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SSRI Discontinuation Syndrome


What is the SSRI Discontinuation Syndrome
The abrupt withdrawal of paroxetine and other selective serotonin reuptake inhibitors (SSRI) has been associated with numerous physical and psychological reactions.

Why Does a Discontinuation Syndrome occur?
Prolonged use of psychoactive drugs leads to adaptive changes within the central nervous system including changes in neurotransmitter release and receptor numbers. After drug stoppage the central nervous system must readjust to achieve the neurophysiological status present before treatment. If the plasma level falls rapidly, central nervous system readjustment cannot keep pace and discontinuation symptoms occur. (Haddad 1998)

Which drugs are associated with the SSRI discontinuation Syndrome?
Antidepressant discontinuation syndromes were first reported with imipramine and are well recognized with other tricyclic antidepressants. More recently there have been a number of reports indicating discontinuation syndromes occur in higher numbers with SSRIs, particularly those that have a short plasma half life. For example the incidence is higher with paroxetine and fluvoxamine than with fluoxetine. The first two agents have a plasma half-life of about 20 hours, while fluoxetine has a half-life of about 6 days. The discontinuation syndrome can also occur with sertraline and citalopram. (Haddad 1998)

How frequently does the SSRI discontinuation Syndrome occur?
The frequency of the discontinuation syndrome varies with the drug and the study methodology. In studies specifically designed to detect the discontinuation syndrome, rates are higher than those found in retrospective chart reviews. The rates of the discontinuation syndrome for paroxetine can range from 20% to 50% of patients. Likewise rates for fluvoxamine and sertraline are similar to those found for paroxetine. Rates for the longer half life fluoxetine are much lower. (Rosenbaum 1998)

Who is most likely at risk of SSRI discontinuation Syndrome?
The patients most at risk have the following characteristics:
  • Greater than 2 months use*
  • Abrupt dose reduction or discontinuation+
  • A previous episode of SSRI discontinuation syndrome^
  • Female gender+
(*Coupland 1996, +Bogetto 2002, ^Schatzberg 1997)

What are the typical symptoms associated with SSRI discontinuation?
Typical Symptoms (Rosenbaum 1998)
Worsened Mood Irritability Agitation Dizziness Confusion Headache Nervousness Crying Fatigue Emotional Lability Trouble Sleeping Dreaming Anger Nausea Amnesia

Can the discontinuation syndrome occur in children?
The discontinuation syndrome can occur at any age. Diler in a letter to the Journal of Clinical Psychopharmacology describes the syndrome in a nine-year-old boy. (Diler 2000)

Can the SSRI discontinuation syndrome occur with a dose reduction?
Yes. The discontinuation syndrome can occur whenever there is an abrupt drop in the plasma level of serotonin reuptake inhibitors.

Why is SSRI discontinuation Syndrome a clinical problem?
The discontinuation syndrome can lead to unnecessary and avoidable suffering. For some patients it can be mild and of short duration, for others however, the consequences can be quite severe. Sometimes the discontinuation symptoms are interpreted as being caused by a recurrence of depression. Both the physician and the patient may conclude they should stay on an antidepressant when that may not be the case. For other patients discontinuation symptoms can signify possible serious medical problems leading to unnecessary invasive and costly medical diagnostic procedures. (Strickland 2000)

What we can do to help you help your patients:

Step-Wise™10X10 Tapering Kit

This is a proprietary kit developed at Pharmacy.ca to assist physicians in tapering their patients and help patients avoid the negative effects of abruptly stopping a medication.

The words "Step-Wise" indicates that we are decreasing the strength of the medication in steps rather than an abrupt cessation.

The 10 X 10 refers to a 10% decrease in strength, each week for 10 weeks. In fact decreasing the amount by 10% of the patient's usual dose every week, it will take 9 weeks to completely discontinue the medication. The last step (the 10th week), is set at half of the amount the patient takes during the ninth week as an added precaution to step them down as gently as possible.

While the standard tapering kit is a 10X10 format we can prepare any tapering schedule you would like to use.

Why do we recommend a 10% reduction?
The Paxil monograph in the CPS recommends a gradual tapering but does not indicate what constituents gradual or how to taper. Our review of the literature indicates that there are case reports in which a 25% dose reduction was associated with the discontinuation syndrome. (Bogetto 2002) Another report indicates that a 16% taper was not associated with the discontinuation syndrome. (Keuthen 1994) The purpose of the taper is to avoid the syndrome, thus a very cautious approach is recommended.

Why do we recommend reduction at 1-week intervals?
Since paroxetine, fluvoxamine sertraline and citalopram, all have a half-life ranging from 20 to 33 hours and it takes about 5 to 6 half-lives to reach a new steady state condition, one week is the most appropriate interval. (Haddad 1998)

However we will prepare any tapering schedule requested by the physician and patient.

Example of a taper schedule
In the graph below we have presented a 10X10 tapering schedule. Note the strength in week 10 - 50% of the strength in week 9 - for a very gentle step down.


References
  1. Barr, L. C., W. K. Goodman, et al. (1994). "Physical symptoms associated with paroxetine discontinuation." Am J Psychiatry 151(2): 289.
  2. Bogetto, F., S. Bellino, et al. (2002). "Discontinuation syndrome in dysthymic patients treated with selective serotonin reuptake inhibitors: a clinical investigation." CNS Drugs 16(4): 273-83.
  3. Coupland, N. J., C. J. Bell, et al. (1996). "Serotonin reuptake inhibitor withdrawal." J Clin Psychopharmacol 16(5): 356-62.
  4. Diler, R. S., L. Tamam, et al. (2000). "Withdrawal symptoms associated with paroxetine discontinuation in a nine-year-old boy." J Clin Psychopharmacol 20(5): 586-7.
  5. Haddad, P. (1998). "The SSRI discontinuation syndrome." J Psychopharmacol 12(3): 305-13.
  6. Keuthen, N. J., P. Cyr, et al. (1994). "Medication withdrawal symptoms in obsessive-compulsive disorder patients treated with paroxetine." J Clin Psychopharmacol 14(3): 206-7.
  7. Rosenbaum, J. F., M. Fava, et al. (1998). "Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial." Biol Psychiatry 44(2): 77-87.
  8. Schatzberg, A. F., P. Haddad, et al. (1997). "Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus panel." J Clin Psychiatry 58(Suppl 7): 5-10.
  9. Strickland, G. M. and D. W. Hough (2000). "Unilateral facial numbness and visual blurring associated with paroxetine discontinuation." J Clin Psychopharmacol 20(2): 271-2.

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311 Sherbourne St, Toronto, On M5A 3Y1 1-416-960-7768 OCP Accreditation number 17533, owner is Central Medical Pharmacy Inc. Designated manager is Veronique Koo, B Sc Phm. Pharmacists are available for counselling during operating hours.
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