How Should Antidepressant-Associated Anxiety Be Managed?

Sarah T. Melton, PharmD


November 05, 2013


How do you manage antidepressant-induced anxiety during initiation of therapy?

Response from Sarah T. Melton, PharmD
Associate Professor of Pharmacy Practice, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee

The first-line treatment for depression and anxiety disorders is often a selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI). Therapy with SSRIs or SNRIs can take up to 4 weeks for efficacy to be apparent and may make anxiety worse before improvement of symptoms is seen. During this acute phase of initial treatment, patients may experience new or worsening anxiety. This worsening anxiety is also called "jitteriness syndrome" and is often cited as reason for early discontinuation of therapy. There are no validated or commonly used measures for jitteriness/anxiety syndrome, so little objective evidence exists in the literature pertaining to it.

Emergent anxiety after starting an antidepressant is more common in younger patients and females.[1] An increase in anxiety and distress may lead to increases in suicidality.[2] A study examining anxiety after a single dose of citalopram showed that citalopram increased existing anxiety but was not anxiogenic in people without anxiety at baseline.[3] A short-term study of patients being treated for depression with an SSRI found a 15% incidence of increased anxiety during the initiation period.[4]

Managing increased anxiety during initial antidepressant therapy can be challenging, but several options exist to decrease the incidence or to manage symptoms.

In patients with anxiety disorders, especially panic disorder, it is advisable to start with a low dose of antidepressant and increase as tolerated. Patients with panic disorder are very sensitive to the anxiogenic effects of antidepressants, but jitteriness syndrome can be limited by starting with 25%-50% of normal starting doses for depression. This option may be appropriate for most patients. The total daily dose required for treatment of anxiety is often higher than those necessary for treating depression, especially with obsessive-compulsive disorder. Doses should be titrated slowly over a few weeks until efficacy is attained.[5]

To achieve rapid symptomatic relief of increased anxiety, benzodiazepines, such as clonazepam or lorazepam, may be started concurrently with antidepressant therapy.[2,6] Effectiveness and rapid relief of anxiety make benzodiazepines good short-term options to decrease the incidence of jitteriness syndrome.[2,5] Limitations include minimal effect on depressive mood, cognitive impairment, and abuse potential. Patients with a history of drug or alcohol abuse should not be prescribed these medications.

The benzodiazepine should be prescribed for the first 2-3 weeks of antidepressant therapy in patients requiring rapid relief of anxiety while the antidepressant begins to work. Patients prescribed benzodiazepine therapy should be educated that the medication is being prescribed for a limited period and will be discontinued after the first 2-3 weeks of therapy.

Beta-blockers provide some symptomatic relief of the increased anxiety associated with antidepressant therapy.[5] Addition of propranolol was shown to decrease jitteriness and restlessness in patients on fluoxetine.[7] However, evidence is lacking in this area, as only case reports currently exist.

Hydroxyzine is a histamine 1-receptor antagonist and can be used for symptomatic relief of anxiety symptoms.[6] This medication does not have the abuse potential of a benzodiazepine but is more sedating. Because of the anticholinergic side effects of this medication, it should not be used in elderly persons.

Currently, evidence is lacking concerning the use of hydroxyzine specifically in patients with emergent anxiety after initiation of an antidepressant. Hydroxyzine is indicated for the treatment of generalized anxiety disorder, but is frequently prescribed in the primary care setting to help with acute symptoms of anxiety.[6]

Antidepressant dose titration and use of adjunctive medications are possible methods to manage jitteriness syndrome associated with antidepressant therapy. Patients and providers should be aware of signs and symptoms of jitteriness syndrome when starting antidepressant therapy. Patients should be monitored closely for this adverse effect in order to relieve symptoms and promote adherence with antidepressant therapy.

Dr. Melton acknowledges the research assistance of Kyle Hagen and Jennifer Skeens, Doctor of Pharmacy Candidates at Gatton College of Pharmacy, East Tennessee State University.


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