Chiefs’ Inquiry Corner — 10/13/21

  Many patients in primary care are often started on anti-depressants for extended periods of time with an unclear time frame as to whether the medication should be discontinued or continued as a long term medication. Often in clinical practice, we consider discontinuation of medication after a single episode of major depressive order after 9-12 months but the guidelines are less clear for patients with more than 1 episode. A recent randomized, double blind trial conducted in the UK looked at patients with at least 2 episodes of major depressive disorder taking anti-depressants for 2 years or longer and randomized them in 1:1 ratio to a taper with placebos vs. maintenance therapies. Medications that were used included sertraline, fluoxetine, citalopram, and mirtazapine. The primary outcome studied was the first relapse of depression during the 52 week trial period. 478 patients were enrolled in the trial which was predominantly women (72%). By 52 weeks, relapse occurred in 39% of the maintenance group and 56% in the discontinuation group, resulting in a Hazard Ratio of 2.06 (P<0.001). This article suggests that among patients who feel well enough or stable on long term anti-depressant therapy, they may actually benefit from being maintained on their current regimen to avoid a relapse for major depressive disorder.

References: Maintenance or Discontinuation of Antidepressants in Primary Care

  For patients with IBS, there’s overall limited disease-altering pharmacotherapy, and we primarily focus on symptom management. Physicians typically use a combination of bulking agents, antispasmodics, and antidepressants for management; antispasmodics and antidepressants seem to have the most evidence supporting their effectiveness. A Cochrane Review examined several of these agents, and Peppermint Oil emerged as a supplement of interest. They found potential benefit for improvement in symptoms of abdominal pain when compared to placebo. One of these randomized-controlled trials examined the use of enteric-coated peppermint oil capsules versus placebo in 57 patients with IBS. After 4 weeks of therapy, they found that 75% of patients in the experimental group showed a greater than 50% reduction in their symptoms, compared to 38% in the placebo group. Factors to consider include the dose used (225 mg, compared to the typical 50 mg in available over the counter pills), as well as the duration of follow up at only 4 weeks. You may consider a short trial of this supplement in your patients, or if patients have already started taking it, this may provide some support for allowing them to complete a course.

References: Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome

 Over the last 15 years, there has been debate about the safety of morphine use in the management of patients with ACS. Initially, it was thought to have beneficial effects by decreasing cardiac filling pressures as well as reducing sympathetic activity. It has recently been suggested that morphine may suppress effects of anti-platelet agents and impair the ability to block platelet aggregation. In 2005, the CRUSADE trial results suggested that use of morphine in patients with non-ST elevation MI was associated with increased risk of death; however, this was a nonrandomized, retrospective, observational registry. A subsequent study in 2018 used a database from the CIRCUS trial to examine patients admitted for anterior STEMI and PCI. They failed to demonstrate an increased risk of major adverse cardiovascular events when the patients were followed up to 1 year. Most recently, The Comparison of Morphine, Fentayl and Ticagrelor randomized controlled trial compared the effects of morphine and fentanyl on platelet aggregation in patients with ACS who were treated with Ticagrelor. They measured platelet aggregation using light transmittance aggregometry at baseline and 2 hours after loading with Ticagrelor. Though a small number of patients were randomized (136), they found no difference in median platelet inhibition at baseline and 2 hour follow-up. However, on post-hoc analyses they reported potential differences in residual platelet aggregation. The ACC/AHA still has morphine as a class IIa recommendation (previously class I); further randomized trials will likely be needed to further clarify these recommendations as data emerges.

References: Comparison of the effect of Morphine and Fentanyl in patients with acute coronary syndrome receiving Ticagrelor – The COMET (Comparison Morphine, Fentayl and Ticagrelor) randomized controlled trial