Nortriptyline is a prescription-only medication approved for the treatment of depression or major depressive disorder (MDD). It belongs to the group of second-generation tricyclic antidepressant (TCA). Just like most antidepressive agents in this group, nortriptyline starts to take effect around two weeks; however, significant therapeutic effects can take longer to achieve. Remission has been reported within 10–14 weeks using standard antidepressants. But 30% to 45% of treated patients will only experience modest effects, and a considerable number of patients will not have satisfactory improvement despite long-term therapy.
The challenges of antidepressant therapy
While there are other treatment modalities available for depression, antidepressant drugs remain the standard of care. There are many types of commercially available antidepressants that have shown excellent efficacy and safety profiles through the years. Yet, the use of pharmacological methods to treat depression and other mental disorders remains a difficult endeavor. One of the challenges of antidepressant therapy is delayed onset of action. Aside from being a recurrent and disabling illness, MDD is highly prevalent worldwide and often associated with devastating impact on medical health, quality of life, and productivity. Thus, rapid improvement of depressive symptoms must be the goal of future pharmacologic interventions.
Delayed onset of action
Most drugs take several weeks to months to show significant effects. This leaves patients vulnerable to impairments associated with depression, and may lead to an increased risk of suicide. This also increases the likelihood that a patient will discontinue treatment prematurely. In the case of nortriptyline and other similar TCAs, symptoms can get worse before its antidepressant action takes effect. If you experience worsening of symptoms while taking nortriptyline, do not discontinue treatment without consulting your doctor. Missing a dose can cause withdrawal symptoms or discontinuation syndrome that can be more severe than your previous symptoms (e.g., increased feelings of depression). If you want to stop taking Pamelor, Allegron or Aventyl, talk to your prescriber first. Your doctor will taper off your medication to lower the likelihood of withdrawal symptoms.
Increased adverse effects
Generally, TCAs are not used as first-line treatment for depression as rates of patient discontinuance is high due to adverse effects. Cardiac side effects are also higher with TCAs than SSRIs; these negative effects include rapid heart rate, postural hypotension, slowed cardiac conduction, and seizures. Tricyclic drugs must be used with caution in patients with heart problems and it is contraindicated in the first six months following a myocardial infarction (heart attack). Dosulepin is the most toxic TCA and is rarely used nowadays. The least toxic TCA is nortriptyline. It may be preferred in patients with chronic nerve pain or non-responders requiring combination treatment.
Because of the narrow therapeutic index of TCAs, they are susceptible to significant drug-drug interactions, especially when combined with CYP enzymes inducers or inhibitors. They are contraindicated with other antidepressive agents such as bupropion, fluoxetine, duloxetine, and fluvoxamine, as well as other medications that can increase their plasma levels, including cimetidine, cinacalcet, and fluconazole. While Nortriptyline is not as toxic as other TCAs and also have less potential to interact with other medications, they still must be used with caution if you are taking antiarrhythmic, antipsychotic, and other antidepressant drugs. Other drugs that may cause significant interactions with nortriptyline include: tramadol, fentanyl, buspirone, lithium, and St. John’s Wort. Nortriptyline may interact with other drugs, food, and substances that are not listed here.
Switching to another antidepressant agent
Traditionally, it was believed that a wait time of two to three weeks is necessary to assess the patients’ response to antidepressants and that the therapeutic effects of these drugs cannot be fully assessed until after eight to 12 weeks. Some studies have suggested that lack of at least 20% improvement over the first two weeks of therapy could be enough reason for medication change. However, in a Genome Based Therapeutic Drugs for Depression (GENDEP) study, researchers advised against early stopping of treatment. The time course of improvement following an antidepressant treatment varies from patient to patient. You may experience rapid improvement in a couple of weeks or a delayed onset of action at two to four weeks. Even if you don’t experience notable improvement in the first two weeks of treatment, the study suggested continuing treatment in adequate doses, as patients still have a 40% to 50% chance of responding to nortriptyline if they continue treatment for six to eight weeks.