ed with benzodiazepine use, particularly during the first trimester, when fetal development is rapid. Benzodiazepine use during the Antidepressants Antidepressants are an important modality in the treatment of many painful conditions. Antidepressants seem to work best for treating pain related to the nervous system, such as neuropathy, nerve damage (post-herpetic neuralgia), migraine and fibromy - algia. They may also be helpful adjuvants in lower back pain, arthritis and pelvic pain (Mayo Clinic, 2019). The mechanism by which these drugs address pain is not clearly understood, but it is thought that inhibiting norepinephrine reuptake leads to up-reg- ulation of inhibitory pain pathways. Antidepressants take two to four weeks to exhibit analgesic effects, so some patience is re- quired (Tauben & Stacey, 2021b). The evidence is most supportive of the use of tricyclic antide- pressants (TCAs) and serotonin-norepinephrine reuptake inhibi- tors (SNRIs) for the treatment of pain. Studies have shown that only 3.6 to 6.4 patients with neuropathic pain need to be treated for one patient to achieve at least a 50% reduction in pain relief. TCAs and SNRIs are indicated for the treatment of pain even in the absence of mood disorders, since analgesic effects are known to occur in patients who are not depressed. However, their use in patients with comorbidities of depression and pain can provide significant benefits in the treatment of both disease states (Tau - ben & Stacey, 2021b). Among the SNRIs, duloxetine and venlafaxine have the most ev- idence for use in neuropathic pain, and duloxetine also has evi- Tricyclic antidepressants Since TCAs are sedating, administration with barbiturates, alcohol or other agents with CNS depressant effects can cause overse- dation, impaired functioning and falls. Medications that increase serotonin levels, including herbal preparations such as St. John’s wort and SAM-e can lead to serotonin syndrome when co-ad- ministered. Agents that cause QT prolongation, such as certain broad-spectrum antibiotics, should be used with caution with cy- clic antidepressants, due to additive risk. Other agents that low- er the seizure threshold, such as tramadol, can increase the risk of seizures when administered with cyclic antidepressants. Side effects associated with cyclic antidepressants include (Hirsch & Birnbaum, 2021): ● Overdose: as little as 10 times the daily dose of cyclic antide- pressants can be fatal, due to QT prolongation causing fatal arrhythmias. Topical lidocaine Data supporting the use of topical lidocaine is limited, though it is used frequently in the treatment of chronic pain. It is considered an adjuvant agent in the treatment of neuropathic pain, with the best evidence supporting its use in postherpetic neuralgia and diabetic neuropathy (Tauben & Stacey, 2021b). Opioids Due to the high risk of abuse, dependence, and addiction, pre- scribers should consider opioid therapy only if the benefits for function and pain are expected to outweigh the potential risks to the patient. When used appropriately, opioids are useful for treating pain that does not respond to other therapies. Their use should be combined with nonpharmacologic and nonopioid ther- apy as appropriate to maximize pain control (Dowell et al., 2016). Short-acting oral opioids typically have a rapid effect (15 to 30 minutes) but may take longer to achieve peak efficacy because of the time required to pass the blood brain barrier. Generally speaking, elimination half-lives average three to four hours, offer- ing a relatively narrow duration of action. As a result, they are best used for acute, intermittent, or breakthrough pain (pain occurring against a background of constant pain) (Michigan State University College of Human Medicine, nd).
third trimester has been associated with neonatal withdrawal, se- dation, and hypothermia in the infant (DiPiro et al., 2019).
dence of efficacy in musculoskeletal pain. Duloxetine is FDA ap - proved for the treatment of fibromyalgia, chronic low back pain, osteoarthritis and diabetic neuropathy. It is typically used in doses of 30 to 120mg daily, with lower doses preferred in patients who are concerned about side effects. Duloxetine should be avoided in patients with hepatic or severe renal insufficiency. Venlafaxine is used in doses of 75-225mg daily for the treatment of acute and chronic neuropathic pain (Tauben & Stacey, 2021b). SNRIs are contraindicated in patients taking MAOIs within the previous two weeks due to the risk of serotonin syndrome, and in some cases, hypertensive crisis. Duloxetine has moderately po- tent inhibitory effects on the hepatic cytochrome P450 enzyme CYP2D6, resulting in drug interactions with other medications that affect or are affected by this enzyme. Side effects associated with SNRIs include (Nelson, 2021): ● Nausea, which appears to diminish over time. ● Dizziness. ● Diaphoresis. ● Increased blood pressure, due to the effects on norepineph- rine. ● Headaches. ● Sexual dysfunction. ● Increased risk of bleeding. ● Hyponatremia. ● Cardiac side effects, such as orthostatic hypotension, QT pro- longation, tachycardia and arrhythmias. ● Lower seizure threshold. ● Bone fractures. ● Anticholinergic effects due to muscarinic receptor blockage, including dry mouth, blurred vision, constipation, urinary re- tention, confusion, and delirium. ● Antihistaminic effects due to histamine receptor blockage, including sedation, increased appetite causing weight gain, confusion and delirium. ● Sexual dysfunction. ● Diaphoresis. ● Tremor. Lidocaine 5% patches are commonly used; a single patch contains 700mg of lidocaine. Up to three patches can be applied at a time for up to 12 hours in a 24-hour period; a 12 hour patch-free period is required each day due to the risk of lidocaine toxicity. Systemic absorption with lidocaine patches is low, averaging 3%, but this requires cautious use in patients with renal, hepatic, or cardiac dysfunction (Tauben & Stacey, 2021b). Single-agent immediate-release products are made using a va- riety of opioids, including codeine, morphine, hydromorphone, and oxycodone. Combination products typically combine a non- opioid analgesic with an opioid such as oxycodone or hydroco- done combined with acetaminophen usually for use in patients with moderate pain (McAuley, 2017). In 2014, FDA recommended that prescribers discontinue the use of combination products con- taining more than 325 mg of acetaminophen per dosage unit. This decision is based on data suggesting that the increased risks of liver damage associated with larger doses of acetaminophen are not outweighed by any initial efficacy benefits (FDA, 2018). Extended-release or long-acting opioid formulations are purpose- ly engineered to control the release of drugs in such a way as to provide relatively consistent and prolonged drug levels in the blood. The onset of action is typically slower than that of immedi-
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