Day # 78: "Other" Meds used in Anxiety Disorders

Welcome back to our current theme of anxiety disorders. Today is our last lesson during the anxiety disorder theme and we are going to round out the discussion with a brief overview of some of the "other" meds used in anxiety disorders to include hydroxyzine, alpha-2 agonists (clonidine, guanfacine), and beta-blockers (propranolol).


Today's Content Level: Intermediate



INTRODUCTION


•During an earlier lesson we discussed an overview of the treatment of anxiety disorders. If you haven't already read that lesson, then I highly recommend taking five minutes to read it. We learned that SSRIs are considered the first-line medications for these disorders.


•In addition to SSRIs and SNRIs there are other options for augmentation or as second-line agents. Some examples that we have covered previously are TCAs, MAOIs, benzodiazepines, buspirone, pregabalin/gabapentin, mirtazapine, and even antipsychotics and mood stabilizers in some cases.


•Today we well provide a brief overview of some miscellaneous pharmacological treatment options for anxiety disorders that do not fit into one of the previously covered categories.

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HYDROXYZINE


Hydroxyzine = Atarax, Vistaril


Mechanism

  • Hydroxyzine is an antihistamine.

  • Blocks histamine 1 (H1) receptors.

  • First-generation antihistamine that does have anticholinergic activity which does lead to some unwanted side effects.


Indications

  • Anxiety disorders: It is unclear whether its efficacy is due to an anxiolytic effect or a sedative effect. Approved for treatment of anxiety and tension "associated with psychoneurosis" and in "organic disease states in which anxiety is manifested". Is quick-acting (within 15-20 minutes) and a short-term medication, so it can be used prn as a non-benzodiazepine alternative for those who cannot or should not take benzodiazepines for various reasons. If used as a scheduled medication it is dosed three or four times per day due to short half-life.

  • Other indications: It is an antihistamine, so it has a bunch of other indications to include pruritus, nausea/vomiting, sedation, and more.


Side Effects

  • DRY (dry mouth, constipation, urinary retention, blurry vision)

  • Sedation

  • Tremors

  • Can impair cognitive and psychomotor performance.

  • Rare/Serious at high doses -> convulsions, respiratory depression, cardiac arrest (IM formulation combined with CNS depressants).


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ALPHA-2 AGONISTS


Clonidine (Catapres)

Guanfacine (Intuniv)


Mechanism

  • Alpha 2 adrenergic receptor agonist.

  • For hypertension -> stimulates these receptors in the brain stem which reduces sympathetic outflow from the CNS. This also decreases peripheral vascular resistance, renal vascular resistance, heart rate, and blood pressure.

  • For psychiatric use -> not fully understood but presumed to due to central actions on either pre or postsynaptic alpha 2 receptors and/or actions at imidazoline receptors.


Indications

  • Hypertension: FDA approved for the treatment of hypertension. Relatively fast-acting and blood pressure may be lowered 30-60 minutes after the first dose with greatest reduction in 2-4 hours. May take weeks for adequate blood pressure control. Not often used as first-line treatment due to significant rebound hypertension that can occur with missed doses or discontinuation without an adequate taper.

  • Attention deficit hyperactivity disorder (ADHD): FDA approved as non-stimulant option for the treatment ADHD in children and adolescents (clonidine and guanfacine) and adults (clonidine). They are less effective than stimulants for ADHD. Alpha 2 agonists usually are used when children respond poorly to a trial of stimulants or atomoxetine, have unacceptable side effects, or have significant coexisting conditions such as Tourette syndrome, tics, significant anxiety, or autism spectrum disorder. May be used as monotherapy or as adjunctive with ongoing stimulant. They have been reported to reduce stimulant-induced insomnia as well as impulsivity.

  • Anxiety disorders: Due to its anxiolytic properties these medications are sometimes used off-label to treat anxiety disorders to include panic disorder, social anxiety disorder, generalized anxiety disorder, and PTSD. The utility is likely due to blockade of the autonomic symptoms in anxiety (ex: palpitations, sweating, tremulousness), but also seems to improve subjective anxiety. Due to rapid onset it may also be useful as a prn. For anxiety disorders it is most frequently prescribed as an augmentation to SSRIs or other first or second line treatments.

  • Other indications: Treat symptoms of opioid withdrawal, tic disorders including Tourette's syndrome, vasomotor symptoms associated with menopoause, and insomnia.


Side Effects

  • Dry mouth

  • Sedation / Fatigue / Weakness

  • Dizziness

  • Hypotension / Occasional Syncope / Reflex Tachycardia

  • Constipation

  • Nausea / Vomiting

  • Sexual side effects: loss of libido or impotence

  • Worsened depression

  • Paradoxical worsening of anxiety/agitation

  • May disrupt sleep

  • Rare or Serious -> rebound hypertension (during withdrawal) and in some cases can lead to hypertensive emergency (encephalopathy, CVAs, etc). Can cause sinus bradycardia and even atrioventricular block. Overdose is characterized by sedation, hypotension, hypertension, bradycardia, dysrhythmia, respiratory depression, miosis, hypothermia, decreased reflexes, coma, and death (rare).


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BETA BLOCKERS


Propranolol (Inderal)

•Atenolol (Tenormin)


Mechanism

  • These medications work by.... blocking beta receptors. Surprise!

  • Three types of beta-receptors are spread throughout the body (β1, β2, β3). β1 are prevalent in the heart and kidneys and β2 in the lung and blood vessels.

  • Some beta blockers are β1 selective and bind preferentially to this receptor. These are commonly used in the treatment of various cardiovascular conditions such as coronary artery disease, heart failure, arrhythmias, etc... One example is metoprolol.

  • Other beta-blockers are nonselective and bind equally to β 1, 2, and 3 receptors. Nonselective beta-blockers, propranolol in particular, are the agents most frequently prescribed by psychiatrists.


Indications

  • Cardiac indications: As mentioned above beta-blockers are used in a variety of cardiovascular indications including heart failure, cardiomyopathy, myocardial infarction (early treatment and secondary prevention), arrhythmias (supraventricular arrhythmias and ventricular tachycardias), angina, and hypertension.

  • Anxiety: Used off-label particularly in the treatment of performance-only social anxiety disorder. Propranolol is the most commonly used beta-blocker for this indication. Can be taken 30-60 minute prior to the anxiety-inducing situation. There is no significant evidence from clinical trials that this is effective. Clinical experience suggests that roughly half of patients find prn beta-blockers useful for performance anxiety. 1 Has also been used as an adjunct in other anxiety disorders particularly in patients who have prominent awareness of physiological symptoms such as tachycardia or tremor or sweating.

  • Tremors: Used to treat familial or hereditary essential tremor. Also used off-label to treat lithium-induced tremors.

  • Migraine headaches: Evidence for effectiveness in prophylaxis of common migraine headaches.

  • Other indications: Akathisia (antipsychotic-induced), thyroid storm, pheochromocytoma (adjunct to alpha blockade), variceal hemorrhage prophylaxis.


Side Effects

  • Fatigue / Weakness

  • Dizziness

  • Bradycardia / Hypotension

  • GI upset / Nausea / Diarrhea / Constipation

  • Insomnia

  • Cold fingers or toes

  • Alopecia (hair loss)

  • Sexual side effects: loss of libido or impotence

  • May worsen depression (controversial)

  • Rare or Serious -> bronchospasm (worsen asthma and other lung conditions), severe bradycardia or heart block, raynaud phenomenon, hypersensitivity reaction or anaphylaxis, and if abrupt discontinuation without taper in rare cases have caused myocardial infarction or angina exacerbation and ventricular arrhythmia.



CONCLUSION


Great work today. Next post will be our last review quiz for anxiety disorders. After that we will begin a new theme of "emergency psychiatry".



Resources for today's post include the Stahl's Essentials for Psychopharmacology and the Maudsley Prescribers Guide.


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