Pharmacotherapy for Panic Disorder

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When it comes to medication management, practitioners often treat anxiety disorders as though they are all the same. However, there are specific clinical pearls that you should be aware of to adequately treat your clients with panic disorder.

This review will provide you with a quick overview of panic disorder treatment options, including which medications work best, and when (and how) to use psychotherapy and medications together. Before beginning treatment, think about realistic treatment goals for your client. For example, a reduction in the number of panic attacks is important, but you should also seek to achieve more client-specific goals. These may include goals for the client such as: the ability to leave the house, drive to the grocery store, or travel on an airplane without anxiety.

Pharmacological treatment of panic disorder generally entails the use of antidepressants and/or benzodiazepines. Current treatment guidelines from the American Psychiatric Association (APA) (Practice Guideline for the Treatment of Patients with Panic Disorder, 2009) state that research data have not established superiority of either antidepressants or benzodiazepines or psychosocial interventions. Rather, the decision on how
to treat panic disorder with medication should be based on client preference and other factors.

Use of Antidepressants

The APA treatment guidelines indicate that, for treating clients with co-occurring depression or substance use disorders, antidepressants are preferable to benzodiazepines. Within the category of antidepressants, SSRIs and SNRIs are preferable to tricyclic antidepressants (TCA) because of the latter’s greater toxicity, side effects, and resultant lower acceptability to clients.

When choosing among these agents, consider that the only types of antidepressants that have been approved by the FDA, to date, for the treatment of panic disorder are SSRIs and an SNRI. The approved SSRIs are paroxetine (Paxil, Pexeva), sertraline (Zoloft), and fluoxetine (Prozac). The SNRI is venlafaxine (Effexor XR).

Other SSRIs and SNRIs are used “off-label” for treatment of panic disorder, and although they are not FDA-approved for such use, there is research evidence for the effectiveness of fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro).

Once you have chosen your initial agent, dosing becomes particularly important. Antidepressant-induced stimulation—which can result in symptoms such as anxiety, agitation, and insomnia—is common when starting treatment. For this reason, you should “start low and go slow.” For example, you should start paroxetine at 5 mg to 10 mg daily and slowly increase to a goal of 20 mg to 40 mg daily, as opposed to the 20 mg start dose you may use for treating depression (Lydiard RB, FOCUS 2011;9(3):253–263).

Are TCAs really viable treatment options for your client? The answer is yes, but only if you have tried two separate SSRI or SNRI trials unsuccessfully.

TCAs, which are among the earliest antidepressants developed, have generally been replaced by antidepressants that cause fewer side effects. Before moving to a TCA, you should aim to achieve therapeutic doses of your initial treatment for at least eight to 12 weeks. Two of these TCAs, imipramine (Tofranil) and clomipramine (Anafranil), have reasonable efficacy data if your client can tolerate such treatments. Unfortunately, anticholinergic side effects such as constipation and dry mouth, along with dizziness, sedation, and toxicity in overdose often limit TCA use.

Table 1: FDA-Approved Drug Treatments for Panic Disorder

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Use of Benzodiazepines

If you are seeking a more rapid treatment response, benzodiazepines are another pharmacotherapy treatment option. Benzodiazepine treatment will target the physical symptoms of anxiety, as well as anticipatory fear and avoidant behavior. Initial response to treatment may occur as early as the first day, as opposed to four to six weeks with antidepressants.

The two benzodiazepines FDA-indicated for panic disorder are alprazolam (Xanax) and clonazepam (Klonopin). Of the two, clonazepam is preferred due to its longer half-life and once to twice daily dosing. Alprazolam has a very short half-life, which increases the risk of rebound anxiety between dose administrations. These properties are why the recommended dosing is three to four times daily, and why the Prescribing Information calls for distributing the dosing as evenly as possible during waking hours to avoid interdose symptoms. Alprazolam also has a higher abuse potential because it crosses the blood-brain barrier more quickly than other benzodiazepines.

Should you avoid the use of benzodiazepines because of their abuse potential? Truthfully, benzodiazepines are rarely abused by clients who do not have an alcohol or drug abuse history (Pull CB and Damsa C, Neuropsychiatr Dis Treat 2008;4(4):779–795).

Because of the immediate calming effect your clients will experience with benzodiazepines, they may be inclined to want to take alprazolam as needed or during a panic attack. It is important to educate clients that panic attacks usually peak in 10 minutes. The onset of action of most benzodiazepines is 30 minutes to one hour, so don’t prescribe benzodiazepines PRN (as needed) for panic disorder. Treatment will be much more effective at preventing and treating panic attacks when clients take the medication every day on a set schedule.

Use of Medications with Psychotherapy

The medication that you choose for your client may have a positive or negative impact on the psychotherapy that you provide. There may be an advantage to starting your client on both cognitive behavior therapy (CBT) and antidepressants at the same time.

There are limited data indicating that antidepressant medications such as clomipramine, imipramine, fluoxetine, and paroxetine have increased treatment response when added to CBT. A systematic review of 21 studies comparing psychotherapy plus antidepressants to antidepressants alone indicated that combination treatment was 1.24 times (24%) more likely to be effective during the acute phase of treatment and 1.63 times (63%) more likely during the continuation phase of treatment (Furukawa TA et al, Br J Psychiatry 2006;188:305–312). Furukawa et al concluded that, “Either combined therapy [ie, pharmacotherapy and psychotherapy] or psychotherapy alone may be chosen as first-line treatment for panic disorder with or without agoraphobia, depending on the patient’s preferences.”

On the flip side, there are data showing that benzodiazepine treatment may reduce the durability of response to CBT (Lydiard RB, FOCUS 2011;9(3):253–263). For this reason, if using a benzodiazepine, it may be wise to initiate treatment with an antidepressant and a benzodiazepine, and then discontinue the benzodiazepine in four to six weeks when the antidepressant becomes effective. If using a benzodiazepine, a major advantage to also using psychotherapy is that the concomitant CBT will increase the likelihood that your client will successfully be able to stop benzodiazepine treatment (Otto MW et al, Behav Res Ther 2010;48(8):720–727).

TCRBH’s Verdict: Research suggests that first-line treatment for panic disorder should entail psychotherapy alone or psychotherapy combined with pharmacotherapy. Although medications have been shown to be beneficial, careful assessment of several factors is critical to maximizing that benefit. Factors to consider include: client preference, comorbid conditions, and, understanding how medication (and the timing of introducing and withdrawing medication) interacts with psychotherapy and with other medications. Indeed, it seems that without such careful consideration, use of medication that might otherwise help, can complicate and compromise treatment outcome.

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