Nortriptyline chemical structure
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Nortriptyline

Nortriptyline hydrochloride is 1-Propanamine, 3-(10,11-dihydro, 5H-dibenzo cyclohepten- 5-ylidene)-N-methyl-,hydrochloride. It is a second generation tricyclic antidepressant marketed under the tradenames Aventyl® and Pamelor®. It is used in the treatment of depression and childhood nocturnal enuresis (bedwetting). In addition it is sometimes used for chronic pain modification. more...

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Clinical Pharmacology

Nortriptyline inhibits the reuptake of norepinephrine (noradrenalin) and, to a lesser extent, serotonin. Operant conditioning techniques in rats and pigeons suggest that nortriptyline has a combination of stimulant and depressant properties.

Indications

FDA-approved for treatment of depressive disorders. In UK also may be used for treating nocturnal enuresis with courses of treatment lasting no moer than 3 months. Also off-label used for the treatment of panic disorder, prevention of migraine headaches and chronic pain or neuralgia modification (particularly Temporomandibular joint disorder).

Metabolism

Nortriptyline is metabolised in the liver by hepatic enzyme CYP2D6. Approximately 7 to 10 percent of caucasians are poor metabolisers and might experience more adverse effects, thus, a lower dosage is often necessary in these individuals. Blood levels of nortriptyline should be obtained during long term treatment to avoid toxicity and optimise response.

Dosage

25 - 75mg at bedtime. The dosage may be higher or lower depending on your prescribing physician. Doses above 150 mg/day are not recommended.

Side Effects

Dry mouth, drowsiness, orthostatic hypotension, urinary retention, constipation, and rapid or irregular heartbeat. Some sexual side effects may be a problem as well. Less commonly, seizures and ECG/EKG changes have been reported, especially in overdose. However, the incidence of side effects with nortriptyline is somewhat lower than with the first generation tricyclics (e.g. imipramine (Tofranil®), amitriptyline (Elavil®)).

Warnings

Persons with a history of cardiovascular disease, stroke, glaucoma and/or seizures should be given nortriptyline only under close supervision as well as those who are hyperthyroid or receiving thyroid medication. Patients should be cautioned against the use of alcohol during nortriptyline therapy.

Precautions

Pregnancy and lactation. Children under the age of 18.

Contraindications

In the acute recovery phase after myocardial infarction (e.g. heart attack). Do not use MAO Inhibitors (e.g. phenelzine, tranylcypromine, etc) with nortriptyline as hyperpyretic crises, severe convulsions, and fatalities have occurred when similar tricyclic antidepressants were used in such combinations.

Do not use if you have had serious reactions to other tricyclic antidepressants unless under the close supervision of your prescribing physician.

Overdose

Deaths may occur from overdosage with tricyclic antidepressants. Serious cardiac arrhythmias and coma are also possible. Keep this medication away from infants and children in a child-proof container.

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Drug therapy and psychologic support in smoking cessation - Tips from Other Journals
From American Family Physician, 2/1/03 by Karl E. Miller

Bupropion and nortriptyline are effective adjuncts in the treatment of tobacco dependency. Both have been proved to improve abstinence rates compared to placebo. However, in the trials that studied the effectiveness of these agents, participants received psychotherapy or had extensive contact with the project's staff, including physician reinforcement for smoking cessation, multiple episodes of brief counseling, and group meetings. All of these methods were helpful during the trials but do not meet guidelines from the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality), which state that the practice-based management for smoking cessation should include one to three brief physician follow-up visits and perhaps a referral to a smoking cessation group. The impact of psychologic intervention in combination with antidepressant therapy in smoking cessation is unknown. Hall and colleagues studied the effectiveness of antidepressant therapy and psychologic intervention on smoking cessation alone and in combination.

Persons who smoked at least 10 cigarettes per day were recruited for the study through advertisements. Those who met the inclusion criteria were randomized into one of six groups. This was a two (medical management versus psychologic intervention) by three (bupropion versus nortriptyline versus placebo) clinical trial. Medical management consisted of four sessions of five to 20 minutes with physicians who provided basic information and answered questions. The psychologic intervention consisted of five 90-minute group sessions with counselors educated at the master's degree level.

The medication arm of the study used nortriptyline titrated to a therapeutic serum level of 50 to 150 ng per mL. Bupropion was started at 150 mg per day for three days, then increased to 300 mg per day. Assessments, which included patient interviews, expired carbon monoxide measurements, and urinary cotinine levels, were made at 12, 24, 36, and 52 weeks. Smoking cessation rates were based on both patient information and laboratory confirmation.

An analysis of the six groups found no significant differences in baseline variables. Early abstinence rates for the bupropion and nortriptyline groups were equal and significantly higher than those of the placebo groups. Intense psychologic intervention had better abstinence rates than routine medical management. The combination of intense psychologic intervention and medication did not substantially improve abstinence rates over rates for either intervention alone. Minimal side effects were reported in the medication portion of the study; the number of side effects reported by the nortriptyline group was only slightly higher than the number reported by the placebo group, and rates between the bupropion and placebo groups were equal. The one-year abstinence rates for all interventions were the same as those for placebo.

The authors conclude that bupropion and nortriptyline improve abstinence rates in smokers, and that psychologic intervention produces higher abstinence rates than routine medical management. However, the combination of antidepressant medications and psychologic intervention is not more effective than use of antidepressants alone.

EDITOR'S NOTE: Recent advances in the understanding of nicotine addiction have provided physicians with multiple treatment strategies to assist patients with smoking cessation. The addition of nortriptyline as an adjuvant therapy in smoking cessation has provided physicians with a less expensive alternative to bupropion. The study by Hall and colleagues demonstrates that there is no difference in the effectiveness of bupropion, nortriptyline, and extensive psychologic intervention on smoking cessation rates. The authors also noted that at the end of the study period, all cessation rates were similar to those of placebo. This finding demonstrates the need for follow-up after the initial success of smoking cessation to maintain abstinence. The challenge is not only to assist our smoking patients to stop but also to stay tobacco free.--K.E.M.

COPYRIGHT 2003 American Academy of Family Physicians
COPYRIGHT 2003 Gale Group

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