Effects of nortriptyline: A Synthesis of Findings from 6 Studies

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Original Abstract of the Article

Major findings

Multiple studies have investigated the effects of nortriptyline in treating depression in elderly patients. 4 found that 24% of elderly inpatients with late-life depression did not receive nortriptyline due to medical contraindications or side effects. The study also showed that bethanechol can be effective in reducing anticholinergic side effects of nortriptyline. 2 examined the relationship between the levels of 10-hydroxynortriptyline, a main metabolite of nortriptyline, and treatment effects in elderly outpatients. The study found no relationship between 10-hydroxynortriptyline levels and clinical response, but a correlation between lower levels of E-10-hydroxynortriptyline and symptoms of dizziness and orthostatic hypotension. 6 assessed the side effects of nortriptyline during a 3-year maintenance treatment in elderly patients with recurrent major depression. The study found a higher incidence of dry mouth in patients receiving nortriptyline compared to placebo, but no increased association with constipation, weight change, or orthostatic symptoms. 3 investigated the effects of nortriptyline and its metabolite on heart rate, blood pressure, and plasma noradrenaline levels in healthy subjects. The study found that E-10-hydroxy-NT significantly increased heart rate compared to nortriptyline and placebo. 1 found that high plasma levels of nortriptyline can inhibit its antidepressive effects and that a therapeutic plasma range of 50-150 ng/ml is recommended. 5 analyzed the clinical relevance of serum nortriptyline and 10-hydroxy-nortriptyline levels in depressed elderly patients. The study found that patients with moderate to severe anticholinergic side effects had significantly higher nortriptyline levels compared to those with mild or no symptoms, and higher levels of 10-hydroxy-nortriptyline were associated with fewer anticholinergic side effects.

Benefits and Risks

Benefits Summary

Nortriptyline may be effective in treating depression in elderly patients. It has been shown to be helpful in maintaining treatment effects in patients with recurrent major depression. 6

Risks Summary

Nortriptyline can cause side effects such as dry mouth, constipation, weight change, and orthostatic hypotension. 4 6 High plasma levels may inhibit the antidepressive effects. 1 Side effects can vary between individuals, so monitoring and adjustments are crucial.

Comparison of Studies

Commonalities

All studies highlight the potential effectiveness of nortriptyline in treating depression in elderly patients, while acknowledging the risks of side effects such as dry mouth. They also underscore the need for careful monitoring and individual tailoring of treatment.

Differences

The studies varied in their findings regarding the tolerability of nortriptyline and the prevalence of specific side effects. 4 found that 24% of patients did not receive nortriptyline due to contraindications or side effects, whereas 6 reported no discontinuations in a study of 37 patients. This disparity may be influenced by factors such as study design, patient characteristics, and dosage.

Consistency and Contradictions

The studies demonstrate both consistent and contradictory findings regarding nortriptyline’s effects and side effects. While consistent findings include the increased occurrence of dry mouth in nortriptyline-treated patients ( 4 and 6 ), there are contradictions regarding the relationship between 10-hydroxynortriptyline levels and clinical response. 2 found no correlation, while 5 observed higher levels associated with fewer anticholinergic side effects. These contradictions suggest the need for further investigation and clarification.

Considerations for Real-World Application

When considering nortriptyline for elderly patients with depression, it's crucial to be mindful of potential side effects. Dry mouth, constipation, weight change, and orthostatic hypotension are common side effects, and patients should be monitored for these. 4 Consult with a physician to discuss individual risks and benefits, especially in patients with pre-existing conditions such as heart or liver disease.

Limitations of Current Research

The studies reviewed were conducted on specific populations, primarily elderly patients with depression, and their findings may not be directly generalizable to the broader population. The study designs and patient characteristics can also impact the results, leading to limitations in generalizability and the need for further research.

Future Research Directions

Further research is needed to validate the effectiveness and safety of nortriptyline in treating depression in a larger, more diverse population. Exploring new therapeutic approaches to mitigate side effects is also essential.

Conclusion

Nortriptyline shows potential as a treatment for depression in the elderly population, but side effects should be carefully monitored. Consultation with a physician is crucial to weigh the risks and benefits and ensure the safest and most effective treatment plan for each individual. Further research is encouraged to solidify the findings and address remaining questions regarding nortriptyline’s effectiveness and safety in a broader context.

Literature analysis of 6 papers
Positive Content
4
Neutral Content
1
Negative Content
1
Article Type
6
0
0
0
6
1.

Self-inhibiting action of nortriptylin's antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression.

Author: Kragh-SorensenP, HansenC E, BaastrupP C, HvidbergE F

Effective for depression
Few side effects

A therapeutic plasma range of 50-150 ng/ml of nortriptyline was recommended for treating endogenous depression, with higher levels being associated with poorer antidepressive effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

10-Hydroxynortriptyline and treatment effects in elderly depressed patients.

Author: McCueR E, GeorgotasA, SuckowR F, CooperT B

Dizziness
Orthostatic hypotension

Nortriptyline treatment in elderly depressed patients showed no relationship between 10-hydroxynortriptyline levels and clinical response, and a correlation between lower E-10-hydroxynortriptyline levels and dizziness and orthostatic hypotension.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

3.

Effects of nortriptyline and its 10-hydroxy metabolite on plasma noradrenaline (NA) concentrations, heart rate and blood pressure during intravenous NA infusion.

Author: NordinC, CollsteP, OtaniK, ScheininM

Increased heart rate
Decreased heart rate
Increased blood pressure

Nortriptyline (NT) and its metabolite E-10-hydroxy-NT (E-10-OH-NT) were studied for their effects on heart rate and blood pressure during noradrenaline infusion. Both drugs increased heart rate before NA infusion, with E-10-OH-NT showing a greater effect. During NA infusion, both drugs showed a non-significant tendency to increase blood pressure and decrease heart rate. Plasma NA concentrations were not significantly affected by either drug.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Nortriptyline in the hospitalized elderly: tolerance and side effect reduction.

Author: RosenJ, SweetR, PollockB G, MulsantB H

Reduced antimuscarinic side effects
Side effects

Nortriptyline (NT) was generally well tolerated in elderly depressed inpatients. Bethanechol effectively reduced antimuscarinic side effects associated with NT.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

5.

Clinical relevance of serum nortriptyline and 10-hydroxy-nortriptyline measurements in the depressed elderly: a multicenter pharmacokinetic and pharmacodynamic study.

Author: KinN M, KlitgaardN, NairN P, AminM, Kragh-SorensenP, SchwarizG, AhmedS K, HolmP, KatonaC, StageK

Depression treatment
Anticholinergic side effects

This study investigated the pharmacokinetics, efficacy, and side effects of nortriptyline in elderly patients with depression. Nortriptyline levels were within the therapeutic range for most patients, and efficacy was observed, but anticholinergic side effects were associated with higher nortriptyline levels.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

A double-blind, placebo-controlled assessment of nortriptyline's side-effects during 3-year maintenance treatment in elderly patients with recurrent major depression.

Author: MarracciniR L, ReynoldsC F, HouckP R, MillerM D, FrankE, PerelJ M, CornesC, MazumdarS, KupferD J

Dry mouth
Increased heart rate

This study assessed the severity of nortriptyline side effects in older patients with recurrent major depression during long-term treatment. The study found that nortriptyline was associated with increased dry mouth, but other side effects were not significantly increased compared to placebo.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

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