Antidepressant discontinuation syndrome

Perspectives in Psychiatric Care, Jul-Sep 2003 by Antai-Otong, Deborah

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Question: One of my patients called several days after she abruptly stopped taking her SSRI antidepressant. She had been on 30 mg of paroxetine for several months and stopped because she felt better. Her chief complaints were dizziness, sleep disturbances, shakiness, and nervousness. What caused these symptoms? Are SSRIs and other novel antidepressants addictive?

Deborah Antai-Otong responds: Antidepressants are not addictive; nonadherence or abrupt withdrawal, however, can produce uncomfortable and sometimes serious reactions. There is growing evidence that a sizeable number of patients who are nonadherent or who abruptly discontinue SSRIs and other novel and older antidepressants report somatic, mood, and psychomotor symptoms or discontinuation syndrome. Typical presentations of discontinuation syndrome include lightheadedness, dizziness, headaches, GI disturbances, diaphoresis, lethargy, vivid dreams, and flu-like symptoms (Coupland, Bell, & Potokar, 1996; Fava & Rosenbaum, 1996). This syndrome is more evident in patients receiving short-acting agents, such as paroxetine (Paxil), fluvoxamine (Luvox), sertraline (Zoloft), and venlafaxine (Effexor), and less evident in patients receiving long-acting agents, such as fluoxetine (Prozac) with a longer half-life, nefazodone (Serzone), and citalopram (Celexa) (Antai-Otong, 2003; Coupland et al., 1996; Schatzberg et al., 1997).

Signs and Symptoms

As a rule, symptoms emerge within 24 to 72 hours of discontinuation and may persist from 1 to 2 weeks. A differential diagnosis is necessary to rule out other causes (Schatzberg et al., 1997). A rule of thumb concerning discontinuation syndromes is that the shorter the halflife of the antidepressant, the higher the incidence of the syndrome with abrupt withdrawal (Coupland et al., 1996). In essence, most factors that affect discontinuation syndromes include time on the drug (e.g., > or =2. months), drug potency, and half-life. Drugs with a shorter half-life wash out of the brain before the brain adapts or stabilizes its receptors resulting in withdrawal symptoms. For example, compare the half-life of paroxetine (15-22 hours) with fluoxetine (1-3 days) and its active metabolite (7-15 days). Abrupt cessation of fluoxetine decreases brain levels slowly over several weeks (Schatzberg et al., 1997), whereas abrupt withdrawal of paroxetine rapidly decreases brain levels and does not allow for brain adaptation, hence the increased risk of discontinuation syndrome.

The Discontinuation Consensus Panel (Schatzberg et al., 1997) describes major discontinuation symptoms as physical and psychological, and characterized by the following clusters:

* Disequilibrium (e.g., dizziness [exacerbated by movement or postural changes], lightheadedness, vertigo, ataxia, headaches)

* GI (e.g., nausea, vomiting, loose stools, dry mouth)

* Flu-like symptoms (e.g., myalgia, fatigue/lethargy, shaking chills, rhinorrhea)

* Sensory disturbance (e.g., paresthesia, sensations of "electric shock," burning, tingling)

* Sleep disturbances (e.g., vivid dreams, initial and middle insomnia)

* Psychological (e.g., anxiety, agitation, mania, crying spells, cognitive disturbances, slowed thinking)

Sometimes discontinuation symptoms are mistaken for worsening depression or even emergence of mania. It is imperative for nurses to distinguish discontinuation syndrome-mania from mania as a natural course of bipolar disorder (Ali & Milev, 2003). Misdiagnosis can lead to inappropriate treatment and affect future treatment adherence. A definitive diagnosis can be confirmed if symptoms abate within 12 to 24 hours after restarting the antidepressant.

Treatment Considerations

When choosing an antidepressant, psychiatric nurses must consider the possibility of a discontinuation reaction. Typically, discontinuation syndromes can arise with nonadherence (missed doses), abrupt discontinuation, and, less frequently, during dose reduction. Normally, discontinuation syndromes emerge within 24 to 72 hours after termination and are mild and transient, but sometimes they can become serious (e.g., induce mania or hypomania) (Schatzberg et al., 1997). Most reactions require no treatment other than reassurance. Psychiatric nurses must provide health education concerning strategies to avoid this syndrome, the importance of adherence, symptoms to report, and reassurance that it is time-limited.

More severe symptoms can be treated symptomatically or by restarting the antidepressant or starting one with similar properties or a longer half-life such as fluoxetine (Coupland et al., 1996; Haddad, 2001). In severe cases, fluoxetine can be used to taper a shorter half-life and minimize symptoms. The syndrome may last up to several weeks and may improve or abate within 24 hours by restarting the antidepressant (Preskorn, 1999). Additional preventive measures include tapering antidepressants over a 4-week period rather than abruptly, and offering reassurance that symptoms are short-lived and will abate within several days.

In brief, all antidepressants have the potential to produce discontinuation syndrome. Most data indicate that the time of onset and severity of symptoms vary among antidepressants with the shortest half-life SSRI, paroxetine, having the highest incidence, and the longest halflife, fluoxetine, having the lowest incidence post discontinuation. Treatment considerations must include psychoeducation with an emphasis on adherence, a 3- to 4-week graded withdrawal regimen, possibly with fluoxetine to minimize discontinuation symptoms in patients taking antidepressants with a short half-life.