Side-Effects

Bupropion Increased Fall Risk in Elderly; Nortriptyline Did Not: In 104 Major Depression patients on paroxetine for 21 weeks, those with an orthostatic drop in systolic BP, more memory impairment, and who received supplementary bupropion had more falls. Of 13 on bupropion, 28% or five patients fell. Age, depression, nortriptyline, and lithium were not associated with falling. Joo J, et al: Risk factors for falls during treatment of late-life depression. J Clin Psychiatry 2002;63:936-41. Univ Pittsburgh and NIMH.

Dry Mouth, Faster Heart Rate: In a DB 3 year follow-up study of 29 nortriptyline patients and 8 on placebo, most complaints were due to residual depression, not nortriptyline. There were no constipation or orthostatic problems. A double-blind, placebo-controlled assessment of nortriptyline's side-effects during 3-year maintenance treatment in elderly patients with recurrent major depression. Marraccini RL, Reynolds CF 3rd, et al. Int J Geriatr Psychiatry 1999 Dec;14(12):1014-8

ECG Changes Not Cause Problems: 50 elderly in long-term follow-up on nortriptyline had ECG baseline, 7 weeks, and at end averaging 55 weeks. Tachycardia and ECG changes, but no more common in cardiac patients and did not progress. Long-term ECG changes in depressed elderly patients treated with nortriptyline. ECG reverted on placebo. A double-blind, randomized, placebo-controlled evaluation. Miller MD, Curtiss EI, et al. Am J Geriatr Psychiatry 1998 Winter;6(1):59-66

Trazodone, SSRIs, Nortriptyline Low OD Potential: British Data 1993-7 Fatal toxicity index (deaths per million prescriptions): Desipramine 201; Amoxapine 93, Dothiepin 53, Tranylcypromine 44, Amitriptyline 38, Imipramine 33, Doxepin 25, Trimipramine 17, Phenelzine 15, Venlafaxine 13, Clomipramine 12, lithium 7, Moclobemide 6, Nortriptyline 5, Maprotiline 5, Trazodone 4, Mianserin 3, Mirtazapine 3, Fluvoxamine 3, Citalopram 2, Sertraline 1, Fluoxetine 1, Paroxetine 1, Nefazodone 0, Isocarboxazide 0 (isocarboxazide had a small number of prescriptions), Reboxetine 0; Anti-depressant overdose accounts for only 4-7% of all successful suicides. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. Buckley NA, McManus PR. BMJ 2002 Dec 7;325(7376):1332-3. Ed: It should be noted that research shows that patients on SSRIs kill themselves just as often as those on tricyclics due to the fact that many depressed individuals use much more deadly means of killing themselves, such as hanging, guns, and carbon monoxide, and that these far outweigh the above overdose deaths.

Main Psychiatric Drugs Affect QTc Interval: Haloperidol, Trazodone, Clozapine, Olanzapine, Carbamazepine, Tricyclics with Nortriptyline Not a Concern for Adults, Except the Elderly: The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated as a risk factor for the development of torsades de pointes and sudden death, particularly in patients predisposed to these complications due to cardiovascular impairment. In a review of all of the available literature and contacts with pharmaceutical firms, the greatest concern is concerns haloperidol, droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide, sertindole, nortriptyline, clomipramine, doxepin and the long-term use of clozapine, olanzapine and carbamazepine. Among the antidepressants, the tertiary tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have a more general impact, while the secondary tricyclic antidepressants (nortriptyline, desipramine) may impact more on children and the elderly. Torsades de pointes appeared to occur with mirtazapine. Psychotropic drugs and the ECG: focus on the QTc interval. Goodnick PJ, et al. University of Miami. . Expert Opin Pharmacother. 2002 May;3(5):479-98

Being Elderly Risk Factor for QTc: ECGs were obtained from 101 healthy individuals and 495 psychiatric patients. Abnormal QTc was defined from the healthy reference group as more than 456 ms and was present in 8% of patients. Age over 65 years (odds ratio 3.0), use of tricyclic antidepressants), thioridazine (5.4), and droperidol (6.7) were predictors of QTc lengthening, as was antipsychotic dose (high dose 5.3; very high dose 8.2). QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Reilly JG, et al. University of Newcastle Upon Tyne, UK. Lancet. 2000 Mar 25;355(9209):1048-52.

Effects of Nortriptyline on ECG in Children and Teens Called Mild: In 82 children and adolescents treated with nortriptyline (NT), all patients with available EKGs and serum NT levels were included with the exception of those receiving concomitant antipsychotic agents. Forty-three percent of subjects were receiving medications in addition to NT. The average NT dose was 2.0 mg/kg yielding mean serum NT levels of 105 ng/mL. There was a linear relationship of NT dose (mg/kg) to serum NT levels (r = 0.50, p < 0.0001). NT treatment resulted in small increases in heart rate, and PR, QRS, and QTc intervals (all ps < 0.01), of similar magnitude in children and adolescents. Individuals with the highest baseline EKG indices had the least amount of change in those indices with NT treatment. There were only a few statistically significant associations between NT dose or serum NT levels and EKG parameters. NT treatment was significantly associated with the onset of asymptomatic sinus tachycardia (heart rate > 100 beats per minute), and prolongation of the EKG QRS (> 100 msec) and QTc (> 440 msec) intervals. The effect of NT on the EKG in this age group is mild. A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents. Wilens TE, et al. MGH-Harvard. J Am Acad Child Adolesc Psychiatry. 1993 Mar;32(2):270-7.

Nortriptyline Called Little Risk in 1st Degree AV Block or Hemiblock: Ten depressed, elderly patients with cardiac conduction abnormalities were given therapeutic doses of nortriptyline. Serial ECGs revealed no clinically significant adverse cardiac changes. These data, added to the findings of previous research, suggest that tricyclic antidepressants (TCAs) present little risk in patients with first degree atrioventricular block or hemiblock. Patients with bundle-branch block and bifascicular block are at greater risk of adverse cardiac sequelae but can be treated with TCAs. To maximize safety, the authors recommend monitoring serial ECGs and plasma TCA levels. The effect of nortriptyline in elderly patients with cardiac conduction disease. Dietch JT, et al. University of California--Irvine Medical Center. J Clin Psychiatry. 1990 Feb;51(2):65-7.