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. 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.
Antidepressants in General
The world of antidepressants is diverse and the choice of an individual antidepressant for a… read more
Nefazodone, another SARI, and various monoamine oxidase inhibitors (MAOIs) should be avoided in pain management unless the practitioner is intimately familiar with such medications. The latter has an inordinate number of dangerous drug interactions because of its inherent activity to block the hepatic metabolism of many drugs and foods that contain neuroamines and/or tannins. Common foods that are especially problematic include aged foods such as wine, cheese, pickles, pickled herring, smoked salmon, and more. Nefazodone has been associated with hepatic failure and MAOIs may be unsafe when used in combination with a wide variety of medications.
As described herein, antidepressants offer opioid alternatives for the management of certain chronic pain and comorbid conditions, especially depression, anxiety, and insomnia. These medications, however, may be under-prescribed due to a lack of awareness about their potential benefits in pain care and, most importantly, the inexperience of pain practitioners in matching a specific medication to a specific patient.
It should be noted, importantly, that pharmacological treatment is only a part of potential success in managing chronic pain. The combined effort of a diverse treatment team is likely to produce the most desirable outcome in the patient. Psychiatry, psychology, physical therapy, osteopathic approaches, interventional treatments, and specialty treatments are all needed for rehabilitation and functional restoration.
Clinical Pearls for TCA Use in Pain Management:
Use nortriptyline over amitriptyline.
Consider using topical forms of TCAs.
Remember that combining this class of medications with other serotonergic and noradrenergic medications may be unsafe.
If one medication, for example, induces an enzyme that metabolizes a second medication, a blood level of the second medication may disproportionately decrease. Carbamazepine is a well-known example of a medication that decreases the blood level of many other medications (and of itself) by inducing enzymes. Methadone, ketoconazole, and fluvoxamine are well-known inhibitors of enzymes; therefore they may increase the blood level of a number of medications. Hence, methadone increasing its own blood level becomes a known safety issue. In present-day medicine, it is imperative, therefore, to pay attention to not only medication’s properties but to how they play in an individual patient.
Clinical Pearls for Atypical Antidepressant Use for Pain Management:
Mirtazapine may be useful in the treatment of abdominal pain, especially in undernourished patients.
Trazodone offers an option for managing comorbid insomnia.
The Importance of CYP 450 Metabolism in Medication Selection for Optimal Pain Management
Over 80% of medications on the market presently are metabolized through the CYP P-450 enzyme system, which is present not just in the liver but in multiple other organs as well.
Those enzymes may be activated or inhibited by various medications and foodstuffs. They also may be biologically more or less active. Enzymes’ function is to metabolize and remove active medications (oxycodone, for instance, or fentanyl). The same enzymes do opposite to inactive medications by metabolizing them into active chemicals (codeine, for instance, has to be turned into morphine and tramadol into O-desmethyltramadol before they can control pain. Medications may be substrates (meaning they are activated or deactivated by a certain enzyme); they also may induce or inhibit different enzymes
Clinical Pearls on SSRI Use for Pain Management:
Based on a combination of properties, sertraline is the author’s SSRI of choice for pain management.
Consider vortioxetine as a possible choice for the treatment of pain patients with depression, especially for those with mild cognitive dysfunction.
Clinical Pearls for SNRI Use in Pain Management:
When possible, avoid combining serotoninergic medications due to the risk of serotonin syndrome and possible aggravation of pain.
Avoid duloxetine in polypharmacy when possible, especially with P-450 2D6 dependent medications.
When possible, avoid combining TCAs, SSRIs, and SNRIs, which may lead to serotonin syndrome, including seizures).
Venlafaxine (Effexor) is the oldest representative of this medication group. Although not specifically approved for pain, it is commonly and successfully used off-label in the management of chronic painful conditions, especially those of a neuropathic nature. It is worth noting that venlafaxine has been associated with increases in blood pressure and severe sexual adverse effects. The medication also may cause unpleasant withdrawal symptoms, whether stopped abruptly and even with slow discontinuation. It may, however, be deemed safer than duloxetine in polypharmacy.
Desvenlafaxine (Pristiq) is more noradrenergic than its racemic mixture relative venlafaxine, but it seems to be less effective in the treatment of chronic pain.
Mirtazapine (Remeron) is a tetracyclic antidepressant. It works through alpha-2 antagonism and, as such, may provide a good fit for pain management. It normalizes gut motility, decreases abdominal pain, eases nausea, and helps to reduce anxiety. Unfortunately, the medication is sedating and weight gain is common. These effects seem to relate inversely to the dose of mirtazapine: the higher the dose, the less the sedation. This reaction likely occurs as histamine receptors are blocked with smaller doses; plus, norepinephrine action increases with dosage, gradually offsetting sedation. The ideal patient would, therefore, be an older, undernourished, anxious individual with abdominal pain. Mirtazapine is metabolized by multiple P-450 enzymes and represents little challenges in polypharmacy but caution should be exercised when prescribing this medication for patients with liver problems or in combination with other sedating medications.
Trazodone and serotonin antagonist reuptake inhibitor (SARI) is a weak antidepressant with a unique sedating effect and, while it has no label for the treatment of insomnia, has been widely used for sleep induction and maintenance. Due to its long onset of action, it is recommended that trazodone be taken one hour or more before sleep to avoid morning drowsiness. Generally, the most troublesome adverse effect of this medication is priapism. Due to its non-addictive nature and benign impact in polypharmacy, trazodone remains understandably popular in pain management.