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SAMe

Scientific Name(s): ADE-SD4, Ademetionine, S-adenosyl-L-methionine, S-adenosylmethionine
Common Name(s): SAM, SAMe

Clinical Overview

Use

SAMe has been studied for the treatment of depressive disorders. It has been shown to be equivalent to tricyclics, and there is a paucity of comparative data versus newer agents. Information regarding its use in osteoarthritis is conflicting and information regarding its use in liver disorders and cholestasis is limited.

Dosing

Depression: 200 to 1,600 mg/day. Liver disease: 800 to 1,000 mg/day. Osteoarthritis: 1,200 mg/day initially; then maintenance 400 mg/day in some studies.

Contraindications

SAMe should not be used in patients with bipolar depression because of reports of increased anxiety and mania.

Pregnancy/Lactation

Trials conducted in pregnant women documented no harmful effects.

Interactions

None well documented.

Adverse Reactions

Available data indicate nausea, diarrhea, constipation, mild insomnia, dizziness, irritability, anxiety, and sweating are the most commonly reported adverse reactions associated with SAMe use. Data from long-term use are lacking.

Toxicology

Toxicological studies concluded that SAMe is safe at high doses.

Source

SAMe is a naturally occurring molecule produced endogenously by a reaction of the amino acid methionine with adenosine triphosphate. Although SAMe is found in all living cells, the liver is where approximately 85% of transmethylation chemical reactions and 50% of methionine metabolism occur.1 SAMe acts as a substrate in many biological reactions and is the precursor of certain essential amino acids.2, 3 A supplement or biochemical commercially produced in yeast cell cultures, one SAMe manufacturing process utilizes fermentation of the yeast Saccharomyces cerevisiae enriched in the presence of methionine.2

History

Since SAMe's discovery in Italy in 1952, numerous clinical studies have been performed to determine its efficacy. SAMe has been used in Europe, where it has been available by prescription since the 1970s, to treat arthritis and depression. It has been available in the United States as a supplement under the Dietary Supplement and Health Education Act since 1999.3

Chemistry

SAMe is produced from L-methionine and is the principle contributor of methyl groups in a number of biochemical reactions involving enzymatic transmethylation.4 It is a precursor of the amino acids cysteine, taurine, and glutathione. SAMe initiates 3 metabolic pathways in the human body: transmethylation, transsulfuration, and polyamine synthesis.1

Transmethylation is the methyl-group transfer to other molecules, enabling them to proceed to certain anabolic or catabolic reactions. Transsulfuration is the exchange resulting in sulfates and reduced glutathione, an important antioxidant, which provides sulfhydryl groups to bind to and detoxify certain compounds. After donating the methyl group, SAMe is converted to cysteine, which is important for synthesis of glutathione and other sulfur-containing compounds.2, 3, 5

Determination of SAMe using high performance liquid chromatography has been reported.6 The native form of SAMe is labile and rapidly degrades. Stable toluenedisulfonate and 1,4-butanedisulfonate salts have been developed, and stable enteric-coated forms are now used in clinical studies.3, 7

Uses and Pharmacology

Experiments found that orally administered SAMe crosses the intestinal wall, leading to increased plasma concentrations. Oral and parenteral SAMe have been demonstrated to cross the blood-brain barrier and increase concentrations in cerebrospinal fluid.3

Depression

Because SAMe is a methyl donor in over 100 methyltransferase reactions, it is postulated that supplementation with SAMe may be effective in patients with atypical methylation processes that occur in CNS disorders such as depression.8 The exact mechanism of action is unclear, but preclinical studies demonstrated that SAMe treatment affected monoamine metabolism, as well as increased norepinephrine, dopamine, and serotonin levels. Vitamin B12 or folate deficiency are also known to decrease SAMe levels, with an associated link to depression.3, 8, 9, 10, 11, 12, 13

Animal data

The relevance of animal data for the treatment of depression with SAMe is limited by the availability of clinical trial data.

Clinical data

Despite showing a positive effect, many of the earlier trials conducted in depression had methodological limitations.14 However, several meta-analyses of quality trials and newer multicenter trials3, 9, 10, 15, 16 have confirmed SAMe's efficacy in depression to be equivalent to that of tricyclic antidepressants and greater than placebo.3, 9, 10 It has been suggested that SAMe has a more rapid onset of action compared with conventional antidepressants, the effect generally seen within a few days to 2 weeks.13 Doses of 200 to 3,200 mg/day have been used in some trials, whereas others have suggested efficacy with doses of up to 3,000 mg/day.9, 81

A randomized, double-blind, placebo-controlled 12-week study (N = 189) compared SAMe 1,600 to 3,200 mg/day to escitalopram 10 to 20 mg/day and placebo in adults with major depressive disorder (MDD). No significant differences between groups were seen, with all 3 treatments yielding a 5 to 6 point improvement in 17-item Hamilton Depression scores (HAMD-17). Response rates were 36%, 34%, and 30% for SAMe, escitalopram, and placebo, respectively. Remission rates were 28% for both SAMe, and escitalopram, and 17% for placebo.81 A subsample from this study was assessed for antidepressant efficacy of SAMe as well as contribution of histamine or carnitine to any antidepressant effects. After 12 weeks of SAMe (1,600 mg/day), data from 102 participants supported a significant group x time difference for SAMe versus placebo at every time point from week 1 to 12. Additionally, significant differences were seen in remission rates between placebo and SAMe (P = 0.003) as well as escitalopram 10 mg/day (P = 0.023). No correlation in response and either histamine or carnitine were found.87 SAMe augmentation was found to be beneficial in SSRI nonresponders. Specifically, 73 patients with MDD received SAMe 800 mg twice daily or placebo for 6 weeks, and responses and remission rates on the Hamilton rating scale for depression scores were higher for those receiving SAMe compared with placebo (36.1% vs 17.6% and 25.8% vs 11.7%, respectively).17 Seconday analysis of that study’s data showed that those receiving SAMe augmentation had significantly improved self-rated information recall, and nonsignificantly improved word finding ability.82, 83 Another study in 30 postpartum women found that SAMe 1,600 mg/day improved symptoms of depression.18, 19 Whereas a small (n = 17) double-blind trial found no statistically or clinically significant differences between SAMe or placebo add-on therapy in Hamilton Depression Scale or Montgomery-Asberg Depression Rating Scale scores among adults with refractory bipolar disorder experiencing a depressive episode of at least moderate severity.88

SAMe does not appear to be associated with an increased risk of suicide.19

Trials reported few adverse reactions with SAMe except increased anxiety and mania in patients with bipolar disorder. Methionine has increased symptoms of schizophrenia when administered in large doses.9

Other uses of SAMe may include the treatment of depression in opioid detoxification, Parkinson disease, and alcoholism.9, 20

Guidelines have been published concerning SAMe and major depressive disorder. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Major Depressive Disorder (MDD) recognizes that evidence for SAMe is modest at best either as monotherapy or augmentation therapy; data are insufficient to make a recommendation for its use in the treatment of major depressive disorder. The guidelines also state that in patients who prefer complementary and alternative therapies, SAMe may be considered.78 The Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of MDD in adults (2016) recommends SAMe as second line monotherapy in mild to moderate MDD (Level 1) and moderate to severe MDD (Level 2).79

Gastrointestinal

The liver is the main organ involved in the conversion of methionine to SAMe. Oral and parenteral SAMe increase hepatic glutathione, the primary antioxidant involved in hepatic detoxification.3, 21 Studies suggest a link between abnormal SAMe synthesis and chronic liver disorders. SAMe may act through multiple mechanisms, including inhibition of normal hepatocytes apoptosis.22

Animal data

In a study of mice, SAMe was found to attenuate liver damage caused by acetaminophen when given both before and after acetaminophen administration. Specifically, SAMe was found to reduce ALT elevations and lipid peroxidation caused by acetaminophen.23

Clinical data

The majority of SAMe trials in hepatic disease and cholestasis resulted in improved biochemical markers (eg, serum bilirubin, alkaline phosphatase) and subjective clinical symptoms (pruritus, fatigue).20, 22, 24 Improvements in mortality and time to liver transplant have not been clearly demonstrated,7, 20, 22 although a subgroup analysis of patients with mild and moderate alcohol liver cirrhosis (Child-Pugh class A and B) found a trend toward improvement.20, 24

The few trials evaluating the efficacy of SAMe versus placebo in gestational cholestasis show improvement in laboratory indices and measures of pruritus, but it appears to be less effective than ursodeoxycholic acid. Synergism between these 2 agents has been suggested.25, 26 Trial methodology has been too variable to allow for meta-analysis.25A 2013 Cochrane review involving 4 clinical trials reported SAMe as effective in reducing pruritus associated with cholestasis in pregnancy.47 In a small study of 78 women less than 36 weeks pregnant with moderate to severe intrahepatic cholestasis, the combination of SAMe and ursodeoxycholic acid improved the serum concentration of bile acids and transaminases.48

Thirty-six pregnant women with chronic hepatitis B were randomized to receive SAMe 1,000 mg intravenously (IV) once daily or stronger neo-minophagen C (containing glycyrrhizin 160 mg, glycine 1,600 mg, and L-cysteine 80 mg) IV once daily for 4 weeks. Both treatments were found to be effective therapies in normalizing ALT levels (ie, 21.4% vs 64.3%, respectively; odds ratio 6.60; 95% confidence interval, 1.2 to 35.44; P = 0.054) as well as in reducing ALT and AST levels compared with baseline, with stronger neo-minophagen. All infants were found to be healthy up to 1 year postpartum.27

A study was conducted using SAMe in patients with hepatitis C genotype-1 who did not respond to combination treatment with interferon or peginterferon and ribavirin. Specifically, patients received peginterferon and weight-based ribavirin for 2 weeks, which were then discontinued for a 1-month washout period. Patients were then given SAMe 800 mg twice daily for 2 weeks followed by peginterferon and ribavirin with SAMe for 48 weeks. SAMe was found to improve viral decline and greater induction of interferon-stimulated gene expression also occurred with the addition of SAMe. Four patients developed mild GI symptoms with SAMe, which were believed to be due to lactose in the formulation. The inclusion of lactase supplementation resulted in improvement of symptoms in 3 of these patients. It was concluded that SAMe, when added to standard therapy for hepatitis C in nonresponders, improves early viral kinetics, most likely through its effects on interferon signaling.28

A small, open-label, dose-escalation pilot study (N = 6) evaluated the effect of SAM-e among children (mean age, 14 years) with functional abdominal pain. SAM-e doses were initiated at 200 mg/day and increased 200 mg/week to a maximum of 1,400 mg; a daily multivitamin was recommended to maintain folate and vitamin B12 levels. Self-reported pain scores improved significantly over the 2-month study.80

Osteoarthritis

SAMe's efficacy in osteoarthritis was noted in earlier depression trials.3 SAMe appears to enhance native proteoglycan synthesis and secretion in human chondrocyte cultures in the cartilage of patients with osteoarthritis.29 Other postulated mechanisms for its efficacy in osteoarthritis include reducing mediators of inflammation; reversing depletion of glutathione to increase levels of the antioxidant enzyme, glutathione peroxidase; inhibiting enzymes that break down cartilage; and signaling of cartilage synthesis and maintaining DNA methylation.30, 31, 85 It also restored basal conditions after cytokine-induced cell damage in in vitro experiments, but no clinical studies have validated this observation.3, 32 The antidepressant activity of SAMe is a possible mechanism of action for the effects seen in osteoarthritis.33

Animal data

In a 6-week study of dogs with osteoarthritis, clinical signs of the disease as measured by the peak vertical force, the vertical impulse, goniometry, the Canine Brief Pain Inventory score, and the examination score, did not improve with SAMe treatment compared with placebo.34

Clinical data

Meta-analyses, primarily involving trials in Italy, have been published describing the efficacy of SAMe in reducing pain and improving function compared with nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, aspirin, ibuprofen, sulindac, piroxicam, celecoxib).3, 32, 33, 35, 36 A Cochrane systematic review examining evidence for the use of SAMe in osteoarthritis of the hip or knee was inconclusive given the small trials of questionable quality.37 A randomized, double-blind, 8-week trial in Koreans with knee OA published after the Cochrane review found no significant difference between SAMe and nabumetone for pain reduction, patient- and physician-rated treatment response, and use of acetaminophen rescue use.85

In some studies, the recommended dosage of 1,200 mg/day was exceeded for 2 weeks and was followed by a maintenance dosage of 400 mg/day.38 Oral administration of 400 mg/day for 7 days resulted in increases in synovial SAMe concentrations.3 However, a trial of SAMe versus celecoxib reported a slower onset of action for SAMe, with at least 30 days of treatment required for the onset of efficacy.33 A systematic review reported that SAMe had the lowest dropout rates from clinical trials compared with those of NSAIDs and placebo.39

Cancer

Animal/In vitro data

In a study of human umbilical vein endothelial cells in a tumor environment, SAMe inhibited angiogenesis, a process necessary for tumor growth and metastasis.40

SAMe and its metabolite 5-methylthioadenosine reduced tumor load by 43% and 40%, respectively, in mice with inflammation-induced colon cancer. Induction of genes playing a role in the pathogenesis of colon cancer was reduced with both treatments except for the expression of tumor necrosis factor-alpha and inducible nitric oxide synthase.41

SAMe was also found to prevent hepatocellular carcinoma in rats; however, it was not effective in treating established carcinoma. Its preventive effects may be associated with its pro-apopotic action and inhibition of angiogenesis.42

Clinical data

There are no clinical data to support the use of SAMe for the treatment of cancer.

Alzheimer disease

In Alzheimer disease, there appears to be a reduction in glutathione S-transferaseactivity and an increase in S-adenosylhomocysteine when there is a lack of folate. SAMe may be beneficial in Alzheimer disease because of its effects on glutathione S-transferase activity.43

Animal data

In a study of mice with vitamin B12 deficiency, supplementation with SAMe was found to decrease the production of amyloids, enhance spatial memory, and influence gene expression caused by vitamin B12 deficiency. The spreading of plaques was also reduced with supplementation.44

Clinical data

A nutraceutical formulation containing SAMe 400 mg, vitamin E, folic acid, vitamin B12, N-acetyl cysteine, and acetyl-L-carnitine improved Dementia Rating Scale (DRS) score and clock-drawing tests in patients with early-stage Alzheimer disease. Improvements were also noted by caregivers on domains of the Neuropsychiatric Inventory (NPI) and performance in the Alzheimer's Disease Cooperative Study—Activities of Daily Living. The improvements noted on the NPI at 3 and 6 months were similar to those seen with donepezil and better than those with galantamine.45 This formulation was also tested in 12 institutionalized patients with moderate- to late-stage Alzheimer disease who subsequently experienced a delay in the decline of the DRS score and clock-drawing test. Caregivers within the institution reported about a 30% improvement in the NPI, which remained elevated for at least 9 months.46

Other uses

The role of SAMe in the management of remyelination in diseases of the spinal cord has been studied.3

Decreased concentrations of SAMe in the cerebrospinal fluid of HIV-infected patients may play a role in HIV-related myelopathy.3 However, a trial among HIV-patients found L-methionine 6 g/day ineffective in reducing symptoms of myelopathy.49

A small study investigated the effects of SAMe in 44 patients with fibromyalgia. A dosage of SAMe 800 mg/day for 6 weeks improved clinical disease activity (P = 0.04), pain occurring during the last week (P = 0.002), fatigue (P = 0.02), morning stiffness (P = 0.03), and mood (P = 0.006), but tender-point scores were not impacted.50 The European League Against Rheumatism revised recommendations for the management of fibromyalgia (2016) does not recommend the use of SAMe due to limited data from small sample studies (weak recommendation against, 93% agreement).90

A meta-analysis assessing effects of antidepressants as long-term (at least 6 months) aids to smoking cessation identified 1 trial that evaluated 2 daily doses of SAMe (1,600 mg vs 800 mg). Lower quit rates were documented with SAMe versus placebo, and outcomes were similar for the 2 doses; however, the difference was not significant enough to warrant futher studies.86

Older trials have explored the potential for SAMe in migraines, aging, and sleep modulation.51, 52, 53, 54

A phase 2 trial (n = 43) assessed the efficacy of SAMe to treat hot flashes in women 18 years and older with at least 14 hot flashes per week for at least a month and sufficient enough in severity for them to seek treatment. SAMe was initiated at 400 mg once daily for 7 days on an empty stomach 30 minutes prior to breakfast, then increased to 400 mg twice daily prior to breakfast and evening meal for 5 more weeks. The primary outcome was not met, which was a target reduction in hot flash activity of at least 50%, which would be considered significantly better than the documented placebo-induced reduction of 25% to 35% in noncancer patients. Secondary quality of life outcomes identified 9 symptoms that improved and 5 that worsened. Abnormal sweating, trouble sleeping, fatigue, and muscle or joint aches and pains showed significant improvement on one scale while total mood disturbance, fatigue, mood, sleep, and concentration improved significantly on 2 other scales. SAMe was well tolerated with 1 incident of grade 3 insomnia possibly related to treatment.89

Dosing

Doses of 200 to 1,600 mg/day have typically been used in depression trials, but doses of up to 3,200 mg/day have been administered.81 One dosing strategy is to start with 400 mg/day, increasing every 5 to 7 days up to 800 mg twice daily. Due to its antidepressant effects, SAMe should ideally be taken earlier in the day (ie, before 4 PM) to prevent insomnia.8 In osteoarthritis trials, 1,200 mg/day has been used, with a maintenance dose of 400 mg/day (recommended).38 Doses of 800 to 1,000 mg/day intramuscularly, IV, and orally have been used in trials investigating liver disease and gestational cholestasis.20, 25, 26

Pregnancy / Lactation

Trials conducted in pregnant women documented no harmful effects.25 Infants naturally have SAMe levels that are 3 to 7 times higher than adults during brain development.19

Interactions

Agents with Antiplatelet Properties: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification.55, 56, 57, 58

Amphetamines: Amphetamines may enhance the adverse/toxic effect of Serotonin Modulators. The risk of serotonin syndrome may be increased. Monitor therapy.59, 60, 61

Anticoagulants: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification.55, 56, 57, 58

Antiemetics: Antiemetics (5HT3 antagonists) may enhance the serotonergic effect of serotonin modulators. This could result in serotonin syndrome. Monitor therapy.91, 92, 93, 94, 95, 96, 97, 98, 99

Antipsychotics: Serotonin modulators may enhance the adverse/toxic effect of antipsychotic agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of serotonin modulators. This could result in serotonin syndrome.Monitor therapy.62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75

Daptomycin: Dapoxetine may enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination.76, 77, 100, 101

Herbs (anticoagulant/antiplatelet properties): Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.55, 56, 57, 58

Linezolid: Linezolid may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Consider therapy modification.102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125

Metaxalone: Metaxalone may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy.126, 127, 128, 129

Methylene Blue: Methylene Blue may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination.97, 98, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157

Methylphenidate: Methylphenidate may enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy.158, 159, 160, 161

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy.62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 162

Monoamine Oxidase Inhibitor: Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Transdermal selegiline product labeling states that use with any serotonin modulator is contraindicated. Labeling for other selegiline products, rasagiline, and safinamide state that their use with certain serotonin modulators is contraindicated (meperidine, tramadol, methadone, St. John’s wort, cyclobenzaprine, dextromethorphan, and any other monoamine oxidase inhibitor) while caution is advised when combined with others. Consider therapy modification.163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186

Opioid Analgesics: Opioid Analgesics may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy.95, 140, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242

Nonsteroidal Anti-Inflammatory Agents: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Consider therapy modification.55, 56, 57, 58

Salicylates: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Consider therapy modification.57, 58

Serotonin Modulators: Serotonin modulators may enhance the adverse/toxic effect of other serotonin modulators. The development of serotonin syndrome may occur. Monitor therapy.76, 77

Tedizolid: Tedizolid may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy.92, 104, 105, 110, 111, 124, 243, 244

Thrombolytic Agents: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Consider therapy modification.55, 56, 57, 58

Tramadol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy.187, 197, 198, 203, 207, 208, 212, 214, 216, 217, 218, 219, 221, 222, 224, 227, 230, 236, 237, 239, 241, 242, 245, 246, 247

Adverse Reactions

Available data indicate nausea, diarrhea, constipation, mild insomnia, dizziness, irritability, anxiety, and sweating to be the most commonly reported adverse reactions associated with the use of SAMe. No serious adverse reactions have been reported.4, 5, 9, 15, 38, 49

Data from long-term use of SAMe are lacking. SAMe should not be used in people with bipolar disorder due to reports of increased anxiety and mania.9

Toxicology

Toxicological studies concluded that SAMe is safe even at the highest doses. Mutagenicity and carcinogenicity studies conducted in the 1980s and 1990s resulted in no safety concerns.2 More recent studies are lacking.

References

1. Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012;92(4):1515-1542.23073625
2. Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics and pharmacodynamics. Am J Med. 1987;83(5A):35-42.3318439
3. Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002;76(5):1151S-1157S.12418493
4. Deligiannidis KM, Freeman MP. Complementary and alternative medicine for the treatment of depressive disorders in women. Psychiatr Clin North Am. 2010;33(2):441-463.20385346
5. Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs. 1989;38(3):389-416.2680435
6. Delabar U, Kloor D, Luippold G, Mühlbauer B. Simultaneous determination of adenosine, S-aldenosylhomocysteine and S-adenosylmethionine in biological samples using solid-phase extraction and high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1999;724(2):231-238.10219663
7. Lieber CS. S-adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr. 2002;76(5):1183S-1187S.12418503
8. Bottiglieri T. Folate, vitamin B12, and S-adenosylmethionine. Psychiatr Clin North Am. 2013;36(1):1-13.23538072
9. Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002;76(5):1158S-1161S.12420702
10. Young SN. Clinical nutrition: 3. The fuzzy boundary between nutrition and psychopharmacology. CMAJ. 2002;166(2):205-209.11826946
11. Young SN. The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatry Neurosci. 1993;18(5):235-244.8297922
12. Ravindran AV, da Silva TL. Complementary and alternative therapies as add-on to pharmacotherapy for mood and anxiety disorders: a systematic review. J Affect Disord. 2013;150(3):707-719.23769610
13. Mischoulon D. Update and critique of natural remedies as antidepressant treatments. Obstet Gynecol Clin North Am. 2009;36(4):789-807.19944301
14. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.7941964
15. Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002;76(5):1172S-1176S.12418499
16. Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl. 1994;154:15-18.7941961
17. Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167(8):942-948.20595412
18. Cerutti R, Sichel MP, Perin M, Grussu P, Zulian O. Psychological distress during puerperium: a novel therapeutic approach using S-adenosylmethionine. Curr Ther Res. 1993;53(6):707-716.
19. Qureshi NA, Al-Bedah AM. Mood disorders and complementary and alternative medicine: a literature review. Neuropsychiatr Dis Treat. 2013:9:639-658.23700366
20. Rambaldi A, Gluud C. S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst Rev. 2006;(2):CD002235.11687153
21. Kaplowitz N. The importance and regulation of hepatic glutathione. Yale J Biol Med. 1981;54(6):497-502.7342494
22. Purohit V, Abdelmalek MF, Barve S, et al. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium. Am J Clin Nutr. 2007;86(1):14-24.17616758
23. Song Z, McClain CJ, Chen T. S-adenosylmethionine protects against acetaminophen-induced hepatotoxicity in mice. Pharmacology. 2004;71(4):199-208.15240996
24. Martínez-Chantar ML, García-Trevijano ER, Latasa MU, et al. Importance of a deficiency in S-adenosyl-L-methionine synthesis in the pathogenesis of liver injury. Am J Clin Nutr. 2002;76(5):1177S-1182S.12418501
25. Roncaglia N, Locatelli A, Arreghini A, et al. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. BJOG. 2004;111(1):17-21.14687046
26. Burrows RF, Clavisi O, Burrows E. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2001;(4):CD000493.11687082
27. Sun QF, Ding JG, Wang XF, et al. Efficacy and safety of intravenous stronger neo-minophagen C and S-adenosyl-L-methionine in treatment of pregnant woman with chronic hepatitis B: a pilot study. Med Sci Monit. 2010;16(8):PR9-PR14.20671623
28. Feld JJ, Modi AA, El-Diwany R, et al. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology. 2011;140(3):830-839.20854821
29. Harmand MF, Vilamitjana J, Maloche E, Duphil R, Ducassou D. Effects of S-adenosylmethionine on human articular chondrocyte differentiation. An in vitro study. Am J Med. 1987;83(5A):48-54.3120586
30. Hosea Blewett HJ. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis. Crit Rev Food Sci Nutr. 2008;48(5):458-463.1846403410.1080/10408390701429526
31. Lopez HL. Nutritional interventions to prevent and treat osteoarthritis. Part II: focus on micronutrients and supportive nutraceuticals. PM R. 2012;4(5 suppl):S155-S168.22632695
32. Morelli V, Naquin C, Weaver V. Alternative therapies for traditional disease states: osteoarthritis. Am Fam Physician. 2003;67(2):339-344.12562155
33. Glass GG. Osteoarthritis. Dis Mon. 2006;52(9):343-362.17142123
34. Imhoff DJ, Gordon-Evans WJ, Evans RB, Johnson AL, Griffon DJ, Swanson KS. Evaluation of S-adenosyl l-methionine in a double-blind, randomized, placebo-controlled, clinical trial for treatment of presumptive osteoarthritis in the dog. Vet Surg. 2011;40(2):228-232.21244443
35. Montrone F, Fumagalli M, Sarzi Puttini P, et al. Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis. Clin Rheumatol. 1985;4(4):484-485.3913558
36. Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med. 1987;83(5A):66-71.3318442
37. Rutjes AW, Nüesch E, Reichenbach S, Jüni P. S-adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009;(4):CD007321.1982140310.1002/14651858.CD007321.pub2
38. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002;51(5):425-430.12019049
39. De Silva V, El-Metwally A, Ernst E, Lewith G, Macfarlane GJ; Arthritis Research UK Working Group on Complementary and Alternative Medicines. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford). 2011;50(5):911-920.21169345
40. Sahin M, Sahin E, Gümüşlü S, Erdoğan A, Gültekin M. Inhibition of angiogenesis by S-adenosylmethionine. Biochem Biophys Res Commun. 2011;408(1):145-148.21463611
41. Li TW, Yang H, Peng H, Xia M, Mato JM, Lu SC. Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice. Carcinogenesis. 2012;33(2):427-435.22159228
42. Lu SC, Ramani K, Ou X, et al. S-adenosylmethionine in the chemoprevention and treatment of hepatocellular carcinoma in a rat model. Hepatology. 2009;50(2):462-471.19444874
43. Panza F, Frisardi V, Capurso C, et al. Polyunsaturated fatty acid and S-adenosylmethionine supplementation in predementia syndromes and Alzheimer’s disease: a review. ScientificWorldJournal. 2009;9:373-389.19468660
44. Fuso A, Nicolia V, Ricceri L, et al. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol Aging. 2012;33(7):1482.e1-1482.e16.22221883
45. Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a 1-year, open-label pilot study with an 16-month caregiver extension. Am J Alzheimers Dis Other Demen. 2008;23(6):571-585.19047474
46. Remington R, Chan A, Paskavitz K, Shea TB. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to late-stage Alzheimer’s disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen. 2009;24(1):27-33.19056706
47. Gurung V, Middleton P, Milan SJ, Hague W, Thornton JG. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013;6:CD000493.2379428510.1002/14651858.CD000493.pub2
48. Binder T, Salaj P, Zima T, Vítek L. Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy. J Perinat Med. 2006;34(5):383-391.16965225
49. Di Rocco A, Werner P, Bottiglieri T, et al. Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study. Neurology. 2004;63(7):1270-1275.15477550
50. Jacobsen S, Danneskiold-Samsøe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol. 1991;20(4);294-302.1925418
51. Baldessarini RJ, Kopin IJ. S-adenosylmethionine in brain and other tissues. J Neurochem. 1966;13(8);769-777.5911850
52. Bohuon C, Caillard L. S-adenosylmethionine in human blood. Clin Chim Acta. 1971;33(1):256.4938435
53. Stramentinoli G. Ademetionine, a new candidate for nutraceutical. Scandinavica. 1994;(suppl 154)59:5-41.
54. Volkmann H, Nørregaard J, Jacobsen S, Danneskiold-Samsøe B, Knoke G, Nehrdich D. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol. 1997;26(3):206-211.9225876
55. Mousa SA. Antithrombotic effects of naturally derived products on coagulation and platelet function. Methods Mol Biol. 2010;663:229-240.20617421
56. Stanger MJ, Thompson LA, Young AJ, Lieberman HR. Anticoagulant activity of select dietary supplements. Nutr Rev. 2012;70(2):107-117.22300597
57. Spolarich AE, Andrews L. An examination of the bleeding complications associated with herbal supplements, antiplatelet and anticoagulant medications. J Dent Hyg. 2007;81(3):67.17908423
58. Ulbricht C, Chao W, Costa D, Rusie-Seamon E, Weissner W, Woods J. Clinical evidence of herb-drug interactions: a systematic review by the Natural Standard Research Collaboration. Curr Drug Metab. 2008;9(10):1063-1120.19075623
59. Prior FH, Isbister GK, Dawson AH, Whyte IM. Serotonin toxicity with therapeutic doses of dexamphetamine and venlafaxine. Med J Aust. 2002;176(5):240-241.11999244
60. Parrott AC. Recreational ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002;71(4):837-844.11888574
61. Sloviter RS, Drust EG, Connor JD. Evidence that serotonin mediates some behavioral effects of amphetamine. J Pharmacol Exp Ther. 1978;206(2):348-352.308099
62. Verre M, Bossio F, Mammone A, et al. Serotonin syndrome caused by olanzapine and clomipramine. Minerva Anestesiol. 2008;74(1-2):41-45.18004234
63. Kohen I, Gordon ML, Manu P. Serotonin syndrome in elderly patients treated for psychotic depression with atypical antipsychotics and antidepressants: two case reports. CNS Spectr. 2007;12(8):596-598.17667887
64. Kaufman KR, Levitt MJ, Schiltz JF, Sunderram J. Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis. Ann Clin Psychiatry. 2006;18(3):201-204.16923659
65. Marlowe K, Schirgel D. Quetiapine and citalopram: aetiological significances in serotonin syndrome. N Z Med J. 2006;119(1237):U2058.16862204
66. Chopra P, Ng C, Schweitzer I. Serotonin syndrome associated with fluoxetine and olanzapine. World J Biol Psychiatry. 2004;5(2):114-115.15179671
67. Karki SD, Masood GR. Combination risperidone and SSRI-induced serotonin syndrome. Ann Pharmacother. 2003;37(3):388-391.12639169
68. Fisher AA, Davis MW. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. Ann Pharmacother. 2002;36(1):67-71.11816261
69. Kontaxakis VP, Havaki-Kontaxaki BJ, Christodoulou NG, Paplos KG, Christodoulou GN. Olanzapine-associated neuroleptic malignant syndrome: is there an overlap with the serotonin syndrome? Ann Gen Hosp Psychiatry. 2003;2(1):10.14613516
70. Kim JM, Lee ST, Song EC, et al. Neurotoxic syndrome developed after taking sertraline and risperidone. J Clin Neurol. 2007;3(3):165-167.19513287
71. Gambassi G, Capurso S, Tarsitani P, Liperoti R, Bernabei R. Fatal neuroleptic malignant syndrome in a previously long-term user of clozapine following its reintroduction in combination with paroxetine. Aging Clin Exp Res. 2006;18(3):266-270.16804375
72. Matsumoto R, Kitabayashi Y, Nakatomi Y, Tsuchida H, Fukui K. Neuroleptic malignant syndrome induced by quetiapine and fluvoxamine. Am J Psychiatry. 2005;162(4):812.15800166
73. Duggal HS, Kithas J. Possible neuroleptic malignant syndrome with aripiprazole and fluoxetine. Am J Psychiatry. 2005;162(2):397-398.15677611
74. Kontaxakis VP, Havaki-Kontaxaki BJ, Pappa DA, Katritsis DE, Christodoulou GN. Neuroleptic malignant syndrome after addition of paroxetine to olanzapine. J Clin Psychopharmacol. 2003;23(6):671-672.14624202
75. Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome. Ann Pharmacother. 2008;42(9):1290-1297.18628446
76. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635-642.12925718
77. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148(6):705-713.2035713
78. Gelenberg AJ, Freeman, MP, Markowitz JC, et al. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd Edition. http://psychiatryonline.org/data/Books/prac/PG_Depression3rded.pdf.
79. Ravindran AV, Balneaves LG, Faulkner G, et al; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments. Can J Psychiatry. 2016;61(9):576-587.27486153
80. Choi LJ, Huang JS. A pilot study of s-adenosylmethionine in treatment of functional abdominal pain in children. Altern Health Med. 2013;19(5):61-64.23981407
81. Mischoulon D, Price LH, Carpenter LL, et al. A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder. J Clin Psychiatry. 2014;75(4):370-376.24500245
82. Levkovitz Y, Alpert JE, Brintz CE, Mischoulon D, Papakostas GI. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. Eur Psychiatry. 2012;27(7):518-521.21665441
83. Levkovitz Y, Alpert JE, Brintz CE, Mischoulon D, Papakostas GI. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. J Affect Disord. 2012;136(3):1174-1178.21911258
84. Lopez HL. Nutritional interventions to prevent and treat osteoarthritis. Part II: focus on micronutrients and supportive nutraceuticals. PMR. 2012;4(5 suppl):S155-S168.2263269410.1016/j.pmrj.2012.02.023
85. Kim J, Lee EY, Koh EM. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther. 2009;31(12):2860-2872.20110025
86. Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;1:CD000031.24402784
87. Sarris J, Papakostas GI, Vitolo O, Fava M, Mischoulon D. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord. 2014;164:76-81.24856557
88. Murphy BL, Babb SM, Ravichandran C, Cohen BM. Oral SAMe in persistent treatment-refractory bipolar depression a double-blind, randomized clinical trial. J Clin Psychopharmacol. 2014;34(3):413-416.24699040
89. Kadakia KC, Loprinzi CL, Atherton PJ, Fee-Schroeder KC, Sood A, Barton DL. Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Support Care Cancer. 2016;24(3):1061-1069.26248653
90. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328.27377815
91. Altman CS, Jahangiri MF. Serotonin syndrome in the perioperative period. Anesth Analg. 2010;110(2):526-528.19955502
92. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.15784664
93. George M, Al-Duaij N, O’Donnell KA, Shannon MW. Obtundation and seizure following ondansetron overdose in an infant. Clin Toxicol (Phila). 2008;46(10):1064-1066.18803119
94. Gener B, Burns JM, Griffin S, Boyer EW. Administration of ondansetron is associated with lethal outcome. Pediatrics. 2010;125(6):e1514-e1517.20439600
95. Gollapudy S, Kumar V, Dhamee MS. A case of serotonin syndrome precipitated by fentanyl and ondansetron in a patient receiving paroxetine, duloxetine, and bupropion. J Clin Anesth. 2012;24(3):251-252.22537574
96. Sorscher SM. Probable serotonin syndrome variant in a patient receiving a selective serotonin reuptake inhibitor and a 5-HT3 receptor antagonist. J Psychopharmacol. 2002;16(2):191.12095081
97. Stanford BJ, Stanford SC. Postoperative delirium indicating an adverse drug interaction involving the selective serotonin reuptake inhibitor, paroxetine? J Psychopharmacol 1999;13(3):313-317.10512094
98. Stanford SC, Stanford BJ, Gillman PK. Risk of severe serotonin toxicity following co-administration of methylene blue and serotonin reuptake inhibitors: an update on a case report of post-operative delirium. J Psychopharmacol. 2010;24(10):1433-1438.19423610
99. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT(3) antagonist agents. Psychosomatics. 2001;42(3):258-260.11351116
100. Priligy (dapoxetine) [summary of product characteristics]. Mapletree Business City, Singapore: A. Menarini Singapore Pte. Ltd.; September 2013.
101. Priligy (dapoxetine) [summary of product characteristics]. Wooburn Green, Buckinghamshire, United Kingdom: A. Menarini Farmaceutica Internazionale SRL; December 2013.
102. Bergeron L, Boule M, Perreault S. Serotonin toxicity associated with concomitant use of linezolid. Ann Pharmacother. 2005;39(5):956-61.15827071
103. Bernard L, Stern R, Lew D, et al. Serotonin syndrome after concomitant treatment with linezolid and citalopram. Clin Infect Dis. 2003;36(9):1197.12715317
104. Clark DB, Andrus MR, Byrd DC. Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature. Pharmacotherapy. 2006;26(2):269-76.16466332
105. DeBellis RJ, Schaefer OP, Liquori M, et al. Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient. J Intensive Care Med. 2005;20(6):351-3.16280409
106. Go AC, Golightly LK, Barber GR. Linezolid interaction with serotonin reuptake inhibitors: report of two cases and incidence assessment. Drug Metabol Drug Interact. 2010;25(1-4):41-7.21417793
107. Hachem RY, Hicks K, Huen A, et al. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis. 2003;37(1):e8-11.12830431
108. Hendershot PE, Antal EJ, Welshman IR, et al. Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr. J Clin Pharmacol. 2001;41(5):563-72.11361053
109. Jones SL, Athan E, O'Brien D. Serotonin syndrome due to co-administration of linezolid and venlafaxine. J Antimicrob Chemother. 2004;54(1):289-90.15140859
110. Lavery S, Ravi H, McDaniel WW, et al. Linezolid and serotonin syndrome. Psychosomatics. 2001;42(5):432-4.11739912
111. Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis. 2006;42(11):1578-83.16652315
112. Lorenz RA, Vandenberg AM, Canepa EA. Serotonergic antidepressants and linezolid: a retrospective chart review and presentation of cases. Int J Psychiatry Med. 2008;38(1):81-90.18624020
113. Mason LW, Randhawa KS, Carpenter EC. Serotonin toxicity as a consequence of linezolid use in revision hip arthroplasty. Orthopedics. 2008;31(11):1140.19226083
114. McClean M, Walsh JC, Condon F. Serotonin syndrome in an orthopaedic patient secondary to linezolid therapy for MRSA infection. Ir J Med Sci. 2011;180(1):285-6.20886306
115. Miller DG, Lovell EO. Antibiotic-induced serotonin syndrome. J Emerg Med. 2011;40(1):25-27.18455905
116. Morales N, Vermette H. Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine. Psychosomatics. 2005;46(3):274-5.15883150
117. Packer S, Berman SA. Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. Am J Psychiatry. 2007;164(2):346-7.17267801
118. Sola CL, Bostwick JM, Hart DA, et al. Anticipating potential linezolid-SSRI interactions in the general hospital setting: an MAOI in disguise. Mayo Clin Proc. 2006;81(3):330-4.16529136
119. Steinberg M, Morin AK. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health Syst Pharm. 2007;64(1):59-62.17189581
120. Strouse TB, Kerrihard TN, Forscher CA, et al. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol. 2006;26(6):681-3.17110838
121. Tahir N. Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram. J Am Med Dir Assoc. 2004;5(2):111-113.14984623
122. Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43(2):180-7.16779744
123. Thomas CR, Rosenberg M, Blythe V, et al. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry. 2004;43(7):790.15213578
124. Wigen CL, Goetz MB. Serotonin syndrome and linezolid. Clin Infect Dis. 2002;34(12):1651-2.12032904
125. Zyvox (linezolid) [prescribing information]. New York, NY: Pharmacia and Upjohn Company; June 2015.
126. Bosak AR, Skolnik AB. Serotonin syndrome associated with metaxalone overdose. J Med Toxicol. 2014;10(4):402-405.24805103
127. Martini DI, Nacca N, Haswell D, Cobb T, Hodgman M. Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor. Clin Toxicol (Phila). 2015;53(3):185-187.25671244
128. Skelaxin (metaxalone) [prescribing information]. Bristol, TN: King Pharmaceuticals Inc; March 2018.
129. Surmaitis RM, Nappe TM, Cook MD. Serotonin syndrome associated with therapeutic metaxalone in a patient with cirrhosis. Am J Emerg Med. 2016;34(2):346.e5-e6.26159819
130. Bach KK, Lindsay FW, Berg LS, Howard RS. Prolonged postoperative disorientation after methylene blue infusion during parathyroidectomy. Anesth Analg. 2004;99(5):1573-1574.15502068
131. Grubb KJ, Kennedy JL, Bergin JD, Groves DS, Kern JA. The role of methylene blue in serotonin syndrome following cardiac transplantation: a case report and review of the literature. J Thorac Cardiovasc Surg. 2012;144(5):e113-e116.22982035
132. Hanna ER, Clark JA. Serotonin syndrome after cardiopulmonary bypass: a case demonstrating the interaction between methylene blue and selective serotonin reuptake inhibitors. A Case Rep. 2014;2(9):113-114.25611876
133. Harvey BH, Duvenhage I, Viljoen F, et al. Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analogues. Biochem Pharmacol. 2010;80(10):1580-1591.20699087
134. Heritier Barras AC, Walder B, Seeck M. Serotonin syndrome following methylene blue infusion: a rare complication of antidepressant therapy. J Neurol Neurosurg Psychiatry. 2010;81(12):1412-1413.20547626
135. Hencken L, To L, Ly N, Morgan JA. Serotonin syndrome following methylene blue administration for vasoplegic syndrome. J Card Surg. 2016;31(4):208-210.26934199
136. Izdes S, Altintas ND, Soykut C. Serotonin syndrome caused by administration of methylene blue to a patient receiving selective serotonin reuptake inhibitors. A Case Rep. 2014;2(9):111-112.25611875
137. Kartha SS, Chacko CE, Bumpous JM, Fleming M, Lentsch EJ, Flynn MB. Toxic metabolic encephalopathy after parathyroidectomy with methylene blue localization. Otolaryngol Head Neck Surg. 2006;135(5):765-768.17071309
138. Khan MA, North AP, Chadwick DR. Prolonged postoperative altered mental status after methylene blue infusion during parathyroidectomy: a case report and review of the literature. Ann R Coll Surg Engl. 2007;89(2):W9-W11.17346391
139. Khavandi A, Whitaker J, Gonna H. Serotonin toxicity precipitated by concomitant use of citalopram and methylene blue. Med J Aust. 2008;189(9):534-535.18976207
140. Larson KJ, Wittwer ED, Nicholson WT, Weingarten TN, Price DL, Sprung J. Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy. J Clin Anesth. 2015;27(3):247-251.25499271
141. Majithia A, Stearns MP. Methylene blue toxicity following infusion to localize parathyroid adenoma. J Laryngol Otol. 2006;120(2):138-140.16359577
142. Martindale SJ, Stedeford JC. Neurological sequelae following methylene blue injection for parathyroidectomy. Anaesthesia. 2003;58(10):1041-1042.12969068
143. Martino EA, Winterton D, Nardelli P, et al. The blue coma: the role of methylene blue in unexplained coma after cardiac surgery. J Cardiothorac Vasc Anesth. 2016;30(2):423-427.26703972
144. Mathew S, Linhartova L, Raghuraman G. Hyperpyrexia and prolonged postoperative disorientation following methylene blue infusion during parathyroidectomy. Anaesthesia. 2006;61(6):580-583.16704594
145. Methylene blue [product monograph]. Toronto, Ontario, Canada: Alveda Pharmaceuticals Inc; September 2014.
146. McDonnell AM, Rybak I, Wadleigh M, Fisher DC. Suspected serotonin syndrome in a patient being treated with methylene blue for ifosfamide encephalopathy. J Oncol Pharm Pract. 2012;18(4):436-439.22235061
147. Nicolaou G, Lee D. Methylene blue-induced serotonin syndrome presenting with ocular clonus and failure of emergence from general anesthesia [published online March 4, 2016]. Can J Anaesth. 2016;63(7):896-897.26943644
148. Ng BK, Cameron AJ, Liang R, Rahman H. Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review. Can J Anaesth. 2008;55(1):36-41.18166746
149. Pollack G, Pollack A, Delfiner J, Fernandez J. Parathyroid surgery and methylene blue: a review with guidelines for safe intraoperative use. Laryngoscope. 2009;119(10):1941-1946.19598213
150. Provayblue (methylene blue) [prescribing information]. Shirley, NY: American Regent; April 2016.
151. Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152(6):946-951.17721552
152. Rowley M, Riutort K, Shapiro D, Casler J, Festic E, Freeman WD. Methylene blue-associated serotonin syndrome: a 'green' encephalopathy after parathyroidectomy. Neurocrit Care. 2009;11(1):88-93.19263250
153. Schwiebert C, Irving C, Gillman PK. Small doses of methylene blue, previously considered safe, can precipitate serotonin toxicity. Anaesthesia. 2009;64(8):924.19604213
154. Shanmugam G, Kent B, Alsaiwadi T, Baskett R. Serotonin syndrome following cardiac surgery. Interact Cardiovasc Thorac Surg. 2008;7(4):656-657.18334520
155. Smith CJ, Wang D, Sgambelluri A, Kramer RS, Gagnon DJ. Serotonin syndrome following methylene blue administration during cardiothoracic surgery. J Pharm Pract. 2015;28(2):207-211.25613051
156. Sweet G, Standiford SB. Methylene-blue-associated encephalopathy. J Am Coll Surg. 2007;204(3):454-458.17324781
157. Top WM, Gillman PK, de Langen CJ, Kooy A. Fatal methylene blue associated serotonin toxicity. Neth J Med. 2014;72(3):179-181.24846936
158. Ishii M, Tatsuzawa Y, Yoshino A, Nomura S. Serotonin syndrome induced by augmentation of SSRI with methylphenidate. Psychiatry Clin Neurosci. 2008;62(2):246.18412855
159. Metadate (methylphenidate) [prescribing information]. Smyrna, GA: Upstate Pharma LLC; February 2017.
160. Park YM, Jung YK. Manic switch and serotonin syndrome induced by augmentation of paroxetine with methylphenidate in a patient with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(4):719-720.20298736
161. Turkoglu S. Serotonin syndrome with sertraline and methylphenidate in an adolescent. Clin Neuropharmacol. 2015;38(2):65-66.25768857
162. Metozolv ODT (metoclopramide) [prescribing information]. Raleigh, NC: Salix Pharmaceuticals, Inc., Oct 2011.
163. Azilect (rasagiline) [prescribing information]. North Wales, PA: TEVA Pharmaceuticals USA Inc; May 2014.
164. Dingemanse J, Kneer J, Wallnofer A, et al. Pharmacokinetic-pharmacodynamic interactions between two selective monoamine oxidase inhibitors: moclobemide and selegiline. Clin Neuropharmacol. 1996;19(5):399-414.8889283
165. Duval F, Flabeau O, Razafimahefa J, Spampinato U, Tison F. Encephalopathy associated with rasagiline and sertraline in Parkinson disease: possible serotonin syndrome. Mov Disord. 2013;28(10):1464.23495033
166. Emsam (selegiline) transdermal [prescribing information]. Morgantown, WV: Somerset Pharmaceuticals Inc; March 2015.
167. Fernandes C, Reddy P, Kessel B. Rasagiline-induced serotonin syndrome. Mov Disord. 2011;26(4):766-777.21370275
168. Garcia-Monco JC, Padierna A, Gomez Beldarrain M. Selegiline, fluoxetine, and depression in Parkinson's disease. Mov Disord. 1995;10(3):352.7651457
169. Gitlin MJ. Venlafaxine, monoamine oxidase inhibitors, and the serotonin syndrome. J Clin Psychopharmacol. 1997;17(1):66-67.9004070
170. Hilli J, Korhonen T, Laine K. Lack of clinically significant interactions between concomitantly administered rasagiline and escitalopram. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1526-1532.19733607
171. Jermain DM, Hughes PL, Follender AB. Potential fluoxetine-selegiline interaction. Ann Pharmacother. 1992;26(10):1300.1421659
172. Hinds NP, Hillier CE, Wiles CM. Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism. J Neurol. 2000;247(10):811.11127542
173. Laine K, Anttila M, Heinonen E, et al. Lack of adverse interactions between concomitantly administered selegiline and citalopram. Clin Neuropharmacol. 1997;20(5):419-433.9331518
174. Lefebvre H, Noblet C, Moore N, Wolf LM. Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline. Clin Endocrinol (Oxf). 1995;42(1):95-98.7889639
175. Montastruc JL, Chamontin B, Senard JM, et al. Pseudophaeochromocytoma in a parkinsonian patient treated with fluoxetine plus selegiline. Lancet. 1993;341(8844):555.8094789
176. Panisset M, Chen JJ, Rhyee SH, Conner J, Mathena J; STACCATO study investigators. Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: retrospective study (STACCATO). Pharmacotherapy. 2015;34(12):1250-1258.25314256
177. Richard IH, Kurlan R, Tanner C, et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group. Neurology. 1997;48(4):1070-1077.9109902
178. Ritter JL, Alexander B. Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. Ann Clin Psychiatry. 1997;9(1):7-13.9167831
179. Smith KM, Eyal E, Weintraub D; ADAGIO Investigators. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA Neurol. 2015;72(1):88-95.25420207
180. Suchowsersky O, deVries JD. Interaction of fluoxetine and selegiline. Can J Psychiatry. 1990;35(6):571-572.2119876
181. Toyama SC, Iacono RP. Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? Ann Pharmacother1994;28(3):405-406.8193438
182. Waters CH. Fluoxetine and selegiline - lack of significant interaction. Can J Neurol Sci. 1994;21(3):259-261.8000982
183. Wu ML, Deng JF. Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline. J Chin Med Assoc. 2009;72(8):446-449.19687003
184. Xadago (safinamide) [prescribing information]. Louisville, KY: US WorldMeds, LLC; March 2017.
185. Zelapar (selegiline) orally disintegrating tablet [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; July 2014.
186. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991;337(8735):246.1670882
187. Abadie D, Rousseau V, Logerot S, Cottin J, Montastruc JL, Montastruc F. Serotonin syndrome: analysis of cases registered in the French pharmacovigilance database. J Clin Psychopharmacol. 2015;35(4):382-388.26082973
188. Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther. 2007;32(2):199-202.17381671
189. Alkhatib AA, Peterson KA, Tuteja AK. Serotonin syndrome as a complication of fentanyl sedation during esophagogastroduodenoscopy. Dig Dis Sci. 2010;55(1):215-216.19165596
190. Altman EM, Manos GH. Serotonin syndrome associated with citalopram and meperidine. Psychosomatics. 2007;48(4):361-363.17600178
191. Asch DA, Parker RM. The Libby Zion case. One step forward or two steps backward? N Engl J Med. 1988;318(12):771-775.3347226
192. Brown TM, Skop BP. Nitroglycerin in the treatment of the serotonin syndrome. Ann Pharmacother. 1996;30(2):191-192.8835057
193. Bush E, Miller C, Friedman I. A case of serotonin syndrome and mutism associated with methadone. J Palliat Med. 2006;9(6):1257-1259.17187532
194. Das PK, Warkentin DI, Hewko R, Forrest DL. Serotonin syndrome after concomitant treatment with linezolid and meperidine. Clin Infect Dis. 2008;46(2):264-265.18171260
195. Davis JJ, Buck NS, Swenson JD, Johnson KB, Greis PE. Serotonin syndrome manifesting as patient movement during total intravenous anesthesia with propofol and remifentanil. J Clin Anesth. 2013;25(1):52-54.23391344
196. Dougherty JA, Young H, Shafi T. Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine. Ann Pharmacother. 2002;36(10):1647-1648.12243617
197. El-Okdi NS, Lumbrezer D, Karanovic D, Ghose A, Assaly R. Serotonin syndrome after the use of tramadol and ziprasidone in a patient with a deep brain stimulator for Parkinson disease. Am J Ther. 2014;21(4):e97-e99.24158007
198. Falls BA, Gurrera RJ. Serotonin syndrome in a patient on tramadol, bupropion, trazodone, and oxycodone. Psychosomatics. 2014;55(3):305-309.24360532
199. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm. Published March 22, 2016. Accessed March 24, 2016.
200. Filter ER, Gorczynski L, Fernandes JR. Fatal intoxication with a selective serotonin reuptake inhibitor, lorazepam, and codeine. Am J Forensic Med Pathol. 2007;28(4):361-363.18043028
201. Fluoxetine and hydromorphone: serotonin syndrome? Prescrire Int. 2004;13(70):57.15148975
202. Gillman PK. Possible serotonin syndrome with moclobemide and pethidine. Med J Aust. 1995;162(10):554.7776924
203. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005;95(4):434-441.16051647
204. Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB. Interaction of serotonergic antidepressants and opioid analgesics: is serotonin syndrome going undetected? J Am Med Dir Assoc. 2005;6(4):265-269.16005413
205. Guo SL, Wu TJ, Liu CC, Ng CC, Chien CC, Sun HL. Meperidine-induced serotonin syndrome in a susceptible patient. Br J Anaesth. 2009;103(3):369-370.19556270
206. Hansen TE, Dieter K, Keepers GA. Interaction of fluoxetine and pentazocine. Am J Psychiatry. 1990;147(7):949-950.2356884
207. Hillman AD, Witenko CJ, Sultan SM, Gala G. Serotonin syndrome caused by fentanyl and methadone in a burn injury. Pharmacotherapy. 2015;35(1):112-117.25615513
208. Houlihan DJ. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. Ann Pharmacother. 2004;38(3):411-413.14970364
209. Hunter B, Kleinert MM, Osatnik J, Soria E. Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil? Anesth Analg. 2006;102(5):1589.16632855
210. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ. Cardiac surgery in a patient taking monoamine oxidase inhibitors: an adverse fentanyl reaction. Anesth Analg. 1994;78(3):593-597.8109782
211. Isenberg D, Wong SC, Curtis JA. Serotonin syndrome triggered by a single dose of suboxone. Am J Emerg Med. 2008;26(7):840.e3-840.e5.18774063
212. John AP, Koloth R. Severe serotonin toxicity and manic switch induced by combined use of tramadol and paroxetine. Aust N Z J Psychiatry. 2007;41(2):192-193.17484083
213. Karunatilake H, Buckley NA. Serotonin syndrome induced by fluvoxamine and oxycodone. Ann Pharmacother. 2006;40(1):155-157.16368927
214. Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. J R Soc Med. 1999;92(9):474-475.10645303
215. Kirschner R, Donovan JW. Serotonin syndrome precipitated by fentanyl during procedural sedation. J Emerg Med. 2010;38(4):477-480.18757161
216. Kitson R, Carr B. Tramadol and severe serotonin syndrome. Anaesthesia. 2005;60(9):934-935.16115263
217. Lamberg JJ, Gordin VN. Serotonin syndrome in a patient with chronic pain polypharmacy. Pain Med. 2014;15(8):1429-1431.22925399
218. Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K. Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology. J Clin Psychopharmacol. 2002;22(4):440-441.12172351
219. Lantz MS, Buchalter EN, Giambanco V. Serotonin syndrome following the administration of tramadol with paroxetine. Int J Geriatr Psychiatry. 1998;13(5):343-345.9658268
220. Lee J, Franz L, Goforth HW. Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine. Psychosomatics. 2009;50(6):638-639.19996237
221. Mahlberg R, Kunz D, Sasse J, Kirchheiner J. Serotonin syndrome with tramadol and citalopram. Am J Psychiatry. 2004;161(6):1129.15169709
222. Marechal C, Honorat R, Claudet I. Serotonin syndrome induced by tramadol intoxication in an 8-month-old infant. Pediatr Neurol. 2011;44(1):72-74.21147393
223. Martinez TT, Martinez DN. A case of serotonin syndrome associated with methadone overdose. Proc West Pharmacol Soc. 2008;51:42-44.19544673
224. Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother. 1997;31(2):175-177.9034418
225. Mateo-Carrasco H, Munoz-Aguilera EM, Garcia-Torrecillas JM, Abu Al-Robb H. Serotonin syndrome probably triggered by a morphine-phenelzine interaction. Pharmacotherapy. 2015;35(6):e102-e105.25903219
226. Meyer D, Halfin V. Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: a case report and critical review. J Clin Psychopharmacol. 1981;1(5):319-321.7334144
227. Mittino D, Mula M, Monaco F. Serotonin syndrome associated with tramadol-sertraline coadministration. Clin Neuropharmacol. 2004;27(3):150-151.15190240
228. Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth. 1992;39(10):1061-1066.1464133
229. Ozkardesler S, Gurpinar T, Akan M, et al. A possible perianesthetic serotonin syndrome related to intrathecal fentanyl. J Clin Anesth. 2008;20(2):143-145.18410872
230. Peacock LE, Wright F. Serotonin syndrome secondary to tramadol and citalopram. Age Ageing. 2011;40(4):528.21414947
231. Pedavally S, Fugate JE, Rabinstein AA. Serotonin syndrome in the intensive care unit: clinical presentations and precipitating medications. Neurocrit Care. 2014;21(1):108-113.24052457
232. Rang ST, Field J, Irving C. Serotonin toxicity caused by an interaction between fentanyl and paroxetine. Can J Anaesth. 2008;55(8):521-525.18676387
233. Robles LA. Serotonin syndrome induced by fentanyl in a child: case report. Clin Neuropharmacol. 2015;38(5):206-208.26366964
234. Rosebraugh CJ, Flockhart DA, Yasuda SU, Woosley RL. Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient. J Clin Pharmacol. 2001;41(2):224-227.11210406
235. Roy S, Fortier LP. Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafaxine. Can J Anaesth. 2003;50(1):32-35.12514147
236. Shahani L. Tramadol precipitating serotonin syndrome in a patient on antidepressants. J Neuropsychiatry Clin Neurosci. 2012;24(4):E52.23224488
237. Shakoor M, Ayub S, Ahad A, Ayub Z. Transient serotonin syndrome cause by concurrent use of tramadol and selective serotonin reuptake inhibitor. Am J Case Rep. 2014;15:562-564.25540831
238. Song HK. Serotonin syndrome with perioperative oxycodone and pregabalin. Pain Physician. 2013;16(5):e632-e633.24077214
239. Tashakori A, Afshari R. Tramadol overdose as a cause of serotonin syndrome: a case series. Clin Toxicol (Phila). 2010;48(4):337-341.20367390
240. Tissot TA. Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology. 2003;98(6):1511-1512.12766667
241. Venlafaxine and tramadol: serotonin syndrome. Prescrire Int. 2004;13(70):57.15148976
242. Vizcaychipi MP, Walker S, Palazzo M. Serotonin syndrome triggered by tramadol. Br J Anaesth. 2007;99(6):919.18006535
243. Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother. 2013;57(7):3060-3066.23612197
244. Sivextro (tedizolid phosphate) [prescribing information]. Lexington, MA: Cubist Pharmaceuticals US; June 2014.
245. Ultram (tramadol) [prescribing information]. Raritan, NJ: Ortho-McNeil Pharmaceutical Inc; September 2009.
246. Durela (tramadol) [product monograph]. Mississauga, Ontario, Canada: Cipher Pharmaceuticals Inc; May 2014.
247. Egberts AC, ter Borgh J, Brodie-Meijer CC. Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Int Clin Psychopharmacol. 1997;12(3):181-182.9248876

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