Contents part 1: Introduction

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See Topical analgesics, where it is explained that any compounded product that contains at least one drug (or drug class) that is not recommended is not recommended. The use of compounded agents requires knowledge of the specific analgesic effect of each agent and how it will be useful for the specific therapeutic goal required.

Topical NSAIDs

See Non-steroidal antinflammatory agents (NSAIDs) entry under Topical analgesics.

Topiramate (Topamax®)

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


See Ketorolac (Toradol®).

Tramadol (Ultram®)

See DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for general information on opioids. Tramadol is a centrally acting synthetic opioid analgesic and it provides inferior analgesia compared to a combination of Hydrocodone/ acetaminophen. (Turturro, 1998) As of November 2013, Tramadol has been designated a Schedule IV controlled substance. (DEA, 2013) Tramadol has unreliable analgesic activity and potential side effects such as serotonin syndrome. (Ray, 2013)

Tramadol/Acetamin-ophen (Ultracet®)

See specific Tramadol/Acetaminophen (Ultracet®) listing for more information and references.

Transcutaneous electrical nerve stimulation (TENS)

See TENS, chronic pain (transcutaneous electrical nerve stimulation); & TENS, post operative pain (transcutaneous electrical nerve stimulation).

Transcutaneous electrotherapy

See Electroceutical therapy (bioelectric nerve block); Galvanic stimulation;

H-wave stimulation (devices); Interferential current stimulation (ICS); Microcurrent electrical stimulation (MENS devices); RS-4i sequential stimulator; Sympathetic therapy; TENS, chronic pain (transcutaneous electrical nerve stimulation); & TENS, post operative pain (transcutaneous electrical nerve stimulation).

Treatment for CRPS

See CRPS, treatment.


Trepadone™ is not recommended for the treatment of chronic pain. It is a medical food that is a proprietary blend of L-arginine, L-glutamine, choline bitartrate, L-serine and gammaaminobutyricacid [GABA]. See Medical foods.


Not recommended. See Benzodiazepines.


Recommended. Tricyclics are generally considered a first-line agent unless they are ineffective, poorly tolerated, or contraindicated. Analgesia generally occurs within a few days to a week, whereas antidepressant effect takes longer to occur. For peripheral neuropathic pain the NNT for tricyclics is 2.3, versus SSRIs of 6.8 and SNRIs of 4.6. See Antidepressants for chronic pain for general guidelines, as well as specific Tricyclics listing for more information and references.

Trigger point injections (TPIs)

Recommended for myofascial pain syndrome as indicated below, with limited lasting value. The advantage appears to be in enabling patients to undergo remedial exercise therapy more quickly. The primary goal of trigger point therapy is the short-term relief of pain and tightness of the involved muscles in order to facilitate participation in an active rehabilitation program and restoration of functional capacity. TPIs are generally considered an adjunct rather than a primary form of treatment and should not be offered as either a primary or a sole treatment modality. (Scott, 2005) See Myofascial pain. A recent systematic review came to the conclusion that the efficacy of TPIs was no more certain than it was a decade ago, and that there continued to be no clear cut evidence of either benefit or ineffectiveness. There is no evidence-based or consensus research to suggest an optimal technique. The mechanism of inactivation of the trigger point remains unknown. Many consider dry needling as effective as a TPI. It has been suggested that the main effect is placebo. (Cummings, 2001) There are no studies that compare “stretching” treatment alone or “no treatment” to TPIs. Most current studies have evaluated the use of a TPI as a stand-alone treatment. (Scott, 2008) (Staal, 2008)

Indications: The main indication is to inactivate the trigger point in order to reduce pain and restore function. This may enable physical therapy. The injection is also used as a diagnostic tool. (Scott, 2008) Whiplash and chronic head, neck, shoulder and back pain: The evidence for TPIs when used as a sole treatment for patients with whiplash syndrome or chronic head, neck, shoulder or back pain (regardless of injectate) is inconclusive and the treatment does not appear to be more effective than treatments such as laser or ultrasound. These injections are not recommended for typical chronic low back or neck pain, nor are they recommended for radicular pain. Fibromyalgia: There is no evidence to support trigger point injections for this condition using randomized controlled trials. Uncontrolled trials suggest that dry needling or soft-tissue injections with lidocaine are equally effective. (Goldenberg, 2004) Cervicogenic headaches: The effectiveness is unknown. (Scott, 2005) Osteoarthritis: There is one randomized controlled trial that indicates that the addition of TPIs to intra-articular injections improves pain and function over and above the latter injection alone. (Yentur, 2003)

Needling procedures: The standard definition of TPIs (also called direct wet needling) involves injecting fluid directly into the trigger point. (Cummings, 2001) Other needling techniques include injection of fluid over the trigger point into the skin or subcutaneous tissue, direct dry needling, or indirect dry needling (the needle is placed superficially or deep into classic acupuncture points or over a tender spot, but not into the trigger point). See Acupuncture.

Injection fluids: The injection of a local anesthetic can reduce the pain of a trigger point. TPIs with an anesthetic such as bupivacaine are recommended for non-resolving trigger points. In addition, the addition of a local anesthetic can reduce the pain of injection. The addition of a corticosteroid is not generally recommended and there is moderate evidence that TPIs with corticosteroids do not produce significantly different results from placebo injections using short-term self reports. Current evidence does not support the use of Botulinum toxin in trigger point injections for myofascial pain. (Ho, 2007) (Peloso, 2007)

Adverse effects: The following have been published in case reports: cervical epidural abscess; accidental intrathecal injection; muscle atrophy at the injection site; pneumothorax; development of asystole. There is also a concern that when used as a primary therapy patients may become dependent on this treatment, diverting from the underlying factors causing and maintaining pain. (Borg-Stein, 2002) Vasovagal responses are the most frequent complication. Other complications include bleeding, cuts or tears to the muscle, injury to nerve fibers, damage to blood vessels, infection, and allergic reactions (including anaphylaxis). Contraindications: Acute cases of muscle trauma; Allergies to anesthetic agents; Bleeding disorders; Local or systemic infection; Anticoagulant use.

Trigger point definitions: A trigger point is a hyperirritable foci located in a palpable taut band of skeletal muscle, which produces a local twitch in response to stimulus to the band. Pain is generally reported on compression, with common evidence of characteristic referred pain. This may or may not be accompanied by an autonomic response. Trigger points may be present in up to 33-50% of the adult population. There is currently no satisfactory objective, biochemical, electromyographic, or diagnostic imaging test to diagnosis trigger points. (Scott, 2008) Active trigger point: Continuous pain is generated in the zone of reference with or without palpitation. Latent trigger point: No evidence of spontaneous pain but evidence of restricted movement and muscle weakness. Primary trigger point: develop independently of other trigger points. Satellite trigger points: result from stress and muscle spasm caused by neighboring trigger points. (Scott, 2005) Myofascial pain syndrome is a regional painful muscle condition with a direct relationship between a specific trigger point and its associated pain region. A cluster of symptoms is noted including pain, autonomic phenomena and muscle dysfunction. Examples of primary myofascial pain syndrome include tennis elbow, frozen shoulder and chronic tension type headache. Secondary myofascial pain is found in the presence of conditions such as whiplash, TMJ dysfunction, and osteoarthritis. Psychosocial factors may contribute to muscle tension and an increase in pain, in particular, anxiety. (Esenyel, 2000) (Nifosi, 2007) (Altindag, 2008) (Graff-Radford, 2004) (BlueCross BlueShield, 2004) (Nelemans-Cochrane, 2002)

Criteria for the use of TPIs (Trigger point injections):

TPIs with a local anesthetic may be recommended for the treatment of myofascial pain syndrome when all of the following criteria are met: (1) Documentation of circumscribed trigger points with evidence upon palpation of a twitch response as well as referred pain; (2) Symptoms have persisted for more than three months; (3) Medical management therapies such as ongoing stretching exercises, physical therapy, NSAIDs and muscle relaxants have failed to control pain; (4) Radiculopathy is not present (by exam, imaging, or neuro-testing); (5) No more than 3-4 injections per session; (6) No repeat injections unless a greater than 50% pain relief with reduced medication use is obtained for six weeks after an injection and there is documented evidence of functional improvement; (7) Frequency should not be at an interval less than two months; (8)TPIs with any substance (e.g., saline or glucose) other than local anesthetic with or without steroid are not recommended; (9) There should be evidence of continued ongoing conservative treatment including home exercise and stretching. Use as a sole treatment is not recommended; (10) If pain persists after 2 to 3 injections the treatment plan should be reexamined as this may indicate a lack of appropriate diagnosis, a lack of success with this procedure, or a lack of incorporation of other more conservative treatment modalities for myofascial pain. It should be remembered that trigger point injections are considered an adjunct, not a primary treatment.

Tumor necrosis factor (TNF) modifiers

Not recommended. This drug was recently included in a list of 20 medications identified by the FDA's Adverse Event Reporting System which are under FDA investigation. (FDA, 2008) See also relevant DWC MTUS body chapters.


Not recommended for treatment of chronic pain. UltraClear is a medical food that is a proprietary blend of nutrients in a low-allergen-potential rice protein base. See Medical foods.

Ultram® (tramadol)

Ultram® is a brand of tramadol supplied by Ortho-McNeil Pharmaceutical. See Tramadol (Ultram®).

Ultrasound, therapeutic

Not recommended for the treatment of chronic pain. Therapeutic ultrasound is one of the most widely and frequently used electrophysical agents. Despite over 60 years of clinical use, the effectiveness of ultrasound for treating people with pain, musculoskeletal injuries, and soft tissue lesions remains questionable. There is little evidence that active therapeutic ultrasound is more effective than placebo ultrasound for treating people with pain or a range of musculoskeletal injuries or for promoting soft tissue healing. (Robertson, 2001)

Uncaria Tomentosa (Cat's Claw)

Not recommended for the treatment of chronic pain.

Urine drug testing (UDT)

See DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for additional information on urine drug testing.

Valium (diazepam)

See Benzodiazepines.

Venlafaxine (Effexor®)

Recommended as an option in first-line treatment of neuropathic pain. Venlafaxine (Effexor®) is a member of the Selective serotonin and norepinephrine reuptake inhibitors (SNRIs) class of antidepressants. It has FDA approval for treatment of depression and anxiety disorders. It is off-label recommended for treatment of neuropathic pain, diabetic neuropathy, fibromyalgia, and headaches. The initial dose is generally 37.5 to 75 mg/day with a usual increase to a dose of 75 mg b.i.d or 150 mg/day of the ER formula. The maximum dose of the immediate release formulation is 375 mg/day and of the ER formula is 225 mg/day. It may have an advantage over tricyclic antidepressants due to lack of anticholenergic side effects. Dosage requirements are necessary in patients with hepatic and renal impairment. (Namaka, 2004) See Antidepressants for chronic pain for general guidelines, as well as specific Venlafaxine listing for more information and references.


See DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for information on opioids. Also see Hydrocodone/Acetaminophen (Vicodin®).


See DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for information on opioids. Also see Hydrocodone/Ibuprofen (Vicoprofen®).

Vimovo (esomeprazole magnesium/ naproxen)

See Proton pump inhibitors (PPIs) & Naproxen. In May 2010 FDA approved Vimovo, a fixed-dose tablet combination of delayed-release enteric-coated naproxen and immediate-release esomeprazole magnesium (Nexium). The NSAID/PPI combo is indicated to relieve signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis while decreasing the risk for NSAID-related gastric ulcers in susceptible patients. (FDA, 2010) As with Nexium, a trial of omeprazole and naproxen or similar combination is recommended before Vimovo therapy.

Vimpat® (lacosamide)

See Lacosamide (Vimpat®).

Vioxx® (rofecoxib)

Not recommended. Note: Pulled from market 10/5/04. See Anti-inflammatory medications and NSAIDs (non-steroidal anti-inflammatory drugs). Recent studies have shown an increase in the risk of myocardial infarction for rofecoxib (Vioxx), compared to NSAID’s with an antiplatelet effect. (Choi, 2004) (Solomon, 2004)

Vitamin B

Not recommended for the treatment of chronic pain. Vitamin B is frequently used for treating peripheral neuropathy but its efficacy is not clear. A recent meta-analysis concluded that there are only limited data in randomized trials testing the efficacy of vitamin B for treating peripheral neuropathy and the evidence is insufficient to determine whether vitamin B is beneficial or harmful. In the comparison of vitamin B with placebo, there was no significant short-term benefit in pain intensity while there is a small significant benefit in vibration detection from oral benfotiamine, a derivative of thiamine. In comparing different doses of vitamin B complex, there was some evidence that higher doses resulted in a significant short-term reduction in pain and improvement in paraesthesiae, in a composite outcome combining pain, temperature and vibration, and in a composite outcome combining pain, numbness and paraesthesiae. There was some evidence that vitamin B is less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in the short-term improvement of clinical and nerve conduction study outcomes. Vitamin B is generally well-tolerated. (Ang-Cochrane, 2008)

Vitamin D (cholecalciferol)

Not recommended for the treatment of chronic pain. Although it is under study as an isolated pain treatment, vitamin D supplementation is recommended to supplement a documented vitamin deficiency, which is not generally considered a workers' compensation condition. Musculoskeletal pain is associated with low vitamin D levels but the relationship may be explained by physical inactivity and/or other confounding factors. Adjusting for these factors attenuated the relationship, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels. (McBeth, 2010) Inadequate vitamin D may represent an under-recognized source of nociperception and impaired neuromuscular functioning among patients with chronic pain. Physicians who care for patients with chronic, diffuse pain that seems musculoskeletal - and involves many areas of tenderness to palpation - should consider checking vitamin D level. For example, many patients who have been labeled with fibromyalgia may be suffering from symptomatic vitamin D inadequacy. Patients with inadequate vitamin D may benefit from cholecalciferol 50,000 international units dosed according to the level of deficiency, but caution is necessary for patients with calcium- or phosphate- processing disorders because increasing vitamin D levels could be problematic in patients with kidney failure or stones or primary hyperparathyroidism or sarcoidosis. For patients with adequate vitamin D looking to maintain levels, 10 to 15 minutes of sun exposure might be recommended with no sunscreen on the trunk and arms and legs 3 times a week. (Turner, 2008)

Vitamin K

Not recommended for the treatment of chronic pain. There is insufficient literature to support the use of Vitamin K for chronic pain.

Vivitrol® (naltrexone)

See Naltrexone (Vivitrol®).


See Diclofenac Sodium (Voltaren®, Voltaren-XR®), where the oral form is recommended with cautions, but not as a first-line drug.

Voltaren® Gel (diclofenac)

Not recommended as a first-line treatment. See Diclofenac Sodium (Voltaren®), where Voltaren Gel is recommended for osteoarthritis after failure of an oral NSAID, or contraindications to oral NSAIDs, or for patients who cannot swallow solid oral dosage forms, and after considering the increased risk profile with diclofenac, including topical formulations. According to FDA MedWatch, postmarketing surveillance of Voltaren Gel has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation. (FDA, 2011) For more details see Topical analgesics, Non-steroidal antinflammatory agents (NSAIDs), and the diclofenac topical listing.


See Weaning, benzodiazepines (specific guidelines); Weaning, carisoprodol (Soma®); Weaning, pregabalin (Lyrica®); Weaning, scheduled medications (general guidelines); Weaning, stimulants.

Weaning, benzodiazepines (specific guidelines)

Recommended for selected patients. See Weaning, scheduled medications (general guidelines). There is no specific or internationally recognized treatment for dependence on this class of drugs. Researchers suggest that serious dependence involves individuals who (1) are prescribed this class of drugs for underlying pathology and progress to inappropriate use, or (2) individuals who use this class of drugs for recreational use. Serious problematic use includes evidence of mixing benzodiazepines, repeated evidence of escalating doses, or use to enhance effects of other substances. Unfortunately, most current research on weaning of benzodiazepines addresses patients who are not abusing this class of drugs (i.e. are using their medication for legitimate diagnoses with no evidence of abuse). (Liebrenz, 2010)

Guidelines: Tapering is generally required if used for greater than 2 weeks. The concomitant use of alcohol and/or other sedative hypnotics should be ascertained. A history of anxiety disorder (particularly panic) should be elicited. Medical supervision is recommended for withdrawal as there are significant possible complications. Withdrawal is considered more severe for benzodiazepines with shorter elimination half-life. (Rickels, 1999) (Maremmani, 2013) (Ashton, 2009) (Lingford-Hughes, 2004) (Voshaar, 2006) (Parr, 2009)

Weaning setting: Outpatient weaning is generally only recommended for patients who are taking drugs in a therapeutic range, who are on monotherapy (benzodiazepines only), are considered reliable and have the help of significant others to monitor progress.

Chance of achieving long-term abstinence: Due to risks of weaning the most attainable goal may be to simply achieve a lower dose of this class of medication with preference for a switch from rapid onset, short-acting formulations to slower-onset, longer-acting formulations (such as clonazepam). See Benzodiazepine dependence, maintenance. (O’Brien, 2005) (Liebrenz, 2010) (Maremmani, 2013)

Current weaning protocol recommendations: Weaning of benzodiazepines in general is more dangerous than opioid withdrawal, and takes more time. A step-wise approach is indicated based on limited research. The initial recommendation is to use minimal interventions including advisory letters, education and single-visit doctor’s consults addressing use of this class of drugs. The next step is gradual drug reduction. As noted, there is no currently universal weaning protocol available. One current recommendation is the following: (1) The recommended rate of tapering is about 1/8 to 1/10 of the daily dose every 1 to 2 weeks; (2) An alternative weaning schedule is to decrease by 10% a week or 5 mg (whichever is smaller); (3) The first 50% of weaning is generally smoother than the last 50%; (4) When the final 25% to 35% of dose is reached it is suggested that the decrease in dose be lowered to 5% at a two-week interval; (5) Rate of withdrawal should be individually tapered based on signs and symptoms; (6) Visits should occur on a weekly basis during weaning or more often if clinically indicated; (7) Recurrent assessment is required, particularly at the time of dose changes; (8) High-dose abusers or those with polydrug abuse may need in-patient detoxification; & (9) Withdrawal can occur when a chronic user switches to a benzodiazepine with a different receptor activity. A recent review suggests not prolonging weaning for over six months. (Lee, 2002) (TIP 45, 2006) (Lader, 2009) (Morin, 2004) (Alexander, 1991) (Ashton, 1994) It should be noted that the above recommendation for weaning is often not effective for patients taking short-acting benzodiazepines (lorazepam, oxazepam, triazolam, alprazolam and temazepam). A recommendation has been made to switch to a long-acting drug such as chlordiazepoxide or clonazepam or alternatively, phenobarbital, prior to an attempted wean from these drugs.

Benzodiazepine withdrawal signs and symptoms: These fall into four general categories: (1) Relapse of the symptoms that the drugs were first prescribed for (such as anxiety or insomnia); (2) Rebound of symptoms (a short-duration, intense phenomenon which is self-limited); (3) Pseudowithdrawal (expectations of withdrawal lead to expectations of abstinence); (4) True withdrawal. Prolonged withdrawal has also been described. Seizures are the most worrisome medical complication of withdrawal. Specific signs and symptoms include anxiety, insomnia, restlessness, agitation, irritability and muscle tension. Less frequently reported are nausea, diaphoresis, lethargy, aches and pains, blurred vision, nightmares, depression, hyperreflexia and ataxia. Elderly patients in particular are at risk for delirium, risks of falls, and myocardial infarctions. (TIP 45, 2006) (Dickenson, 2009) (Petursson, 1994)

Adjunct drugs used for weaning from benzodiazepines: Converting to phenobarbital or a long-acting benzodiazepine from a short-acting formulation has been recommended as a step in weaning. Conversion tables are available for specific benzodiazepines to phenobarbital equivalents with recommendations for weaning. (TIP 45, 2006 - figure 4.5) (Dickenson, 2009 - p. 581) Anticonvulsants such as carbamazepine and valproate have been used. (Denis, 2006) (Cluver, 2009)

Equianalgesic doses of benzodiazepines with half-life:

Multiple tables are available suggesting approximate equianalgesic doses. The expanded ranges presented in this table are noted in part where different disease pathology is addressed with the same drug (i.e. addressing anxiety vs. sedation).


Time to peak onset (hrs)

Half-life (hrs)

Approximate Equivalent Oral Dose (in mgs)




































0.25 mg

Changing to long-acting formulations: This may take several days, with substitution at intervals, generally starting with the night-time dose.

Comorbid medical conditions and age: The risk of adverse effects due to withdrawal may outweigh long-term benefits of discontinuing benzodiazepines. This is particularly a concern for patients with adrenergic stress factors (i.e. cardiac disease and asthma), or psychologic stress.

Important points to remember: (1) There is a high risk of the use of alcohol in patients taking benzodiazepines. (2) There is a high risk of anxiety disorders in patients taking benzodiazepines. (3) Withdrawal in elderly patients may be prolonged and the clinician needs to address severity of high-dose withdrawal due to pharmacokinetics. (Benzon, 2005) (Ashton, 2005) (Kahan, 2006) (Lader, 2009) (Smith, 1990) (Dickenson, 2009)

Benzodiazepine dependence, maintenance treatment: Recommended for selected patients. Early research indicates that switching from rapid-onset, short-acting benzodiazepines to slow-onset, long-acting formulations is an option. In some cases this will actually allow for ultimate discontinuation of this class of drugs. Clonazepam is the suggested drug to switch to. It has a slow onset of action, half-life of 18-50 hours, high potency and lack of active metabolites. (Liebrenz, 2010) (Maremmani, 2013)

Weaning, carisoprodol (Soma®)

Recommended for selected patients (the majority). See Weaning, scheduled medications (general guidelines). This medication is metabolized to meprobamate, a schedule C-IV controlled anxiolytic agent. There is little research in terms of weaning of high dose carisoprodol and there is no standard treatment regimen for patients with known dependence. Most treatment includes treatment for symptomatic complaints of withdrawal.

Weaning: For patients on low to moderate doses of carisoprodol or for short-term duration a slow taper of 2-4 weeks is recommended. One option for withdrawal for patients using high doses of carisoprodol (particularly for those using the drug in doses over what is prescribed) or for long durations is to switch to phenobarbital with subsequent tapering. A conversion table is available for Soma to phenobarbital equivalents (700 mg to 30 mg, respectively) with recommendations for weaning. (Dickenson, 2009 - p. 581) A maximum suggested dose of phenobarbital is 500 mg/day and the taper is 30 mg/day with a slower taper in an outpatient setting. Tapering should be individualized for each patient.

Symptoms of withdrawal: Thought to be secondary to both withdrawal for carisoprodol and meprobamate. Symptoms consist of insomnia, vomiting, tremors, muscle twitching, anxiety, and ataxia with abrupt cessation of large doses. Hallucinations and delusions may also occur. (Reeves, 2010) (Reeves, 2007) (Boothby, 2003) (Heacock, 2004) (Washington, 2002) (Wright, 2009) See also Weaning, scheduled medications (general guidelines); Detoxification; & Rapid detox.

Weaning, opioids

See DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for guidelines on weaning opioids.

Weaning, pregabalin (Lyrica®)

Recommended for selected patients. The manufacturer of this drug recommends weaning over at least one week when used as seizure therapy. There is no formal protocol available to guide in weaning when used for treatment of chronic pain, and the drug is rarely used as a monotherapy. A consensus recommendation of a minimum of weaning over two to four weeks is made when used for chronic pain. See also Weaning, scheduled medications (general guidelines); Detoxification; & Rapid detox.

Weaning, scheduled medications (general guidelines)

Recommended when there is evidence of substance misuse, abuse or addiction, as indicated below. See Substance abuse (tolerance, dependence, addiction) for definitions. While the main indication as related to substance-related disorders is evidence of aberrant drug behaviors, other indications for weaning include the following: (1) Intolerable side effects; (2) Lack of significant symptomatic response to current pain medication treatment (particularly when there is evidence of increasingly escalating doses of substances known for dependence); (3) Refractory comorbid psychiatric illness; (4) Lack of sustained functional improvement related to opioid use; and/or (5) Risks exceeding benefits.

Initial Evaluation: Patients considered for weaning should undergo an assessment of their general medical, psychiatric, surgical and pain treatment history, with education regarding rationale for weaning, symptoms and potential adjunctive agents or alternative treatments. Vital signs should be monitored throughout the weaning process. Urine toxicology screening may be indicated. If performed in a patient with substance-related disorder (abuse, misuse or addiction), a psychiatric evaluation may not reveal an accurate diagnosis until months after weaning is achieved.

Setting for weaning: Important variables as to the setting in which weaning should occur include the presence of comorbid medical and psychiatric pathology and evidence of use of poly-pharmacy. Medical conditions that may favor inpatient detoxification include a history of significant TBI or seizures (seizure risk, delirium), cardiac disease (sympathetic hypersensitivity), significant liver or kidney disease. Psychiatric conditions potentially favoring inpatient weaning include suicidal or homicidal risks, delirium, and diagnosis of bipolar disorder and other significant psychiatric disease. Patients with alcoholism and history of delirium tremens may merit inpatient treatment. Many of the patients that are recommended for inpatient weaning are using high doses and/or multiple substances that are prescribed, and may also be using other substances such as alcohol and/or illicit substances (street drugs). Benzodiazepines and sedative-hypnotics in particular contribute to increased withdrawal symptoms, including the possibility of seizures, and a less predictable course. More intensive monitoring will be necessary when these variables are present. (TIP 40, 2004) Weaning for specific classes of drugs are listed in the following entries in the Pain Chapter: Weaning, benzodiazepines (specific guidelines); Weaning, carisoprodol (Soma®); Weaning, pregabalin (Lyrica®); Weaning, stimulants.

Weaning, stimulants

Recommended in selected patients (consensus). The stimulant class includes armodafinil, modafinil, methylphenidate, dextroamphetamine, & amphetamine salt combinations. See Weaning, scheduled medications (general guidelines). Stimulant withdrawal is generally not medically life threatening. The most serious problem with withdrawal is that patients may become severely depressed (to the point of suicide), and develop agitation and insomnia. Antidepressant therapy may be required. Withdrawal symptoms develop within hours to days after heavy use. In patients who are abusing this class of drugs, concomitant use of other drugs and/or alcohol should be evaluated for. Patients who are abusing stimulants or show evidence of abuse of multiple substances should be weaned under the direction of a specialist.

Withdrawal signs and symptoms: Jittery reactions with agitated paranoia; Intense drug craving; Weight loss; Anorexia; Dehydration; Fatigue; Dulled senses; Psychomotor lethargy and retardation with impaired memory; Hunger; Chills; Insomnia followed by hypersomnia; Dysphoric mood; Anxiety; Social withdrawal. (TIP 33, 1999)

Recommendations for weaning specific drugs in situations where abuse is not suspected (i.e. the drugs are taken as prescribed):

- Armodafinil (Nuvigil®): There is no recommendation for weaning of this drug by the manufacturer.

- Modafinil (Provigil®): In one clinical trial withdrawal did not occur with abrupt discontinuation. If given for excessive daytime sleepiness, symptoms may return to baseline.

- Stimulants requiring gradual weaning: Methylphenidate (Ritalin®, Methylin®, Metadate ER®, Methylin ER®, Ritalin SR®); Amphetamine salt combo (Adderall®, Adderall XR®);

- Dextroamphetamine (Dexedrine®, Dextrostat®, Dexedrine Spansules)

Gradual withdrawal over two to four weeks is recommended as abrupt discontinuation can unmask severe depression and precipitate withdrawal. See Weaning, scheduled medications (general guidelines).

Wellbutrin® (bupropion)

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