5ĭesipramine (Norpramin) is a secondary amine and metabolite of imipramine (Tofranil). Therefore, topical formulations of TCAs may be considered off-label for the treatment of peripheral neuropathies. As with other TCAs, doxepin is a potent sodium channel blocker, more so than lidocaine. 4ĭoxepin is among the most anticholinergic of its class and is available in a topical formulation approved for itching. While they produce pain control similar to that of serotonin norepinephrine reuptake inhibitors (SNRIs, see below), they generally are not considered first-line therapy due to potential increased anticholinergic and cardiotoxic adverse effects. Both medications are significantly anticholinergic. The latter is more noradrenergic than its predecessor thus, it may produce fewer adverse effects. By slowing the heart, these drugs may cause\s QT prolongation and, therefore, may stop the heart if combined with other QT prolonging influences. For these reasons and more, the use of TCAs in the elderly may be problematic.Īmitriptyline (Elavil), a tertiary amine that is metabolized into a secondary amine nortriptyline (Pamelor), is commonly used for pain management. This class of medications is anti-arrhythmogenic. However, there are many safety issues and adverse effects associated with TCAs, primarily from potent anticholinergic effects. Headaches, neuropathic pain, sleep disorders, OCD, and fibromyalgia are just a few common applications, and the use of topical tricyclic antidepressants (TCAs) seems to be on the rise. This ancient group of antidepressants is frequently used in pain management. A black-box warning regarding an increase in suicidal thoughts is attached to all antidepressants, however, epidemiologic studies consistently show a decrease in completed suicides for individuals who take antidepressants. The goal when using antidepressants to manage a patient’s pain is to avoid increasing or decreasing noradrenergic system activity and instead to balance that activity. It should be noted that excess of norepinephrine is often no better than its deficiency and may, in and of itself, be associated with pain. Additionally, venlafaxine and levomelnacipran, as well as certain atypical antidepressants such as mirtazapine, are commonly used off label. Norepinephrine reuptake inhibitors are, therefore, the widely used antidepressants in pain practice specifically, duloxetine and milnacipran are FDA approved for pain and fibromyalgia, respectively. For instance, some antidepressants have indirect analgesic properties while others are solely indicated for depression, anxiety, and/or obsessive compulsive disorder (OCD).Ī good rule of thumb to remember is that the pain control provided by antidepressants is based mainly on their noradrenergic function. The world of antidepressants is diverse and the choice of an individual antidepressant for a patient needs to be based on multiple factors. Recommendations are based on the author’s observational clinical experience individual outcomes may vary and larger population studies are needed to demonstrate long-term efficacy.
This article focuses on the use of non-opioid medications-with a specific focus on antidepressants-as alternative options for the treatment of chronic pain. During the general wide acceptance of this paradigm, treatment plans using opioids, which were effective in relieving acute pain, were applied to chronic pain management models in many ways, this practice contributed to today’s nationwide challenges around opioid addiction and misuse. For more than two decades, chronic pain was delineated from acute pain if it continued beyond the expected healing period and persisted for 90 days or beyond.
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