1. Recognize fibromyalgia in patients who present with musculoskeletal pain.

2. Address other features of fibromyalgia, such as sleep disturbances.

3. Select effective therapy for fibromyalgia, based on clinical evidence.

4. Select effective therapy for children with attention-deficit/hyperactivity disorder (ADHD).

5. Differentiate ADHD from oppositional defiant disorder.

Fibromyalgia
Mark S. Wallace, MD, Professor of Clinical Anesthesiology, University of California, San Diego, School of Medicine

Chronic pain: pain that persists for ≥3 mo beyond normal healing period; fewer drugs available for treatment of chronic pain than for acute pain

Categories of pain: nociceptive—pain that travels through normal functioning nervous system; neuropathic— injury or insult to nervous system leads to long-term persistent changes in function; visceral—likely to possess components of nociceptive and neuropathic pain; many pain syndromes (eg, fibromyalgia) mixed

“The pain experience”: concept of both physical and psychologic components of pain; patients must embrace concept of interaction between mind and body

Diagnosis of fibromyalgia: essential to successful management; since patients have diffuse, generalized body pain, work-up may be negative, and pain may be attributed to psychologic disturbances; patients diagnosed with fibromyalgia tend to respond to treatment better; patients must be evaluated for underlying disorders; primary fibromyalgia—no underlying cause identified; secondary fibromyalgia—underlying cause (eg, rheumatoid disorder, lupus, rheumatoid arthritis, thyroid disorder) identified; treatment of underlying problem often leads to improvement in pain

Features of fibromyalgia: chronic, widespread musculoskeletal pain lasting ≥3 mo; other systemic conditions that may account for pain ruled out; multiple tender points; fatigue; sleep disturbances; other sensations (eg, paresthesias, swelling sensations); headaches; mood disturbances; improving sleep can improve daytime pain

Definition of fibromyalgia: American College of Rheumatology—widespread pain for ≥3 mo; pain on digital palpation in ≥11 of 18 tender point sites; pain in control sites (scalp, back of forearm, and thumb) “probably not fibromyalgia,” but helps identify nonorganic symptoms and psychologic issues (patients tend not to respond well to therapy); tender points—occiput at occipital muscle insertions; cervical; trapezius; supraspinatus; second rib; lateral pectoral epicondyle; lateral medial epicondyle; gluteal; greater trochanter; knee; pain above and below waist and bilateral

Diagnostic work-up: confirm history of widespread pain lasting ≥3 mo; physical examination; look for other causes of pain; review medication history (eg, statins commonly cause diffuse muscle pain); consider laboratory testing for, eg, thyroid disorders

Epidemiology and pathophysiology: 2% to 5% of US population affected; 90% of cases in women; evidence of genetic component (eg, gene mutations, polymorphisms) emerging; many patients describe triggers (eg, car accident, viral syndrome, psychologic stress); other causes may include osteoarthritis, immune disorders, rheumatoid arthritis, and hypothyroidism; central sensitization syndrome—central nervous system (mainly spinal cord) hypersensitive to input from periphery; common in pain syndromes; evidence of greater release of excitatory neurotransmitters in cerebrospinal fluid; fibromyalgia patients have significantly elevated levels of substance P in response to stimuli; functional magnetic resonance imaging (fMRI) studies of brain response to painful stimuli found fibromyalgia patients light up at ≥13 areas in brain, compared to matched controls who light up at 1 to 2 areas; patients appear to have abnormal release of neurotransmitters (may be associated with calcium channel), hyperalgesia (increased pain response to normally painful stimulus), and allodynia (pain response to nonpainful stimulus); evidence suggests changes in muscle metabolism, but not when controlled for fitness (stresses importance of fitness); evidence of DNA fragmentation and changes in mitochondrial function, hypothalamic-pituitary axis hyperfunction, elevated cortisol, flattened diurnal patterns of cortisol release, and decreased secretion of growth hormone (leads to sleep disturbances)

Sleep disturbances: multiple awakenings during night; early morning awakening; nonrestorative sleep; poor sleep quality; alpha intrusion (more than normal time spent in alpha phase of sleep); stages of sleep—stage 1 (transition sleep); stage 2 (baseline sleep); stages 3 and 4 (involve deep sleep, rapid eye movement [REM] sleep, and dreaming); ≈50% of night spent in stage 2 and ≈50% spent in REM sleep; patients with fibromyalgia have—abnormal sleep patterns (eg, unable to achieve REM sleep); delta sleep anomaly similar to that seen in patients with stage 4 sleep deprivation; disturbances similar to pain-induced sleep disturbances; disrupted sleep may worsen symptoms

Mood disturbances: common comorbidities of chronic pain include depression, anxiety disorders, and substance abuse; fibromyalgia patients do not necessarily have more mood disturbances than general population; many chronic pain patients have preexisting psychologic comorbidities

Treatment: combination of patient education, exercise, cognitive therapy, and selected medication recommended; tailor to individual patient

Nonpharmacologic: strong evidence of efficacy— low-impact cardiovascular exercise (eg, stationary bicycle or swimming; aim to increase heart rate [HR] for 30 min/day); cognitive behavioral therapy; combination of therapies; moderate evidence—strength training, acupuncture, hypnotherapy, biofeedback, and pool therapy; weak evidence— chiropractic therapy (may be effective for other musculoskeletal disorders), massage therapy, electrotherapy, and ultrasonography (US); no evidence of efficacy—trigger point injections or flexibility exercises; promote—physical activity of moderate intensity for 30 min/day

Pharmacologic agents: choosing correct treatment important; tricyclic antidepressants—shown effective; some conflicting data about amitriptyline; analgesic effect independent of antidepressant effect (doses that do not result in antidepressant effect may result in pain relief); consider checking blood levels in certain patients to check therapeutic range; start low at bedtime and titrate up; side effects include dry mouth, constipation, confusion, and urinary retention; delayed onset of action (4-8 wk) results in low compliance; serotonin and norepinephrine reuptake inhibitors (SNRIs)—duloxetine approved by Food and Drug Administration (FDA) for treatment of fibromyalgia; fibromyalgia patients require slightly higher doses than patients with other neuropathic pain syndromes; selective serotonin reuptake inhibitors (SSRIs)—conflicting data about fluoxetine and citalopram (“they’re good antidepressants, but not that good analgesics”); opioids—small studies of morphine and opioids showed no difference compared to placebo; generally not good choice for patients with fibromyalgia; tramadol has SNRI and mild opioid effects (200 times less potent than morphine) and shown effective; may be beneficial in select patients with fibromyalgia (refer to pain clinic); patients rapidly develop tolerance to effects, resulting in rapid dose escalation; clarify expectations, stopping rules, and dosing ranges before starting opioid therapy; side effects include effects on activities of daily living, cognitive effects, and abuse potential; tramadol—available in 50-mg dose and in combination with acetaminophen; shown to provide significant pain relief; common side effects include dizziness, somnolence, orthostatic hypotension, and increased risk for seizures (especially in patients taking SSRI and patients with history of seizures); initial dose, 25 or 50 mg bid (titrate up); extended-release preparation available (100 mg bid); onset of action fast; duration of action short

Pregabalin and gabapentin: anticonvulsants; evidence clearly supports use; pregabalin first FDA-approved treatment for fibromyalgia; mechanism of action—bind to α2 δ subunit of calcium channel; decrease time calcium channel in open state; reduce amount of neurotransmitter release; pregabalin has linear kinetics, gabapentin has nonlinear kinetics (ie, “the more you give, the less it’s absorbed”); dosing—effective dose of pregabalin for neuropathic pain, 150 mg (300 mg for fibromyalgia); effective dose of gabapentin for fibromyalgia uncertain, but 1800 to 3600 mg likely effective; start with single bedtime dose of 75 mg of pregabalin (repeat dose in morning if patient feels fine; if patient unable to tolerate morning dose, maintain evening dose for few days, then double evening dose and monitor tolerance); some patients respond to single bedtime dose; study on pregabalin—14-wk fixed-dose fibromyalgia trial of 300-, 450-, and 600-mg doses showed significant improvement, compared to placebo; global impression of change significantly better than placebo with 300- and 450-mg doses; durability study found loss of effect in placebo group at 19 days (at 180 days, pregabalin group maintained effect)

Other therapies: muscle relaxants—trials using 10 to 40 mg showed conflicting efficacy; nonsteroidal anti-inflammatory drugs (NSAIDs)—no evidence of efficacy; not recommended for fibromyalgia; benzodiazepines—no evidence of efficacy; use with caution; routine use not recommended; tender point injections—no good evidence of efficacy; no difference between lidocaine and saline injections; US guidance may improve efficacy

Attention-Deficit/Hyperactivity Disorder
Lloyd A. Darlow, MD, Assistant Clinical Professor, Department of Family Medicine, University of Rochester School of Medicine, Rochester, NY

Standardized approach to attentional, behavioral, and educational concerns: improves efficiency, ability to answer parents’ questions, communication with colleagues, and safety of medication refills; encompasses several office visits; during initial telephone call, staff should inform patients and parents that work-up required, and prescription might not be obtained after first visit; initial visit—history and physical examination; vision and hearing assessment; memory test; electrocardiography (ECG) “at your discretion”; distribution of educational and resource materials; educational testing; counseling; follow-up visits—assess target symptoms; 18 attention-deficit/ hyperactivity disorder (ADHD) symptoms in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV); ask about 3 to 4 main symptoms and assess them at each visit; ask for progress notes from school (can be brought in by parent or e-mailed by teacher; impairment must be present in ≥2 settings); discuss medication refills; consider modifying individual education plans (IEPs) and Section 504 plans; discuss drug holidays; when making changes, “things are new,” or if patient unhappy, arrange monthly (or sooner) follow-up visits, then, every 3 mo; patients on controlled substances should be seen regularly

Rating scales: American Academy of Pediatrics (AAP) and American Academy of Family Physicians (AAFP) recommend use of Vanderbilt rating scale; “pick one you are most familiar with”; for oppositional defiant disorder (ODD) and conduct disorder, Disruptive Behavior Rating Scale easy to use; for depression, Children’s Depression Index simple to use (younger children can complete 27-question questionnaire with help from nurse; older children can complete at home); for anxiety, Hamilton Anxiety Rating Scale (HAM-A; observational scale) can be completed after visit; for bipolar disorders in older teenagers and adults, Mood Disorders Questionnaire useful (use in younger children questionable because many of criteria used for older teenagers and adults do not apply as well to children); for learning disorders, formal educational assessment by child’s school or school psychologist (or independent psychologist if necessary); important to consider comorbidities (most children have ≥1 other diagnoses; treatment of one condition can adversely affect another)

ADHD treatment principles: identify comorbidities (assess history and use rating scales); identify impairments (eg, symptoms that interfere with social, academic, or vocational function); consider counseling for child and/or family; set expectations and limits; cognitive therapy shown effective; best response obtained with medication and behavior modification, followed by medication, then by behavior modification alone; results with use of FDA-approved stimulants or nonstimulants “good” (given lack of evidence of differences in effectiveness between drugs, “the model is driven by cost”)

Stimulants: backbone of ADHD treatment; side effects—anorexia; insomnia; headache; exacerbation of tics or Tourette’s syndrome; increased blood pressure (BP) and pulse rate (patients taking stimulants with no preexisting history or findings consistent with arrhythmias not at increased risk for tachydysrhythmias, compared to general population); in children with positive family or personal history of structural heart disease or chest pain or syncope with exertion should be worked up before receiving stimulant; ECG “at your discretion”; stimulants may worsen anxiety (may indicate comorbid anxiety; anecdotal); patients who do not respond to one stimulant, eg, methylphenidate, may respond to another, eg, dextroamphetamine (or within specific agent, patient may respond to different formulation [eg, consider starting with shorter-acting formulation, then transition to extended-release form]); short- and long-acting formulations may need to be combined (monitor dinner appetite and weight; watch for insomnia)

Nonstimulants: 24-hr medications (ie, no redosing required); good options for patients who have problems in morning before school or later in day; side effects different from those of stimulants; off-label use of combination of nonstimulant and stimulant done regularly and found effective (studies show no increases in BP and HR, over that seen with monotherapy)

Differentiating ADHD from ODD: onset of symptoms of ODD at age 5 to 6 yr, younger in ADHD; ODD more difficult to treat; children with ODD challenge authority (requires effort to be neutral), while ADHD children not intentionally defiant; parenting more at issue with ODD; treatment differs; resolve conflicts

Treatment of ODD: medications not particularly effective; results with long-term off-label use of, eg, buspirone, tricyclic antidepressants, α-agonists, or valproic acid “not great”; watch for side effects; options—long-acting stimulant; clonidine; behavior modification; anger management; buspirone (10 mg bid shown helpful); off-label use of divalproex (Depakote) for persistent symptoms; counseling