Nortriptyline Bupropion

Withdrawal from nicotine is treated in the outpatient setting. Symptomatic detoxification from nicotine is achieved with any single or combination of NRTs. Additional nonnicotine medications such as bupropion, nortriptyline, and clonidine may be helpful to reduce craving and various other withdrawal symptoms. Including a behavioral therapy component increases abstinence rates when combined with pharmacologic treatment. 

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. 

Depression SSRIs SNRIs Mirtazapine Bupropion Nortriptyline Desipramine ... 

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... 

Drug therapies include tricyclic antidepressants and SSRIs. Treatment should be continued for at least 29 weeks. Nortriptyline, amitriptyline, clomipramine, desipramine, fluvoxamine, and bupropion have been used successfully. 

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. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

The so-called atypical antidepressants such as venlafaxine and bupropion can be tried, but their safety and efficacy in treating patients with dementia have not been well studied. The older tricyclic antidepressants and monoamine oxidase inhibitors are not tolerated well by demented patients and should be avoided. Two possible exceptions are nortriptyline (Pamelor) and desipramine (Norpramin), but even these should be tried only after the newer antidepressants have proved ineffective. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

C. Nortriptyline (Pamelor) is a TCA, and as a class these drugs require at least one steady-state blood level to safely and effectively use the medication. Paroxetine, venlafaxine, and bupropion have not had blood levels correlated to response, and their relatively low toxicity does not require therapeutic blood monitoring. Nardil is a MAOI, which can be... 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Antidepressants appear sometimes useful in aiding withdrawal attempts, rather as they can he in withdrawal from benzodiazepines or alcohol. There is some positive evidence for serotonin re-uptake inhibitors and nortriptyline, but the strongest is for bupropion, which in the UK at least is the only antidepressant licensed for use as a cessation aid. Success rates for this seem to be very similar to those with nicotine replacement, approximately doubling a smoker s chances (Hughes et al. 2007). The latest option is varenicline, which acts as a partial agonist on one of the nicotinic receptors. 

Maprotiline and bupropion cause more seizures than agents such as imipramine, amitriptyline, and nortriptyline. This issue, plus other safety concerns, has significantly limited the use of maprotiline. If maprotiline is used, many clinicians start with a low dose (75 mg per day or less in elderly patients), gradually increasing by 25-mg increments over 2 or more weeks (the drug has a half-life of about 48 hours). Average doses in outpatients are 150 mg, with a maximum of 225 mg. 

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. 

FIGURE 7—40. Adrenergic combo 1 Bupropion plus norepinephrine reuptake inhibitor (NRI). Here the NE actions of bupropion are double-boosted by the NRI (either selective reboxetine or nonselective desipramine, maprotilene, nortriptyline, or protriptyline). Dopamine is single-boosted by bupropion only. 

OFFICIAL NAMES Amitriptyline (Elavil), amoxapine (Asendin), bupropion (Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), fluoxetine (Prozac), imipramine (Norfranil, Tofranil), isocarboxazid (Marplan), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Aventyl, Pamelor), paroxetine (Paxil), phenelzine (Nardil), protriptyline (Vivactil), sertraline (Zoloft), thioridazine (Mellaril), tranylcypromine (Parnate), trazodone (Desyrel), trimipramine (Sur-montil), venlafaxine (Effexor) the herb St. John s wort (Hypericum perforatum) is sold over-the-counter without prescription STREET NAMES Happy pills... 

FIGURE 3.2. Protocol for thr STARED project, (a) Level 1 (b) level 2 (c) level 3 (d) level 4. CIT, citalopram SER, sertraline BUP, bupropion VEN, venlafaxine CT, cognitive-behavioral therapy BUS, Buspirone MIRT, mirtazpine NTP, nortriptyline LI, lithium THY, thyroid hormone TCP, tranylcypromine. 

Bupropion, reboxetine, nortriptyline, desipramlne, maprotlllne, atomoxetine (all potentially powerful enhancers of noradrenergic action, but observe for activation of bipolar disorder and suicidal Ideation)... 

Add or switch to or from pro-noradrenergic agents (e.g., atomoxetine, reboxetine, other SNRIs, mirtazapine, maprotiline, nortriptyline, desipramine, bupropion) with caution... 

Nortriptyline Bupropion P-blockers Propanolol Metoprolol Timolol Bufaralol... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, fluoxetine, fluvoxamine, imipramine, meperidine, nefazodone, nortriptyline, paroxetine, pizotifen, protriptyline, rizatriptan, sertraline, sibutramine, sumatriptan, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Bupropion SR and nortriptyline appear to be effective with this population. 

Simultaneous amoxapine, clovoxamine, desipramine, fenfluramine, fluvoxamine, nor-fluoxetine, nortriptyline, propranolol, protriptyline, sertraline Noninterfering amitriptyline, atenolol, bupropion, carbamazepine, chlordiazepoxide, ci-talopram, clomipramine, clozapine, cyclobenzaprine, doxepin, imipramine, loxapine, me-toprolol, mianserin, moclobemide, nomifensine, pindolol, thioridazine, tranyl[Pg.626]

OTHER THERAPEUTIC USES OE THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologicaUy to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nortriptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy. 

Carbamazepine induces hepatic catabolic enzymes, with a consequent reduction in serum levels of antidepressants (mainly described with amitriptyline, desipramine, doxepin, imipramine, mianserin, and nortriptyline). A decrease in bupropion serum levels was also reported with carbamazepine. These effects were not observed with clomipramine. Fluoxetine and fluvoxamine inhibit the metabolism of carbamazepine and valproate (up to 30% and 50% increases in serum levels, respectively). No significant interaction has yet been found between paroxetine and carbamazepine or valproate. 

Nortriptyline, a tricyclic antidepressant (TCA), is a non-selective norepinephrine reuptake inhibitor, and long-term abstinence outcomes are not significantly different from bupropion. However, only NRT and bupropion are currently approved by the FDA for the treatment of tobacco dependence. ... 

---