What is the next step for a patient with MDD experiencing agitation and restlessness after starting paroxetine?

From the Guidelines

The most appropriate next step for this 38-year-old male experiencing agitation and restlessness after starting paroxetine for major depressive disorder is to reduce the paroxetine dose and consider a more gradual titration schedule. The patient is likely experiencing activation syndrome, a common side effect of selective serotonin reuptake inhibitors (SSRIs) like paroxetine, particularly when initiated at higher doses. This syndrome typically manifests as increased anxiety, insomnia, restlessness, and agitation within the first few weeks of treatment. Reducing the dose to 10 mg daily (from the typical starting dose of 20 mg) and then gradually increasing by 10 mg increments every 1-2 weeks as tolerated can help minimize these effects while maintaining therapeutic benefit. Additionally, temporary use of a benzodiazepine like lorazepam 0.5 mg twice daily for 5-7 days may help manage acute symptoms while the dose adjustment takes effect, as suggested by the clinical policy for managing adult psychiatric patients in the emergency department 1. It's essential to reassure the patient that these symptoms are typically transient and to schedule a follow-up within 1-2 weeks to reassess symptoms. If symptoms persist despite dose reduction, switching to an alternative SSRI with a potentially more favorable side effect profile, such as sertraline or escitalopram, may be warranted, considering the guidelines for treating depressive disorders with second-generation antidepressants 1. Key considerations include:

• Monitoring for symptoms of serotonin syndrome, especially when adjusting doses or combining serotonergic medications 1.
• Assessing patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis, beginning within 1 to 2 weeks of initiation of therapy 1.
• Being cautious of potential drug-drug interactions, particularly with SSRIs that may interact with drugs metabolized by CYP2D6, such as paroxetine 1.

From the FDA Drug Label

The use of paroxetine or other SSRIs has been associated with the development of akathisia, which is characterized by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment PAXIL may be associated with these serious side effects: agitation, hallucinations, coma, or other changes in mental status Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: feeling agitated, restless, angry, or irritable

The most appropriate next step is to monitor the patient's symptoms and consult with the healthcare provider as the patient is experiencing agitation and restlessness, which are potential side effects of paroxetine, particularly akathisia. The healthcare provider may consider dose adjustment or alternative treatment options. 2 2

From the Research

Patient Presentation

The patient is a 38-year-old male with major depressive disorder who has been started on paroxetine and reports feeling agitated and restless.

Possible Causes of Agitation and Restlessness

• The patient's symptoms could be due to the paroxetine, as it is known to cause agitation and restlessness in some patients 3.
• The patient's symptoms could also be related to their underlying major depressive disorder.

Treatment Options

• The study by 3 suggests that paroxetine is generally well tolerated, but it can cause adverse events such as nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor, and decreased appetite.
• Another option could be to add a benzodiazepine, such as clonazepam, to the patient's treatment regimen, as studies have shown that combined treatment with paroxetine and clonazepam can result in more rapid response than with paroxetine alone 4, 5.
• However, it's important to note that benzodiazepines can be addictive and should be used with caution, especially in patients with a history of substance abuse 6.

Next Steps

• The patient's symptoms should be closely monitored, and the treatment regimen should be adjusted as needed.
• The patient's dose of paroxetine could be adjusted, or another medication could be added to help manage their symptoms.
• The study by 5 suggests that initiating combined treatment with paroxetine and clonazepam, followed by benzodiazepine taper after a few weeks, may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.