From the Guidelines
Amitriptyline can be added to Lyrica (pregabalin) with careful medical supervision, as this combination is sometimes prescribed for neuropathic pain management, but it requires monitoring for intensified side effects like dizziness and drowsiness. The combination of these two medications is based on their different mechanisms of action, with amitriptyline affecting neurotransmitters like serotonin and norepinephrine, and pregabalin binding to calcium channels in the nervous system 1.
When considering the addition of amitriptyline to pregabalin, it's crucial to start with a low dose of amitriptyline, typically 10-25mg at bedtime, and continue with the prescribed dose of pregabalin. Patients should be aware of the potential for increased sedation and should avoid activities that require alertness until they develop tolerance to the combination.
The guidelines for managing neuropathic pain suggest that first-line treatments may include secondary-amine tricyclic antidepressants (TCAs) like amitriptyline, selective serotonin norepinephrine reuptake inhibitors (SSNRIs), or calcium channel α2δ ligands like pregabalin 1. The choice of medication and the decision to combine them should be based on the individual patient's condition, including the type of neuropathic pain, comorbidities, and potential side effects.
Given the potential for drug interactions and side effects, it's essential for patients to inform their healthcare provider about all medications they are taking and to never adjust dosages without medical guidance. The goal of combining amitriptyline with pregabalin is to achieve better pain management while minimizing adverse effects, and this should be done under the close supervision of a healthcare provider.
Key considerations for this combination include:
- Starting with a low dose of amitriptyline and gradually increasing as needed and tolerated.
- Monitoring for side effects such as dizziness, drowsiness, and dry mouth, which may be intensified by the combination.
- Adjusting the dose of either medication based on the patient's response and tolerance.
- Regular follow-up with a healthcare provider to assess the effectiveness of the treatment and to manage any side effects.
From the Research
Combination of Amitriptyline and Lyrica (Pregabalin)
- The combination of amitriptyline and pregabalin has been studied in various clinical trials for the treatment of neuropathic pain and fibromyalgia syndrome 2, 3, 4.
- A multicentre, double-blind, randomised crossover trial compared the efficacy and tolerability of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain, and found that combination treatment was well tolerated and led to improved pain relief in patients with suboptimal pain control with monotherapy 2.
- A controlled, randomized study investigated the hypothesis that the combined use of pregabalin plus paroxetine for fibromyalgia management would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological Studies Depression Scale (CESDS) scores, but higher tolerability than the combined use of pregabalin plus either amitriptyline or venlafaxine, and found that the combined use of pregabalin plus paroxetine resulted in significantly lower SSS-8 and CESDS scores and higher medication tolerability compared to the other combinations 3.
- A randomized, controlled trial compared the efficacy and safety of pregabalin and amitriptyline monotherapy with their low-dose combination in patients with neuropathic pain, and found that combining pregabalin and amitriptyline at low doses proved to be equally effective but more tolerable compared to individual higher dosage monotherapy 4.
Efficacy and Safety
- The studies suggest that the combination of amitriptyline and pregabalin is effective and well tolerated for the treatment of neuropathic pain and fibromyalgia syndrome 2, 3, 4.
- However, the studies also report some adverse events, such as dizziness, nausea, and dry mouth, which were more common in the amitriptyline monotherapy group 3, 4.
- The combination of amitriptyline and pregabalin may be a useful treatment option for patients who do not respond to monotherapy or who experience adverse events with higher doses of individual medications 2, 4.
Pharmacokinetics
- A drug-drug interaction study found that the combination of mirtazapine and amitriptyline altered the pharmacokinetics of either compound to a minor extent, but had no major effects on tolerability 5.
- However, the study did not investigate the combination of amitriptyline and pregabalin, and more research is needed to fully understand the pharmacokinetic interactions between these medications.