Which of the following statements is incorrectly matched: Nicotine binding to the mesolimbic a4ß2 subtype of Nicotinic Receptor (Nn), Smoking enhancing the release of Acetylcholine (Ach) and norepinephrine, Nicotine Replacement Therapy (NRT) having a long safety record, or Varenicline (Chantix) improving depressive symptoms precipitated by quitting?

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From the Guidelines

The incorrectly matched statement is "Varenicline (Chantix) improving depressive symptoms precipitated by quitting." Varenicline actually carries a risk of worsening mood and causing depressive symptoms in some patients who are trying to quit smoking, as noted in the guidelines 1. In fact, it has a boxed warning for neuropsychiatric side effects including depression, suicidal ideation, and mood changes. The other statements are correctly matched:

  • Nicotine does bind to mesolimbic α4β2 nicotinic receptors (which is key to its addictive properties)
  • Smoking does enhance the release of acetylcholine and norepinephrine in the brain
  • Nicotine replacement therapy does have a long safety record spanning decades of clinical use, with studies showing its efficacy and safety 1. When prescribing varenicline for smoking cessation, it's essential to monitor patients for mood changes, especially those with pre-existing psychiatric conditions, and to discontinue the medication if concerning neuropsychiatric symptoms develop. Key points to consider when using varenicline include its efficacy in smoking cessation, potential side effects, and the importance of patient monitoring, as outlined in recent guidelines and studies 1.

From the FDA Drug Label

Varenicline binds with high affinity and selectivity at α 4β 2 neuronal nicotinic acetylcholine receptors. The statement that is incorrectly matched is:

  • A Nicotine: Binds to the mesolimbic a4ß2 subtype of Nicotinic Receptor (Nn) is correct as the drug label for Varenicline mentions that it binds to α 4β 2 neuronal nicotinic acetylcholine receptors, and nicotine also binds to these receptors.
  • B Smoking: Enhances the release of Ach and norepinephrine is correct, but the label does not provide information about this.
  • C NRT: Long safety record is correct, but the label does not provide information about this.
  • D Varenicline: Improving depressive symptoms precipitated by quitting is not supported by the label, which does not mention improving depressive symptoms. The FDA drug label does not answer the question about NRT and smoking, but it does provide information about Varenicline and nicotine binding to α 4β 2 receptors. The correct answer is D, as the label for Varenicline does not mention improving depressive symptoms precipitated by quitting 2.

From the Research

Incorrectly Matched Statement

The following statements are correctly matched except for one:

  • A Nicotine: Binds to the mesolimbic a4ß2 subtype of Nicotinic Receptor (Nn)
  • B Smoking: Enhances the release of Ach and norepinephrine
  • C NRT: Long safety record
  • D Varenicline: Improving depressive symptoms precipitated by quitting

Analysis of Options

  • Option A is correct as nicotine does bind to the mesolimbic a4ß2 subtype of Nicotinic Receptor (Nn) 3.
  • Option B is correct as smoking does enhance the release of Ach and norepinephrine.
  • Option C is correct as NRT has a long safety record 3, 4.
  • Option D is incorrect as varenicline has been associated with depressive symptoms and suicidal behavior, rather than improving them 3, 4, 5, 6, 7.

Correct Answer

The correct answer is D Varenicline: Improving depressive symptoms precipitated by quitting, as varenicline has been linked to an increased risk of depression and suicidal behavior, rather than improving depressive symptoms 4. Some studies suggest that varenicline may be well-tolerated and effective for smoking cessation in certain populations, such as those with schizophrenia 5, and may even have cognitive-enhancing effects 7. However, the overall evidence suggests that varenicline is not associated with an improvement in depressive symptoms, but rather an increased risk of depression and suicidal behavior 3, 4, 6.

Key Points

  • Nicotine binds to the mesolimbic a4ß2 subtype of Nicotinic Receptor (Nn) 3.
  • Smoking enhances the release of Ach and norepinephrine.
  • NRT has a long safety record 3, 4.
  • Varenicline is associated with an increased risk of depression and suicidal behavior, rather than improving depressive symptoms 3, 4, 5, 6, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nicotine receptor partial agonists for smoking cessation.

The Cochrane database of systematic reviews, 2008

Research

Nicotine receptor partial agonists for smoking cessation.

The Cochrane database of systematic reviews, 2007

Research

Effects of short-term varenicline administration on emotional and cognitive processing in healthy, non-smoking adults: a randomized, double-blind, study.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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