Nonresponse to maintenance pharmacotherapy for panic disorder in adults and young people

Consider modifying treatment for panic disorder in an adult or young person if symptoms persist despite:

  • using an effective dose of at least 2 selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) as sequential monotherapy, each for a minimum of 4 weeks (full benefit may take 6 weeks or longer); and
  • discounting alternative reasons for treatment nonresponse.

Options for treatment modification include:

  • combining psychosocial interventions (if not already used) with pharmacotherapy
  • referral to a psychiatrist or age-appropriate mental health service—psychiatrists may use clonazepam, a tricyclic antidepressant (TCA) or phenelzine (see below)
  • a trial of clonazepam (see below).

For treatment considerations for females of childbearing potential, including advice on contraception, preconception planning and psychotropic use, see here.

For considerations in managing anxiety disorders such as panic disorder during the perinatal period, see here or for considerations in partners see here.

Studies have shown that clonazepam is an effective treatment for panic disorder and may be associated with lower rates of long-term relapse compared to SSRIs. However, benzodiazepines should not be used as first-line pharmacotherapy because of potential harms (including increased risk of falls, memory problems, motor vehicle accidents, daytime sedation and dependence). These risks are of particular concern in older people and people with a history of problem substance use (particularly problem alcohol use); in these people, harms of benzodiazepine use may outweigh benefits.

Benzodiazepine use is usually restricted to acute crises (see Panic attack) and short-term initial therapy. In treatment resistance, they may be considered for maintenance therapy, ideally in consultation with a psychiatrist. Follow the principles for the use of benzodiazepines in anxiety disorders.

If a benzodiazepine is considered appropriate for panic disorder, a suitable regimen in adults and young people is:

clonazepam 0.25 mg orally, twice daily. Assess the patient’s response to therapy after 2 to 4 weeks to determine whether dose adjustment is needed. If it is, increase the daily dose by 500 micrograms every 2 to 4 weeks, as tolerated, until an acceptable response is achieved or a daily dose of 4 mg is reached. If there is an acceptable response, continue the same dose for 6 to 12 months, then consider deprescribing. panic disorder clonazepam clonazepam clonazepam

Psychiatrists may use a tricyclic antidepressant (TCA) (clomipramine, imipramine) for panic disorder. A TCA can be considered first line if the patient has responded well to them previously. Doses of TCAs for treating panic disorder are often higher than the doses for treating depression; however, the dose must be increased gradually to reduce initial adverse effects. Lower doses may be needed in older people; consult a source of drug information. Intolerance commonly limits the use of TCAs, and toxicity in overdose must be considered. TCAs can cause changes in cardiac conduction—an electrocardiogram (ECG) should be obtained before treatment is started and repeated once the dose is stabilised, usually after 6 weeks. If either ECG shows abnormalities, seek advice from a cardiologist before starting or continuing treatment.

If a TCA is considered appropriate for panic disorder, a suitable regimen in adults and young people is:

1 clomipramine 25 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed, to a maximum of 300 mg at night. If an acceptable response is achieved, continue treatment for 6 to 12 months, then consider deprescribing panic disorder clomipramine clomipramine clomipramine

OR

1 imipramine 25 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed, to a maximum of 300 mg at night. If an acceptable response is achieved, continue treatment for 6 to 12 months, then consider deprescribing. panic disorder imipramine imipramine imipramine

Psychiatrists may use phenelzine (a monoamine oxidase inhibitor [MAOI]) in treatment resistance; however, dietary restrictions hinder its use (see Principles of using irreversible nonselective monoamine oxidase inhibitors [MAOIs]).