36.20 - Lithium

Authors: Sadock, Benjamin James; Sadock, Virginia Alcott

Title: Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition

Copyright ©2007 Lippincott Williams & Wilkins

> Table of Contents > 12 - Substance-Related Disorders > 12.9 - Nicotine-Related Disorders


Nicotine-Related Disorders

Nicotine is one of the most highly addictive and heavily used drugs in the United States and around the world. It causes lung cancer, emphysema, and cardiovascular disease and secondhand smoke is associated with lung cancer in adults and respiratory illness in children.


The landmark 1988 publication called The Surgeon General's Report on the Health Consequences of Smoking: Nicotine Addiction increased the awareness of the hazards of smoking to the American public. However, the fact that about 30 percent continue to smoke despite the mountain of data showing how dangerous the habit is to their health is testament to the powerfully addictive properties of nicotine. The ill effects of cigarette and cigar smoking are reflected in the estimate that 60 percent of the direct health care costs in the United States go to treat tobacco-related illnesses and amount to an estimated $1 billion a day.


The 2004 Monitoring the Future Survey concluded that, despite the demonstrated health risk associated with cigarette smoking, young Americans continue to smoke. However, 30-day smoking rates among high school students declined from peaks reached in 1996 for eighth-graders (21.0 percent) and tenth-graders (30.4 percent) and in 1997 for seniors (36.5 percent). In 2004, 30-day rates reached the lowest levels ever reported by Monitoring the Future surveys for eighth-graders (9.2 percent) and tenth-graders (16.0 percent). Of high school seniors, 25 percent reported smoking during the month preceding their responses to the survey.

Lifetime cigarette use among tenth-graders decreased significantly, from 43.0 percent in 2003 to 40.7 percent in 2004. Among tenth-graders, a significantly decreased number of students reported that they smoke one-half pack or more cigarettes per day.

The decrease in smoking rates among young Americans corresponds to several years in which increased proportions of teens said they believe a “great” health risk is associated with cigarette smoking and expressed disapproval of smoking one or more packs of cigarettes a day. Students' personal disapproval of smoking had risen for some years, but showed no further increase in 2004. In 2004, 85.7 percent of eighth-graders, 82.7 percent of tenth-graders, and 76.2 percent of twelfth-graders stated that they “disapprove” or “strongly disapprove” of people smoking one or more packs of cigarettes per day. In addition, eighth- and tenth-graders reported significant increases in the perceived harmfulness of smoking one or more packs of cigarettes per day.

The World Health Organization (WHO) estimates there are 1 billion smokers worldwide, and they smoke 6 trillion cigarettes a year. The WHO also estimates that tobacco kills more than 3 million persons each year. Although the number of persons in the United States who smoke is decreasing, the number of persons smoking in developing countries is increasing. The rate of quitting smoking has been highest among well-educated white men and lowest among women, blacks, teenagers, and those with low levels of education.

Tobacco is the most common form of nicotine. It is smoked most commonly in cigarettes, then, in descending order, cigars, snuff, chewing tobacco, and in pipes. About 3 percent of all persons in the United States currently use snuff or chewing tobacco, and about 6 percent of young adults ages 18 to 25 use those forms of tobacco.

Currently, about 25 percent of Americans smoke, 25 percent are former smokers, and 50 percent have never smoked cigarettes. The mean age of onset of smoking is 16 years, and few persons start smoking after 20. Dependence features appear to develop quickly. Classroom and other programs to prevent initiation are only mildly effective, but increased taxation does decrease initiation.

More than 75 percent of smokers have tried to quit, and about 40 percent try to quit each year. On a given attempt, only 30 percent remain abstinent for even 2 days, and only 5 to 10 percent stop permanently. Most smokers make 5 to 10 attempts, however, so eventually 50 percent of “ever smokers” quit. In the past, 90 percent of successful attempts to quit involved no treatment. With the advent of over-the-counter (OTC) and nonnicotine medications in 1998, about one third of all attempts involved the use of medication.

In terms of the diagnosis of nicotine dependence per se, about 20 percent of the population develops nicotine dependence at some point, making it one of the most prevalent psychiatric disorders. According to the text revision of the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), approximately 85 percent of current daily smokers are nicotine dependent. Nicotine withdrawal occurs in about 50 percent of smokers who try to quit.

According to the CDC, regional differences exist in smoking throughout the United States. The 12 areas with the highest prevalence of current smoking are Kentucky, Nevada, Missouri, Indiana, Ohio, West Virginia, North Carolina, Tennessee, New Hampshire, Alabama, Arkansas, and Alaska. The 12 areas with lowest prevalence are Utah, Puerto Rico, California, Arizona, Montana, Hawaii, Minnesota, Connecticut, Massachusetts, Colorado, Maryland, and Washington. Utah had the lowest prevalence for men (14.5 percent), and Puerto Rico had the lowest for women (9.9 percent).


Level of education attainment correlated with tobacco usage. Of adults who had not completed high school, 37 percent smoked cigarettes, whereas only 17 percent of college graduates smoked.

Psychiatric Patients

Psychiatrists must be particularly concerned and knowledgeable about nicotine dependence because of the high proportion of psychiatric patients who smoke. Approximately 50 percent of all psychiatric outpatients, 70 percent of outpatients with bipolar I disorder, almost 90 percent of outpatients with schizophrenia, and 70 percent of substance use disorder patients smoke. Moreover, data indicate that patients with depressive disorders or anxiety disorders are less successful in their attempts to quit smoking than other persons; thus, a holistic health approach for these patients probably includes helping them address their smoking habits in addition to the primary mental disorder. The high percentage of patients with schizophrenia who smoke has been attributed to nicotine's ability to reduce their extraordinary sensitivity to outside sensory stimuli and to increase their concentration. In that sense, such patients are self-monitoring to relieve distress.


Death is the primary adverse effect of cigarette smoking. Tobacco use is associated with approximately 400,000 premature deaths each year in the United States—25 percent of all deaths.


The causes of death include chronic bronchitis and emphysema (51,000 deaths), bronchogenic cancer (106,000 deaths), 35 percent of fatal myocardial infarctions (115,000 deaths), cerebrovascular disease, cardiovascular disease, and almost all cases of chronic obstructive pulmonary disease and lung cancer. The increased use of chewing tobacco and snuff (smokeless tobacco) has been associated with the development of oropharyngeal cancer, and the resurgence of cigar smoking is likely to lead to an increase in the occurrence of this type of cancer.

Researchers have found that 30 percent of cancer deaths in the United States are caused by tobacco smoke, the single most lethal carcinogen in the United States. Smoking (mainly cigarette smoking) causes cancer of the lung, upper respiratory tract, esophagus, bladder, and pancreas and probably of the stomach, liver, and kidney. Smokers are eight times more likely than nonsmokers to develop lung cancer, and lung cancer has surpassed breast cancer as the leading cause of cancer-related deaths in women. Even secondhand smoke (discussed below) causes a few thousand cancer deaths each year in the United States, about the same number as are caused by radon exposure. Despite these staggering statistics, smokers can dramatically lower their chances of developing smoke-related cancers simply by quitting.


The psychoactive component of tobacco is nicotine, which affects the central nervous system (CNS) by acting as an agonist at the nicotinic subtype of acetylcholine receptors. About 25 percent of the nicotine inhaled during smoking reaches the bloodstream, through which nicotine reaches the brain within 15 seconds. The half-life of nicotine is about 2 hours. Nicotine is believed to produce its positive reinforcing and addictive properties by activating the dopaminergic pathway projecting from the ventral tegmental area to the cerebral cortex and the limbic system. In addition to activating this dopamine reward system, nicotine causes an increase in the concentrations of circulating norepinephrine and epinephrine and an increase in the release of vasopressin, β-endorphin, adrenocorticotropic hormone (ACTH), and cortisol. These hormones are thought to contribute to the basic stimulatory effects of nicotine on the CNS.


The DSM-IV-TR lists three nicotine-related disorders (Table 12.9-1), but contains specific diagnostic criteria for only nicotine withdrawal (Table 12.9-2) in the nicotine-related disorders section. The other nicotine-related disorders recognized by DSM-IV-TR are nicotine dependence and nicotine-related disorder not otherwise specified.

Table 12.9-1 DSM-IV-TR Nicotine-Related Disorders

Nicotine use disorder
Nicotine dependence
Nicotine-induced disorder
Nicotine withdrawal
Nicotine-related disorder not otherwise specified
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Table 12.9-2 DSM-IV-TR Diagnostic Criteria for Nicotine Withdrawal

  1. Daily use of nicotine for at least several weeks.
  2. Abrupt cessation of nicotine use, or reduction in the amount of nicotine used, followed within 24 hours by four (or more) of the following signs:
    1. dysphoric or depressed mood
    2. insomnia
    3. irritability, frustration, or anger
    4. anxiety
    5. difficulty concentrating
    6. restlessness
    7. decreased heart rate
    8. increased appetite or weight gain
  3. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  4. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Nicotine Dependence

The DSM-IV-TR does have a diagnosis of nicotine dependence (see Tables 12.1-4,12.1-5), but not nicotine abuse. Dependence on nicotine develops quickly, probably because nicotine activates the ventral tegmental area dopaminergic system, the same system affected by cocaine and amphetamine. The development of dependence is enhanced by strong social factors that encourage smoking in some settings and by the powerful effects of tobacco company advertising. Persons are likely to smoke if their parents or siblings smoke and serve as role models. Several recent studies have also suggested a genetic diathesis toward nicotine dependence. Most persons who smoke want to quit and have tried many times to quit but have been unsuccessful.

Nicotine Withdrawal

The DSM-IV-TR does not have a diagnostic category for nicotine intoxication, but does have a diagnostic category for nicotine withdrawal (Table 12.9-2). Withdrawal symptoms can develop within 2 hours of smoking the last cigarette; they generally peak in the first 24 to 48 hours and can last for weeks or months. The common symptoms include an intense craving for nicotine, tension, irritability, difficulty concentrating, drowsiness and paradoxical trouble sleeping, decreased heart rate and blood pressure, increased appetite and weight gain, decreased motor performance, and increased muscle tension. A mild syndrome of nicotine withdrawal can appear when a smoker switches from regular to low-nicotine cigarettes.

Nicotine-Related Disorder Not Otherwise Specified

Nicotine-related disorder not otherwise specified is a diagnostic category for nicotine-related disorders that do not fit into one of


the categories discussed above (Table 12.9-3). Such diagnoses may include nicotine intoxication, nicotine abuse, and mood disorders and anxiety disorders associated with nicotine use.

Table 12.9-3 DSM-IV-TR Diagnostic Criteria for Nicotine- Related Disorder Not Otherwise Specified

The nicotine-related disorder not otherwise specified category is for disorders associated with the use of nicotine that are not classifiable as nicotine dependence or nicotine withdrawal.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Clinical Features

Behaviorally, the stimulatory effects of nicotine produce improved attention, learning, reaction time, and problem-solving ability. Tobacco users also report that cigarette smoking lifts their mood, decreases tension, and lessens depressive feelings. Results of studies of the effects of nicotine on cerebral blood flow (CBF) suggest that short-term nicotine exposure increases CBF without changing cerebral oxygen metabolism, but long-term nicotine exposure decreases CBF. In contrast to its stimulatory CNS effects, nicotine acts as a skeletal muscle relaxant.

Adverse Effects

Nicotine is a highly toxic alkaloid. Doses of 60 mg in an adult are fatal secondary to respiratory paralysis; doses of 0.5 mg are delivered by smoking an average cigarette. In low doses the signs and symptoms of nicotine toxicity include nausea, vomiting, salivation, pallor (caused by peripheral vasoconstriction), weakness, abdominal pain (caused by increased peristalsis), diarrhea, dizziness, headache, increased blood pressure, tachycardia, tremor, and cold sweats. Toxicity is also associated with an inability to concentrate, confusion, and sensory disturbances. Nicotine is further associated with a decrease in the user's amount of rapid eye movement (REM) sleep. Tobacco use during pregnancy has been associated with an increased incidence of low birth weight babies and an increased incidence of newborns with persistent pulmonary hypertension.

Health Benefits of Smoking Cessation

Smoking cessation has major and immediate health benefits for persons of all ages and provides benefits for persons with and without smoking-related diseases. Former smokers live longer than those who continue to smoke. Smoking cessation decreases the risk for lung cancer and other cancers, myocardial infarction, cerebrovascular diseases, and chronic lung diseases. Women who stop smoking before pregnancy or during the first 3 to 4 months of pregnancy reduce their risk for having low birth weight infants to that of women who never smoked. The health benefits of smoking cessation substantially exceed any risks from the average 5-pound (2.3 kg) weight gain or any adverse psychological effects after quitting.


Psychiatrists should advise all patients to quit smoking. For patients who are ready to stop smoking, it is best to set a “quit date.” Most clinicians and smokers prefer abrupt cessation, but because no good data indicate that abrupt cessation is better than gradual cessation, patient preference for gradual cessation should be respected. Brief advice should focus on the need for medication or group therapy, weight gain concerns, high-risk situations, making cigarettes unavailable, and so forth. Because relapse is often rapid, the first follow-up phone call or visit should be 2 to 3 days after the quit date. These strategies have been shown to double self-initiated quit rates (Table 12.9-4).

Psychosocial Therapies

Behavior therapy is the most widely accepted and well-proved psychological therapy for smoking. Skills training and relapse prevention identify high-risk situations and plan and practice behavioral or cognitive coping skills for those situations in which smoking occurs. Stimulus control involves eliminating cues for smoking in the environment. Aversive therapy has smokers smoke repeatedly and rapidly to the point of nausea that associates smoking with unpleasant, rather than pleasant, sensations. Aversive therapy appears to be effective but requires a good therapeutic alliance and patient compliance.


Some patients benefit from a series of hypnotic sessions. Suggestions about the benefits of not smoking are offered and assimilated into the patient's cognitive framework as a result. Posthypnotic suggestions that cause cigarettes to taste bad or to produce nausea when smoked are also used.

Psychopharmacological Therapies

Nicotine Replacement Therapies

All nicotine replacement therapies double cessation rates, presumably because they reduce nicotine withdrawal. These therapies can also be used to reduce withdrawal in patients on smoke-free wards. Replacement therapies use a short period of maintenance of 6 to 12 weeks often followed by a gradual reduction period of another 6 to 12 weeks.

Nicotine polacrilex gum (Nicorette) is an OTC product that releases nicotine via chewing and buccal absorption. A 2-mg variety for those who smoke fewer than 25 cigarettes a day and a 4-mg variety for those who smoke more than 25 cigarettes a day are available. Smokers are to use one to two pieces of gum per hour up to a maximum of 24 pieces per day after abrupt cessation.


Venous blood concentrations from the gum are one third to one half the between-cigarette levels. Acidic beverages (coffee, tea, soda, and juice) should not be used before, during, or after gum use because they decrease absorption. Compliance with the gum has often been a problem. Adverse effects are minor and include bad taste and sore jaws. About 20 percent of those who quit use the gum for long periods, but 2 percent use gum for longer than a year; long-term use does not appear to be harmful. The major advantage of nicotine gum is its ability to provide relief in high-risk situations.

Table 12.9-4 Typical Quit Rates of Common Therapies

Therapy Rate (%)
Self-quit 5
Self-help books 10
Physician advice 10
Over-the-counter patch or gum 15
Medication plus advice 20
Behavior therapy alone 20
Medication plus group therapy 30

Nicotine lozenges (Commit) deliver nicotine and are also available in 2-mg and 4-mg forms; they are useful especially for patients who smoke a cigarette immediately on awakening. Generally, 9 to 20 lozenges a day are used during the first 6 weeks with decrease in dosage thereafter. Lozenges offer the highest level of nicotine of all nicotine replacement products. Users must suck the lozenge until dissolved and not swallow it. Side effects include insomnia, nausea, heartburn, headache, and hiccups.

Nicotine patches, also sold OTC, are available in a 16-hour, no-taper preparation (Nicotrol) and a 24- or 16-hour tapering preparation (Nicoderm CQ). Patches are administered each morning and produce blood concentrations about half those of smoking. Compliance is high, and the only major adverse effects are rashes and, with 24-hour wear, insomnia. Using gum and patches in high-risk situations increases quit rates by another 5 to 10 percent. No studies have been done to determine the relative efficacies of 24- or 16-hour patches or of taper and no-taper patches. After 6 to 12 weeks, the patch is discontinued because it is not for long-term use.

Nicotine nasal spray (Nicotrol), available only by prescription, produces nicotine concentrations in the blood that are more similar to those from smoking a cigarette, and it appears to be especially helpful for heavily dependent smokers. The spray, however, causes rhinitis, watering eyes, and coughing in more than 70 percent of patients. Although initial data suggested abuse liability, further trials have not found this.

The nicotine inhaler, a prescription product, was designed to deliver nicotine to the lungs, but the nicotine is actually absorbed in the upper throat. It delivers 4 mg per cartridge and resultant nicotine levels are low. The major asset of the inhaler is that it provides a behavioral substitute for smoking. The inhaler doubles quit rates. These devices require frequent puffing—about 20 minutes to extract 4 mg of nicotine—and have minor adverse effects.

Non-nicotine Medications

Non-nicotine therapy may help smokers who object philosophically to the notion of replacement therapy and smokers who fail replacement therapy. Bupropion (Zyban) (marketed as Wellbutrin for depression) is an antidepressant medication that has both dopaminergic and adrenergic actions. Bupropion is started at 150 mg per day for 3 days and increased to 150 mg twice a day for 6 to 12 weeks. Daily dosages of 300 mg doubles quit rates in smokers with and without a history of depression. In one study, combined bupropion and nicotine patch had higher quit rates than either alone. Adverse effects include insomnia and nausea, but these are rarely significant. Seizures have not occurred in smoking trials. Interestingly, nortriptyline (Pamelor) appears to be effective for smoking cessation and is recommended as a second-line drug.

Clonidine (Catapres) decreases sympathetic activity from the locus ceruleus and, thus, is thought to abate withdrawal symptoms. Whether given as a patch or orally, 0.2 to 0.4 mg a day of clonidine appears to double quit rates; however, the scientific database for the efficacy of clonidine is neither as extensive nor as reliable as that for nicotine replacement; also, clonidine can cause drowsiness and hypotension. Some patients benefit from benzodiazepine therapy (10 to 30 mg per day) for the first 2 to 3 weeks of abstinence.

A nicotine vaccine that produces nicotine-specific antibodies in the brain is under investigation at the National Institute on Drug Abuse (NIDA).

Combined Psychosocial and Pharmacological Therapy

Several studies have shown that combining nicotine replacement and behavior therapy increases quit rates over either therapy alone.

Smoke-Free Environment

Secondhand smoke can contribute to lung cancer death and coronary heart disease in adult nonsmokers. Each year, an estimated 3,000 lung cancer deaths and 62,000 deaths from coronary artery disease in adult nonsmokers are attributed to secondhand smoke. Among children, secondhand smoke is implicated in sudden infant death syndrome, low birth weight, chronic middle ear infections, and respiratory illnesses (e.g., asthma, bronchitis, and pneumonia). Two national health objectives for 2010 are to reduce cigarette smoking among adults to 12 percent and the proportion of nonsmokers exposed to environment tobacco smoke to 45 percent.

Involuntary exposure to secondhand smoke remains a common public health hazard that is preventable by appropriate regulatory policies. Bans on smoking in public places reduce exposure to secondhand smoke and the number of cigarettes smoked by smokers. Support is nearly universal for bans in schools and day-care centers and strong support for bans in indoor work areas and restaurants. Clean indoor air policies are one way to change social norms about smoking and reduce tobacco consumption. Bans on outdoor smoking in areas, such as public parks, are increasing and in 2006 one municipality in California banned smoking entirely within city limits except in one's own home or car and windows had to remain closed.


Abrams DB, Niaura R, Brown RA, Emmons KM, Goldstein MG, Monti PM. The Tobacco Dependence Treatment Handbook. A Guide to Best Practices. Barlow DH, ed. New York: The Guilford Press; 2003.

Dudas MM, George TP. Non-nicotine pharmacotherapies for nicotine dependence. Essential Psychopharmacol. 2005;6(3):158–172.

Einarson A, Sarkar M, Djulus J, Koren G. Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol. 2006;107:1167.

Giovino GA. Epidemiology of tobacco use in the United States. Oncogene. 2002;21:7326–7340.

Hughes JR. Nicotine-related disorders. In: Sadock BJ, Sadock VA, eds. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. 8th ed. Vol. 1. Baltimore: Lippincott Williams & Wilkins; 2005:1257.


Montoya ID, Herbeck DM, Svikis DS, Pincus HA. Identification and treatment of patients with nicotine problems in routine clinical psychiatry. Am J Addict. 2005;14:441–454.

National Cancer Institute. Those Who Continue to Smoke: Is Achieving Abstinence Harder and Do We Need to Change Our Interventions? Smoking and Tobacco Control Monograph No. 15. Bethesda, MD: USDHHS, National Institutes of Health, National Cancer Institute; 2003.

Niaura R, Abrams DB. Smoking cessation: Progress, priorities, and prospects. J Consult Clin Psychol. 2002;70:494–509.

O'Malley SS, Cooney JL, Krishnan-Sarin S, Dubin JA, McKee SA, Cooney NL, Blakeslee A, Meandzija B, Romano-Dahlgard D, Wu R, Makuch R, Jatlow P. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern Med. 2006;166:667–674.

Patton GC, Coffey C, Carlin JB, Sawyer SM, Lynskey M. Reverse gateways? Frequent cannabis use as a predictor of tobacco initiation and nicotine dependence. Addiction. 2005;100:1518–1525.

Piasecki M, Newhouse PA. Nicotine in Psychiatry. Psychopathology and Emerging Therapeutics. Washington, DC: American Psychiatric Press; 2002.

Rigotti NA. Clinical practice: Treatment of tobacco use and dependence. N Engl J Med. 2002;346:506.

Upadhyaya H, Deas D, Brady K. A practical clinical approach to the treatment of nicotine dependence in adolescents. J Am Acad Child Adolesc Psychiatry. 2005;44:942–946.