Unraveling Unusual Indications - PowerPoint Presentation

Slide1

Unraveling Unusual Indications

Emily Ellsworth,

PharmD

& Janna Hawthorne,

PharmD

UAMS College of Pharmacy

Slide2

Objectives:

Explain

the pathophysiological rationale for the off-label utilization of six selected medications:

methylphenidate

,

clonidine, amantadine,

prazosin

, oxybutynin, and gabapentin.

  

Review the most recent literature regarding specific off-label medication use in the elderly

.

Identify appropriate duration of therapy, monitoring

parameters,

and discontinuation strategies for the medications listed.

Describe

the place in therapy that each of the medications discussed should have for off-label utilization.

Slide3

How many of you come in contact with off-label prescribing on a regular basis?

Slide4

Off-Label Prescribing

Prescribing medications for:

U

nregistered therapeutic indications and age groups

Using unregistered doses or methods of administration

In 2001, 150 million prescriptions were provided for off-label utilization

73% lacked evidence of clinical efficacy

Most common off-label prescribed medications were gabapentin, amitriptyline, amoxicillin, dexamethasone, risperidone, and

temazepam

Radley D, Finkelstein S, Stafford R. Off-label prescribing among office-based physicians.

Arch Intern Med

. 2006; 16

6

: 1021-1026.

Slide5

Impact on Geriatric Medicine

Geriatric patients are often excluded from clinical trials

66%

of cancer patients are

>

65 but only 25% of cancer

trial subjects are this ageClinical trial participation of older adults is low

Alzheimer’s disease, incontinence, epilepsy, arthritis, cardiovascular diseaseGeriatric patients carry 60% of the disease burdenOnly represented in 32% of phase II and phase III clinical trialsFailings may limit generalizability, provide insufficient data about positive or negative effects of treatment among specific populations,

and hinder much-needed access to new treatmentsHerrera A, Snipes S, King D, et al. Disparate inclusion of older adults in clinical trials: priorities and opportunities for

policy

and

practice change.

Am J Public Health

. 2010 April; 100(

Suppl

1): S105–S112.

Slide6

Strategies to Rationalize Off-Label Prescribing

Know the licensed indications of a drug

Prescribe off-label drugs only if no approved drug is available or a specific patient characteristic does not allow prescribing of approved drugs

Evaluate data to support off-label indication

Discuss potential off-label indications with a pharmacist and/or colleague

Inform patient of potential risks of off-label prescribing

Assess and monitor for the expected therapeutic effect and any adverse effects

Regularly assess if there is still an indication for an off-label prescriptionJackson S, Jansen P,

Mangom A. Off-label prescribing in older adults. Drugs Aging. 2012; 29 (6): 427-434.

Slide7

Methylphenidate and Apathy in Alzheimer’s Disease

Slide8

Patient Case

ST is a 86yo female with a PMH of atrial fibrillation, CVA (1/2016), CAD, and HTN who has been recently diagnosed with Alzheimer’s disease. ST’s family reports that she is beginning to withdrawal herself from social events and hobbies that she used to enjoy. ST’s family is inquiring if there are any additional medications that can help with this symptom of Alzheimer’s disease.

Vitals: Medications:

HR: 74 Donepezil 10mg daily Metoprolol XL 100mg daily

BP: 146/78 Aspirin 81mg daily Warfarin 1mg daily

RR: 18 Atorvastatin 20mg daily

T: 98.6° F Lisinopril 20mg daily

Slide9

Pathophysiology

Apathy in Alzheimer’s disease = dopamine neurotransmission

National Institute on Drug Abuse: www.drugabuse.gov

Slide10

Pathophysiology

Methylphenidate = dopamine in synapse

Slide11

Methylphenidate

Efficacy and Safety

Rosenberg P,

Lanctot

K,

Drye

L, et al. Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: a randomized, placebo-controlled trial. J Clin Psychiatry. 2013; 74(8): 810-816.

Slide12

Methylphenidate Efficacy and Safety

Rosenberg P,

Lanctot

K,

Drye

L, et al. Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: a randomized, placebo-controlled trial.

J

Clin

Psychiatry. 2013; 74(8): 810-816.

Slide13

Methylphenidate Efficacy and Safety

Slide14

Monitoring for Efficacy & Safety

Depends on duration of therapy and dose

Taper vs. cold turkey

Hardy S. Methylphenidate for depressive symptoms, apathy, and fatigue in medically ill older adults and terminally ill older adults

.

Am J

Geriatr

Pharmacother

.

2009;

7(1): 34–59.

Slide15

Patient Case

ST is a 86yo female with a PMH of atrial fibrillation, CVA (1/2016), CAD, and HTN who has been recently diagnosed with Alzheimer’s disease. ST’s family reports that she is beginning to withdrawal herself from social events and hobbies that she used to enjoy. ST’s family is inquiring if there are any additional medications that can help with this symptom of Alzheimer’s disease.

Vitals: Medications:

HR: 74 Donepezil 10mg daily Metoprolol XL 100mg daily

BP: 146/78 Aspirin 81mg daily Warfarin 1mg daily

RR: 18 Atorvastatin 20mg daily

T: 98.6° F Lisinopril 20mg daily

Slide16

Clonidine and Hot Flashes in Menopause

Slide17

Patient Case

MS is a 55yo menopausal female with a past medical history of breast cancer (in remission) and HTN. Patient is complaining of hot flashes and night sweats interfering with her normal routine and sleep. MS is wondering if there is a safe medication to treat her bothersome symptoms of menopause.

Vitals: Medications:

HR: 82 Lisinopril 20mg daily

BP: 108/66 Raloxifene

60mg daily RR: 18 T: 97.5° F

Slide18

Pathophysiology

Morrow P,

Mattair

D,

Hortobagyi

G. Hot flashes: a review of pathophysiology and

treatment modalities.

Oncologist

. 2011 Nov; 16(11): 1658–1664

Slide19

Pathophysiology

Clonidine

Slide20

Clonidine

Efficacy and Safety

Buijs C, Mom C,

Willemse

P, et al. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.

Breast Cancer Res Treat. 2009; 115:573-580.

Slide21

Clonidine Efficacy and Safety

Buijs C, Mom C,

Willemse

P, et al. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.

Breast Cancer Res Treat.

2009; 115:573-580.

Slide22

Monitoring for Efficacy & Safety

Dose greater than

>

1.2mg/day for

>

1 month should be tapered to avoid rebound hypertension

Caution with concomitant beta-blocker use

Buijs C, Mom C,

Willemse

P, et al. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.

Breast Cancer Res Treat.

2009; 115:573-580.

Lexicomp Online

®, Clonidine Drug Information,

Hudson, Ohio: Lexi-Comp, Inc.;

Accessed August 14, 2016.

Slide23

Place in Therapy

Li, L., Xu, L., Wu, J. et al.

Comparative efficacy of

nonhormonal

drugs on menopausal hot flashes.

Eur

J

Clin Pharmacol (2016) 72: 1051.

Slide24

Patient Case

MS is a 55yo menopausal female with a past medical history of breast cancer (in remission) and HTN. Patient is complaining of hot flashes and night sweats interfering with her normal routine and sleep. MS is wondering if there is a safe medication to treat her bothersome symptoms of menopause.

Vitals: Medications:

HR: 82 Lisinopril 20mg daily

BP: 108/66 Raloxifene

60mg daily RR: 18 T: 97.5° F

Slide25

Amantadine and Cognitive Dysfunction in Total Brain Injury

Slide26

Patient Case

RR is a 80yo male who was admitted to the hospital with a traumatic brain injury s/p a severe motor vehicle accident. Patient’s PMH includes depression, HTN, and BPH. The geriatric team is consulted to treat this patient’s neurocognitive disorders due to this traumatic brain injury. Patient’s family is very distraught due to the cognitive decline RR is experiencing.

Vitals: Medications:

HR: 64 Amlodipine 5mg daily

BP: 110/86

Tamsulosin 0.4mg daily RR: 16 Sertraline 100mg daily T: 97.5° F Metoprolol XL 100mg daily

Slide27

Pathophysiology

Mechanism unclear

Amantadine = indirect dopamine agonist and NMDA antagonist

I

nhibitory

effect on microglial activation and

neuroinflammation.

Nobel Prize: http

://www.nobelprize.org/nobel_prizes/medicine/laureates/2000/press.html

Slide28

Amantadine

Efficacy and Safety

Giacino J, Whyte J,

Bagiella

E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N

Engl

J Med. 2012: 366;9: 819-826.

International, multicenter, randomized, placebo-controlled trial

Amantadine (n=87) vs. placebo (n=97)

Primary outcome: rate of improvement in the Disability Rating Scale (DRS) during the 4 weeks of treatment and 2 weeks post treatment

Secondary outcome: frequency of adverse events

Slide29

Amantadine Efficacy and Safety

Giacino J, Whyte J,

Bagiella

E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N

Engl

J Med. 2012: 366;9: 819-826.

Slide30

Monitoring for Efficacy & Safety

Gradually taper dose over 2-3 days to avoid rebound agitation, delirium, anxiety

Giacino

J, Whyte J,

Bagiella

E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N

Engl

J Med. 2012: 366;9: 819-826.

Lexicomp Online

®, Amantadine Drug Information,

Hudson, Ohio: Lexi-Comp, Inc.;

Accessed August 14, 2016.

Slide31

Place in Therapy

Wheaton P, Mathias J,

Vink

R.

Impact of Pharmacological Treatments on Cognitive and Behavioral Outcome in the

Postacute

Stages of Adult Traumatic Brain

Injury. J

Clin Psychoharmacol. 2011 Dec;31(6):745-57

Slide32

Patient Case

RR is a 80yo male who was admitted to the hospital with a traumatic brain injury s/p a severe motor vehicle accident. Patient’s PMH includes depression, HTN, and BPH. The geriatric team is consulted to treat this patient’s neurocognitive disorders due to this traumatic brain injury. Patient’s family is very distraught due to the cognitive decline RR is experiencing.

Vitals: Medications:

HR: 64 Amlodipine 5mg daily

BP: 110/86

Tamsulosin 0.4mg daily RR: 16 Sertraline 100mg daily T: 97.5° F Metoprolol XL 100mg daily

Slide33

Prazosin and Agitation in Alzheimer’s Disease

Slide34

Patient Case

GP is a 78yo male with a PMH of DM II, osteoporosis, HTN, and early onset Alzheimer’s Disease. Per GP’s caregiver, he has become agitated lately and will “lash out” about things that he never has before. He has also become aggressive towards small children. His family has become concerned about his aggression and has presented to clinic inquiring about what options they have.

Vitals:

HR: 81

BP: 130/86

RR: 16

Temp: 98.7

o

Current Medications: Metformin 1,000 mg BIDAlendronate 70 mg once weeklyLisinopril 20 mg daily

HCTZ 25 mg

daily

Galantamine

8 mg

BID

Glipizide

5 mg daily

Slide35

Pathophysiology of Agitation in Dementia

Compensatory upregulation of locus

ceruleus

NE outflow

Increased density of

α

-1 receptors in the hippocampus and prefrontal cortex

Reduction in 5-HT receptors within the brainDecrease in GABA function

Lindenmayer J. The pathophysiology of agitation. J Clin Psychiatry. 2006; 61(14): 5-10. Sharp S, Ballard C, Chen C, & Francis P. Aggressive behavior and neuroleptic medication are associated with increased number of alpha-1

adrenoreceptors

in patients with Alzheimer Disease.

Am J

Geriatr

Psychiatry

. 2007; 15(5): 435-437

Slide36

Pathophysiology of Prazosin Use for Agitation in Dementia

Prazosin

NE binding to

α

-1 receptors through direct inhibition

Wang L,

Shofer

J,

Rodhe

K, et al.

Prazosin

for the treatment of behavioral symptoms in patients with Alzheimer Disease with agitation and aggression.

Am J

Geriatr

Psychiatry

. 2009; 17(9): 744-751.

Slide37

Prazosin Efficacy and Safety

Wang L,

Shofer

J,

Rodhe

K, et al.

Prazosin

for the treatment of behavioral symptoms in patients with Alzheimer Disease with agitation and aggression.

Am J Geriatr Psychiatry. 2009; 17(9): 744-751.

Slide38

Prazosin Efficacy and Safety

Wang L,

Shofer

J,

Rodhe

K, et al.

Prazosin

for the treatment of behavioral symptoms in patients with Alzheimer Disease with agitation and aggression.

Am J Geriatr Psychiatry. 2009; 17(9): 744-751.

Slide39

Monitoring for Efficacy & Safety

Depends on duration of therapy and dose

Taper vs. cold turkey based upon risk of rebound hypertension

Wang L,

Shofer

J,

Rodhe

K, et al.

Prazosin for the treatment of behavioral symptoms in patients with Alzheimer Disease with agitation and aggression. Am J Geriatr Psychiatry. 2009; 17(9): 744-751.

Slide40

Place in Therapy

Madhusoodanan S & Ting M. Pharmacological management of behavioral symptoms associated with dementia.

World J of Psychiatry

. 2014; 4(4): 72-79.

Slide41

Patient Case

Patient Case

GP is a 78yo male with a PMH of DM II, osteoporosis, HTN, and early onset Alzheimer’s Disease. Per GP’s caregiver, he has become agitated lately and will “lash out” about things that he never has before. He has also become aggressive towards small children. His family has become concerned about his aggression and has presented to clinic inquiring about what options they have.

Vitals:

HR: 81

BP: 130/86

RR: 16

Temp: 98.7

o

Current Medications:

Metformin

1,000 mg BID

Alendronate 70 mg once weekly

Lisinopril

20 mg daily

HCTZ 25 mg

daily

Galantamine

8 mg

BID

Glipizide

5 mg daily

Slide42

Oxybutynin and Hyperhidrosis

Slide43

Patient Case

CS is a 62yo female who has suffered from hyperhidrosis for about 30 years. She reports sweating all day, no matter the surrounding temperature or current activity. There have been instances where after sitting for along period of time, the chair is left damp from sweat. Along with her hyperhidrosis, CS has a PMH of hypothyroidism with associated constipation, HTN, and GERD. She has presented to clinic to discuss the appropriateness of oxybutynin for her symptoms since her sister was prescribed that a few months ago.

Vitals:

HR: 74

BP: 119/76

RR: 19

Temp: 96.8

o

Current Medications: Levothyroxine 88 mcg dailyMiralax 17 g daily

Docusate 100 mg BID

Lisinopril 40 mg daily

Omeprazole 20 mg BID

Slide44

Pathophysiology

of Hyperhidrosis

Eccrine

vs. apocrine sweat glands

Innervation by cholinergic neurons

Dysregulation by the cortex of hypothalamic sweating centers = sympathetic CNS outflow = ACH activity on

eccrine

sweat glands

Leung A, Chan P, & Choi M. Hyperhidrosis.

Int

J of

Derm

. 1999; 38: 561-567.

Lakraj A,

Moghimi

N, &

Jabbari

B. Hyperhidrosis: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins.

Toxins

. 2013; 5(4): 821-840.

Slide45

Pathophysiology of Oxybutynin Use For Hyperhidrosis

Blockade of ACH binding = sweating at

eccrine

glands

Lakraj A,

Moghimi

N, &

Jabbari

B. Hyperhidrosis: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins.

Toxins

. 2013; 5(4): 821-840.

Slide46

Oxybutynin Efficacy and Safety

Wolosker

N,

Milanez

de Campos J, Kauffman P, &

Luech-Leão

P. A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis.

J of Vasc Surg. 2012; 55(6): 1696-1700.

Slide47

Oxybutynin Efficacy and Safety

Outcomes at 6 weeks

Oxybutynin

Placebo

Significance

Symptom improvement

(PH and AH

combined)

73.9% of patients with moderate-great

symptom improvement

27.3% of patients with moderate-great

symptom improvement

p<0.001

QOL

improvement

73.9%

improvement in QOL

13.6% improvement in QOL

p<0.001

Side effects

34.8% with moderate to severe dry mouth

9.1%

with moderate to severe dry mouth

P=0.388

Wolosker

N,

Milanez

de Campos J, Kauffman P, &

Luech-Leão

P. A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis.

J of

Vasc

Surg. 2012; 55(6): 1696-1700.

Slide48

Oxybutynin Efficacy and Safety

Wolosker

N,

Milanez

de Campos J, Kauffman P, &

Luech-Leão

P. A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis.

J of Vasc Surg. 2012; 55(6): 1696-1700.

Slide49

Monitoring for Efficacy & Safety

Wolosker

N,

Milanez

de Campos J, Kauffman P, &

Luech-Leão

P. A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis.

J of Vasc Surg. 2012; 55(6): 1696-1700.Wolosker N, Teivelis M, Krutman M, et al. Long-term results of the use of oxybutynin for the treatment of axillary hyperhidrosis. Annals of Vasc Surg. 2014; 28(5): 1106-1112.

Slide50

Place in Therapy

Lakraj A,

Moghimi

N, &

Jabbari

B. Hyperhidrosis: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins.

Toxins

. 2013; 5(4): 821-840.

Slide51

Patient Case

Patient Case

C

S is a 62yo female who has suffered from hyperhidrosis for about 30 years. She reports sweating all day, no matter the surrounding temperature or current activity. There have been instances where after sitting for along period of time, the chair is left damp from sweat. Along with her hyperhidrosis, CS has a PMH of hypothyroidism with associated constipation, HTN, and GERD. She has presented to clinic to discuss the appropriateness of oxybutynin for her symptoms since her sister was prescribed that a few months ago.

Vitals:

HR: 74

BP: 119/76

RR: 19

Temp: 96.8o

Current Medications:

Levothyroxine 88 mcg daily

Miralax

17 g daily

Docusate 100 mg BID

Lisinopril 40 mg daily

Omeprazole 20 mg BID

Slide52

Gabapentin and Restless Leg Syndrome (RLS)

Slide53

Patient Case

KM is a 67

yo

male who was recently diagnosed with RLS. His diagnosis was based upon symptoms of having an urge to move his legs, that is worse at night, and relieved by movement. KM and his wife have become very distressed with this problem because they are both waking up a lot at night due to the continued movement and restlessness. The daily fatigue is beginning to interrupt KM’s daily activities. PMH includes gout, HLD, RLS, essential tremor, and HTN. What other options should be considered?

Vitals:

HR: 98

BP: 148/90

RR: 20

Temp: 98.7oCurrent Medications: Allopurinol 100 mg dailyColchicine 0.6 mg PRNAtorvastatin 40 mg dailyRamipril 10 mg daily

Hydrochlorothiazide 25 mg daily

Slide54

Pathophysiology of RLS

Genetic component

Binding dysfunction of dopamine to presynaptic and postsynaptic receptors in the basal ganglia

Iron deficiency that leads to limited synthesis of tyrosine hydroxylase

Possible increase CNS levels of hypocretin-1

Diminished inhibition of descending spinal tracts to the periphery

Nagandla K & De S. Restless legs syndrome: pathophysiology and modern management.

Postgrad Med J

. 2013; 89: 402-410.Trenkwalder C, Paulus W, & Walters A. The restless legs syndrome. Lancet Neurol. 2005; 4: 465-475.

Slide55

Pathophysiology of Gabapentin for RLS

Binds to voltage-dependent calcium channels at the

α

2

-

δ

receptor = release of neurotransmitters

Binding in the CNS results in increased inhibition

Sills G. The mechanisms of action of gabapentin and

pregabalin

.

Current Opinion in Pharmacology

. 2006; 6: 108-113.

Slide56

Gabapentin Efficacy and Safety

Happe S,

Sauter

C,

Klösch

, et al. Gabapentin versus

ropinirole

in the treatment of idiopathic restless legs syndrome.

Neuropsychobiology. 2003; 48: 82-86.

Slide57

Gabapentin Efficacy and Safety

Happe S,

Sauter

C,

Klösch

, et al. Gabapentin versus

ropinirole

in the treatment of idiopathic restless legs syndrome.

Neuropsychobiology. 2003; 48: 82-86.

Slide58

Gabapentin Efficacy and Safety

Happe S,

Sauter

C,

Klösch

, et al. Gabapentin versus

ropinirole

in the treatment of idiopathic restless legs syndrome.

Neuropsychobiology. 2003; 48: 82-86.

Slide59

Gabapentin Efficacy and Safety

Happe S,

Sauter

C,

Klösch

, et al. Gabapentin versus

ropinirole

in the treatment of idiopathic restless legs syndrome.

Neuropsychobiology. 2003; 48: 82-86.

Slide60

Monitoring for Efficacy & Safety

Happe S,

Sauter

C,

Klösch

, et al. Gabapentin versus

ropinirole

in the treatment of idiopathic restless legs syndrome.

Neuropsychobiology. 2003; 48: 82-86.Ellenbogen A, Thein S, Winslow D, et al. A 52-week study of gabapentin enacarbil in restless legs syndrome. Clin Neuropharmacology. 2011; 34(1): 8-16.

Slide61

Place in Therapy

Hydrocodone

Oxycodone

Methadone

Nagandla K & De S. Restless legs syndrome: pathophysiology and modern management.

Postgrad Med J

. 2013; 89: 402-410.

Slide62

Patient Case

Patient Case

KM is a 67

yo

male who was recently diagnosed with RLS. His diagnosis was based upon symptoms of having an urge to move his legs, that is worse at night, and relieved by movement. KM and his wife have become very distressed with this problem because they are both waking up a lot at night due to the continued movement and restlessness. The daily fatigue is beginning to interrupt KM’s daily activities. PMH includes gout, HLD, RLS, essential tremor, and HTN. What other options should be considered?

Vitals:

HR: 98

BP: 148/90

RR: 20Temp: 98.7o

Current Medications:

Allopurinol 100 mg daily

Colchicine 0.6 mg PRN

Atorvastatin 40 mg daily

Ramipril 10 mg daily

Hydrochlorothiazide 25 mg daily

Slide63

Conclusions

Off-label prescribing in geriatrics is a common practice

Based on the literature:

Appropriate monitoring and discontinuation strategies should be utilized once these off-label medications have been selected

Medication

Indication

Place

in Therapy

MethylphenidateApathy in Alzheimer’s Disease

First line option

Amantadine

Cognitive

dysfunction in Total Brain Injury

First line option

Clonidine

Hot flashes

Second line option

Prazosin

Agitation in Alzheimer’s Disease

Second line option

Oxybutynin

Hyperhidrosis

Second line option

Gabapentin

RLS

Second line

option

Slide64

References

Buijs C, Mom C,

Willemse

P, et al. Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.

Breast Cancer Res Treat.

2009; 115:573-580.

Ellenbogen

A, Thein S, Winslow D, et al. A 52-week study of gabapentin

enacarbil in restless legs syndrome. Clin Neuropharmacology. 2011; 34(1): 8-16.Giacino J, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012: 366;9: 819-826.

Happe

S,

Sauter

C,

Klösch

, et al. Gabapentin versus

ropinirole

in the treatment of idiopathic restless legs syndrome.

Neuropsychobiology

. 2003; 48: 82-86.

Hardy S. Methylphenidate for depressive symptoms, apathy, and fatigue in medically ill older adults and terminally ill older adults.

Am J

Geriatr

Pharmacother

. 2009; 7(1): 34–59.

Herrera A, Snipes S, King D, et al. Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change.

Am J Public Health

. 2010 April; 100(

Suppl

1): S105–S112.

Jackson S, Jansen P,

Mangom

A. Off-label prescribing in older adults.

Drugs Aging.

2012; 29 (6): 427-434.

Lakraj

A,

Moghimi

N, &

Jabbari

B. Hyperhidrosis: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins.

Toxins

. 2013; 5(4): 821-840.

Leung

A, Chan P, & Choi M. Hyperhidrosis.

Int

J of

Derm

. 1999; 38: 561-567.

Lexicomp Online®, Amantadine Drug Information, Hudson, Ohio: Lexi-Comp, Inc.; Accessed August 14, 2016.

Lexicomp

Online®, Clonidine Drug Information, Hudson, Ohio: Lexi-Comp, Inc.; Accessed August 14, 2016.

Li, L., Xu, L., Wu, J. et al. Comparative efficacy of

nonhormonal

drugs on menopausal hot flashes.

Eur

J

Clin

Pharmacol

(2016) 72: 1051.

Lindenmayer

J. The pathophysiology of agitation.

J

Clin

Psychiatry.

2006; 61(14): 5-10.

Slide65

References

Madhusoodanan

S & Ting M. Pharmacological management of behavioral symptoms associated with dementia.

World J of Psychiatry

. 2014; 4(4): 72-79.

Morrow P,

Mattair

D, Hortobagyi G. Hot flashes: a review of pathophysiology and treatment modalities. Oncologist. 2011 Nov; 16(11): 1658–1664

Nagandla K & De S. Restless legs syndrome: pathophysiology and modern management. Postgrad Med J. 2013; 89: 402-410. National Institute on Drug Abuse: www.drugabuse.govNeuropsychopharmacology (2010) 35, 278-300; doi: 10.1038/npp.2009.120Nobel Prize: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2000/press.html

Radley D, Finkelstein S, Stafford R. Off-label prescribing among office-based physicians.

Arch Intern Med

. 2006; 16

6

: 1021-1026.

Rosenberg

P,

Lanctot

K,

Drye

L, et al. Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: a randomized, placebo-controlled trial.

J

Clin

Psychiatry.

2013; 74(8): 810-816.

Sharp S, Ballard C, Chen C, & Francis P. Aggressive behavior and neuroleptic medication are associated with increased number of alpha-1

adrenoreceptors

in patients with Alzheimer Disease.

Am J

Geriatr

Psychiatry

. 2007; 15(5): 435-437.

Sills G. The mechanisms of action of gabapentin and

pregabalin

.

Current Opinion in Pharmacology

. 2006; 6: 108-113.

Trenkwalder

C, Paulus W, & Walters A. The restless legs syndrome.

Lancet Neurol.

2005; 4: 465-475.

Wang L,

Shofer

J,

Rodhe

K, et al.

Prazosin

for the treatment of behavioral symptoms in patients with Alzheimer Disease with agitation and aggression.

Am J

Geriatr

Psychiatry

. 2009; 17(9): 744-751.

Wheaton P, Mathias J,

Vink

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Slide66

Question #1

All of the following are side effects of prazosin:

Hypotension

Syncope

Decreased energy

All of the above

Slide67

Question #2

Why must amantadine be tapered over 2-3 days?

Rebound agitation

Delirium

Anxiety

Seizures

A, B, and C

Slide68