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  1. #1
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    Default Melatonin = Depression (I confirmed it Guys)

    OK, now using the term "confirmed" loosely here Gentlemen, but here is the story:

    A while ago I had used 2-3 mgs of Melatonin per night to treat my lifelong insomnia with great initial success. However, after about 2 weeks, I started feeling immensely depressed. I started a thread on this but that thread seems to have vanished. In fact, i was able to locate another post of mine where I am linking to that thread about melatonin, yet the link has turned dead. Check it out:

    http://www.mindandmuscle.net/forum/566420-post18.html

    (click on the link in this post and see what happens... Mods, any way I can access that thread? I am pretty sure it wasn't locked by Mods)

    Anyways, 10 days ago I started Melatonin again to give it one more shot. This time, my goal was to use it every other day or maybe 4 nights a week max. I was under the very analytically-confirmed and ultra-intelligent impression that the depression during the prior episode was the result of not melatonin itself but excess sleep, one of the logical paths leading to this conclusion being that sleep deprivation can be a short term treatment for severe depression. Hence, I thought, the reverse may be true and sleeping too much can cause depression. Ex Dubsy slapped me on the head and said that such is not really possible but I knew the depressive thoughts came out of nowhere and had nothing else to attribute them to other than melatonin or longer/ deeper sleep hours.

    Long story short, I have used melatonin for the last 10-11 days every other night and for the last 2-3 days I am depressed as hell. This is VEEEEERY unusual for me. I have not had depressive episodes in hyears and certainly never experienced depressive thoughts out of the blue like this at any point in my life.
    The thoughts and emotions that I have can be best summed up by the word pessimism. I developed such a bleak outlook and such negative future projections, which is exactly what I had experienced last time melatonin.

    I have done a pubmed search with the words depression and melatonin and only get abstracts where melatonin is used to treat depression. They are having a moderate amount of success with it, but that is to be expected. If an individual who is severely depressed and hasn't had a good night's sleep in months if not years is sleeping well for the first time with melatonin, of course they are going to feel better (am I doing something wrong here? any ideas for ways/keywords to use in order to uncover studies where the effects of melatonin was observed on un-depressed people?)
    However, a google search does bring up some anecdotal reports of "since I began using melatonin, I am feeling depressed". Also check this out:
    Melatonin
    University of Maryland Medical Center
    "Some studies show that melatonin supplements worsened symptoms of depression." though which of the studies they cite at the bottom of the page -if this study is even included- says so is unclear.

    Now, one more time, am I seeing ghosts where there are none or is there a possible MOA whereby melatonin can cause depression?

    The reason I pursue melatonin is that it really does make a huge difference and seems to work in a different way than all other sleep meds I tried (and I tried a lot). Two critical differences:
    1- It produces a very alert state the next day. With all other medicines, some part of the psyche is still asleep the day after, even if you have tons of physical energy. With melatonin -and this doesn't happen every time I use melatonin but happens often- the next day I am fully awake. Every dimension of the soul is there, ready for action and fully present as opposed to dormant. I know, this is somewhat of an esoteric description, but I am sure the intelligent members of this forum got the point.
    2- The effects go beyond the immediate future while melatonin is still in the blood. Melatonin seems to reset something. After I quit using it the last time, I felt different and better for a month if not longer. I was falling asleep more easily and the next day I was more fully awake. This carryover effect dissipated with time. This time too, I feel the same may (only may) happen if I can continue to use melatonin for a while as I am feeling a change that is likely deeper and more profound than I have achieved with any other sleep medicine.
    (disclaimer here: Lunesta + 100 mg pregabalin have a similar effect and they even more dramatically reduce the need for sleep, yet I have never tried that combo two noghts in a row, let alone twice over the course of one week, and do not intend to)

    My question here is: could melatonin "reset" something and have lasting effects based on what we know of it?

    Finally, could it be helpful to try either ramelteon or agomelatine? They bind to melatonin receptor subtypes, so maybe they could still result in similar benefits in terms of sleep but due to specific as opposed to general melatonin receptor affinity, the side effetct of melatonin can be avoided. Am I kind of right or totally off base here? Other similar drugs worth looking into?

    Thanks in advance everyone....


    Finally,
    A man can be happy with any woman, as long as he is not in love with her...
    Oscar Wilde

  2. #2
    Senior Member Tussmann's Avatar
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    2-3 mg is probably overkill: http://web.mit.edu/newsoffice/2001/melatonin-1017.html

    The study used those age 50 and over, but even if participants had a "deficiency" in their natural melatonin levels, 0.3 mg seemed to correct that. In my opinion, we may even require less. But then again, standardization of supplements to an exact .1 of a mg probably isn't a norm.

    Basically, anything around 3 mg is like playing Russian roulette with your circadian rythym. Furthermore, I believe Ex Dubio and others have mentioned that melatonin should be avoided with atypical (?) depression.

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    Quote Originally Posted by Tussmann View Post
    2-3 mg is probably overkill: http://web.mit.edu/newsoffice/2001/melatonin-1017.html

    The study used those age 50 and over, but even if participants had a "deficiency" in their natural melatonin levels, 0.3 mg seemed to correct that. In my opinion, we may even require less. But then again, standardization of supplements to an exact .1 of a mg probably isn't a norm.

    Basically, anything around 3 mg is like playing Russian roulette with your circadian rythym. Furthermore, I believe Ex Dubio and others have mentioned that melatonin should be avoided with atypical (?) depression.

    Good point
    However I was not trying to restore natural melatonin levels. I am using it as a sleep aid and even 1 mg won't be enough to get the job done, because I do feel a difference between 2 and 3 mg and 2 mg is barely good enough to do what I am looking for.

    Also, take a look at this quote
    "However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3 mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100 mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled."
    from
    Melatonin and its analogs in insomnia and depre... [J Pineal Res. 2011] - PubMed - NCBI

    they are talking about 50-100 mg. Can 2-3 mg really be unsafe?
    just thinking aloud here really
    A man can be happy with any woman, as long as he is not in love with her...
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  4. #4
    Senior Member John Barleycorn's Avatar
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    Quote Originally Posted by Sub7 View Post
    they are talking about 50-100 mg. Can 2-3 mg really be unsafe?
    Depends whether you're talking oral or sublingual.

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    Quote Originally Posted by John Barleycorn View Post
    Depends whether you're talking oral or sublingual.
    should have mentioned that I tried both
    is bioavailability very different?
    I have found sublingual more effective but did not note an immense difference. It hits faster though
    A man can be happy with any woman, as long as he is not in love with her...
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    See the thread I started a while back on sleep duration and mood. One of the theories as to the effectiveness of SSRIs and also sleep deprivation is the reduction in REM sleep which is elevated in depressed individuals.

    Messing around with this part of your brain produces a wide range of effects in different people. Its a complex system with many interactions. Case in point, a drug (from memory it was Tianeptine but I can't be assed looking it up at the moment) is a SSRE (re-uptake enhancer) -which on paper has the exact opposite action to an SSRI - logic suggests this shouldn't alleviate depression but it does for some people.

    Long story short, last time I tried Melatonin for a week or so I got similar results to you - made me feel 'off' and I couldn't work out why.

  7. #7
    Senior Member Trouble33's Avatar
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    I'm using melatonine 6mg sublingual per night for 1.5 years. It doesn't make me depressed, only groggy in the morning. Sleep deprivation or delayed sleep phase syndrome is far more depressing.

  8. #8
    Member Requiel's Avatar
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    Interesting topic.

    I'll add some abstracts to the topic to spark up the discussion:
    Am J Psychiatry. 1976 Oct;133(10):1181-6.
    Negative effects of melatonin on depression.
    Carman JS, Post RM, Buswell R, Goodwin FK.

    In order to test the efficacy of the pineal neurohumor melatonin on depression, the hormone was administered in varying doses to six moderately to severely depressed patients and two patients with Huntington's chorea in double-blind crossover study. Melatonin exacerbated symptoms of dysphoria in these patients, as well as causing a loss of sleep and weight and a drop in oral temperature. Melatonin increased cerebrospinal fluid 5-hydroxyindoleacetic acid and calcium in three of four patients studied. The authors discuss the implications of this finding.

    PMID: 788529
    Got to add, can't really make much of this one; only six patients and no placebo control. Haven't been able to find the full text though.

    J Perinat Med. 2010 Nov;38(6):585-7. Epub 2010 Aug 13.
    The role of melatonin in post-partum psychosis and depression associated with bipolar disorder.
    Anderson G.
    Clinical Research Centre/Communications, Glasgow, UK. anderson.george@rocketmail.com

    Recent data has highlighted the association of a bipolar disorder (BD) with an increased risk of post-partum psychosis and depression. It is suggested that genetic- and environmental-induced decrease in the levels of melatonin in BD contributes to post-partum disorders. Melatonin may also have some efficacy in the treatment of BD, especially in decreasing the side-effects associated with lithium and the neuroleptics. It is proposed that the optimization of melatonin levels, perhaps in conjunction with optimized vitamin D3 level, would decrease post-partum psychosis and depression associated with BD.

    PMID: 20707614
    Psychiatry Res. 2010 Jun 30;178(1):205-7. Epub 2010 May 14.
    Phase relationships between core body temperature, melatonin, and sleep are associated with depression severity: further evidence for circadian misalignment in non-seasonal depression.
    Hasler BP, Buysse DJ, Kupfer DJ, Germain A.
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

    Misalignment between the timing of sleep and the circadian pacemaker has been linked to depression symptoms. This study sought to extend earlier findings by comparing sleep and circadian markers in healthy controls and individuals with major depression. Two markers of circadian misalignment correlated with depression severity in the depressed group.

    PMID: 20471106
    Psychiatry Res. 1998 Jan 16;77(1):57-61.
    Melatonin treatment of winter depression: a pilot study.
    Lewy AJ, Bauer VK, Cutler NL, Sack RL.
    Department of Psychiatry, Oregon Health Sciences University, Portland 97201-3098, USA. lewy@ohsu.edu

    Five patients with winter depression received low doses of melatonin in the afternoon, and five patients received placebo capsules. Melatonin treatment significantly decreased depression ratings compared to placebo. If these findings are replicated in a larger sample with documentation of expected phase shifts, the phase shift hypothesis will be substantially supported.

    PMID: 10710176
    Lancet. 1979 Dec 22-29;2(8156-8157):1362.
    Abnormal 24 hour pattern of melatonin secretion in depression.
    Mendlewicz J, Linkowski P, Branchey L, Weinberg U, Weitzman ED, Branchey M.

    PMID: 92694
    Prog Neuropsychopharmacol Biol Psychiatry. 1984;8(4-6):715-8.
    Circadian rhythm of plasma melatonin in endogenous depression.
    Nair NP, Hariharasubramanian N, Pilapil C.

    The circadian rhythm of plasma melatonin was investigated in normal men 18-30 years (N = 5), normal men 50-70 years (N = 5) and in six patients with endogenous depression. The environmental photoperiod was 11 hours. The subjects and patients were indoors with lights on from 07:00 until 23:00 hours. Blood samples were obtained every 4 hours over a 24 hour period, with additional sampling at 22:00 and 02:00 hours. Plasma melatonin was estimated by radioimmunoassay compared to both groups of controls. In the depressed patients, the levels of melatonin were low throughout the 24 hour period. The depressives had a delayed onset of the dark phase of the rhythm. The patients also showed peak melatonin levels occurring earlier than in the controls. Circadian rhythm of melatonin and therefore of its pacemaker may be altered in endogenous depression.

    PMID: 6531443
    Psychoneuroendocrinology. 2004 Jan;29(1):1-12.
    Serum melatonin and urinary 6-sulfatoxymelatonin in major depression.
    Crasson M, Kjiri S, Colin A, Kjiri K, L'Hermite-Baleriaux M, Ansseau M, Legros JJ.

    Psychoneuroendocrinology Unit, Service d'Endocrinologie, Université de Liège, B-35, CHU, B-4000, Liège, Belgium. mcrasson@ulg.ac.be

    In this study, serum melatonin and urinary 6-sulfatoxymelatonin (aMT6s) were measured in 14 major depressive inpatients, compared to 14 matched controls according to age, gender, season and hormonal treatment in women. Moreover, the relationship between serum melatonin and urinary aMT6s levels was analysed in the two groups. Results indicated that the two groups of subjects showed a clear melatonin rhythm without significant difference in the mean level of melatonin or aMT6s, in the area under the curve of melatonin or in the melatonin peak. However, the time of the nocturnal melatonin peak secretion was significantly delayed in depressive subjects as compared to healthy controls. Moreover, the depressed patients showed urinary aMT6s concentrations enhanced in the morning compared to night time levels, while these concentrations were lowered from the night to the morning in the control group. These results suggest that the melatonin production is phase-shifted in major depression.

    PMID: 14575725
    Biol Psychiatry. 1984 Aug;19(8):1215-28.
    A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression.
    Claustrat B, Chazot G, Brun J, Jordan D, Sassolas G.

    The temporal organization of plasma melatonin and cortisol secretion was examined in healthy rested controls and in depressed patients: 11 patients suffering from a primary affective disorder (10 female, 1 male) and 8 male controls were studied over a 24-hr period; blood was collected at 2-hr intervals during the day at 1-hr intervals at night. Plasma melatonin and cortisol levels were determined by radioimmunoassay. In addition, melatonin was determined in plasma sampled at 3 AM in older male controls (n = 8) and in females (n = 10) at ovulation. The controls showed low or undetectable (less than 5 pg/ml) diurnal plasma melatonin levels and a very marked nocturnal rhythm (acrophase: 2.27 AM, mesor: 34.4 pg/ml, amplitude: 58.7 pg/ml). For the three control groups, no significant difference was observed in the nocturnal melatonin peak at 3 AM. The depressed patients also showed a significant melatonin rhythm but with lower amplitude (14.5 pg/ml) and mesor (19.1 pg/ml). The latter rhythm was not significantly phase-advanced with respect to the controls (acrophase at 1.18 and 2.34 AM, respectively). In 9 of the 11 patients, nocturnal melatonin secretion was less marked and frequently associated with hypercortisolemia. An additional episodic melatonin secretion was observed in the late afternoon in only two patients. In depressed patients, there was an increase in the mean cortisol secretion level (mesor at 13.6 micrograms/100 ml against 9.1 micrograms/100 ml in the controls), but the amplitude and the acrophase were not significantly modified. These data are discussed in terms of both the hypothalamus-pituitary-adrenal-epiphysis and aminergic abnormalities.

    PMID: 6498244
    So yeah, evidence suggests people suffering from depression have a fucked up melatonin secretion cycle.

  9. #9
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    Wondering if this one has any practical implications

    Psychiatry Res. 1998 Jan 16;77(1):57-61.
    Melatonin treatment of winter depression: a pilot study.
    Lewy AJ, Bauer VK, Cutler NL, Sack RL.
    Department of Psychiatry, Oregon Health Sciences University, Portland 97201-3098, USA. lewy@ohsu.edu

    Five patients with winter depression received low doses of melatonin in the afternoon, and five patients received placebo capsules. Melatonin treatment significantly decreased depression ratings compared to placebo. If these findings are replicated in a larger sample with documentation of expected phase shifts, the phase shift hypothesis will be substantially supported.

    PMID: 10710176


    So I guess they received the melatonin several hours before going to bed. Long ago I used to take a very low dose of amitriptiline around 6 PM and go to bed at 11 PM or so. This allowed me to wake up easier the next day with less hangover. I am not at all having a hangover, but curious if there is any merit to this approach to maybe more gently lead the brain into a sleep-ready state well before going to bed
    A man can be happy with any woman, as long as he is not in love with her...
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    Member Requiel's Avatar
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    I have a book about ADHD from a local research center PsyQ in The Hague (Netherlands) that describes a technique to restore normal DLMO (Dim Light Melatonin Onset) and associated circadian rhythm. Normal DLMO should be about 2 hours before sleep (14 hours after waking up).

    It works as follows: you take 3mg melatonin one hour before sleep, for example 23:00 (11pm), but also you take a small dose of 0.5mg melatonin 6 hours before DMLO (8 hours before sleep). If the 0.5mg makes you sleepy, you cas use less (0.2-0.3). This is supposed to adjust your circadian rhythm. The 3mg right before sleep you take for 2 weeks and is then lowered or discontinued. The 0.5 you keep taking.

    It stresses how important timing is when taking melatonin. Taking it after 24:00 or before 15:00 can further delay sleep phase and is associated with winter depression.

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    Quote Originally Posted by Requiel View Post
    I have a book about ADHD from a local research center PsyQ in The Hague (Netherlands) that describes a technique to restore normal DLMO (Dim Light Melatonin Onset) and associated circadian rhythm. Normal DLMO should be about 2 hours before sleep (14 hours after waking up).

    It works as follows: you take 3mg melatonin one hour before sleep, for example 23:00 (11pm), but also you take a small dose of 0.5mg melatonin 6 hours before DMLO (8 hours before sleep). If the 0.5mg makes you sleepy, you cas use less (0.2-0.3). This is supposed to adjust your circadian rhythm. The 3mg right before sleep you take for 2 weeks and is then lowered or discontinued. The 0.5 you keep taking.

    It stresses how important timing is when taking melatonin. Taking it after 24:00 or before 15:00 can further delay sleep phase and is associated with winter depression.
    Since I have problems with the 3mg dose -even if taken daily for a week let alone 2 weeks- I am wondering if I should just start the 0.5 mg 8 hours before sleep. Will start it tonight actually
    A man can be happy with any woman, as long as he is not in love with her...
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    Member Requiel's Avatar
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    Quote Originally Posted by Sub7 View Post
    Since I have problems with the 3mg dose -even if taken daily for a week let alone 2 weeks- I am wondering if I should just start the 0.5 mg 8 hours before sleep. Will start it tonight actually
    Great! I'm very interested if this will help for you. I haven't tried this method myself because I only have 1mg melatonin pills (which I've exclusively used 1 hour before sleep and never more than one pill).

    I think I will try this soon as well, since my DSPS sleep deprivation is getting out of hand. I'd really like to restore healthy sleep patterns (sleep at 11pm and wake up at 7am).

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    Senior Member Jin Xie's Avatar
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    My cardiologist, who treats me for POTS, encourages me to experiment with 6 mgs. She claims studies suggest safety at 10+ mgs, contrary to what many thought. I haven't researched it. Even at 10 mgs, I don't find that helps meaningfully, for sleep inception or quality. It doesn't affect my REM. FWIW.

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    bumpy
    any input from neuroscience experts as to what MAO may be responsible for melatonin-depression link, and what remedies may work...?

    thanks a lot in advance
    A man can be happy with any woman, as long as he is not in love with her...
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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by Sub7 View Post
    bumpy
    any input from neuroscience experts as to what MAO may be responsible for melatonin-depression link, and what remedies may work...?

    thanks a lot in advance
    It has direct antidopaminergic effects and attenuates HPA activity.

    The best way to remedy this is...to not take melatonin.

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    Just a follow-up question that is rather intended to satisfy my curiosity than anything else:
    As I mentioned above, I experienced a marked sense of pessimism during melatonin use. An additional symptom, that I didn't get into very much in prior posts, is the negative emotions towards others. I would be sitting in Starbucks, for instance and someone would speak on his cell phone a little loudly. Even though I can handle such annoyances relatively well normally, I would get very pissed very easily (huge difference the melatonin made, huge!!!).

    Would you say the pessimism, worry and lack of patience/tolerance towards others indicates lack of serotonin rather than dopamine? (while understanding that such sweeping statements are very hard to make without more specific comments about each brain region).

    Illuminatus may also be interested in providing an opinion on this as far as I can tell based on his prior posts.

    Thanks everyone...
    A man can be happy with any woman, as long as he is not in love with her...
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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by Sub7 View Post
    Would you say the pessimism, worry and lack of patience/tolerance towards others indicates lack of serotonin rather than dopamine? (while understanding that such sweeping statements are very hard to make without more specific comments about each brain region).
    You know I hate neurotransmitter reductionism, but if we're going to dig into it, I'd say this is more a balance issue. Irritability tends to be associated with inappropriate tonic/phasic DA balance, inappropriate DA/NE balance, and also inappropriate low levels of 5-HT. It's really hard to conclude much.

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    Quote Originally Posted by Sub7 View Post
    Illuminatus may also be interested in providing an opinion on this as far as I can tell based on his prior posts.
    I coincidentally had already ordered some melatonin when I saw this post go up, and when it arrives I will test and put my thoughts up here.

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    Senior Member Ubiyca's Avatar
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    I've been using 3mg sublingual a night for years (used to use 5mg+ too for awhile) and I feel grrrrrrrrrrrrrrrr8.

    I work night shift though.. FWIW. I usually take it in the late morning-afternoon'ish and wakeup 9pm approx.
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    Quote Originally Posted by Ubiyca View Post
    usually take it in the late morning-afternoon'ish and wakeup 9pm approx.
    so how long before going to bed do you take it?

    I really wish I could use melatonin
    It provides excellent sleep, but the side effects -which I am very reluctant to attribute to placebo or coincidence- are very harsh
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