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, DLFAPANovember 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 occasionssome 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 usuallytaken 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

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 duringa blackout.

What are some of the common side effects of these drugs?

• Drowsiness• Dizziness• Ataxia• Disinhibition• Amnesia• Paradoxical agitation• Respiratory depression1

• Dependence• Use in pregnancy not advised

1 I learned this first hand as a junior medical student from my first DO mentor. I gave an elderly womanlorazepam 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-actingMidazolamTriazolam

Intermediate-actingAlprazolam

OxazepamLorazepam

Long-actingClonazepamClorazepate

Diazepam

1-2 hours2-4 hours

6-10 hours5-10 hours10-20 hours

18-50 hours50-80 hours50-100 hours

What are some of the therapeutic dose ranges of these drugs?

DiazepamLorazepam

ClorazepatePrazepamOxazepam

AlprazolamClonazepam

Halazepam

5-40 mg/day1-6 mg/day15-60 mg/day20-60 mg/day10-120 mg/day1-8 mg/day0.5-6 mg/day20-120 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 providea 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

• Dizziness• Concentration

difficulties• Nausea, loss of

appetite• Observable

depression• Derealization• Depersonalization

1 Some 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

• 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

1 Some 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 withdrawal1 This medication takes a while to work. It works best in benzodiazepine virgins. They are hard to find. 2 It reminds me of ordering a Virgin Mary in Las Vegas.

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 anti-anxiety 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.

1 If the chronic administration of medication for anxiety is required, these are the drugs of choice. Mostpsychiatrists see the toughest cases, and we all have patients on both antidepressants and benzodiazepines.

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 mg7.5-30 mg1-2 mg10-25 mg.25-1.0 mg.5-2 mg.5-2 mg7.5-15 mg15-30 mg

Where can you learn more?

• 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?

• 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 OfficerSouthern Ohio Medical Center

Chairman & CEOThe SOMC Medical Care Foundation, Inc.

1805 27th StreetWaller Building

Suite B01Portsmouth, Ohio 45662

740.356.8153

StewartK@somc.org KendallLStewartMD@yahoo.com

www.somc.orgwww.KendallLStewartMD.com

1Speaking and consultation fees benefit the SOMC Endowment Fund.

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Are there other questions?

Carolyn Arnett, DOOUCOM 1993

Kevin Kammler, DOOUCOM 1993