Across the United States, mid-level providers are more commonly gaining authority to prescribe controlled substances. A controlled substance is a drug, compound, preparation, mixture, or substance contained in Schedule I, II, III, IV, or V. This list is updated annually and substances are put into their schedules based on the substances current medical use, abuse potential and likelihood of causing dependence when abused.
Controlled substances are laced with risks. Understanding the risks of controlled substances is critical for proper prescribing. The prescriber who understands the medications and how to prescribe them properly will provide better and safer care for their patients.
Prescription opioid abuse takes a heavy toll on the patient, health care provider and society. Abuse and misuse of controlled substances occurs for multiple reasons including: self-medication, use for reward, diversion for profit and compulsive use. The use of opioids has increased in recent times, leading to an increase in abuse and opioid overdoses. Proper screening will reduce the risk of iatrogenic addiction. Unfortunately, no currently available screening method accurately predicts who is at high risk to abuse or misuse opiates (Sehgal, Manchikanti, & Smith, 2012).
Using prescribed medications not as directed describes potentially aberrant drug-taking behaviors. In a study of 202 patients, only 44.1 percent were screened for potentially aberrant drug-taking behaviors. It was concluded that screening for abuse or misuse of opioids does not occur frequently in a large family medicine training program. More training and set policies for risk evaluation and monitoring for opioid abuse is needed (Lewis, Herndon, & Chibnall, 2012).
Prescriber lack of training and inexperience can have a profound impact on misuse of medications. In a recent study, resident physicians (when compared to attending physicians) more often prescribed opioids for more than three months, were more likely to have their patients report that their prescriptions were lost/stolen, were more likely to have patients who exhibited substance misuse and were more likely to have their patients get opioids prescribed by a different prescriber in addition to them (Colburn, Jasinski & Rastegar, 2012).
Prescribers receive little training in how to prescribe scheduled substances, how to screen for substance abuse and how to refer patients who need treatment for substance abuse. Proper continuing education is one way to address this problem (Brown, Swiggar, Dewey & Ghulyan, 2012).
In 1970, section 812 of the Controlled Substance Act was enacted which lists substances that are controlled (Drug Enforcement Agency, 2014). The list describes basic or parent chemicals that may be classified as controlled substances. The Controlled Substance Act divides the drugs and other substances into five schedules, which is updated annually at http://www.deadiversion.usdoj.gov/21cfr/cfr/2108cfrt.htm.
Schedule I controlled substances have no accepted medical use in the United States, have a high potential for abuse and lack safety data. Substances in this class include: heroin, marijuana, 3, 4-methylenedioxymethamphetamine ("Ecstasy") and lysergic acid diethylamide (LSD).
Schedule II and IIN substances may potentially be abused and may lead to severe physical or psychological dependence. Schedule II narcotics includes: oxycodone (OxyContin, Percocet), fentanyl (Sublimaze, Duragesic), methadone (Dolophine), hydromorphone (Dilaudid), morphine, opium, and codeine. Examples of Schedule IIN stimulants include: methylphenidate (Ritalin) and amphetamine (Dexedrine, Adderall).
Schedule III or IIIN substances have less abuse potential than those substances that are Schedule I or II. They are high risk for psychological dependence and low to moderate risk of physical dependence. Examples of medications in this class include: buprenorphine (Suboxone) and products that have less than 90 milligrams of codeine per dosage unit such as Tylenol with Codeine. Medications that are considered Schedule IIIN include: anabolic steroids such as Depo-Testosterone and ketamine.
Schedule IV controlled substances have a lower potential for abuse when compared to Schedule III controlled substances. Examples of medications in this class include: benzodiazepines, midazolam (Versed), modafinil (Provigil) and carisoprodol (Soma).
Schedule V controlled substances have a low abuse potential relative to Schedule IV substances. Examples of medications in this class include cough preparations that contain less than 200 milligrams of codeine per 100 milliliters or per 100 grams such as Robitussin AC, lacosamide (Vimpat), and pregabalin (Lyrica).
The Controlled Substance Act regulates five classes of medications: anabolic steroids, depressants, hallucinogens, narcotics and stimulants. Each class has different properties and substances in each class typically produce similar effects. Most controlled substances alter mood, feeling or thought due to their effect on the central nervous system. Medications likely to produce euphoria are more likely to be abused, but medications may be abused to aid in sleep, reduce pain, reduce anxiety, reduce depression and improve energy.
Opioids have the potential to provide analgesia and improve function. These benefits must be weighed against the potential risks including: misuse, addiction, physical dependence, tolerance, overdose, abuse by others, drug-to-drug and drug-to-disease interactions.
Opioid misuse and abuse is a major public health problem and it affects 34.2 million Americans over the age of 12 (SAMHSA, 2012). According to the Center for Disease Control, in the United States, 46 people die each day from an overdose of prescription painkillers. In 2012, health care providers wrote 259 million prescriptions for painkillers (Center for Disease Control, 2014). Two times as many painkiller prescriptions are written in the United States as in Canada.
Misuse prevalence is variable.
The number of people who sought treatment for non-heroin opioid substance abuse increased from 1.0 percent in 1995 to 8.7 percent in 2010 (Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality, 2013). Research also shows that white individuals account for 88 percent of those who reported non-heroin opioid substance abuse and the majority of these individuals lived in rural setting. Those who live in rural settings account for 10.6 percent of cases and urban individuals accounting for 4.0 percent of non-heroin opioid abuse individuals who sought treatment (Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality, 2012).
In 2010, there were 16,650 cases of drug overdose deaths involving opioid analgesics out of approximately 38,000 overdoses (Jones, Mack, & Paulozzi, 2013). Of the overdose deaths from opioid analgesia, thirty percent also involved benzodiazepines.
OPIOID DEPENDENCE COSTS THE UNITED STATES HEALTH CARE SYSTEM ONE BILLION DOLLARS ANNUALLY (NATIONAL CONSENSUS DEVELOPMENT PANEL ON EFFECTIVE MEDICAL TREATMENT OF OPIATE ADDICTION, 1998). IN ADDITION, OPIOID DEPENDENCE COSTS LOST WORK PRODUCTIVITY, LEGAL COSTS AND PSYCHOLOGICAL EFFECTS OF THE VICTIMS OF THE CRIMES CAUSED BY THE OPIOID ABUSE. IN ADDITION, OPIOID MISUSE LEADS TO OTHER DISEASES SUCH AS HIV, HEPATITIS AND SEXUALLY TRANSMITTED DISEASE.
Risk factors for opioid analgesic misuse in those who have it prescribed for chronic pain include (Liebschutz, Saitz, Weiss, Averbuch, Schwartz, Meltzer, Claggett-Bourne, Cabral, & Samet, 2010 & Edlund, Steffick, Hudson, Harris, & Sullivan, 2007): history of substance abuse, tobacco use, family history of substance abuse, history of legal problems, white race, diagnosis of depression or posttraumatic stress disorder and being less than 40 years old.
Prescription drug misuse is the use of a prescription medication in a method or intent inconsistent of how it was prescribed. This includes using a medication to get high, selling or sharing it with other (diversion), overuse, having multiple prescribers, and concurrent use of alcohol or other illicit substances. Misuse is a necessary but not solely a sufficient criterion for a substance use disorder.
Susceptible individuals are at risk to misuse medications that stimulate the reward center of the brain which may include: opioid analgesics, stimulants, benzodiazepines or tranquilizers.
Drug abuse is when drugs are not used medically or socially appropriately. Controlled substances may lead to dependence, either physical or psychological. Physical dependence transpires when there are withdrawal symptoms such as anxiety, tachycardia, hypertension, diaphoresis, a volatile mood, or dysphoria after the rapid discontinuation of the substance. Psychological dependence is the perceived need for the substance. It makes the person feel as though they cannot function if they do not have the substance. Psychological dependence often kicks in after physical dependence wears off. It typically lasts much longer than physical dependence and often is a strong contributing factor to relapse.
Addiction is psychological dependence and extreme behavior patterns associated with the drug. At this point there is typically a loss of control regarding drug use. The drug is continued despite serious medical and/or social consequences. Tolerance, increasing doses of the medication needed to produce an equivalent effect, is typically seen by the time addiction is present. Physical dependence can occur without addiction. Individuals who take chronic pain medication may be dependent on the medication, but not addicted.
Addiction is a major concern in those taking opioids. When prescribing opioids it is important to determine who is likely to participate in aberrant drug related behaviors. This may occur in those with major depression, psychotropic medication use, younger age or those with a family or personal history of drug or alcohol misuse (Boscarino, Rukstalis, Hoffman, Han, Erlich, Gerhard, & Steward, 2010). Those at high risk for addiction should likely be managed in concert with a specialist (Sehgal, Manchikanti, & Smith, 2012).
Aberrant behaviors may include abuse, misuse or addiction. Examples of aberrant drug related behaviors include: requests for early refills, not taking medications as prescribed, failure to keep appointments, visits in distress, frequent reports of lost medication, using multiple prescribers, positive urine drug test for illicit substances, altering prescriptions, resistance to referrals, resistance to providing prior medical records, resistance to change in therapy, increasing the dose without telling the prescriber, or requests for specific drugs.
The Federal government has an important role in combating substance abuse. They have the responsibility to support states and provide tools, data and guidance to help health care providers prescribe safely. Increased access to mental health care and substance abuse treatment programs will reduce the risk and consequences of substance abuse. The government can also work to increase access to naloxone for first responders.
Many states have prescription drug monitoring programs. Health care providers need to assure that they are using these drug monitoring programs to find patients who are misusing prescriptions and placing them at risk to overdose.
Multiple factors are associated with a risk of overdose death. Some factors include: using 4 or more prescribers, using four or more pharmacies and getting more than 100 morphine equivalents per day (Gwira Baumbladd, Weideman, Dunn, Schaffner, Paulozzi, & Jones, 2014).
In addition to opioids, other medications are associated with misuse. These include: stimulants, sedatives, hypnotics and others. The use of stimulants has increased over recent years. Abuse is most common in those 18-25 years old. In the last year, 2-5 percent of high school students misused methylphenidate (Wilens, Adler, Adams, Sgambati, Rotrosen, Sawtelle, Utzinger, & Fusillo, 2008). Among college students, 5-6 percent misused stimulants in the last year and 5-43 percent misused stimulants over their life (Bogle & Smith, 2009).
Stimulants have the potential to cause tachycardia, high blood pressure, increased body temperature, reduced appetite, anxiety, reduce sleep, agitation and paranoia. Overdose of stimulants may lead to agitation, tremor, confusion, anxiety, delirium, mydriasis, hyperreflexia, aggressiveness, hallucinations, delirium, paranoia, seizures and movement disorders (Spiller, Hays, & Aleguas, 2013).
Risk factors for abuse of stimulants include (Kaye & Darke, 2012 & Substance Abuse and Mental Health Services Administration, 2013): white race, past-month use of cannabis, grade point average less than 3.5, being a member of a fraternity or sorority and one episode or more of binge drinking in the last two weeks.
Of those 12 and older, there was a 0.1-0.2 percent non-medical use of sedatives and 0.7 to 0.9 percent non-medical uses of tranquilizers (Substance Abuse and Mental Health Services Administration, 2013). The combination of sedatives and hypnotics, especially with alcohol or opioids is often the cause of overdose death (Hall, Logan, Toblin, Hall, Logan, Toblin, Kaplan, Kraner, Bixler, Crosby, & Paulozzi, 2008).
Risk factors for non-medical use of tranquilizers and sedatives include: white race, female, panic symptoms, cigarette use, illicit drug use, alcohol abuse, unemployed and uninsured (Becker, Fiellin, & Desai, 2007).
To prevent prescription drug abuse the clinician needs to assure:
Patients risk should be assessed and contraindications should be immediately identified. Contraindications to opioid treatment include those who have erratic follow up, suffer from current untreated addiction or have poorly controlled mental illness (Chou, Fanciullo, Fine, Adler, Ballantyne, Davies, Donovan, Fishbain, Foley, Fudin, Gilson, Kelter, Mauskop, O'Connor, Passik, Pasternak, Portenoy, Rich, Roberts, Todd, Miaskowski, American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel, 2009).
When taking a patient history document the opioid currently prescribed, its dose, the frequency of use and the duration of use. It is important to query the state prescription drug monitoring program (PDMP) to confirm the patient's report of prescription use. In addition, it is important to contact past providers to obtain medical records.
Before controlled substances are prescribed the risk of abuse, substance abuse and psychiatric history should be considered. A history of illegal substances use, alcohol use, tobacco use, prescription drugs use, family history of substance abuse and psychiatric disorders, history of sexual abuse, legal history, behavioral problems, employment history, marital history, social network and cultural background should be assessed. History of substance abuse does not prohibit treatment with opioids but may necessitate more intensive monitoring or referral to an addiction specialist.
Multiple tools are available to evaluate for opioid risk. The Opioid Risk Tool is a tool that is used in primary care to screen adults for the risk of aberrant behaviors when they are prescribed opioids for chronic pain. It is a copyrighted tool, encompasses five questions and takes about one minute to use. It classifies a patient as low, moderate or high risk to abuse opioids. Those who are high risk have a high likelihood for aberrant drug-related behavior. It is not validated in the individuals without pain. The five questions include asking about family and personal history of substance abuse (alcohol, prescription drugs or illegal drugs), age (risk is 16-45 years old), psychological disease and a history of preadolescence sexual abuse. The questions are scored with different points assigned for each question which is variable between men and women and total score is tallied. The patient is placed into low, moderate or high risk.
Regular follow up is important and should occur at minimum of every three months. When assessing the pain patient the five As should be assessed: analgesia, addiction, activities of daily living, adherence and adverse effects. Part of follow up should be urine drug testing which can be used to detect medication adherence as well as illicit and non-prescription drug use. It is critical the clinician adequately document any and all interactions with patients, assessments, results of testing and treatment plans.
Written treatment agreements, which should be used between prescribers and patients when controlled substances are used, help guide the conversation between patient and prescriber. It discusses expectations, the risks and the monitoring that will occur to limit the complications of controlled substances (Table 1).
Prescription monitoring programs are available in the majority of states. They provide an online database which list all prescriptions of controlled substances dispensed for each patient by pharmacies. Ideally, the prescriber should check the database before prescribing controlled substances. If a patient has an undisclosed prescription for controlled substances it is prescription drug misuse.
When abuse/misuse is detected how should the clinician respond? If it is a lone, minor deviation than counseling along with more intensive monitoring may be all that is needed. Tapering controlled substance to reduce the risk of withdrawal is appropriate in more severe or persistent cases of misuse. When diversion is the cause of misuse, immediate removal of the prescription is likely the best course. If a substance abuse disorder is suspected, a referral to an addiction specialist is recommended.
Safe prescription methods are listed below in the section on prescribing controlled substances.
Chronic pain affects approximately 76.2 million Americans (National Centers for Health Statistics, 2006). Pain is a common problem seen in primary care with about 20% of outpatient visits being for pain issues (Alford, Liebschutz, & Chen, 2008). Chronic pain affects about one in two long-term care residents (American Medical Director Association, 2009).
Persistent pain is often associated with anxiety, depression, functional impairment, sleep disturbances, disability, and impairment in activities of daily living. Every year, chronic pain leads to more than 50 million lost work days in the United States and costs the American tax payer over 100 billion dollars (Stewart, Ricci & Chee, 2003).
Chronic pain is defined as pain lasting more than 3 months and may affect any part of the body. Chronic pain is most frequently caused by back pain (10%), leg/foot pain (7%), arm/hand pain (4.1%), headache (3.5%), and wide spread pain (3.6%). Many affected by chronic pain have more than one type of pain (Hardt, Jacobsen, & Goldberg, 2008).
A comprehensive medical history is the first step in the workup of those with chronic pain. Many clinicians believe pain is the fifth vital sign (Lorenz, Sherbourne, & Shugarman, 2009). The medical history should include an evaluation of the patient's medical and surgical history and a medication list.
The history must include a comprehensive description of the pain. The pneumonic: OLD CARTS is sometimes used to evaluate pain.
Document the impact pain has on quality of life. Ask:
Measuring the intensity of pain is often done on scales and are meant to compare the intensity of the patient's pain at different points in time, not to compare one persons pain to another. The use of pain scales helps the prescriber assess the effectiveness of pain treatment.
The best scales are brief, valid, require minimal training to use, and use both behavioral and descriptive measures of pain (American Medical Director Association, 2009). A scale commonly used rates pain from 0 to 10. Another scale allows the patient to rate their pain as no pain, mild pain, moderate pain, severe pain, or unbearable pain. Other scales have the patient select the degree of pain on a pictorial scale with facial expressions. Pain maps are helpful in individuals who have a difficult time speaking. Pain maps have a front and rear view of the body on a piece of paper and the patient marks the location of the pain and rates the severity of the pain.
The patient's perception of the pain should be reviewed. What are the patient's treatment goals? Why does the patient think they have persistent pain? Does the patient feel there was sufficient work-up done on their condition? Psychological factors that contribute to the pain should be assessed. It is important for patients to have reasonable expectations about the pain and its management.
All patients with chronic pain should have a complete physical exam. It is important to have a baseline examination so ensuing evaluations will permit the health care team to establish progress in how well the pain is being managed.
The physical exam should include:
Diagnostic testing is often part of the workup of painful conditions. It is important to realize that an abnormal diagnostic test does not necessary diagnose the source of the pain. Blood tests may be helpful in certain diseases that cause pain. For example, an elevated C-reactive protein or an elevated erythrocyte sedimentation rate is often present in individuals in with polymyalgia rheumatica, infection or rheumatoid arthritis.
Imaging can be used in some cases of chronic pain. X-rays, computed tomography and magnetic resonance imaging help define the cause of pain. Diagnostic testing needs to be interpreted carefully as some abnormalities may be incidental and not the source of the pain.
An electromyogram (EMG) or nerve condition studies assess the cause of pain. The EMG measures electrical activity of the muscle and can help find damaged muscle, nerves or neuromuscular abnormalities such as a herniated disc or myasthenia gravis. The nerve conduction study measures the capacity of the nerves to transmit electrical signals and assists in the diagnosis of multiple types of neuropathies.
Mental health and pain are connected as individuals with chronic pain often have a psychiatric co-morbid condition. Those with a combination of mental illness and chronic pain are more likely to misuse controlled substances. In order to adequately treat pain it is imperative to assess and manage mental illness. Those who have a mental health diagnosis are more likely to use opioid medications than individuals who do not have a mental health diagnosis (Closs & Briggs, 2002).
It is complex to differentiate between those who have primary psychopathology from individuals with psychological symptoms secondary to their pain. Mental health referral is often helpful to differentiate these factors and manage pain.
The management of pain may include: medications, behavioral interventions, physical medicine, neuromodulation, medical interventions or surgery. The use of a multidisciplinary approach is typically used in the management of chronic pain.
Current treatments to manage chronic pain result in approximately a 30 percent reduction in pain (Turk, Wilson, & Cahana, 2011). One of the problems is general physicians have limited training in the management of chronic pain (Institute of Medicine, 2011). The use of a pain management specialist is often needed to manage pain properly.
The World Health Organization (WHO) analgesic ladder was created for the management of cancer pain and published in the 1980s (World Health Organization, 2014). Key points of the analgesic ladder include:
Adjunctive medications are used to enhance the analgesic effect, reduce side effects and assist with co-existent symptoms. Different patients will respond distinctively to different treatments in regard to efficacy and side effects. Trial and error is often used in the treatment of chronic pain.
When starting therapy, the dose should be initiated at a low dose and titrated to obtain pain control and minimize side effects. Tolerance often develops as a patient gets used to the medication.
Treatment is typically started with short-acting medication and the medication is titrated upwards to control pain while side effects are monitored. After determining the dose of the medication required to provide adequate pain relief with minimal side effects, the medication can then be converted to a sustained release form and be administered once or twice a day. When long-acting medication is used, breakthrough medication can be given.
While the patient is being treated for pain the clinician should assess and document the effect on functional status, pain control, intensity of pain and side effects.
Analgesic agents are often given orally as this is convenient and allows a relatively steady blood concentration of the drug. Pain medication may be administered on an as needed basis for episodic pain or it may be given routinely for chronic pain. The use of routine, around-the-clock medication sustains a steady state in the blood and offers better pain relief for those with persistent pain.
Classes of medications include: non-opioid analgesic agents, antidepressants, muscle relaxants, antiepileptic medications, topical agents, opioids, alpha 2 adrenergic agonists and N-methyl-d-aspartate (NMDA) receptor antagonists. Some get effective relief from one medication, but some get better pain relief from a combination of medications that work on different pathways. Unfortunately, research is sparse on combination medication in the management of pain.
Considering all co-morbidities is an important step in the management of pain. For example, when a patient is afflicted with chronic pain and depression some medications may help effectively manage both conditions (for example, duloxetine is approved to treat chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain in addition to depression). It is also important to establish the pathophysiology of the pain syndrome, evaluate the medication list, and consider the side effects of the medications being prescribed.
The clinician should distinguish between neuropathic pain and nociceptive pain. The etiology of neuropathic pain must be established and if the etiology is reversible, manage the underlying problem. For example, if a medication (e. g., metronidazole, nitrofurantoin, isoniazid, or many cancer agents) is the etiology of the neuropathy stop that medication.
Medications used in the treatment of neuropathic pain include: calcium channel alpha 2-delta ligands (gabapentin and pregabalin), tricyclic antidepressants, serotonin norepinephrine uptake inhibitors (SNRIs), the lidocaine patch and narcotic analgesics.
Nociceptive pain is typically treated with non-narcotic and opioid analgesia. Common causes of nociceptive pain include arthritis and chronic low back pain. Acetaminophen is often used as a first line agent in the management of nociceptive pain. Before stepping up therapy, the prescriber must assure the proper dose of acetaminophen, up to 1000 mg per dose, is being used.
Non-steroidal anti-inflammatory agents (NSAIDs) are used as alternative options to acetaminophen and are indicated for mild to moderate pain, while some are indicated for severe pain. Like acetaminophen, they act synergistically with opioids.
NSAIDs are laced with risks and some patients are unable to tolerate NSAIDs due to side effects and co-morbid conditions. The risk associated with NSAIDs is one reason many clinicians choose an opioid to manage pain. Opioid therapy is effective in the management of many chronic pain conditions including osteoarthritis, low back pain, neuropathic pain, and post herpetic neuralgia.
In recent times opioids therapy has become more commonly used, in the past it was only used for severe acute pain and cancer pain. It is now the most common class of medications prescribed in the United States (Kuehn, 2007).
A recent position paper from the American Academy of Neurology suggested that there is evidence for good short-term pain relief with opioids, but no good evidence exists for continuation of pain relief or improved function for extended periods of time without sustaining serious risk of dependence, overdose, or addiction (Franklin, 2014).
When non-opioid therapy is ineffective or there is severe nociceptive pain, opioid therapy is often used. In chronic back pain opioids do not improve pain scores any more than non-opioid therapy (Martell, O'Connor, & Kerns, 2007). Opioid therapy is often used to manage neuropathic pain, but is commonly thought to be second line to antidepressants and anticonvulsants.
Opioid medications are associated with multiple side effects including constipation, nausea, vomiting, pruritus, abdominal cramping, sedation, and mental status changes. Multiple interventions are available to reduce side effects.
Numerous non-pharmacologic therapies are used in the management of pain. Methods used other than medications include: physical therapy, exercise, massage, ultrasound therapy, heat/cold application, chiropractic manipulation, biofeedback, psychotherapy, relaxation therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS), injections, neuromodulation, spinal cord stimulation, deep brain stimulation, and radiofrequency ablation of nerve tissue.
Anxiety is a condition commonly treated with controlled substances, specifically the benzodiazepines. Common anxiety disorders include: generalized anxiety disorder, panic disorder, social phobia and obsessive compulsive disorder. Anxiety affects 40 million Americans (Anxiety and Depression Association of America, 2013).
The person with GAD is anxious, worries about numerous things and has a difficult time managing the anxiety. Individuals afflicted with GAD are in a constant state of tension and anxiety. Symptoms persist at least six months and are caused to a variety of stressors. GAD is associated with fatigue; poor concentration; irritability; muscle tension; sleep disturbances; and feeling restless, on edge or keyed up. These symptoms are enough to impair normal functioning. The symptoms of GAD cannot be related to a different medical or psychological problem.
The patient with anxiety may have vague complaints and may complain of nausea, vomiting, diarrhea, dry mouth, weakness, sweating, palpitations, flushing, urinary frequency and chills. The physical exam in the patient with GAD may include: elevated blood pressure, tachycardia, dilated pupils, sweating, muscle tension, tremor and cold clammy hands.
The differential diagnosis of GAD includes: hyperthyroidism, asthma, cardiac dysrhythmia, diabetes, electrolyte disturbance, substance abuse, withdrawal from drugs or alcohol, or adverse effects to medications. Many medications - thyroxin, theophylline, albuterol, digoxin, steroids, narcotics, amphetamines, marijuana, cocaine, nicotine or sedative-hypnotics - may lead to signs and symptoms of anxiety.
When assessing a patient with anxiety a social history should be taken to look for the death of a loved one, a divorce, recent marriage, or change in living condition as these situations may be associated with anxiety. In addition, a family history of mental illness is associated with a personal history of an anxiety disorder. Medical conditions in the differential diagnosis may present similar to anxiety.
Multiple screening tools such as the Beck Anxiety Inventory, the Hamilton Anxiety Rating Scale and the Anxiety Disorders Interview Schedule are helpful in the evaluation of anxiety.
Panic attacks are short-periods of intense fear that come on quickly. Symptoms experienced during a panic attack may include chest pain, shortness of breath, diaphoresis, dizziness, palpitations, tachycardia, tremor, syncope, nausea, gastrointestinal distress, numbness, depersonalization, hot flashes, chills, the feeling of choking, or an pending fear of death.
Obsessive compulsive disorder (OCD) is a disease characterized obsessions and compulsions. Obsessions are repeated and unrelenting thoughts, impulses or images that lead to anxiety and stress. Compulsions are repetitive actions done to lessen anxiety caused by the obsession.
Phobias are strong illogical fears of something that is unlikely to cause any real danger. Agoraphobia is an anxiety disorder where one stays away from situations that have the potential to cause panic. Individuals with phobias often become social isolated and do not leave their home.
Social anxiety disorder (SAD) is an unrelenting fear in ordinary social interactions that leads to illogical fear, anxiety, embarrassment, and self-consciousness.
A disorder that starts after experiencing a frightening event or ordeal where significant physical harm transpired or was threatened is post-traumatic stress disorder (PTSD). Symptoms include: flashbacks, reliving the event, recurrent dreams, psychological distress from the initial trauma, and/or physiological changes when trauma reminders are presented.
Anxiety is a clinical diagnosis, although laboratory tests and diagnostic testing may be performed to rule out other diagnoses that may imitate anxiety disorders.
Numerous methods are used to treat anxiety and ideally should include a multidisciplinary approach. Treatment should strive to achieve remission or at least reduce symptoms, enhance function and prevent deterioration.
Lifestyle changes and psychotherapy are important aspects in the management of anxiety, but they will not be addressed here. Many medications used to treat anxiety do not have an immediate effect, but some medications, specifically benzodiazepines, have an immediate effect an anxiety.
Medications are a commonly used weapon to combat anxiety. The major classes of medications used to manage generalized anxiety include: selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) benzodiazepines, and buspirone. A minimum of two to four weeks are required for SSRIs or SNRIs to show effectiveness and occasionally an increase in anxiety may be noted as therapy is started. This initial increase in anxiety may be managed with the addition of a benzodiazepine.
Benzodiazepines - lorazepam (Ativan), alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), and chlordiazepoxide (Librium) - offer short-term, immediate reduction of anxiety.
Benzodiazepines have the potential to significantly reduce anxiety, but have the potential to lead to abuse, dependency and many side effects. Common side effects of benzodiazepines include: change in mental status, sedation, falls, psychomotor impairment and weight gain.
With the continued use of benzodiazepines, tolerance will develop. In addition, dependence may occur within months of starting therapy. For individuals who have been on benzodiazepines for an extended period of time, they should be weaned to limit withdrawal symptoms or rebound anxiety.
PTSD is managed with medications and therapy. Treatment should be started shortly after the traumatic event. The pharmacotherapy manages the physiological symptoms while psychotherapy is used to manage the source of the problem. Many medications are used to manage PTSD, but benzodiazepines are a commonly used controlled substance in the management of PTSD.
Panic disorder is often treated with SSRIs or an SNRI. Benzodiazepines can be used for immediate control of symptoms while the SSRI or SNRI takes effect. Benzodiazepines are occasional used long-term in those who are not responsive to other medications or psychotherapy. Clonazepam is a favored benzodiazepine in the long-term management of panic disorder as it has a long-half life. Those taking clonazepam tend to have fewer withdrawal effects and less dependency issues than those taking shorter acting agents (e.g., alprazolam).
OCD is typically not managed with benzodiazepines.
Benzodiazepine, a commonly used medication to control anxiety, work effectively and quickly for those suffering from anxiety and agitation. Unfortunately, they have significant side effects and have issues with tapering and withdrawal. Benzodiazepines became popular agents (they replaced barbiturates) in the 1960s. Chlordiazepoxide (Librium) and diazepam (Valium) were commonly used in the 1960s and 1970s. In the 1980s alprazolam (Xanax) became a popular agent that was used for panic disorder, as it became a new diagnosis in the DSM-III. Clonazepam was also a popular medication used in the 1980s.
Benzodiazepines affect the gamma aminobutyric acid (GABA) receptor site a major inhibitory neurotransmitter. Typically, GABA fastens to postsynaptic GABA-A receptors, which opens the chloride ion channels and slows down neurotransmission. The benzodiazepines enhance the opening of the ion channel, reducing neuronal firing in the brain, leading to less anxiety. Benzodiazepines are absorbed through the GI tract and then absorbed in the small intestine within 30 minutes.
Depending on the condition, benzodiazepines can be prescribed on an as needed basis or on a routine basis. The fixed dose will more predictably control symptoms, especially in those with constant or frequent anxiety. When they are given on an as needed basis they work well when the anxiety is less constant, such as panic disorder. As needed benzodiazepines may interfere with cognitive behavioral therapy, as patients are supposed to get more comfortable with emotions related to the panic and work though their emotions and automatic thoughts without reliance on a pill (Cloos & Ferreira, 2009).
Benzodiazepines are tapered very slowly and depending on the dose that the patient is on, it may take months to taper the medication. A five percent reduction every two days may be considered. For individuals on over 2 mg of daily alprazolam the dose may be reduced 0.25 mg every two days and once the dose is less than 2 mg a day reducing the dose by 0.125 mg every two days may be used to taper the medication (Otto & Pollack, 2009) This five percent reduction may be extrapolated to other benzodiazepines.
Treatment with stimulants for ADHD constitutes the best first-line treatment (Tcheremissine & Salazar, 2008). The use of methylphenidate, dexmethylphenidate, and dextroamphetamine are commonly used medications. Stimulants have similar effectiveness, but they have different dosing, durations of action, and side effects. When used the dose should be started low and titrated upwards while monitoring for symptoms.
Stimulants come in an immediate release formulation which are typically dosed every 4-6 hours and longer acting formulations which are typically dosed one time a day. Dosing should not be done close to bedtime as this may lead to sleep impairment. Common side effects of stimulants include: insomnia, headaches, depression, irritability, weight loss and poor appetite. There is also concern that they may lead to substance abuse, but recent studies have showed that there is no link between stimulant therapy and future substance abuse (Volkow & Swanson, 2008).
Multiple formulations of stimulants exist in the management of ADHD (See Table 4). The short acting stimulants have a longer history of safety and a lot of data efficacy, but they need to be taken multiple times a day. The long acting stimulants are only dosed once a day, but are more expensive and have side effects that last into the evening.
Sustained release preparations (eg, Dexedrine Spansule, Ritalin LA, Focalin XR, Adderall XR, and Metadate CD) can be sprinkled onto soft food for those who are unable to swallow pills, they should not be taken with a high fat meal (delays onset of action) or medications that lower the acidity of the stomach.
Methylphenidate is available as a transdermal patch, Daytrana, which is placed on for 9 hours and off for 15 hours each day. The patch should be applied two hours before the effect is needed and the patch may be removed when effects are no longer needed. The effect lasts about 2-3 hours after the patch is removed.
Lisdexamfetamine (Vyvanse) is a stimulant that has a lower abuse potential than other stimulants. The capsule may be opened and mixed with water for those who cannot swallow the capsule.
Stimulants are sometimes abused. They can be used to stay awake or improve cognitive performance (Webb, Valasek, & North, 2013). They may also be used to get high. Some individuals will crush the tablets and snort or inject them.
Other treatment options for ADHD include: atomoxetine (Strattera), tricyclic antidepressants, atypical antidepressants, clonidine and guanfacine. Psychotherapy is also used in the management of ADHD. The use of environmental restructuring and behavioral therapy can be used, but are often not effective in more severe causes of ADHD.
Attention deficit hyperactivity disorder (ADHD) is condition of distractibility and inattention. It may or may not be associated with hyperactivity. The pathology is ADHD is unknown, but it is theorized that certain parts of the brain linked to attention are lacking in neural transmission. The incidence of ADHD is 3-7 percent in school aged children and is more common in boys than in girls, but the inattentive type is more common in girls. Those with ADHD are at increased risk to have substance abuse problems. In adults, its prevalence is estimated at 2-7% (Sofeff, 2014).
There are three types of ADHD.
The inattention type must have at minimum six symptoms of inattention persisting for at minimum six months to a point it is maladaptive and not consistent with the developmental level. These include: difficulty maintaining attention in play or tasks, forgetful in daily activities, avoids tasks/strongly dislikes tasks that require mental effort, easily distracted, loses items necessary for tasks or activities, does not seem to listen, difficulty organizing tasks and activities, fails to pay close attention to details or makes careless mistakes and does not follow through on instructions.
The hyperactive/impulsive type (Sofeff, 2014) must have at minimum four of the following symptoms for at minimum six months to a point it is maladaptive and not consistent with the developmental level. These include: hyperactive with difficulty playing or engaging in leisure activities quietly; fidgeting with feet and/or hands or squirming in the seat; running around, climbing excessively when it is inappropriate; impulsive with blurting out answers to questions prior to the question being asked; difficulty waiting in line or waiting for their turn in a group situation; and leaving the seat when the individual is expected to remain sitting.
Other features include (Sofeff, 2014): onset is not later than 7 years of age; symptoms present in two or more situations (e.g., work, home or school); these symptoms cause significant distress or impairment in academic, occupational, or social functioning; and symptoms are not better explained by another mental illness.
Prior to prescribing medications for ADHD the clinician must assure that the patient:
Prescribing controlled substances is an important role the practitioner. Controlled substances are laced with risks and it is important for the prescriber to realize that a primary goal of prescribing opioids should be to maintain patient safety. A responsible prescriber should follow multiple steps to assure safe and effective care of their patient.
Steps a prescriber can take include (Manchikanti, Abdi, & Atluri, 2012):
Prescribing controlled substances is an important role the practitioner. Controlled substances are laced with risks and it is important for the prescriber to realize that a primary goal of prescribing opioids should be to maintain patient safety. A responsible prescriber should follow multiple steps to assure safe and effective care of their patient.
Steps a prescriber can take include (Manchikanti, Abdi, & Atluri, 2012):
When prescribing medications the term opioid tolerance is often used. Patients who are opioid tolerant are less vulnerable to the effects of opioids including their analgesic effect and adverse effects. It is defined based on the amount of opioid medication that the patient is already taking. Opioid tolerance is defined as: patients already taking at least 60 mg of oral morphine daily, 25 mcg/hr of transdermal fentanyl, 30 mg of oral oxycodone daily, 8 mg oral hydromorphone daily, 25 mg of oral oxymorphone daily, or an equivalent dose of another opioid for at least 1 week. This is an important concept to understand when prescribing narcotics.
While there are many opioids, morphine is considered by many as a standard comparator for other drugs. Morphine can be given orally, rectally, intravenously, subcutaneously or intramuscularly.
Morphine is used for moderate to severe acute pain and chronic serious pain. It comes in multiple formulations. For acute pain it is dosed at 10-30 mg every 4 hours for those who are opioid nave. It is available as tablet, solution, suppository and parenteral solution. The immediate release tablet is dosed 15-30 mg every 4 hours as needed and the oral solution is dosed 10-20 mg every 4 hours as needed. It can also be given rectally and is often dosed 10-20 mg every 4 hours as needed. Morphine also comes in a controlled release form, a sustained release form and an extended release form.
Longer acting formulations include:
Avinza: The initial dose for the opioid nave patient is typically 30 mg a day and 90 mg and 120 mg are only indicated for use in opioid-tolerant patents. When converting over from immediate-release morphine the first dose of Avinza may be taken with the last dose of IR formulation. The medication may be adjusted in 15-30 mg increments every 3-4 days. The maximum dose is 1600 mg a day because of the fumaric acid content.
Kadian: It is not indicated for initial opioid analgesia. For non-opioid tolerant patients, 30 mg once a day is recommended. Higher doses are indicted for opioid-tolerant patients. Titration may be done every 1- 2 days. When converting from other forms of morphine it may be given once or twice a day.
MS Contin is started at 15 mg every 8-12 hours with the dosage being adjusted every 1-2 days.
Side effects of morphine are similar to other opioid analgesics and include: dry mouth, constipation, bradycardia, hypotension, nausea, drowsiness, dizziness, mental status changes, fever, itching, weakness, hypoxia and urinary retention.
Morphine should not be used in those with a hypersensitivity to morphine, those with toxin mediated diarrheal disease, and those with severe/acute asthma, paralytic ileus or severe respiratory depression. The extended release form should not be used in those with GI obstruction.
The extended release forms of morphine are not interchangeable. Changing from one medication to another should be done only by those experienced in how to do this. Extreme caution should be used when using highly concentrated solution so over doses do not occur.
Drug interactions commonly seen with morphine include:
Morphine is pregnancy category C. It does enter breast milk and it is not recommended in those who are breast feeding.
Fentanyl can be given as an injection, transdermal patch (Duragesic), an oral transmucosal lozenge (Actiq), a sublingual tablet (Abstral), a sublingual spray (Subsys), a buccal tablet (Fentora), a buccal film (Onsolis) and a nasal spray (Lazanda). The transdermal patch is used in opioid tolerant patients with moderate to severe pain and is often started at 25 mcg per hour and changed every 72 hours.
Fentanyl can be used for multiple reasons including premedication for surgery, for general anesthesia, as an adjunct to general and regional anesthesia, and chronic pain management. The transdermal patch is indicated for around the clock pain management in those with chronic severe pain. Fentanyl transmucosal and intranasal is indicated for cancer pain.
While no official dosage adjustment is recommended in those with renal or hepatic impairment, those with mild to moderate renal or hepatic impairment should likely have the dose reduced by 50 percent with the patch and the use is not recommended in severe renal or hepatic impairment. Transmucosal and nasal spray has no specific recommendations for dose reduction in renal or hepatic impairment.
Common side effects of fentanyl include: edema, bradycardia, dehydration, respiratory depression, shortness of breath, diaphoresis, nausea/vomiting, constipation, dry mouth, application site erythema (patch), weakness, muscle rigidity, mental status changes, headache, sedation, and CNS depression.
As with most opioids contraindications includes: hypersensitivity, toxin mediated diarrheal disease, and paralytic ileus. It should not be used for short-term pain, post-operative pain and should not be used for those who have a severe respiratory disease. The transmucosal and nasal form of fentanyl is typically only used by specialists for opioid tolerant cancer patients.
The patch form should not be exposed to external heat as this may increase absorption of the medication. In addition, patients with a fever may also notice an increase in absorption of the medication. The patch should only be applied to intact skin and it contains aluminum and must be removed prior to an MRI.
Like many medications there are multiple potential interactions. Some more common interactions include:
Fentanyl is pregnancy category C. It does enter the breast milk and is not recommended in the breast feeding mother.
Oxycodone is a schedule II controlled substance and is available in multiple forms.
Those with a creatinine clearance less than 60 mL/min should have the dose adjusted down as serum concentration of oxycodone will increase in renal insufficiency. Those with hepatic impairment should have doses reduced; with the extended release formulation the starting dose should be lowered one-third to one-half and slowly titrated up to affect.
Side effects include: drowsiness, dizziness, itching, constipation, nausea and vomiting. Less common side effects include: dry mouth, headache, abnormal dreaming, blood pressure changes, diaphoresis, weakness and fever.
Oxycodone is contraindicated in those with paralytic ileus, significant respiratory depression, hypercarbia, acute or severe bronchial asthma, and GI obstruction.
Caution should be used in those with biliary tract impairment such as acute pancreatitis as it may lead to constriction of the sphincter of Oddi. It may lead to an elevation of intracranial pressure (ICP) and should be used carefully those with intracranial lesions, elevated ICP or a head injury.
Extended release tablets may be lodged into the GI tract including the throat in those with swallowing issues. It may also lad to intestinal obstruction or diverticulitis.
Common drug interactions with oxycodone:
Oxycodone is pregnancy category B and D if used for an extended period of time or near term. It does enter breast milk and is not recommended in those who are breast feeding.
Hydrocodone, which was classified as a Schedule II Controlled Substance in October of 2014, is available as a combination pill with non-narcotic analgesia (e.g., Lorcet, Lortab, Norco and Vicodin) and by its self in an extended release form. The combination pill has a short acting version of hydrocodone and is dosed 2.5 to 10 mg of hydrocodone every 4-6 hours as needed for moderate to severe pain.
Hydrocodone extended release (Zohydro ER) is typically dosed 10 mg every 12 hours in treatment naive patients. It is used for severe pain requiring around the clock dosing of hydrocodone. The dose may be increased every 3-7 days in 10 mg increments.
Those with severe hepatic impairment should start at the lowest dose and titrate up very slowly while monitoring for side effects. Caution should be used with renal impairment as plasma concentration may rise.
Side effects include: constipation, nausea, vomiting, dry mouth, drowsiness, headache, dizziness, pruritus and nausea.
Contraindications to hydrocodone include: paralytic ileus, severe asthma, severe respiratory depression and hypercarbia.
This is pregnancy category C. The extended release form minimally enters the breast milk and should be used with caution in breastfeeding and the combination pill has been shown to enter breast milk and its use is not recommended.
As of August 18, 2014 the DEA placed tramadol into a Schedule IV of the Controlled Substance Act. It is indicated for moderate-to-severe pain and the immediate release form is dosed at 50-100 mg every 4-6 hours for a maximum of 400 mg a day.
Tramadol is also indicated for chronic moderate-to-severe pain. For those who do not need a rapid onset of pain relief and/or affected by side effects, it may be dosed at 25 mg/day and titrated up every 3 days to 50-100 mg every 4-6 hours to a maximum of 400 mg a day.
Tramadol also comes in an extended release form, ConZip and Ultram ER, which is dosed 100 mg once a day and may be titrated by 100 mg every five days to a maximum dose of 300 mg a day.
When prescribing tramadol to older adults use the lower end of the dosage range and titrate slowly. In those over 75 years old, 300 mg a day should not be exceeded and utilize extreme caution with the extended release form.
In those with a creatinine clearance less than 30 mL/min, only the immediate release formulation should be used with doses of 25-100 mg split every 12 hours (maximum dose of 200 mg a day). In those with severe liver impairment, the immediate release form should be given at a maximum of 50 mg every 12 hours.
Side effects include: flushing, dizziness, constipation, nausea, vomiting, dyspepsia, itching, headache, somnolence, insomnia and weakness. Less common side effects include: orthostatic hypotension, mental status changes, euphoria, rash, hot flashes, diarrhea, dry mouth, anorexia, joint pain, blurred vision and sweating.
Patients may experience withdrawal symptoms from tramadol that may include nausea, diarrhea, anxiety, pain, sweating, tremor and rigors. Extended use of tramadol may lead to dependence and these medications should be tapered slowly to reduce the risk of withdrawal symptoms.
Tramadol is contraindicated in those who are hypersensitive to the agent and those with severe liver or kidney impairment. The extended release tablet should not be used with psychotropic drugs, opioids, hypnotics, acute intoxication with alcohol or centrally acting analgesics and the extended release capsule formulation should not be used in those with severe respiratory depression, severe asthma or hypercapnia.
Tramadol has been shown to increase the risk of seizures. This risk is increased in those who take serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, other opioids, or other drugs that lower the seizure threshold. Risk may also be increased in those who have seizures or are at risk for seizures such as those who have a CNS infection, cancer, history of head trauma or while patients are going through drug or alcohol withdrawal.
Caution should be used in those with respiratory disease as those with significant disease may be at increased risk for respiratory depression.
Tramadol is pregnancy category C. It enters the breast milk and is not recommended in lactating women.
|Drug||Initial dose |
|Duration of effect |
|Immediate-release||10-30 mg every 3-4 hours as needed||3-6|
|Controlled-release ((MS Contin, Oramorph SR)||15 mg two times a day||8-12|
|Sustained-release (Kadian)||30 mg one to two times a day||12-24|
|Extended-release (Avinza)||30 mg once a day||24|
|Immediate-release||2 - 4 mg every 3-4 hours as needed||3-6|
|Extended-release (Exalgo)||8 mg every 24 hours||24|
|Immediate-release||5-15 mg every 4-6 hours||3-6||Often combined with acetaminophen or aspirin|
|Controlled-release (OxyContin)||10 mg two time per day||8-12|
|Extended-release (with acetaminophen) (Xartemis XR))||15 mg oxycodone with 650 mg acetaminophen every 12 hours||8-12|
|Immediate-release||5-10 mg every 6 hours||4-8||Combined with acetaminophen or ibuprofen|
|Extended-release (Zohydro ER)||10 mg every 12 hours||12|
|Fentanyl patch||25 mcg per hour changed every 72 hours||48 to 72 (12 hours after removal)||Not for opioid nave patients, or acute pain; onset 12-24 hours.|
|Immediate-release (Opana)||5-20 mg every 4-6 hours||4-6|
|Extended-release (Opana ER)||5 mg two times a day||12|
|2.5 mg every 8-12 hours||First dose 4-8 hours, up to 48 hours with repeated doses||High risk for overdose partly due to the long half-life; prescribed only by a trained prescriber|
|Immediate-release (Nucynta)||50 - 100 mg every 6 hours||3-6|
|Extended-release (Nucynta ER)||50 mg every 12 hours||unsure|
|Immediate-release (tramadol)||50-100 mg every 4-6 hours||4-6||Max dose 400 mg/day|
|Extended-release (Ultram ER, ConZip)||100 mg once a day||Unsure||Max dose: 300 mg/day|
Oxymorphone, a schedule II medication, can be given intravenously, subcutaneously, intramuscularly or orally. For acute pain the immediate-release tablet (Opana) is used at 5-20 mg every 4-6 hours as needed for opioid nave patients. For those with chronic severe pain the extended release tablet is used (Opana ER) and is started at 5 mg every 12 hours and may be titrated up at 5-10 mg increments every 12 hours every three to seven days. Caution should be used in those with a creatinine clearance less than 50 mL/minute and the medication should not be used in moderate to severe hepatic impairment. Oxymorphone is pregnancy category C and it is unclear if it is excreted in breast milk and should therefore be used cautiously.
Hydromorphone can be given orally, rectally, subcutaneously, intramuscularly or intravenously. The oral medication comes in standard and extended release forms. The standard form is used for moderate to severe pain and is often dosed 2 to 4 mg every 4-6 hours. The oral liquid is typically dosed 2.5 to 10 mg every 3 to 6 hours. Parental and oral doses are not equivalent. The parenteral dose is five times more potent than the oral dose. The long acting form (Exalgo) is used for opioid tolerant patients who have chronic severe pain. It is dosed 8-64 mg once a day. Hydromorphone is pregnancy category C and is excreted in breast milk. It is not recommended for lactating women.
Methadone can be given intravenously, subcutaneously, intramuscularly or orally. The oral dose is started in the opioid nave patient at 2.5 every 8-12 hours. Methadone is a high risk drug to lead to overdose. It has a half-life of up to five days and may accumulate in the body. Methadone may also prolong the QT interval leading to cardiac arrhythmias especially at doses higher than 120 mg a day. Methadone should be used for severe pain that has not been responsive to other agents and only by clinicians with specific training in the use of methadone. Methadone is also used in detoxification.
Tapentadol (Nucynta, Nucynta ER) is used for acute moderate to severe pain and started at 50-100 mg every six hours for the immediate-release formulation. The starting dose for the extended-release tablet is 50 mg every 12 hours. For chronic pain it is typically dosed 50-250 mg two times a day as needed. The maximum dose is 500 mg a day. This medication is not recommended for those with severe liver or renal insufficiency. It is also indicated for diabetic peripheral neuropathy.
Propoxyphene has been taken off the US market as it has been linked with fatal cardiac arrhythmias. Meperidine is not recommended as a first line agent for chronic pain as it is associated with high rates of central nervous system toxicity.
Alprazolam (Xanax) is indicated for anxiety and panic disorder. Approved in 1981, the immediate-release form is available as a 0.25 mg, 0.5 mg, 1 mg and 2 mg tablet. It is also available as an oral disintegrating tablet and oral solution. For anxiety it is dosed 0.25 to 0.5 mg every 6-8 hours with titration every 3-4 days. It is also available as an extended release form as alprazolam XR (Xanax XR) which is available as 0.5 mg, 1 mg, 2 mg, and 3 mg. It is started at 0.5 to 1 mg once a day and increased every 3-4 days to effect. Caution is recommended in those with renal impairment and advanced hepatic impairment. It is pregnancy category D and is excreted in the breast milk.
Diazepam (Valium) is available as a 2 mg, 5 mg and 10 mg tablet and as an oral solution, rectal gel and injectable solution. It is dosed for anxiety at 2-10 mg every 6-12 hours orally. It has a long half-life and can lead to problems as it accumulates and may lead to increased side effects when dosed chronically. In addition to anxiety, diazepam can also be used for alcohol withdrawal, sedation, muscle spasm or seizures. It is pregnancy category D and is excreted in the breast milk.
Chlordiazepoxide (Librium) is indicated for anxiety and is available as a 5 mg, a 10 mg, and a 25 mg capsule and is often dosed 5-10 mg every 6-8 hours for mild to moderate anxiety and 20-25 mg every 6-8 hours for severe anxiety. It is also used commonly for alcohol withdrawal. Dose adjustment is not necessary in renal impairment until the creatinine clearance is less than 10 mL/min. It is pregnancy category D and is excreted in the breast milk.
Clonazepam (Klonopin) is indicated for panic disorder and seizure disorder. Approved in 1975, it is available as a tablet in a 0.125 mg, 0.25 mg, 0.5 mg, 1mg and 2 mg tablet. For anxiety it is dosed 0.25 mg every 12 hours to start and may be titrated up after three days. It is pregnancy category D and is excreted in the breast milk.
Lorazepam is available as a tablet, oral concentrate and injectable solution. It is available as a 0.5 mg, 1 mg and 2 mg tablet. For anxiety disorders it is given 2-3 mg every 8-12 hours as needed to a maximum of 10 mg a day. It can also be used for sedation, status epileptics and short-term insomnia. No dosage adjustment is necessary in renal impairment with the oral formulation. Those with severe hepatic impairment require caution when using lorazepam. It is pregnancy category D and is excreted in the breast milk.
Lorazepam, along with oxazepam (Serax) and temazepam (Restoril), are safer benzodiazepines for those with cirrhosis, multiple medical issues, on multiple medications or are older as they are metabolized in the liver through glucuronidation.
|Benzodiazepine||Equivalent oral dose (approximate)||Typical starting dose|
|Alprazolam (Xanax)||0.5 mg||0.25 to 0.5 mg every 6-8 hours|
|Chlordiazepoxide (Librium)||25 mg||5-10 mg every 6-8 hours|
|Clonazepam (Klonopin)||0.25 mg||0.25 mg every 12 hours|
|Diazepam (Valium)||5 mg||2-10 mg every 6-12 hours|
|Lorazepam (Ativan)||1 mg||2-3 mg every 8-12 hours|
|Oxazepam (Serax)||15 mg||10-15 mg every 6-8 hours|
|Temazepam (Restoril)||10 mg||15-30 mg before bed|
This is a Schedule II stimulant approved for ADHD in those 6 years old and older. It comes in multiple formulations including: Ritalin, Ritalin SR, Ritalin LA, Daytrana, Metadate, Metadate ER, Metadate CD, Methylin, Concerta, and Quillivant XR.
Methylin and Ritalin are available as immediate-release tablets, chewable tablets, and an oral solution. It is typically started at 10-30 mg divided every 8 to 12 hours and should be given 30-45 minutes before meals. Doses are titrated up and dosing range may be from 10 to 60 mg a day. Ritalin SR, Metadate ER and Methylin ER all have a duration of action eight hours and may be substituted for the immediate-release formulation.
Ritalin LA is initially dosed 10 - 20 mg in the morning, increasing the dose by 10 mg every week to effect with a maximum dose of 60 mg a day. Metadate CD is started at 20 mg a day in the morning and increased 10-20 mg to a maximum of 60 mg a day. Metadate CD and ER are contraindicated in those with severe hypertension, hyperthyroidism, heart failure, recent MI, angina and arrhythmias.
Concerta is started at 18-36 mg every day and is increased at 18 mg increments every week to a maximum of 72 mg a day in adults and 54 mg a day in children 6-12 years old.
Quillivant XR is indicated for those 6 years old and above, is dosed 20 mg every morning and titrated weekly by 10-20 mg to a maximum of 60 mg a day.
Methylphenidate particularly the short acting formulation - has the potential to be chronically abused and should be used carefully in those with a history of drug dependence. Methylphenidate is contraindicated in those with glaucoma; hypersensitivity to the medication; marked agitation, anxiety or tension; those with a family history of Tourette syndrome or motor tics; and within 2 weeks of taking a MAO inhibitor. It should be used carefully in those with hypertension, bipolar disease, psychosis and those with seizures.
Potential side effects include: headache, nausea, seizures, increased blood pressure, increased heart rate, arrhythmias, anxiety, angina, fatigue, anger, irritability, rash, constipation, cough, blurred vision and priapism.
Methylphenidate has multiple interactions; always check all other medications prior to prescribing methylphenidate. Compliance is an issue and therefore long-acting (once a day) medications are better at improving compliance.
The exact mechanism of action of this medication is unknown, but it may work by stimulating the CNS, stimulating the cerebral cortex and blocking the reuptake of norepinephrine and dopamine.
Dexmethylphenidate is available as Focalin or Focalin XR. The immediate release tablet is dosed 2.5 mg twice a day and increased every week by 2.5 to 5 mg increments with a maximum dose of 20 mg a day. The extended release formulation is dosed 5-10 mg a day and increased to a maximum of 30 mg in children and 40 mg in adults.
Common side effects of dexmethylphenidate include: headache, insomnia, abdominal pain, anxiety and restlessness. Other side effects include: poor appetite, dizziness, nausea, sore throat, irritability, dyspepsia, blurred vision and priapsim.
This medication is contraindicated in those who have a hypersensitivity to dexmethylphenidate, those with Tourette syndrome, motor tics, significant agitation, glaucoma or anxiety. It should not be used within 14 days of taking a MAO inhibitor.
It should be used carefully in those with a history of drug dependence, bipolar disease, hypertension or any structural cardiac abnormalities.
This medication acts as a stimulant and blocks the reuptake of dopamine and norepinephrine.
Other ADHD medications are listed below in Table 4 and 5.
|Medications||Starting Dose||Titration||Usual dosage|
|Short Acting (Ritalin, Methylin)||10 mg two times a day before breakfast and lunch||Increased 5 or 10 mg weekly||40 to 60 mg per day divided two or three times|
|Ritalin SR||20 mg once each morning||Increase 10 mg weekly||40 to 60 mg once each morning|
|Metadate ER||10 mg one or two times a day||Increase 10 mg weekly||40 to 60 mg once each morning|
|Metadate CD and Quillivant XR||20 mg each morning||Increase 10 or 20 mg weekly||40 to 60 mg once each morning|
|Ritalin LA||10 or 20 mg each morning||Increase 10 mg weekly||40 to 60 mg once per morning|
|Concerta||18 or 36 mg per morning||Increase 18 mg weekly||54 to 72 mg each morning|
|Focalin||2.5 mg two times a day||Increase 2.5-5 mg weekly||10 mg two times a day (maximum 20 mg a day)|
|Focalin XR||10 mg each morning||Increase 10 mg weekly||30 mg each morning (maximum 40 mg once per day)|
|Dextroamphetamine and amphetamine (mixed salts)|
|Short-acting - Adderall||5 mg one or two times a day||Increase 5-10 mg weekly||40 to 60 mg a day in 1 to 3 divided doses|
|Long-acting - Adderall XR||20 mg each morning||Increase 10 mg weekly||40 to 60 mg each morning|
|Lisdexamfetamine (Vyvanse)||30 mg each morning||Increase 10-20 mg weekly||30 to 70 mg each morning|
|Medications||Starting Dose||Titration||Usual dosage|
|Short-acting (Ritalin, Methylin)||2.5 to 5 mg before breakfast and lunch if less than 25 kg - 2.5 mg per day||Increase 5-10 mg weekly||60 mg|
|Ritalin SR||20 mg per morning||Increase 20 mg weekly||60 mg|
|Metadate ER||10 mg per morning||Increase 10 mg weekly||60 mg|
|Metadate CD and Quillivant XR||20 mg per morning||Increase 10 mg weekly||60 mg|
|Ritalin LA||10 or 20 mg each morning||Increase 10 mg weekly||60 mg|
|Daytrana transdermal patch (on for 9 hours and off for 15 hours each day;|
Apply patch two hours before needed onset)
|10 mg once daily||Increase to next transdermal dose each week||30 mg|
|Concerta||18 mg per morning||Increase 18 mg each week||Less than 13 years: 54 mg; 13 years-old or older: 72 mg|
|Focalin||2.5 mg two times each day (at least 4 hours apart)||Increase 2.5 to 5 per week||20 mg|
|Focalin XR||5 mg per morning Increase||5 mg per week||30 mg|
|Short-acting||5 mg one or two times a day||Increase 5 mg each week||40 mg|
|Long-acting Dexedrine spansule||5 mg once or twice a day||Increase 5 mg each week||40 mg|
|Dextroamphetamine and amphetamine (mixed salts)|
|Short acting - Adderall||2.5 - 5 mg one or two times a day||Increase by 2.5 - 5 mg each week||40 mg|
|Long-acting - Adderall XR||5-10 mg each morning||Increase 5-10 mg weekly, may be increased by 20 mg in those over 13 years old||30-40 mg|
|Lisdexamfetamine -Vyvanse||20-30 mg||Increase 10 or 20 mg each week||70 mg|
John is 38 year-old male with chronic back pain due to three herniated discs and spinal stenosis which was first diagnosed after a motor vehicle accident three years ago. He currently rates the severity of his back pain as a 9/10 and has been unable to work as a plumber due to his pain. The pain is described as dull and constant with occasional sharp exacerbation in the low back with the pain increasing with bending, prolonged standing and walking. The patient denies any loss or change of bowel/bladder control, history of IV drug use, recent infection, progressive neurological complaints, night pain, night sweats, weight loss or fever. The pain occasionally radiates into the right buttock. The patient is able to do all of his ADLs, but does report poor sleep at night.
He has a past medical history of hypertension and recently has developed stage II chronic kidney disease thought to be secondary to hypertension and excessive use of ibuprofen. His only current medication is lisinopril to control his blood pressure.
He has had multiple treatment modalities including four rounds of physical therapy, chiropractic treatment and multiple medications. He tried to control his back pain on acetaminophen, naproxen, ibuprofen, the lidocaine patch and topical NSAIDs without relieve. The patient experienced significant tremor and an increase in blood pressure while on tramadol. A series of epidural injections did not help. Surgery was discussed, but the patient refused this option.
John is married and has one daughter who lives over 500 miles away with her biological mother. He has limited financial means and lives pay check to pay check. He has a prior history of alcohol abuse, but has not had a drink in five years. He is currently a smoker. He denies any history of substance abuse and there is no family history of alcohol or substance abuse.
Physical exam showed a patient with a slow deliberate gait, a limited range of motion in the spine with no obvious deformity, swelling or erythema. There is mild tenderness on the right side of the spine from the area of L4 to S1 as well as tenderness in the right sacroiliac joint. Normal reflexes, normal sensation, normal strength and no atrophy is noted in the lower extremities. The straight leg raise test is normal.
An MRI was done one year ago that was significant a herniated disc at the L5/S1 level and mild spinal stenosis.
The Opioid Risk Tool was administered and it was determined that the patient is at moderate risk for opioid abuse. He signs a written opioid treatment agreement that outlines the conditions of the opioid therapy. His past medical records were verified suggesting he is not lying.
The patient is prescribed hydrocodone/acetaminophen 5 mg/500 mg, two tablets every six hours as needed (56 tablets) for 1 week.
Five days later he calls for an early refill and reports that the medication is really not helping his pain and he just lies around all day.
He comes back into the office for a re-evaluation. He reports he needed to take more pain medication than prescribed. His wife confirms that he has been lying around all day and she believes it is because he is having so much pain. It was reviewed with the patient that he violated the opioid agreement. A urine sample was obtained that showed no illicit substances or medications that would not be expected in the urine.
While the patient is at moderate risk to abuse medication, his past medical history was all confirmed. He was referred to a psychiatrist and a pain specialist. He was agreeable to both. He was able to get into the psychiatrist within one week, but the pain specialist appointment was four weeks out. The patient saw the psychiatrist and he diagnosed the patient with depression and started him on a sertraline. The psychiatrist was unable to make an assessment related to opioid abuse.
With the help of the pain specialist, oxymorphone ER 5 mg was ordered every 12 hours. The patient was told to follow up in one week to assess effectiveness. After one week the patient reports he is more functional but still in a lot of pain. The dose of oxymorphone ER was increased to 10 mg every 12 hours. After one more week he was given oxymorphone IR 5 mg to be used one hour before exercise. This allowed the patient to not only function well, but begin participating in an exercise program. The patient was ordered a bowel stimulant (Senna) with a stool softener (Colace) to prevent constipation.
The patient is prescribed fourteen pills oxymorphone ER 10 mg (to be taken twice a day) and seven pills of oxymorphone IR 5 mg (to be taken once a day before exercise) once a week. Part of the agreement was that they are to be given by the patient's wife to reduce the risk of misuse.
Ms. L is a 52 year old female with a history of bilateral knee pain; she currently rates the pain as an 8/10 in her right knee and 5/10 in her left knee. She takes meloxicam 7.5 mg twice a day and uses 1000 mg of acetaminophen for breakthrough pain about 3 times a day. She has been using this regime for the past 6 months, but over the last month she has not been getting adequate relief from her pain and has been progressively disabled and has stopped exercising.
The pain is attributed to osteoarthritis and has been progressively worsening over the last 1-2 years. She has a past medical history of hypertension, dyslipidemia, depression, obesity and osteoarthritis. She has a past-surgical history of a hysterectomy approximately five years ago. She is currently on simvastatin, lisinopril, meloxicam, acetaminophen and aspirin. She has no known allergies.
She has no history of alcohol, drug or substance abuse. She has a strong family network including a supportive husband of 25 years and 2 sons who live within twenty miles of her home. She has a past history of depression, but is currently not depressed.
The physical exam is significant for obesity (BMI of 34). She has crepitus to both of her knees and is unable to fully extend the right knee due to pain.
An x-ray demonstrates moderate arthritic changes in both knees. The patient is unwilling to consider surgery of her knees.
The prescriber offers tramadol immediate release 25 mg in the morning, which is titrated every three days in 25 mg increments as distinct doses to 100 mg/day (25 mg four times a day). Pain control was still not adequate and the dose was then increased by 25 mg every three days to 50 mg every 6 hours.
Pain control was significantly improved and then the patient was give tramadol SR 200 mg once a day. The patient was able to function and exercise. Her quality of life was much improved.
Controlled substances are a common weapon used by prescribers to manage a variety of conditions including pain, anxiety, attention deficit disorder and others. Proper use of these medications is critical because there is significant risk including addiction, misuse, constipation, falls and even death with these agents. Prescribers need to be well versed in their use.
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