Amitriptyline withdrawal effects
Pro Research Analysisby 
Searched over 200M research papers
Amitriptyline Withdrawal Effects: A Comprehensive Overview
Introduction to Amitriptyline Withdrawal
Amitriptyline, a tricyclic antidepressant (TCA), is widely used for treating depression and various types of chronic pain. However, abrupt discontinuation of amitriptyline can lead to significant withdrawal effects, which can sometimes be challenging to distinguish from the symptoms of the original condition or even from acute toxicity1. This article synthesizes the current research on the withdrawal effects of amitriptyline, highlighting key findings from multiple studies.
Common Withdrawal Symptoms
Exacerbation of Original Symptoms
One of the most common withdrawal effects is the recurrence or exacerbation of the symptoms for which amitriptyline was initially prescribed. Studies have shown that patients who discontinue amitriptyline often experience a return of depressive symptoms, including psychomotor retardation and sleep disturbances, within a few weeks of stopping the medication2 3. This recurrence can be particularly severe in patients who have been on long-term treatment3.
Neurological and Cholinergic Symptoms
Withdrawal from amitriptyline can also present with neurological signs and symptoms of cholinergic hyperactivity. These may include irritability, restlessness, and disturbances in sleep and dreams1 3. In some cases, these symptoms can mimic those of acute toxicity, making diagnosis challenging without biochemical analysis1.
Biochemical and Physiological Changes
Hyponatraemia
Hyponatraemia, a condition characterized by low sodium levels in the blood, has been reported in some cases of amitriptyline withdrawal. This condition can exacerbate the overall clinical picture, contributing to the severity of withdrawal symptoms1.
Sleep EEG Changes
Research has shown that withdrawal from amitriptyline can lead to significant changes in sleep patterns, as evidenced by alterations in sleep EEG recordings. These changes include a decrease in REM sleep, which is a common effect of many antidepressants4. Such alterations can contribute to the sleep disturbances often reported during withdrawal.
Comparative Studies and Treatment Approaches
Maintenance vs. Early Withdrawal
Studies comparing maintenance therapy with early withdrawal have found that continuing amitriptyline treatment provides a significant advantage in preventing the recurrence of depressive symptoms. There were no significant differences between double-blind and overt withdrawal methods, suggesting that the manner of withdrawal does not significantly impact the outcome2.
Amitriptyline vs. Other Treatments
In the context of treating withdrawal symptoms, amitriptyline has been compared to other medications. For instance, in the treatment of opiate-withdrawal insomnia, amitriptyline was found to be as effective as lorazepam, although it did have a hangover effect9. This suggests that amitriptyline can be a viable option for managing certain withdrawal symptoms, albeit with some side effects.
Conclusion
Amitriptyline withdrawal can lead to a range of symptoms, including the recurrence of depressive symptoms, neurological and cholinergic signs, and sleep disturbances. The severity and nature of these symptoms can vary, but they often complicate the clinical picture, making management challenging. Maintenance therapy appears to offer significant benefits in preventing symptom recurrence, and amitriptyline remains a useful option for managing specific withdrawal-related issues. Understanding these effects is crucial for clinicians to provide effective care during the withdrawal process.
Sources and full results
Most relevant research papers on this topic
Acute Amitriptyline Withdrawal and Hyponatraemia
Amitriptyline withdrawal can cause symptoms similar to acute toxicity, with hyponatraemia potentially exacerbating the patient's condition.
Case ReportEffects of maintenance amitriptyline and psychotherapy on symptoms of depression
Maintenance amitriptyline effectively prevents symptom recrudescence, while psychotherapy shows no significant advantage over low contact on symptoms.
RCT
Highly CitedRecurrence of depression after discontinuation of long-term amitriptyline treatment.
Discontinuing long-term amitriptyline treatment can lead to depression and psychomotor retardation in some patients, but longstanding side effects are relieved.
Non-RCTAcute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression.
Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile, both decreasing REM sleep, and both have an alerting effect on sleep without negatively impacting subjective sleep quality.
RCTHighly CitedThe treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo
L-tryptophan, amitriptyline, and L-tryptophan-amitriptyline combination are more effective than placebo in treating depression in general practice.
RCTHighly CitedTime course of improvement under antidepressant treatment: A survival-analytical approach
The time course of improvement under antidepressant treatment is identical for responders in all three groups, regardless of treatment modality.
Meta-AnalysisHighly CitedAmitriptyline in childhood enuresis
Amitriptyline effectively reduces nighttime enuresis in children aged 12 and over, with minimal adverse effects.
RCTAmitriptyline influences the mechanical withdrawal threshold in bone cancer pain rats by regulating glutamate transporter GLAST
Amitriptyline injections can prevent the decline in mechanical withdrawal threshold in bone cancer pain rats, potentially by inhibiting protein kinase A/protein kinase C expression and promoting glutamate-aspartate transporter trafficking onto glial cell surfaces.
Non-RCT
Animal Study
Very Rigorous JournalAmitriptyline vs. lorazepam in the treatment of opiate‐withdrawal insomnia: a randomized double‐blind study
Amitriptyline is as effective as lorazepam in treating opiate-withdrawal insomnia, except for the hangover effect.
RCTOrg 3770 versus amitriptyline: A 6‐week randomized double‐blind multicentre trial in hospitalized depressed patients
Org 3770 has similar antidepressant efficacy to amitriptyline with a more favourable tolerability profile in patients with major depression.
RCT