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Pharmacotherapy in Generalized Anxiety Disorder (GAD)

Practitioner’s Information

Dan Egli


Winter 2005 - Table of Contents

Contents
Editorial
President’s Message/Jeff Barnett

From the Editor/Ed Lundeen

Special Editor’s Column -- The Lost Tribe/Stanley Graham


The National Perspective
New Faces – New Opportunities /Pat DeLeon

Washington Update/Ron Levant

APA Council of Representatives Report/Melba Vasquez

Florida’s Hurricane’s/Hilda Besner


Classic Reprints
The Dark Side of Evidence Based Treatment/Ron Fox

On Being Called a Provider/Karen Shore

Hallucinations/Ed Zuckerman

Schneiders First Rank Symptoms

Consumer Groups Listing


Practioner's Information
How Psychotherapy Works/Stanley Moldawsky

Pharmacotherapy in GAD/Dan Egli

The Importance of Documenting Your Training/J.B. Goebel

LGB Clients amd Their Therapists/Armand R. Cerbone and Kristin A. Hancock

Stalkers: Not Just for celebrities Anymore, Part 1/Linda Grounds

The 97532 Procedure Code/Peter Magaro


Early Career Professionals and Continuing Education
My Experience with Psychopharmacology Training/Sally Horwatt

Mentors Corner/Miguel E. Gallardo and Michael J. Murphy


Eine Kleine Dummheit
A New DSM Disorder/Rodney Timbrook

This article summarizes the author’s impressions (based on clinical experience, review of the literature, clinical supervision, and CE/CME) of what is currently being done when psychopharmacologic interventions are used in the treatment of generalized anxiety disorder (GAD).

This article, although focusing exclusively on the pharmacotherapeutic interventions with GAD, presumes that this is being done in the context of psychotherapy, probably a more “CBT-like” form of treatment. In other words, although focusing on the medications, I am coming from a “both-and” perspective rather than an “either-or” perspective. In many cases, 1+1=3. That is to say, it may be that the combination approach may be better than either approach by itself.

I will not take the time to review the DSM-IV criteria for GAD in this article and will simply lead into the pharmacologic interventions by suggesting the following:

  • the prevalence of GAD is ~2-5% of the population (women more than men and older more than younger)
  • there is a high degree of co-morbidity - especially major depression and substance abuse [so-called “self-medicating”].
  • DSM-IV requires at least a 6-month duration, with significant symptoms of worry,fatigue, insomnia, muscle tension, decreased concentration, and irritability).
  • GAD is a chronic illness
  • relapse rates are high
  • diagnostically, many clinicians see GAD as a possible obsessive-compulsive (O-C) spectrum variant, similar in some ways to hypochondriasis, given the ruminative focus, the cognitive style, the behavioral avoidance, and the rituals surrounding the GAD obsession (often the body, illness, health, etc.).
  • in the initial work-up, it is very important to rule out intoxication or withdrawal (e.g. from benzodiazepines) as a contributing factor. Intoxication could be something as simple as excessive caffeine usage.

This author, for the psychotherapeutic intervention, uses a CBT-like intervention that focuses primarily on anxiety-provoking, therapist-assisted, out-of-office, in-vivo exposure protocol. In general, this author does not use pharmacotherapeutic interventions in mild-to moderate GAD and tends to use pharmacotherapeutic interventions in a high percentage of moderate-to-severe GAD.

As with all Axis I anxiety disorders, before starting pharmacotherapy (in conjunction with the psychotherapy of choice), the clinician needs to first rule out:

  • a causative medical problem presenting as symptoms of GAD
  • a prescription medication presenting as symptoms of GAD (an iatrogenic cause)
  • rule out substance abuse (drug and/or alcohol).

Having ruled out the above three concerns, and assuming a moderate-to-severe degree of GAD, the informed prescriber (as with any other Axis I disorder) will try to find a first-line agent that is effective, at the lowest possible dose, with the fewest side-effects.

Some of the factors that influence this choice include:

  • age (pediatric/geriatric might affect dose, medically compromised, etc.)
  • co-morbid psychiatric/psychological conditions - Axis I, II [particularly Cluster C, the “anxious-fearful” cluster]
  • concurrent prescription (psychotropic or otherwise) medication (rule out activating or stimulating effects)
  • concurrent OTC (including “herbal”/organic) products (rule out activation. e.g. ephedrine)
  • co-morbid medical conditions (Axis III “hyper-” or “hypo-” conditions that have similar-to-GAD presentations)
  • personal or family history of response (positive or negative) to a particular class of medication (possible genetic predisposition to preferential response?)
  • personal or family history of response (positive or negative) to a particular agent within a particular class of medication
  • personal bias (positive or negative) about a particular class or medication within that class
  • concurrent substance abuse/history of addiction (avoid benzodiazepines)
  • cultural, religious beliefs/values about the use of medication

As with all prescription trials, the first-line agent (especially if not just being used on a p.r.n. [as needed] basis) needs to be geared to doing an adequate trial. An adequate trial is defined as an adequate dose for an adequate duration of time. Most of the patients this author has seen in consultation for so-called “treatment-resistant GAD” have been on many medications but have literally never had an adequate trial of a single medication based on the above definition. An exception to that would be the patient who was clearly compliant with the pharmacologic recommendations but had unremitting and severe side-effects. Obviously the most important clinical intervention in such a case is to discontinue the drug and try something else. This would neither be non-compliance nor false treatment-resistance.

Table 1 outlines the various medication classes and dosage ranges used in GADclick here to open larger pdf version of Table]

TABLE 2: ADVANTAGES/DISADVANTAGES

DRUG CLASS ADVANTAGES DISADVANTAGES
SNRI/SSRI safety
non-addiction
long-term efficacy
efficacy with co-morbid MDE
~1 month latency of onset of action sexual dysfunction (SSRIs)
BZ rapid onset of action
concomitant use in 1st month with SNRI/SSRI
? long-term efficacy
cognitive impairment
abuse potential
CNS depressants
b.i.d. dosing
drug-drug interactions with some antidepressants (e.g. (Luvox® and Serzone®)
AZAPIRONE Non-addictive
mild, transient side-effects
minimal sedation
1- month onset of action
no antidepressant efficacy
b.i.d. or t.i.d. dosing
ANTIHISTAMINE Non-addictive
mild, transient side-effects
Sedation
? long-term efficacy
EXP/INVESTIGATIONAL Non-addictive
Concomitant antidepressant properties
more rapid onset of action
b.i.d. dosing
? long-term efficacy

TABLE 3: PREFERRED ORDER OF PHARMACOLOGIC INTERVENTION

  • 1st-LINE: SSRI/SNRI
  • 2nd-LINE: BZ (prn)/Azapirone
  • 3rd-LINE: Polypharmacy/Experimental-Investigational

TABLE 4: PHARMACOLOGIC AGENTS NOT PREFERRED

DRUG/CLASS REASON
bupropion (Wellbutrin®, SR®, XL®) Anxiogenic
Few to no anxiolytic properties
mirtazapine (Remeron®/Remeron SolTab®) Significant weight gain & sedation
nefazodone (Serzone®) Liver toxicity
TCA Side-effects Cardiotoxicity Lethality in overdose
MAOI Dietary restrictions/tyramine
interactions (hypertension)
Long-term BZ Addiction CNS depressants State dependent learning Anterograde amnesia
Beta-blockers (e.g. atenolol [Tenormin®] or propranolol [Inderal®]) Efficacy data lacking in GAD Physical symptoms in performance
anxiety only
Kava kava (Piper methysticum)-herbal Liver toxicity (3/25/02 FDA Advisory)

TABLE 5: GAD INTERVENTIONS

SEVERITY TREATMENT
Mild-to-Moderate Psychotherapy/Non-pharmacologic (typically CBT-like)
Moderate-to-Severe Psychotherapy PLUS Pharmacotherapy (BZ if p.r.n.; SSRI/SNRI if long-term)

REFERENCES

Goodman, Wayne K. Selecting Pharmacotherapy for GAD. Journal of Clinical Psychiatry, 2004, 65, (Supplement 13), 8-13.

Van Meter, S.A. & Doraiswamy, P.M. Anxiety Disorders. In: Rakel, R.E., Bope, E.T. (eds.). Conn’s Current Therapy. Philadelphia, PA: W.B. Saunders Co., 2001, 1137-1142.

Dr. Egli is in full-time solo clinical practice in Williamsport, PA. Comments and questions can be directed to him at: sixeggs@suscom.net.

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