Đang tải... (xem toàn văn)
(BQ) Part 1 book Principles of addiction medicine the essentials presents the following contents: Basic science and core concepts, pharmacology, diagnosis, assessment and early intervention, overview of addiction treatment, special issues in addiction medicine, management of intoxication and withdrawal, pharmacologic interventions.
treatment of cocaine dependence because they block the development of cocaine-induced kindling in animals Kindling (increased neuronal sensitivity to a drug because of prior intermittent exposure) has been hypothesized as a neurophysiologic mediator of cocaine craving in humans At the neurotransmitter level, anticonvulsants might be effective because they increase inhibitory g-aminobutyric acid (GABA) activity and decrease excitatory glutamate activity in the brain, both actions that would decrease the response to cocaine in the dopaminergic corticomesolimbic brain reward circuit Cavacuiti_Chap51.indd 274 2/11/2011 12:32:12 PM CHAPTER 51 | Pharmacologic Interventions for Cocaine, Methamphetamine, and Other Stimulant Addiction 275 Carbamazepine, the most-studied anticonvulsant, has not shown efficacy, nor have gabapentin or baclofen Other anticonvulsants studied in recent trials with some beneficial effects on cocaine use: Tiagabine, topiramate, vigabatrin Phenytoin (300 mg daily) significantly reduced cocaine use in one controlled clinical trial, especially at serum concentrations above 6.0 mg/mL Nutritional Supplements and Herbal Products Nutritional Supplements The use of amino acid mixtures, either alone or with other nutritional supplements (vitamins and minerals), has been widely publicized in the drug abuse treatment field, encouraged by their freedom from the regulations imposed on prescription medications and their perceived safety and absence of side effects The majority of these studies have shown little benefit Herbal Products Various herbal and plant-derived products have been touted as treatments for drug abuse, but few have undergone controlled clinical evaluation Calcium Channel Blockers Calcium channel blockers have been suggested as treatment for cocaine dependence However, amlodipine showed no efficacy in a controlled clinical trial Other Physical Treatments Acupuncture of the outer ear (auricular) has enjoyed growing popularity as a treatment for drug withdrawal, especially using five standard locations recommended by the National Acupuncture Detoxification Association (NADA): kidney, liver, lung, shen men, and sympathetic Meta-analyses of nine published studies (six using the NADA locations) did not find a significant benefit of active acupuncture over sham treatment Transcranial magnetic stimulation (TMS) involves activation of brain cells by magnetic fields generated by electromagnetic coils placed on the scalp Single and multiple sessions of rTMS of the prefrontal cortex (either right or left) have been reported to reduce cocaine craving AMPHETAMINE DEPENDENCE Many of the medications evaluated for the treatment of cocaine dependence have also been studied for the treatment of amphetamine dependence, often for the same pharmacologic rationale As with cocaine dependence, most controlled clinical trials not show efficacy The most promising approaches to date appear to be agonist substitution with stimulants and enhancement of GABA activity Two of three controlled clinical trials with D-amphetamine found a significant reduction in amphetamine use compared with placebo Slow-release methylphenidate (54 mg daily) reduced amphetamine use significantly more than did placebo in one controlled clinical trial Modafinil (200 mg twice daily) reduced amphetamine use in a case report and is currently undergoing a controlled clinical trial Vigabatrin, an anticonvulsant that increases GABA activity by inhibiting the breakdown of GABA by GABA transaminase, substantially reduced methamphetamine use in two open-label trials SPECIAL TREATMENT SITUATIONS Mixed Dependence Opioid Dependence Concurrent opioid use, including dependence, is a common clinical problem among cocaine-dependent individuals Some individuals use cocaine and opioids simultaneously (as in the so-called speedball) to enhance the drugs’ subjective effects Up to 20% or more of opioid-dependent patients in MMT also use cocaine for a variety of reasons, including continuation of prior polydrug abuse, replacement for the “high” no longer obtained from opioids, Cavacuiti_Chap51.indd 275 2/11/2011 12:32:12 PM 276 SECTION | Pharmacologic Interventions self-medication for the sedative effects of high methadone doses, or attenuation of opioid withdrawal symptoms Three different pharmacologic approaches have been used for the treatment of such dual cocaine and opioid dependence: Adjustment of methadone dose Maintenance with another opioid medication, e.g., high-dose buprenorphine (16–32 mg daily) Addition of medication targeting the cocaine dependence Higher methadone doses (usually 60 mg or more daily) generally are associated with less opioid use by patients in methadone maintenance This relationship also holds in general for cocaine use among patients in methadone maintenance, although exceptions have been reported Increasing the methadone dose as a contingency in response to cocaine use can be effective in reducing such use (and more so than decreasing the methadone dose in response to a cocaine-positive urine sample) Alcohol Dependence Alcohol dependence is a common problem among cocaine-dependent individuals, both in the community and in treatment settings, with rates of comorbidity as high as 90% Alcohol use by cocaine-dependent patients is associated with poorer treatment outcome Due to Production of the toxic psychoactive metabolite cocaethylene Stimulation of cocaine craving by alcohol Alteration of medication metabolism by the hepatic effects of alcohol Two medications used in the treatment of alcohol dependence have been studied in the treatment of outpatients concurrently dependent on cocaine and alcohol, disulfiram and naltrexone Both separate and combined treatment with disulfiram and/or naltrexone (100–150 mg daily) significantly improved abstinence from cocaine and alcohol Psychiatric Comorbidities Treatment-seeking, cocaine-dependent individuals have high rates of psychiatric comorbidity (i.e., psychiatric diagnoses other than another substance use disorder), with rates as high as 65% for lifetime disorders and 50% for current disorders The most common comorbid disorders tend to be major depression, bipolar spectrum, phobias, and posttraumatic stress disorder Personality disorders are common among treatment-seeking, cocaine-dependent individuals, with rates in this population as high as 69% The most common of these is antisocial personality disorder Depression Desipramine, imipramine, and bupropion have usually, but not always, been found effective, whereas selective serotonin reuptake inhibitors (e.g., fluoxetine) are usually not effective Bipolar Disorder Case series and open-label trials suggest that anticonvulsants such as valproate, divalproex, lamotrigine, and carbamazepine have some efficacy in reducing cocaine use in dually diagnosed patients Combining lithium with an anticonvulsant may be helpful in treatment-resistant patients The second-generation antipsychotics have generated mixed results in cocaine-dependent patients with comorbid bipolar disorder Attention Deficit/Hyperactivity Disorder Up to one fourth of cocaine-dependent adults have either adult ADHD or a history of childhood ADHD Stimulant and dopaminergic medications are the mainstay of treatment for ADHD, suggesting that some of these patients may be self-medicating their ADHD with cocaine Case series and clinical trials generally find that such medications successfully treat ADHD symptoms and reduce cocaine use in adults: dextroamphetamine (up to 60 mg per day), methamphetamine (15 mg per day), and bupropion (up to 100 mg three times a day) Cavacuiti_Chap51.indd 276 2/11/2011 12:32:12 PM CHAPTER 51 | Pharmacologic Interventions for Cocaine, Methamphetamine, and Other Stimulant Addiction 277 Schizophrenia Although schizophrenia is not a common comorbid psychiatric disorder among cocaine-dependent individuals, cocaine use and abuse are common among treatment-seeking patients with schizophrenia Clinical experience indicates that first-generation antipsychotics, at doses that are effective in the treatment of schizophrenia, not significantly alter cocaine craving or use Depot flupenthixol (40 mg of decanoate intramuscularly every weeks) reduced cocaine use and improved psychopathology in a small case series of cocaine-using patients with schizophrenia Several case series and open-label trials suggest that the second-generation antipsychotics, including clozapine, olanzapine, quetiapine, risperidone, and aripiprazole, may be more effective in reducing cocaine and other drug use among patients with schizophrenia The use of cocaine or amphetamines can exacerbate or provoke antipsychotic-induced movement disorders and increase vulnerability to the neuroleptic malignant syndrome Gender-Specific Issues Women tend to be excluded from or underrepresented in many clinical trials of cocaine dependence pharmacotherapy, in part because of concern, embodied in former FDA regulations, over risk to the fetus and neonate should a female subject become pregnant In the absence of directly relevant and systematically collected data, caution should be used when prescribing medications to pregnant women with stimulant dependence and to those with pregnancy potential, keeping in mind both the risks of medication and the risks of continued stimulant use Tricyclic antidepressants, bupropion, and buprenorphine appear to have little potential for morphologic teratogenicity or disruption of pregnancy, although there are little or no data on behavioral teratogenicity Amantadine is associated with pregnancy complications, lithium with cardiac malformations and neonatal toxicity, anticonvulsants with increased risk of congenital malformations, and antipsychotics with nonspecific congenital anomalies and neonatal withdrawal Disulfiram and naltrexone may generate different treatment responses in men versus women The reasons for such gender differences are poorly understood, but may include differences in Medication pharmacokinetics Hormonal interactions Subjects’ psychological/socioeconomic status Age Although adolescents make up a substantial minority of heavy cocaine users, they have been largely excluded from clinical trials of cocaine pharmacotherapies because of legal and informed consent considerations Cavacuiti_Chap51.indd 277 2/11/2011 12:32:12 PM CHAPTER 52 Summary Author: Ashok Krishnamurthy Richard D Hurt • Jon O Ebbert • J Taylor Hays Pharmacologic Interventions for Tobacco Dependence PATHOPHYSIOLOGY OF TOBACCO DEPENDENCE Nicotine binds to and causes conformational changes in nicotinic acetylcholine receptors (located in all areas of the human brain) → receptor stimulated → release of dopamine, norepinephrine, glutamate, vasopressin, serotonin, g-aminobutyric acid, b-endorphins, and other neurotransmitters High concentrations of nicotinic acetylcholine receptors exist in the mesolimbic dopamine system and locus coeruleus Although not completely understood, up-regulation of the high affinity a4b2 nicotinic acetylcholine receptor is critical for the development of tolerance to and dependence on nicotine Repeated exposure to high concentrations of nicotine causes up-regulation of the a4b2 nicotinic acetylcholine receptors, leading to an absolute increase in their numbers Neuroadaptation of the mesolimbic system in smokers and its target neurons in the nucleus accumbens may be longer lasting than previously thought, which could explain the observation that cravings to smoke last for months after a smoker stops smoking The mesolimbic system area is also involved with the positive reinforcing effects of amphetamines, cocaine, and opiates Nicotine-induced dose-dependent increases in feelings of pleasure have been observed to occur simultaneously with increases in the functional MRI of neuronal activity in the nucleus accumbens, amygdala, cingulate, and frontal lobes In laboratory animals, self-administered intravenous nicotine increases the sensitivity of brain reward systems and imprints an indelible memory of its effects in reward systems, an action that appears unique to nicotine among drugs of abuse This may partially explain the rapid relapse to former levels of smoking that frequently follows a smoker having a few cigarettes after a prolonged period of smoking abstinence Tobacco dependence may carry a genetic component as well Twin studies have confirmed an inherited component for tobacco use and dependence, and familial transmission of smoking behavior has been observed across three generations of families The evidence for a contribution of specific genes to smoking behavior remains modest Further work is needed to study the spectrum of heritable traits that influence genetic susceptibility to tobacco dependence MEASURING NICOTINE EXPOSURE One approach to the therapeutic use of nicotine replacement therapy (NRT) for the treatment of tobacco dependence is to determine the patient’s level of nicotine exposure After this exposure is determined, a nicotine replacement dose approximating the dose the individual receives from smoking can be prescribed Factors making the above difficult: Smokers exposed to the same amount of nicotine through inhaled tobacco smoke have marked interindividual differences in venous nicotine concentrations 278 Cavacuiti_Chap52.indd 278 2/11/2011 12:34:14 PM CHAPTER 52 | Pharmacologic Interventions for Tobacco Dependence 279 Cigarette smoking produces initial arterial nicotine concentrations that are severalfold higher than concomitant venous nicotine levels In addition, nicotine has a short half-life (i.e., 120 minutes) and, with smoking, tends to have peaks and troughs in both the venous and the arterial circulation Cotinine, the major metabolite of nicotine, has a half-life of 18 to 20 hours and can be used to quantify an individual’s exposure to nicotine Venous nicotine concentrations (albeit less than arterial levels) reflect acute nicotine exposure, whereas cotinine reflects nicotine exposure over to days Anabasine is a tobacco alkaloid that is not a metabolic product of nicotine Anabasine is present in the urine of tobacco users but not in the urine of patients using NRT Anabasine thus can be especially useful in distinguishing abstinent tobacco users who are using NRT from those who are continuing to use tobacco NICOTINE REPLACEMENT THERAPY Every patient who is willing to make an attempt to stop smoking should be offered counseling and medications Clinical trials have shown that adding pharmacotherapy to a behavioral intervention generally doubles smoking abstinence rates and that the combination of medication and counseling is more effective than either alone NRT remains a mainstay of pharmacotherapy for the treatment of tobacco dependence To date, the FDA has approved five nicotine replacement products: nicotine gum, nicotine patches, nicotine nasal spray, a nicotine vapor inhaler, and nicotine lozenges Gum, patches, and lozenges are available over the counter; nasal spray and inhaler are available by prescription only The dose and duration of therapy should be based on the patient’s subjective need for relief of withdrawal symptoms and support of smoking abstinence Nicotine Gum Nicotine gum is available as an over-the-counter product in both the 2- and 4-mg doses and has been shown to be effective as monotherapy or in combination with other NRT Venous nicotine concentrations achieved through the proper use of nicotine gum are relatively low compared with those produced by smoking cigarettes The 4-mg dose is indicated for use in smokers who are more dependent and is recommended for those who smoke 25 or more cigarettes per day Patients should be instructed to bite into a piece of nicotine gum a few times until a mild tingling or peppery taste indicates nicotine release Patients then should “park” the gum between the cheek and gum for several minutes before chewing it again Because the absorption of nicotine is lowered by a more acidic pH, patients should be instructed not to drink beverages or eat for several minutes before and while using the gum When nicotine gum is used as a single agent, most patients should use a minimum of 10 to 15 pieces per day to achieve initial smoking abstinence The most common adverse effects of nicotine gum are nausea and indigestion, which can be minimized with the proper “chew-and-park” technique Other adverse effects reported include gingival soreness and mouth ulcerations Nicotine Lozenge The nicotine lozenge is available in 2- and 4-mg doses The 4-mg strength is used in “high” dependence smokers (i.e., time to first cigarette of the day, 30 minutes after arising) The lozenge is simpler to use than the gum and likely will demonstrate improved patient compliance As with the other short-acting NRT products, it can be used alone or in combination with other NRT Nicotine Patch Nicotine patch therapy delivers a steady dose of nicotine for 24 hours after a single application The once-daily dosing requires little effort on the part of the patient, which enhances compliance Nicotine patches are available without a prescription in doses of 7, 14, and 21 mg, which deliver nicotine over 24 hours In almost every randomized clinical trial performed to date, the nicotine patch has been shown to be effective compared with placebo usually with a doubling of the stop rate Cavacuiti_Chap52.indd 279 2/11/2011 12:34:14 PM 280 SECTION | Pharmacologic Interventions TABLE 52.1 Nicotine Patch Dose Based on Baseline (While Smoking) Blood Cotinine Concentration Cotinine in ng/mL Nicotine patch dose 300 ≥42 mg/day Standard-dose nicotine patch therapy is 21 mg per 24 hours However, the standard-dose patch approach is not effective in all smokers In fact, it has been shown that a standard dose (21 mg per 24 hours) of nicotine patch therapy achieves a median serum cotinine level of only 54% of the cotinine concentrations achieved through smoking Uses of high doses of nicotine patch therapy (i.e., doses >21 mg per day) are appropriate for smokers who previously failed single-dose patch therapy or for those whose nicotine withdrawal symptoms are not relieved sufficiently with standard therapy This approach can be especially important for heavy smokers because they will be significantly underdosed with single-dose patch therapy High-dose nicotine patch therapy has been shown to be safe and well tolerated in patients who smoke >20 cigarettes per day By employing the concept of therapeutic drug monitoring, clinicians can use serum cotinine concentrations to tailor the nicotine replacement dose so that it approaches 100% replacement A baseline cotinine concentration is obtained while the smoker is smoking his or her usual number of cigarettes An initial nicotine patch dose based on the baseline cotinine concentration (or cigarettes per day) is prescribed After the patient reaches steady state, the serum cotinine concentration is rechecked and the replacement dose can be adjusted to achieve a steady-state cotinine level that approaches the baseline level For special populations in whom a need to use the lowest possible effective dose exists (e.g., pregnant women), therapeutic drug monitoring with cotinine can be used to maintain nicotine replacement levels close to baseline Serum cotinine is the test of choice for calculating the percentage replacement, even though urine nicotine or cotinine can be used If serum cotinine testing is not available, the replacement dose can be estimated based on the number of cigarettes smoked per day (Tables 52.1 and 52.2) Abstinence from smoking during the first weeks of patch therapy has been shown to be highly predictive of longterm abstinence The first weeks of nicotine patch therapy are critical If the patient continues to smoke at all during the first weeks, the treatment must be changed by changing the nicotine patch dose, by adding additional pharmacotherapy, or by intensifying behavioral counseling Nicotine patch doses should be increased for patients experiencing pronounced withdrawal symptoms such as irritability, anxiety, loss of concentration, or craving, or for patients who not achieve 100% replacement based on the second serum cotinine concentration TABLE 52.2 a Cavacuiti_Chap52.indd 280 Recommended Initial Dosing of Nicotine Patch Therapy Based on Number of Cigarettes Smoked Daily Cigarettes/day Patch dose (mg/day)a 40 42+ Nicotine patches are available in the following doses: 7, 14, and 21 mg 2/11/2011 12:34:14 PM CHAPTER 52 | Pharmacologic Interventions for Tobacco Dependence 281 Most patients use the nicotine patch for to weeks, but it is safe to use it longer if needed to maintain abstinence Optimal length of treatment has not been determined Side effects of nicotine patch therapy are relatively mild and include localized skin reactions at the patch site Such reactions generally begin to occur about weeks after initiation of patch therapy Lesions vary from erythema to erythema plus vesicles Rotation of the patches to different sites of the skin helps to reduce the frequency of this side effect Although sleep disturbance is another side effect that has been attributed to nicotine patch therapy, it often is difficult to ascertain whether this is attributable to nicotine withdrawal or to the administration of nicotine during the evening hours If there is a concern that nicotine patch therapy is causing sleep disturbance, the patch can be removed at night to see if the sleep disturbance resolves Some concern was expressed in the lay press that smokers might be at increased risk of myocardial infarction if they continued to smoke while using the patch Subsequent studies have shown no adverse effects in smokers with a history of coronary artery disease receiving the 14- or 21-mg patch doses Nicotine patch doses up to 63 mg per day were not associated with short-term adverse cardiovascular effects in smokers Nicotine Nasal Spray This device delivers nicotine more rapidly than other therapeutic nicotine replacement delivery systems and reduces withdrawal symptoms more quickly than nicotine gum Each spray contains 0.5 mg of nicotine, and one dose is one spray in each nostril (a total of mg) Recommended dosing is one to two doses per hour, not to exceed five doses per hour or 40 doses per day When using the nicotine nasal spray as a single agent, most patients initially use 12 to 16 doses per day The recommended length of treatment is up to 12 weeks of ad lib use, followed by a tapering schedule Patients should be instructed to spray against the lower nasal mucosa and not to sniff the spray into the upper nasal passages or to attempt to inhale it The most common adverse side effects are rhinorrhea, nasal and throat irritation, watery eyes, and sneezing These irritant side effects decrease significantly within the 1st week of use Nicotine nasal spray should be used with caution in patients with reactive airway disease There is no abuse liability with the nicotine spray Nicotine Inhaler This device is a plastic holder into which a cartridge containing a cotton plug impregnated with 10 mg of nicotine is inserted The device delivers a nicotine vapor that is absorbed across the oral mucosa Although the device is called an inhaler, this is a misnomer because little of the nicotine vapor reaches the pulmonary alveoli even with deep inhalations When the nicotine inhaler is used as a single therapy, efficacy is increased when more than six cartridges per day are used The recommended initial dose of the nicotine inhaler when used alone is to 16 cartridges per day The recommended length of treatment is approximately 12 weeks followed by a tapering schedule, although the inhaler could be used longer This device requires frequent puffing to deliver substantial amounts of nicotine and to some smokers the puffing mimics some of the behavior of smoking Adverse effects generally are mild and most often involve mouth or throat irritation, with occasional coughing NONNICOTINE PRODUCTS Bupropion SR Smokers are more likely than nonsmokers to have a history of major depression During the course of an attempt to stop smoking, many smokers develop a depressed affect and some become overtly depressed The development of a depressed affect during an attempt to stop smoking is associated with relapse to smoking Among the antidepressants evaluated, bupropion is the first nonnicotine pharmacologic treatment approved for the treatment of tobacco dependence Bupropion is a monocyclic antidepressant that inhibits reuptake of both norepinephrine and dopamine Dopamine release in the mesolimbic system and the nucleus accumbens is thought to be the basis for the reinforcing properties of nicotine and other drugs of addiction Cavacuiti_Chap52.indd 281 2/11/2011 12:34:14 PM 282 SECTION | Pharmacologic Interventions The efficacy of bupropion in smoking cessation is hypothesized to stem from its dopaminergic activity on the pleasure and reward pathways in the mesolimbic system and nucleus accumbens Bupropion also has been shown to have an antagonist effect on nicotinic acetylcholine receptors Treatment with bupropion SR alone or in combination with the nicotine patch resulted in a significantly higher long-term rate of abstinence from smoking than did use of either the nicotine patch alone or placebo Treatment with bupropion SR should be initiated about week before the patient’s stop date at an initial dose of 150 mg per day for days, then 150 mg twice daily The usual length of treatment is to 12 weeks, but bupropion SR can be used safely for much longer As with other antidepressants, a small risk (0.1%) of seizures is associated with this medication Bupropion SR is contraindicated in patients who have a history of seizures, serious head trauma with skull fracture or a prolonged loss of consciousness, an eating disorder (i.e., anorexia nervosa or bulimia), or concomitant use of medications that lower the seizure threshold The most common adverse side effects are insomnia and dry mouth Treatment-emergent hypertension can occur rarely during treatment with bupropion SR, especially when it is used in combination with nicotine patch therapy However, lower smoking rate, prior abstinence from smoking for brief periods (4 weeks), and male gender all were predictors of better outcome independent of the bupropion SR dose The extended use of bupropion SR for relapse prevention is effective for smokers with or without a history of depression Because of the high prevalence of a history of depression in smokers, clinicians often encounter smokers who want to stop smoking but already are being treated with an antidepressant No drug–drug interactions exist to preclude the use of bupropion SR with either selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants Thus, adding bupropion SR to an SSRI is preferable to discontinuing that medication and using bupropion SR only Varenicline Varenicline is a partial nicotine agonist/antagonist that selectively binds to the nicotinic a4b2 acetylcholine receptor Varenicline both blocks nicotine from binding to the receptor (antagonist effect) and stimulates (agonist effect) receptor-mediated activity leading to the release of dopamine, which reduces craving and nicotine withdrawal symptoms Varenicline: • • • • • • Rapidly absorbed after one administration Reaches peak serum concentration in hours Steady-state serum concentrations after days Is not metabolized Excreted virtually unchanged in the urine Half-life is approximately 17 hours Varenicline was more effective at achieving smoking abstinence compared to placebo or bupropion SR, with end-of-treatment continuous smoking abstinence rates of 44% versus 30% for bupropion SR and 18% for placebo, in two key clinical trials Varenicline showed better smoking abstinence outcomes compared with NRT and was equally effective and safe in smokers with or without a mental illness Varenicline has not been studied systematically in combination with other medications to treat tobacco dependence Varenicline is not recommended for use in combination with NRT; however, some patients may need short-acting NRT for nicotine withdrawal symptom control, especially in the first few days per weeks of varenicline therapy Bupropion SR and varenicline have different mechanisms of action and no drug interactions between these drugs are likely Clinical trials assessing this combination are ongoing However, no clinical trial data to support this treatment approach are available The most frequent adverse effect of varenicline is nausea reported by approximately 30% of the participants However, the nausea was most often mild to moderate, and participant dropouts related to nausea were infrequent In February 2008, the FDA issued a public health advisory because of reports of suicidal thoughts and aggressive and erratic behavior in a patient who have taken varenicline In addition, some case reports have Cavacuiti_Chap52.indd 282 2/11/2011 12:34:14 PM CHAPTER 52 | Pharmacologic Interventions for Tobacco Dependence 283 suggested that varenicline could exacerbate psychiatric symptoms in individuals with severe mental illness, so these types of patients should be monitored carefully when on varenicline Nortriptyline Nortriptyline is a tricyclic antidepressant recommended as a second-line drug for treating tobacco dependence Systematic reviews demonstrate the efficacy of nortriptyline in contrast to SSRIs, which have not been shown to help smokers stop Nortriptyline seems to be as efficacious as bupropion SR in treating smokers with chronic obstructive pulmonary disease The most common adverse effects with nortriptyline are sedation and dry mouth Nortriptyline produces higher smoking abstinence rates than placebo, independent of a history of depression Nortriptyline is contraindicated in combination with an MAOI (monamine oxidase inhibitor) or within 14 days of discontinuing one, nortriptyline allergy, or in the acute recovery phase after a myocardial infarction Clonidine Clonidine is a centrally acting alpha-agonist that can be used as a second-line drug The transdermal form is easier to use with a recommended dose of 0.2 mg per day for to 10 weeks The clonidine patch should be initiated a week before the patient’s stop date and changed weekly thereafter Common side effects include dry mouth and drowsiness The only contraindication to its use is a clonidine allergy COMBINATION PHARMACOTHERAPIES The 2008 United States Public Health Service (USPHS) Guideline states that certain combinations of first-line medications have been shown to be effective Long-term (>14 weeks) nicotine patch therapy combined with nicotine gum or nicotine nasal spray, nicotine patch therapy plus nicotine inhaler, and nicotine patch therapy plus bupropion SR are cited as examples Whether the superiority of combination therapy is due to the use of two types of delivery systems or to the fact that two delivery systems tend to produce higher blood nicotine levels remains unclear Combination pharmacotherapy or higher than usual doses of NRT effectively relieve withdrawal symptoms especially in more dependent smokers Based on the treatment of over 45,000 smokers, the Mayo Clinic’s Nicotine Dependence Center offers the following clinical pearls: (1) Nicotine patch therapy, bupropion SR, and/or varenicline are the “foundation medications” on which to begin building a patient’s pharmacotherapeutic regimen (2) Most medication regimens for treating tobacco dependence should contain at least one if not more than one of these medications (3) Short-acting NRT products (such as nicotine gum, nicotine inhaler, nicotine lozenge, or nicotine nasal spray) are added to “foundation medications” to help control intermittent withdrawal symptoms or cravings Short-acting NRT should rarely be used alone (4) Patients with tobacco dependence will usually require combination therapy, and those with more severe dependence often need three or more products simultaneously CLINICAL DECISIONS ABOUT PHARMACOTHERAPY The 2008 USPHS Guideline observes that there is stronger evidence that counseling is an effective tobacco dependence treatment strategy and that counseling adds significantly to the efficacy of the approved medications Practical counseling (problem solving/skills training) and social support delivered as part of treatment are especially effective Guidelines state that the combination of counseling and medication is more effective than either alone; thus, both should be routinely offered to smokers Self-Help Materials and Longer Term Pharmacotherapy for Relapse Prevention Specific self-help materials, such as the National Cancer Institute’s Forever Free, have been effective in helping smokers maintain smoking abstinence Longer use of pharmacotherapy is useful in some patients to maintain smoking abstinence long enough to stabilize the initial treatment effect The optimal length of pharmacotherapy has not been established for any of the available medications Cavacuiti_Chap52.indd 283 2/11/2011 12:34:14 PM ... Cigarettes/day Patch dose (mg/day)a 40 42+ Nicotine patches are available in the following doses: 7, 14 , and 21 mg 2 /11 /2 011 12 :34 :14 PM CHAPTER 52 | Pharmacologic... stabilize the initial treatment effect The optimal length of pharmacotherapy has not been established for any of the available medications Cavacuiti_Chap52.indd 283 2 /11 /2 011 12 :34 :14 PM CHAPTER... and other drugs of addiction Cavacuiti_Chap52.indd 2 81 2 /11 /2 011 12 :34 :14 PM 282 SECTION | Pharmacologic Interventions The efficacy of bupropion in smoking cessation is hypothesized to stem from