Transcript Main Title * Futura Heavy

Prescribing and Tapering
Benzodiazepines
Introduction
• The use of benzodiazepines has grown over time and
evidence has shown that long term use of these drugs
has very little benefit with many risks involved.
• Many providers are receiving new patients on
benzodiazepines and are uncomfortable with managing
their treatment regimen
• This is an evidence based guideline for the use of
benzodiazepines and related drugs in clinical office
practice.
• A multidisciplinary work group was formed to develop
this guideline for use
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Rule #1
• Assess the symptoms
• Diagnosis Criteria
• SSRIs are first line in
depression
• Adequate dosage
• At least 6-8 weeks
• Don’t fire your
antidepressant or first
line agent too soon.
What Are the Symptoms of an Anxiety Disorder?
Feelings of panic, fear, and uneasiness
Problems sleeping
Cold or sweaty hands and/or feet
Shortness of breath
Heart palpitations
An inability to be still and calm
Dry mouth
Numbness or tingling in the hands or feet
Nausea
Muscle tension
Dizziness
Medical causes
Anemia
Infection
Heart disease
Diabetes
Thyroid problems, such as hypothyroidism or hyperthyroidism
Asthma
Drug abuse or withdrawal
Irritable bowel syndrome
Rare tumors that produce certain "fight-or-flight" hormones
Premenstrual syndrome
Medical causes
Breathing, difficulty Aortic Insufficiency Asthma Bronchitis Cardiac Arrhythmia Collagen Disease Emphysema Guillain-Barre Syndrome Hemothorax Left Ventricular Failure
Lupus Mitral Stenosis Myasthenia Gravis Ovarian Cancer Pericardial Effusion Pleural Effusion Pneumoconiosis Pneumothorax Pulmonary Edema
Chest Pain Angina Pectoris Coronary Artery Disease Heart attack Lupus
Concentration, lack of Alzheimer's Disease Attention Deficit/Hyperactivity Disorder (ADHD) Brain Cancer Chronic Fatigue Syndrome Depression Insomnia Post Traumatic
Stress Disorder Premenstrual Syndrome
Dizziness Benign Positional Vertigo Cerebral Embolism Cerebral Hemorrhage Cerebral Thrombosis Dental Problems Ear Infections Fibromyalgia Food Allergy Food Poisoning
Head Injury Heat Exhaustion Hypertension Insect Bites and Stings Labyrinthitis Meniere's Disease Menopause Miscarriage Motion Sickness Myocardial Infarction Nystagmus
Postural Orthostatic Hypotension Stroke Temporomandibular Joint Dysfunction Transient Ischemic Attacks
Dyspnea (Breathing discomfort or breathlessness) Anemia Asthma Bronchitis Chronic Obstructive Pulmonary Disease Collagen disease Colorectal Cancer Congestive Heart
Failure Edema Emphysema Endocarditis Food Allergy HIV and AIDS Hyperkalemia Hypoxia Insect Bites and Stings Laryngitis Leukemia Lupus Myocardial Infarction Ovarian
Cancer Pericarditis Pharyngitis Pulmonary Edema Pulmonary Fibrosis Pulmonary Hypertension Thyroiditis
Fatigue Allergic Rhinitis Anemia Atherosclerosis Bone Cancer Bronchitis Chronic Fatigue Syndrome Cirrhosis Colorectal Cancer Congestive Heart Failure Crohn's Disease
Cystic Fibrosis Depression Diabetes Mellitus Endocarditis Erythema Fibromyalgia Heat Exhaustion Hepatitis, Viral Herpes Zoster and Varicella Viruses Hyperkalemia
Hypoglycemia Influenza Insomnia Intestinal Parasites Leukemia Lupus Lyme Disease Lymphoma Mononucleosis Motion Sickness Multiple Sclerosis Myeloproliferative
Disorders Osteomyelitis Ovarian Cancer Pericarditis Premenstrual Syndrome Pulmonary Hypertension Radiation Damage Rheumatoid Arthritis Sarcoidosis Sleep Apnea
Systemic Lupus Erythematosus Tension Headache Tuberculosis
Heart symptoms Anemia arrhythmia Coronary artery disease Heart Attack Hyperthyroidism Infections Pericarditis Post-myocardial infarction
Irritability Common Cold Depression Diabetes Mellitus Herpes Simplex Virus Hypoglycemia Hypothermia Insomnia Meningitis Menopause Migraine Headache Osteomyelitis
Post Sleep Apnea Traumatic Stress Disorder Premenstrual Syndrome Seizure Disorders Tension Headache Food Allergy
Sleep disorders Alcoholism Alzheimer's Disease Amyloidosis Chronic Fatigue Syndrome Depression Fibromyalgia Hyperthyroidism Menopause Premenstrual Syndrome Sleep
Apnea
Sweating Anaphylaxis Asthma Heat Exhaustion Hyperthyroidism Hypoglycemia Lung Cancer Motion Sickness Pancreatitis Radiation Damage Seizure Disorders Syncope
Thyroiditis
GABAA Structure
4 or more subunits (alpha, beta, gamma, and delta)
multiple subtypes of each subunit
5 subunits come together to form the receptor complex
• approximately 100 variants of GABAA receptor possible
• several exist in the mammalian CNS4 transmembrane
regions
• both C and N terminus is extracellular
• gamma unit must be present for BZDs to modulate
GABA
How do benzodiazepines work?
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GABA Receptor
CNS Depressant
Hypnotic/ Sedative
Most are fast acting and develop tolerance
and dependency quickly, thus requiring more
to get the same effect.
• Works on the pleasure center of the brain
• Just like alcohol to the brain!!!
Benzodiazepines (BZDs)
Hypnotic
Amnestic
Produce confusion
Short Term Use
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Short Term Use Definition: 2-6 weeks maximum
Benzodiazepines are not first line therapy agents
Benzodiazepine use beyond 4 to 6 weeks will result in:
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loss of effectiveness
the development of tolerance
dependence and potential for withdrawal syndromes
persistent adverse side effects
interference with the effectiveness of definitive medication and
counseling.
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Indications for Short Term Use
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GAD
Phobias
PTSD
Panic Disorders
Severe anxiety associated with depression,
while waiting for the full effect of the
antidepressant.
Indications for Short Term Use Continues
Insomnia
There is evidence for the effectiveness of benzodiazepines and other
hypnotics in the relief of short-term (1 to 2 weeks), but not long-term
insomnia.
Muscle relaxant
Benzodiazepines are indicated for the short-term relief (1 to 2 weeks) of
muscular discomfort associated with acute injuries or flare-ups of chronic
musculoskeletal pain. Benzodiazepines may be combined with analgesics
and nondrug therapies but not with other sedatives, hypnotics, or other
muscle relaxants.
Other Indications:
• Urgent treatment of acute psychosis with agitation
• As part of a protocol for treating alcohol withdrawal
• Seizures and a limited number of other neurological disorders
• Sedation for office procedures
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Indications for Long Term Use
Benzodiazepines may be used for longer than 6
weeks in the:
• terminally ill
• severely handicapped patient
• certain neurological disorders
• restless leg syndrome
• no evidence to support long term use for a
mental health disorder
Contraindications to Benzodiazepine Use:
• Pregnancy and the patient at risk for pregnancy.
Benzodiazepines are category D. If a hypnotic is necessary,
Zolpidem (Ambien), which is category B, is preferred. Patients
who conceive while on benzodiazepines should be tapered off
completely or to the lowest possible dose.
• Active substance abuse, including alcohol.
• Medical and mental health problems that may be aggravated
by benzodiazepines.
• Fibromyalgia, chronic fatigue syndrome, other somatization
disorders,
• depression (except for short-term use to treat associated anxiety),
• bipolar disorder (except for urgent sedation in acute mania),
• ADHD, kleptomania, and other impulse control disorders.)
Contraindications to Benzodiazepines Continued
• Benzodiazepines may worsen hypoxia and hypoventilation in asthma,
sleep apnea, COPD, CHF, and other cardiopulmonary disorders.
• Patients being treated with opioids for chronic pain or replacement
therapy for narcotic addiction.
• Grief reactions. Benzodiazepines are often used for short term treatment
of insomnia in acute grief but should otherwise be avoided in treating
grief reactions, as they may suppress and prolong the grieving process.
• PTSD – longer term use of these agents compromise the needed exposure
and cognitive processing of the trauma which is known to result in
symptom amelioration.
There is no evidence supporting the long-term use of benzodiazepines for any
mental health indication
Do not prescribe - No Effectiveness:
Clinical trials have shown no effectiveness with the use of
benzodiazepines in the following conditions:
• Tinnitus
• Chronic tension headache
• Essential Tremor
• Meniere’s
• Post-traumatic stress disorder (Provided a “D” rating as being
of “No Benefit/Harm ” classification by the VA/DOD official
PTSD CPG)
• Concussion
• Evidence of substance abuse
Dose Equivalency
Alprazolam (Xanax)
Chlordiazepoxide
(Librium)
Clonazepam
(Klonopin)
Diazepam (Valium)
Lorazepam (Ativan)
Oxazepam (Serax)
Temazepam
(Restoril)
Triazolam (Halcion)
Approximate
Equivalent Oral
Doses, mg
0.5
25
0.25
5
1
15
10
0.25
Time to Peak Level,
hours
1-2
1-4
1-4
1-2
1-4
1-4
2-3
1-2
Half-life, hours
12
100
34
100
15
8
11
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New Prescriptions
• Only use for the short-term treatment of severe anxiety or
insomnia
• anxiety maximum of 4-8 weeks
• insomnia maximum of 10 nights
• Duration should be as short as possible. The risk of
dependence increases with dose and duration.
• Urine Drug Screen should be completed prior to prescribing
controlled substances
• History and ROI for previous provider if needed
• Alternatives have been tried or are combination
New Prescriptions
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Provide information on behavioral strategies for anxiety
reduction. Supplement with sleep guides, diaries and leaflets
e.g.: relaxation techniques, biofeedback, etc.
Educate patient on short term use and non drug therapies
Non-drug strategies can be effective in the management of
anxiety and insomnia and may address the underlying cause,
rather than just relieving symptoms.
Write one script for a specific amount of days and no refills.
Tapering Benzodiazepines
Basic principles:
• Expect anxiety, insomnia, and resistance. Patient education
and support very important.
• Try decrease dose and frequency with long term users at first.
• The slower the taper, the better the change is tolerated.
• Only one provider should prescribe the benzodiazepine and
should be agreed upon by the treatment team when patient is
treat across specialties.
• Calculate exactly how many pills they will need and give only
one prescription with no refills.
• Abrupt withdrawal is not recommended. Risk of seizures
and/or delirium increases with abrupt withdrawal.
Slow Taper (3-6 months)
1. Calculate the total daily dose. Switch from short acting agent
(alprazolam, lorazepam) to longer acting agent (diazepam,
clonazepam). Upon initiation of taper reduce the calculated
dose by 25% to adjust for possible metabolic variance.
2. First Follow up is 1 week after initiating the taper to
determine need to adjust initial calculated dose.
3. Reduce the total daily dose by 5-10% per week in divided
doses.
4. Once ½ of the original dose has been reach, the taper can be
slowed further by decreasing the dose each month
thereafter.
Slow Taper (3-6 months)
5. Consider an adjunctive agent to help with symptoms or to
replace the benzodiazepine such as: buspirone, vistaril
(advised not to use with the elderly), clonidine, SSRIs (Celexa
40mg maximum with elderly – get ekg), and/or sleeping aids.
6. Educate patient on nondrug therapies available to assist with
symptoms such as: relaxation techniques, deep breathing,
exercise, psychotherapy, etc.
Dose Equivalency
Alprazolam (Xanax)
Chlordiazepoxide
(Librium)
Clonazepam
(Klonopin)
Diazepam (Valium)
Lorazepam (Ativan)
Oxazepam (Serax)
Temazepam
(Restoril)
Triazolam (Halcion)
Approximate
Equivalent Oral
Doses, mg
0.5
25
0.25
5
1
15
10
0.25
Time to Peak Level,
hours
1-2
1-4
1-4
1-2
1-4
1-4
2-3
1-2
Half-life, hours
12
100
34
100
15
8
11
2
Fast Taper (2-6 Weeks)
1. Use an equivalent dose - replace with diazepam or
clonazepam two times daily for 1-2 weeks.
2. Add an anticonvulsant (carbamazepine, valproate,
gabapentin) at a maintenance dose. These work on the same
GABA receptors and help to facilitate a faster taper.
3. Consider an adjunctive agent to help with symptoms or to
replace the benzodiazepine such as: buspirone, vistaril
(advised not to use with the elderly), clonidine, SSRIs (Celexa
40mg maximum with elderly – get ekg), and/or sleeping aids.
After 1-2 weeks decrease the dose of diazepam to once daily.
4. Then cut the diazepam or clonazepam to ¼ of the initial dose
once daily for 1-2 weeks
Fast Taper (2-6 Weeks)
5. Discontinue the Diazepam.
6. Continue the anticonvulsant for 2-3 months after
discontinuing the benzodiazepine.
7. Educate patient on nondrug therapies available to assist with
symptoms such as: relaxation techniques, deep breathing,
exercise, psychotherapy, etc.
Dose Equivalency
Alprazolam (Xanax)
Chlordiazepoxide
(Librium)
Clonazepam
(Klonopin)
Diazepam (Valium)
Lorazepam (Ativan)
Oxazepam (Serax)
Temazepam
(Restoril)
Triazolam (Halcion)
Approximate
Equivalent Oral
Doses, mg
0.5
25
0.25
5
1
15
10
0.25
Time to Peak Level,
hours
1-2
1-4
1-4
1-2
1-4
1-4
2-3
1-2
Half-life, hours
12
100
34
100
15
8
11
2
BZD Tolerance
The higher the dose, and
The more frequently the dose is taken, and
The longer the dose is taken, then
The greater the tolerance
BZD Dependence
The higher the dose, and
The more frequently the dose is taken, and
The longer the dose is taken, then
The greater the physical dependence
Physical Dependence = an abstinence syndrome
when:
• drug administration stops (spontaneous)
• an antagonist is given (precipitated)
BZD Dependence
Shorter half-life drugs give nastier signs and
symptoms of withdrawal
Longer half-life drugs give less severe signs
and symptoms of withdrawal, but they are
more protracted.
If withdrawal is threatening to become
intolerable or if seizures are likely, consider
administering a longer acting BZD
Drug Interactions with BZDs
Cimetidine (Tagamet) inhibits liver mixedfunction oxidase. Prolongs the action of most
BZDs.
• Use alprazolam, lorazepam or oxazepam for
patients taking cimetidine
Alternative Medications
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Vistaril/Atarax 25-50mg TID
Propranolol 10-20mg TID caution low blood pressure
Clonidine 0.1 mg BID caution low blood pressure
Buspirone 5-20mg TID
Lyrica 50-150mg TID off label indication
Neurontin/Gabapentin 100-300mg TID off label indication
BZD Dependence
Nasty problem
1. Initial anxiety returns during withdrawal
2. Additional anxiety occurs because of
withdrawal
Net effect is intolerable anxiety
Symptoms of withdrawal occur before signs
of withdrawal, and anxiety is the first
withdrawal symptom
Withdrawal symptoms – feeling tapped behind (Xanax) bars
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Severe sleep disturbance
Irritability
Increased tension and anxiety
Hand tremor
Sweating
Difficulty with concentration
Confusion and cognitive difficulty
Headache
Muscular pain and stiffness
Seizures
Psychosis
Tachycardia
Hypertension
Loss of appetite
Delirium Tremens
Managing Resistance
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Understand the etiology of withdrawal
Educate early
Need network wide consistency
Provide support and alternatives
Don’t argue but remain firm
For those that have been using long term the goal is to
decrease dosage and frequency
Thank you
Questions?
Elimination half-lives
What Is Autonomic Dysfunction?
The autonomic nervous system (ANS) controls many basic bodily
functions including: heart rate, body temperature, breathing
rate, and digestion
The ANS provides the connection between your brain and your
internal organs - connects to the heart, liver, sweat glands, and
interior muscles of your eye.
The ANS:
sympathetic autonomic nervous system (SANS) fight or flight
parasympathetic autonomic nervous system (PANS)