anxiety – Notes of a Neuropsychiatry Amateur

Yerba Mate (Ilex Paraguariensis) articles summary using NLP

The following summary was created using a google search for specific phrases and then performing natural language processing steps for sentence scoring. Yerba mate is an evergreen tree/shrub that grows in subtropical regions of South America. The leaves of the plant are used to make tea. Yerba mate tea contains caffeine and theobromine, which are known to affect the mood. I was interested in summarizing the existing articles in regards to research on this plant in psychiatry.

The first search phrase used was “yerba mate psychiatry depression research evidence“, and the number of collected articles for this phrase was 18. The text from all articles was combined, and relative word frequencies were calculated (after removing stop-words). These relative frequencies were then used to score each sentence. Sentence length distribution was checked, and the 90th percentile of 30 words was chosen to select sentences below the maximum length. Below are the 10 highest scoring sentences that summarize the text from the 18 articles.

We can infer from the summary that studies have been performed using the yerba mate extract on rats and tasks for chosen as proxies for the rats’ depression and anxiety levels. There are no mentions of human studies in the summary. Also the chosen sentences indicate that based on these studies, yerba mate has potential antidepressant activity, and it may improve memory as well. The results of the anxiety study were not mentioned and it’s not clear whether there were any side effects from yerba mate. These results are in line with descriptions of personal experiences of reddit users that I have reviewed, as many report better mood and improved focus after drinking yerba mate tea. Some users do report increased anxiety correlated with yerba mate consumption.

View abstract. J Agric.Food Chem. Vitamin C Levels Cerebral vitamin C (ascorbic acid (AA)) levels were determined as described by Jacques-Silva et al. Conclusion: In conclusion, the present study showed that Ilex paraguariensis presents an important effect on reducing immobility time on forced swimming test which could suggest an antidepressant-like effect of this extract. Despite previous some studies show the antidepressant-like activity of flavonoids [31, 32] which are present in the extract of I. paraguariensis, any study has evaluated the possible antidepressant-like activity of it. The presence of nine antioxidants compounds was investigated, namely, gallic acid, chlorogenic acid, caffeic acid, catechin, quercetin, rutin, kaempferol, caffeine, and theobromine. Abstract In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Another study showed that an infusion of I. paraguariensis can improve the memory of rats treated with haloperidol and this effect was related to an indirect modulation of oxidative stress . In addition to flavonoids as quercetin and rutin and phenolic compounds as chlorogenic and caffeic acids, yerba mate is also rich in caffeine and saponins . After four weeks, behavioral analysis of locomotor activity and anxiety was evaluated in animals receiving water (n = 11) or I. paraguariensis (n = 9). In the same way, we evaluated if the presence of stimulants compounds like caffeine and theobromine in the extract of I. paraguariensis could cause anxiety. In the present study, we evaluated the possible antidepressant-like effect of I. paraguariensis by using forced swimming test (FST) in rats. Forced Swimming Test This experiment was performed using the FST according to the method previously published by Porsolt et al. In this context, Yerba mate (Ilex paraguariensis) is a beverage commonly consumed in South America especially in Argentina, Brazil, Uruguay, and Paraguay. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test.

I also tried several other search phrases, such as “yerba mate mood anxiety evidence” and “yerba mate side effects evidence“. In total of 17 articles were collected for the first query and 19 articles for the second query. The summaries are presented below. There was nothing in the summary directly discussing mood or anxiety, but there are mentions of neuroprotective effects and antioxidant effects. We can also learn that a cup of yerba mate tea has similar caffeine content as a cup of coffee, and that drinking yerba mate is not recommended while pregnant or breastfeeding. As in the previous summary, no human trials were mentioned, so it seems that all the summarized studies were performed on rats. The side effects query summary mentions the risk of transferring the caffeine from the tea to the fetus when pregnant, as well as a link to cancer for those who drink both alcohol and yerba mate. It also mentions and anxiety is a side effect of the tea.

Query 1:
View abstract. J Agric.Food Chem. On the other hand, studies conducted on an animal model showed chemopreventive effects of both pure mate saponin fraction and Yerba Mate tea in chemically induced colitis in rats. Yerba Mate Nutrition Facts The following nutrition information is provided by the USDA for one cup (12g) of a branded yerba mate beverage (Mate Revolution) that lists just organic yerba mate as an ingredient. Researchers found that steeping yerba mate (such as in yerba mate tea) may increase the level of absorption. Yerba mate beverages are not recommended for children and women who are pregnant or breastfeeding. Chlorogenic acid and theobromine tested individually also had neuroprotective effects, but slightly weaker than Yerba Mate extract as a whole, but stronger than known neuroprotective compounds, such as caffeine [ 83 ]. The caffeine content in a cup (about 150 mL) of Yerba Mate tea is comparable to that in a cup of coffee and is about 80 mg [ 1 , 11 , 20 ]. In aqueous and alcoholic extracts from green and roasted Yerba Mate, the presence of chlorogenic acid (caffeoylquinic acid), caffeic acid, quinic acid, dicaffeoylquinic acid, and feruloylquinic acid was confirmed. After consumption of Yerba Mate tea, antioxidant compounds are absorbed and appear in the circulating plasma where they exert antioxidant effects [ 55 ]. According to the cited studies, Yerba Mate tea consumption attenuates oxidative stress in patients with type 2 diabetes, which may prevent its complications.

Query 2:
View abstract. J Agric.Food Chem. Because yerba mate has a high concentration of caffeine, drinking mate tea while pregnant can increase the risk of transferring caffeine to the fetus. J Ethnopharmacol. South Med J 1988;81:1092-4.. View abstract. J Am Coll Nutr 2000;19:591-600.. View abstract. Am J Med 2005;118:998-1003.. View abstract. J Psychosom Res 2003;54:191-8.. View abstract. Yerba mate consumed by those who drink alcohol is linked to a higher risk of developing cancer. Anxiety and nervousness are a side effect of excessive yerba mate tea consumption.

NLP: Summarizing l-theanine articles

In this post I will describe my use of NLP (Natural language processing, not neuro-linguistic programming. Natural language processing is cool, while neuro-linguistic programming is some pseudoscience stuff) in the application of summarizing articles from the internet. Specifically, I chose the topic of l-theanine and psychiatry, as previously I have already summarized the Nootropics subreddit discussions on l-theanine. The next step, therefore, is to summarize existing articles on this topic.

Summarizing experience with green tea from the Nootropics subreddit

The first step was to perform an automated Google search for a specific term. I chose the term “l-theanine psychiatry” and set the number of unique urls to be 15. Some of the resulting urls are listed below:

Can L-Theanine Help Treat Symptoms of Bipolar Disorder?

Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial

L-theanine

How does the tea L-theanine buffer stress and anxiety

It can be seen that the article titles are quite relevant to our topic. The next step is formatting the text and summarizing the information.

The idea behind the summarization technique is calculating word frequencies for each word in the combined text of all articles (after stop words removal), and then selecting words in the top 10% of frequencies. These words will be the ones used in scoring each sentence. More frequent words will be given more importance, as they are deemed more relevant to the chosen topic, therefore sentences containing those words will receive higher scores. This is not a machine learning approach, but a basic frequency count method. In total, 148 words were used for sentence scoring. Some of the most frequent words (from all articles combined) are listed below:

Theanine, administration, effects, placebo, weeks, study, four, sleep, scores, cognitive, may, stress, function, fluency, studies, related, symptoms, participants, bacs, anxiety

BACS was one of the top frequent words, it stands for the Brief Assessment of Cognition in Schizophrenia. Once each sentence was scores, 15 highest scoring sentences were selected in order to create a summary. The summary of the articles is presented below. From the summary we can infer that l-theanine was studied for its effects on cognition, anxiety, and stress. Some studies had positive results, indicating that l-theanine performed significantly better than placebo in regards to positive cognitive effects such as improved verbal fluency and executive function. Studies also noted significant improvements in stress reduction with the use of l-theanine. Other studies did not find any significant differences between l-theanine and placebo.

Second, only about 20% of symptoms (the PSQI subscales) and cognitive functions (the BACS verbal fluency, especially letter fluency and executive function) scores showed significant changes after L- theanine administration compared to the placebo administration, suggesting that the effects are not large on daily function of the participants.

Although psychotropic effects were observed in the current study, four weeks L-theanine administration had no significant effect on cortisol or immunoglobulin A levels in the saliva or serum, which was inconsistent with previous studies reporting that salivary cortisol [34] and immunoglobulin A [33] levels were reduced after acute L-theanine administration.

Considering the comparison to the placebo administration, the current study suggests that the score for the BACS verbal fluency, especially letter fluency, but not the Trail Making Test, Stroop test, or other BACS parameters, significantly changes in response to the 4 weeks effects of L-theanine.

The BACS verbal fluency, especially letter fluency (p = 0.001), and executive function scores were significantly increased after L-theanine administration (p = 0.001 and 0.031, respectively; ), while the Trail Making Test A and B scores were significantly improved after placebo administration (p = 0.042 and 0.038, respectively).

When score reductions in the stress-related symptoms were compared between L-theanine and placebo administrations, changes in the PSQI sleep latency, sleep disturbance, and use of sleep medication subscales were significantly greater (p = 0.0499, 0.046, and 0.047, respectively), while those in the SDS and PSQI scores showed a non-statistically significant trend towards greater improvement (p = 0.084 and 0.073, respectively), during the L-theanine period compared to placebo.

Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores.

Discussion In this placebo-controlled study, stress-related symptoms assessed with SDS, STAI-T, and PSQI scores decreased, while BACS verbal fluency and executive function scores improved following four weeks L-theanine administration.

The present study aimed to examine the effects of four weeks L-theanine administration (200 mg/day, four weeks) in a healthy population, i.e., individuals without any major psychiatric disorder.

The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05).

The effects on stress-related symptoms were broad among the symptom indices presented in the study, although a comparison to the placebo administration somewhat limits the efficacy of L-theanine administration for some sleep disturbance measurements.

For cognitive functions, BACS verbal fluency and executive function scores improved after four weeks L-theanine administration.

PMID: 31623400 This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults.

The anti-stress effects of L-theanine (200 mg/day) have been observed following once- [ 33 , 34 ] and twice daily [ 35 ] administration, while its attention-improving effects have been observed in response to treatment of 100 mg/day on four separate days [ 36 ] and 200 mg/day single administration [ 37 ], which was further supported by decreased responses in functional magnetic resonance imaging [ 38 ].

These results suggest that four weeks L-theanine administration has positive effects on stress-related symptoms and cognitive function in a healthy population.

Health habits – some interesting myths

There are some advice that we hear many times from multiple people, but some common beliefs about health habits are not actually true. Fat was thought to be a cause of obesity, but that is contradictory to the more recent findings that low carb high fat diets can promote weight loss. Low fat products turned out to be high in carbs, and actually less healthy. Unsaturated fats such as olive oil and avocado are now promoted as health foods, and salmon, which contains high levels of fat, is considered to be very nutritious and beneficial for brain health. What are then some of the other myths about health habits?

Hot cocoa before bed can help you sleep – actually the National Sleep Foundation recommends avoiding dark chocolate/cocoa/cacao in the evening. Dark chocolate contains caffeine, therefore a cup of hot cocoa would not be caffeine free. The USDA National Nutrient Database indicates that a cup would contain 7.44 mg caffeine. That’s not a lot, but chocolate also contains theobromine, which increases hearth rate and can cause sleeplessness. Theobromine is an alkaloid, it is found in the cacao plant, the tea plant, and the kola nut. All of these plants are known stimulants. Therefore the combination of caffeine and theobromine for a lot of people would create a state of alertness, and therefore it will not help you sleep. Interesting fact – caffeine is partly metabolized into theobromine in humans. Theobromine is also an antagonist of adenosine receptors, just as caffeine, but weaker. Wakefulness is promoted when adenosine receptors are blocked in the brain.

Coffee increases anxiety – I don’t think there is a yes or no answer to this question, that’s why this statement is not correct. It seems that it varies for people. For some it seems that it does increase cortisol and therefore can contribute to feelings of anxiety and fear. For others it may actually be helpful. Some studies indicate that coffee is beneficial for people with OCD and helped to reduce intrusive thoughts and compulsive behaviours.
The roles of arousal and inhibition in the resistance of compulsive cleansing in individuals with high contamination fears

We are better off taking a multivitamin every day – no, we don’t actually know that. Maybe, maybe it makes no difference, maybe worse off. Obtaining vitamins and minerals from food, plus from a multivitamin, may lead to overconsumption. And more, as we know, is definitely not always better. Over consumption of folate may increase the risk of some cancers, overconsumption of iodine may lead to thyroid disorders, too much vitamin A can be harmful, and iron build up in the brain may be associated with declines in thinking and memory.
Folate consumption
Iron and the brain

Mood supplements that are sold over the counter are safer than antidepressants – they are really not. For example, 5-HTP supplement is sold in most pharmacies in Canada and in health stores, that doesn’t make it safer than Prozac. From Wiki: 5-Hydroxytryptophan is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin. So if you consume it, will it just raise your serotonin and make you happier? Not necessarily. If someone is unaware that they are bipolar, taking supplements such as SAMe, 5-HTP, or St. John’s Word could make them manic. These supplements are not mood stabilizers. And since it can affect serotonin levels, it is not without side effects, just as antidepressants are not. Some people experience increased suicidal thoughts when taking medications or supplements that increase serotonin. You can also read user reviews of 5-HTP to see for yourself that it is not completely safe. Some users state experiencing elevated heart rate, vivid nightmares, suicidal thoughts, and insomnia. Be careful with any supplement that you try, observe any changes that happen, read about possible side-effects and contraindications.
https://www.drugs.com/comments/5-hydroxytryptophan/

Red meat and dairy are bad for you – I heard this often, but it’s not what actually recent studies show. I’m sure in some high amounts, daily consumption of red meat and dairy would lead to too much saturated fat, but that does not mean that the optimal amount is zero. A recent article in Nature states that the longest life expectancy in Japan may be related to the balanced diet consisting of a typical Japanese diet food products, as well as Western diet items such as meat and dairy. “The decreasing mortality rates from cerebrovascular disease are thought to reflect the increases in animal foods, milk, and dairy products and consequently in saturated fatty acids and calcium, together with a decrease in salt intake which may have led to a decrease in blood pressure… The typical Japanese diet as characterized by plant food and fish as well as modest Westernized diet such as meat, milk and dairy products might be associated with longevity in Japan.“
https://www.nature.com/articles/s41430-020-0677-5

There are also inconclusive results in regards to red meat consumption and mental health. A systematic review of meat abstention and depression, 2020, indicated that “the most rigorous studies demonstrated that the prevalence or risk of depression and/or anxiety were significantly greater in participants who avoided meat consumption.” On the other hand, a cross-sectional study published in 2021 concluded that “after controlling for potential confounders, women in the highest quartile of red meat had a highest prevalence of depressive symptoms.”
https://www.tandfonline.com/doi/full/10.1080/10408398.2020.1741505
https://www.sciencedirect.com/science/article/pii/S0965229920318550

Developing a schedule for a healthier pregnancy

Pregnancy can be very difficult, especially if you already have chronic health problems. Personally, I felt very sick starting week three, and until around week 12 – 13. The sickness presented itself in terms of nausea, extreme fatigue, and increased anxiety. Only once I started to feel less nauseous, I was able to go back to my regular diet which limits refined carbs and continue with intermittent fasting again. I did then also start feeling worse in the third trimester, around after week 34. From my experience, these are the actions which have helped me to feel better:

Start taking folic acid as soon as possible, preferably before conception. Folic acid supplementation has been found to reduce neural tube defects, as well as congenital heart defects. Taking folic acid supplement every day can provide a positive feeling that you are doing the right thing for your baby’s health.
From Health Canada: “Folic acid is vital to the normal growth of your baby’s spine, brain and skull. Taking a daily vitamin supplement that has folic acid can reduce the risk of your baby having a neural tube defect. The benefits of taking folic acid to reduce the risk of NTDs are highest in the very early weeks of pregnancy. At this stage, most women do not know they are pregnant. For this reason, taking folic acid before you become pregnant and in the early weeks of pregnancy is very important.”
https://www.canada.ca/en/public-health/services/pregnancy/folic-acid.html
Recent studies have shown that high folate intake is associated with a reduced risk of birth defects other than NTDs. Higher maternal folate or periconceptional use of folic acid is associated with a lower risk of congenital heart defects (20-23) and oral clefts (24). A recent meta-analysis of 1 randomized controlled trial, 1 cohort study, and 16 case-control studies has shown that maternal folate supplementation is associated with a lowered CHD risk (RR =0.72, 95% CI: 0.63–0.82) (25). However, the results showed considerable heterogeneity, but after excluding the outliers the risk estimate was almost unchanged: the corresponding pooled RRs were not materially altered (RR =0.78, 95% CI: 0.69–0.89) (25).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837928/#:~:text=Recent%20studies%20have%20shown%20that,and%20oral%20clefts%20(24).
Iron supplements – Iron deficiency is the most common nutritional deficiency during pregnancy. It happens most often during the third trimester. The iron in meat, fish and poultry is the easiest for our bodies to absorb and use. Foods rich in vitamin C help you absorb more iron. You can start taking an iron supplement during pregnancy in order to make sure you get enough and to prevent anemia. Low iron can lead to more fatigue, shortness of breath, weakness, headache, dizziness. All these symptoms in turn can make you more depressed. If low iron will lead to anemia, there will not be enough hemoglobin, and less oxygen will get to your cells. Cells won’t be functioning properly, and this can also contribute to depression and anxiety.
Prenatal vitamins – you can easily buy prenatal vitamins in a pharmacy or online. Nutritional yeast flakes also contain multiple vitamins. I’ve experienced more and more lethargy in the third trimester, and I started adding small doses of nutritional yeast flakes to smoothies. I have the Bob’s Red Mill brand, it is fortified inactive yeast, contains high doses of B vitamins – thiamine, riboflavin, niacin, B6, folate, and B12. It’s very cheap, given that the whole pack was around $8, and I consume less than a teaspoon a day, as the vitamin concentration is very high. I don’t see the need to take more than the needed daily value of B vitamins. I found that actually taking overly high doses of B vitamins for me can lead to panic attacks. Small doses of nutritional yeast do help me with energy during the third trimester, it can get me out of a very lethargic vegetative state to at least being able to wash the dishes, write in my blog, etc.
Sleep more – pregnancy can cause extreme fatigue. I found that instead of 7 – 8 hours, I currently need to sleep 9 hours. It helped me to start going to bed earlier, before 12am, then I am able to wake up for work before 9am. I also found that staying asleep became more difficult, I would wake up at around 4:30am, unable to fall back asleep. What helped me is eating the last meal four hours before bed, and the meal consisting mostly of non-refined starch, and not a lot of protein. The best sleep occurs for me if I eat short grain brown rice or potatoes (not fries) with something for dinner. Some studies mention that it is the prebiotic foods which can help sleep. “More commonly eaten foods that contain prebiotics include asparagus, onions, garlic, cashews, pistachios, and cooked and cooled grains and potatoes.” On the other hand, I found that eating cheese or red meat in the evening causes nightmares for me during the night, therefore I only eat those foods earlier on in the day.
https://www.sbs.com.au/food/article/2020/03/13/science-suggests-prebiotic-foods-might-help-you-sleep
Foods for anxiety – even though there is no recommendation to completely avoid coffee during pregnancy, I had to stop drinking any coffee as it would increase my anxiety more than before pregnancy. I also had to figure out which foods exacerbate acid reflux, which got worse. Ongoing acid reflux would make it uncomfortable for me to sit, lie down, sleep, and relax. It’s hard to calm down and do any breathing exercises, or just read a book, if your throat is burning, and you feel acid going up. I had to stop eating chocolate, spicy foods, coffee, black tea, lemon, soups, and meals containing a lot of tomatoes. I found oolong tea to be a good option. I also found helpful choosing complex carbs over refined carbs – making my own oat whole wheat pancakes, eating brown rice, potatoes, lentil pasta, plantains. Eat some protein with each meal.
From the Mayo Clinic: “Carbohydrates are thought to increase the amount of serotonin in your brain, which has a calming effect. Eat foods rich in complex carbohydrates, such as whole grains — for example, oatmeal, quinoa, whole-grain breads and whole-grain cereals. Steer clear of foods that contain simple carbohydrates, such as sugary foods and drinks.“
I also had to stop consuming all dairy products, I noticed they were making my anxiety worse, as well as increasing brain fog. Again, from the Mayo Clinic:
“Pay attention to food sensitivities. In some people, certain foods or food additives can cause unpleasant physical reactions. In certain people, these physical reactions may lead to shifts in mood, including irritability or anxiety.“
Food sensitivities – if you are avoiding any foods due to food sensitivities, make sure you get enough nutrients from other foods. I used to eat dark chocolate, which contains a lot of magnesium, but had to stop due to acid reflux. I made sure to eat other magnesium containing foods such as peanuts, bananas, and flax seeds. I also had to stop consuming any dairy, as I noticed that it was increasing my anxiety, rumination, and brain fog. I had to start consuming fortified soy milk, tofu, dairy-free yogurts, etc., in order to get calcium. I also took calcium supplements, and made my own supplement from egg shells.
Exercise – an important step with exercise, as with all pregnancy symptoms/issues in general, for me was acceptance. Acceptance that I could no longer do what I used to do several weeks ago. I used to dance for my mental health, because I enjoy reggaetón, and moving freely, and aerobic exercise is supposed to reduce depressive symptoms. I had to accept that I could no longer do that on most of the days due to nausea, fatigue, migraines. But still when I could, I tried to move – going for a walk near my house, going up and down the stairs (the house where I live has a staircase), doing a physical chose – washing the floor, vacuuming. Some movement is better than no movement at all, and I accepted that is it the situation right now, but it is also temporary.
Mindfulness – sometimes you cannot solve a problem. I have been feeling pretty lethargic throughout the whole pregnancy, especially in the third trimester. I was also not able to resolve the acid reflux issue and the stuffy nose, only reduce the symptoms somewhat. Mindfulness helps to observe your experiences from the side and accept that these are the current sensations/emotions/symptoms. I think observation can help realize how negative symptoms come in waves, so that you don’t end up generalizing or catastrophizing – “every day is terrible”, “I always feel awful”. I’m also mindful of the fact that I chose to be pregnant, as my goal is to have my own family, therefore this is something I have to go though in order to achieve my goal. I also remind myself that pregnancy is definitely a temporary condition, no one has stayed permanently pregnant.

It’s not always about some serotonin imbalance… let’s pay more attention to neurology

I get articles recommended by my Anroid phone, I assume based on an algorithm that performs some sort of machine learning model based on my browsing history. I actually like this feature, because I find the recommendations often actually interesting. So thumbs up for machine learning!

Today I came across an article about a woman with recurring severe depression, and in her case for many years no medical tests were performed, and her psychiatrist kept prescribing her different kinds of antidepressants, without considering any other potential causes or treatments. This reminds me of my own experience with autoimmune encephalitis, luckily I did get treated after two years from my first hospitalization in the psychiatric unit, not after more than a decade. In the case of this woman, eventually a brain tumour of a significant size was found, in 2019. She had recurring episodes of severe depression starting from 2002. As I understood, it’s not possible to find out at this point when the tumour actually originated, and whether it was the cause of depression, but it’s clear from the story that after the treatment of the tumour, the woman’s life significantly improved – she went back to her scientific career, finding a job as a scientist in a biotech firm. She got married, resumed activities she used to enjoy, and was weaned off antidepressants. Given these observations, it seems to me that the tumour and her depression were not just a correlation, but there is a causation here.

Unfortunately it seems rare that psychiatrists would order any medical tests even in the case of treatment resistant depression. I had to switch a few family doctors, and in the end went to one whom my mother knows for decades, and she agreed to order an MRI for me, and blood tests for thyroid hormones, infections, and antibodies. My psychiatrist never proposed to do any tests. Only after I received back the results, and some of them were abnormal, specifically the antibody levels, I was able to refer myself to neurology. Seems that we, psychiatric patients, have to often be very proactive in demanding medical testing. For this reason I think it is important to be aware of cases where depression was resistant to standard antidepressant treatments, but later on a specific medical cause was found.

Not ‘just depression.’ She seemed trapped in a downward mental health spiral.

Blaine’s first bout of depression occurred in 2002 when she was in her first year of a doctoral program in materials science at the University of California at Santa Barbara
She was prescribed Prozac, recovered and returned to California. Six months later she left school for good and found full-time work in a coffee shop
In 2005, Blaine began working as a research associate at a polymer film company
Her illness seemed to follow a pattern: after a few years the antidepressant inexplicably stopped working; her psychiatrist would prescribe a new drug and she would get better
In 2018 Blaine had lost her job of 10 years and she seemed trapped in a downward spiral
She left her job as a research scientist in 2018 and began working as a server at a variety of restaurants in Charlottesville
By late summer Blaine had developed what she assumed were frequent migraine headache, sometimes her balance was off and she complained that her vision had deteriorated and she needed new glasses, psychiatric medication was not effective
On Jan. 2 2019, a hospital psychiatrist doubled the dose of her antidepressant
Several days later Blaine suddenly collapsed and began vomiting, at the ER where she was diagnosed with a “vasovagal episode” — fainting that results from certain triggers including stress
Her sister and mother insisted doctors take a closer look, Blaine underwent an MRI scan of her brain
MRI findings showed a tumor the size of an orange had invaded the right frontal lobe of Blaine’s brain, there was evidence of herniation, a potentially fatal condition that occurs when the brain is squeezed out of position
During a 10-hour operation, University of Virginia neurosurgeon Ashok Asthagiri removed a grade 2 astrocytoma, a slow-growing malignancy that he said “could have been there for years.”
“especially in the setting of mental illness,” the neurosurgeon cautioned, “it is easy to disregard symptoms that maybe should be evaluated.” Doctors “need to be vigilant. Once [a patient] gets labeled, everything is viewed as a mental health problem.”
After recovering from surgery, Blaine underwent radiation and chemotherapy; she finished treatment in December 2019
Recently Blaine was hired as a scientist at a biotech firm. She has resumed the activities she previously enjoyed: rowing, cooking and walking her dogsHer psychological health has improved significantly and her new psychiatrist is weaning her off her antidepressant

More articles on this subject:

Why are women with brain tumours being dismissed as attention-seekers?

Women with serious medical conditions are more likely than men to have their symptoms attributed to depression and anxiety
Historically, women’s health has been viewed with a “bikini approach”, the primary focus being breasts and the reproductive system
One study drew data from 35,875 cardiac patients, 41% of them women, across nearly 400 US hospitals. It found that women faced a higher risk of dying in hospital, subsequent heart attacks, heart failure, and stroke. They were less likely to have an ECG within 10 minutes and to receive crucial medications. And women younger than 65 years old are more than twice as likely to die from a heart attack than men of the same age
A Bias Against Women in the Treatment of Pain, found that women were less likely to receive aggressive treatment when diagnosed, and were more likely to have their pain characterised as “emotional,” “psychogenic” and therefore “not real”

Woman misdiagnosed with anxiety actually had a brain tumour the size of a tennis ball

Laura Skerritt, 22, began suffering migraines, sickness and psychosis and was told her symptoms were caused by anxiety, depression – and even bi-polar disorder
She was prescribed anti-depressants but the medication had no effect on her condition which continued to deteriorate
By November 2018, the young swimming instructor, from Templecombe, Somerset, was struggling to walk and was having seizures.
A scan at Yeovil District Hospital revealed a tennis ball-sized brain tumour

Brain tumor revealed by treatment-resistant depression

The 54-year-old woman had been depressed for 6 months, but treatment with the antidepressant fluoxetine and the anti-anxiety medication bromazepam was discontinued after 5 months because these were not found to be effective
She had suicidal thoughts, admitted self-accusation due to ineffectiveness in her job, and lost interest in her usual past times
A neurological examination was normal. However, a brain CT scan and MRI revealed meningiomatosis with a giant meningioma–the most common primary benign brain tumour–in her left frontal lobe
The patient underwent emergency surgery, and made a recovery. The depressive symptoms disappeared within one month
Recommendation – brain scan should be performed if the patient presents a late onset of depressive syndrome after 50 years of age, if a diagnosis of treatment-resistant depression is made or if the patient is apathetic

1 gram of shrooms helped me realize that I have a caffeine addiction which negatively impacts my BPD symptoms

I recently did 1 gram of shrooms and even though it was not such a dose that I would see any visuals, it was a very useful experience for me.

I have been diagnosed with having borderline personality disorder traits, which then lead to depression and anxiety.

Caffeine definitely is not the cause of my BPD symptoms, but the recent shrooms experience helped me realize that I do have a caffeine addiction which negatively impacts my life. I think I have been denying it, saying to my self that – it’s just caffeine, it’s not like I do illegal stimulant drugs. Shrooms helped me accept that brain biochemistry doesn’t care about the legal status of caffeine. I had to accept that even though being completely legal and sold everywhere, I do get mood crashes from caffeine as I would from cocaine (which I tried a long time ago in high school). I can have a few cups of tea in a day, but I do like to drink several in a row, I also like coffee and yerba mate. I have been observing my symptoms for a while and I do notice that I get dysphoric later on in the day if I have coffee or yerba mate in the morning, especially on an empty stomach. I also get more paranoid about being alone, not having any friends (even though I do have several good friends), etc. I knew this for a while, just shrooms helped me accept that I really should do something about the caffeine addiction as it really negatively impacts my mood and sense of self.

I don’t think I need to completely give up tea, but I did have to quit coffee and yerba mate, which actually did help me to have a more even mood throughout the day. I also have been taking CBD oil that I made at home, I think that also helps with anxiety and mood swings. I will still have a few cups of black tea, which I love, but I need to limit myself at only three-four cups of tea per day, not very strong.

This realization might seem not very important, maybe some people expect some enlightenment or spiritual experiences from shrooms, but whenever I do shrooms I actually feel very logical and I am able to see myself from a side. I was able to analyze the correlation between my caffeine consumption and my BPD symptoms in a more unbiased way and this is actually an important realization for me, as BPD symptoms really worsen my quality of life, so if something like reducing caffeine can help – it’s not a breakthrough for humanity, but a big improvement for me. And also hoping to help anyone else reading it affected by BPD – I do believe caffeine might worsen psychiatric symptoms for some individuals.

Observations on calcium and PMS/PMDD symptoms. Observaciónes sobre calcio y síntomas de SPM/TDPM.

After several visits to the doctor, I finally received references for hormone blood tests. I definitely do not regret spending time on doctor visits and laboratory tests, because it was really interesting to observe hormonal fluctuations throughout the cycle. The results clearly showed that my progesterone level quickly rises during the luteal phase, close to 50 nmol/l. One day/several days before menstruation, my progesterone drops to 1.8 nmol / l. At the peak, my progesterone was close to the top threshold. The level was not exactly abnormal, but research indicates that some women react negatively to changes in hormone levels.

Premenstrual dysphoric disorder (PMDD) – a much more severe form of premenstrual syndrome (PMS). It may affect women of childbearing age. The exact cause of PMDD is not known. It may be an abnormal reaction to normal hormone changes that happen with each menstrual cycle. The hormone changes can cause a serotonin deficiency.

What is premenstrual dysphoric disorder (PMDD)?

I also came across an article in the Journal of Clinical Endocrinology & Metabolism, which states that there may be cyclical changes in calcium metabolism during the menstrual cycle in women with PMDD. Interesting points from the article:

Irritability, anxiety, and mania have been associated with hypocalcemia, whereas increased calcium concentrations have been noted in some patients with depression.
Three separate investigations have demonstrated that the dysphoria, anxiety, depression, and somatic symptoms of PMS all respond favorably to either increased dietary calcium intake or daily calcium supplementation
Increased calcium intake proved to benefit significantly all four major categories of PMS symptoms (negative affective symptoms, water retention symptoms, food cravings, and pain symptoms).
When compared with asymptomatic women, women with PMS were shown to have exaggerated fluctuations of the calcium-regulating hormones across the menstrual cycle with evidence of vitamin D deficiency and secondary hyperparathyroidism.

For the authors’ study – a total of 129 women completed the timed biochemical and hormone evaluation with 115 (68 PMDD and 47 controls) providing hormone data meeting criteria for analysis. Results – Although the screening baseline 24-h urine calcium was not found to be significantly different between the groups, the random urine calcium collections during hormonal sampling were significantly lower in the PMDD group compared with controls.

In the PMDD group, total serum calcium was found to be significantly lower at 3 points: at follicular phase 1 (menses) (9.17 ± 0.55 mg/dl, P < 0.001) compared with later phases 2, 3, and 4; at midcycle phase 3 (9.25 ± 0.55 mg/dl) compared with phase 2 (9.33 ± 0.58 mg/dl, P = 0.036); and during late luteal phase 5 (9.18 ± 0.73 mg/dl) compared with phase 4 (9.27 ± 0.55 mg/dl, P = 0.018). Ionized calcium did not fluctuate as dramatically as did total calcium, but a large difference was noted between early phases 1 and 2 of the menstrual cycle again with phase 1 having the lowest ionized calcium concentration (1.166 ± 0.072 vs. 1.175 ± 0.073 mmol/liter, P = 0.069). Intact PTH peaked in follicular phase 2 (56.9 ± 35.3 pg/ml) following the decline in serum calcium during phases 1 and 5. Follicular phase intact PTH was significantly higher than luteal phase concentrations and reached its nadir in luteal phase 4 (50.9 ± 34.4 pg/ml, P < 0.01). In conjunction with the follicular phase rise in intact PTH, serum pH was lower in the follicular phase 1 and 2 compared with midcycle phase 3 and luteal phase 4 (phase 1, 7.36 ± 0.004 vs. phase 3, 7.37 ± 0.023; P = 0.015; data not shown). The concentration of 1,25(OH)₂D declined precipitously in luteal phase 4 and was significantly lower compared with all earlier phases (phase 4, 45.0 ± 27.5 vs. phase 3, 49.6 ± 27.5 pg/ml; P = 0.006). Urine calcium and 25OHD concentrations did not appear to vary between individual phases in the PMDD group.

Cyclical Changes in Calcium Metabolism across the Menstrual Cycle in Women with Premenstrual Dysphoric Disorder

*************************************************************************************

Después varias visitas al doctor, finalmente recibí referencias para análisis de sangre de hormonas. Definitivamente no me arrepiento de pasar tiempo en las visitas al médico y las pruebas de laboratorio, porque fue realmente interesante observar las fluctuaciones hormonales a lo largo de ciclo. Los resultados mostraron claramente que mi nivel de progesterona sube rápidamente durante la fase lútea, cerca de 50 nmol / l. Un día/ varios días antes la menstruacion, mi progesterona baja a 1.8 nmol / l. En el pico, mi progesterona estaba cerca del umbral superior. El nivel no era exactamente anormal, pero la investigación indica que algunas mujeres reaccionan negativamente a los cambios en los niveles hormonales.

Trastorno disfórico premenstrual (TDPM): una forma mucho más grave de síndrome premenstrual (SPM). Puede afectar a mujeres en edad fértil. La causa exacta de TDPM no se conoce. Puede ser una reacción anormal a los cambios hormonales normales que ocurren con cada ciclo menstrual. Los cambios hormonales pueden causar una deficiencia de serotonina.

También me encontré con un artículo en el Journal of Clinical Endocrinology & Metabolism, que establece que puede haber cambios cíclicos en el metabolismo del calcio durante el ciclo menstrual en mujeres con TDPM. Puntos interesantes del artículo:

La irritabilidad, la ansiedad y la manía se han asociado con hipocalcemia, mientras que se han observado concentraciones elevadas de calcio en algunos pacientes con depresión.
Tres investigaciones separadas han demostrado que la disforia, la ansiedad, la depresión y los síntomas somáticos del síndrome premenstrual responden favorablemente al aumento de la ingesta de calcio en la dieta o a la suplementación diaria de calcio.
El aumento de la ingesta de calcio demostró beneficiar significativamente las cuatro categorías principales de síntomas de SPM (síntomas afectivos negativos, síntomas de retención de agua, antojos de alimentos y síntomas de dolor).
En comparación con las mujeres asintomáticas, las mujeres con síndrome premenstrual mostraron fluctuaciones exageradas de las hormonas reguladoras de calcio a lo largo del ciclo menstrual con evidencia de deficiencia de vitamina D e hiperparatiroidismo secundario.

Para el estudio de los autores, un total de 129 mujeres completaron la evaluación bioquímica y hormonal cronometrada con 115 (68 TDPM y 47 controles) que proporcionaron datos hormonales que cumplían los criterios para el análisis. Resultados: aunque no se encontró que el calcio basal en orina de 24 h para la detección sea significativamente diferente entre los grupos, las recolecciones aleatorias de calcio en orina durante el muestreo hormonal fueron significativamente más bajas en el grupo TDPM en comparación con los controles.

En el grupo TDPM, se encontró que el calcio sérico total era significativamente más bajo en 3 puntos: en la fase folicular 1 (menstruación) (9.17 ± 0.55 mg / dl, P <0.001) en comparación con las fases posteriores 2, 3 y 4; en la fase 3 del ciclo medio (9,25 ± 0,55 mg / dl) en comparación con la fase 2 (9,33 ± 0,58 mg / dl, P = 0,036); y durante la fase lútea tardía 5 (9,18 ± 0,73 mg / dl) en comparación con la fase 4 (9,27 ± 0,55 mg / dl, P = 0,018). El calcio ionizado no fluctuó tan dramáticamente como el calcio total, pero se observó una gran diferencia entre las fases tempranas 1 y 2 del ciclo menstrual nuevamente con la fase 1 con la concentración más baja de calcio ionizado (1.166 ± 0.072 vs. 1.175 ± 0.073 mmol / litro , P = 0,069). La PTH intacta alcanzó su punto máximo en la fase folicular 2 (56,9 ± 35,3 pg / ml) después de la disminución del calcio sérico durante las fases 1 y 5. La PTH intacta en la fase folicular fue significativamente mayor que las concentraciones de la fase lútea y alcanzó su punto más bajo en la fase lútea 4 (50,9 ± 34,4 pg / ml, P <0,01). Junto con el aumento de la fase folicular en la PTH intacta, el pH sérico fue menor en la fase folicular 1 y 2 en comparación con la fase 3 del ciclo medio y la fase lútea 4 (fase 1, 7.36 ± 0.004 vs. fase 3, 7.37 ± 0.023; P = 0.015 ; datos no mostrados). La concentración de 1,25 (OH) 2D disminuyó precipitadamente en la fase lútea 4 y fue significativamente menor en comparación con todas las fases anteriores (fase 4, 45.0 ± 27.5 vs. fase 3, 49.6 ± 27.5 pg / ml; P = 0.006). Las concentraciones de calcio en la orina y 25OHD no parecen variar entre las fases individuales en el grupo TDPM.

SSRIs, fungi, and exotic botanicals

This post is about comparing my experiences with fluoxetine (Prozac – an SSRI), psilocybe mushrooms, lion’s mane mushroom, and yerba mate tea. Of course this is my personal experience, not a medical study. Remember that everyone is affected differently by psychoactive compounds. In fact recently my friend told me an interesting scientific theory in regards to why humans differ a lot psychologically. Have you heard of fungi that make ants climb on top of a leaf, hook themselves, and stay there without eating, basically committing ant suicide? The spores of the fungi then burst from the ant and go on to grow into new fungi. Ophiocordyceps unilateralis is called the zombie-ant fungus.

“Researchers think the fungus, found in tropical forests, infects a foraging ant through spores that attach and penetrate the exoskeleton and slowly takes over its behavior.

As the infection advances, the enthralled ant is compelled to leave its nest for a more humid microclimate that’s favorable to the fungus’s growth. The ant is compelled to descend to a vantage point about 10 inches off the ground, sink its jaws into a leaf vein on the north side of a plant, and wait for death.

Meanwhile, the fungus feeds on its victim’s innards until it’s ready for the final stage. Several days after the ant has died, the fungus sends a fruiting body out through the base of the ant’s head, turning its shriveled corpse into a launchpad from which it can jettison its spores and infect new ants.”

So what does this have to do with humans being different? The theory says that humans evolved to react differently to same psychoactive molecules in order to not become victims to simple fungi organisms. Since the infectious fungi are not very complex organisms, they can only release so many molecules. By evolving to have complex brains and having individuals react differently to the same psychoactive molecule, humans became resistant to being overtaken by simple fungi. The theory is that there is no one molecule that a fungi could produce that would make all humans act the same, stop whatever they were doing, walk to a nice moist and wooded area, lie down, and wait for fungi spores to emerge from them.

Back to fluoxetine and shrooms

Fluoxetine

Fluoxetine is a selective serotonin reuptake inhibitor. N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine. It delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Also dopamine and norepinephrine may contribute to the antidepressant action of fluoxetine in humans.

From wiki: Fluoxetine elicits antidepressant effect by inhibiting serotonin re-uptake in the synapse by binding to the re-uptake pump on the neuronal membrane to increase its availability and enhance neurotransmission. Norfluoxetine and desmethylfluoxetine are metabolites of fluoxetine and also act as serotonin re-uptake inhibitors, so increase the duration of action of the drug. Fluoxetine appeared on the Belgian market in 1986. In the U.S., the FDA gave its final approval in December 1987, and a month later Eli Lilly began marketing Prozac.

fluoxetine

Fluoxetine is one of medications considered to be effective for PMDD (premenstrual dysphoric disorder). Also research indicates that low doses of fluoxetine could help with PMS. PMS appears to be triggered by the fall in secretion of the ovarian sex steroid hormone progesterone that occurs towards the end of the menstrual cycle and leads to a decline in its breakdown product allopregnanolone, which acts in the brain as a potent sedative and tranquilising agent. In other words, women with PMS are undergoing a type of drug withdrawal response from an in-built, tranquilising steroid chemical in their brains. New research shows that antidepressants such as fluoxetine inhibit a specific enzyme in the brain, which deactivates allopregnanolone, therefore maintaining the chemical balance of this in-built tranquiliser in the brain. Recent findings published in the British Journal of Pharmacology, show that short-term treatment with a low dose of fluoxetine immediately prior to the rat’s premenstrual period not only raised brain allopregnanolone and prevented the development of PMS-like symptoms but also blocked the increase in excitability of brain circuits involved in mediating the stress and fear responses that normally occur during this phase of the cycle.

Enzyme identified that could lead to targeted treatment for PMS

A review of studies found that fluoxetine was more tolerabled by female patients than tricyclic amine antidepressants (Amitriptyline, Imipramine). ” In this study, a retrospective analysis of 11 randomized, double-blind, well-controlled trials was done to compare data from 427 female patients on fluoxetine and 423 female patients on TCAs. Both fluoxetine and TCAs significantly reduced the HAMD17 total mean score from baseline to end point, week 5 (fluoxetine, 24.35 to 14.37; TCAs, 24.57 to 14.43; p < 0.001). Both treatment groups were associated with significant reductions in the HAMD17 anxiety/somatization and insomnia subfactor scores. Abnormal vision, constipation, dizziness, dry mouth, and somnolence occurred more frequently (p < 0.05) in the TCA group. Insomnia and nausea were the only adverse events more common (p < 0.05) in the fluoxetine group. This study demonstrates that fluoxetine is an effective and tolerable agent for the treatment of major depressive disorder in women.”

Fluoxetine vs. tricyclic antidepressants in women with major depressive disorder

My experience with fluoxetine – the first time that I took 10mg of fluoxetine, I felt a difference in less than three hours. It was as if I was taken out of a dark basement and into a sunny day in July. Unfortunately I also experienced insomnia that did not go away and I had a sense of apathy, in the end I stopped taking fluoxetine, but I know many women who swear by it.

Psilocybin

Next I will mention psilocybin. Psilocybin is a psychedelic compound produced by more than 200 species of mushrooms. Psilocybin is quickly converted in human body to psilocin. Psilocin is a prtial agonist for several serotonin receptors. An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Recently there has been increased reseach interest in psilocybin and how it could help with depression.

“A landmark study conducted by the Beckley/Imperial Research Programme has provided the first clinical evidence for the efficacy of psilocybin-assisted psychotherapy to treat depression, even in cases where all other treatments have failed. We gave oral psilocybin to 20 patients with treatment-resistant depression, all of whom had previously tried at least two other treatment methods without success. Participants had suffered from depression for an average of 18 years, with severity ranging from moderate to severe. Each patient received two doses of psilocybin (10 and 25mg) 7 days apart, accompanied by psychological support before, during, and after each session. All participants also underwent brain scans to investigate the neural underpinnings of psilocybin mechanisms of action on depression. Follow-up examinations were carried out at 5 weeks, and three and six months. Results highlights All patients showed some reductions in their depression scores at 1-week post-treatment and maximal effects were seen at 5 weeks, with results remaining positive at 3 and 6 months. Notably, reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. The drug was also well tolerated by all participants, and no patients sought conventional antidepressant treatment within 5 weeks of the psilocybin intervention. While it is important to note that this was a relatively small study with no control group, placebo, or ‘blinding’ (meaning participants were fully aware what they were getting), the results are extremely encouraging and confirm that psilocybin is safe to give to depressed patients, warranting further research into this area.”

Sceletium tortuosum (Kanna) – a plant commonly found in South Africa. Laboratory studies have found that Sceletium alkaloids are selective serotonin reuptake inhibitors (SSRIs). Thus, they have the same action as pharmaceutical SSRIs such as Prozac. Animal studies have found that Sceletium can improve mood and reduce anxiety-related behaviours.

Caffeine experimentation

The take on caffeine is that it’s bad for anxiety and intrusive thoughts. Yet there is research indicating that coffee drinkers have a lower risk of depression. On the other hand caffeine could contribute to a panic attack? Evidence is therefore inconclusive – should you consume caffeine if you have mental problems, and how much?

I know there are diets such as the autoimmune protocol diet (AIP) that eliminate coffee, but I have not found much evidence contraindicating coffee consumption. AIP diet includes eliminating a lot of food groups, including nuts and coffee, but Harvard Health Publishing actually states and nuts and coffee are anti-inflammatory foods. I will trust Harvard on that (as the AIP diet blogs don’t provide any actual evidence that coffee and nuts are inflammatory). From Harvard Health – “studies have also associated nuts with reduced markers of inflammation and a lower risk of cardiovascular disease and diabetes. Coffee, which contains polyphenols and other anti-inflammatory compounds, may protect against inflammation, as well.” So here we go – one point for coffee.

The question is though – perhaps coffee drinking in the long-term reduces some inflammation, but what if in the short-run, it increases anxiety in a few hours. Is it really worth it? And does it actually increase anxiety? What do we know so far about what coffee does to the brain? “By blocking adenosine, caffeine actually increases activity in the brain and the release of other neurotransmitters like norepinephrine and dopamine. This reduces tiredness and makes us feel more alert. There are numerous studies showing that caffeine can lead to a short-term boost in brain function, including improved mood, reaction time and general cognitive function.” “Caffeine helps the brain release dopamine into the prefrontal cortex, a brain area important for mood regulation. Caffeine may also help storage of dopamine in the amygdala, another part of the brain important for anxiety regulation.“

One recent study with some mice (don’t really know if that is applicable to humans), found that acute caffeine administration also reduced anxiety-related behaviors in mice without significantly altering locomotor activity. I think the researchers had only 12 mice, I guess they weren’t able to get a grant to afford more, so I wouldn’t take the study very seriously.

I have consumed caffeine since childhood, since in Russia black tea is a very common drink. Coffee I started consuming regularly later on, when I was a teenager. I did quit coffee in 2016 as I was hoping that would help with panic attacks and also I started the AIP diet which eliminates coffee. Later on, in summer of 2017, I did go caffeine free for more than a week, but I noticed that my obsessive thoughts and aggressiveness were only exacerbated. I continued to consume black tea and this week I decided to try and reintroduce coffee.

Caffeine is the quintessential mimic of a neurochemical called adenosine. While you’re awake, the neurons in your brain fire away and produce a compound called adenosine as a byproduct. Adenosine is constantly monitored by your nervous system through receptors. In the brain adenosine is an inhibitory neurotransmitter. This means, adenosine can act as a central nervous system depressant. In normal conditions, it promotes sleep and suppresses arousal. When awake the levels of adenosine in the brain rise each hour. Typically, when adenosine levels drop and hit a certain low level in your spinal cord and brain, your body will signal to you to start relaxing to prepare for sleep. Caffeine mimics adenosine’s shape and size, and enter the receptors without activating them. The receptors are then effectively blocked by caffeine (in clinical terms, caffeine is an antagonist of the A1 adenosine receptor). By blocking the receptors caffeine disrupts the nervous system’s monitoring of the adenosine tab. The neurotransmitters dopamine and glutamate, the brain’s own home-grown stimulants, are freer to do their stimulating work with the adenosine tab on hold. When a substantial amount of caffeine is ingested—such as the typical 100 to 200 milligrams from a strong, eight-ounce cup of coffee, caffeine tricks your body into thinking that it’s not yet time for sleep by acting like adenosine. Generally, caffeine lasts about five to six hours in the body before wearing off.

Research on depression, anxiety, and caffeine is still in its early stages. One study from the Journal of Alzheimer’s Disease links moderate caffeine intake (fewer than 6 cups of coffee each day) to a lower risk of suicide. Conversely, in rare cases high doses of caffeine can induce psychotic and manic symptoms, and more commonly, anxiety. Patients with panic disorder and performance social anxiety disorder seem to be particularly sensitive to the anxiogenic effects of caffeine, whereas preliminary evidence suggest that it may be effective for some patients with obsessive-compulsive disorder. In a small study, seven of twelve patients with OCD saw “immediate improvement” on 300 milligrams of coffee daily. The author suggests that caffeine may work better in one concentrated dose each morning than spaced out throughout the day, and reminds us that caffeine remains a “well-known anxiety producer in many people.”

If all of this research seems a bit contradictory, it is. Like almost anything in science, there’s no conclusive verdict about coffee.

Since my coffee reintroduction experiment starting this Monday, so far mu experiences are more positive than negative. During these past four days, it seems that I had a reduction in obsessive and anxious thoughts. A negative effect was yesterday night, I drank a decaf Americano around 11pm, and then woke up in the middle of the night from a nightmare in which I was kidnapped by a serial killer. Today I decided to have just two cups of coffee – in the morning and in the afternoon, and stop caffeine after 5pm. I don’t particularly enjoy participating in serial killer action dreams. I don’t know whether it was the decaf that lead to the nightmare, but there is one study in which Swiss scientists studying caffeine’s effects in a small group of people report markedly elevated blood pressure and increased nervous system activity when occasional coffee drinkers drank a triple espresso, regardless of whether or not it contained caffeine. The results suggest that some unknown ingredient or ingredients in coffee – not caffeine – is responsible for cardiovascular activation, he explains. Coffee contains several hundred different substances.

New Buzz On Coffee: It’s Not The Caffeine That Raises Blood Pressure

I have also come across an article discussing the best times to drink coffee. It states that The peak production of cortisol occurs between 8–9 am (under normal circumstances.) This means that at the time that many people are having their first cup of coffee on the way to work, their bodies are actually “naturally caffeinating” the most effectively. Cortisol is considered a stress-related hormone and consumption of caffeine has been shown to increase the production of cortisol when timed at periods of peak cortisol levels. An increased tolerance for caffeine can therefore lead to heightened cortisol levels which can disturb circadian rhythms and have other deleterious effects on your health. The article suggests that the times of peak cortisol levels in most people are between 8-9 am, 12-1 pm and 5:30-6:30 pm. Therefore, timing your “coffee breaks” between 9:30am-11:30am and 1:30pm and 5:00pm takes advantage of the dips in your cortisol levels when you need a boost the most.

List of medications and supplements for depression and obsessive thoughts

Here I will list different medications, supplements, and procedures that are used to treat depression, anxiety, and obsessive/suicidal thoughts. I am not suggesting that you go out and buy a bunch of antidepressants and try them one by one, I just want you to be aware of what exists out there so that you can discuss this with your doctor. Some things, such as a daylight lamp, or omega 3s, don’t require prescription. Since I have been dealing with autoimmune encephalitis for more than three years already, I have tried most of these treatments in attempts to reduce my depressive symptoms, psychosis, and intrusive thoughts.

Many people do get better with antidepressants. I have to note though, that in my case, the most useful treatment was high-dose intravenous steroids (IV Solu-Medrol) for five days. I did have severe psychotic depression with suicidal tendencies, my neurologist and psychiatrist propose that this was due to autoimmune encephalitis (Hashimoto’s encephalitis) – brain inflammation. Many people have milder depression and do well after antidepressant treatment. My state has improved but it is not without moments of intrusive thoughts and for this reason I continue trying different methods.

Medication

Antidepressants

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How does your psychiatrist determine which antidepressant to try? It seems that in general this is not based on any specific medical tests, but is based on the discussion with you about your symptoms. I did get a genetic test done on my saliva. This was part of CAMH Impact Study in Toronto, the provided report is called GeneSight Psychotropic Test. The company states that their test “analyzes how your genes affect your response to psychotropic medications commonly prescribed to treat depression, anxiety, bipolar disorder, posttraumatic stress disorder (PTSD), obsessive compulsive disorder, schizophrenia and other behavioral health conditions. There are dozens of medications used to treat depression and other mental illnesses and selecting the right antidepressant medication or other medication can be a challenging and frustrating process. GeneSight Psychotropic’s genetic testing enables your clinician to identify and avoid depression, anxiety and/or other medications that are unlikely to work or may cause side effects.” This test was provided to me for free by CAMH in Toronto.

GeneSight Psychotropic Test link

New antidepressants:

There are three new antidepressants that have become recently available in US and Canada – vortioxetine, levomilnacipran extended-release (ER), and vilazodone. Vortioxetine – may enhance serotogenic activity via reuptake inhibition of serotonin receptors. Levomilnacipran is a a serotonin norepinephrine reuptake inhibitor. Vilazodone is a serotonin reuptake inhibitor and partial serotonergic 5-HT1A receptor agonist.

The role of new antidepressants in clinical practice in Canada: a brief review of vortioxetine, levomilnacipran ER, and vilazodone

Antipsychotics

Sometimes antipsychotics are added to antidepressants during treatment. Usually antipsychotics are used to treat schizophrenia, why are they given to depressed patients? I think the reason is that many patients don’t achieve remission with antidepressants, so other medications/methods must be tried. In the large National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, only about 30% of patients achieved remission (virtual absence of depressive symptoms) after up to 12 weeks of first-line treatment with citalopram. Evidence of the usefulness of atypical antipsychotics in treating MDD goes back more than 7 years (statement from 2009). A controlled trial found that the combination of olanzapine and fluoxetine was more helpful in treating patients with MDD (without psychosis) than fluoxetine or olanzapine alone.2 The group that received combination therapy did significantly better than the others. In November 2007, the FDA approved aripiprazole as the first atypical antipsychotic to treat MDD. It is specifically for adjunctive treatment, along with an antidepressant, for the treatment of refractory MDD.

Atypical Antipsychotics for Treating Major Depression

Aripiprazole (Abilify) – was approved by FDA for major depressive disorder in 2007, for patients who had inadequate response to antidepressants. Aripiprazole is a partial agonist at dopamine D(2) and D(3) and serotonin 5-HT1A receptors, and is an antagonist at 5-HT(2A) receptors.

Ripseridone – risperidone has actions at several 5-HT (serotonin) receptor subtypes. A study showed that depression symptoms improved modestly but significantly more in the risperidone group compared with the placebo group, as measured by clinician-rated symptom response and patient-rated self-assessment. The 17-item Hamilton Rating Scale for Depression score improved more in the risperidone group versus the placebo group.

Quetiapine (Seroquel) – quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties. Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors. One study involved more than 700 people who had suffered from depression for at least one month but less than one year. Patients were randomly assigned to take one of three doses of Seroquel or a placebo once a day for six weeks. Those taking Seroquel showed greater improvement in depression symptoms than those on placebo.

Supplements

St. John’s Wort – hypericum perforatum, it is a flowering plant. Sold in health stores/drug stores/online. A 2008 review of 29 international studies suggested that St. John’s wort may be better than a placebo and as effective as different standard prescription antidepressants for major depression of mild to moderate severity. A 2015 meta-analysis review concluded that it has superior efficacy to placebo in treating depression, is as effective as standard antidepressant pharmaceuticals for treating depression, and has fewer adverse effects than other antidepressants.[23] The authors concluded that it is difficult to assign a place for St. John’s wort in the treatment of depression owing to limitations in the available evidence base, including large variations in efficacy seen in trials performed in German-speaking relative to other countries. In Germany, St. John’s wort may be prescribed for mild to moderate depression, especially in children and adolescents.

Omega – 3 – omega-3 fatty acids are found in oily fish such as salmon. You can also purchase fish oil supplements in health stores/online. In general eating oily fish is considered to be a healthy choice. There is some evidence that omega-3s might help with depression, but this evidence is not very strong. From Cochrane review: “At present, we do not have enough high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD. We found a small-to-modest positive effect of n-3PUFAs compared to placebo, but the size of this effect is unlikely to be meaningful to people with depression, and we considered the evidence to be of low or very low quality, with many differences between studies.“

SAMe – S-adenosyl-L-methionine (SAMe) is a compound found naturally in the body. SAMe helps produce and regulate hormones and maintain cell membranes. A synthetic version of SAMe is available as a dietary supplement in the U.S. In Europe, SAMe is a prescription drug. From Cochrane review: “We included eight studies involving 934 people in this review. There was no strong evidence of a difference in effectiveness between SAMe and imipramine or escitalopram when used alone. It was superior to placebo when used in combination with selective serotonin reuptake inhibitor antidepressants, but this evidence was of low quality. There was no significant difference in terms of effectiveness between SAMe and placebo alone, but again this evidence was of very low quality.“

Folic acid – also known as vitamin B9. Foods that are naturally high in folate include leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, fruits (such as bananas, melons, and lemons) beans, yeast, mushrooms, meat (such as beef liver and kidney), orange juice, and tomato juice.

“The evidence for a link between depression and folate levels comes from various sources. Along with vitamins B6 and B12, folate helps break down the amino acid homocysteine. High blood levels of homocysteine are associated with Alzheimer’s disease and depression, although a cause-and-effect relationship hasn’t been proven. The breakdown of homocysteine generates SAMe, a major constituent of brain cells and, some think, a possible treatment for depression. Low levels of SAMe might explain any connection between folate and depression.”

Folate for depression

Probiotics – there is one combination of two bacterial strains that has shown some promise in treating mental health issues. Bifdobacterium longum R0175 and L. helveticus R0052 have been found to reduce symptoms of stress and anxiety. In Canada there are two brands with these strains – CalmBiotic and Jamieson Probiotic Sticks.

Clinical Guide to Probiotic Products Available in Canada

Other things to consider