ssri_discont_synd

PIC QUESTION OF THE WEEK: 03/07 /05 Q: Should the dosage of a patient taking paroxetine 40 mg daily for 4 years be gradually tapered or can the drug be abruptly discontinued?

A: Withdrawal effects can occur upon rapid cessation of all SSRIs. Signs and symptoms include dizziness, nausea, paresthesias, tremor, anxiety, shock-like sensations, insomnia, headache, irritability, lightheadedness, and dysphoria. These symptoms do not represent a recurrence of the original disease state, but are due to a true drug withdrawal syndrome (sometimes known as SSRI discontinuation syndrome). This condition can be diagnosed if at least two or more of the identified symptoms occur within 1-7 days of terminating therapy or during dosage reduction and must cause functional impairment or significant distress. Symptoms rarely occur if SSRI treatment is less than one month. Most cases of SSRI withdrawal are mild and self-limiting and do not require treatment. The frequency and severity of SSRI discontinuation syndrome depends on several pharmacokinetic and pharmacodynamic factors. These include half-life, absorption, protein binding, metabolite formation, and enzyme inhibition. SSRI discontinuation syndrome is least common with fluoxetine due to the long half-lives of the parent compound and active metabolite. On the other hand, paroxetine causes a high frequency of discontinuation syndrome because of its short half-life and lack of active metabolites. This results in an abrupt increase in serotonin reuptake and understimulation of serotonin receptors upon drug removal. The occurrence of discontinuation syndrome with paroxetine is ten times higher than with sertraline or fluvoxamine and one-hundred times higher than with fluoxetine. Due to the patient’s specific SSRI and length of therapy, abrupt withdrawal should not be attempted because the possibility of discontinuation syndrome is high. A tapering dose of ten mg per day can be attempted at one week intervals. If symptoms of withdrawal occur, a slower taper can be initiated.

References: • Abramowicz M, ed. Drugs for psychiatric disorders. Treatment GuidelinesMedical Letter 2003;1:69-76.

• Black K, Shea C. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000;25:225-61.

Kathryn A. Bayer, Pharmacy Clerkship Student Jennifer R. Snyder, Pharmacy Clerkship Student