Ademetionine

Soeken 2002 meta-analysis (J Fam Pract) included 11 SAMe vs NSAID and placebo RCTs in knee and hip osteoarthritis: SAMe 1200 mg/day was as effective as NSAIDs (ibuprofen, naproxen, piroxicam) on pain and function scales with better gastrointestinal tolerability. AAOS 2021 (Management of Osteoarthritis of the Knee) does not recommend SAMe: low evidence quality, insufficient large modern RCTs. ESCEO 2019 for knee osteoarthritis lists prescription glucosamine sulfate and chondroitin sulfate, paracetamol, topical NSAIDs, then systemic NSAIDs at the lowest effective course and intra-articular hyaluronic acid. If SAMe was recommended as a substitute for NSAIDs or for severe osteoarthritis with arthroplasty indication, consider seeking a second opinion from an orthopaedic surgeon.

ICD-10: M17 · ICD-11: FA01

Sharma 2017 (J Clin Psychiatry) systematic review analysed SAMe RCTs in major depressive disorder: in monotherapy and SSRI/SNRI augmentation in partial responders, SAMe 800-1600 mg/day orally showed moderate HAM-D and MADRS reductions. NICE 2022 (NG222) and SEP 2014 list CBT and SSRIs/SNRIs (sertraline, escitalopram, venlafaxine) first-line for mild-to-moderate depression; SAMe is not in the first-line list. In treatment-resistant depression and intolerance to standard antidepressants, SAMe may be considered as an adjunct after psychiatry consultation. AEMPS registers Samyr for major depression in injectable form. If SAMe was recommended for depression instead of psychiatric consultation and SSRI selection, consider seeking a second opinion.

ICD-10: F32.0 · ICD-11: 6A70.0

AEMPS registers Donamet (Abbvie) and Samyr (Abbott) for intrahepatic cholestasis in liver disease (chronic hepatitis, cirrhosis, drug- and alcohol-induced injury, intrahepatic cholestasis of pregnancy). In Russia Heptral has the same indications. For non-alcoholic fatty liver disease (NAFLD/MASLD) and steatohepatitis there is no evidence base with histological steatohepatitis resolution or fibrosis endpoints. EASL-EASD-EASO 2024 list 7-10 % weight loss via Mediterranean diet and physical activity first-line for MASLD; with concomitant T2DM – SGLT2i and GLP-1 RA; for confirmed steatohepatitis – resmetirom (Rezdiffra, FDA 2024). SAMe is not in MASLD guidelines. For intrahepatic cholestasis of pregnancy SAMe may be used as an adjunct to ursodeoxycholic acid.

ICD-10: K76.0 · ICD-11: DB92

In treatment-resistant depression (no response to two adequate antidepressant trials) SAMe is considered as one of the adjuncts alongside lithium, quetiapine, aripiprazole and triiodothyronine. Sharma 2017 systematic review included several adjunctive SAMe 800-1600 mg/day to SSRI/SNRI RCTs: moderate placebo advantage. NICE 2022 (NG222) in resistant depression lists first-line SSRI/SNRI augmentation with lithium or a second-generation antipsychotic, switching to nortriptyline or venlafaxine, and ECT in severe forms; SAMe is not first-line but is acceptable as an option after psychiatry consultation. SAMe augmentation should occur only under psychiatric supervision due to theoretical serotonin syndrome risk with SSRI/SNRI combination.

ICD-10: F33 · ICD-11: 6A72

For intrahepatic cholestasis of pregnancy, first-line therapy remains ursodeoxycholic acid. Recommended by RCOG 2022 and SMFM 2021. Ademetionine is mentioned in these documents as second-line therapy with limited data. Meta-analyses show improvement in biochemical markers (bilirubin, bile acids) but not in maternal or perinatal outcomes.

Used in hospital intravenously when ursodeoxycholic acid is ineffective or not tolerated.

ICD-10: O26.6 · ICD-11: JA65.0