Nortriptyline adverse effects

Bupropion may increase the levels of tricyclic antidepressants that are metabolised by CYP2D6, including desipramine, imipramine, and nortriptyline. Adverse effects including confusion, lethargy and unsteadiness have been reported with nortriptyline and bupropion. A seizure occurred in a patient given trimipramine and bupropion. 

In healthy elderly patients, cautious use of a secondary amine TCA (desi pramine or nortriptyline) may be appropriate because of their defined therapeutic plasma concentration ranges, well-established efficacy, and well-known adverse-effect profiles. 

Nortriptyline 0 Second-line Titrate up to 75-100 mg orally daily 6-12 months Dry mouth, blurred vision, and constipation are dose-dependent adverse effects. B2... 

The adverse effects of TCAs are also similar to those reported in adults (see Chapter 7). The secondary amine TCAs (e.g., desipramine, nortriptyline) are generally as well tolerated as newer antidepressants. Increased blood pressure may be more likely to occur in children than in adults but hypertension per se is rare ( 135). The most common cardiovascular effect is mild tachycardia. Despite their generally favorable adverse effect profile, secondary amine TCAs can cause serious toxicity in children and adolescents just as in adults when a taken in an overdose or when a high TCA plasma level occurs as a result of slow metabolism ( 136). For that reason, most clinicians reserve TCAs for the child or adolescent who has at least a moderate depressive disorder unresponsive to a trial of one or more newer antidepressants. In such instances, TDM should be done at least once to ensure plasma concentrations greater than 450 ng/mL do not develop ( 137). Such levels are associated with an increased risk of the following ... 

As a result, these subjects require twofold to threefold higher daily doses of nortriptyline (a 2D6 substrate) to achieve therapeutic plasma levels. Conversely, in these ultrarapid-metabolizing populations, the prodrug codeine (another 2D6 substrate) is metabolized much faster to morphine, often resulting in undesirable adverse effects of morphine, such as abdominal pain. 

The primary adverse effects of TCAs have been described in the previous text. Anticholinergic effects are perhaps the most common. These effects result in dry mouth, constipation, urinary retention, blurred vision, and confusion. They are more common with tertiary amine TCAs such as amitriptyline and imipramine than with the secondary amine TCAs desipramine and nortriptyline. The potent a-blocking property of TCAs often results in orthostatic hypotension. Hi... 

The usual daily dose ranges of antidepressants are shown in Table 30-4. Doses are almost always determined empirically the patient s acceptance of adverse effects is the usual limiting factor. Tolerance to some of the objectionable effects may develop, so that the usual pattern of treatment has been to start with small doses, increasing either to a predetermined daily dose, or to one that produces relief of depression, or to the maximum tolerated dose (except in the case of nortriptyline, which loses efficacy at plasma concentrations over 150 ng/mL). 

There are no accurate data on the worldwide use of the many tricyclic compounds listed in Table 1, and the availability of particular drugs varies from country to country. The dosage range for all these compounds is 50-300 mg/ day, with the exception of nortriptyline, which has an upper limit of 200 mg, and protriptyline, which is more potent (range 10-60 mg/day). Well-controlled comparisons are few, but it is clear that these drugs resemble each other more than they differ. Their adverse effects will be discussed for the class as a whole, with distinguishing features of specific compounds mentioned when appropriate. 

Psychodynamic supportive psychotherapy (n = 107) has been compared with psychotherapy plus medication (n = 101) in patients with major depressive disorder (93). The medications included venlafaxine, selective serotonin reuptake inhibitors, nortriptyline, and nortriptyline plus lithium. Lithium was used as an augmentation strategy in the patients who took lithium and nortriptyline (number not given). There were no differences in outcomes between the two treatment groups. No adverse effects specific to lithium were reported. 

AMOXAPINE, CLOMIPRAMINE, DOXEPIN, IMIPRAMINE, NORTRIPTYLINE, TRIMIPRAMINE PROTEASE INHIBITORS Possibly t adverse effects of amoxapine with atazanavir and ritonavir Inhibition of CYP3A4-mediated metabolism of amoxapine, clomipramine and doxepin inhibition of CYP3A4-, CYP2D6-and CYP2C9-mediated metabolism of imipramine inhibition of CYP2D6-mediated metabolism of nortriptyline and trimipramine Monitor closely... 

There are few reports on the excretion of antidepressant drugs in breast milk, even though postpartum depression is relatively common. In a 32-year-old woman who took imi-pramine 200 mg/day from 1 month postpartum imipramine and desipramine were detectable in breast milk (135). There have also been reports that amitriptyline (136), desipramine (137), and nortriptyline (138,139) were detectable in the milk of nursing mothers and in the plasma of the mothers and infants. Neither parent compound nor metabolite were detected in infants serum, except for two infants who had low concentrations of 10-hydroxynortriptyline. There were no adverse effects in any of the infants. The use of antidepressants during lactation has been reviewed, including 15 studies in which serum concentrations of antidepressants were obtained from nursing infants (140). 

This can increase TCA serum levels (clomipramine and nortriptyline). Desipramine levels were not found to be impaired, although an additive adverse effect profile is evident (nausea, tremor, and tachycardia). 

Thiothixene levels are usually increased by TCAs (doxepin and nortriptyline). Additive adverse effects have also been reported when co-administered with ciomipramine (rapid development of tardive dyskinesia). Marked extrapyramidal side-effects have been reported (a few cases only) with suipiride or thiothixene when fluoxetine is added to the regimen. Unlike the established interactions between most phenothiazines and TCAs, in which serum levels of both agents could increase, no apparent interaction is evident to date between fiupenthixoi and imipramine or any other TCA. 

The SSRIs are reported to have fewer side effects than the TCAs, which have strong anticholinergic and cardiotoxic properties (50). Among the SSRIs, there are few differences in adverse effects. The adverse effects observed for the SSRIs include nausea, diarrhea, anxiety, agitation, insomnia, and sexual dysfunction. Fewer patients have discontinued SSRIs than TCAs (amitriptyline and imipramine, and not nortriptyline, desipramine, doxepin, and clomipramine). 

A group of patients taking enzyme inhibitors (cimetidine, dox-epin, isoniazid, nortriptyline, propranolol) had a tiotixene clearance of 9.51 L/minute, which was 71% less than that seen in patients taking tiotixene alone. It seems possible that the tiotixene dose will need to be reduced in those taking these drugs but this needs confirmation. Monitor concurrent use for tiotixene adverse effects and adjust the dose accordingly. 

A case report describes a patient whose serum nortriptyline levels were raised about one-third while taking cimetidine. Another patient complained of abdominal pain and distention (but no other antimuscarinic adverse effects) when treated with nortriptyline and cimetidine. ... 

The interactions with cimetidine are well established, well documented and of clinical importance. The incidence is uncertain hut most patients could be affected. Those taking amitriptyline, desipramine, doxepin, imi-pramine or nortriptyline who are given cimetidine should be warned that adverse effects such as mouth dryness, urine retention, blurred vision, constipation, tachycardia, postural hypotension may be more likely to occur. Other tricyclic antidepressants would be expected to be similarly affected. If symptoms are troublesome reduce the dosage of the antidepressant (33 to 50% has been suggested) or replace the cimetidine with ranitidine, which does not appear to interact. Other H2-ieceptor antagonists that do not cause enzyme inhibition (e.g. famotidine and nizatidine) would also not be expected to interact. 

Venlafaxine can cause a marked increase in the antimuscaiinic adverse effects of clomipramine, desipramine and nortriptyline. There are isolated reports of seizures in a patient taking venlafaxine and trimipramine and the serotonin syndrome has been seen in patients taking venlafaxine with, or shortly before, the use of tricyclics. 

A 73-year-old man developed anticholinergic delirium on a combination of VPA and amitriptyline. The adverse effects included muscular rigidity, ataxia, dysarthria, somnolence, agitation, and disorientation. This prompted a retrospective review in which it was discovered that patients taking tricyclic antidepressant medications (amitriptyline or nortriptyline) in conjunction with VPA had higher mean serum levels of amitriptyline or nortriptyline compared to those taking tricyclic antidepressants without VPA [194 ]. 

Tricyclic Antidepressants (TCAs). The TCAs have been nsed to treat ADHD for 30 or more years. Most often used are imipramine (Tofranil) and desipramine (Norpramin), mainly becanse they are the TCAs that most specihcally increase norepinephrine activity. Remember, boosting norepinephrine activity in the brain shonld improve attention. Other TCAs, namely, amitriptyline (Elavil, Endep) and nortriptyline (Pamelor), have been used, though they also increase norepinephrine activity. TCAs do offer a modest benefit for both the inattention and the hyperactivity of ADHD. In addition, they are often effective at doses mnch lower than those required to treat depression. However, their effectiveness nsnally falls short of the stimulant medications. In addition, TCAs have considerable side effects including dry mouth, constipation, drowsiness, weight gain, and adverse cardiac effects. 

A 69-year-old man with bipolar disorder, who had been taking venlafaxine up to 337.5 mg daily, thioridazine 25 mg at night, and sodium valproate 1.2 g daily for several months with no adverse motor symptoms, experienced extrapyramidal effects 3 to 4 days after the venlafaxine had been gradually replaced by nortriptyline 50 mg daily. Symptoms persisted despite withdrawal of thioridazine, but improved on reduction of the nortriptyline dosage to 20 mg daily. The cause of the reaction was not known, but it was suggested that there may have been an interaction between venlafaxine and nortriptyline possibly modulated by thioridazine or sodium valproate. 

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