Nortriptyline Smoking

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Hall SM, Reus VI, Munoz RF, et al Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen Psychiatry 55 683-690, 1998 Hall SM, Humfleet GL, Reus VI, et al Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry 59 930-936, 2002 Hayford KE, Patten CA, Rummans TA, et al Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry 174 173-178, 1999... 

Oncken CA, Hatsukami DK, Lupo VR, et al Effects of short-term use of nicotine gum in pregnant smokers. Clin Pharmacol Ther 59 654-61, 1996 Pomerleau OF, Pomerleau CS Neuroregulators and the reinforcement of smoking towards a biobehavioral explanation. Neurosci Biobehav Rev 8 503—513, 1984 Prochazka AV, Weaver MJ, Keller RT, et al A randomized trial of nortriptyline for smoking cessation. Arch Intern Med 158 2035-2039, 1998 Puska P, Korhonen HJ, Vartiainen E, et al Combined use of nicotine patch and gum compared with gum alone in smoking cessation a clinical trial in North Karelia. Tob Control 4 231-235, 1995... 

Hall, S., Reus, V., Munoz, R. et al. Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch. Gen. Psychiatry. 55 683, 1998. 

Nicotine replacement therapies can be combined with each other and/or bupropion to increase long-term abstinence rates. bOo not abruptly discontinue. Taper up initially, and taper off once therapy is complete. cClonidine and nortriptyline are not FDA approved for smoking cessation. 

Volpicelli JR, Alterman Al, Hayashida M, O Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49 876-880 Wagena EJ, Knipschild P, Zeegers MP (2005) Should nortriptyline be used as a first-line aid to help smokers quit Results from a systematic review and meta-analysis. Addiction 100 317-326 Waters AJ, Shiffman S, Sayette MA, Paty JA, Gwaltney CJ, Balabanis MH (2004) Cue-provoked craving and nicotine replacement therapy in smoking cessation. J Consult CUn Psychol 72 1136-1143... 

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

Other antidepressants may also have a role in the treatment of smoking cessation. Nortriptyline has been shown to be helpful in smoking cessation, but the effects have not been as consistent as those seen with bupropion. 

The use of antidepressants outside the treatment of MDD tends to require specific agents. For example, the TCAs and SNRIs appear to be useful in the treatment of pain conditions, but other antidepressant classes appear to be far less effective. SSRIs and the highly serotonergic TCA, clomipramine, are effective in the treatment of OCD, but noradrenergic antidepressants have not proved to be as helpful for this condition. Bupropion and nortriptyline have usefulness in the treatment of smoking cessation, but SSRIs have not been proven useful. Thus, outside the treatment of depression, the choice of antidepressant is primarily dependent on the known benefit of a particular antidepressant or class for a particular indication. 

When treating nicotine dependence, nortriptyline should be initiated 10-28 days before cessafion of smoking fo achieve sfeady drug sfafes... 

Noradrenergic reuptake inhibitors such as nortriptyline can be used as a second-line treatment for smoking cessation, cocaine dependence, and attention deficit disorder... 

Barbiturates and heavy smoking induce nortriptyline metabolism and decrease therapeutic efficacy phenothiazines and haloperidol decrease its metabolism, decreasing therapeutic efficacy methylphenidate, cimetidine, oral contraceptives, propoxyphene, and beta-blockers may inhibit nortriptyline metabolism, increasing plasma levels and toxicity (see Tables 5 through 7). 

Smoking tobacco reduces the plasma levels of amitriptyline, clomipramine, desipramine, imipramine and nortriptyline, but this does not appear to result in a clinically significant interaction. 

Two studies found no difference between the steady-state nortriptyline plasma levels of tobacco smokers and non-smokers, but others have found that smoking tobacco lowers the plasma levels of amitriptyline, clomipramine, desipramine, imipramine" and nortriptyline. For example a 25% reduction in plasma nortriptyline levels was found in one study, and a 45% reduction in total levels of imipramine and its metabolite, desipramine, was found in another." ... 

Narmati TR, Burrows GD, Maguire KP, Rubinstein G, Sechins BA, Davies B. Cigarette smoking and plasma nortriptyline levels. Clin Pharmacol Ther 911) 21, 453-6. 

Perry PJ, Browne JL, Prince RA, Alexander B, Tsuang MT. Effects of smoking on nortriptyline plasma concentrations in depressed patients. TherDrugMonit (1986) 8, 279-84. 

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