Skip to main content

Advertisement

Log in

Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Despite established links between nicotine dependence and depression, little research has examined the effects of nicotine on depression symptoms.

Objective

This study evaluated the acute and chronic effects of transdermal nicotine in nonsmokers with baseline depression symptoms during a 4-week, double-blind, placebo-controlled trial.

Methods

Nonsmokers with scores ≥10 on the Center for Epidemiological Studies Depression scale (CES-D) were recruited from the community. Mood and cognitive performance were measured at baseline (day 0) and at 1, 8, 21, and 28 days. Participants were randomly assigned to wear a placebo or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and 4; 7 mg/day during weeks 2 and 3). The final sample consisted of 11 nonsmokers with a mean baseline CES-D score of 27.36 (SD=10.53).

Results

Salivary nicotine levels indicated the majority of participants were compliant with treatment. Acute nicotine did not alter mood. After adjusting for baseline values, chronic nicotine resulted in a significant decline in CES-D scores at day 8 (3.5 mg/day), but returned to placebo levels by the last visit. This return to baseline levels was coincident with a decrease in nicotine administration from 7 to 3.5 mg/day. A similar trend for improved response inhibition as measured by the Conners Continuous Performance Task was also observed. Reported side effects were infrequent and minimal.

Conclusion

These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Anda RF, Williamson DF, Escobedo LG, Mast EE, Giovino GA, Remington PL (1990) Depression and the dynamics of smoking. A national perspective. JAMA 264:1541–1545

    Article  PubMed  CAS  Google Scholar 

  • Audrain-McGovern J, Lerman C, Wileyto EP, Rodriguez D, Shields PG (2004) Interacting effects of genetic predisposition and depression on adolescent smoking progression. Am J Psychiatry 161:1224–1230

    Article  PubMed  Google Scholar 

  • Bearden CE, Glahn DC, Monkul ES, Barrett J, Najt P, Villarreal V, Soares JC (2006) Patterns of memory impairment in bipolar disorder and unipolar major depression. Psychiatry Res 142:139–150

    Article  PubMed  Google Scholar 

  • Belluardo N, Blum M, Mudo G, Andbjer B, Fuxe K (1998) Acute intermittent nicotine treatment produces regional increases of basic fibroblast growth factor messenger RNA and protein in the tel- and diencephalon of the rat. Neuroscience 83:723–740

    Article  PubMed  CAS  Google Scholar 

  • Belluardo N, Mudo G, Blum M, Amato G, Fuxe K (2000) Neurotrophic effects of central nicotinic receptor activation. J Neural Transm Suppl:227–245

  • Belluardo N, Olsson PA, Mudo G, Sommer WH, Amato G, Fuxe K (2005) Transcription factor gene expression profiling after acute intermittent nicotine treatment in the rat cerebral cortex. Neuroscience 133:787–796

    Article  PubMed  CAS  Google Scholar 

  • Castagnoli K, Steyn SJ, Magnin G, Van Der Schyf CJ, Fourie I, Khalil A, Castagnoli N Jr (2002) Studies on the interactions of tobacco leaf and tobacco smoke constituents and monoamine oxidase. Neurotox Res 4:151–160

    Article  PubMed  CAS  Google Scholar 

  • Conners CK (1994) The Conners Continuous Performance Test. Multi-Health Systems, Inc., Toronto, Canada

    Google Scholar 

  • Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J (1996) Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull 32:67–73

    PubMed  CAS  Google Scholar 

  • Covey LS, Glassman AH, Stetner F (1997) Major depression following smoking cessation. Am J Psychiatry 154:263–265

    PubMed  CAS  Google Scholar 

  • Cox LS, Patten CA, Krahn LE, Hurt RD, Croghan IT, Wolter TD, Schroeder DR, Tri D, Offord KP (2003) The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study. J Addict Dis 22:75–85

    Article  PubMed  Google Scholar 

  • Djuric VJ, Dunn E, Overstreet DH, Dragomir A, Steiner M (1999) Antidepressant effect of ingested nicotine in female rats of Flinders resistant and sensitive lines. Physiol Behav 67:533–537

    Article  PubMed  CAS  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    Article  PubMed  CAS  Google Scholar 

  • Dursun SM, Kutcher S (1999) Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research. Med Hypotheses 52:101–109

    Article  PubMed  CAS  Google Scholar 

  • Ferguson SM, Brodkin JD, Lloyd GK, Menzaghi F (2000) Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression. Psychopharmacology (Berl) 152:295–303

    Article  CAS  Google Scholar 

  • Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, MacGregor R, Alexoff D, Shea C, Schlyer D, Wolf AP, Warner D, Zezulkova I, Cilento R (1996a) Inhibition of monoamine oxidase B in the brains of smokers. Nature 379:733–736

    Article  PubMed  CAS  Google Scholar 

  • Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, Shea C, Alexoff D, MacGregor RR, Schlyer DJ, Zezulkova I, Wolf AP (1996b) Brain monoamine oxidase A inhibition in cigarette smokers. Proc Natl Acad Sci USA 93:14065–14069

    Article  PubMed  CAS  Google Scholar 

  • Gilbert DG, McClernon FJ, Rabinovich NE, Plath LC, Jensen RA, Meliska CJ (1998) Effects of smoking abstinence on mood and craving in men: influences of negative-affect-related personality traits, habitual nicotine intake and repeated measurements. Pers Individ Differ 25:399–423

    Article  Google Scholar 

  • Gilbert DG, Crauthers DM, Mooney DK, McClernon FJ, Jensen RA (1999) Effects of monetary contingencies on smoking relapse: influences of trait depression, personality, and habitual nicotine intake. Exp Clin Psychopharmacol 7:174–181

    Article  PubMed  CAS  Google Scholar 

  • Gilbert DG, McClernon FJ, Rabinovich NE, Plath LC, Masson CL, Anderson AE, Sly KF (2002) Mood disturbance fails to resolve across 31 days of cigarette abstinence in women. J Consult Clin Psychol 70:142–152

    Article  PubMed  Google Scholar 

  • Glassman AH, Covey LS, Stetner F, Rivelli S (2001) Smoking cessation and the course of major depression: a follow-up study. Lancet 357:1929–1932

    Article  PubMed  CAS  Google Scholar 

  • Hannay HJ, Levin HS (1985) Selective Reminding Test: an examination of the equivalence of four forms. J Clin Exp Neuropsychol 7:251–263

    PubMed  CAS  Google Scholar 

  • Heishman SJ (1998) What aspects of human performance are truly enhanced by nicotine? Addiction 93:317–320

    Article  PubMed  CAS  Google Scholar 

  • Heishman SJ, Henningfield JE (2000) Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers. Psychopharmacology (Berl) 152:321–333

    Article  CAS  Google Scholar 

  • Heishman SJ, Taylor RC, Henningfield JE (1994) Nicotine and smoking: a review of effects on human performance. Exp Clin Psychopharmacol 2:345

    Article  CAS  Google Scholar 

  • Jacob P 3rd, Wilson M, Benowitz NL (1981) Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatogr 222:61–70

    PubMed  CAS  Google Scholar 

  • Jamner LD, Shapiro D, Jarvik ME (1999) Nicotine reduces the frequency of anger reports in smokers and nonsmokers with high but not low hostility: an ambulatory study. Exp Clin Psychopharmacol 7:454–463

    Article  PubMed  CAS  Google Scholar 

  • Kelton MC, Kahn HJ, Conrath CL, Newhouse PA (2000) The effects of nicotine on Parkinson’s disease. Brain Cogn 43:274–282

    PubMed  CAS  Google Scholar 

  • Kendler KS, Neale MC, MacLean CJ, Heath AC, Eaves LJ, Kessler RC (1993) Smoking and major depression. A causal analysis. Arch Gen Psychiatry 50:36–43

    PubMed  CAS  Google Scholar 

  • Kleykamp BA, Jennings JM, Blank MD, Eissenberg T (2005) The effects of nicotine on attention and working memory in never-smokers. Psychol Addict Behav 19:433–438

    Article  PubMed  Google Scholar 

  • Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH (2000) Smoking and mental illness: a population-based prevalence study. JAMA 284:2606–2610

    Article  PubMed  CAS  Google Scholar 

  • Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG (1998) Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene. Health Psychol 17:56–62

    Article  PubMed  CAS  Google Scholar 

  • Levin ED, Conners CK, Silva D, Canu W, March J (2001) Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder. Exp Clin Psychopharmacol 9:83–90

    Article  PubMed  CAS  Google Scholar 

  • Levin ED, McClernon FJ, Rezvani AH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology (Berl) 184:523–539

    Article  CAS  Google Scholar 

  • Lorr M, McNair D (1984) Manual: Profile of Mood States. Educational and Industrial Testing Service, San Diego, CA

    Google Scholar 

  • Maggio R, Riva M, Vaglini F, Fornai F, Molteni R, Armogida M, Racagni G, Corsini GU (1998) Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. J Neurochem 71:2439–2446

    Article  PubMed  CAS  Google Scholar 

  • Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562–1571

    Article  PubMed  CAS  Google Scholar 

  • McClernon FJ, Gilbert DG, Radtke R (2003) Effects of transdermal nicotine on lateralized identification and memory interference. Hum Psychopharmacol 18:339–343

    Article  PubMed  CAS  Google Scholar 

  • Perkins KA, Gerlach D, Vender J, Grobe J, Meeker J, Hutchison S (2001) Sex differences in the subjective and reinforcing effects of visual and olfactory cigarette smoke stimuli. Nicotine Tob Res 3:141–150

    Article  PubMed  CAS  Google Scholar 

  • Poltavski DV, Petros T (2006) Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits. Physiol Behav 85:833–843

    Google Scholar 

  • Potter A, Corwin J, Lang J, Piasecki M, Lenox R, Newhouse PA (1999) Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer’s disease. Psychopharmacology (Berl) 142:334–342

    Article  CAS  Google Scholar 

  • Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Google Scholar 

  • Reeves D, Kane R, Winter K (1995) Automated Neuropsychological Assessment Metrics (ANAM): test administrators guide version 3.11. National Cognitive Recovery Foundation, San Diego, CA

    Google Scholar 

  • Rose JE, Levin ED, Benowitz N (1993) Saliva nicotine as an index of plasma levels in nicotine skin patch users. Ther Drug Monit 15:431–435

    PubMed  CAS  Google Scholar 

  • Salin-Pascual RJ (2002) Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients. Rev Invest Clin 54:36–40

    PubMed  CAS  Google Scholar 

  • Salin-Pascual RJ, Drucker-Colin R (1998) A novel effect of nicotine on mood and sleep in major depression. Neuroreport 9:57–60

    PubMed  CAS  Google Scholar 

  • Salin-Pascual RJ, Rosas M, Jimenez-Genchi A, Rivera-Meza BL, Delgado-Parra V (1996) Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry 57:387–389

    PubMed  CAS  Google Scholar 

  • Smith RC, Singh A, Infante M, Khandat A, Kloos A (2002) Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. Neuropsychopharmacology 27:479–497

    Article  PubMed  CAS  Google Scholar 

  • Terracciano A, Costa PT Jr (2004) Smoking and the five-factor model of personality. Addiction 99:472–481

    Article  PubMed  Google Scholar 

  • Tizabi Y, Overstreet DH, Rezvani AH, Louis VA, Clark E Jr, Janowsky DS, Kling MA (1999) Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology (Berl) 142:193–199

    Article  CAS  Google Scholar 

  • Watkins SS, Koob GF, Markou A (2000) Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal. Nicotine Tob Res 2:19–37

    Article  PubMed  CAS  Google Scholar 

  • Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54:1063–1070

    Article  PubMed  CAS  Google Scholar 

  • White HK, Levin ED (1999) Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology (Berl) 143:158–165

    Article  CAS  Google Scholar 

  • White HK, Levin ED (2004) Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment. Psychopharmacology (Berl) 171:465–471

    Article  CAS  Google Scholar 

  • Wilens TE, Biederman J, Spencer TJ, Bostic J, Prince J, Monuteaux MC, Soriano J, Fine C, Abrams A, Rater M, Polisner D (1999) A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder. Am J Psychiatry 156:1931–1937

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression. Dr. Rose is an inventor named on several nicotine patch patents and receives royalties from sales of certain nicotine patches.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. Joseph McClernon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McClernon, F.J., Hiott, F.B., Westman, E.C. et al. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology 189, 125–133 (2006). https://doi.org/10.1007/s00213-006-0516-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0516-y

Keywords

Navigation