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.

Autoimmune Encephalitis vs. Schizophrenia

I don’t have schizophrenia so I can’t say that I experienced it, but I was misdiagnosed with it, therefore it’s possible that some of my experiences are similar to those of people with schizophrenia. Unfortunately autoimmune encephalitis is often  misdiagnosed as a psychiatric disorder. I spent a lot of time in the Understanding Hashimoto’s Encephalopathy Facebook group and after talking to the women there, the commont story that emerged was that most of them were initially referred to a psychiatrist and treated with antipsychotics/antidepressants/benzodiazepines. I say women because the group members are mostly female, probably over 90%. Autoimmune diseases affect women more often than men and this seems to hold true for autoimmune encephalitis. Schizophrenia on the other hand is more common among males.

I am not a schizophrenia expert, but since my psychiatrist assumed that I had it and I was treated for it, from experience I can say that schizophrenia is usually treated with antipsychotics such as risperidone and olanzapine. Psychotherapy can also be recommended but in addition to the antipsychotics, it would not be enough on its own usually. Autoimmune encephalitis does not improve with antipsychotics. AE is inflammation of the brain that is caused by the immune system and it required immune suppression such as IV steroids, IVIG or plasmapheresis. Many patients have to stay on oral immune suppressants such as prednisone or Cellcept. Some get regular Rituxan infusions. Some patients do take antidepressants or antipsychotics in addition to the immunosuppressant treatment, but the first step should really be suppressing the immune system.

Autoimmune encephalitis often does cause psychiatric symptoms such as intense fear, panic, paranoia, delusional thoughts and depression. All these symptoms could be present in patients with schizophrenia. Schizophrenia is also much more common than autoimmune encephalitis, it affects about 1% of population. Since psychosis due to autoimmune reaction is quite rare, it’s reasonable for a psychiatrist to assume schizophrenia, schizoaffective disorder, or psychotic depression. I do think though that if the psychosis is present along with physical symptoms, a blood test for autoimmune conditions should be performed as well. I don’t think schizophrenia is associated with facial swelling, lightheadedness, brain fog, extreme fatigue, etc. Autoimmune encephalitis on the other hand does cause all these physical symptoms and more severe ones as well such as seizures and going into a coma. Also I think that if a patient has tried different antipsychotics for several months and has not responded to them, it’s probably time to consider that there might be a different cause and perform further testing. My psychiatrist for some reason did not consider this. I was not aware of existence of autoimmune diseases, it was my mom who suggested specific blood tests.

BBC – Some psychosis cases an immune disorder

Further on, once I started reading more about causes of panic, anxiety, and mood swings, I bought a glucometer and decided to check my blood glucose. My fasting blood sugar was checked previously at the hospital and it was fine, but after performing my own measures, I noticed a problem. After specific meals that contained high glycemic index foods, my blood sugar could stay at higher than 11 mmol/L two hours after eating. Diabetes UK states that blood glucose over 8 mmol / L two hours after a meal is of concern. Later on I spoke about these results to a doctor and she said I may have hyperglycemia. I also noticed feeling psychologically worse when my blood sugar was high. My point here is that if you are not responding to antipsychotics, there are further things to investigate. There is autoimmune testing – high levels of thyroid antibodies could indicate Hashimoto’s encephalitis, there are also other types of autoimmune encephalitis with different antibodies (NMDA receptor encephalitis, for example). TSH, free T3, and free T4 is a standard test to check the thyroid function, hypo/hyper thyroidism can also cause psychosis. Diabetes/hyperglycemia can affect your mood. Usually fating blood sugar is checked, but I would also verify blood glucose levels two hours after a meal with high glycemic carboydrates.

Diabetes UK – Diabetes and Hyperglycemia

 

Hashimoto’s Encephalitis – Diagnosis and Treatment

Hashimoto’s Encephalitis (HE) is a diagnosis that is made through exclusions of other causes. There is no one specific test to diagnose HE, but usually the tests that are performed are thyroid antibodies (Anti-Tg and Anti-TPO) blood test, MRI, EEG, and spinal tap. HE is a quite rare disease, therefore it is definitely not something that would be tested for right away. Many healthy people have elevated thyroid antibodies, these antibodies can also be an indicator of Hashimoto’s thyroiditis, which is not the same as Hashimoto’s Encephalitis. After I continued to not respond well to anti-depressants and anti-psychotics, I consulted with an endocrinologist to discuss whether I had any thyroid issues. My thyroid hormone levels were normal but elevated Anti-Tg and Anti-TPO antibody levels were discovered. At that point the endocrinologist diagnosed me with Hashimoto’s thyroiditis and stated that the thyroid antibodies were not something to worry about at the current moment as they were just an indicator that I might develop thyroid disease twenty years from now on. There is still no exact proof that it is these thyroid antibodies that caused my symptoms, but my condition did improve after intra-venous treatment with Solu-Medrol (anti-inflammatory glucocorticoid), and my antibody levels decreased as well. I will not claim causation, but there is correlation here, and my neurologist agrees that I have improved since the steroids treatment.

I am not sure whether the numbers are meaningful, it had been stated that specific values are not correlated with the severity of HE symptoms, but initially in June 2016 my Anti-Tg levels were over 1,000 and my Anti-TPO levels were above 40. This was during the period of time when I lost my job and was on Latuda and Sertraline. I was finding it physically difficult to wake-up, to move, and to talk. My speech was becoming slower and everything was also followed by intense emotional pain. It was sort of a state of grief without cause. As I mentioned in my previous posts, I did go on AIP (autoimmune protocol diet) diet after discovering that I potentially had autoimmune disease, and my symptoms did improve. I was able to go back to full-time work in November 2016 and after awhile tests showed that my Anti-Tg levels decreased to around 500, Anti-TPO levels stayed about the same. Again, this is anecdotal evidence, and I cannot claim that it is specifically the AIP diet that helped me. A gastrointerologist did advise me to try a low-FODMAP diet and AIP overlaps with low-FODMAP. Also I did have a ‘maybe’ result for celiac testing and I went gluten-free. I also stopped taking anti-psychotics and a new diagnosis of Hashimoto’s thyroiditis (at that time), instead of schizophrenia (diagnosis that I received previously), provided me with psychological benefits. Therefore it is not possible to untangle all the changes that I made during the summer and we don’t know which factor improved my condition. Some conditions improve and relapse in cycles as well, therefore changes in symptoms could be not due to the actions of the individual.