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.

 

 

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