Acute administration of nicotine has beneficial effects on a variety of neurological
            and psychiatric disorders. The purpose of this study was to determine the long-term
            effects of transdermal nicotine on sleep and major depression. Under a single blind
            protocol study where patients initially received nicotine and then switched to placebo.
            Fourteen non-smoking patients with major depression (Hamilton Rating ≥ 18) served
            as subjects. Transdermal nicotine (17.5 mg), was administered five days weekly for
            six months, three days weekly on month 7 and one day per week on month 8. From the
            9th to the 24th month, once a week a patch without nicotine substituted the nicotine patch. Sleep
            and depression was assessed throughout. REM sleep latency changed from 32.6 min. to
            78.2 min. at the end of the study, wakefulness decreased, slow wave sleep increased
            throughout the study and a transient decrease of REM sleep duration upon nicotine
            withdrawal was observed. Hamilton scores went from an initial mean score of 29.7 to
            a final score of 10.8. The results support the possible therapeutical effects of long-term
            transdermal nicotine on sleep and mood, with a carryover effect into the withdrawal
            period, even though, the conclusions should be taken with caution due to the design
            applied.
         
         
         
            
Key words
         
         
            Nicotine - Depression - Sleep disorders - REM-latency
          
      
    
   
      
         References
         
         
            - 1 
               Benca R -M, Obermeyer W -H, Thisted R -A, Gillin J -C. 
               Sleep and psychiatric disorders. A meta-analysis. 
               Arch Gen Psychiat. 
               1992; 
               49 
               651-668 
               
 
            - 2 
               Berger M, Lund R, Bronisch T, von Zerssen D. 
               REM latency in neurotic and endogenous depression and the cholinergic REM induction
               test. 
               Psychiatry Res. 
               1983; 
               10 
               13-23 
               
 
            - 3 
               Berger M,  Riemann D, Höchli D, Spiegel R. 
               The cholinergic rapid eye movement sleep induction test with RS-86. 
               Arch Gen Psychiat. 
               1989; 
               46 
               421-428 
               
 
            - 4 
               Blier P, de Montigny C, Chaput Y. 
               Modifications of the serotonin system by antidepressant treatments: implications for
               the therapeutic response in major depression. 
               J Clin Psychopharm. 
               1987; 
               7 
               24S 
               
 
            - 5 
               Borbély A, Tobler I, Loepfe M, Kupfer D -J, Ulrich R -F, Grochocinski V ,.  et al
               .
               All-night spectral analysis of the sleep EEG in untreated depressives and normal controls. 
               Psychiat Res. 
               1984; 
               12 
               27-33 
               
 
            - 6 
               Breslau N, Kilbey M -M, Andreski P. 
               Nicotine withdrawal symptoms and psychiatric disorders: findings from an epidemiological
               study of young adults. 
               Am J Psychiat. 
               1992; 
               149 
               464-469 
               
 
            - 7 
               Brunello N, Armitage R, Feinberg I, Holsboer-Trachsler E, Léger D, Linkowski P ,.
               et al .
               Depression and sleep disorders: Clinical relevance, economic burden and pharmacological
               treatment. 
               Neuropsychobiology. 
               2000; 
               42 
               107-119 
               
 
            - 8 
               Buchberger R, Wagner W. 
               Fluvoxamine: safety profile in extensive post-marketing surveillance. 
               Pharmacopsychiatry. 
               2002; 
               35 
               101-108 
               
 
            - 9 
               Buysse D -J, Hall M, Begley A, Cherry C -R, Houck P -R, Land S ,.  et al .
               Sleep and treatment response in depression: new findings using power spectral analysis. 
               Psychiat Res. 
               2001; 
               103 
               51-67 
               
 
            - 10 
               Frieboes R -M, Sonntag A, Yassouridis A, Eap C -B, Baumann P, Steiger A. 
               Clinical outcome after Trimipramine in patients with delusional depression - a pilot
               sudy. 
               Pharmacopsychiatry. 
               2003; 
               36 
               12-17 
               
 
            - 11 
               Gilbert D -J, Meliska C -J, Welser R, Estes S -L. 
               Depression, personality, and gender influence EEG, cortisol, beta-endorphin, heart
               rate, and subjective responses to smoking multiple cigarettes. 
               Personal Ind Differ. 
               1994; 
               16 
               247-264 
               
 
            - 12 
               Giles D -E, Jarrett R -B, Roffwarg H -P, Rush A -J. 
               Reduced rapid eye movement latency. A predictor of recurrence in depression. 
               Neuropsychopharmacol. 
               1987; 
               1 
               51-59 
               
 
            - 13 
               Gillin J C, Sutton L, Ruiz C. 
               The effects of scopolamine on sleep and mood in depressed patients with a history
               of alcoholism and a normal comparison group. 
               Biol Psychiatry. 
               1991; 
               30 
               157-69 
               
 
            - 14 
               Guzmán-Marín R, Alam N, Mihailescu S, Szymusiak R, McGinty D, Drucker-Colin R. 
               Subcutaneous administration of nicotine changes dorsal raphe serotonergic neurons
               discharge rate during REM sleep. 
               Brain Res. 
               2001; 
               888 
               321-325 
               
 
            - 15 
               Hasler G, Schnyder U, Klaghofer R, Angst J. 
               Treatment of depressive disorders with and without medication - A naturalistic study. 
               Pharmacopsychiatry. 
               2002; 
               35 
               235-238 
               
 
            - 16 
               Jamner L -D, Shapiro D, Jarvik M -E. 
               Nicotine reduces the frequency of anger reports in smokers and nonsmokers with high
               but not low hostility: an ambulatory study. 
               Exp Clin Psychopharmacol. 
               1999; 
               7 
               454-463 
               
 
            - 17 
               Janson A -M, Fuxe K, Agnati L -F, Jansson A, Bjelke B, Sundstrom E ,.  et al .
               Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine
               neurons in the male rat. 
               Prog Brain Res. 
               1989; 
               79 
               257-265 
               
 
            - 18 
               Leibenluft E, Wehr T -A. 
               Is sleep deprivation useful in the treatment of depression?. 
               Am J Psych. 
               1992; 
               149 
               159-168 
               
 
            - 19 
               Marks M -J, Burch J -B, Collins A -C. 
               Effects of chronic nicotine infusion on tolerance development and cholinergic receptors. 
               J Pharmacol Exp Ther. 
               1983; 
               226 
               806-816 
               
 
            - 20 
               Marks M -J,  Pauly J -R, Gross S -D, Deneris E -S, Hermans-Borgmeyer I, Heinemann F.
               et al .
               Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. 
               J Neurosci. 
               1992; 
               12 
               2765-2784 
               
 
            - 21 
               McGinty D -J, Harper R -M. 
               Dorsal raphe neurons: depression of firing during sleep in cats. 
               Brain Res. 
               1976; 
               101 
               569-575 
               
 
            - 22 
               Mihailescu S, Drucker-Colín R. 
               Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. 
               Arch Med Res. 
               2000; 
               31 
               131-144 
               
 
            - 23 
               Mihailescu S, Guzmán-Marín R, Drucker-Colín R. 
               Nicotine stimulation of dorsal raphe neurons: effects on laterodorsal and pedunculopontine
               neurons. 
               Eur Neuro-psychopharmacol. 
               2001; 
               11 
               359-366 
               
 
            - 24 
               Pomerleau C -S, Pomerleau O -F. 
               Euphoriant effects of nicotine in smokers. 
               Psychopharmacol. 
               1992; 
               108 
               460-465 
               
 
            - 25 Rechtschaffen A, Kales A -A. A Manual of Standardized Terminology, Techniques and
               Scoring System for Sleep Stages of Human Subjects. Washington; Public Health Service
               1968 
 
            - 26 
               Riemann D, Voderholzer U, Cohrs S, Rodenbeck A, Hajak G, Rüther E ,.  et al .
               Trimipramine in primary insomnia: Results of a polysomnographic double-blind controlled
               study. 
               Pharmacopsychiatry. 
               2002; 
               35  
               165-174 
               
 
            - 27 
               Rush A -J, Erman M -K, Giles D -E, Schlesser M -A, Carpenter G, Vasavada N ,.  et
               al .
               Polysomnographic findings in recently drug-free and clinically remitted depressed
               patients. 
               Arch Gen Psychiat. 
               1986; 
               43 
               878-884 
               
 
            - 28 
               Salín-Pascual R -J, de la Fuente J -R, Galicia-Polo L, Drucker-Colín R. 
               Effects of transdermal nicotine on mood and sleep in nonsmoking major depressed patients. 
               Psychopharmacol. 
               1995; 
               121 
               476-479 
               
 
            - 29 
               Salín-Pascual R -J, Drucker-Colín R. 
               A novel effect of nicotine on mood and sleep in major depression. 
               NeuroReport. 
               1998; 
               9 
               57-60 
               
 
            - 30 
               Schwartz R, Kellar K. 
               In vivo regulation of [3H] acetylcholine recognition sites in brain by nicotinic cholinergic
               drugs. 
               J Neurochem.. 
               1985; 
               
               45 
               211-219 
               
 
            - 31 
               Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G.  et al .
               The inflammatory response system and the availability of plasma tryptophan in patients
               with primary sleep disorders and major depression. 
               J Affect Disorders. 
               1998; 
               49 
               211-219 
               
 
            - 32 
               Ueda N, Yoshimura R, Shinkai K, Nakamura J. 
               Plasma levels of cathecolamine metabolites predict the response to sulpride or fluvoxamine
               in major depression. 
               Pharmacopsychiatry. 
               2002; 
               35 
               175-181 
               
 
            - 33 
               Van den Hoofdakker R -H, Beersma D -G-M. 
               On the contribution of sleep wake physiology to the explanation and the treatment
               of depression. 
               Acta Psychiat Scand. 
               1988; 
               S341 
               53-71 
               
 
            - 34 
               Vázquez J, Guzmán-Marín R, Salín-Pascual R -J, Drucker-Colín R. 
               Transdermal nicotine on sleep and PGO spikes. 
               Brain Res. 
               1996; 
               737 
               317-320 
               
 
            - 35 
               Velázquez-Moctezuma J, Gillin J -C, Shiromani P -J. 
               The effects of specific M1 and M2 receptor agonists on REM sleep generation. 
               Brain Res. 
               1989; 
               503 
               128-131 
               
 
            - 36 
               Velázquez-Moctezuma J, Shalauta M -D, Gillin J -C, Shiromani P -J. 
               Microinjections of nicotine in the medial pontine reticular formation elicits REM
               sleep. 
               Neurosci Lett. 
               1990; 
               115 
               265-268 
               
 
            - 37 
               Warburton D -M. 
               Smoking within reason. 
               J Smoking Rel Disorders. 
               1992; 
               3 
               55-59 
               
 
         
         
         Dr. René Drucker-Colín
            Depto. de Neurociencias
            
            Instituto de Fisiología Celular
            
            Apdo. Postal 70-600
            
            Universidad Nacional Autónoma de México
            
            04510 México, D.F., México
            
            Telefon: (52-55) 5550-6662
            
            Fax: (52-55) 5550-0904
            
            eMail: drucker@servidor.unam.mx