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  Disease summary:

  
  
  
  
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    Nicotine dependence (ND) is a complex psychiatric disorder determined by both genetics and environment, as well as gene-gene and gene-environment interactions.

    
    
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    About 20% of US adults use tobacco (primarily cigarettes); 70% of smokers want to quit, but only 4% to 7% are successful on a long-term basis without assistance.

    
    
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    Tobacco use is the leading preventable cause of morbidity and death in the United States.

    
    
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    It is the most common cause of cancer-related deaths in many countries, including cancers of the lung, larynx, esophagus, oral tissues, and bladder.

    
    
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    Tobacco use is also a leading cause of coronary artery disease, myocardial infarction, peripheral vascular disease, stroke, and chronic obstructive pulmonary disease (COPD).

    
    
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    Tobacco use is directly responsible for more than 443,000 premature deaths annually in the United States, with direct and indirect healthcare costs exceeding $193 billion.

    
    
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    Extensive research documents the relation between tobacco use and psychiatric conditions, particularly depression, anxiety disorders, substance abuse, and schizophrenia. Nicotine-dependent individuals appear more likely to develop depressive and anxiety disorders, and quitting partially reduces that risk. Tobacco users with psychiatric disorders are less likely to quit and are at risk for a substantially shortened life spans. Tobacco use prevalence rates for those with psychotic, depressive, or anxiety disorders or for those who are alcohol dependent is much higher than for the general population. In addition, nicotine alters the metabolism of many medications, including psychotropics, requiring close monitoring and dosage adjustment.

  
  
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  Monogenic forms:

  
  
  
  
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    No single-gene cause of ND is known.

  
  
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  Family history:

  
  
  
  
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    Initiation of smoking is two to four times more likely for adolescents whose parents and siblings smoke.

  
  
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  Twin studies:

  
  
  
  
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    Monozygotic twins have a significantly higher concordance rate for ND than dizygotic twins. For example, one study revealed the concordance rate for ND in monozygotic twins to be 72% versus 28% for dizygotic twins.

  
  
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  Environmental factors:

  
  
  
  
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    Many factors such as peers, friends, and family members who smoke, low socioeconomic status, or stressful environments are implicated as environmental triggers for ND.

  
  
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  Association studies:

  
  
  
  
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    Many studies, including candidate gene-based association and genome-wide association (GWA) studies, have been conducted. Genetic variants associated with ND provide insight into the etiology of ND; however, testing for single-nucleotide polymorphisms (SNPs) is not yet clinically validated to diagnose or guide the management of ND.

  
  
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  Pharmacogenomics:

  
  
  
  
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    There are reproducible and clinically significant associations of a phenotypic biomarker of nicotine metabolism rate (and CYP2A6 enzyme activity) with smoking cessation and response to nicotine replacement therapies. Although there is promising evidence for a role in smoking cessation for SNPs in the nicotinic receptor subunit genes β2, α5, and α3, effects are small and not consistently replicated.

Diagnostic Criteria for ND

DSM-IV diagnosis of ND requires an individual to meet at least three of the following criteria during a 12-month period:

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  Tolerance: the need for a markedly increased amount of nicotine to produce the desired effect or a diminished effect with continued use of the same amount of nicotine.

  
  
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  Withdrawal, as manifested by either the characteristic syndrome, or use of nicotine or related substance to relieve or avoid withdrawal symptoms (ie, depressed mood, insomnia, irritability, anxiety, concentration difficulties, restlessness, decreased heart rate, and increased appetite or weight gain).

  
  
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  Nicotine is used in larger amounts or over a longer period than intended.

  
  
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  The individual has a persistent desire or makes unsuccessful attempts to cut down on use of tobacco.

  
  
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  A great deal of time is spent in obtaining or using the substance.

  
  
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  Reduced important social, occupational, or recreational activities because of tobacco use.

  
  
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  Use of tobacco continues despite recurrent physical or psychological problems caused or exacerbated by tobacco; for example, continuing to smoke despite diagnoses such as hypertension, heart disease, cancer, bronchitis, and chronic obstructive lung disease.

The DSM-IV criteria for ND have been criticized for a variety of reasons. Primary among these is that a diagnosis of ND does not assess the degree of dependence. Thus, other instruments have been used as a supplement or replacement. The Fagerström Test for Nicotine Dependence (FTND) is one of the most commonly used questionnaires to characterize the degree to which the patient is physically dependent on cigarette smoking (Table 140-1).

Another option for measuring ND is the Wisconsin Inventory for Smoking Dependence Motives (WISDM), which provides greater information regarding various domains of smoking motivation. This is a relatively new scale with accumulating evidence suggesting its utility. Other scales are used less frequently and tend to be restricted to research applications.

Given the problems identified with the DSM-IV diagnostic criteria, substantial revisions are planned for the DSM-V edition. These proposed criteria call for (a) a total of 11 possible symptoms: the seven DSM-IV dependence criteria, three nicotine abuse criteria, and one new craving item; (b) reducing the number of required symptoms from three to two; and (c) establishing a severity indicator (ie, two or three symptoms for moderate, four or more symptoms for severe ND). However, only limited direct research has evaluated the viability of these new criteria to date.

Clinical Characteristics

Patterns of tobacco use vary considerably. Individuals may consume tobacco sporadically or on a daily basis, from small to relatively large amounts, and use a single versus multiple forms. The degree to which an individual’s pattern of use is elicited by exposure to tobacco stimuli (eg, others smoking, distressing circumstances) is variable, as is the type, intensity, and duration of the particular withdrawal symptoms experienced. The general characteristics of the tobacco-using population are changing, with higher prevalence rates now evident among those of lower socioeconomic status and educational attainment and those with psychiatric diagnoses or symptoms. Overall, the risk of relapse postcessation generally is high, particularly for those who quit without professional assistance, or among certain subgroups (eg, pregnant women who smoke). Patients who have used tobacco products for an extended period often present with signs of compromised health, generally related to the length of smoking history. Depressive or anxiety symptoms or both are relatively common, but the clinician should be aware that the suicide rate for smokers is substantially higher than for the general population; the risk for former smokers falls in between.