Download The Anxiety Disorders Some Practical Questions & Answers

The Anxiety
Medications
A Patient-Centered, Evidence-Based
Treatment Approach
A Presentation for the Students of Ohio University
Heritage College of Osteopathic Medicine
Kendall L. Stewart, MD, MBA, DLFAPA
November 6, 2012
Please read, The Truth About Drug Companies, Marcia Angell (2004) and subscribe to The Medical Letter.
(www.medicalletter.com).
Why should I learn about these
medications?
• They are among the most widely prescribed
drugs.1
• Some of the older medications are dangerous.
• The benzodiazepines are safe and effective, but
they cannot always be used interchangeably.
• Only those persons with a history of alcohol and
drug misuse are likely to abuse the
benzodiazepines.
1 Anxiety
can make you irrational. Larry Fried was trying to make a big, nervous fellow feel more at ease.
What are some examples of
antianxiety drugs?
• All these drugs are sedating, but that’s not all they
do.
• The late 1800s brought alcohol, bromide salts,
chloral hydrate and paraldehyde.1
• Then came popular barbiturates in the 1950s.
• Meprobamate was the sedative of the 50s and
60s.
• Then came the safe and effective
benzodiazepines, and they have become the gold
standard.
1 I’m
not a drinker, but I’ve been around a lot of them. Alcohol clearly has some appeal. And it occasions
some unhappiness. I returned to my office to find a drunk, but Jeff Hill saved me.
What are some of the indications for
benzodiazepine use?
• Secondary anxiety
– Stressful circumstances
– Another psychiatric disorder
– General medical disorders
• Anxiety disorders
–
–
–
–
Generalized anxiety disorder
Panic disorder
Social phobia
Posttraumatic stress disorder
What are some of the guidelines for
benzodiazepine use?
• Fully utilize the non-medicinal anti-anxiety
strategies.
• Short-term use is preferred if possible.
• Inadequate dosage is the most common cause of
treatment failure.
• Don’t forget to identify and treat the primary
disorder.
• Remember to taper slowly when discontinuing these
drugs.
• Don’t confuse dependence and addiction.1
• Use short-acting drugs in the elderly—if you must
use them at all.
1 These
drugs are widely misunderstood. They are not abused by most people. In fact, they are usually
taken less often than they are prescribed. Be cautious in patients with a history of substance abuse.
How do the benzodiazepines work?
• Gamma-aminobutyric acid is an
inhibitory neurotransmitter in the CNS.
• Benzodiazepines potentiate the
inhibitory effects of GABA by increasing
the flux of chloride ions into neurons.
• This may result in decreased neuronal
firing and diminish anxiety.1
This sedation produces undesirable consequences when these drugs are used in high dosages. This is
true for all sedatives. A patient on lorazepam didn’t remember talking to me. A woman shot herself during
a blackout.
1
What are some of the common side
effects of these drugs?
•
•
•
•
•
•
•
•
•
1I
Drowsiness
Dizziness
Ataxia
Disinhibition
Amnesia
Paradoxical agitation
Respiratory depression1
Dependence
Use in pregnancy not advised
learned this first hand as a junior medical student from my first DO mentor. I gave an elderly woman
lorazepam and then endured the jabs of my colleagues as I bagged her in the hall.
How are the benzodiazepines
metabolized?
• These drugs are metabolized by microsomal
enzyme systems in the liver.
• Most undergo transformation of the diazepine
ring or hydroxylation followed by conjugation by
glucuronic acid.
• Ring transformation and hydroxylation may be
compromised in medically ill patients.
• These capacities also decrease with aging.
• Select those benzodiazepines that only require
conjugation in the elderly (i.e., lorazepam,
oxazepam, temazepam)1
1 Elderly
people who take these drugs are more likely to be involved in accidents and to sustain hip
fractures. If you decide to use them, choose a short-acting agent.
What are the elimination half-lives of
some of these drugs?
Short-acting
Midazolam
Triazolam
Intermediate-acting
Alprazolam
Oxazepam
Lorazepam
Long-acting
Clonazepam
Clorazepate
Diazepam
1-2 hours
2-4 hours
6-10 hours
5-10 hours
10-20 hours
18-50 hours
50-80 hours
50-100 hours
What are some of the therapeutic
dose ranges of these drugs?
Diazepam
Lorazepam
Clorazepate
Prazepam
Oxazepam
Alprazolam
Clonazepam
Halazepam
5-40 mg/day
1-6 mg/day
15-60 mg/day
20-60 mg/day
10-120 mg/day
1-8 mg/day
0.5-6 mg/day
20-120 mg/day
What are the characteristics of
benzodiazepine dependence?
• It usually only becomes apparent during the drug
discontinuation phase.
• Of those who have taken a benzodiazepine
regularly for 4-6 months, 50% will have
developed dependence.1
• Withdrawal symptoms from the short-acting
drugs appear more rapidly, but they are not more
severe.
• Discomfort instead of danger is the rule, but there
are exceptions.
1 Patients
will blame all sorts of undesirable behavior on medication. A businessman wanted me to provide
a statement that he signed an unfavorable contract while on lorazepam. He fired me when I refused.
What are some of the common
benzodiazepine withdrawal symptoms?
•
•
•
•
•
•
Anxiety
Irritability1
Insomnia
Fatigue
Headache
Muscle twitching or
aching
• Tremor, shakiness
1 Some
• Dizziness
• Concentration
difficulties
• Nausea, loss of
appetite
• Observable
depression
• Derealization
• Depersonalization
people are just irritable by nature. A farmer was griping at his wife at breakfast. She couldn’t fix
The eggs to please him, and he was critical of her metabolic syndrome.
How should the benzodiazepines be
tapered?
• First, discuss the
possibilities
– No reaction
– Discontinuation
syndrome
– Reoccurrence of the
underlying disorder
– Rebound
• If taken less than two
weeks, just stop
1 Some
• Higher daily dosages
and longer duration of
treatment demand
slower taper
• The duration of the
taper will depend on
the initial response
• Adherence to an agreed
upon schedule is key1
• Tapering sometimes
fails
patients are highly resistant to taking even small, infrequent dosages of these medications. Some
prefer to get through their panic attacks on their own. Education and experience are very helpful.
What about buspirone?
• Selective agonist of the 5HT1A
receptor
• Safe and effective treatment for
Generalized Anxiety Disorder1,2
• Not effective for Panic Disorder
• Dependence does not develop
• Will not protect from
benzodiazepine withdrawal
1
This medication takes a while to work. It works best in benzodiazepine virgins. They are hard to find.
reminds me of ordering a Virgin Mary in Las Vegas.
2 It
What about the antihistamines?
• These drugs are relatively safe
hypnotics, but they are not superior to
the benzodiazepines.
• They are not effective as long-term antianxiety drugs.
• They still have some short-term
usefulness in patients for whom the use
of benzodiazepines is not desirable.
What about antidepressants?
• These are effective anti-anxiety agents.1
• They are preferred for long-term use and in
persons with a history of substance abuse.
• They often must be started at lower dosages and
titrated up more slowly in anxiety patient who
are more sensitive to side effects.
• They take longer to work.
• Most antidepressants block panic attacks and
possess sedative side effects.
• Some of them are specifically helpful in OCD.
If the chronic administration of medication for anxiety is required, these are the drugs of choice. Most
psychiatrists see the toughest cases, and we all have patients on both antidepressants and benzodiazepines.
1
What are some of the benzodiazepines
currently used as sedative-hypnotics?
Zolpidem (Ambien)
Triazolam (Halcion)
Temazepam (Restoril)
Estazolam (Prosom)
Oxazepam (Serax)
Alprazolam (Xanax)
Lorazepam (Ativan)
Clonazepam (Klonopin)
Quazepam (Doral)
Flurazepam (Dalmane)
2.5-10 mg
.125-0.25 mg
7.5-30 mg
1-2 mg
10-25 mg
.25-1.0 mg
.5-2 mg
.5-2 mg
7.5-15 mg
15-30 mg
Where can you learn more?
•
•
•
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•
•
•
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•
American Psychiatric Association, Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision, 2000
Sadock, B. J. and Sadock V. A., Concise Textbook of Clinical Psychiatry, Third
Edition, 2008
Stern, et. al., Massachusetts General Hospital Comprehensive Clinical
Psychiatry, 2008. You can read this text online here.
Flaherty, AH, and Rost, NS, The Massachusetts Handbook of Neurology, April
2007
Stead, L, Stead, SM and Kaufman, M, First Aid© for the Psychiatry Clerkship,
Second Edition, March 2005
Klamen, D, and Pan, P, Psychiatry Pre Test Self-Assessment and Review,
Twelfth Edition, March 20093
Oransky, I, and Blitzstein, S, Lange Q&A: Psychiatry, March 2007
Ratey, JJ, Spark: The Revolutionary New Science of Exercise and the Brain,
January 2008
Medina, John, Brain Rules: 12 Principles for Surviving and Thriving at Home,
Work and School, February 2008
Stewart KL, “Dealing With Anxiety: A Practical Approach to Nervous
Patients,” 2000
Where can you find evidence-based
information about mental disorders?
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•
•
•
•
•
•
Explore the site maintained by the organization where evidence-based
medicine began at McMaster University here.
Sign up for the Medscape Best Evidence Newsletters in the specialties of your
choice here.
Subscribe to Evidence-Based Mental Health and search a database at the
National Registry of Evidence-Based Programs and Practices maintained by
the Substance Abuse and Mental Health Services Administration here.
Explore a limited but useful database of mental health practices that have
been "blessed" as evidence-based by various academic, administrative and
advocacy groups collected by the Iowa Consortium for Mental Health here.
Download this presentation and related presentations and white papers at
www.KendallLStewartMD.com.
Learn more about Southern Ohio Medical Center and the job opportunities
there at www.SOMC.org.
Review the exceptional medical education training opportunities at Southern
Ohio Medical Center here.
How can you contact me?1
Kendall L. Stewart, M.D.
VPMA and Chief Medical Officer
Southern Ohio Medical Center
Chairman & CEO
The SOMC Medical Care Foundation, Inc.
1805 27th Street
Waller Building
Suite B01
Portsmouth, Ohio 45662
740.356.8153
[email protected]
[email protected]
www.somc.org
www.KendallLStewartMD.com
1Speaking
and consultation fees benefit the SOMC Endowment Fund.
Are there other questions?
Carolyn Arnett, DO
OUCOM 1993
Kevin Kammler, DO
OUCOM 1993
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