today, i want to talk about my battle with seasonal depression. my most recent foray into antidepressant treatment this winter has been a fun one. my regimen is a culmination of things from last year that worked, and surprisingly, when it comes to the additions, there was little fuss and churn. i attribute this to two things – one, i’ve got the money to liberally fuck around and find out, and two,,,
i finally found a psychiatrist willing to indulge me and pretty much prescribe whatever tf i want, as long as he doesn’t think it’d be dangerous. goddamn finally someone whose ego and sense of misplaced “responsibility” and authority doesn’t get in the way of engaging with what their patients are telling them. someone who doesn’t rigidly stick to what’s commonly prescribed and isn’t ruled by their comfortably priors. someone who will let me fkn experiment on myself like i want to 😌
it’s kinda funny because some of the drugs i suggest, he hadn’t heard of being effective treatments for that which i posited, but will rx them anyway just after hearing me talk about the justifications. i’ve built up this rapport with him to the point where he’s told me that he actively enjoys our sessions because he thinks i’m “very intelligent” and “interesting to talk to.” despite having heard mixed things about going to one’s doctor and explaining the neurochemistry of a proposed therapy not always going well, he seems to value this and be able to remain humble in the face of a patient claiming to know more about a topic.
as for the things that have been continued from the year before: one was high dose EPA/DHA fish oil @ 900mg BID (walmart). it gives me a mild mood boost, but doesn’t effect my overall energy. (research links: study (mirror), and the relevant examine research on depression, but also note that there’s some mixed evidence pointing toward this dose possibly having immunosuppressive effects (examine). proceed with caution and form your own risk-benefit analysis!)
after eight (8) whole months of painfully slow titration and wait ‘n see periods, my dose of Adderall XR dose has stabilized at 30mg/day. it was a pleasant surprise that this turned out to be a rather effective antidepressant! 🙏 (if interested, see related reading abt my initial struggle to introduce stimulant therapy)
this makes sense and there’s been many such cases i’ve heard of through the grapevine. people with adhd sometimes find their depression isn’t actually isolated but rather a consequence, probably in part due to the disappointment from executive function being very much maimed by PFC/limbic system impairments.
using those two tactics alone i observed that by mid-december the number of sad days per week were averaging out to merely two, and at a lower impact to my overall functioning than two years ago. this was a big improvement to me that made me hopeful for once! i felt like i was finally getting somewhere after over 5 years of wrestling with mental health during these times of the year ^.^
i continued with light therapy, previously having built a couple lumenators – box-style, and pole. on particularly overcast days, i’d sit about a foot from the doomstar for 15-20 minutes, peering as closely to the giant, directional LED corn bulbs as possible. every day, i turned on 1-2 of the pole fixtures, running 11-22 cheap, omnidirectional LED bulbs about 3-4 feet from my face. these guys land an underwhelming lumen count at my photoreceptors because of the distance and diffusion into the room, unfortunately 😕 on the upside, they did help, if only somewhat. on the days i went to the office, i noticed my days were subjectively really shit comparatively.
regardless, it does appear that i have seasonal affective disorder, and now that i’ve been with this psychiatrist for a couple years, he’s finally diagnosed me with it. i thought long and hard about what i wanted to add, stretching into the winter months before becoming desperate enough to give something a go. that led to trying low-dose naltrexone, titrated up to 4mg a milligram at a time from just 1mg.
naltrexone is super interesting!! there’s, again, not a load of human research on it, but y’know, by this point, it seems like those are the options i have as far as medications are concerned. ssri’s don’t do much, and produce a ton of side effects, so i won’t take them. antipsychotics are also out for fear of extrapyrmiddal effects that there isn’t compelling enough evidence to say what the prevalence is… or if it’s permanenct.
Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen’s d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). (source)
these instruments all attempt to measure the presence and severity of depression. for HAM-D, higher is worse: 8-16 being mild, 17-23 interpreted as moderate, and >24 being severe. in the aforementioned trial, we see participants’ scores for the 17-item variant falling, on average, from moderate depression down to mild presentation (source).
that’s pretty promising to me, given my depression is typically moderate, and had been this winter. i tried to remain skeptical, but couldn’t help but to be a bit hopeful, despite the low participant count in this trial; n=12.
i didn’t do a ton of searching for studies, cause by this point, i was pretty desperate for some relief. there are others. some much older clinical trials done with related opioid antagonists seemed to position this sort of treatment as fairly reliable, albeit uncommon, which explains the poor knowledge of it within the field of psychiatry except for treatment resistant cases.
Paradoxically, LDN enhances the eﬀects of opioid agonists by blocking the opioid receptor transiently which causes a positive feedback mechanism that increases the production of endogenous peptides. Increased levels of endogenous opioids peptides are known to promote healing, inhibit cell growth, and reduce inflammation. Naltrexone works by binding to the C-terminal pentapeptide of the scaffolding filamin A with strong affinity. Filamin A is also found on dopaminergic D2 and D3 receptors which might explain the effect of LDN on prevention of desensitization to D2/D3 agonists. (source)
this is fascinating to me. it brings me back to tales of microdosing LSD. i dont know if the evidence in that developing space points to a similar paradoxical mechanism, but the fact that these sorts of conditionals exist… ffff it all makes me so excited! i can’t even fangirl enough over stuff!! the human brain is fascinating in its complexity and self-regulation 😩 😌
i was somewhat concerned about potential interactions with other medications, as usual… it wasn’t until after i started it, though, that i realised the full implications and looked into its downstream dopaminergic effects. apparently, it’s also useful for potentiating adhd medication. i won’t get too far into that though, as i’d like to write a separate post on the matter of attenuating long-term desensitization.
the weirder trial was, again, d-Limonene. v experimental and not a particularly compelling amount of evidential support behind it’s use in humans (pubmed, mirror, mirror), but accessible, cheap, and most importantly, does work for me. i’ve recommended it to others and seen similar results, but yeah, the n is rather low, even taking into account what research there is to peruse.
my last trial was with oral capsules. this didn’t do much more than EPA in terms of noticeable mental qualia. using drops (amzn: small batch, larger batch) in an ultrasonic diffuser, though, produced vastly different results! 😮 this did exert a change on my energy levels – alertness and cheerfulness pours over me in just a minute or two. the one human study that found positive and significant p-value shifts in depression instrument scores used exactly this method.
examine has little to say about it, but there have been some pharmacological studies, albeit in rodents. this one indicates increased brain NT levels of dopamine, GABA, glutamate, and serotonin, whereas another narrows down the serotonergic modulation to 5-HT1A agonism. from the latter:
[…] to evaluate interference with the 5HT1A serotonin receptor. Administering [WAY100635, a selective 5HT1A receptor antagonist] with the EO reversed all of the effects of the EO in the LDB. Thus, it appears that the serotonergic system, through 5HT1A receptor, is linked to the anxiolytic-like action […] To rule out the possibility of a nonspecific effect, WAY was also co-administered with [diazepam] without any observable effect.
i’ll be elaborating more on the significance and intricacies of this and other neuroreceptors in another post on the medications i researched and discarded this round, so for now, have a snippet from wikipedia on 5-HT1A:
5-HT1A receptor agonists […] show efficacy in relieving anxiety and depression […]
5-HT1A autoreceptor desensitization and increased 5-HT1A receptor postsynaptic activation via general increases in serotonin levels by serotonin precursor supplementation, serotonin reuptake inhibition, or inhibition of monoamine oxidase has been shown to be a major mediator in the therapeutic benefits of most mainstream antidepressant supplements and pharmaceuticals […]
5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus […]
5-HT1A activation is known to improve cognitive functions associated with the prefrontal cortex, possibly via inducing prefrontal cortex dopamine and acetylcholine release.
using d-Limonene in this way sometimes produced some anxiety and hyperfocus for me with myrcene (amzn) in the mix (which i was using as a mild boost to endorphins for my spinal injury). eventually i figured out a nice balance by fiddling with the dose. also, adding a bit of β-Caryophyllene (amzn) occassionally took the edge off, but was too unrealiable and paltry in efficacy to be particularly notable; that said, i want to explore more essential oils for anxiety as i’ve seen promise there with the pines.
when i went into the office, i’d use diffusing necklace (amzn), which worked slightly less well, but did give notable results that were good enough to get me through most of the day. it was, unfortunately, not enough to get me to make any regularity out of the commute. combined with the annoyances of my daily routine + covid prevention tactics reducing overall productivity on those days, i didn’t keep it up. for shorter outings though, i found myself reaching for this, if only as a placebo 🤷
(maybe i’ll write more about these other terpenes at another time, but for now i’ll just say that they have even less research on them, mainly in vitro and behavioral mouse models. they seem fairly mild though, and have short acting effects when diffused into the air and inhaled)
of the two trials this year, i think naltrexone made the larger difference. introducing it, immediately i knew i was in for something more than placebo! excerpts from my log:
compounded 1mg taken the morning of 12/16/2020 around 7AM with usual medications incl. 30mg adderall XR, 100mg progesterone, etc
an hour later:
- increased visual appreciation (awareness of and awe over light, vibrancy)
- mildly increased intensity of light and vibrancy of colors ala gaba, 5-ht, opioid agonism (but without the dulling effects of strong opioids)
- mild tingly stimulatory effects characteristic of dopaminergic or opioid euphoria (hands, face)
- no impairment in cognitive clarity; to the contrary, a sharpening of focus
- dramatically improved mood; excitement, joy, contentment, gratitude, empathy
these effects persisted through the day, gradually lessening in the afternoon, but still somewhat present in the evening, finally tapering off as i got sleepier
- horniness was increased from baseline
- intermittent attachment-related anxiety when chatting with a partner
took my usual night-time medication including 50mg trazodone, 10mg sildenafil, etc at bedtime and was somewhat discoordinated
didnt experience any stimulatory-induced hynogogic jerks, nor significant respiratory events, though there were a few periods where my breathing stopped between inhales that lasted only for ~1 second longer than nominal. adrenaline-flavored startle responses from this did not cause significant arousals, but only mild chest surge sensations that were notable.
i laid on my back for 15 minutes until feeling uncomfortable, switching to my right side and using a body pillow to support my arm and leg in proper 90deg leg positioning and ~60deg elbow angle. close to the T+30m mark, this position became uncomfortable, with pain developing along the nerve junction in my elbow and with tension/nerve compression sensations in the hip making contact with the mattress, and supported by the body pillow.
i switched to my back, and the pain moved with it to my buttocks, persisting in elbows. i perceived dopaminergic stimulatory effects, noting likely serotonergic agonism downstream effects, no longer drowsy whatsoever.
over the next 2.5h this pain slowly intensified, and body temperature lowered. the former manifested in seemingly mild muscle tension that i couldnt easily confirm running my hands over most major muscle groups other than buttocks, hips, and shoulders. this discounted rhabdomyelosis but did suggest dopaminergic central and peripheral CNS overactivation. i continued to experience radiating pain along nerve paths that made contact with the bed. my lower back did not seem to make contact with the bed from gluteal weight depressing the pad, so it was fine.
the most distracting issue though was reduction in body temperature/radiant heat in extremities, and asymmetric numbness in toes and hands. i increased room temperature by 6deg via heater, and as the night progressed, put on clothes, ate a small portion of oatmeal, and listened to music. not until this point did i feel warm enough under the covers to let that distraction leave my mind.
i urinated 3 times, completely clear each time, despite only having drank maybe 6oz of water before bed. the urge was distracting despite this not being a trend over the last couple weeks. i worried about this meaning something but not knowing what it could be. i had fear responses since initially lying down over my apartment getting broken into and getting assaulted or raped, with imagery of people standing over my bed looking menacing. i ended up turning on a small light to counteract this, and listened to music.
up until this point i was exhausted enough to not be able to summon the thoughts of doing many things that might help me calm my mind. i tried unfocusing my eyes and relaxing my thoughts, but this only worked to a limited degree. there was some anxiety over medical worries of serotonin syndrome or some sildenafil interaction. i dispelled them to the best of my ability, but could not practice visual meditation.
eventually, i was on the cusp of sleep, experiencing impaired perception of time. i eventually found a comfortable enough position and reached what i thought to be alpha wave sleep around T+3~T+3.5h (though this not confirmed). around T+4h, my body temperature normalized, i became intensely drowsy, and was nearly in deep sleep. i had to get up, shirk my clothes, and turn the heaters down. at which point i promptly fell into deep sleep with no arousals.
i woke at 7am, about 5 hours later in no pain remotely like i had experienced, but tired
the night time effects sound pretty bad in retrospect, but didn’t recur. the high-like state did persist for about 3 days though.
the day after introduction, i had surgery on my nose to correct a deviated septum. the medications and pain related to this completely ruined my sleep, and i attribute remaining functional, in part, due to LDN. see below; the highlighted date is that of the surgery:
by february, i had mostly recovered and feeling like i was getting back to my usual self. if i were to rate my depression over the course of winter: in december, i experienced 1-2 days per week feeling depressed. in january, this rose to 3-4/wk. on LDN for 2 weeks, initial titration to 2mg produced no notable and predominantly depressed days that i couldn’t correlate to something situational.
now that i’ve discontinued it with a slow taper, i can say it definitely had a large effect… specifically, i had withdrawals 😒 the last two weeks were low energy, as if i had reduced my dose of adderall. i was irritable, being snappy with friends and coworkers. i got less done at work and didn’t enjoy my job as much. all that is totally worth it in comparison to being miserable for 4-6 months every year!
astonishingly, last month was my most productive month at work out of the entire year. i was adaptable, able to put in extra hours to meet quarterly objectives, and, most incredibly to me, kept this up for the entire month without it have being detrimental to total energy or well being. i have never in my life been able to consistently do this, even since stabilizing on stimulant therapy several months ago.
in closing: a+++ will be making use of this terrific solution in the ensuing years. i hope to be able to say that it remains effective! to have a solution for this blight that’s tormented me for so many damn years would be wonderful 😌 i honestly can’t recommend it enough, having months and years of joy stolen from my life by these fucked off badbrains. if you’re in a similar situation of having failed multiple traditional ADs, or simply find them unpalatable, give low-dose natrexone a try as an adjunct 😁