(b) SNRIs:Duloxetine (Cymbalta®, no generic available):also approved for major depressive disorder. Dosing information:30-120 mg daily.Venlafaxine extended release (Effexor XR®, generic available):also recommended for PD and SAD as well as major depressive disorder.Dosing information: 75-225 mg daily. It may be recommended for some patients to start at 37.5 mg for the first 4 to 7 days. (Package insert)
(c) 5-HT1A Agonist: Buspirone (Buspar®, generic available): also approved for short-term relief of anxiety symptoms. Efficacy is decreased in patients with recent prior benzodiazepine use. (Chessick, 2006) Dosing information: 5-15 mg three times daily. (Package insert)
(d)Benzodiazepines: Effective for acute treatment. Long-term use is problematic as few patients achieve and sustain remission with monotherapy. These agents are used primarily as an adjunct for stabilization during initiation of an SSRI or SNRI. The disadvantage of use is the risk of abuse and physiological dependence with long-term use. These drugs also have no anti-depressant effect. Diazepam (Valium®, generic available): Dosing information: 5-15 mg daily. Clonzaepam (Klonopin®, generic available): Dosing information: 1-2 mg up to TID.
(e) TCAs (Tricyclic antidepressants): This class of medications is an effective treatment for GAD but few studies have investigated their use for DSM-IV defined GAD. Their use is limited by poorer tolerability.
(f) Other medications that may be useful: Hydroxyzine (Atarax®, generic available): Dosing information: 50 mg/day. Pregabalin (Lyrica®, generic available): Non-FDA approved indication. Dosing information: 50-200mg three times daily (with a general range of 200-450 mg a day) Atypical antipsychotics: Olanzapine (Zyprexa®) and Risperidone (generic available): used as an adjunct agent.
(2) PANIC DISORDER (PD) with and without agoraphobia: Panic disorder (PD) is described by the DSM-IV-TR to include periods of intense fear that peak within 10 minutes. Symptoms include palpitations, sweating, shortness of breath and lightheadedness. Patients often have persistent worry about having further attacks. PD can occur with or without agoraphobia (anxiety about and avoidance of being in situations where escape may be difficult). Outcomes are measured in terms of frequency and change in the total number of attacks. Testing includes the Panic Disorder Severity Scale (PDSS). (Hoffman, 2008) (Mitte, 2005) (Otto, 2001) (Furukawa, 2007)
(a) Maintenance treatment: SSRIs are first-line medications based on safety and tolerability. If the patient does not respond, another SSRI should be attempted. If this fails, another class of medications should be attempted (SNRI, TCA or benzodiazepine). Fluoxetine (Prozac®, generic available): Also approved for major depressive disorder, OCD and premenstrual dysphoric disorder. Dosing information: 20-60 mg daily. Paroxetine (Paxil®, generic available): Also recommended for GAD, SAD, OCD, and PTSD as well as major depressive disorder. Dosing information: dosing is typically 10-60 mg daily. Paroxetine CR (Paxil® CR): Also approved for SAD, major depressive disorder, and premenstrual dysphoric disorder. Sertraline (Zoloft ®, generic available): Also approved for PTSD, SAD, OCD, major depressive disorder and premenstrual dysphoric disorder. Dosing information: 50-200 mg once daily. Citalopram (Celexa®, generic available): Non-FDA approved indication. Dosing information: 20-60 mg once daily. Fluvoxamine (Luvox®, generic available): Non-FDA approved indication. Dosing information: Initially 50mg at bedtime, doses should be titrated upward to daily doses of 100-300 mg daily. Daily doses greater than 100mg should be divided, with the larger dose given at bedtime. Escitalopram (Lexapro®): Non-FDA approved indication. Dosing information: 10-20 mg once daily. SNRI: Venlafaxine (Effexor XR®, generic available): also approved for GAD, SAD and major depressive disorder. Dosing information: 37.5-225 mg daily.
(b) Secondary treatment options, when other medications have failed or been intolerable to patients: Tricyclic Antidepressants (TCAs): Clomipramine (Anafranil®, generic available): Dosing information: 75-250 mg daily. (Bandelow, 2002) Imipramine (Tofranil®, generic available): Dosing information: 75-250 mg daily. (Bandelow, 2002) MAOI: Phenelzine (Nardil®, no generic available): Dosing information: 45-90 mg daily in divided doses, three times daily. Other anti-depressants: Mirtazapine (Remeron®, generic available): Dosing information: 45 mg daily.
(c) Acute treatment: Benzodiazepines may be recommended with initial treatment as an adjunct agent to SSRIs as the latter class of drugs is titrated. Benzodiazepines (short acting): Alprazolam (Xanax®, generic available): Dosing information: 0.25-1 mg TID or QID. Clonazepam (Klonopin®, generic available): Dosing information: 1-4 mg daily in two divided doses. The dose should be tapered downward during discontinuation by 0.125mg twice daily every 3 days. Doses of 1 mg are just as effective as higher doses, with less adverse effects. However, some patients may benefit from higher doses. (Roche Laboratories, 2001)
(3) POST-TRAUMATIC STRESS DISORDER (PTSD)
Characterized in DSM-IV by three symptom clusters which persist for more than one month, and cause clinically significant distress: re-experiencing the event; emotional numbing/avoidance of stimuli associated with trauma; and hyperarousal. DSM-V adds another cluster, negative alterations in cognitions and mood associated with the traumatic event.
Most clinical guidelines recommend pharmacotherapy as a first-line treatment for PTSD. Long-term trials show that while 30% of patients remit within 12 weeks, a substantial percentage does not achieve remission within 6 months (Friedman, 2013)
(a) SSRIs: considered first-line agents in the treatment of PTSD. Paroxetine (Paxil®, generic available): Also recommended for GAD, SAD, OCD, and PD as well as major depressive disorder. Dosing information: 20-50mg daily (Bandelow, 2002) (PPI GlaxoSmithKline, 2004) Sertraline (Zoloft ®, generic available): Also approved for PD, SAD, OCD, major depressive disorder and premenstrual dysphoric disorder. Dosing information: 50-200mg daily. Fluoxetine (Prozac®, generic available): Dosing information: 20-40mg daily. (Bandelow, 2002) (Clinical Pharmacology, 2008)
(c) Other antidepressants Venlafaxine (Effexor-XR) is effective for symptoms of PTSD, and is associated with improved resilience (Davidson, 2006). Mirtazapine, an antidepressant with both serotonergic and adrenergic activity has proven efficacy for PTSD, and is recommended as a second-line agent (Friedman, 2013). Trazodone may be used in conjunction with SSRIs to counter medication induced insomnia.
(d) Alpha-1 Adrenergic Agents: Prazosin, is effective for hyperarousal symptoms, including nightmares of PTSD. (Raskind, 2003, 2007)
(e) Topiramate has a broad spectrum effect on PTSD symptoms, comparable to other psychopharmacological agents. (Akuchekian, 2004), (Tucker, 2007), (Yeh, 2011)
Antipsychotics like Risperidone may be beneficial as an adjunct treatment.
Benzodiazepines are not recommended for PTSD, unless they are needed for comorbid disorders.
(4) SOCIAL ANXIETY DISORDER (SAD):
The DSM-IV-TR describes generalized SAD as a persistent fear of social situations, with exposure leading to anxiety and avoidance. Outcomes: Most studies have used the Liebowitz Social Anxiety Scale (LSAS). (Hoffman, 2008) (Schneier, 2006) (Hedges, 2007) (Ipser, 2008)
(a) SSRIs: generally recommended as first-line agents for treating SAD, due to effectiveness and favorable side effect profile. The initial dose is generally half of the usual dose. Titration can occur over 1 week to 4 weeks. A trial of a SSRI is recommended for at least 12 weeks as some patients take over 8 weeks for a response. Maintenance therapy is recommended for those patients who take over 8 weeks for response to prevent relapse. Medications are indicated for at least 6 to 12 months with follow-up for relapse. (Schneier, 2006) Paroxetine (Paxil®, generic available): Also recommended for GAD, PD, OCD, and PTSD as well as major depressive disorder. Dosing information: 20-60mg daily. (Bandelow 2002) Paroxetine controlled release (Paxil CR®, generic available): Also approved for PD, major depressive disorder, and premenstrual dysphoric disorder. Dosing information: Initially 12.5 mg daily, may increase up to 37.5mg daily. (PPI GlaxoSmithKline) Sertraline (Zoloft®, generic available: Also approved for OCD, major depressive disorder and premenstrual dysphoric disorder. Dosing information: 50-150 mg daily (max 200 mg daily). Escitalopram (Lexapro®, no generic available): Non-FDA approved indication. Dosing information: 10-20 mg once daily. Fluvoxamine (Luvox®, generic available): Non-FDA approved indication. Dosing information: Initially 50 mg at bedtime, doses should be titrated upward to daily doses of 100-300 mg daily. Daily doses greater than 100 mg should be divided, with the larger dose given at bedtime.
(b) SNRI: Considered a first-line medication for generalized SAD. Venlafaxine (Effexor XR®, generic available): also approved for GAD, PD and major depressive disorder. Dosing information: 37.5-225mg daily. Generally started at half of the usual dose and increased over the first week of treatment. Doses can then be increased over a 4-week period.
(c)Other agents used as secondary or alternative treatment to SSRIs: (Schneier, 2006) Benzodiazepines: Clonazepam (Klonopin®, generic available): Dosing information: See Generalized Anxiety Disorder. Anticonvulsants: Gabapentin (Neurontin®, generic available): non-FDA approved indication. Dosing information: 900-3600 mg per day in divided doses. Pregabalin (Lyrica®): Non-FDA approved indication. Dosing information: 300-600 mg.
(5) OBSESSIVE COMPULSIVE DISORDER (OCD): Characterized by recurrent obsessional ruminations, images or impulses, and/or recurrent physical or mental rituals. These ruminations interfere with social and occupational function. OCD is thought to respond selectively to drugs that inhibit the synaptic reuptake of serotonin. An adequate trial should consist of 10-12 weeks with at least 4-6 weeks at the maximum tolerated dose. Cognitive-behavioral therapy may need to be considered. (Soomro, 2008) (Baldwin, 2005)
(a) SSRIs:Fluoxetine (Prozac®, generic available): Dosing information: 20-80 mg daily, doses greater than 40 mg daily should be divided. Fluvoxamine (Luvox®, generic available): Dosing information: doses should be titrated to a range of 100-300 mg, with doses greater than 100 mg daily in divided doses. Paroxetine (Paxil®, generic available): Dosing information: Initially 20mg (optimal dose is 40mg/day); max dose is 60mg daily. Sertraline (Zoloft®, generic available): Dosing information: 50-200 mg daily.
(b) TCAs:Clomipramine (Tofranil®, generic available): Dosing information: Initially 25 mg daily, dose should be titrated upward to doses from 75-250 mg daily. Dose may be given at bedtime to reduce the incidence of daytime sedation. Note: During the initial titration of clomipramine, the dose may be given in divided daily doses in order to minimize GI effects. (PPI Mallinkrodt Inc.)
(c) Benzodiazepines for severe cases, treatment resistant cases or adjunctive therapy:Clonazepam (Klonopin®, generic available).
(d) Other agents used for treatment resistant patients (Adjunct therapy): If there is no response to one of the above drugs, the suggestion is to try another first-line alternative. Then adjunct therapy is suggested. This includes the combination of a SSRI and clomipramine, or the use of one of the above with a benzodiazepine, buspirone, antipsychotic, or mood stabilizer. If there is no response a MAOI inhibitor may be required. (Dell’Osso, 2007)
APAP is an abbreviation for N-acetyl-para-aminophenol, which is acetaminophen. APAP is used especially when combined with a prescription drug. See Acetaminophen.
Recommended as an optional form of exercise therapy, where available, as an alternative to land-based physical therapy. Aquatic therapy (including swimming) can minimize the effects of gravity, so it is specifically recommended where reduced weight bearing is desirable, for example extreme obesity. For recommendations on the number of supervised visits, see Physical therapy. Water exercise improved some components of health-related quality of life, balance, and stair climbing in females with fibromyalgia, but regular exercise and higher intensities may be required to preserve most of these gains. (Tomas-Carus, 2007)
Armodafinil is used to treat excessive sleepiness caused by narcolepsy or shift work sleep disorder. It is very similar to Modafinil. Studies have not demonstrated any difference in efficacy and safety between armodafinil and modafinil. (Tembe, 2011) For more information see also Modafinil (Provigil®), Recently Cephalon produced a campaign advertising Nuvigil’s ability to help shift workers stay alert on the job without impeding their ability to sleep during the day. The FDA is conducting an investigation into the possibility that this advertising or promotional information may have violated current regulations. (SEC, 2011)
Arthrotec® (diclofenac/ misoprostol)
See NSAIDs (non-steroidal anti-inflammatory drugs); NSAIDs, GI symptoms & cardiovascular risk; NSAIDs, hypertension and renal function; & NSAIDs, specific drug list & adverse effects for general guidelines, as well as specific Arthrotec® (diclofenac/ misoprostol) listing for more information and references. See also Diclofenac, where it is not recommended as first line due to increased risk profile. The package insert for Arthrotec includes a boxed warning that also relates to potential toxicities of misoprostol. In the treatment of NSAIDs induced ulcers, omeprazole has proved to be at least as effective as misoprostol, but significantly better tolerated, and therefore misoprostol should not be considered a first choice treatment. (FDA, 2011)
Recommended. See Nonprescription medications; & Medications for acute pain (analgesics). Usual Adult Dose for Pain: 325 to 650 mg every 4 hours as needed, up to 3 grams per day in divided doses (spondyloarthropathies may require up to 4 grams per day in divided doses). (FDA, 2012)
Not recommended. The evidence is insufficient to evaluate the effect of auricular electroacupuncture on acute and chronic pain. In the only published RCT, use of the P-Stim device was not associated with improved pain management. Auricular electrostimulation or ear-acupuncture is a type of ambulatory electrical stimulation of acupuncture points on the ear. Devices, including the P-Stim™ and E-pulse, have been developed to provide continuous or intermittent stimulation over a period of several days. This type of electrostimulation is being evaluated for a variety of conditions, including pain, depression, and anxiety. Both the P-Stim (NeuroScience Therapy Corp) and the E-pulse (AMM Marketing LLC) devices have received marketing clearance through the FDA abbreviated 510(k) process for use in treating acute or chronic pain by a qualified practitioner of acupuncture. (Holzer, 2011) (Zhang, 2014) (Sator-Katzenschlager, 2007) see also Acupuncture.
Autonomic nervous system function testing
Not generally recommended as a diagnostic test for CRPS. See CRPS, diagnostic tests.
Autonomic test battery
Not generally recommended as a diagnostic test for CRPS. See CRPS, diagnostic tests.
Avinza® (morphine sulfate)
Avinza capsules are a brand of modified-release morphine sulfate. The capsules contain an immediate-release component that rapidly achieves a morphine concentration and an extended-release component that allows for extended concentration through a 24-hour dosing interval. Use: It takes approximately 2-3 days to achieve steady state and this drug is not recommended as an as needed (prn) drug or for acute pain. The manufacturer now specifically states that the 90 mg and 120 mg capsules are only recommended for patients for whom a tolerance to an opioid of comparable potency is established. A maximum dose of this drug has been established at 1600 mg due to the presence of fumaric acid. Comparison to other opioids (including extended-release and immediate-release morphine): There is one study that compares the pharmacokinetics of Avinza to MS Contin (the latter at a twice-a-day dose). This study was open-label and non-randomized. Clinical efficacy and safety were comparable for both formulations.(Portenoy, 2002) The original researchers indicated that analgesia was statistically identical to that produced by MS Contin, OxyContin and six doses of oral morphine sulfate administered every 4 hours. (Caldwell, 2004) Black Box Warning: The current Black Box Warning for Avinza is that patients must not consume alcohol with this drug (including that included in prescription and non-prescription medications). Consumption of alcohol may result in the rapid release and absorption of a potentially fatal dose of morphine. (FDA, 2008) The current FDA Orange Book (accessed March 2013) has determined that actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence.
See DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for recommendations on the use of opioids.
Axon-II neural scan
Not recommended. See Quantitative sensory threshold (QST) testing.
See CRPS, treatment. See also Muscle relaxants.
Barbiturate-containing analgesic agents (BCAs)
Not recommended for chronic pain. The potential for drug dependence is high and no evidence exists to show a clinically important enhancement of analgesic efficacy of BCAs due to the barbiturate constituents. (McLean, 2000) Fioricet is commonly used for acute headache, with some data to support it, but there is a risk of medication overuse as well as rebound headache. (Friedman, 1987) The AGS updated Beers criteria for inappropriate medication use includes barbiturates. (AGS, 2012) See also Opioids.
Recommended. Please review “Introduction to the MTUS Chronic Pain Guideline” for background on psychosocial variables and their potential role in delayed recovery and chronic pain. Risk Factors for delayed recovery include catastrophic thinking, fear-avoidance, and perceived injustice.
The identification and reinforcement of coping skills is often more useful in the treatment of pain than ongoing medication or therapy, which could lead to psychological or physical dependence. Several recent reviews support the assertion of efficacy of cognitive-behavioural therapy (CBT) in the treatment of pain, especially chronic back pain (CBP). (Kröner-Herwig, 2009)
The CBT treatment model has three stages: (1) skill education (2) skill acquisition and (3) skill maintenance / generalization. Homework assignments are an essential part of CBT. When possible, CBT should be coordinated with physical therapy. There are no studies that delineate specific quantity and frequency of CBT sessions for chronic pain. Please refer to the ODG Psychotherapy Guidelines (just below) for further recommendations.
Please refer to the DWC MTUS chapter on Low Back Complaints. See also “Behavioral treatment.”
ODG Psychotherapy Guidelines:
- Up to 13-20 visits over 7-20 weeks (individual sessions), if progress is being made.
(The provider should evaluate symptom improvement during the process, so treatment failures can be identified early and alternative treatment strategies can be pursued if appropriate.)
- In cases of severe Major Depression or PTSD, up to 50 sessions if progress is being made.
Not recommended for long-term use because long-term efficacy is unproven and there is a risk of psychological and physical dependence or frank addiction. Most guidelines limit use to 4 weeks. Benzodiazepines are a major cause of overdose, particularly as they act synergistically with other drugs such as opioids (mixed overdoses are often a cause of fatalities). Their range of action includes sedative/hypnotic, anxiolytic, anticonvulsant, and muscle relaxant. Chronic benzodiazepines are the treatment of choice in very few conditions. Tolerance to hypnotic effects develops rapidly (3-14 day). Tolerance to anxiolytic effects occurs within months and long-term use may actually increase anxiety. A more appropriate treatment for anxiety disorder is an antidepressant. Tolerance to anticonvulsant and muscle relaxant effects occurs within weeks. Tolerance to lethal effects does not occur and a maintenance dose may approach a lethal dose as the therapeutic index increases. The best prevention for substance use disorders due to benzodiazepines is careful prescribing. (Baillargeon, 2003) (Ashton, 2005) (Dickinson, 2009) (Lader, 2009) Adults who use hypnotics, including benzodiazepines such as temazepam, have a greater than 3-fold increased risk for early death, according to results of a large matched cohort survival analysis. The risks associated with hypnotics outweigh any benefits of hypnotics, according to the authors. In 2010, hypnotics may have been associated with 320,000 to 507,000 excess deaths in the U.S. alone. A dose-response effect was evident, with a hazard ratio of 3.60 for up to 18 pills per year, 4.43 for 18-132 pills per year, and 5.32 for over 132 pills per year. (Kripke, 2012) The AGS updated Beers criteria for inappropriate medication use includes benzodiazepines. (AGS, 2012) See also Anxiety medications in chronic pain; & Insomnia treatment. Benzodiazepines that are commonly prescribed include the following: alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, & triazolam. (Clinical Pharmacology, 2010)