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Attfield, 2016 Preparation of Lower Dosages of SNRI Antidepressants to Ameliorate Discontinuation Symptoms: Two Case Studies

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University of British Columbia

Pharmaceutical Sciences Student Journal, Volume 3, Issue 1, March 21 2016, pages 31-33. 


Preparation of Lower Dosages of SNRI Antidepressants to Ameliorate Discontinuation Symptoms: Two Case Studies.

Benton Attfield, B.Sc. (Biology), B.Sc. (Pharm) Lori Bonertz, B.Sc. (Pharm)
Cory Hermans, B.Sc. (Pharm)
Valerie Kantz, Senior Pharmacy Technician.


Full text pssj-v03-i01_attfield.pdf



There is a large body of evidence showing that adverse effects experienced with antidepressant treatment ameliorate over time and that disease-state symptoms improve for many patients.

However, there is a paucity of information relating to how to stop these medications when a patient’s depression has remitted. Presented here are two cases that demonstrate the role pharmacists play in helping patients discontinue SNRI medications through the preparation of lower strength dosage forms.


From the paper:





Interestingly, when we contacted the medical information department at Eli Lilly, we were provided with a summary of discontinuation-emergent adverse events that included more detailed information than the product monograph.


The product monographs for both duloxetine (Cymbalta®) and desvenlafaxine (Pristiq®) provide information about discontinuation symptoms. Following abrupt or tapered discontinuation in placebo-controlled clinical trials, the following symptoms occurred at a rate greater than or equal to 1% and at a significantly higher rate in Cymbalta®-treated patients compared to those discontinuing from placebo: dizziness, nausea, headache, paresthesia, fatigue, vomiting, irritability, nightmares, insomnia, diarrhea, anxiety, hyperhidrosis, vertigo, somnolence, and myalgia. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response.


We performed a search of Index Medicus and Medline (OvidSP) using the search terms duloxetine, desvenlafaxine, Cymbalta, or Pristiq, and withdrawal or discontinuation. In a letter, Hou reported long-term withdrawal syndrome in a patient of Asian ancestry treated for depression (9). Indeed, the patient experienced intermittent duloxetine withdrawal syndrome for 10 months. There is a report of withdrawal syndrome in a newborn whose mother was taking 90 mg of duloxetine before and during her pregnancy (10). Another case report described shock-like sensations associated with duloxetine discontinuation (11).


There has been a phase IV, manufacturer-sponsored trial investigating the discontinuation of desvenlafaxine (12). This trial included 357 patients taking a 24-week course of desvenlafaxine who were randomly assigned to three groups: abrupt discontinuation of 50 mg dosages, continuation, or a one-week taper to 25 mg prior to discontinuation. No statistically significant difference in discontinuation events was found in DESS (Discontinuation-Emergent Signs and Symptoms) scores assessed by the trial investigators. However, there was a trend to greater adverse events with abrupt discontinuation, and the fact that both discontinuation groups had higher rates of adverse events suggest there is still a need for strategies to ameliorate withdrawal. Further, this study did not address relapse, was only conducted in patients taking a relatively short course of medication, and did not address previous treatment for depression. Curiously, Pfizer’s USA market monograph still mentions the availability of the 25 mg dosage form to assist with discontinuation, despite the results of this trial.



Although not recommended by the manufacturer [personal communication, 02/02/15], preparing lower dosages of duloxetine is effective for blunting withdrawal reactions. In the case of desvenlafaxine, the monograph states that tapering is an option; however, there is no practical way of achieving this with commercially available dosage forms. Switching to venlafaxine XR compounded capsules provides the ability to slowly taper a patient’s dose and reduce discontinuation symptoms.


A recent article published in the Journal of Pharmacy Practice acknowledges the difficulty in selecting a medication regimen for discontinuing antidepressants (13). The authors noted that many trials are not designed to effectively track outcomes after discontinuation. This reiterates the need for including discontinuation outcomes in clinical trials of new antidepressant medications. For those medications already on the market, this represents an area where further research needs to be conducted. It would be helpful to have established guidelines for tapering, such as alternate day scheduling or decreasing by a certain percentage of the dose over time, to try to lessen the likelihood of withdrawal symptoms. Pharmaceutical companies manufacturing SSRIs and SNRIs should be encouraged to produce tapering dosage suggestions in conjunction with initiation schedules.


We encourage pharmacists to highlight to patients and prescribers considering cessation of treatment with duloxetine or desvenlafaxine the possibility of withdrawal symptoms on discontinuation. There is potential for patients and their health care professionals to mistake withdrawal symptoms for a recurrence of depression (6). Pharmacists should follow-up with patients in the weeks following discontinuation to monitor for changes in depressive and withdrawal symptoms.




Edited by Altostrata
Added selection from the paper

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This is a very interesting and germane paper, thank you @Andie


Here are two topics about papers in the citations:




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