Anxiety: Pharmacotherapy

Text adapted from: "The adult patient with an anxiety disorder," in Psychiatry in primary care by Alina R. Brotea and Richard Swinson (CAMH, 2019).

Pharmacotherapy

Medications are a common treatment for anxiety disorders, and should be used when non-pharmacological interventions have not been helpful or when it is expected that non-pharmacological treatment alone will not suffice, such as when patients present with moderate to severe symptoms.

First And Second-line Medication

Recommended medications for anxiety disorders fall into the following groups:

• Antidepressants
• Anxiolytics
• Atypical antipsychotics
• Mood stabilizers
• Anticonvulsants.

Antidepressants are the first-line medications in the treatment of anxiety disorders. Anxiolytics may be used for a brief duration, but only if needed while an antidepressant is being initiated and titrated up. Atypical antipsychotics, mood stabilizers and anticonvulsants are used mainly to augment antidepressants.
First- and second-line medications are identified in the Canadian clinical guidelines for treating anxiety disorders (Katzman et al., 2014). Table 1 summarizes these medications. Table 2 lists usual daily dosing ranges of select antidepressants.
Antidepressants

All antidepressants have been shown to reduce anxiety symptoms. SSRIs and SNRIs are effective in treating panic disorder, agoraphobia, social anxiety disorder and generalized anxiety disorder. There is also evidence for noradrenergic and specific serotonergic antidepressants (NaSSA). The tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOI) and reversible inhibitors of monoamine oxidase A (RIMA) are effective as well, but they are less well tolerated than SSRIs and SNRIs, and are reserved for later choice.

For anxiety disorders, start antidepressants at a very low dose. Patients with anxiety disorders can be extremely intolerant of the side-effects of agitation and akathisia that may occur at the onset of treatment. To start, use the lowest available dose of SSRIs (e.g., escitalopram, 5 mg daily) or SNRIs (e.g., venlafaxine XR, 37.5 mg daily), and titrate up as clinically indicated and tolerated. It is better to start at a low dose with gradual increases over a long period than it is to challenge patients with doses they cannot tolerate because that can lead to frequent medication switching and discontinued treatment. The ultimate effective dose is usually the same as for major depression, or even higher. Patients with anxiety disorders often need prolonged treatment before the desired results are achieved.

If the first SSRI or SNRI does not help at all after eight to 12 weeks, or after a reasonable therapeutic dose has been reached, titrate off of the medication and switch to another SSRI or SNRI. When you titrate off of the initial medication, do it slowly, using a compounding pharmacy (e.g., for even smaller dosing options) if the patient experiences significant discontinuation side-effects. If two separate medication trials do not produce the targeted benefit, consider referring the patient for a specialist opinion.

Generally, pharmacotherapy for anxiety disorders lasts 12 months or more, followed by slow tapering if the patient is doing well and there are no significant concerns about relapse. Monitor patients because they may relapse during the withdrawal phase. Relapse is less likely if the patient receives CBT alongside pharmacotherapy or if CBT is introduced when the medication is being tapered.

Anxiolytics

Benzodiazepines are an effective short-term intervention for most anxiety disorders. Dependence is a significant problem, so avoid long-term use. Inter-dose exacerbation of anxiety, for example, when you are changing the dosage, can be confused with worsening of the original disorder. Contract with the patient about the discontinuation date. In any case, the suggested time limit for benzodiazepines is one to two weeks while an antidepressant is co-administered and then continued while the benzodiazepines are tapered.

Buspirone can be helpful in GAD and to augment antidepressant treatment, but it does not have the acute therapeutic effects of benzodiazepines.

Atypical antipsychotics

Atypical antipsychotics have been extensively studied as monotherapy in anxiety disorders, but they are not approved for this indication in Canada. However, in certain cases (e.g., significant sleep deprivation leading to overvalued ideas), short-term augmentation with atypical antipsychotics such as quetiapine XR (e.g., while the patient is on an SSRI or SNRI) has boosted the improvement made with antidepressant treatment.

Nevertheless, do not use antipsychotics unless absolutely indicated. Patients on these medications require baseline metabolic screening and close monitoring for metabolic changes, and the ongoing need for antipsychotics should also be monitored. If the medication is no longer needed or indicated, it should be titrated down and discontinued. If chronic use of antipsychotics is indicated or required (e.g., due to ongoing psychosis, paranoid thinking or overvalued ideas), consider referring the patient to a psychotic disorders specialist for further assessment.

Mood stabilizers and anticonvulsants

Mood stabilizers typically are not indicated in the treatment of anxiety disorders, but they are used if a patient also has bipolar disorder or other concerns that require a mood stabilizer or anticonvulsant. Pregabalin can be used as monotherapy for certain anxiety disorders, such as social anxiety disorder (Katzman et al., 2014). However, the side-effects associated with mood stabilizers and anticonvulsants are not as well tolerated as they are with SSRIs and SNRIs. If there is no comorbid bipolar disorder, SSRIs and SNRIs remain the first pharmacological choice for managing anxiety disorders.

Augmentation Strategies

Many medications can enhance the effect of antidepressants in all of the anxiety disorders. Consider the patient’s age, medical history and side-effect tolerance when deciding whether to use an augmentation strategy. If an anxiety disorder occurs with a second disorder, augmenting the anti-anxiety treatment with a medication to treat the second disorder can be very useful, but requires closer monitoring and caution (e.g., low-dose SSRI plus mood stabilizer in patients with co-occurring anxiety disorder and bipolar disorder; SSRI/SNRI plus stimulant in patients with co-occurring ADHD).

Medication Side Effects

Certain medications carry an increased risk of suicidality (SSRIs, SNRIs), metabolic syndrome (atypical antipsychotics), unfavourable side-effects such as serotonin syndrome (SSRIs, SNRIs), food restrictions (TCAs, MAOIs) and dependence (benzodiazepines). Be sure to inform patients of the risks and benefits associated with each medication, and monitor closely for side-effects.

In Anxiety

• The Primary Care Practitioner Role
• Screening & Assessment
• Diagnosis
• Treatment
  • Pharmacotherapy
  • Psychotherapy
• Clinical Tools
• Other Resources & References