eMedicine Specialties > Psychiatry > Adult
Panic Disorder: Treatment & Medication
Updated: Jul 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Pharmacotherapy, cognitive and behavioral psychotherapy, and other psychological treatment modalities are used to treat panic disorder.
Pharmacotherapy
Selective serotonin reuptake inhibitors (SSRIs) are generally used as first-line agents, followed remotely by tricyclics. Benzodiazepines can achieve long-term control but should be reserved for patients with refractory panic disorder and should generate a psychiatric referral for pharmacologic management review and potentially a psychotherapist for any additional nonpharmacologic treatment options.
Fluoxetine (Prozac) can be used (especially if panic disorder occurs with depression); however, patients may poorly tolerate it initially because it may initially increase anxiety, except at very low starting doses. Fluoxetine has a long half-life, making it a good choice in marginally compliant patients.
Mirtazapine (Remeron)2 has a much more sedating effect, generally reducing its potential to aggravate initial anxiety. Remeron acts distinctly as an alpha-2 antagonist, consequently increasing synaptic norepinephrine and serotonin, while also blocking some postsynaptic serotonergic receptors that conceptually mediate excessive anxiety when stimulated with serotonin. Remeron may cause residual morning sedation that often improves with continued therapy and may cause an increase in appetite or weight gain.
Sedating antidepressants like Paxil, Remeron, and TCAs are usually prescribed only at night before bed to help improve sleep but should include a warning not to operate a motor vehicle or machinery if feeling sedated or directly after the dose. Prozac alters metabolism of cytochrome P-450 2D6–cleared agents; this fact should be considered. Paxil (paroxetine) represents a partially sedating SSRI option that is also available in a controlled release preparation (Paxil CR), which may improve tolerability, but Paxil still inhibits P450 2D6.
Citalopram (Celexa) and escitalopram (Lexapro) are likely to cause fewer hepatic enzyme interactions and may be appropriate initial choices for patients with complicated medical regimens or those who are concerned about drug interactions. Escitalopram also appears particularly well tolerated in preliminary studies, although it may be restricted from some formularies due to the large difference in cost with Celexa without a commensurate improvement in efficacy or tolerability for many patients. Sertraline (Zoloft) represents a similar SSRI option with a slightly different pharmacodynamic profile, including sigma receptor effects, although it has some P450 3A4 interactions.
Benzodiazepines act quickly but carry the liability of physiologic and psychologic dependence. Benzodiazepines can be reasonably used as an initial adjunct while SSRIs are titrated to an effective dose. Benzodiazepines then can be tapered over 4-12 weeks while the SSRI is continued. This approach can improve short-term tolerability, although it may increase the risk of sedation and requires warnings not to operate motor vehicles after taking benzodiazepines or if feeling sedated.
Alprazolam (Xanax) has been widely used for panic disorder, but it is currently discouraged because of its higher dependence potential; alprazolam has a short half-life, which makes it particularly prone to rebound anxiety and psychological dependence. Clonazepam (Klonopin) has become a favored replacement because it has a longer half-life and empirically elicits fewer withdrawal reactions upon discontinuation.
Cognitive and behavioral psychotherapy
Cognitive and behavioral psychotherapy can be used alone or in addition to pharmacotherapy. The combination approach yields superior results for most patients compared to either single modality.
Cognitive therapy helps patients understand how automatic thoughts and false beliefs/distortions lead to exaggerated emotional responses, such as anxiety, and can lead to secondary behavioral consequences. Specific patterns of cognitive distortions (twisted thoughts) tend to respond best to specific techniques described in cognitive behavior therapy books (eg, The Feeling Good Handbook by David Burns, MD). While intended for use in conjunction with therapy, patients can purchase these books and complete the course themselves.
Behavioral therapy involves sequentially greater exposure of the patient to anxiety-provoking stimuli; over time, the patient becomes desensitized to the experience. Relaxation techniques also help control patients' levels of anxiety. Respiratory training can help control hyperventilation during panic attacks and help patients control anxiety with controlled breathing. Other forms of psychological treatment, including psychodynamic psychotherapy for specific issues, are available but exceed the scope of this article.
- Prehospital care
- Reassure and calm the patient.
- Transport the patient to a medical treatment facility to exclude medical causes for the first attack or when suspected on subsequent attacks.
- Emergency Department care
- Acute panic disorder is best treated with benzodiazepines. The natural history of panic attacks is spontaneous remission of panic symptoms with anxiety about recurrence during the episode.
- Prompt use of benzodiazepines can ease the uncomfortable anxiety associated with the attack and can provide the patient with definitive confidence that treatment can control the symptoms. This is particularly helpful for preventing subsequent visits to emergency services while longer-term therapy is helping the patient gain control.
- Consultation with a psychiatrist is helpful to initiate longer-term therapy and to provide follow-up planning. Longer-term therapy currently consists of SSRIs, often with additional psychotherapeutic techniques.
Medication
Benzodiazepine therapy should be provided if acute symptoms are still present at the time of the interview or if significant apprehension about future attacks remains. If necessary, benzodiazepines are continued for a brief period (<2 wk if prescribed on a scheduled basis).
Clonazepam has become the benzodiazepine of choice for outpatient use. Selecting patients for whom benzodiazepine therapy will be helpful rests on the clinician's judgment of a patient's ability to control his or her symptoms in their native environment, until the next psychiatric appointment, or until an SSRI begins to control the symptoms (about 2 wk, although sometimes much longer as the SSRI may require dose escalation). Alprazolam (Xanax) has been reviewed in the literature, although its use is currently discouraged because of its higher potential to elicit dependency.
Some patients may benefit from a standing dose of a benzodiazepine, whereas others do better with an as-needed (prn) dosing regimen. Longer-term control should be attempted with SSRIs if appropriate follow-up care (including the PCM) is available. SSRIs are usually well tolerated, and appropriate follow-up care merely consists of meeting with the patient in 2 weeks to assess treatment efficacy and to deal with temporary symptom exacerbations right after beginning SSRIs and ensuring the patient has no emergence of suicidal thoughts. Serotonergic drugs may contain warnings about potential increases in suicidal thoughts, particularly in those younger than age 25 years, but this is generally NOT associated with an increase in completed suicides compared with patients who receive no treatment. Potential suicide risk should be assessed routinely for every patient, whether they take SSRI treatment or not.
Other antidepressants that have an effect on the serotonergic system have been used, especially when SSRIs have been ineffective or poorly tolerated. Prior to SSRIs, the tricyclics and the monoamine oxidase inhibitors (MAOIs) were used much more commonly. More recently, venlafaxine (Effexor) and mirtazapine (Remeron) have been used, which act on both serotonin and norepinephrine. Beta-blockers, clonidine, calcium channel blockers, atypical antipsychotics (Abilify, Zyprexa, Seroquel, Risperdal, Geodon), buspirone, and anticonvulsants such as divalproex (Depakote) and gabapentin (Neurontin) have also been used as adjunctive agents in patients with refractory panic disorder, although these uses have not been approved by the US Food and Drug Administration.
Intermediate-acting benzodiazepines
By binding to specific receptor-sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters. These agents are effective on standing-dose and prn schedules.
Lorazepam (Ativan)
Sedative hypnotic with short onset of effects and relatively intermediate half-life. By increasing action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Adult
0.5-1 mg IV/IM or 1-2 mg PO bid/tid
Elderly: Begin with half dose
Pediatric
Not established
Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, narcotic analgesics, phenothiazines, barbiturates, and MAOIs
Documented hypersensitivity; end-stage COPD with tenuous respiratory function (could impact oxygenation/ventilation by lowering respiratory rate, even if tachypneic); advanced hepatic synthetic failure (decreases first-pass metabolism and prolongs half-life); history of addiction to alcohol/sedative-hypnotics (can initiate cravings/relapse, use with caution); acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease
Clonazepam (Klonopin)
Facilitates inhibitory GABA neurotransmission and other inhibitory transmitters. Relatively longer half-life (approx 36 h)
Adult
0.5-2 mg PO bid/tid
Pediatric
Not established
Phenytoin and barbiturates may reduce effects; coadministration of CNS depressants increases toxicity similar to lorazepam
Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation
Selective serotonin reuptake inhibitors
First-line agents for long-term management of anxiety disorders, with control gradually achieved over a 2- to 4-wk course, depending on required dosage increases.
All commonly used SSRIs appear to have a role in the treatment of panic disorder. Fluoxetine is covered herein because it has a very long half-life. This makes it well suited for patients who have difficulty remembering to take all of their medications each day. The longer half-life also minimizes the risk and severity of SSRI withdrawal that can occur when patients exhaust or abruptly discontinue their SSRI.
Fluoxetine (Prozac)
Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in reuptake of norepinephrine or dopamine.
Adult
20-60 mg PO qd; consider starting at 10 mg without benzodiazepine coverage (for 1-2 wk) or 20 mg with coverage
Pediatric
Not established
Phenobarbital and phenytoin may decrease effects; cimetidine may increase toxicity; because of its effects on cytochrome P-450 (especially 2D6) enzyme systems and on protein binding, can increase blood levels of antipsychotics, anticonvulsants, other antidepressants, beta-blockers, type 1C antiarrhythmics, and warfarin (Coumadin); serotonin syndrome may occur when used with other serotonergic agents such as buspirone, meperidine, tramadol, dextromethorphan, triptans, mirtazapine, nefazodone, or other SSRIs, but especially with MAOIs
Documented hypersensitivity; concurrently taking MAOIs or took them in the last 2 wk.
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in hepatic impairment and history of seizures; MAOIs should be discontinued at least 14 d before initiating therapy; Prozac has a long half-life and requires a longer wash-out period (typically 4-6 wk).
Paroxetine (Paxil)
Alternative sedating SSRI. Potent selective inhibitor of neuronal serotonin reuptake. Also has weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance dosing, make dosage adjustments to maintain patient on lowest effective dosage, and periodically reassess patient to determine need for continued treatment.
Adult
10-40 mg PO qhs
Pediatric
Not established
Phenobarbital and phenytoin may decrease effects; cimetidine may increase toxicity; because of its effects on cytochrome P-450 enzyme systems and on protein binding, can increase blood levels of antipsychotics, anticonvulsants, other antidepressants, beta-blockers, type 1C antiarrhythmics, and warfarin (Coumadin); serotonin syndrome may occur when used with other serotonergic agents such as buspirone, meperidine, tramadol, dextromethorphan, triptans, mirtazapine, nefazodone, or other SSRIs, but especially with MAOIs; inhibits CYP450 2D6
Documented hypersensitivity; concurrent administration with MAOIs or administering within 14 d of discontinuing an MAOI
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in history of seizures, mania, renal disease, and cardiac disease.
More on Panic Disorder |
| Overview: Panic Disorder |
| Differential Diagnoses & Workup: Panic Disorder |
 Treatment & Medication: Panic Disorder |
| Follow-up: Panic Disorder |
| References |
| « Previous Page | Next Page » |
References
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Press; 2000.
Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23(5):427-52. [Medline].
American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. American Psychiatric Association. Am J Psychiatry. May 1998;155(5 Suppl):1-34. [Medline].
Bandelow B, Behnke K, Lenoir S, et al. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. J Clin Psychiatry. Mar 2004;65(3):405-13. [Medline].
Bohni MK, Spindler H, Arendt M, Hougaard E, Rosenberg NK. A randomized study of massed three-week cognitive behavioural therapy schedule for panic disorder. Acta Psychiatr Scand. Mar 10 2009;[Medline].
Fogel BS, Schiffer RB, Rao SM, eds. Neuropsychiatry. ed. Baltimore, Md: Williams & Wilkins; 1996:263-8.
Hales RE, Yudofsky SC, Talbott JA, eds. APA Textbook of Psychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1999.
Kaplan HI, Sadock BJ, eds. Synopsis of Psychiatry. Behavioral Sciences/Clinical Psychiatry. 8th ed. Baltimore, Md: Williams & Wilkins; 1997:594-603.
Kim YW, Lee SH, Choi TK, Suh SY, Kim B, Kim CM, et al. Effectiveness of mindfulness-based cognitive therapy as an adjuvant to pharmacotherapy in patients with panic disorder or generalized anxiety disorder. Depress Anxiety. 2009;26(7):601-6. [Medline].
Kushner MG, Sletten S, Donahue C, Thuras P, Maurer E, Schneider A, et al. Cognitive-behavioral therapy for panic disorder in patients being treated for alcohol dependence: Moderating effects of alcohol outcome expectancies. Addict Behav. Jun-Jul 2009;34(6-7):554-60. [Medline].
Marcks BA, Weisberg RB, Keller MB. Psychiatric treatment received by primary care patients with panic disorder with and without agoraphobia. Psychiatr Serv. Jun 2009;60(6):823-30. [Medline].
Pfeiffer PN, Ganoczy D, Ilgen M, Zivin K, Valenstein M. Comorbid anxiety as a suicide risk factor among depressed veterans. Depress Anxiety. Jun 18 2009;[Medline].
Pollack MH, Simon NM, Worthington JJ, et al. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. Sep 2003;17(3):276-82. [Medline].
Sadock BJ, Sadock VA, Kaplan HI. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. Baltimore, Md: Williams & Wilkins; 2000:1445-90.
Stahl SM, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. Nov 2003;64(11):1322-7. [Medline].
Stahl's Essential Psychopharmacology, Neuroscientific Basis and Practical Applications. 3rd Ed. New York: Cambridge University Press; 2008.
Swoboda H, Amering M, Windhaber J, Katschnig H. The long-term course of panic disorder--an 11 year follow-up. J Anxiety Disord. 2003;17(2):223-32. [Medline].
Further Reading
Keywords
anxiety attack, panic attack, mood disorder, agoraphobia, phobia, anxiety disorder, anxiety provocation, acute anxiety, panic, panic disorder
