Antiepileptic medications Gabapentin and pregabalin are anticonvulsants that are approved by the FDA for the treatment of neuropathic pain. Gabapentin and pregabalin both work by binding to the voltage-gated calci- um channels in the central nervous system; their true mechanism in pain control is not clear and likely multifactorial. Gabapentin was primarily studied for the treatment of postherpetic neuralgia and diabetic neuropathy; evidence of efficacy in other types of neuropathic pain is limited. When used for neuropathic pain, it is typically initiated at a dose of 300mg at night; older adults and those who are sensitive to sedation should consider starting at 100mg. The daily dose range of 1200 to 2400mg per day is typi- cally most effective for neuropathy, with doses divided into three daily doses. An adequate trial of gabapentin can take two months or longer. Patients with renal impairment require dosage adjust- ment (Tauben & Stacey, 2021b). A systematic review in 2019 found that among 45 randomized trials, pregabalin was found to be more effective than place- bo in treating diabetic neuropathy, postherpetic neuralgia, and mixed neuropathic pain; daily doses of 300 to 600mg were most effective. Pregabalin is also the only medication FDA approved Muscle relaxants Muscle relaxants describe a diverse category of medications with similar effects of analgesia and skeletal muscle relaxation or mus- cle spasm relief. Muscle relaxants have been shown to provide short term pain relief in patients with low back pain when com- pared with a placebo, though their utility in long term use is un- clear (Knight et al, 2021). However, some patients may benefit from the addition of a muscle relaxant, such as those with low back pain who have pain disrupting their sleep and may bene- fit from their sedating effects, and those at risk of opioid misuse (Cook, 2021). Skeletal muscle relaxants are recommended as second-line ther- apy in patients with low back pain whose symptoms are not man- aged with acetaminophen or NSAIDs alone. If used, cycloben- zaprine and tizanidine are preferred agents because they have more data available to support their use and they have less abuse potential than other agents such as carisoprodol. The lowest ef- fective dose and frequency should be utilized, and these medi- cations are often given on an ‘as needed’ basis. Muscle relaxants include agents such as (Cook, 2021; Knight et al, 2021): Benzodiazepines Benzodiazepines are Schedule IV controlled substances that work by potentiating the inhibitory activity of GABA and increasing its ability to exert calming effects. This effect can be helpful in the treatment of anxiety, but can also be addictive (Bystritsky, 2021). Benzodiazepines are also effective in treating muscle spasms, though their high abuse potential and availability of alternative agents for this purpose make them a non- preferred agent for the treatment of chronic pain (Tauben & Stacey, 2021b). The most commonly reported side effects associated with ben- zodiazepines are related to central nervous system depression: drowsiness, amnesia, psychomotor impairment, and confusion. Drowsiness is more commonly experienced during the first few days of treatment though tolerance can develop to this side ef- fect. Rebound anxiety can occur after short term treatment; high- er doses can result in withdrawal symptoms and learning impair- ment. Benzodiazepines with shorter half-lives, such as alprazolam and lorazepam are more likely to cause acute withdrawal when abruptly stopping treatment after prolonged use. Those with lon- ger half-lives, such as diazepam, typically produce more delayed and attenuated withdrawal symptoms (Bystritsky, 2021). Benzodiazepines must be tapered very slowly when discontinuing after long term use. A reduction of around 10% per 1-2 weeks is preferred, if circumstances allow. Patients should be monitored for symptoms of withdrawal such as anxiety, dysphoria, tremor, perceptual disturbances, psychosis, or even seizures. If withdrawal
for the treatment of neuropathic pain associated with spinal cord injury. It is recommended to initiate pregabalin at a daily dose of 150mg per day, divided into two to three daily doses. It can be increased to 300 to 600mg per day over the course of two to four weeks if needed. Patients with renal impairment require dosage adjustment. Pregabalin may provide more rapid analgesia than gabapentin, due to the use of lower doses and shorter titration schedules (Tauben & Stacey, 2021b). The most common side effects associated with gabapentin and pregabalin are dizziness and sedation, which are dose-depen- dent. These effects can be reduced with lower starting doses and slow titration. In addition, respiratory depression has been report- ed in older adults and patients who received gabapentin along with opioids or other sedatives. One study reported that co-pre- scribing pregabalin with opioids was associated with a dose-relat- ed increase in the risk of opioid related mortality; similar results have been reported when combining gabapentin with opioids. There is also increasing reports of abuse potential with gabapen- tin and pregabalin; they should be used with caution in patients with substance use disorders (Tauben & Stacey, 2021b). ● Cyclobenzaprine 5 to 10mg three times daily as needed, with one dose at bedtime to help with sleep. ● Carisoprodol 250 to 350mg three times daily for a maximum of 2 to 3 weeks. ● Methocarbamol 750 to 1500mg three times daily. ● Metaxalone 800mg 3 to 4 times daily. ● Tizanidine 4 to 8mg three times daily as needed. Use of muscle relaxants is associated with significant adverse events, including drowsiness and dizziness. Sedation can be sig- nificant, and can limit the patient’s ability to drive or work; these effects are more likely in older patients and those with organ dys- function. Combination with other sedating agents such as opioids and benzodiazepines can exacerbate sedation. It may be best to avoid the use of muscle relaxants in patients with substance use disorders, particularly those who are also utilizing opioids, due to the significant risk of misuse. Use of muscle relaxants should be limited to adjunctive therapy for short-term treatment of acute musculoskeletal conditions (Knight et al, 2021). symptoms develop, the rate of dose reduction should be slowed accordingly (Bystritsky, 2021). Drug interactions must also be considered when prescribing benzodiazepines. Because they exert depressant effects on the central nervous system (CNS), administration of additional CNS depressants such as opiates, muscle relaxers, sleep medications, and alcohol should be minimized because of the risk of respirato- ry depression and death (DiPiro et al., 2019). The U.S. Food and Drug Administration added a black box warning in 2018 to the labels of all opioids and benzodiazepines advising against using these medications together. Because both are CNS depressants, the combination puts patients at increased risk of slowed or diffi - cult breathing, over sedation, respiratory depression, and death. The CDC recommends that these medications should be pre- scribed together only when alternate treatments are inadequate. When co- prescribed, the dosages and durations should be kept to the minimum possible (Dowell et al., 2016). Benzodiazepines must be used especially cautiously in the elderly. Elderly patients are more susceptible to drug accumulation be- cause of hepatic insufficiency, decreased oxidation, and altered volume of distribution. They are also more sensitive to the central nervous system effects of benzodiazepines regardless of the half- life of the agent used. This results in an increased frequency of falls and associated fractures (DiPiro et al., 2019). Benzodiazepines should be avoided in pregnant patients. Terato- genic effects such as cleft lip and cleft palate have been associat-
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