Nicotine Use Disorder

Tobacco use is the leading cause of preventable death in the world. Tobacco use is directly related to a higher risk of chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)), cardiovascular diseases, and various cancers. Nicotine, the psychoactive component of tobacco, stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous systems. Nicotine is highly addictive through its effects on the dopaminergic system. Treatment includes medications to prevent cravings, nicotine-replacement therapy, and psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy.

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Overview

Definition

Nicotine use disorder is defined as the chronic (> 12 months) maladaptive use of tobacco.

  • Most common substances: cigarettes, chewing tobacco
  • Intoxication: 
    • Much milder symptoms than are present in intoxication with other substances
    • Presents with mild restlessness/anxiety and increased GI motility 
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Mild physical symptoms: weight gain, poor concentration
    • Mild psychological symptoms: depression, perceived need to use the substance 
  • Tolerance: 
    • Need to increase the dose of the substance to achieve desired effect (diminished effect if using the same amount of the substance)

Epidemiology

  • Tobacco use is the leading cause of preventable deaths worldwide. 
  • Prevalence: 
    • 15% of adults in the United States smoke regularly.
    • Higher in those with other comorbid psychiatric disorders such as bipolar disorder Bipolar disorder Bipolar disorder is a highly recurrent psychiatric illness characterized by periods of manic/hypomanic features (distractibility, impulsivity, increased activity, decreased sleep, talkativeness, grandiosity, flight of ideas) with or without depressive symptoms. Bipolar Disorder (70%), schizophrenia Schizophrenia Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia (90%), or other substance use disorders (70%) 
    • Smoking rates among young people in the United States are decreasing. 
  • Level of education is a protective factor in tobacco use.

Pharmacology

Nicotine is the main psychoactive component of tobacco:

  • Agonist at the nicotinic subtype of acetylcholine receptor in the central nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System
  • Activates the dopaminergic pathway from the ventral tegmental area to the cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex to produce its rewarding effects 
  • Leads to increasing circulation of the following neurotransmitters:
    • Norepinephrine
    • Epinephrine
    • Beta-endorphin
    • Adrenocorticotropic hormone
    • Cortisol

Only 25% of inhaled nicotine enters the bloodstream, but it reaches the brain in 15 seconds.

Clinical Presentation

Active nicotine use

  • Immediate effects of nicotine include improved attention and elevated mood.
  • Usually, there are no severe intoxication symptoms from tobacco use.
  • Nicotine intoxication: 
    • Nausea/vomiting 
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Tachycardia, elevated blood pressure 
    • Tremor
    • Cold sweats
  • Note: Nicotine is a CNS stimulant but a skeletal muscle relaxant.

Nicotine withdrawal

  • Intense craving
  • Dysphoria
  • Anxiety
  • Poor concentration
  • Increased appetite, weight gain
  • Irritability, restlessness, and insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia

Management and Complications

Pharmacotherapy for nicotine use disorder

  • Nicotine-replacement therapy:
    • 1st-line treatment; doubles chances of cessation
    • Available as transdermal patch, gum, lozenge, nasal spray, and inhaler
  • Nicotine cessation: 
    • Varenicline: 
      • Partial agonist to the alpha-4 beta-2 (α4β2) nicotinic cholinergic receptor 
      • Mimics the action of nicotine
      • Reduces the rewarding effects of nicotine
      • Prevents withdrawal symptoms
      • Side effects: sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep disturbance, depressed mood
    • Bupropion: 
      • Inhibitor of dopamine and norepinephrine reuptake
      • Helps reduce cravings and withdrawal symptoms
      • Side effects: tachycardia, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, headaches, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures in bulimic patients (contraindicated in this group)

Psychotherapy and preventive measures for nicotine use disorder

  • Behavioral counseling:
    • Includes face-to-face or phone sessions, print materials, and software programs 
    • The goal is to help eliminate cues for smoking.
  • Motivational interviewing: 
    • Offered by providers to patients to uncover internal reasons for tobacco cessation 
    • The 1st step is to set a “quit date.”
  • Prevention and education are recommended in school-aged children and adolescents. 
  • Public health policies such as a ban on public smoking

Management of nicotine withdrawal

  • Symptomatic treatment 
  • Supportive, psychosocial interventions (e.g., contingency management, groups, etc.)

Complications

  • Smoking increases the risk for several types of cancers: 
    • Lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer: Tobacco smoking is the most common risk factor for the most deadly form of cancer in the United States.
    • Chronic obstructive pulmonary disease ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)): 90% of cases of COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) can be attributed to tobacco smoking.
    • Esophageal cancer Esophageal cancer Esophageal cancer is 1 of the most common causes of cancer-related deaths worldwide. Nearly all esophageal cancers are either adenocarcinoma (commonly affecting the distal esophagus) or squamous cell carcinoma (affecting the proximal two-thirds of the esophagus). Esophageal Cancer
    • Gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer
    • Renal cell carcinoma Renal cell carcinoma Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma
    • Transitional cell carcinoma
    • Salivary gland tumors
    • Cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer
  • Cardiovascular diseases ( atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis, angina)
  • Vasculitis (Buerger disease)
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care-related complications: 
    • Low birth weight
    • Preterm labor Preterm labor Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth
    • Placental problems
    • Intrauterine growth restriction 
    • Sudden infant death syndrome Sudden Infant Death Syndrome Sudden infant death syndrome (SIDS) describes the sudden death of an otherwise healthy infant (< 1 year of age) with no identifiable cause. Sudden infant death syndrome is the leading cause of death in children between 1 and 12 months of age in the United States. Sudden Infant Death Syndrome
    • Ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy
  • Secondhand smoke 
    • Refers to involuntary exposure to tobacco smoke 
    • Similar complications as above although in lower numbers

Benefits of smoking cessation

Short-term benefits (< 12 months):

  • Lowered heart rate and blood pressure
  • Return of blood carbon monoxide level to normal
  • Improved circulation and lung function 
  • Decreased coughing and shortness of breath 
  • Women who stop smoking during the 1st trimester reduce their risk of low birth weight to that of women who never smoked.

Long-term benefits (> 12 months):

  • Increased life expectancy 
  • Decreased risk of lung cancer, myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, cerebrovascular diseases  
  • Decreased risk of oropharyngeal, bladder, cervical, lung, and pancreatic cancer

Differential Diagnosis

  • Organophosphate poisoning: chemicals commonly found in insecticides, classified as irreversible cholinesterase inhibitors. When these chemicals are ingested in toxic amounts, symptoms include salivation, lacrimation, urination, diarrhea, GI upset, and emesis. These symptoms are similar to nicotine intoxication. However, the severity of symptoms observed in organophosphate poisoning is unlikely to occur from excessive tobacco consumption. 
  • Cannabis use disorder Cannabis use disorder Cannabis use disorder (CUD) is characterized by the pathologic consumption of cannabis, which is the most commonly used illicit substance worldwide. While cannabis has some beneficial medical uses, it also has the potential to cause intoxication characterized by psychosis or cognitive impairment, especially in chronic use. Cannabis Use Disorder: cannabis is the most commonly used illicit substance worldwide. Intoxication symptoms include euphoria, laughter, lethargy, impaired reaction time, conjunctival injection, and increased appetite. Withdrawal symptoms include irritability, anxiety, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, and decreased appetite. While the withdrawal symptoms of irritability and anxiety are similar in cannabis and tobacco use, appetite is usually increased during withdrawal from tobacco use. Careful history taking of the substance ingested will also help distinguish the diagnosis.

References

  1. Ganti L, et al. (2016). First Aid for the Psychiatry Clerkship. 4th ed., Chapter 7, Substance-related and addictive disorders, pages 80, 94.
  2. Bhushan V, et al. (2019). First Aid for the USMLE Step 1. 29th ed. McGraw-Hill Education/Medical. Page 564.
  3. Rigotti N. (2021). Overview of smoking cessation management in adults. UpToDate. Retrieved April 30, 2021, from https://www.uptodate.com/contents/overview-of-smoking-cessation-management-in-adults 
  4. Sadock BJ, Sadock VA, & Ruiz P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.), Chapter 20, Substance use and addictive disorders, pages 680–685. Philadelphia, PA: Lippincott Williams and Wilkins.

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