Tips for Recognizing, Treating Symptoms of SSRI Discontinuation

People who abruptly stop taking antidepressants or forget to take multiple doses of the medication in a row may experience the emergence of flu-like symptoms, insomnia, anxiety, and more. While such symptoms of antidepressant discontinuation tend to be mild and resolve within a matter of weeks, physicians should educate patients about this risk before initiating treatment.

Be Aware of Those Most Likely to Experience Symptoms

Any patient who discontinues or greatly reduces their antidepressant dose is at risk of experiencing symptoms, but studies show that those taking paroxetine—the selective serotonin reuptake inhibitor (SSRI) with the shortest metabolic half-life—may be at greatest risk (1, 2). Studies have also found that patients who develop depression at an earlier age, those with comorbid panic disorder, and those with a history of discontinuation symptoms are at higher risk of developing discontinuation syndrome (2, 3).

While some research with older antidepressant classes such as tricyclics has found that longer medication use increases discontinuation syndrome risk, duration of therapy beyond the initial four to six weeks does not appear to predict development of discontinuation symptoms for SSRIs (1), nor does the length of the antidepressant taper (1, 4).

Rule Out Other Causes of Symptoms

When evaluating a patient for symptoms associated with SSRI discontinuation, it is prudent to rule out other causes for the symptoms. These include the flu or infectious diseases, seasonal and other allergies, or foodborne illness (5). Additionally, changes in other medications may be responsible for the emergence of discontinuation symptoms. If a patient is undergoing cross-tapering—whereby one antidepressant is discontinued while another is initiated—discontinuation symptoms may be confused with treatment-emergent side effects of the new medication (6).

Symptoms of depression relapse can also have a similar presentation as symptoms of SSRI discontinuation; however, SSRI discontinuation syndrome typically manifests within days of stopping the medication whereas relapse occurs weeks or months later. To further confirm relapse or discontinuation syndrome, physicians can compare the post-discontinuation symptoms with the original depressive symptoms; if there is a high degree of overlap then it is likely a relapse.

Manage Severe Symptoms

Once identified, physicians should monitor the frequency, intensity, and burden of discontinuation symptoms in their patients. While mild symptoms are most common, there are several strategies that can be used to treat patients whose symptoms are more severe. If symptoms emerge during antidepressant tapering as part of a medication switch, then the symptoms should resolve within two to three days once the new SSRI is introduced (7, 8). If SSRI discontinuation is initiated to begin treatment with a nonserotonergic antidepressant such as bupropion, then a brief trial of fluoxetine (which has the longest half-life and lowest rates of discontinuation symptoms among SSRIs) can be undertaken while the new medication is titrated up. If a patient has an elevated risk for discontinuation syndrome, then augmenting an existing SSRI with an atypical antipsychotic or anxiolytic may be preferred to medication switching.

If the goal of SSRI discontinuation is to stop all antidepressant treatment, then a gradual taper may reduce the severity of discontinuation symptoms (even though it may not reduce overall risk of symptoms occurring). Low-dose liquid formulations are available for several SSRIs, including citalopram (10 mg/5 mL), escitalopram (5 mg/5 mL), paroxetine (10 mg/5 mL), fluoxetine (20 mg/5 mL), and sertraline (100 mg/5 mL) to help draw out tapering. If problematic discontinuation symptoms emerge, then restoring the original SSRI is an option. Additionally, antidepressant discontinuation symptoms can be managed briefly with other medications, such as antihistamines for acute dystonia, benzodiazepines for anxiety, and antipsychotics for hallucinations.

Educate Patients About Risks

There are preventive measures physicians can take to reduce the occurrence and severity of discontinuation symptoms from poor patient adherence. One is to educate patients about the risk and symptoms of discontinuation syndrome when starting any SSRI treatment. Physicians should also try and maintain patients on their maximum tolerated dose if possible and avoid large dose reductions. Use of measurement-based care practices, which emphasize regular use of symptom, adherence, and side-effect measures can assist physicians in this process.

Developing new or rebound symptoms after stopping a medication is not unique to antidepressants; patients also experience symptoms when stopping treatments for other chronic conditions, such as beta-blockers for hypertension and hypoglycemic agents for diabetes. In addition to educating patients about the risk of SSRI discontinuation symptoms when stopping or changing treatment with these medications, physicians should be sure to remind patients about the importance of medication adherence, as even skipping a couple of doses of a medication with a short half-life such as paroxetine can produce discontinuation symptoms. ■