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Shapiro, 2018. Subtherapeutic doses of SSRI antidepressants demonstrate considerable serotonin transporter occupancy: implications for tapering SSRIs

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bubbles

The whole paper isn't available, just the first para or two, so it's hard to see where they go with it but the second para cuts off where they start talking about three different groups of symptoms after discontinuing the med. The author's email address is there, if someone feels inclined to contact him.

 

Psychopharmacology

September 2018, Volume 235, Issue 9, pp 2779–2781 | Cite as

Subtherapeutic doses of SSRI antidepressants demonstrate considerable serotonin transporter occupancy: implications for tapering SSRIs

Shapiro, Bryan

https://link.springer.com/article/10.1007/s00213-018-4995-4

(Pubmed didn't have an abstract for this paper, however, the link above has the first paragraph and a bit. I have not posted as uncertain about the copyright status in this case.)

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Altostrata

https://www.semanticscholar.org/paper/Subtherapeutic-doses-of-SSRI-antidepressants-for-Shapiro/0afdb525d3a049649c31ad91b02876a86ab51408

 

Subtherapeutic doses of SSRI antidepressants demonstrate considerable serotonin transporter occupancy: implications for tapering SSRIs

Antidepressants are usually tapered to mitigate the risk of antidepressant discontinuation syndrome, a new entity in DSM-5 characterized by nonspecific sensory, somatic and cognitiveemotional symptoms emerging within 2–4 days of the dose reduction or abrupt discontinuation of antidepressants taken continuously for at least 1 month (American Psychiatric Association 2013). Selective serotonin reuptake inhibitors (SSRIs) are commonly implicated, and among these, discontinuation symptom risk is highest with paroxetine and lowest with fluoxetine (Rosenbaum et al. 1998). Three patterns of symptomatology have been observed in patients discontinuing SSRI antidepressants: (1) New symptoms, which consist of Bclassic^ withdrawal symptoms that are not part of the patient’s original psychiatric illness, (2) rebound symptoms, consisting of the patient’s initial psychiatric symptoms necessitating SSRI treatment but of greater intensity; and (3) persistent postwithdrawal disorders, which resemble rebound symptoms but persist at least 6 weeks and may include features of a new psychiatric illness (Chouinard and Chouinard 2015). Because SSRI discontinuation symptoms are broad and nonspecific, patients may undergo unnecessary medical investigation or be misdiagnosed with a new or recurrent psychiatric illness. Intuitively, a gradual taper of an antidepressant would mitigate the risk of these symptoms but studies in this area are few and mixed. To date, there are no consensus guidelines regarding the optimal taper rate of SSRIs or other antidepressants. Over the last two decades, the development of radioligands highly specific for the serotonin transporter (5-HTT) have allowed for positron emission technology (PET) studies that accurately measure the binding characteristics of serotonin reuptake inhibitors in the brain. These studies demonstrate that minimum effective doses of SSRIs for the treatment of major depressive disorder (20 mg of fluoxetine, paroxetine, or citalopram, and 50 mg of sertraline) are associated with approximately 80% 5-HTT occupancy in the striatum and other regions (Meyer et al. 2004; Arakawa et al. 2016). Because percent 5-HTT occupancy with respect to either maintenance daily SSRI dose or plasma SSRI concentration is a logarithmic expression, a yet-to-be-acknowledged point is that subtherapeutic maintenance doses of SSRIs demonstrate considerable occupancy of 5-HTT. Meyer et al., for instance, extrapolated 50% 5-HTT occupancy at maintenance daily doses of only 2.7 mg of fluoxetine, 5.0 mg of paroxetine, 3.4 mg of citalopram and 9.1 mg of sertraline in chronically dosed subjects (Table 1) (Meyer et al. 2004). Of note, healthy subjects receiving subtherapeutic maintenance doses of SSRIs were included in their study to more accurately estimate the doseoccupancy curve at low dosage strengths. Although the mechanisms underlying SSRI discontinuation syndrome are not well-elucidated, these doseoccupancy data may explain counterintuitive findings of minimal-to-no reduction in discontinuation symptoms with the gradual taper of SSRIs as compared to abrupt discontinuation. In one prospective study of outpatients on maintenance SSRI therapy for panic disorder with agoraphobia, subjects were evaluated for discontinuation symptoms after tapering at the Bslowest possible pace^ (Fava et al. 2007). Fluoxetine, paroxetine, or citalopram doses were reduced by 10 mg every 2 weeks prior to discontinuation and sertraline doses were reduced by 50 mg every 2 weeks. Nonetheless, 45% of patients met criteria for antidepressant discontinuation syndrome 15 days after complete discontinuation and three patients reported discontinuation symptoms lasting at least 6 months. Considering that the subjects’ terminal dosage strengths prior to complete discontinuation were 10 mg of fluoxetine, paroxetine, or citalopram and 50 mg of sertraline, the 5-HTT dose-occupancy curves suggest that these patients may have....
 

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Happy2Heal

wish this info would be more widely available 

 

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bubbles
On 7/19/2020 at 5:45 AM, Altostrata said:

lowest with fluoxetine

 

 

Is it really less likely to get WD with fluoxetine, or does it just take longer?

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Frogie
13 minutes ago, bubbles said:

 

Is it really less likely to get WD with fluoxetine, or does it just take longer?

You will get wd from fluoxetine. It is just much longer lasting that other antidepressants

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Altostrata

It's possible some people will adapt over the 4-week washout period (amount of time for removal from the body) for fluoxetine. This would reduce the incidence of withdrawal. But others still will get withdrawal from fluoxetine.

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bubbles

I always wonder. Cheers.

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