Depression continues as a prevalent mental illness with the burden of disease second to heart disease only. Lifetime prevalence rates for depression in Australia stands at approximately 25 percent for females and 12 percent for males. Antidepressant medication treatment assists with approximately 30 percent of acute episodes of depression and one third of patients treated for depression relapse within a year. Those individuals who have experienced two episodes have a 90 percent chance of experiencing a third, with 40 percent relapsing within 15 weeks.
Pharmacotherapy achieves acceptable results for approximately 30 percent of patients, mixed results for 40 percent and poor results for 30 percent of patients diagnosed with depression. As a result of poor or variable response to treatment, a significant proportion of depressed patients may not experience complete clinical remission of their depression. For this reason, novel approaches to enhance treatment response is currently being considered.
SAMe produces therapeutic effects similar to several classes of commonly used antidepressants, and is well tolerated at high doses. Anti-depressants typically inhibit the reuptake of neurotransmitters (e.g. serotonin), while SAMe’s role as a methylating compound enhances endogenous synthesis of neurotransmitters involved with mood such as serotonin, nor-adrenaline and mono-amines. Hence from a safety perspective SAMe can be used with existing antidepressant medications that only target neurotransmitter reuptake. While there are over 40 clinical trials assessing the efficacy of SAMe for depression with dosage ranging from 400 to 1600 mg daily, only three of these used rigorous empirical designs albeit with very small sample sizes.
In a recent pilot study (2016) participants diagnosed with established sub-optimal response to depression medication prescribed a selective serotonin reuptake inhibitor (SSRI) were randomly allocated to either 1600 mg or 800 mg daily of SAMe for 15 weeks. Both SAMe responses achieved similiar results with a significant proportion of participants (35 percent) achieving significant symptom improvement at the end of 15 weeks supplementation. After a two week washout period, SAMe non-responders were then supplemented with magnesium orotate (Orotate, also referred to as orotic acid, is available as a salt complexed with magnesium, calcium, potassium or zinc ions. It is safe and inexpensive.) for an 8 week duration, resulting in significant clinical improvement.
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