Patients starting an SNRI should be monitored for efficacy of treatment as well as tolerability. SNRIs may cause headaches, drowsiness or insomnia, nervousness, nausea, dry mouth, weight loss and increased sweating. Other SNRIs, such as desvenlafaxine and levomilnacipran, are metabolized by the CYP3A4 enzyme, not the CYP2D6 and could be prescribed instead if a person’s pharmacogenetic profile indicates they are good alternatives. Poor and Ultrarapid metabolizers should not be prescribed these medications due to the availability of other, better alternatives. Ethnic Background and SNRIsĭepending on ethnic background, 30-50% of people in North America have inherently altered CYP2D6 activity and may experience side effects when treated with duloxetine or venlafaxine, and also cannot tolerate SSRIs such as fluoxetine and paroxetine. For CYP2D6 ultrarapid metabolizers, the DPWG guidelines suggest prescribing a dose to a maximum of 150% of the normal dose or to select an alternative to venlafaxine. For CYP2D6 poor and intermediate metabolizers, the Royal Dutch Pharmacists Association – Pharmacogenetics Working Group (DPWG) guidelines recommend an alternative to venlafaxine or to adjust the dose to and to monitor the patient’s plasma metabolite level. Venlafaxine is also metabolized by CYP2D6. Excessive drug dose is one of the most common reasons why some people cannot tolerate SSRIs. In one study, poor CYP2D6 metabolizers of duloxetine experienced a six-fold increase of the the drug in their blood versus those who metabolize it normally. People who do not metabolize duloxetine normally based on their pharmacogenetic profile may experience serious side effects because fluvoxamine interferes with CYP1A2 enzymes and is also metabolized by CYP2D6. Fluvoxamine is used to treat obsessive-compulsive disorder which often occurs with GAD. Sometimes, duloxetine and the drug fluvoxamine are prescribed together. Duloxetine is cleared in the liver by two important enzymes in drug metabolism called CYP2D6 and CYP1A2. Duloxetine is ususally preferred because it may have less sexual side effects than venlafaxine does. Duloxetine may also be useful for patients suffering from neuropathic pain and fibromyalgia. Duloxetine and Venlafaxineĭuloxetine (Cymbalta) and venlafaxine (Effexor) come from another family of medications called SNRIs that are FDA-approved for the treatment of GAD. There are multiple reasons for SSRI intolerance – you can find more details here.īelow we provide an overview of some alternative medications that can be used for treatment of anxiety and the role of pharmacogenetic variations that have an impact on tolerability and response. Some patients with GAD frequently experience SSRI-induced sexual side effects, worsening of anxiety or sleep disruption. A prescribing algorithm, or process to be followed for GAD treatment is available at: psychopharm.mobi. These include serotonin-norepinephrine reuptake inhibitors (SNRIs), buspirone, hydroxyzine, pregabalin, and bupropion. It can help determine which of the other possible treatment options for GAD are right for an individual. Pharmacogenetic testing will indicate if an individual is a normal, intermediate, ultrarapid, or poor metabolizer for commonly prescribed medications. Pharmacogenetic testing, which determines how you respond to medications based on your unique DNA, can help individuals and their healthcare providers to understand why some cannot tolerate SSRIs and help predict how other anxiety medications will work for them. Trials show that only 50% to 60% of people respond to these medications, remission rates between 25% and 35% are achieved, and a large proportion of patients experience significant SSRI side effects. Normally, people are first prescribed the SSRIs citalopram, escitalopram or sertraline. Generalized anxiety disorder (GAD) is often treated with Selective Serotonin Reuptake Inhibitors (SSRIs).
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