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Ask the Mental Health Expert Archives 2001-2004

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Stopping SSRI

Q. Is there a formula for stopping an SSRI, once there has been an effective result for a period of time? The medication is effexor and the patient is on 112.5 dosage.

A. You may be asking three separate, though related, questions, so I will try to cover all three bases. First of all, there is the issue of whether an antidepressant should be stopped at all, after a patient has recovered from one or more bouts of major depression. Many psychiatrists would argue that if a patient has experienced three or more serious bouts of major depression in his/her lifetime, that patient should remain on an prophylactic antidepressant treatment indefinitely (see Maixner & Greden, Depression & Anxiety 1998; 8(suppl 1):43-53)-what Dr. John Greden has called the "three strikes and you on" rule.

This is especially true when the patient has a very strong family history of major depression, or has a personal history of suicidal behavior, prolonged incapacity due to depression, and other risk factors. Then there is the matter of when a patient should be taken off an antidepressant, given that such discontinuation is appropriate.

In general, a patient should be maintained on the antidepressant dose that "got them better", for at least 6-12 months after clinical recovery occurs. This is owing to the high relapse rate of major depression when an antidepressant is stopped too quickly after apparent recovery. Some experts (see Janicak et al, Principles & Practice of Psychopharmacotherapy, 2nd ed, 1997) note that in the patient with a single episode of major depression, the best predictor of relapse is a strong family history of depression; e.g., one or more first-degree relatives with a history of major depression.

In such a case, maintenance antidepressant treatment should be extended to at least one year after recovery from the major depressive episode. Finally, your question might also be asking about discontinuation syndromes or withdrawal symptoms, after stopping an antidepressant. With the SSRIs, the risk may depend on the specific agent. For example, fluoxetine [Prozac] has a markedly longer T1/2 than do the other agents in this class. In theory, sudden discontinuation of fluoxetine should not pose a high risk of withdrawal symptoms, and clinical experience generally confirms this--you can usually stop fluoxetine all at once without serious problems.

Sertraline has a shorter T1/2 than fluoxetine (roughly 24 hours vs. 3-5 days), but sertraline's metabolite, desmethylsertraline, has modest clinical activity and a half-life of about three days. This may act as a buffer against withdrawal symptoms to some extent, but they are still reported with sudden discontinuation of sertraline. Rather severe withdrawal reactions have been reported even with relatively gradual discontinuation of paroxetine [Paxil], which has a T1/2 of only 24 hours and no active metabolites.

This may present as a flu-like syndrome characterized by nausea, vomiting, fatigue, myalgia, vertigo, headache, and insomnia (Barr et al, Am J Psychiatry, 1994). These symptoms have occurred even when paroxetine was tapered over 7-10 days. Venlafaxine (which is technically an SNRI-a serotonin-norepinephrine reuptake inhibitor) may also be associated with withdrawal symptoms when stopped too quickly-perhaps even over a period of two weeks.

For example, Rauch et al (1996) reported the successful use of venlafaxine in a small group of OCD patients; however, minor side effects (especially nausea) were common, and a troublesome withdrawal syndrome developed in four patients tapered off venlafaxine over a period of 4-14 days. Thus, I would usually recommend a slow taper and discontinuation of venlafaxine over a period of 2-3 weeks, if possible. Venlafaxine-induced withdrawal has been treated with fluoxetine, probably owing to the latter's long-lasting serotonergic action (Giakas & Davis, 1997).

I hope I've covered the right bases in answering your question.

January, 2001

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