Table
Recommended doses for antidepressants used to treat panic disorder
| Medication | Starting dose (mg/d) | Therapeutic range (mg/d) |
|---|---|---|
| SSRIs | ||
| Citalopram | 10 | 20 to 40 |
| Escitalopram | 5 | 10 to 40 |
| Fluoxetine | 5 to 10 | 20 to 80 |
| Fluvoxamine | 25 | 100 to 300 |
| Paroxetine | 10 | 20 to 80 |
| Paroxetine CR | 12.5 | 25 to 50 |
| Sertraline | 25 | 100 to 200 |
| SNRIs | ||
| Duloxetine | 20 to 30 | 60 to 120 |
| Venlafaxine XR | 37.5 | 150 to 225 |
| TCAs | ||
| Clomipramine | 10 to 25 | 100 to 300 |
| Imipramine | 10 | 100 to 300 |
| MAOI | ||
| Phenelzine | 15 | 45 to 90 |
| CR: controlled release; MAOI: monoamine oxidase inhibitor; SNRIs: serotonin-norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants; XR: extended release Source: American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd ed. Washington, DC: American Psychiatric Association; 2009 | ||
Treatment nonresponse. True non-response needs to be distinguished from poor response caused by inadequate treatment delivery, eg, patients not completing homework assignments in CBT or not adhering to pharmacotherapy. Asking patients about adverse effects or personal and family beliefs about treatment may reveal reasons for nonadherence.
Second-line treatments
Little data are available to guide next-step treatment options in patients who don’t achieve remission from their initial treatment. Patients who benefit from an SSRI, venlafaxine XR, or CBT but still have symptoms should be started on combination treatment. For a patient who experiences complete non-response to the initial treatment, discontinue the first treatment and switch to the other modality. In general, completely ineffective treatments should be discontinued when another treatment is added, but when partial improvement (>30%) occurs, continue the original treatment and augment it with another approach.
For patients pursuing pharmacotherapy, poor response to an adequate SSRI trial usually should lead to a switch to venlafaxine XR, and vice versa. Failure to respond to both of these medication classes should prompt a switch to a benzodiazepine or TCA.
Benzodiazepines are a fast-acting, effective treatment for PD, with efficacy similar to SSRIs in acute and long-term treatment.14 Benzodiazepines may be prescribed with antidepressants at the beginning of treatment to improve response speed.15 Clonazepam and alprazolam are FDA-approved for treating PD. A high-potency, long-acting agent, clonazepam is the preferred initial benzodiazepine, dosed 0.5 to 4 mg/d on a fixed schedule. Although substantial data support using alprazolam for PD, it requires more frequent dosing and has a greater risk of rebound anxiety and abuse potential because of its more rapid onset of action. Compared with immediate-release alprazolam, alprazolam XR has a slower absorption rate and longer steady state in the blood, but this formulation does not have lower abuse potential or greater efficacy. Although not FDA-approved for PD, diazepam and lorazepam also have proven efficacy for PD.3
Benzodiazepines should be considered contraindicated in patients with a history of substance abuse, except in select cases.4 Benzodiazepines generally should be avoided in older patients because of increased risk for falls, cognitive impairment, and motor vehicle accidents. Table 2 lists situations in which benzodiazepines may be used to treat PD.
Table 2
Clinical scenarios in which to consider using benzodiazepines
| Coadministration for 2 to 4 weeks when initiating treatment with an SSRI or venlafaxine XR to achieve more rapid relief and mitigate potential antidepressant-induced anxiety |
| For patients who wish to avoid antidepressants because of concern about sexual dysfunction |
| For patients who need chronic aspirin or an NSAID, which may increase the risk for upper gastrointestinal bleeding when taken in combination with an SSRI |
| For patients with comorbid bipolar disorder or epilepsy |
| Next-step monotherapy or augmentation in patients who respond poorly to an SSRI, venlafaxine XR, TCA, or CBT |
| CBT: cognitive-behavioral therapy; NSAID: nonsteroidal anti-inflammatory drug; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant; XR: extended release |
TCAs are effective as monotherapy for PD. Most support comes from studies of imipramine or clomipramine.12 Similar to SSRIs and venlafaxine XR, use a low initial dose and gradually increase until the patient remits or side effects prevent further increases. SSRI and TCA combinations rarely are used unless the TCA is a relatively specific norepinephrine reuptake inhibitor (eg, desipramine, nortriptyline). Because TCAs are metabolized via the cytochrome P450 2D6 system and some SSRIs—particularly fluoxetine and paroxetine—strongly inhibit 2D6, combinations of TCAs with these agents may lead to dangerously high plasma TCA levels, placing patients at risk for cardiac dysrhythmias and other side effects.16
Monoamine oxidase inhibitors (MAOIs)—particularly phenelzine—are underused for PD. They have the strongest efficacy data for any class of medications outside the first- and second-line agents and have a unique mechanism of action. In patients who can comply with the dietary and medication limitations, an MAOI generally should be the next step after nonresponse to other treatments.3