For therapeutic monitoring, collect specimen immediately prior to next dose.

Plasma concentrations <50 ng/mL are thought to be ineffective and those >150-175 ng/mL are often associated with a suboptimal response in patients with major depression; therefore, excessive dosage may diminish responsiveness. In addition, active metabolites of nortriptyline may accumulate in elderly patients, and toxic side effects may develop despite plasma nortriptyline concentrations <150 ng/mL. However, in one study, the pharmacokinetic parameters of nortriptyline in frail elderly patients were similar to those in younger individuals.

Nortriptyline may be less likely than other tricyclic agents to produce orthostatic hypotension, particularly in the elderly. It also may be relatively safer than other tricyclic antidepressants in cardiac patients, including those who have received a transplant.

All the tricyclic antidepressants have significant drug interactions. Being potent inducers of hepatic drug-metabolizing enzymes, particularly CYP3A4, CYP1A2, and CYP2C9, the antiepileptic drugs, carbamazepine, phenytoin, phenobarbital, and primidone stimulate the oxidative transformation of concurrently prescribed antidepressants.¹ This results in decreased drug levels of the antidepressant. To a lesser extent, co-administration of oxcarbazepine, topiramate, and felbamate can also result in decreased antidepressant levels. Other tricyclic antidepressant drug interactions: hydrocortisone, methylphenidate, and phenothiazines increase tricyclic levels; tricyclics impair the antihypertensive effectiveness of clonidine and guanethidine; tricyclics and alcohol produce additive sedative effects, tricyclics and antiparkinsonism agents have potent anticholinergic side effects, and tricyclics and MAO inhibitors should not be co-administered because of the potential for antihypertensive and CNS crises.

Tricyclics should be avoided in pregnant and lactating women because these drugs have not been established as safe. Geriatric patients are especially prone to postural hypotension, urinary retention, and sedation.² In general, it has been reported that, “Therapeutic drug monitoring of antidepressants allows us to take into account the influence of factors such as co-medications, diet, smoking habit, impaired organ function, and compliance. Therapeutic drug monitoring and genotyping are thus complementary, and their combined use contributes to improve pharmacotherapy with antidepressants and other drugs.”³