Medication for Anxiety – Anxiolytics

Pharmacological intervention for mental health disorders involving excessive fear

by Tom Cloyd, MS, MA – Counselor / Psychotherapist – Cedar City and St. George, Utah (435)-272-3332 – email: tc (AT) tomcloyd (DOT) com (please read about content licensing)

About this document

Origin and sources. These are my summary notes on this subject (hence the occasional incomplete sentences), developed from a recent review, and supplemented by some explanatory material I have written to ease client use of this information. My principal sources are given below in References. For some excellent, readily available sources of additional information on this and related subjects, please refer to this site’s Links – Medication for mental illness page. Finally, in considering the information on this page, do remember my Disclaimer.

Coverage. Medication for anxiety is a large and complex subject, and this is far from a complete review. Most people with anxiety issues probably don’t medicate, but for those who do, certain topics are of particular interest. For now, the coverage here is somewhat focused on one of the more distressing anxiety disorders: Panic Disorder. The coverage here will become broader over time, as my review continues.

Introduction to the medication of anxiety disorders

Anxiety and fear. While not commonly recognized as such, it is important to recognise that anxiety is simply low-level or moderate fear. Fear is an automatic response to the perception of threat. There are many possible reasons why one might have this perception – some might be immediate, environmental, and utterly realistic, while others might be imperceptible to everyone, including the person experiencing the fear, and have no discernible connection to anything which can be readily identified. A lot goes on in the brain of which we have no awareness, and some of that unconscious process may result in our making anxiety (fear) in our brain.

Anxiolytics and “tranquilizers”. Historically, “major tranquilizers” is a term used to refer to anti-psychotic agents which have a calming effect, and “minor-tranquilizers” to refer to anti-anxiety agents. These terms are increasingly archaic, and may soon completely pass out of usage, at least in professional circles.

Anxiety and organic causes. Both organic brain dysfunction, due to injury (traumatic or chemically-induced), and poor self care (lack of sleep, fatigue, or low blood sugar) sets up the conditions for production of anxiety and fear. However, most anxiety is not directly traceable to organic issues.

I would strongly caution anyone from reflexively assuming that unconsciously produced fear is simply a sign of organic brain malfunction. This assumption can lead to wrong, quite ineffective, and even dangerous treatment strategies. What is wanted is an effective and lasting treatment, to the extent that it can be found. Obvious organic contributors to anxiety should be identified and reduced, when possible, as a first response. Enduring anxiety issues remaining are then best addressed with psychotherapy, and with medication where appropriate.

Appropriate use of anxiolytics. Long term treatment of anxiety with medication is relatively rare. Short term, as-needed, self-administration of anxiolytics as an aid to managing an immediate challenge is, however, fairly common, and can be a productive and appropriate use of these medications.

If this must be done regularly, I advise investigation of ALL the causes of the anxiety, as even anxiety of a primarily organic origin can often be reduced or eliminated with psychotherapy-mediated changes in brain function. Still, at times during such a psychotherapy intervention, use of anxiolytics can be a good thing, and for some people ongoing as-needed (“PRN”) self-administration is an entirely appropriate adaptation to an uncomfortable vulnerability of their brain. It’s simply a pragmatic management strategy and should be approached as such.

Need for professional consultation. Because some of the agents used for anxiety symptom relief can be risky (not as risky as, say lithium, but riskier than the SSRI antidepressants), it is simply foolish to use these medications without professional consultation. This means you must NOT “borrow” such medications from friends, or make major decisions about changing use of your prescriptions without professional consultation. For drug-usage questions, your pharmacist is an excellent source; for application to a specific problem or person, you must consult your medical services provider.

Anxiolytic use shouldn’t cause anxiety! Anti-anxiety agents (more tersely referred to as "anxiolytics"_ have some very appropriate – and very inappropriate – uses in psychotherapy. Knowledge is your friend, here, for some of these medications are strong and even addictive. But don’t allow this to cause you further anxiety! Simply get informed, then relax and engage in wise use.

Anxiolytics vrs. hypnotics. Anxiolytics are similar in effect to hypnotics, another major class of psychotropics, but don’t necessarily cause sedation. Hypnotics are for treatment of insomnia, but anxiolytics focus on relief from anxiety. Newer agents in both classes can be more specific in effect than older ones, which can be helpful for some people.(¹ p. 311)

Disorders for which anxiolytics may be prescribed

Because anxiety is a feature of so many disorders, anxiolytics potentially have a wide range of applications, including:

• Adjustment disorder with anxious mood
• Agoraphobia
• Alcohol and anti-anxiety agent withdrawal
• Anger problems (because anger is a response to fear – which is a high level of anxiety)
• Catatonia (which can be a response to anxiety)
• Delirium
• Dementia
• Generalized anxiety disorder
• Hyphochondriasis (this can be a physical response to chronic anxiety)
• Mania
• Nicotine abuse (attempts to reduce nicotine dependence can provoke considerable anxiety)
• Obsessive-compulsive disorder
• Obsessive-compulsive spectrum disorders (a wide range of compulsive, addictive behaviors, all of which may be seen as attempts to manage or reduce intolerable levels of anxiety)
• Panic disorders
• Posttraumatic stress disorder
• Restless leg syndrome
• Schizophrenia
• Selective mutism
• Separation anxiety disorder
• Social phobia²

Risks

Any consideration of risks of drug usage must also consider risks of non-usage, something often overlooked in casual considerations. Anxiety is not one of the more dangerous psychological symptoms, although it can and does co-occur with others (e.g., depression, substance abuse, psychosis) which certainly are documented risk factors for self-harm behavior and increased mortality.

Anxiolytics are not, in general, especially risky substances. One recent large epidemiological study concluded that when significant confounding variables (those which can cause results to be falsely significant) were formally taken into consideration, the long term mortality increase associated with use of anxiolytics was quite small, and likely non-existent.³

Anxiolytic drug classes and usage

Usage trends

Common belief among psychotherapy professionals is that benzodiazapines are the most prescribed of the four classes (see below) of anxiolytics.

This is supported by 1991 study of hospital prescription practices (it may be presumed that the clients served in this setting had more urgent anxiety-management issues than are normal in non-hospitalized clinical populations). In this study, in a general hospital setting, about one in five patients received anxiolytic prescriptions, and most of these were for benzodiazapines. Post-discharge, drug usage in this population fell to a level equal to the general non-hospitalized population.

Anxiolytic drug classes and names

Benzodiazapines

• Alprazolam “Xanax”
• Chlordiazepoxide “Librium”
• Clonazepam “Klonopin”
• Clorazepate “Tranxine”
• Diazepam “Valium”
• Halazepam “Paxipam”
• Lorazepam “Ativan”
• Oxazepam “Serax”

Azapirones

• Buspirone “BuSpar” (anxiolytic)

Andronergics

• Clonidine “Catapress” (anti-hypertensive)
• Propanolol “Inderal” (beta-blocker)

Antihistamines

• Hydroxyzine “Atarax”/“Vistaril” (antihistamine, anxiolytic)

Antidepressants

All classes of antidepressants can be useful with various anxiety disorders, with selection depending upon the disorder present. All can be helpful with panic disorder.(¹ p. 321]

Benzodiazapines

Principal mode of action

The brain’s principal inhibitory neurotransmitter is GABA, and “benzos” act to enhance their effect. The result is simply that it becomes more difficult for neural networks to be activated – it takes a higher threshold of input stimulation to cause a neural cascade effect. Anxiety simply becomes more difficult to trigger.

Critical distinctions between benzodiazapines

• Speed of action. Some act quickly, while others take more time to have their effect.
• Duration of effect – Half-life. Some are processed out of the body quickly (short half-life), while others linger (longer half-life).
  • Short half-life anxiolytics tend to have faster onset, and more severe, withdrawal effects, and greater inter-dose anxiety.
  • Longer half-life anxiolytics tend to have adverse effects on daytime functioning (a “drugged” feeling) when taken at night. Withdrawal affects are also more delayed, enduring, and mild, when they occur.
• Some have direct effects, while others (a minority) break down metabolically into chemicals which have direct effects.(¹ p. 315)

Dose dependent effects

• With episodic (PRN) doses, speed of absorption and drug half-life are critical factors influencing effect.
• With long term (chronic) dosing, distribution in tissues become more complete and stable, and drug half life becomes dominant factor influencing effect.(¹ p. 315)

Cautions

Anxiolytic use can lead to physical tolerance (lessening of effect per unit dose over time) and physiological and/or psychological dependence. Chronic use is advisable only with caution and for specific, well-defined symptoms. Targeting of well-defined symptoms is a general “best-practice” with benzodiazapines, and repeated dosing is advised to be limited to 1-2 weeks duration.(¹ p.320)

Xanax (alprazolam / anxiolytic)

Alprazolam has a long history of association with panic disorder and its treatment.⁴

Summary of principal features

• Peak plasma levels attained in 1-2 hours.
• Half-life: 12-15 hours.
• Dose: 1-2 mg/daily; extreme levels: 0.5-8.0.
• Distribution speed (how quickly it gets to the parts of the nervous system where an effect is desired) – intermediate(¹ p. 317).
• PRN usage: appropriate for when anxiety challenges are 5 times a week or less (just a rule of thumb).
• Has a high receptor affinity, and more withdrawal effect than its half-life would predict.
• Due to its speed and duration of effect, is ideal for use with panic attacks.(¹ pp. 311-321)

Treatment of panic disorder

Principal medications used are antidepressants and benzodiazapines.

Antidepressants

• Antidepressants (SSRIs and TCAs – tricyclics) are useful and effective even when there is no apparent mood disorder. The effect is more on event frequency than event severity.
• Have been shown to be effective in treatment of panic disorder in both moderately short (1.5-2 months) and longer term (8-12 months) dosing periods. Some meaningful responses may occur in as little time as 2-4 weeks. In some cases they are a better choice than benzodiazapines, as a principal medication.
• Administration of antidepressants needs to be for longer period with panic disorder than for treatment of depression. In general, dosage for at least 6 months is advisable, and should continue until symptoms are gone. Symptom relapse is around 85% if discontinued in 6 months, and 25% if discontinued in 18 months.
• Effectiveness has been demonstrated with fluvoxamine, paroxetine, sertraline, fluoxetine, and citalopram (all SSRIs), as well as the TCAs imipramine, nortriptyline, and others.(¹ pp. 329-331)

Benzodiazapines

• Alprazolam, clonazepam, paroxetine, or diazepam are most often used.
• Patients are frequently very reluctant to stop taking these medications.
• Alprazolam:
  • tid/qid dosing is common, due to short duration of action – which can vary from 2 to 6 hours.
  • Usually effective at around 3-5 mg/day. Up to 10 mg/day may be required.
  • Manic side-effects can occur.
  • Withdrawal is a real concern, where tolerance has built up, but this typically requires higher doses over extended periods of time.⁵
  • Withdrawal symptoms can be worse than original symptoms.
  • To facilitate withdrawal, gradual substitution of clonazepam for alprazolam is a good tactic.
• May be especially useful for anticipatory anxiety.
• Effects often seen in 1-2 weeks (with non-acute dosing).
• For non-acute dosing, clonazepam may be superior:
  • Dosing frequency is much lower (bid, rather than tid/qid).
  • Withdrawal effect less severe than with alprazolam.
  • In one study, 80% of panic disorder patients preferred clonazepam over alprazolam.
• Symptom remission is less in more severely impacted patients
  • These individuals need to be given antidepressants.
  • Higher dosage levels – 4-6 mg/day alprazolam – may be needed.(¹ pp. 329-334)

Adjunctive medication for anxiety – anti-depressants and beta-blockers

A number of medications are can be productively used to supplement the principal medication used in anxiety treatment.

• Antidepressants (see above).
• Beta-blockers – most useful for adjunctive treatment of physical symptoms associated with anxiety, and so is especially useful at times with panic disorder. Propanolol is the main medication used. Heart rate reduction appears to be a good guide to adequacy of dosing level. Negative effects on quality of consciousness are not usually seen with beta-blockers. Fatigue and depression side-effects may be observed.(¹, pp. 322-323)

Notes

¹ Maxmen

² List from Maxmen, pp. 311-312

³ See Hausken.

⁴ See Healy

⁵ See Alprazolam

References

My annotations here are offered to assist the reader in making good use of these resources.

Alprazolam – If you consult one single resource regarding this medication, this might be your best choice. Brief, authoritative, with excellent cross-referencing to related material.

Alprazolam. (2009, March 21). In Wikipedia, The Free Encyclopedia. Retrieved 06:34, March 22, 2009, from http://en.wikipedia.org/w/index.php?title=Alprazolam&oldid=302426521 – This article has been nominated by the Wikipedia community as an example of a “Good Article” – a fairly high honor, actually.

Anxiolytics – There is some good and some not-so-good information here. Read with caution. This should not be considered an authoritative source, although it can start you thinking about things you should think about, and lead you to other sources. As is typical of too many Wikipedia articles, a balanced review of the literature is not in evidence here, in my opinion.

Hausken, et al. (2007). Use of anxiolytic or hypnotic drugs and total mortality in a general middle-aged population

Healy, D. (2000). The Psychopharmacologists, Vol. III: Interviews. London: Arnold. pp. 479–504.

Maxmen, J. S., & Ward, N. G.(2002). Psychotropic drugs fast facts. New York: Norton

MedicineNet.com – An excellent general Internet resource for medication information. Authorship is explicit, and authoritative. For other, possibly even better Internet resources, see this site’s Links – Medication for mental illness page.