Every time I have stopped my supplements it seems to increase my depression for a couple of days. I couldn't tell if the depression was brought on by the supps or by stopping them. I believe it is from stopping them and maybe some others can confirm or deny that. From this article... "Methylation is critical for the synthesis of all monoamine neurotransmitters as well as histamine. For example, the enzyme that converts norepinephrine to epinephrine, phenylethanolamine N-methyltransferase, requires SAMe as a cofactor for activation. The folate and biopterin (BH4) cycles (Figure 1) help ensure adequate monoamine neurotransmitter production. Biopterin is necessary for the conversion of tryptophan to 5-hydroxytryptophan (5-HTP), phenylalanine to tyrosine, and tyrosine to L-DOPA (L-3,4-dihydroxyphenylalanine)." I know that when people start antidepressants there is a period where the receptors need to downregulate before the patient will start to feel the benefit. The time period of this I'm sure varies with the individual and the drug. I'm thinking that was methylation is restarted the "neurological brightening" that I've seen Freddd refer to might be due to the influx of these building blocks (or removing the blocks to neutotransmitter production) and the patient will get a large influx. The receptors are most likely at this time upregulated due to the low quantity of neurotransmitters. The user feels very good until the receptors slightly downregulate to compensate. For me seemed to happen after about 8 hours of feeling really good on my initial attempts at SMP at higher doses of HCbl and Mfolate. I believe when we abruptly stop SMP we are left with downregulated receptors and a lack of neurotransmitters. For me substantially increasing depression and making it extremely hard to leave the bed in the morning. This has lasted for 1-3 days each time so far. Lessening each day. I believe it would be best to taper (titrate down) the SMP supps if one wishes to stop instead of an abrupt stop. And/Or possibly on an abrupt stop compensate with supps like Tryptophan + p5p + B3, Na-Tyrosine, L-Phenylalanine.