension. Improving control of hypertension can improve secondary risk reduction for recurrent stroke. Control of both systolic and diastolic BP is important in this regard, with larger systolic BP reductions having a greater impact on decreasing the risk of recurrent stroke.²⁴ Evidence supports lowering BP to improve secondary risk reduction in people with and without diagnosed hypertension: The goal is to lower systolic BP by ≥ 10 mm Hg and diastolic BP by 5 mm Hg.²⁴ No particular class of antihypertensive is recommended in the first line, although preliminary evidence shows that a diuretic, with or without an angiotensin-converting enzyme inhibitor, might be more beneficial than other options.²⁴

Diabetes. The risk of cardiovascular disease, including stroke, is higher in people with diabetes. Evidence shows that various (but not all) agents in 2 pharmaceutical classes—glucagon-like peptide-1 (GLP-1) receptor agonists and the sodium glucose-2 cotransporter (SGLT2) inhibitors—reduce the risk of major cardiovascular events and improve secondary prevention of recurrent stroke:

• EMPA-REG OUTCOME (ClinicalTrials.gov Identifier: NCT01131676) was the first trial to show cardiovascular benefit from an SGLT2 inhibitor (empagliflozin); subsequent studies confirmed the cardiovascular benefits found in EMPA-REG OUTCOME.^27,28
• The ELIXA trial (ClinicalTrials.gov Identifier: NCT01147250) was the first to show cardiovascular benefit from a GLP-1 receptor agonist (lixisenatide); subsequent studies supported this finding.^29,30

Appropriate agents in these 2 classes should be considered as first-line or adjunctive in patients with both diabetes and known cardiovascular disease, as long as there are no contraindications.^27,28

Pioglitazone, a thiazolidinedione-class antidiabetic agent, was once considered a potential option to improve secondary prevention of stroke. However, the thiazolidinediones are generally no longer considered; instead, the SGLT2 inhibitors and GLP-1 receptor agonists are favored.³¹

Evidence demonstrates the effect of hyperglycemia on cardiovascular events; however, it is important to note that hypoglycemia can result in symptoms and focal changes that mimic a stroke. In addition, some evidence suggests that hypoglycemia can increase cardiovascular risk—thereby supporting the importance of strict control of diabetes and maintenance of euglycemia in reducing overall cardiovascular risk.³²

Continue to: Lipids

Lipids. The SPARCL trial (ClinicalTrials.gov Identifier: NCT00147602) was the first study to demonstrate the benefit of high-­intensity statin therapy—specifically, atorvastatin 80 mg/d—for secondary prevention for recurrent stroke.³³ The recommendation is to use high-intensity statin therapy to decrease the risk of recurrent stroke by reducing the level of LDL-C—by ≥ 50% or to < 70 mg/dL, for maximum risk reduction.^24,34

Common conditions that mimic a TIA are migraine with aura, seizure, and syncope; a TIA is generally not associated with chest pain, generalized weakness, or confusion.

The IMPROVE-IT trial (ClinicalTrials.gov Identifier: NCT00202878) demonstrated the benefit of adding ezetimibe, 10 mg/d, to a moderate-to-high-intensity statin (simvastatin, 40-80 mg/d) to reduce the risk of recurrent stroke.³⁵

Results of recent studies support the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for regulating levels of LDL-C, as an additional option to consider—if needed to further reduce the LDL-C level or if statins are contraindicated in a particular patient.³⁴

Smoking cessation. Cigarette smoking is known to increase the risk of ischemic stroke; newer evidence shows that second-hand exposure to smoke also increases the risk of ischemic stroke.^36,37 Although these studies focused on primary prevention of ischemic stroke, the data can reasonably be applied to secondary prevention.³⁸ The recommendation for secondary prevention is to quit smoking and avoid secondhand smoke.²⁴

Alcohol. Evidence demonstrates that heavy alcohol consumption and alcoholism increase the risk of stroke; similar to what is known about smoking, most available data relate to primary prevention.³⁸ The recommendation for providing secondary stroke prevention is to stop or decrease alcohol intake.²⁴

Weight reduction. Obesity (body mass index > 30) increases the risk of ischemic stroke. However, there is, as yet, no evidence that weight loss diminishes the risk of subsequent stroke for secondary prevention.²⁴

Physical activity. Aerobic exercise and strength-training programs after a stroke improve cardiovascular health and mobility. There is no evidence that exercise leads to a reduction in the risk of subsequent stroke.²⁴

Continue to: Nutrition

Nutrition. No current randomized controlled trials are focused on the relationship between diet and recurrent stroke for purposes of prevention; however, evidence for both BP and lipid control incorporate dietary guidance. Recommendations include reducing intake of saturated fats and of sodium (the latter, to < 2.3 g/d) and increasing intake of fruits and vegetables, both of which are beneficial for controlling BP and lipid levels and promoting overall cardiovascular health.³⁸

Carotid artery stenosis. Several randomized controlled trials have demonstrated benefit from treating carotid stenosis (> 70% stenosis but not < 50%) with carotid endarterectomy to reduce the risk of recurrent stroke after TIA.² The ideal timing of carotid endarterectomy is still being studied; however, available evidence supports intervention within 2 to 6 weeks after TIA or stroke.²⁵ Studies are ongoing that compare carotid angioplasty and stenting against carotid endarterectomy. Medical therapy, with antiplatelet agents and statins, is recommended after carotid endarterectomy.²⁵

Atrial fibrillation increases the risk of recurrent stroke after a TIA, and is the most important indication for secondary stroke prevention with anticoagulation therapy:

• Warfarin. Several studies have shown that warfarin provides a 68% relative risk reduction and a 1.4% absolute risk reduction in the annual stroke rate.²⁴ To achieve this reduction in risk, the optimal international normalized ratio is 2.5 (range, 2-3).²⁴
• Aspirin provides a 13% relative risk reduction for recurrent stroke, although there is evidence that long-term anticoagulation provides more benefit than aspirin after a TIA.^39-41 Optimal dosing of aspirin ranges from 75-100 mg/d; greatest benefit is likely in the 12 weeks after stroke, when the risk of recurrent stroke is highest.^31,41,42
• DOACs have similar efficacy to warfarin but more rapid onset, lower risk of bleeding, fewer drug interactions, and no requirement for monitoring—often making them a more tolerable long-term choice. Options are rivaroxaban 20 mg/d, dabigatran 150 mg twice daily, apixaban 5 mg twice daily, and edoxaban 60 mg/d.³⁹

Initial treatment of a TIA must include antiplatelet therapy, BP management, anticoagulation, and statin therapy; carotid endarterectomy might also be indicated.

When to start anticoagulation and the choice of agent should be weighed against a risk of bleeding, which is highest after the initial stroke. Cost is also a consideration: DOACs are more expensive than warfarin.

CASE

Mr. L is discharged 3 days after carotid endarterectomy and free of residual deficits. He is started on dual antiplatelet therapy (aspirin + clopidogrel) for 21 days, to be followed by a return to monotherapy. He is restarted on a high-intensity statin. He is instructed to resume taking the selective serotonin reuptake inhibitor and melatonin for sleep, as needed. Last, he is told to schedule follow-up with his primary care physician in 7 to 10 days to begin post-stroke care.

Final thoughts

Primary care physicians are often the first point of contact for patients with current or remote TIA symptoms. Based on that ­provider–patient relationship, evidence supports several recommendations for diagnosing and treating a TIA and for reducing the risk of recurrent stroke after TIA. Addressing each of these areas, in this order, is imperative to reduce the risk of recurrent stroke and improve overall cardiovascular outcomes:

• Obtain an accurate diagnosis of a TIA, using DW-MRI or comparable brain imaging, to allow for prompt intervention.
• Initiate BP management promptly in the acute setting and establish optimal BP control over the long term.
• Begin appropriate antiplatelet therapy.
• When indicated (eg, atrial fibrillation), begin anticoagulation therapy with a DOAC or warfarin.
• Begin high-intensity statin therapy.
• Consider treating patients with diabetes using an SGLT2 inhibitor or GLP-1 receptor agonist.
• Encourage smoking cessation, prescribe quit-smoking medications, or refer a smoker for behavioral support.

Education. Last, it is important to educate patients—especially those who have risk factors for a TIA or stroke—about the presentation of events, so that they know to seek immediate medical attention.

CORRESPONDENCE
Kristen Rundell, MD, Department of Family and Community Medicine, University of Arizona College of Medicine, 655 North Alvernon Way, Suite 228, Tucson, AZ 85711; [email protected]

THE CASE

Janice J* visits her family physician with complaints of chest pain, shortness of breath, and heart palpitations that are usually worse at night. Her medical history is significant for deep vein thrombosis secondary to an underlying hypercoagulability condition (rheumatoid arthritis) diagnosed 2 months earlier. She also has a history of opioid use disorder and has been on buprenorphine/naloxone therapy for 3 years. Her family medical history is unremarkable. She works full-time and lives with her 8-year-old son. On physical exam, she appears anxious; her cardiac and pulmonary exams are normal. A completed workup rules out cardiac or pulmonary problems.

• What is your diagnosis?
• How would you treat this patient?

* The patient’s name has been changed to protect her identity.

CO-OCCURRING DISORDERS: SCOPE OF THE PROBLEM

Co-occurring disorders, previously called “dual diagnosis,” refers to the coexistence of a mental health disorder and a substance use disorder. The obsolete term, dual diagnosis, specified the presence of 2 co-occurring Axis I diagnoses or the presence of an Axis I diagnosis and an Axis II diagnosis (such as mental disability). The change in nomenclature more precisely describes the co-existing mental health and substance use disorders.

Currently the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, (DSM-5) includes no diagnostic criteria for this dual condition.¹ The criteria for mental health disorders and for substance use disorders comprise separate lists. Criteria for substance use disorder fall broadly into categories of “impaired [self] control, social impairment, risky behaviors, increased tolerance, and withdrawal symptoms.”¹ It is estimated that 8.5 million US adults have co-occurring disorders, per the 2017 National Survey on Drug Use and Health conducted by the Substance Abuse and Mental Health Services Administration.² Distinguishing which of the 2 conditions occurred first can be challenging. It has been suggested that the lifetime prevalence of a mental health disorder with a coexisting substance use disorder is greater than 40%^3,4 (TABLE 1^1,4-8). For patients with schizophrenia and bipolar disorder, these numbers may be higher.

The consequences of undiagnosed and untreated co-occurring disorders include poor medication adherence, physical comorbidities (and decreased overall health), diminished self-care, increased suicide risk or aggression, increased risky sexual behavior, and possible incarceration.⁹

WHEN SHOULD YOU SUSPECT CO-OCCURRING DISORDERS?

With some patients, only one diagnosis may be apparent at a given point, which could make it difficult to expeditiously recognize the onset of a co-occurring condition. For example, if a patient with anxiety has been treated successfully for years and then experiences a worsening of symptoms, it’s possible a physician might increase the dosage of anxiety medication without reevaluating for a substance use disorder. However, when both co-occurring disorders are present, the patient usually exhibits a greater number of symptoms and, if the full scope of the condition remains unrecognized, will likely respond poorly to therapy and have a prolonged course to resolution.^3,8-13 Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

The estimated lifetime prevalence of coexisting mental health and substance use disorders is > 40%.

Diagnosing a second condition can also be difficult when a patient’s symptoms are actually adverse effects of substances or prescribed medications. For example, a patient with worsening anxiety may also exhibit increasing blood pressure resistant to treatment. The cause of the patient’s fluctuating blood pressures may actually be the result of his or her use of alcohol to self-treat the anxiety. In addition to self-medication, other underlying factors may be at play, including genetic vulnerability, environment, and lifestyle.¹⁴ In the case we present, the patient’s conditions arose independently.

Anxiety disorders, with a lifetime risk of 28.8% in the US population,⁴ may be the primary mental health issue in many patients with co-occurring disorders, but this cannot be assumed in lieu of a complete workup.^2,8,9,15 Substance use disorders in the general population have a past-year and lifetime prevalence of 14.6%.^1,4,16,17 Because the causal and temporal association between anxiety and substance abuse is not always clear, it’s important to separate the diagnoses of the mental health and substance use disorders.

Continue to: MAKING THE DIAGNOSIS

To make an accurate diagnosis of co-occurring disorder, it is essential to take a complete history focusing on the timeline of symptoms, previous diagnoses and treatments, if any, and substance-free periods. Details gathered from these inquiries will help to separate symptoms of a primary mental health disorder from adverse effects of medication, withdrawal symptoms, or symptoms related to an underlying chronic medical condition.

Optimally, the diagnosis of a mental health disorder should be considered following a ­substance-free period. If this is not possible, a chart review may reveal a time when the patient did not have a substance use ­disorder.¹⁸

A diagnosis of substance use disorder requires that the patient manifest at least 2 of 11 behaviors listed in the DSM-5 over a 12-month period.¹ The criteria focus on the amount of substance used, the time spent securing the substance, risky behaviors associated with the substance, and tolerance to the substance.

DON'T DEFER MENTAL HEALTH Tx

It is necessary to treat co-occurring disorders simultaneously. The old idea of deferring treatment of a mental health issue until the substance use disorder is resolved no longer ­applies.^19,20 Treating substance use problems without addressing comorbid mental health ­issues can negatively impact treatment progress and increase risk for relapse. In a similar way, leaving substance use problems untreated is associated with nonadherence in mental health treatment, poor engagement, and dropout.^21,22

Integrated services. Due to this condition’s level of clinical complexity, the optimal treatment approach is an interdisciplinary one in which integrated services are offered at a single location by a team of medical, mental health, and substance use providers (see “The case for behavioral health integration into primary care” in the June issue). An evidence-based example of such an approach is the Integrated Dual Disorder Treatment (IDDT) model—a comprehensive, integrated method of treating severe mental health disorders, including substance use disorders.^21,22 IDDT combines coordinated services such as pharmacologic, psychological, educational, and social interventions to address the needs of patients and their family members. The IDDT model conceptualizes and treats co-occurring disorders within a biopsychosocial framework. Specific services may include medical detoxification, pharmacotherapy, patient and family education, behavioral and cognitive therapies, contingency management, self-help support groups, supported employment, residential/housing assistance, and case management services.^23,24

Continue to: Medications for the mental health component

Medications for the mental health component. For patients who prefer medication treatment to cognitive behavioral therapy (CBT), or for whom CBT is unavailable, treat the mental health disorder per customary practice for the diagnosis (TABLE 2^25-30). For psychotic disorders, use an antipsychotic, adding a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) as needed depending on the presence of negative symptoms.^25,31 For bipolar spectrum disorder, start a mood stabilizer³²; for depressive disorders initiate an SSRI or SNRI.²⁷ Anxiety disorders respond optimally when treated with SSRIs or SNRIs. Buspirone may be prescribed alone or as an adjunct for anxiety, and it does not cause mood-altering or withdrawal effects. Benzodiazepines in a controlled and monitored setting are an option in some antianxiety treatment plans. Consultation with a psychiatrist will help to determine the best treatment in these situations.

In all cases, treat the substance use disorder concurrently. Treatment options vary depending on the substance of choice. Although often overlooked, there can be simultaneous nicotine abuse. Oral or inhaled medications for nicotine abuse treatment are limited. The range of pharmacologic options for alcohol use disorder includes naltrexone, acamprosate, and disulfiram.^29,33 Pharmacologic treatment options for opioid use disorder include naltrexone, methadone, and a combination of naloxone and buprenorphine.³⁴

Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

Physicians who wish to prescribe buprenorphine must qualify for and complete a certified 8 hour waiver-training course, which is then approved by the Drug Enforcement Agency (under the DATA 2000 – Drug and Alcohol Act 2000). The physician obtains the designation of a data-waived physician and is assigned a special identification number to prescribe these medications.^35,36 Methadone may be provided only in a licensed methadone maintenance program. Regular and random drug urine screen requirements apply to all treatment programs.

Psychosocial and behavioral interventions are essential to the successful treatment of co-occurring disorders. Evidence-based behavioral and cognitive therapies are recommended for promoting adaptive coping skills and healthy lifestyle behaviors in co-occurring disorder populations.^23,24,37-40 Motivational interviewing enhances motivation and adherence when patients demonstrate resistance or ambivalence.^41,42 Mindfulness-based interventions have been shown to be effective and may be particularly beneficial for treating cravings/­urges and promoting relapse prevention.^{37,39,40,43-46}

Psychotropic medications, as with other treatment components, are most effective when used in combination with services that simultaneously address the patient’s biological, psychological, and social needs.

Continue to: The grassroots organization...

The grassroots organization National Alliance on Mental Illness (www.nami.org) recommends self-help and support groups, which include 12-step, faith-based and non-faith–based programs.²⁰

For any treatment method to be successful, there needs to be a level of customization and individualization. Some patients may respond to medication or nonmedication treatments only, and others may need a combination of treatments.

CASE

The physician recalls a past diagnosis of anxiety and asks Ms. J if there are any new stressors or changes causing concern. The patient expresses concern about an opioid use relapse secondary to her recent diagnosis of rheumatoid arthritis, which may be life altering or limiting.

Even though she has been doing well and has been adherent to her daily buprenorphine treatment, she worries for the well-being of her family and what would happen if she cannot work, becomes incapacitated, or dies at a young age. She has never considered herself an anxious person and is surprised that anxiety could cause such pronounced physical symptoms.

Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

The physician discusses different modalities of treatment, including counseling with an onsite psychologist, a trial of an anti-anxiety medication such as sertraline, or return office visits with the physician. They decide first to schedule an appointment with the psychologist, and Ms. J promises to find more time for self-wellness activities, such as exercise.

After 3 months of therapy, the patient decides to space out treatment to every 2 to 3 months and does not report any more episodes of chest pain or shortness of breath.

CORRESPONDENCE
Kristen Rundell, MD, Northwood-High Building, 2231 N. High Street, Suite 211, Columbus, OH 43201; [email protected].

THE CASE

Janice J* visits her family physician with complaints of chest pain, shortness of breath, and heart palpitations that are usually worse at night. Her medical history is significant for deep vein thrombosis secondary to an underlying hypercoagulability condition (rheumatoid arthritis) diagnosed 2 months earlier. She also has a history of opioid use disorder and has been on buprenorphine/naloxone therapy for 3 years. Her family medical history is unremarkable. She works full-time and lives with her 8-year-old son. On physical exam, she appears anxious; her cardiac and pulmonary exams are normal. A completed workup rules out cardiac or pulmonary problems.

• What is your diagnosis?
• How would you treat this patient?

* The patient’s name has been changed to protect her identity.

CO-OCCURRING DISORDERS: SCOPE OF THE PROBLEM

Co-occurring disorders, previously called “dual diagnosis,” refers to the coexistence of a mental health disorder and a substance use disorder. The obsolete term, dual diagnosis, specified the presence of 2 co-occurring Axis I diagnoses or the presence of an Axis I diagnosis and an Axis II diagnosis (such as mental disability). The change in nomenclature more precisely describes the co-existing mental health and substance use disorders.

Currently the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, (DSM-5) includes no diagnostic criteria for this dual condition.¹ The criteria for mental health disorders and for substance use disorders comprise separate lists. Criteria for substance use disorder fall broadly into categories of “impaired [self] control, social impairment, risky behaviors, increased tolerance, and withdrawal symptoms.”¹ It is estimated that 8.5 million US adults have co-occurring disorders, per the 2017 National Survey on Drug Use and Health conducted by the Substance Abuse and Mental Health Services Administration.² Distinguishing which of the 2 conditions occurred first can be challenging. It has been suggested that the lifetime prevalence of a mental health disorder with a coexisting substance use disorder is greater than 40%^3,4 (TABLE 1^1,4-8). For patients with schizophrenia and bipolar disorder, these numbers may be higher.

The consequences of undiagnosed and untreated co-occurring disorders include poor medication adherence, physical comorbidities (and decreased overall health), diminished self-care, increased suicide risk or aggression, increased risky sexual behavior, and possible incarceration.⁹

WHEN SHOULD YOU SUSPECT CO-OCCURRING DISORDERS?

With some patients, only one diagnosis may be apparent at a given point, which could make it difficult to expeditiously recognize the onset of a co-occurring condition. For example, if a patient with anxiety has been treated successfully for years and then experiences a worsening of symptoms, it’s possible a physician might increase the dosage of anxiety medication without reevaluating for a substance use disorder. However, when both co-occurring disorders are present, the patient usually exhibits a greater number of symptoms and, if the full scope of the condition remains unrecognized, will likely respond poorly to therapy and have a prolonged course to resolution.^3,8-13 Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

The estimated lifetime prevalence of coexisting mental health and substance use disorders is > 40%.

Diagnosing a second condition can also be difficult when a patient’s symptoms are actually adverse effects of substances or prescribed medications. For example, a patient with worsening anxiety may also exhibit increasing blood pressure resistant to treatment. The cause of the patient’s fluctuating blood pressures may actually be the result of his or her use of alcohol to self-treat the anxiety. In addition to self-medication, other underlying factors may be at play, including genetic vulnerability, environment, and lifestyle.¹⁴ In the case we present, the patient’s conditions arose independently.

Anxiety disorders, with a lifetime risk of 28.8% in the US population,⁴ may be the primary mental health issue in many patients with co-occurring disorders, but this cannot be assumed in lieu of a complete workup.^2,8,9,15 Substance use disorders in the general population have a past-year and lifetime prevalence of 14.6%.^1,4,16,17 Because the causal and temporal association between anxiety and substance abuse is not always clear, it’s important to separate the diagnoses of the mental health and substance use disorders.

Continue to: MAKING THE DIAGNOSIS

To make an accurate diagnosis of co-occurring disorder, it is essential to take a complete history focusing on the timeline of symptoms, previous diagnoses and treatments, if any, and substance-free periods. Details gathered from these inquiries will help to separate symptoms of a primary mental health disorder from adverse effects of medication, withdrawal symptoms, or symptoms related to an underlying chronic medical condition.

Optimally, the diagnosis of a mental health disorder should be considered following a ­substance-free period. If this is not possible, a chart review may reveal a time when the patient did not have a substance use ­disorder.¹⁸

A diagnosis of substance use disorder requires that the patient manifest at least 2 of 11 behaviors listed in the DSM-5 over a 12-month period.¹ The criteria focus on the amount of substance used, the time spent securing the substance, risky behaviors associated with the substance, and tolerance to the substance.

DON'T DEFER MENTAL HEALTH Tx

It is necessary to treat co-occurring disorders simultaneously. The old idea of deferring treatment of a mental health issue until the substance use disorder is resolved no longer ­applies.^19,20 Treating substance use problems without addressing comorbid mental health ­issues can negatively impact treatment progress and increase risk for relapse. In a similar way, leaving substance use problems untreated is associated with nonadherence in mental health treatment, poor engagement, and dropout.^21,22

Integrated services. Due to this condition’s level of clinical complexity, the optimal treatment approach is an interdisciplinary one in which integrated services are offered at a single location by a team of medical, mental health, and substance use providers (see “The case for behavioral health integration into primary care” in the June issue). An evidence-based example of such an approach is the Integrated Dual Disorder Treatment (IDDT) model—a comprehensive, integrated method of treating severe mental health disorders, including substance use disorders.^21,22 IDDT combines coordinated services such as pharmacologic, psychological, educational, and social interventions to address the needs of patients and their family members. The IDDT model conceptualizes and treats co-occurring disorders within a biopsychosocial framework. Specific services may include medical detoxification, pharmacotherapy, patient and family education, behavioral and cognitive therapies, contingency management, self-help support groups, supported employment, residential/housing assistance, and case management services.^23,24

Continue to: Medications for the mental health component

Medications for the mental health component. For patients who prefer medication treatment to cognitive behavioral therapy (CBT), or for whom CBT is unavailable, treat the mental health disorder per customary practice for the diagnosis (TABLE 2^25-30). For psychotic disorders, use an antipsychotic, adding a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) as needed depending on the presence of negative symptoms.^25,31 For bipolar spectrum disorder, start a mood stabilizer³²; for depressive disorders initiate an SSRI or SNRI.²⁷ Anxiety disorders respond optimally when treated with SSRIs or SNRIs. Buspirone may be prescribed alone or as an adjunct for anxiety, and it does not cause mood-altering or withdrawal effects. Benzodiazepines in a controlled and monitored setting are an option in some antianxiety treatment plans. Consultation with a psychiatrist will help to determine the best treatment in these situations.

In all cases, treat the substance use disorder concurrently. Treatment options vary depending on the substance of choice. Although often overlooked, there can be simultaneous nicotine abuse. Oral or inhaled medications for nicotine abuse treatment are limited. The range of pharmacologic options for alcohol use disorder includes naltrexone, acamprosate, and disulfiram.^29,33 Pharmacologic treatment options for opioid use disorder include naltrexone, methadone, and a combination of naloxone and buprenorphine.³⁴

Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

Physicians who wish to prescribe buprenorphine must qualify for and complete a certified 8 hour waiver-training course, which is then approved by the Drug Enforcement Agency (under the DATA 2000 – Drug and Alcohol Act 2000). The physician obtains the designation of a data-waived physician and is assigned a special identification number to prescribe these medications.^35,36 Methadone may be provided only in a licensed methadone maintenance program. Regular and random drug urine screen requirements apply to all treatment programs.

Psychosocial and behavioral interventions are essential to the successful treatment of co-occurring disorders. Evidence-based behavioral and cognitive therapies are recommended for promoting adaptive coping skills and healthy lifestyle behaviors in co-occurring disorder populations.^23,24,37-40 Motivational interviewing enhances motivation and adherence when patients demonstrate resistance or ambivalence.^41,42 Mindfulness-based interventions have been shown to be effective and may be particularly beneficial for treating cravings/­urges and promoting relapse prevention.^{37,39,40,43-46}

Psychotropic medications, as with other treatment components, are most effective when used in combination with services that simultaneously address the patient’s biological, psychological, and social needs.

Continue to: The grassroots organization...

The grassroots organization National Alliance on Mental Illness (www.nami.org) recommends self-help and support groups, which include 12-step, faith-based and non-faith–based programs.²⁰

For any treatment method to be successful, there needs to be a level of customization and individualization. Some patients may respond to medication or nonmedication treatments only, and others may need a combination of treatments.

CASE

The physician recalls a past diagnosis of anxiety and asks Ms. J if there are any new stressors or changes causing concern. The patient expresses concern about an opioid use relapse secondary to her recent diagnosis of rheumatoid arthritis, which may be life altering or limiting.

Even though she has been doing well and has been adherent to her daily buprenorphine treatment, she worries for the well-being of her family and what would happen if she cannot work, becomes incapacitated, or dies at a young age. She has never considered herself an anxious person and is surprised that anxiety could cause such pronounced physical symptoms.

Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

The physician discusses different modalities of treatment, including counseling with an onsite psychologist, a trial of an anti-anxiety medication such as sertraline, or return office visits with the physician. They decide first to schedule an appointment with the psychologist, and Ms. J promises to find more time for self-wellness activities, such as exercise.

After 3 months of therapy, the patient decides to space out treatment to every 2 to 3 months and does not report any more episodes of chest pain or shortness of breath.

CORRESPONDENCE
Kristen Rundell, MD, Northwood-High Building, 2231 N. High Street, Suite 211, Columbus, OH 43201; [email protected].

THE CASE

Janice J* visits her family physician with complaints of chest pain, shortness of breath, and heart palpitations that are usually worse at night. Her medical history is significant for deep vein thrombosis secondary to an underlying hypercoagulability condition (rheumatoid arthritis) diagnosed 2 months earlier. She also has a history of opioid use disorder and has been on buprenorphine/naloxone therapy for 3 years. Her family medical history is unremarkable. She works full-time and lives with her 8-year-old son. On physical exam, she appears anxious; her cardiac and pulmonary exams are normal. A completed workup rules out cardiac or pulmonary problems.

• What is your diagnosis?
• How would you treat this patient?

* The patient’s name has been changed to protect her identity.

CO-OCCURRING DISORDERS: SCOPE OF THE PROBLEM

Co-occurring disorders, previously called “dual diagnosis,” refers to the coexistence of a mental health disorder and a substance use disorder. The obsolete term, dual diagnosis, specified the presence of 2 co-occurring Axis I diagnoses or the presence of an Axis I diagnosis and an Axis II diagnosis (such as mental disability). The change in nomenclature more precisely describes the co-existing mental health and substance use disorders.

Currently the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, (DSM-5) includes no diagnostic criteria for this dual condition.¹ The criteria for mental health disorders and for substance use disorders comprise separate lists. Criteria for substance use disorder fall broadly into categories of “impaired [self] control, social impairment, risky behaviors, increased tolerance, and withdrawal symptoms.”¹ It is estimated that 8.5 million US adults have co-occurring disorders, per the 2017 National Survey on Drug Use and Health conducted by the Substance Abuse and Mental Health Services Administration.² Distinguishing which of the 2 conditions occurred first can be challenging. It has been suggested that the lifetime prevalence of a mental health disorder with a coexisting substance use disorder is greater than 40%^3,4 (TABLE 1^1,4-8). For patients with schizophrenia and bipolar disorder, these numbers may be higher.

The consequences of undiagnosed and untreated co-occurring disorders include poor medication adherence, physical comorbidities (and decreased overall health), diminished self-care, increased suicide risk or aggression, increased risky sexual behavior, and possible incarceration.⁹

WHEN SHOULD YOU SUSPECT CO-OCCURRING DISORDERS?

With some patients, only one diagnosis may be apparent at a given point, which could make it difficult to expeditiously recognize the onset of a co-occurring condition. For example, if a patient with anxiety has been treated successfully for years and then experiences a worsening of symptoms, it’s possible a physician might increase the dosage of anxiety medication without reevaluating for a substance use disorder. However, when both co-occurring disorders are present, the patient usually exhibits a greater number of symptoms and, if the full scope of the condition remains unrecognized, will likely respond poorly to therapy and have a prolonged course to resolution.^3,8-13 Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

The estimated lifetime prevalence of coexisting mental health and substance use disorders is > 40%.

Diagnosing a second condition can also be difficult when a patient’s symptoms are actually adverse effects of substances or prescribed medications. For example, a patient with worsening anxiety may also exhibit increasing blood pressure resistant to treatment. The cause of the patient’s fluctuating blood pressures may actually be the result of his or her use of alcohol to self-treat the anxiety. In addition to self-medication, other underlying factors may be at play, including genetic vulnerability, environment, and lifestyle.¹⁴ In the case we present, the patient’s conditions arose independently.

Anxiety disorders, with a lifetime risk of 28.8% in the US population,⁴ may be the primary mental health issue in many patients with co-occurring disorders, but this cannot be assumed in lieu of a complete workup.^2,8,9,15 Substance use disorders in the general population have a past-year and lifetime prevalence of 14.6%.^1,4,16,17 Because the causal and temporal association between anxiety and substance abuse is not always clear, it’s important to separate the diagnoses of the mental health and substance use disorders.

Continue to: MAKING THE DIAGNOSIS

To make an accurate diagnosis of co-occurring disorder, it is essential to take a complete history focusing on the timeline of symptoms, previous diagnoses and treatments, if any, and substance-free periods. Details gathered from these inquiries will help to separate symptoms of a primary mental health disorder from adverse effects of medication, withdrawal symptoms, or symptoms related to an underlying chronic medical condition.

Optimally, the diagnosis of a mental health disorder should be considered following a ­substance-free period. If this is not possible, a chart review may reveal a time when the patient did not have a substance use ­disorder.¹⁸

A diagnosis of substance use disorder requires that the patient manifest at least 2 of 11 behaviors listed in the DSM-5 over a 12-month period.¹ The criteria focus on the amount of substance used, the time spent securing the substance, risky behaviors associated with the substance, and tolerance to the substance.

DON'T DEFER MENTAL HEALTH Tx

It is necessary to treat co-occurring disorders simultaneously. The old idea of deferring treatment of a mental health issue until the substance use disorder is resolved no longer ­applies.^19,20 Treating substance use problems without addressing comorbid mental health ­issues can negatively impact treatment progress and increase risk for relapse. In a similar way, leaving substance use problems untreated is associated with nonadherence in mental health treatment, poor engagement, and dropout.^21,22

Integrated services. Due to this condition’s level of clinical complexity, the optimal treatment approach is an interdisciplinary one in which integrated services are offered at a single location by a team of medical, mental health, and substance use providers (see “The case for behavioral health integration into primary care” in the June issue). An evidence-based example of such an approach is the Integrated Dual Disorder Treatment (IDDT) model—a comprehensive, integrated method of treating severe mental health disorders, including substance use disorders.^21,22 IDDT combines coordinated services such as pharmacologic, psychological, educational, and social interventions to address the needs of patients and their family members. The IDDT model conceptualizes and treats co-occurring disorders within a biopsychosocial framework. Specific services may include medical detoxification, pharmacotherapy, patient and family education, behavioral and cognitive therapies, contingency management, self-help support groups, supported employment, residential/housing assistance, and case management services.^23,24

Continue to: Medications for the mental health component

Medications for the mental health component. For patients who prefer medication treatment to cognitive behavioral therapy (CBT), or for whom CBT is unavailable, treat the mental health disorder per customary practice for the diagnosis (TABLE 2^25-30). For psychotic disorders, use an antipsychotic, adding a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) as needed depending on the presence of negative symptoms.^25,31 For bipolar spectrum disorder, start a mood stabilizer³²; for depressive disorders initiate an SSRI or SNRI.²⁷ Anxiety disorders respond optimally when treated with SSRIs or SNRIs. Buspirone may be prescribed alone or as an adjunct for anxiety, and it does not cause mood-altering or withdrawal effects. Benzodiazepines in a controlled and monitored setting are an option in some antianxiety treatment plans. Consultation with a psychiatrist will help to determine the best treatment in these situations.

In all cases, treat the substance use disorder concurrently. Treatment options vary depending on the substance of choice. Although often overlooked, there can be simultaneous nicotine abuse. Oral or inhaled medications for nicotine abuse treatment are limited. The range of pharmacologic options for alcohol use disorder includes naltrexone, acamprosate, and disulfiram.^29,33 Pharmacologic treatment options for opioid use disorder include naltrexone, methadone, and a combination of naloxone and buprenorphine.³⁴

Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

Physicians who wish to prescribe buprenorphine must qualify for and complete a certified 8 hour waiver-training course, which is then approved by the Drug Enforcement Agency (under the DATA 2000 – Drug and Alcohol Act 2000). The physician obtains the designation of a data-waived physician and is assigned a special identification number to prescribe these medications.^35,36 Methadone may be provided only in a licensed methadone maintenance program. Regular and random drug urine screen requirements apply to all treatment programs.

Psychosocial and behavioral interventions are essential to the successful treatment of co-occurring disorders. Evidence-based behavioral and cognitive therapies are recommended for promoting adaptive coping skills and healthy lifestyle behaviors in co-occurring disorder populations.^23,24,37-40 Motivational interviewing enhances motivation and adherence when patients demonstrate resistance or ambivalence.^41,42 Mindfulness-based interventions have been shown to be effective and may be particularly beneficial for treating cravings/­urges and promoting relapse prevention.^{37,39,40,43-46}

Psychotropic medications, as with other treatment components, are most effective when used in combination with services that simultaneously address the patient’s biological, psychological, and social needs.

Continue to: The grassroots organization...

The grassroots organization National Alliance on Mental Illness (www.nami.org) recommends self-help and support groups, which include 12-step, faith-based and non-faith–based programs.²⁰

For any treatment method to be successful, there needs to be a level of customization and individualization. Some patients may respond to medication or nonmedication treatments only, and others may need a combination of treatments.

CASE

The physician recalls a past diagnosis of anxiety and asks Ms. J if there are any new stressors or changes causing concern. The patient expresses concern about an opioid use relapse secondary to her recent diagnosis of rheumatoid arthritis, which may be life altering or limiting.

Even though she has been doing well and has been adherent to her daily buprenorphine treatment, she worries for the well-being of her family and what would happen if she cannot work, becomes incapacitated, or dies at a young age. She has never considered herself an anxious person and is surprised that anxiety could cause such pronounced physical symptoms.

Consider a co-occurring substance use disorder if treatment resistance persists, or if a patient has a recurrence or an exacerbation of a previously well-treated psychiatric disorder.

The physician discusses different modalities of treatment, including counseling with an onsite psychologist, a trial of an anti-anxiety medication such as sertraline, or return office visits with the physician. They decide first to schedule an appointment with the psychologist, and Ms. J promises to find more time for self-wellness activities, such as exercise.

After 3 months of therapy, the patient decides to space out treatment to every 2 to 3 months and does not report any more episodes of chest pain or shortness of breath.

CORRESPONDENCE
Kristen Rundell, MD, Northwood-High Building, 2231 N. High Street, Suite 211, Columbus, OH 43201; [email protected].