Learning Objectives:

After reading this article, you should be able to:

1. Understand the pharmacotherapy options for panic disorder, including the use of antidepressants (SSRIs and SNRIs) and benzodiazepines, their benefits, potential side effects, and best practices for their use.
2. Recognize the potential drawbacks of benzodiazepines, such as the risk of dependence, tolerance, and withdrawal symptoms, and considering alternative medications like pregabalin.
3. Understand the importance of integrating medication treatment with psychotherapy, particularly cognitive-behavioral therapy (CBT), and how combination treatment may yield better outcomes. 

As a therapist, it's essential to understand the medications your clients with panic disorder might be taking and how they interact with psychotherapy. In this article we will provide an overview of current pharmacotherapy for panic disorder and discuss ways that therapy and medication can work together synergistically.

Understanding panic disorder and its treatment

Panic disorder is characterized by recurrent and unexpected panic attacks, which are sudden episodes of intense fear accompanied by physical symptoms like a pounding heart, sweating, and trembling. These attacks can lead to significant distress and impair daily functioning.

Pharmacological treatment is often a critical component of managing panic disorder, alongside psychotherapy. The most common medications used to treat panic disorder are antidepressants and benzodiazepines, and it's essential to know their benefits, potential side effects, and best practices for their use.

Antidepressants: The go-to medications for panic disorder

Antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are generally the first-line medications for panic disorder. They are effective and cause minimal side effects. Some examples of SSRIs and SNRIs used in panic disorder treatment include the following (those with FDA approval are in bold):

• Paroxetine (Paxil)
• Sertraline (Zoloft)
• Fluoxetine (Prozac)
• Venlafaxine (Effexor XR)
• Fluvoxamine (Luvox)
• Citalopram (Celexa)
• Escitalopram (Lexapro)

It's crucial to understand that antidepressants may initially cause side effects like anxiety, agitation, and insomnia. Therefore, when starting these medications, it's essential to "start low and go slow" to minimize these effects. For example, paroxetine should be started at 5 mg to 10 mg daily and slowly increased to a goal of 20 mg to 40 mg daily, instead of starting at a higher dose.

Tricyclic antidepressants (TCAs) can be considered if at least two separate trials with SSRIs or SNRIs have been unsuccessful. Examples include nortripyline and imipramine. However, TCAs not commonly used because they cause more side effects than SSRIs, including dry mouth, weight gain, urinary retention, and constipation.

Benzodiazepines: Fast-acting but with caveats

Benzodiazepines are another treatment option for panic disorder, known for their rapid onset of action and ability to quickly target the physical symptoms of anxiety, anticipatory fear, and avoidant behavior. The two benzodiazepines FDA-indicated for panic disorder are alprazolam (Xanax) and clonazepam (Klonopin)—though all benzodiazepines are likely equally effective. 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.

Benzodiazepines have some potential drawbacks, including the risk of dependence, tolerance, and withdrawal symptoms.

Emerging treatments: Pregabalin

In recent years, pregabalin (Lyrica), a medication primarily used for neuropathic pain and epilepsy, has shown promise as a treatment for panic disorder, despite not being FDA-approved for this use (Bighelli I, et al., JAMA Psychiatry 2018;75(2):133-142). Pregabalin may offer some advantages over benzodiazepines, including a lower risk of dependence and potentially fewer interactions with CBT.

Combining medications with psychotherapy

As a therapist, it's crucial to understand how medications can impact the psychotherapy you provide. Research suggests that starting clients on both CBT and antidepressants simultaneously may yield better outcomes. For example, a systematic review of 21 studies comparing psychotherapy plus antidepressants to antidepressants alone indicated that combination treatment was more likely to be effective during the acute and continuation phases of treatment (Furukawa, T. A., Watanabe, N., & Churchill, R. (2006). Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: systematic review. The British journal of psychiatry : the journal of mental science, 188, 305–312. https://doi.org/10.1192/bjp.188.4.305).

However, certain meds, such as benzodiazepines, may reduce the long-term effectiveness of CBT—because a key CBT technique is for the client to learn cognitive and relaxation strategies to relieve anxiety. If they are depending on fast-acting medications to treat anxiety, they are unlikely to master cognitive techniques. For this reason, a standard pharmacologic technique is to start treatment with both an antidepressant and a benzodiazepine and then discontinue the benzodiazepine in four to six weeks when the antidepressant becomes effective. Doing so increases the likelihood that your client will successfully stop benzodiazepine treatment and maintain the benefits of CBT (Otto, M. W., McHugh, R. K., Simon, N. M., Farach, F. J., Worthington, J. J., & Pollack, M. H. (2010). Efficacy of CBT for benzodiazepine discontinuation in clients with panic disorder: Further evaluation. Behaviour research and therapy, 48(8), 720–727. https://doi.org/10.1016/j.brat.2010.04.002).
 
Guidance for discussing medication concerns with clients

As a therapist, you may not always agree with the prescribed medications for your clients. For example, a client may have seen their primary care physician or psychiatrist at a recent visit and received a prescription for a month of benzodiazepines with refills. You may wonder if this will undermine your course of exposure-based CBT. It's crucial to approach these situations with care. Here are a few tips to keep in mind:

1. Prioritize Client Autonomy: Remember that your role is to guide, not to dictate. The patient should make the final decision, with input from their prescribing physician and you as the therapist.
2. Share Your Concerns Professionally: If you have concerns about the medication, voice them constructively. Express your worries about the potential impact on therapy, but avoid overly negative or definitive statements that could undermine the patient's trust in their prescriber.
3. Encourage Dialogue: Recommend the patient to discuss your concerns with the prescriber. If necessary, consider a collaborative conversation involving all parties to ensure clear, consistent communication.
4. Stay Informed and up to date: If you have reservations about a prescribed medication, educate yourself about it. Read up on the latest research, potential side effects, and interactions with other treatments. The better informed you are, the better you can support your client.

CARLAT VERDICT: Understanding the landscape of medication treatment for panic disorder will help you ensure that you and your client’s prescriber are working in synergy to address your client’s symptoms.

FDA-Approved Drug Treatments for Panic Disorder

Editor's note: This article was originally published on July 4, 2024, and has since been updated with the addition of the CME test.