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

  • Getting tested for hypo/hyperthyroidism – potential need for thyroid hormones

Treating an underactive thyroid gland may improve mood

  • Getting tested for anemia

Sometimes the first symptoms of iron deficiency are neurologic

  • Getting tested for coeliac disease – possible benefit from excluding gluten from diet

The Link between Celiac Disease and Depression

  • Autoimmune disease testing – includes coeliac disease, hashimoto’s thyroiditis, autoimmune encephalitis, lupus, type 1 diabetes, etc.

Infection, autoimmune disease linked to depression

  • Don’t forget to exercise and eat healthy! I really mean it, you just really need to do it, there is no other way…

Depression and anxiety: Exercise eases symptoms

Mediterranean diet tied to lower risk of depression

Following the MIND diet for autoimmune encephalitis and depression

So there has been the MIND diet going around. Some research indicates that it can reduce the risk of developing Alzheimer’s/dementia. The MIND diet is very similar to the Mediterranean diet. As most people know, that means eating a lot of oily fish, whole grains, vegetables, nuts, and beans/legumes. The MIND diet is a bit more specific – it recommends green leafy vegetables every day, berries (especially blueberries), whole grains three! times a day, nuts every day. You can see the list below:

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Dietitians provide some information on how this diet might work: “A diet that supports vascular health is certainly protective against vascular dementia, but certain foods and food components have been directly linked to improved neurological function or reduced AD biomarkers in the brain.1,8 “MIND diet foods reflect nutrients shown to slow cognitive decline, lower risk of AD, decrease amyloid in the brain or neuron loss in animal studies, or decrease oxidative stress and inflammation”.

Food for Thought: The MIND Diet — Fighting Dementia With Food

Well since my brain seems to be screwed up, anything that might fight inflammation while improving neurological function sounds good to me! It’s also a lot less restrictive than the AIP diet or ketogenic diet. Definitely much easier than intermittent fasting. I see myself being able to follow this diet long-term. I want to eat my grains, I also haven’t found much evidence that excluding grains helps with depression or inflammation. I like to eat my quail eggs and goat yougurt, so I don’t want to be excluding eggs or dairy (AIP excludes these foods). I don’t think the strict AIP diet should be followed for a long time, neither the ketogenic diet. I am not even sure whether keto diet can help with inflammation and depression, it includes tons of saturated fat. The MIND diet researchers actually recommend limiting saturated fat.

So how do you follow the MIND diet list in practice? Green leafy vegetables every day, berries, olive oil, nuts… how do you fit all of that into one day? And what if you don’t like looking or don’t have time? What if you are not one of those people who post on their vlog about avocado toast? I came up with some quick recipes, here I will post my breakfast idea. The breakfast consists of onions (vegetable √ ), kale (green leafy vegetable √ ), cooked with olive oil √, yougurt with blueberries (berries √), also you can add some toast (I don’t eat gluten, but I make gluten-free sourdough buns  – whole grain flour √), or you can easily make a lot of brown rice pudding – also whole grain √.

I want to make this simple. This is for actual practical eating, now a decorative meal. I prepare several items in the evening so that in the morning I can cook my breakfast in several minutes. I start work at 9 am and I try to wake up as late as possible, I don’t want to be cooking for even fifteen minutes in the morning.

Ingredients to buy:

  • Buy some frozen chopped onions, chopped kale, olive oil, eggs. Yougurt, frozen blueberries, nuts/seeds. Bread/sourdough bread. I don’t consume cow milk, so I buy goat/sheep yougurt, I also make soy yougurt. I also eat gluten-free, so I make sourdough buns at home. I make a lot of buns and a liter yougurt at once, so I don’t have to do this every day.
  • Why frozen vegetables? Because they are chopped and I don’t like chopping. Also they don’t go rotting in my fridge if I forget about them. Also you don’t need to wash frozen vegetables. So many benefits!

Evening preparation:

  • Get a frying pan. I hope you have one in your house. You do need at least one frying pan for this MIND diet project. If you don’t have one – go to the Dollar Store and get one please. Place the pan on your your counter. 20 seconds
  • Take out frozen kale and frozen onions out of the freezer. 10 seconds20181101_213108           20181101_213148 
  • Place some kale and onions into the frying pan. Add salt, pepper, and olive oil. 30 seconds

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  • Place the pan in the fridge. The vegetables will defrost overnight. 10 seconds

Morning cooking:

  • Take out some eggs from the fridge, take out the pan

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  • Turn on the burner, place frying pan on the burner, leave it on medium-high for about five minutes. And don’t just stand there those five minutes, go brush your teeth, or something!
  • After five minutes crack the eggs onto the pan, mix everything together with a spatula
  • Fry for another three- four minutes
  • Place in a container and take to work, if you work in an office using a computer – you can easily enjoy eating while pretending to work
  • Take a jar of yougurt with you, add frozen blueberries – another item checked off from the MIND list

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  • Don’t forget toast/sourdough bread – because they say whole grains three times a day. Can be gluten-free. Eating toast should be easy, not like eating a bunch of kale. Toast is good!

So there, in one breakfast – kale – green leafy vegetable √ , onion – a vegetable , good enough! √, olive oil √, toast/sourdough – whole grains √

What else did they say… nuts? just add them to yougurt √ add blueberries √ don’t add oily fish to your yougurt… Χ

Wine? Well I think you can have that any time 😉

Sourdough for mood and hyperglycemia

Not all carbs are equal. Several months ago I made a discovery of gluten-free sourdough recipes and now I eat it almost daily. I obtained a sourdough starter, and now that I have one, it can live on forever, as long as it gets fed. It can definitely outlive me! Feeding the starter is very simple and requires only two ingredients – brown rice flour and warm water. After being on a strict AIP diet for almost a year (a lot of food group exclusions, including grains), it was very exciting to once again eat bread, burritos, and blueberry muffins. I no longer follow the strict AIP diet since it did not turn out to be a magical cure for me. I did improve a bit, but that does not mean that every food group exclusion contributed to my improvement. One person (me) trying the AIP diet is not a clinical trial with test and control groups.

I do see strong correlation between my psychotic episodes and consumption of gluten/cow’s dairy/corn/chocolate/nightshades (bell peppers are fine, small amounts of tomatoes are also OK)/ high-glycemic foods. I haven’t found issues with eating gluten-free whole grains and also found no evidence that grains are inflammatory. I don’t consider any blog post evidence. If a blog post refers to a research paper, then I will consider their claim. I do agree that anecdotal evidence is also useful, it was other people’s stories that helped me to obtain the right diagnosis after being misdiagnosed with schizophrenia by my psychiatrist. Only we can’t know from anecdotes what actually helped, if someone did the AIP diet and they got better – was it because they eliminated all the foods the diet suggests to exclude, or they could have improved just as well if they only avoided refined carbohydrates?

The evidence that I found so far indicated that whole grains are actually anti-inflammatory. For example, whole grain intake was found to be inversely related with inflammatory protein concentrations, while refined grain intake was positively related with the inflammatory markers. “In summary, whole grain intake was inversely related to PAI-1 and CRP plasma concentrations, but these relationships were attenuated by the addition of metabolic variables to the model. Refined grain intake was positively independently related to plasma PAI-1 concentrations.

Whole and Refined Grain Intakes Are Related to Inflammatory Protein Concentrations in Human Plasma

I introduced whole grains after a year of strict AIP diet with no problem. I find that consumption of whole grains puts me in a more relaxed state of mind, I actually consume half a cup of rolled oats with green banana flour in the evening for better sleep. Sourdough is great because the baked goods end up with a low glycemic index after the fermentation process. I have a glucometer that I use to determine my blood glucose response to different food products. The standard test is a two-hour glucose test. Two slices of gluten-free bread increased my blood sugar to over 11 mmol/L two hours after consumption, which is a sign of high blood sugar. I did the same test with sourdough bread and sourdough muffins and my blood sugar was back to under 6 mmol/L two hours after consumption, which is a big difference. Short grain brown rice is also a high glycemic index food, while long grain brown rice was found to have lower glycemic index.

Sourdough allows me to eat the foods that I missed out on for so long, at the same time it does not cause a blood glucose spike for me. I have used sourdough to make pizza crust, tortillas, bread, and muffins. Currently I am learning to use fermented batter to cook dosas, an Indian dish. Controlling blood sugar for me means also stabilizing my mood. A glucose spike and then crash turns me lethargic and weepy, it takes away my energy, I definitely want to avoid that. Sourdough allows me to have blueberry muffins for breakfast, goat cheese toast, burritos – all without the consequences of an emotional roller coaster. High glycemic foods may also promote inflammation and given my diagnosis of autoimmune encephalitis, that is something that I definitely want to avoid as well.

Hyperglycemia can cause inflammation through varying mechanisms that result in the production of free radicals and pro-inflammatory cytokines (19, 24). Thus, high glycemic index and glycemic load diets may stimulate inflammation. Glycemic index is the blood glucose-raising potential of the carbohydrates in different foods. A more accurate indicator of the relative glycemic response to dietary carbohydrates, however, is glycemic load. Glycemic load incorporates the relative quality of carbohydrates characterized by the glycemic index. Consumption of high-glycemic index foods results in higher and more rapid increases in blood glucose levels than the consumption of low-glycemic index foods. Rapid increases in blood glucose are potent signals to the β-cells of the pancreas to increase insulin secretion, which can cause a sharp decrease in glucose levels and lead to hypoglycemia (25). In contrast, the consumption of low-glycemic index foods results in lower but more sustained increases in blood glucose and lower insulin demands on pancreatic β-cells (26).

Dietary carbohydrates and inflammation

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Yes, I am using this self-made incubator instead of Zoloft to treat depression

Here is my self-made incubator. It was constructed at home from several cheap and available components – a nice big Styrofoam cooler, a light bulb, a light bulb socket, a temperature controller, and some tape. That’s all, very simple. The cooler I got from Canadian Tire for about $14, light bulb, socket, and tape also from Canadian Tire. The temperature controller I purchased on Amazon for $35. What does the incubator do? The light bulb goes inside the cooler, so does the sensor from the controller. You close the lid and choose the desired temperature. The controller keeps the light bulb on until the chosen temperature is reached, then it turns it off. If the temperature drops, the light bulb is turned back on.

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How is any of this relevant to depression treatment? Well turns out that it is, and this incubator has been helping me a lot more than my previous trials of anti-depressants. I use the incubator to make fermented foods and research shows that eating probiotic foods can reduce chronic inflammation in the body and this in turn can reduce symptoms of depression. I have been making goat kefir, goat yougurt, sourdough, fermented fruits. I have also ordered a tempeh starter – spores of a specific mold, Rhizopus, that is used to ferment soy beans. I have also been buying natto (another type of fermented soy beans) in a Japanese store and eating it for breakfast.

It has been a bit more than a month since I started all this fermented food consumption and I think it has definitely improved my brain function in many ways. Correlation doesn’t mean causation, but I have noticed improvement in the way I think, the way I react to stressful events, my ability to sit down and spend time on meditation. I have rediscovered my interest in violin playing and my interest in the opposite sex. Last week I found my headphones because I wanted to listen to David Guetta in the subway on my way to work. Maybe that doesn’t sound like much, but if you’ve experienced severe depression and if you’ve seriously considered suicide, I think you would understand that this means progress. If you have experienced a state of mind in which your only desire was finding a way to end your life, then you know that going to a state where you have a desire for something else, anything else, is definitely an improvement.

I think therefore that constructing this incubator was the best decision this year so far. Last year the best decision that I made was pursuing immunosuppressant with intravenous steroids. I was treated with IV Solu-Medrol for five days in December and after that I saw my mind opening up. No, my depression did not vanish, but I started to have ideas, to be more proactive. Participating. I through of sharing my experience with autoimmune encephalitis, so I started a blog. I took the psychiatrist’s advice to do aerobic exercise in order to reduce brain inflammation. I researched further anti-inflammatory treatments and decided to build an incubator. I also became interested in helminthic therapy, so I learned how to use bitcoin and purchased some helminth larvae in order to infect myself. I don’t think this is all a coincidence, I think the steroids treatment did reduce inflammation that was there in my brain and some neural pathways opened up, more ideas started coming in. My tunnel vision became broader, the world became less black and white.

You can read my previous post about fermented foods and depression treatment here:

Bacteria, yeast, stinky tofu, desire?

My case of severe depression and improvement after immunotherapy is another piece of evidence supporting the idea that depression and suicidal thoughts are not always just caused by imbalance of serotonin, but inflammation can also play an important role.

Recently researchers at the University of Manchester conducted a study measuring level of inflammation in the brains of patients with clinical depression. “Dr. Talbot and colleagues measured the levels of translocator protein (TSPO) in the brains of people diagnosed with major depressive disorder. TSPO generally plays a role in the immune response system and cell death.

In the brain, elevated TSPO levels activate the microglia, which are immune cells specific to this organ. Microglial activation indicates brain inflammation, so this is what the scientists targeted.

People with depression who were experiencing suicidal thoughts were found to exhibit significantly higher levels of TSPO, associated with microglial activation and indicating inflammation of the brain.

Depression: Is brain inflammation tied to suicidal thoughts?

I was suffering from treatment resistant depression, but now I believe that it is not resistant, the treatment was just incorrect. I was put on mirtazapine, bupropion, risperidone, sertraline, multiple combinations of antidepressants and antipsychotics were tried. Well none of those combinations worked, but today I am still alive. I cannot thank my psychiatrist who continued to treat me with the same medications just in different doses and mixes, but I am thankful to all the researchers, journalists, and bloggers, who have written on the topic of the link between inflammation, suicidality, and depression. I am very thankful for Susannah Cahalan for her book “Brain on Fire: My Month of Madness” about her terrifying experience with anti-NMDA receptor encephalitis. I think, maybe not in the average psychiatrist’s office, but in general there has been progress in understanding the impact of our diet, lifestyle, and chronic inflammatory conditions, on mental health. Diet matters, exercising matters, so does our gut microbiome, blood glucose levels, inflammatory markers. All of this cannot be fixed by just taking Zoloft or Prozac and I believe that is why many people don’t get better on antidepressants. They are not treatment resistant, the right treatment is available, it just hasn’t been applied.

Cases of depression treatment with immunotherapy

I am such a case and I want to present other cases found in literature where depression/psychosis was ameliorated with immunotherapy treatment. Dr. Joseph Dalmau is one researcher who has written extensively about psychosis resulting from autoimmune encephalitis and I am very thankful to him for his work. The paper below is a good overview of 100 anti-NMDA receptor encephalitis cases. It’s interesting to note that 91 out of 100 patients were female. This is consistent with the general finding that that autoimmune diseases affect more woman than men. Also not all patients suffered seizures, it was 76 out of 100, therefore seizures are not a necessary symptom of anti-NMDAR encephalitis. I personally was diagnosed not with anti-NMDAR encephalitis, but with Hashimoto’s encephalitis. I had about two seizure-like episodes, but it’s hard to say if they were actual seizures. Given the patient stories from the Hashimoto’s encephalitis Facebook support group, I would say definitely not everyone experiences seizures with autoimmune encephalitis. My neurologist and psychiatrist stated that encephalitis can present itself as ongoing mild chronic inflammation. This can result in severe depression, black and white thinking, experiences of extreme fear, but present no severe physical symptoms. Anti-NMDAR encephalitis is usually not mild, but severe inflammation of the brain. The authors of the paper state that 25 out of the 100 patients were left with severe deficits or died even after receiving treatment.

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

Below is another good case study of a patient who had ongoing depression for many years. The person was not able to work due to his psychiatric state, and his condition did not improve with psychotherapy or psychiatric medications. “At age 29, the patient found himself easily fatigued despite excessive sleep. His energy was persistently low. His capacity to be productive at work was drastically reduced. He was psychiatrically hospitalized for a major depressive episode and was treated aggressively with a combination of psychotherapy and pharmacotherapy…  By age 35, the patient could not sustain work because of persistent mood symptoms and cognitive dysfunction.” Unfortunately the patient got to a neurologist at the age of 39, after clearly suffering for many years, but better late than never. It was found that neurological testing returned some abnormal results, presence of brain inflammation was then confirmed and it was decided to treat the patient with intravenous immunoglobulin (IVIG) therapy. This treatment was quite successful in reducing the patient’s depressive symptoms.

Ten months after initiation of IVIG, a repeat SPECT scan showed complete normalization of frontal hypoperfusion. Of note, the psychotropic regimen remained essentially constant over this 10-month period. At the time of a neuropsychiatric reevaluation 13 months after starting IVIG, the patient reported significant improvement in his mood and much better control of his anxiety. His wife reported a positive personality change in her husband. He was much more active in general and more appropriately engaged with his family. He was more interested in socializing, and he became an active participant in raising his child.  In fact, he was excited to report that he and his wife were expecting a second child.

Brain Biopsy Findings Link Major Depressive Disorder to Neuroinflammation, Oxidative Stress, and Neurovascular Dysfunction

Here is another brief description of a 74 -year-old woman presenting with severe depressive symptoms, not responding to antidepressants, and then being successfully treated with prednisolone: “We report on a 74-year-old female patient with a severe depressive episode who showed no treatment response to citalopram 40 mg/day and venlafaxine 150 mg/day. Diagnostic examination revealed an abnormal EEG, elevated thyroid peroxidase antibodies (TPO-Ab), and older postinflammatory changes in thyroidal sonography. We diagnosed a depression in HE and began treatment with prednisolone 70 mg/day with stepwise dose reduction, continuing treatment with venlafaxine 150 mg/day. Within 4 weeks of treatment, the severe depressive episode disappeared as well as abnormal EEG. In addition, serum values of TPO-Ab decreased.

Depression in Hashimoto’s encephalopathy. Successful treatment of a severe depressive episode with a glucocorticoid as an add-on therapy

The following article describes the case of a 50-year-old patient who presented with depressive symptoms and cognitive impairment and was then diagnosed with Hashimoto’s encephalitis, after not responding to regular antidepressant medication.

“In 2011, after experiencing a noticeable loss of energy and feelings of exhaustion, the patient presented for evaluation of classic depressive symptoms, including melancholic mood, impaired concentration, and psychomotor retardation.

The patient had no prior medical history of psychiatric disorders, and had no family history of psychiatric, neurological, or autoimmune disorders. Physicians diagnosed the patient with major depression, and prescribed 112.5 mg venlafaxine and 25 mg agomelatine in conjunction with cognitive behavioral therapy (CBT).

After 2 years of CBT, the patient showed little to no improvement, with persistent memory loss, depressed mood, and reduced energy level.

This case sounds very similar to mine, as I did not have very pronounced physical symptoms such as multiple seizures. I complained to the doctors about constant fatigue and abdominal pain, and then I had to be involuntarily hospitalized due to severe depression and suicidal thoughts. I did not improve after treatment with mirtazapine, bupropion, risperidone, olanzapine, duloxetine, etc. I have also attended CBT sessions for more than half a year. This patient, like me, was finally diagnosed with Hashimoto’s encephalitis, and treated with immunosuppressant medication, after which the patient improved.

The patient was treated with high-dose methylprednisolone (1000 mg intravenously administered over 3 days; 500 mg over 2 days), which was well-tolerated. Methylprednisolone was then transitioned to oral dosing initiated at 40 mg and then tapered until discontinuation by halving the dose every fifth day. Venlafaxine, agomelatine, and T4 treatment continued unchanged.

The patient reported reduced cognitive impairment and improved alertness after steroid treatment, confirmed by neuropsychological testing. Basal alertness and processing speed were both improved, but remained below average. After 5 weeks, the patient’s mood and energy levels normalized and cognitive impairment had disappeared.”

An Uncommon Presentation of Hashimoto’s Encelophathy

Depression is an awful experience, it literally makes you not want to be alive. I’ve been there. Researchers are starting to have a better understanding of causes of depression and therefore there is hope. If you are suffering from depression resistant to standard antidepressant treatments, consider getting investigated for autoimmune disease/inflammation. I am very thankful to all the researchers who put this information out there and we are able to access it online for free. Learning about the link between depression and inflammation has definitely been helping me climb out from a very dark place.

Helminthic therapy – hello parasites!

So today is day five since I infected myself with parasites. With seven larvae of Necator americanus, a species of hookworm, to be exact. I have never heard of helminthic therapy or helminths until about a month ago, then I was sent a link to a Facebook group by a girl from adult PANDAS/PANS disease support group. Supporters of helminthic therapy have put a lot of effort and created a great wiki section with all the necessary information, you can find it here:

Introduction to helminthic therapy

The idea behind helminthic therapy is based on the same theory as probiotics for depression and autoimmune conditions. With the onset of industrialization we started living in more sanitary conditions, we stopped drinking unpasteurized milk, we no longer spend time with cattle, we don’t milk cows with our bare hands. Well all of this had many benefits – childhood mortality rates decreased dramatically, a lot of children actually used to die from infections obtained while drinking raw milk. Especially given that there were no refrigerators, often by the time the milk got to your house, it would be already somewhat spoiled. There are consequences through of this reduction of contact with bacteria. It seems that there has been depletion in the gut microbiome and decrease in its diversity. We have also lost our macro-biotics – helminths. Helminths are intestinal worms and humans have usually lived their whole life infected with them. People still do in less developed countries, but it’s rare that someone in US or Canada would have these parasites.

Helminthic therapy is experimental, there is no concrete proof that it will help, but the statistics based on user experiences show that 75% of users experienced reduction in their symptoms. Helminthic therapy is also safe because the parasite species that are sold for therapy are not able to reproduce within the human host. Therefore if you infected yourself with ten parasites, you will not end up with thirty in two weeks, then fifty, etc.You will continue to co-habit with the ten worms, if they all survive. Also from what I’ve read, it’s quite easy to get rid of the parasites if you want to, by taking anthelmintic medication.

How can helminths help?

The therapy works by inoculating yourself with larvae either by swallowing it or through skin contact, depending on the species. I chose to get infected with Necator americanus (NA), a species of hookworm, these get to the human intestines  through skin contact. Like all organisms, helminths want to feed and survive. They attach themselves to the walls of the intestines and drink human blood. NA are very tiny, about 1 cm, therefore the amount of blood that you loose given a small number of worms is insignificant. The little guys want to survive and stay in the intestine, they like it there, so they put effort into not being kicked out from the body by your immune system. The exact mechanisms of what helminths do to survive is not yet known, but possibly they excrete some molecules that train the immune system to not react to them. They tweak the immune system to be less active and this seems to be beneficial. In general users found that their immune system worked as well as before in terms of fighting dangerous viruses and bacteria, but their autoimmune symptoms lessened. That is the exactly the outcome that I wish for from any therapy for my autoimmune condition, therefore I was sold on trying this experimental therapy.

Case studies

One parasite immunologist, P’ng Loke, has observed some case studies with human patients and found beneficial results from helminthic therapy. “The results of Loke’s new case study—the most recent of only five studies that investigate helminthic therapy in people instead of animals—suggest that helminths may ease the symptoms of autoimmune diseases by increasing mucus production.

Helminths could suppress immune disorders by promoting healthy mucus production in the intestine

You can read more personal stories on helminthic therapy wiki:

Helminthic therapy personal stories

Is it scary?

Not for me. Scary is doing nothing about my depression, thinking that it will never get better. Scary was imagining that the method with charcoal grills isn’t going to fully work and that I would end but brain damaged but still alive. Experimental therapy is hope, it’s exiting. I think I have already gotten quite far by not accepting my psychiatrist’s statement that my choices were either a state of psychosis or continuing being on anti-psychotics. I experimented with the autoimmune protocol diet, I received treatment with intra-venous steroids – not a standard treatment for depression. I built an incubator and started making fermented foods. The experiments were not randomly chosen, I have read multiple articles and came to a conclusion that these were the most promising methods for reducing inflammation. It did pay off, so I am all for further experimental therapy. I have started a blog this year, I got back to playing my violin. I am less terrified of staying home alone. I have more interest in things, just as I used to – not constantly thinking “what is the point of living”, but able to do something and enjoy it. Being able to simply watch a documentary on YouTube and be interested in it is already great progress for me. So I am all for experimentation, I am against staying in the same depressed spot.

Industrialization, autoimmune diseases, and depression

I used to think that I was in control of my own mind, but it’s clearly not the case. I don’t choose how to feel and how to emotionally respond to situations, just as I don’t choose when to feel hungry. I don’t choose my thoughts as well. I don’t know which thought is going to come next, it’s just going to pop up in my conscious mind and I will observe it, I will react to it. Someone recently told me that all the choice that we have in life is the direction of our view. We don’t choose our emotions, we don’t choose our thoughts, we don’t choose the environment around us, we can only turn our head and change the view, and observe.

That’s why doctors prescribe antidepressants – people don’t choose to be depressed and they can’t just “think their way out of it”. And sometimes antidepressants help, maybe for some people depression is just a lack of serotonin and SSRIs fix that imbalance. The chemical imbalance theory is not 100% confirmed, some scientists debate whether this is a cause of depression at all, perhaps antidepressants help some people not by increasing serotonin, but by decreasing inflammation. Autoimmune diseases are what can cause chronic inflammation.  This is when “the immune system prompts white blood cells to attack nearby healthy tissues and organs, setting up a chronic inflammatory process”. Turns out the brain can be affected by this process as well. “People who had been treated for a severe infection were 62% more likely to have developed a mood disorder than those who never had one. An autoimmune disease increased the risk by 45%. Multiple infections or the combination of severe infection and an autoimmune disease boosted the odds of developing depression, bipolar disorder, or another mood disorder even further.”

Infection, autoimmune disease linked to depression

Next I am going to speculate and talk about the possible causes of rising incidence of autoimmune disease. I am going to mention the idea that the lifestyle that we obtained through industrialization turned out to be pro-inflammatory. I am not proposing to go back to living in a village, but I want to propose making practical lifestyle changes that can help reduce chronic inflammation and in turn depression.

We are participating in less physical activity and are gaining higher body weight

One result of industrialization is we are eating more sugar, moving less, and weighting more. “How could carrying extra weight and sofa-sitting be connected to higher levels of inflammatory chemicals in the body and the development of diabetes?

Researchers discovered that excess body fat, especially in the abdomen, causes continuous (chronic), low levels of abnormal inflammation that alters insulin’s action and contributes to the disease.

The body becomes less sensitive to insulin and the resulting insulin resistance also leads to inflammation. A vicious cycle can result, with more inflammation causing more insulin resistance and vice versa. Blood sugar levels creep higher and higher, eventually resulting in type 2 diabetes.

Are Diabetes and Inflammation Connected?

We are eating high glycemic foods

We are eating more processed and high glycemic foods. The bread that people used to eat when they lived in villages was usually not the white bread from refined flour, it was sourdough, which has more nutrients, and a low glycemic index. I doubt anyone used to eat pasta, pizza, or fries often, if at all. I know that in peasant Russia there was fermented cabbage, sourdough rye bread, barley, and broth, sometimes meat and fish. Also fermented milk products. None of those foods have a high glycemic index.

According to Harvard researchers, healthy, middle-aged women who ate the meals with the lowest glycemic load had the lowest levels of C-reactive protein, a marker of inflammation in the body.

In overweight women who had greater levels of C-reactive protein to begin with, eating higher amounts of low glycemic index foods had an even greater impact on their inflammatory markers.

The Link between Glycemic Index, Diabetes, Inflammation and Heart Disease

We are eating fewer fermented foods

How often do you drink kefir or yougurt, eat kimchi or sauerkraut? Do you eat natto or fermented bean curd? Tempeh? Sourdough bread? Cassava fufu? If the answer is pretty often, I would say that’s good, but many people in US and Canada rarely eat fermented foods. Maybe sometimes yougurt, but it’s questionable whether store bought yougurt has live probiotics. Previously people ate fermented foods more often. They didn’t really have much choice since refrigerators weren’t available. Milk goes bad pretty quickly, so you need to make it into kefir or yougurt. In winter you don’t have fresh vegetables, you have fermented vegetables in jars that you prepared during the summer. Same with fruits. There have been several papers recently linking fermented foods to mental health, here is what is stated in one of them: “The extent to which traditional dietary items may mitigate inflammation and oxidative stress may be controlled, at least to some degree, by microbiota. It is our contention that properly controlled fermentation may often amplify the specific nutrient and phytochemical content of foods, the ultimate value of which may associated with mental health; furthermore, we also argue that the microbes (for example, Lactobacillus and Bifidobacteriaspecies) associated with fermented foods may also influence brain health via direct and indirect pathways.

Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry

We have lost our “old friends”

One of recent theories is that the rise in autoimmune disorders could be due to our gut microbiome depletion. With sanitary toilets, pasteurized milk, less time with animals (urban citizens rarely hang out with farm animals, neither do they milk cows, and now few even have pets due to smaller apartment sizes), we have lost many microbes and parasites that used to inhabit our gut. Turns out this might not be a good thing. It could be that because we as species cohabited with these organisms for so long, our immune system evolved to train on these parasites, and now we are lacking this training. “Diminished exposure to immunoregulation-inducing Old Friends in the perinatal period may enhance the consequences of psychosocial stressors, which induce increased levels of inflammatory mediators, modulate the microbiota and increase the risk for developing all known psychiatric conditions. In later life, the detrimental effects of psychosocial stressors may be exaggerated when the stress occurs against a background of reduced immunoregulation, so that more inflammation (and therefore more psychiatric symptoms) result from any given level of psychosocial stress. This interaction between immunoregulatory deficits and psychosocial stressors may lead to reduced stress resilience in modern urban communities.

Microbial ‘Old Friends’, immunoregulation and stress resilience

Do we need to move back to the village? Or to a cave?

Well I’m hopeful that I won’t have to, because my job is in downtown Toronto, and it would be hard to commute there from a remote village. I hope that given the recent research, we can use this information to improve our immune system function, while still living in a city. We can cook more food at home instead of buying processed food. I rarely buy anything at the food court during the work day, I bring everything from home. I am also making fermented foods – kefir, yougurt, sourdough bread, kombucha. I also purchased some at Asian grocery stores – they have fermented bean curd, natto, fermented Chinese cabbage.

In terms of moving around, I try not to sit at my desk at work for too long. I get up to make tea, go for a walk during lunch. Walk to the subway in the morning instead of taking the streetcar. Walk home after work with a friend. Gym I personally found very boring, but I do exercise at home with an aerobic step. Doctors suggest at least 30 minutes of aerobic exercise a day, heart rate needs to go up!

In terms of bringing back “old friends” – this can partly be done by consuming probiotic and prebiotic foods to increase gut microbiome diversity. There are also soil bacteria that are considered beneficial, we can obtain them by spending time near soil and breathing in the particles. Having a dog is stated to have beneficial effects on our gut microbiome. There is also experimental helminthic therapy – infecting yourself with parasites on purpose. I am planning on trying this therapy and I will write more on this topic later on.