Contents part 1: Introduction

Suggested timelines: 10 visits over 4 weeks, equivalent to up to 30 hours

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Suggested timelines: 10 visits over 4 weeks, equivalent to up to 30 hours.

Xanax® (Alprazolam)

Not recommended for long-term use. See Alprazolam; & Benzodiazepines. Alprazolam, also known under the trade name Xanax and available generically, is a short-acting drug of the benzodiazepine class used to treat moderate to severe anxiety disorders, panic attacks, and as an adjunctive treatment for anxiety associated with major depression.

Xartemis XR (oxycodone & acetaminophen)

Refer to the DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for recommendations on the use of opioids. The FDA has approved an extended-release combination of oxycodone and acetaminophen (Xartemis XR, Mallinckrodt plc), for patients for whom alternative treatment options are ineffective, not tolerated, or would otherwise be inadequate. The drug has both immediate- and extended-release components to allow pain relief within an hour, with twice-daily dosing. The approved label for Xartemis XR does not include abuse-deterrent language. Oxycodone exposes patients to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. (FDA, 2014) Xartemis XR is not an abuse-deterrent formulation and altering the tablets (e.g., crushing, chewing, dissolving) could lead to a potentially fatal overdose or other serious adverse effects. Xartemis XR is only approved in one strength, which is oxycodone 7.5mg/ acetaminophen 325mg. The addition of acetaminophen may also limit its use in patients with concern for liver toxicity. (Clinical Pharmacology, 2014)


See Botulinum toxin.


Recommended as an option for motivated patients. There is considerable evidence of efficacy for mind-body therapies such as yoga in the treatment of chronic pain. Also, the impact on depression and disability could be considered as important outcomes for further study. Since outcomes from this therapy are very dependent on a motivated patient, we recommend approval where requested by a specific patient, but not adoption for use by any patient. (Astin, 2003) (Barrows, 2002) (Galantino, 2004) Women with fibromyalgia can reduce symptoms of the disease and improve their function by practicing the mind-body techniques of yoga, a new RCT concludes. The results suggested that yoga led to a beneficial shift in how patients cope with pain, including greater use of adaptive pain-coping strategies, such as engaging in activities despite pain, acceptance of their condition, the use of religion as a coping mechanism, and the ability to relax. (Carson, 2010) This meta-analysis suggests that yoga is a useful supplementary approach with moderate effect sizes on pain and associated disability, and even short-term interventions might be effective. (Büssing, 2012)

Mindfulness meditation: Mind-body medicine (MBM) therapies broadly include meditation, hypnosis, guided imagery, relaxation therapies, biofeedback, spiritual healing, yoga, tai chi, qigong, art therapy, light therapy, and others. Mindfulness is defined as a nonjudgmental moment-to-moment awareness, including mindful movement (body awareness during yoga postures). The medical literature on mindfulness-based stress reduction (MBSR) is favorable, especially for chronic pain, anxiety, and general psychologic health; however, many of the studies are self-controlled, comparing a patient's pretreatment symptoms with posttreatment. In a study examining chronic pain patients, with mean duration of pain of 8.1 years, including of low back pain, headache, and neck/shoulder pain, patients were evaluated before and after the 8-week intervention, then for 48 months in follow-up. Of patients, 60% to 72% reported moderately or greatly decreased pain, decreased psychologic symptoms, and decreased general medical complaints. 86% responded affirmatively the program. Gains in medical and psychologic symptoms were maintained at 4-year follow-up. (Barrows, 2002)

For mindfulness meditation, see Behavioral interventions/Cognitive Behavioral Therapy (CBT). Also see relevant DWC MTUS body chapters

Zanaflex® (tizanidine)

Zanaflex® is a muscle relaxant. See Muscle relaxants. See also specific Tizanidine (Zanaflex®) listing.

Ziconotide (Prialt®)

Ziconotide (Prialt®) is a synthetic calcium channel blocker that is delivered intrathecally, offering a non-opioid option for treatment of chronic pain, and possibly, spasticity associated with spinal cord trauma. Intrathecal administration of opioids is not recommended.

Adverse effects: Prialt has been associated with severe CNS-related adverse effects, and a “black-box” warning has been issued in this regard. Neurological warnings include hallucinations, paranoid ideation, hostility, delirium, psychosis, manic reactions and decreased alertness. Certain patients may be at increased risk for psychiatric side effects including those with pre-existing history of depression with risk of suicide and patients with pre-existing psychosis. Cognitive impairment was noted in approximately 30% of patients in clinical trials, and this symptom was found to be reversible within about two weeks of discontinuation. Prialt is contraindicated in patients with a pre-existing history of psychosis. Prialt can be discontinued abruptly without evidence of withdrawal effects in the presence of serious adverse events.

Dosage requirements: The current recommendations suggested by the manufacturer for this medication include a low initial infusion rate (0.1 mcg/hour for a total of 2.4 mcg/day) and limiting infusion increases to 2-3 times a week. Current drug trials have evaluated the efficacy of the medication for a 3-week duration only, but preliminary trials suggested that analgesic efficacy would be maintained long-term in open label trials.

Post-marketing dose recommendations: Post-marketing, an expert consensus panel recommended a starting dose of 0.5 mcg/24 hours with upward titration of no more than 0.5 mcg/week due to increased risk of adverse effects with higher doses. (Fisher, 2005)

Filling intervals: The reservoir should be refilled initially at 14 days. For subsequent pump refills, fill the pump at least every 40 days if used diluted. For undiluted Prialt, fill the pump at least every 84 days.

Other precautions: This medication is associated with elevation of serum creatinine kinase, with risk factors including male gender and concomitant use of anti-depressants, anti-convulsants and intrathecal morphine. This lab value should be monitored at least bi-weekly for the first month and at monthly intervals thereafter. Symptoms of myalgia include myasthenia, muscle cramps and unusual fatigue. (Thompson, 2006) (Wermeling 2005) (Lyseng-Williamson, 2006) (Lynch, 2006) (Rauck, 2006) (Deer, 2007) Intrathecal ziconotide may increase risk for suicide. Researchers are calling for a comprehensive psychiatric evaluation in all patients before and during treatment, but ziconotide may pose a threat even in symptom-free patients with pain. Better monitoring of all patients on this medication is necessary, and strict compliance to the contradictions such as a history of depression is key. Ziconotide not only suppresses the transmission of pain stimuli but may also reduce impulse control, promoting suicidal tendencies in vulnerable patients. (Maier, 2010) See Intrathecal drug delivery systems, medications.

Zipsor (diclofenac potassium liquid-filled capsules)

Not recommend diclofenac as first line due to increased risk profile. See Diclofenac listing. Zipsor diclofenac potassium liquid-filled capsules (Xanodyne) were approved by the FDA in June 2009. (FDA, 2009) When compared with absorption characteristics of diclofenac potassium tablets, Zipsor was more rapidly absorbed after bunionectomy, which may be advantageous if rapid pain relief is required, but there were no other advantages over the tablets. (Kowalski, 2009) In dental surgery patients Zipsor provided rapid onset of confirmed perceptible pain relief within 30 minutes of administration. (Zuniga, 2011) See Diclofenac Potassium.


Not recommended. See Hydrocodone. Zohydro ER (Zogenix Inc) is the first single-entity extended-release (ER) formulation of hydrocodone approved by the FDA; unlike Vicodin, Lortab and Norco, it is not buffered with acetaminophen or some other OTC medication. Each pill will be very potent, but Zohydro does not have abuse-deterrent technology. According to the FDA, Zohydro ER should be reserved for use in patients for whom alternative treatment options are ineffective. FDA's Drug Advisory Committee of independent experts voted 11 to 2 to recommended against approval of Zohydro for the treatment of moderate to severe chronic pain because of the potential for abuse of this drug. Refer to the DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for recommendations on the use of opioids.

Zolpidem (Ambien®)

Zolpidem is a prescription short-acting nonbenzodiazepine hypnotic, which is approved for the short-term (usually two to six weeks) treatment of insomnia. Proper sleep hygiene is critical to the individual with chronic pain and often is hard to obtain. Various medications may provide short-term benefit. While sleeping pills, so-called minor tranquilizers, and anti-anxiety agents are commonly prescribed in chronic pain, pain specialists rarely, if ever, recommend them for long-term use. They can be habit-forming, and they may impair function and memory more than opioid pain relievers. There is also concern that they may increase pain and depression over the long-term. (Feinberg, 2008) See Insomnia treatment. Ambien CR offers no significant clinical advantage over regular release zolpidem. Ambien CR is approved for chronic use, but chronic use of hypnotics in general is discouraged, as outlined in Insomnia treatment. Ambien CR causes a greater frequency of dizziness, drowsiness, and headache compared to immediate release zolpidem. (Ambien & Ambien CR package insert) Cognitive behavioral therapy (CBT) should be an important part of an insomnia treatment plan. A study of patients with persistent insomnia found that the addition of zolpidem immediate release to CBT was modestly beneficial during acute (first 6 weeks) therapy, but better long-term outcomes were achieved when zolpidem IR was discontinued and maintenance CBT continued. (Morin, 2009) Due to adverse effects, FDA now requires lower doses for zolpidem. The dose of zolpidem for women should be lowered from 10 mg to 5 mg for IR products (Ambien, Edluar, Zolpimist, and generic) and from 12.5 mg to 6.25 mg for ER products (Ambien CR). The ER product is still more risky than IR. In laboratory studies, 15% of women and 3% of men who took a 10-milligram dose of Ambien had potentially dangerous concentrations of the drug in their blood eight hours later. Among those who took Ambien CR, the problem was more common: 33% of women and 25% of men had blood concentrations that would raise the risk of a motor vehicle accident eight hours later. Even at the lower dose of Ambien CR now recommended by the FDA, 15% of women and 5% of men still had high levels of the drug in their system in the morning. (FDA, 2013) According to SAMHSA, zolpidem is linked to a sharp increase in ED visits, so it should be used safely for only a short period of time.

Zonisamide (Zonegran®)

See Anti-epilepsy drugs (AEDs) for general guidelines, as well as specific Zonisamide listing.

Zorvolex (diclofenac)

Not recommended except as a second-line option, because diclofenac products are are not recommended as first-line choices due to potential increased adverse effects. See Diclofenac. In late 2013 FDA approved diclofenac capsules (Zorvolex, Iroko Pharmaceuticals LLC) at 18-mg and 35-mg doses for the treatment of mild to moderate acute pain in adults. These dosages are 30% lower in strength than the 25-mg and 50-mg diclofenac products already on the market. The FDA also approved another lower-dose NSAID from Iroko Pharmaceuticals, indomethacin capsules (Tivorbex). While diclofenac has potent anti-inflammatory and analgesic properties, research has linked this drug to sometimes serious adverse outcomes, including cardiovascular thrombotic events, myocardial infarction, stroke, gastrointestinal ulcers, gastrointestinal bleeding, and renal events (such as acute renal failure). (FDA, 2014) This new formulation of diclofenac does not present any apparent advantages versus other medications of the class. Zorvolex is pure acid versus salt in other formulations, resulting in faster dissolution using SoluMatrix Fine Particle Technology. However, it has the same side effect profile while more expensive than other NSAIDs that are available as generics. It is an expensive, brand name only, second-line medication with little to no place in the treatment of workers compensation injuries. (FDA, 2013)

Zubsolv (buprenorphine/ naloxone)

Zubsolv (buprenorphine and naloxone), a recently FDA-approved medication for maintenance treatment of opioid dependence, is a once-daily sublingual tablet that offers higher bioavailability that allows patients to use lower strength and reduce the amount of available drug for potential misuse and diversion. (FDA, 2013) See Buprenorphine.

Behavioral Interventions

Complementary Alternative Medicine

Early Return-To-Work

Home Health Services


Medical Treatment Guidelines


Pain – Assessment and Management

Pain – Chronic

Pain – Miscellaneous

Psychosocial Evaluation and Treatment

Reflex Sympathetic Dystrophy/ Complex Regional Pain Syndrome

Therapeutic Intervention

Spinal Cord Stimulation
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