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This report not only focuses on the issue of therapeutic duplication, CNS depressant adverse effects, and consequences of potential combined gabapentin and pregabalin therapy but also highlights the importance of responsible prescribing particularly with centrally acting/psychoactive medications. Gabapentin and Lyrica (pregabalin) generally aren't used together due to their numerous similarities. Taking both gabapentin and Lyrica together would generally be considered a 'therapeutic duplication', but there is some evidence of the potential positive benefits of this. A randomized open-label controlled trial of the addition of gabapentin to opioid use (oral tramadol, transdermal fentanyl, or sustained-release morphine capsules (pooled)) for the treatment of NP associated with cancer demonstrated a clear benefit of combination therapy over opioid therapy alone . Recommended first-line treatments are the gabapentinoids (gabapentin, pregabalin), and antidepressants (duloxetine, amitriptyline). It is important to recognise when treatment is not successful and switch medication early, rather than up-titrating. It should be borne in mind that patients may benefit from combination therapy. We describe here a case of a female patient with a history of diabetes, diabetic neuropathy, and hypertension being prescribed both gabapentin and pregabalin concomitantly which led to adverse effects like drowsiness, dizziness, fatigue, and ataxia. A guide presented as a flowchart for a strategy for combination therapy for neuropathic pain. This flowchart is a strategic proposal for prescribing combination therapy for neuropathic pain that begins with a patient already on opioids or tricyclic antidepressants. The option for those who are already on gabapentinoids or on duloxetine is not Specifically, clinical trials employing combination therapy with pregabalin have demonstrated varying efficacy. 18 In the COMBO-DN clinical trial, pregabalin combined with duloxetine was reported to be noninferior to high-dose monotherapy with either drug. 19 On the other hand, preclinical studies have shown that combinations of pregabalin with Gabapentin (Neurontin 1) and pregabalin (Lyrica 2) are first- and second-generation α2δ ligands, respectively, and are both approved for use as adjunctive therapy in pain control. Although they do not bind to gamma-aminobutyric acid (GABA) receptors they have been successfully used to treat neuropathic pain conditions. Bottom Line: Combination of pregabalin with gabapentin could be a 4th line option in the treatment of neuropathic pain if adequate trials of other guideline-recommended treatment options fail. Review of evidence: Gabapentinoids (gabapentin Main results: We identified 21 eligible studies: four (578 participants) evaluated the combination of an opioid with gabapentin or pregabalin; two (77 participants) evaluated an opioid with a tricyclic antidepressant; one (56 participants) of gabapentin and nortriptyline; one (120 participants) of gabapentin and alpha-lipoic acid, three (90 When failed to relief the PHN with pregabalin or gabapentin, doctor will turn to gabapentin and pregabalin combination therapy. The current study concluded that gabapentin and pregabalin have the same mechanism of action, so the guidelines do not recommend their combined use. A 2022 meta-analysis of the risk of adverse events associated with opioid therapy vs. combination opioid and pregabalin therapy revealed that combination therapy may increase the risk for CNS depression and mortality, despite a tolerable gastrointestinal profile . Thus, while several clinical trials suggest improvements and/or reductions in Yes, Pregabalin in combination with Gabapentin represent a valuable addition to the existing monotherapy with either Gabapentine or Pregabalin alone in patients with neuropathic pain and inflammatory nociception. Combination of pregabalin/gabapentin with TCA is useful in patients who do not gain sufficient pain relief or tolerate either drug in high doses, or to improve sleep disturbance. In conclusion, combining Pregabalin and Gabapentin in therapy can lead to synergistic effects, providing enhanced pain relief and potentially reducing side effects. . Consulting with a healthcare professional is essential for determining the optimal dose and administration strategy for individual patients seeking the benefits of this combination Nightly oral dose of gabapentin 100 mg while titrating pregabalin down to 150 mg daily observed significant improvement in pain control, which eventually resolved while allowing further dose reduction of pregabalin over a three-week period. The patient improved following initiation of 100 mg of gabapentin and gradual reduction of pregabalin to 150 mg per day. The pain subsided completely with additional downward adjustments of pregabalin. After low levels of pain returned, gabapentin was boosted to 100 mg twice a day, with pregabalin at 25 mg. Gabapentin (Neurontin 1) and pregabalin (Lyrica 2) are first- and second-generation α2δ ligands, respectively, and are both approved for use as adjunctive therapy in pain control. Although they do not bind to gamma-aminobutyric acid (GABA) receptors they have been successfully used to treat neuropathic pain conditions. Oxycodone, gabapentin, combination, or placebo [oral] Single- vs. multi-drug comparison: Positive: Better pain relief and fewer adverse events with combination: 40: Mixed neuropathic pain: Oxycodone, pregabalin, or combination [oral] Single- vs. multi-drug comparison: Positive: Better pain relief and fewer adverse events with combination: 30 Although both trials evaluated the combination of gabapentin with an opioid, several differences should be noted: 1) Gilron 2005b evaluated morphine whereas Hanna 2008 evaluated oxycodone and 2) Gilron 2005b used a cross‐over design to compare a morphine‐gabapentin combination to each monotherapy and active placebo (lorazepam), whereas
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