Health - SSRI Withdrawal Syndrome

[Jatelka]

The following criteria define the SSRI (or SNRI) withdrawal syndrome:

Criterion A: A course of treatment in which an SSRI (or venlafaxine) is stopped
or interrupted or the dose is reduced after a period of 4 weeks or more.

Criterion B: Two or more of the following symptoms develop within 1 to 10 days
of criterion A (except for fluoxetine in which case the symptoms must develop
within 28 days):

(a) dizziness or light headedness
(b) nausea and/or vomiting
(c) headaches
(d) lethargy
(e) anxiety and/or agitation
(f) tingling (parasthesias), numbness or "electric" shock-like sensations in the
head or limbs
(g) tremors
(h) sweating
(i) insomnia
(j) irritability
(k) vertigo (dizziness)
(l) diarrhea

Criterion C: The symptoms of criterion B cause clinically significant distress
or impairment in social, occupational, or other important areas of functioning.

Criterion D: The symptoms are not due to a general medical condition or the
direct physiological effects of another substance (e.g., a medication or a drug
of misuse) that has been recently commenced, stopped, or altered in dosage.

Criterion E: The disorder is not better accounted for by an exacerbation/
relapse/recurrence of the psychiatric disorder for which the SSRI was
prescribed.

Adapted from:
Haddad PM The SSRI discontinuation syndrome: literature review and provisional
diagnostic criteria. Presented at: XXIst Collegium Internationale
Neuro-Psychopharmacologicum Congress. July 12-16, 1998; Glasgow, Scotland.
Reprinted in International Drug Therapy Newsletter. 1998, 33, 46.
Visit Depression Central

Revised 12/5//04

The cause of withdrawal syndrome following discontinuation of SSRIs is unknown, but the electric shock sensations reported with neck flexion are identical to Lhermitte's sign, which appears with dysfunction of the posterior spinal cord. This suggests change at a neuronal level.

It has been proposed that inhibition of reuptake initially increases the synaptic concentration of serotonin. Exposure to high concentrations of 5-HT, even for as short as five weeks, may cause down-regulation of receptors. When the SSRI is discontinued the concentration of 5-HT falls. The lower level of 5-HT is insufficient to provide an adequate agonist stimulus for the down-regulated receptors, resulting in withdrawal syndrome. Inhibition of 5-HT and norepinephrine receptors may be involved in withdrawal symptoms from venlafaxine.

Paroxetine possesses muscarinic antichoninergic activity and may cause withdrawal symptoms via the same mechanism as the tricyclic antidepressants. Compared to other SSRIs, paroxetine is the most pharmacologically selective antagonist at the 5-HT reuptake site.

The withdrawal syndrome usually subsides within several weeks of discontinuation in most reports. Withdrawal syndrome is most likely to occur in patients who receive SSRIs with a short half-life. A long half-life of the parent compound and/or active metabolite leads to a more gradual withdrawal. The onset of symptoms following abrupt discontinuation or taper is within one to seven days.

The optimum tapering regimen for each agent has yet to be determined by comparative clinical trials. Here is one suggestion (Skaehill and Welch, 1997)

Fluoxetine

Reduce by 5 mg every two weeks until dose is 5 mg/day, then 2.5 mg every two weeks

Fluvoxamine

Reduce by 25 mg every two weeks until dose is 25 mg/day, then 12.5 mg every two weeks

Paroxetine

Reduce by 10 mg every two weeks until dose is 10 mg/day, then 5 mg/day every two weeks

Sertraline

Reduce by 25 mg every two weeks until dose is 25 mg/day, then 12.5 mg every two weeks

Venlafaxine

Reduce by 25 mg every two weeks until dose is 25 mg/day, then 12.5 mg/day every two weeks ,

Paroxetine appears to be the SSRI most likely to cause withdrawal syndrome, with fluvoxamine and sertraline a close second, possibly due to their high inhibition constants and their shorter half-lives. Published fluoxetine withdrawal reports are scarce, possibly due to the long half-life of fluoxetine and the active metabolite norfluoxetine.

Hope this is of some help/interest

SWIM'll post a literature review in the archives (or at least she would if there was an SSRI section)

Reputation Comments on this post:

It's really great that this got brought up, not many people realize that this happens