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.

Depression, inflammation, and what you could do

I am not a doctor, but I have been to many, so I am going to write out here the information that I have collected over the few years. The first step, if you are feeling depressed, would be going to a doctor. In Canada you can visit your family doctor if you have one, or you can go to ER. In October 2015 I was waiting for a subway train in the station and I thought of jumping under it. The thought was not spontaneous, I have been getting more and more depressed over a period of time. I told my boyfriend about my thoughts of jumping and he convinced me to go to the ER. I was terrified when the doctor who examined me said that I would be involuntarily hospitalized in the psychiatric unit. The first thing that came to mind was probably a scene from One Flew Over the Cuckoo’s Nest. Given that I was in a psychotic state, I imagined that my boyfriend and the doctors conspired to lock me up for an indefinite amount of time. Well, none of this happened. The law is that you can be involuntarily hospitalized for three days, and then your case has to be reviewed. Two opinions of physicians are required to maintain the detention.

Involuntary hospital admission – Canada

Actually I should say I got lucky that when I went to the ER I got seen by several psychiatrists and got to be examined for three days. At the moment there are not enough beds and not enough psychiatrists in Ontario, often people needing help are placed on six to nine months wait lists. Going to ER is therefore a good option because it’s more likely that there will be a psychiatrist available right away (yes, you might sit in the waiting room for five hours, but that’s not six months). Also blood tests would be performed to determine whether any health conditions could be causing your psychiatric symptoms. Tests performed could include the following:

  • TSH level to check for hypo/hyperthyroidism
  • Blood glucose level to check for diabetes
  • Iron/ferritin levels to check for anemia
  • Renal function (for chronic kidney disease)

In my experience doctors did not check for autoimmune diseases as part of the lab work, but if you are experiencing physical symptoms as well, you could ask your doctor to check this. Autoimmune testing:

  • Thyroid antibody levels (Anti-Tg and Anti-TPO antibodies) – high levels can indicate Hashimoto’s thyroiditis, also Hashimoto’s Encephalopathy (but this is quite rare)
  • C-reactive protein – marker of inflammation
  • Antinuclear antibodies (ANA) – checking for lupus
  • Rheumatoid factor – associated with rheumatoid arthritis
  • Anti-NMDAR antibodies – anti-NMDA receptor encephalitis (rare occurrence)
  • Celiac disease testing (it is also an autoimmune disorder)

Gastrointestinal disorders are also associated with depression. Individuals with gastritis are more likely to suffer from anxiety, panic attacks and depression. Depression and anxiety is also more often present in people with irritable bowel syndrome. If you experience any gastrointestinal/abdominal pains and discomfort, it’s important to visit a gastroenterologist. You can be tested for celiac disease. New research also indicates that many people who considered themselves having a gluten sensitivity actually had issues with high FODMAP foods. These are fermentable oligo di mono-saccharides and polyols, short chain carbohydrates and sugar alcohols. Personally I was diagnosed with chronic gastritis a few years ago, even before I got to the psychiatrist. The gastroenterologist who diagnosed me did not have any suggestions for me. A year ago I visited a different gastroenterologist, and she advised me to try a low FODMAP diet. I have been following it for a while, even after I stopped the AIP diet, and it definitely reduced my abdominal pains. Hopefully it is affecting my mood positively as well.

Gastritis linked to mood and anxiety disorders

Is gluten causing your depression

Once you talk to your family doctor or your psychiatrist about depression, if you do get diagnosed with depression, usually anti-depressants are prescribed. If you experience psychosis, anti-psychotics can be prescribed (on their own or along with anti-depressants). I am not a doctor, so it’s not for me to tell you which medication to take, but I just want to bring to your attention recent research on the link between depression and inflammation. I think no matter whether you do or don’t take psychiatric medication, it might be worthwhile to analyze your lifestyle and to think whether there are unhealthy aspects of it that you could change.

New research shows depression linked with inflammation

I know this may sound pointless – it may seem that no medication or lifestyle changes can help because it is life itself that is so meaningless, so emotionally painful, and how is that going to get changed? I used to get angry at suggestions by psychiatrists to attend therapy or my mom telling me to take fish oil. What does fish oil have to do with my life? How will it make me less lonely, how would it make life less dull and meaningless? The thought that helps me to try a suggestion is “what do I have to lose?” If I am already at the point where I no longer want to live, what will I lose by trying fish oil? Yes, it means I will agree to still be alive and try taking these stupid capsules, but I don’t have to be alive forever, it’s not possible anyways. I am not agreeing to suffer forever, I am just agreeing to stay alive for now, and to try.

Back to inflammation discussion – so for example you say “ok, fine, maybe I will try to stay alive, but so what? What is the suggestion?” Well my suggestion is in addition to discussing with your psychiatrist medication/therapy options, look into your daily diet and activities. From the article above, it is stated that the Journal of Clinical Psychiatry published a study with results indicating that increased inflammation in the body may be linked with depression. Inflammation is when there is a response from the immune system. Many different immune cells can be activated during inflammation and they produce different substances, such as antibodies (there are different types).

We need the immune system to be active to fight viruses and bacteria, but what the authors of the paper are saying, is that chronic inflammation does not help us and is damaging instead, reducing chronic inflammation may reduce depressive symptoms. PsychologyToday author in the article recommends avoiding fried foods, soda, white bread and pastries, margarine, lard, and red meat. In general highly processed foods and refined carbohydrates are considered to be linked with inflammation. White bread, white rice, pizza pops, hot dogs, salami, cookies, etc. In general a lot of doctors advise to follow a Mediterranean diet, which means reducing red meat, processed foods, refined carbohydrates and sweets. It includes eating the following:

  • whole grains/pseudograins (quinoa, brown rice, millet, oats, buckwheat, etc.); it is suggested to eat them whole and not in form of grain flour
  • poultry – turkey and chicken
  • fish, especially fatty fish like salmon
  • eggs (I suggest trying quail eggs!)
  • vegetables
  • berries
  • olive oil instead of vegetable and seed oils
  • legumes (checked whether you have issues with high FODMAP foods)
  • nuts and seeds (try finding those that weren’t roasted in vegetable/seed oils, you can eat raw nuts)
  • dairy – if you have issues with cow milk, there is goat milk; there is also goat yougurt and you can make goat kefir
  • some fruits

Mediterannean diet plan

I think no matter what you were diagnosed – depression, schizophrenia, bi-polar, etc., a healthy diet is very important. It’s very important for anyone. Our brain is just an organ like all other organs and it needs proper nutrients and can also get damaged, like other organs, by chronic inflammation. At first I was very skeptical about the correlation between diet and my thoughts, but then as I started experimenting with changes in what I eat, I noticed that it does affect what I think. Sometimes I am really tempted to buy ice-cream or something like that, but I just remind myself that for me it’s not worth it, it can take me to a very dark place. I just have to accept that as someone with diabetes has to watch their carb intake, I also have to watch what I eat because of my chronic autoimmune condition. This is just how it is, I have to accept that it’s chronic, and that I can’t just go to the food court and buy whatever I want. I mostly bring food from home or I buy from places that list all of their ingredients, so that I can make sure it doesn’t have gluten, cow’s dairy, a lot of sugar, high FODMAP items, etc.

Yes, it’s not pleasant having to worry about the ingredients each time you eat, but the benefit for me was a change in my thought process, and I find that the most valuable. Our thoughts and emotions are what matters because that is our experience of life, so that is the number one thing that I want to change myself, I want to have a positive life experience.

 

Autoimmune Encephalitis Story (part 3)

Part 1:

Autoimmune Encephalitis Story (part 1)

Part 2:

Autoimmune Encephalitis Story (part 2)

In June 2016 I actually started to have some hope. No, I didn’t throw away my charcoal grills, but at least now there was something to research, testing to be done. Previously my psychiatrist told me that I had a choice between psychosis and antipsychotics and I don’t think that should ever be said to a patient. If the antipsychotics are not working and the psychosis is emotionally unbearable, what message are you sending your patient? Well you are giving them another reason to commit suicide – why live if the only choices you have are being non-functional and psychotic or being on olanzapine. Anytipsychotics do help some people and therefore they are a good choice for them but for me they were not working at all, so the right thing to say would be that more investigations would be done. As you see from the story, it was not the psychiatrist who ended up investigating, but my mom. So I got lucky, but it should not be this way. Access to proper treatment should not be based on luck and having someone googling your symptoms for you, this is the doctor’s job.

So in June 2016 I went off Trazadone, Latuda, Mirtazapine, Lorazepam. I only continued with Sertraline until October 2016. I started taking Cytomel (man-made version of thyroid hormone T3) and I got tested for celiac disease. The results were a ‘maybe’, inconclusive, but  I still decided to try going gluten free and dairy free as some people with autoimmune disease do report improvement after eliminating those foods. Yes, some will say it is only anecdotal evidence, but when the way you feel on a daily basis makes you purchase hibachi grills, anecdotal evidence is good enough. Especially when the doctors have no suggestions or solutions for you. I was told that Hashimoto’s thyroiditis was not something to be too concerned about because it could affect the thyroid in the long run but at the moment my thyroid hormone levels were normal. I was told that I had nothing to worry about for the next twenty years. But then why were there old women, whom no one else notices, asking me to help them die? Why was I afraid of passing by Starbucks because hearing music from the speaker caused a feeling of grief? At that point I have not yet heard about autoimmune encephalitis, which is brain inflammation, so I had no answers to these questions.

I was now off the antipsychotics and at first I eliminated just dairy and gluten. It was quite difficult for me and I made a mistake of substituting everything with gluten-free labeled products, which actually contain a lot of refined carbs. Still, this change in diet, or coming off the neuroleptics, or feeling some hope after reading overly positive reviews on AIP diet promoters’ blogs, but I started to feel a sort of feeling of waking up.