Bipolar

This is not a home step. The file found clinics offering mesenchymal stem cells, including one Bangkok clinic that lists bipolar disorder as an adjunct for fatigue and brain fog. It says it does not change psychiatric medicines and declines acute patients.

The file’s reading of the mechanism: stem cells can lower TNF-α, which is raised in mania and in bipolar depression. Given into the spinal fluid, they have raised IL-6 in other diseases, and IL-6 is high across bipolar mood states. No study has measured these markers in bipolar patients given these cells.

There is no bipolar result that would show you have passed this. The first test in the file is an IV bone-marrow trial that has not reported outcomes.

No efficacy data. Not solved. The UTHealth trial, intravenous bone-marrow cells for treatment-resistant bipolar depression, is the first test named in the file. It is still recruiting, estimated n=30, primary completion December 2026, no results posted.

Spinal-route complications include meningitis, cauda equina inflammation, and growths. In 9 neurological RCTs (n=540) there were more musculoskeletal adverse events (RR 1.61) and no excess of serious ones. That does not cover unregulated clinics: one review counted 35 reported complications or deaths, including meningitis after spinal injections and tumors.

Travel, sleep loss, and stopping medicines abroad can trigger mania. The Bangkok clinic’s own page says medicines stay unchanged.

The FDA warns that most stem-cell products sold in US clinics are unapproved. Clinic prices in the file run about €7,000–31,000 at one center that does not list bipolar as an indication.

Do not stop bipolar medication to travel for this.

If the label says “lithium (as lithium orotate) 10 mg,” that is elemental, the common US format. Twice a day is 20 mg elemental lithium. That is about 106 mg of lithium carbonate, roughly one-third of a 300 mg capsule, at the bottom of the low-dose band (20–100 mg elemental) in Bloomfield 2026.

If the label means 10 mg of the orotate compound, that is about 0.38 mg elemental per dose. Lithium orotate is 3.83 mg elemental per 100 mg (Pauzé 2007). The file does not know which reading the bottle uses.

This order uses 10 mg twice a day. Tell your prescriber. Do not combine it with prescribed lithium unless they are managing both.

A 2026 editorial argues orotate is not a special salt: stomach acid should dissociate it to ordinary lithium ion, the pharmacokinetics look like carbonate, and no study has shown stable lithium orotate in body fluids.

The file has no trial result that would show this dose prevents mania.

The dose on the shelf is not checked by the FDA. A third-party-tested product and one consistent brand are the file’s answer. It is still lithium: NSAIDs, dehydration, diuretics, and GLP-1 drugs apply. A blood level can be measured.

There is no evidence it prevents bipolar I mania. Users’ reports of smoother anxiety do not replace prescribed lithium, olanzapine, or quetiapine.

An 18-year-old who took 18 tablets of 120 mg lithium orotate (about 83 mg elemental) had a serum level of 0.31 mmol/L at about 90 minutes and 0.40 an hour later, with nausea, vomiting, and tremor that resolved (Pauzé 2007).

The paper gives no doses for ivermectin or albendazole.

If mania will not respond, ask for an eosinophil count and an infection workup. Antiparasitics only if an infection is found. This case was a 31-year-old man from Congo, treated in France, with Wuchereria bancrofti found because of hypereosinophilia. He had no filariasis symptoms. MRI and the neurological exam were normal.

The authors’ main idea is that the infection’s chronic inflammation was interfering with mood stabilizers. They say ivermectin penetrates the brain poorly, so a direct brain effect is unlikely. Albendazole does cross into the brain.

In the case, euthymia came with parasite clearance on immunodiagnosis, and the YMRS was 9. That is one person.

One case, no doses, and spontaneous remission is possible. Not solvable. It stays a single case.

Ivermectin without an infection is a different risk. A 2026 review describes central-nervous-system depression, delirium-like symptoms, and neuromuscular trouble, mainly with veterinary products or repeated high doses. The file’s answer is to test first and use a human dose prescribed for a diagnosed infection.

Albendazole can provoke seizures when brain cysts exist. A neurocysticercosis case that looked like mania was also treated with steroids. The file marks that steroid point as general practice, not a separate source.

Toxoplasma antibodies are more common in bipolar disorder (OR 1.52 and OR 1.26 in two meta-analyses). That is an association. No antiparasitic bipolar trial was found.

A very-low-carbohydrate, high-fat diet aimed at nutritional ketosis, with a clinician, especially if you take lithium or an SGLT2 drug. In the Edinburgh pilot, mean blood ketones were about 1.3 mmol/L.

The file’s mechanism is ketones as an alternative brain fuel, a drop in brain glutamate plus glutamine of 11.6% to 13.6% on MRS, and the metabolic changes.

You stay in ketosis for weeks, your mood chart is stable, and lithium and other drug levels are rechecked. Seven of 20 Edinburgh completers chose to stay on the diet. That is not the same as a changed mood score.

Lithium levels shift with fluids and salt. Check levels when starting, and make an electrolyte plan with the prescriber.

One serious adverse event was euglycemic ketoacidosis in someone on an SGLT2 inhibitor. Do not combine keto with an SGLT2 drug unless the prescriber is running it.

A woman with a history of depression, on venlafaxine and no mood stabilizer, had a first manic episode about four months into keto, with sleep loss, alcohol, and stress. An antidepressant without a mood stabilizer is a separate risk.

It is hard to keep. A process evaluation calls it challenging but potentially transformational. That does not raise the mood-scale result.

One hypomanic episode occurred during the Edinburgh study. Adverse events were otherwise mostly mild.

This is a medical procedure: screened donor stool, given by a gastroenterologist. It is not a home enema from a relative. In both published improvements, psychiatric medicines were tapered with a psychiatrist, not stopped on the patient’s own.

A meta-analysis found lower microbial richness consistently in bipolar disorder, and fewer butyrate-producing bacteria shared with other psychiatric diagnoses. That is a plausibility story. The randomized trial did not show donor stool beating a person’s own stool.

The trial’s authors say a true placebo is still needed. Lasting symptom freedom in two cases is not a passed rung for everyone else.

Placebo, bowel prep, or time may explain the short-term trial. Not solved. The two cases lasted over a year, which is harder to write off as placebo, and they are still two cases.

Donor risk is real: the twin-donor anecdote went into mania, and another anecdote on the same page worsened after one donor and settled after a switch. The file mentions FDA alerts about drug-resistant infections from fecal transplant as known history, not opened this pass. The answer in the file is screened stool under a gastroenterologist, never DIY.

Stopping medicine is not the success story. In both published cases the taper was supervised. Hinton warned of relapse.

Do not stop bipolar medication for this. The trial reported no significant adverse events. That was 35 people.

Propofol 65, then 75–85 µg/kg/min, for about 60 hours, with a breathing tube. After waking, divalproex was restarted at 750 mg then 1,000 mg twice daily, with chlorpromazine and olanzapine 10 mg.

An ICU team decides this. It is not something to request. A 49-year-old woman with bipolar I and severe mania had already failed divalproex, lorazepam, risperidone, haloperidol, droperidol, six ECT sessions, chlorpromazine, chloral hydrate, and amobarbital. Suspected neuroleptic malignant syndrome on hospital day 37. ICU on day 55: intubated, propofol at 65 then 75–85 µg/kg/min, for about 60 hours of general anesthesia.

The file cannot say whether the anesthesia reset the mania or the restarted medicines plus time did.

She was back on the ward five days after ICU admission and discharged on day 72, on divalproex, chlorpromazine, and olanzapine. That is one course.

Intubation, ICU risk, and propofol infusion syndrome at long high-dose infusions are the objections. The infusion-syndrome thresholds are general anesthesia knowledge, not sourced in this pass. They cannot be solved outside an ICU.

Hospital-only. Six ECT sessions had already failed in this case, which is why a failed course of ECT is not ranked as if it outdoes this case, or the other way around.

The dose on this order is 2 mg, up to 3 days. The Cochrane review is not a test of that exact schedule.

A prescriber gives lorazepam 2 mg for a short course, up to about three days, to restore sleep and calm. It is not a mood stabilizer and it does not replace one.

The Cochrane review says the evidence for benzodiazepines alone is not good. The three-day limit on this order matches the file’s reason for a short course: limiting tolerance and dependence. That reason is marked as general pharmacology, not a cited trial.

Sleep is restored and the course stops. If the episode is still rising, this rung was a bridge, not the treatment.

Sedation, falls, and breathing risk with alcohol or opioids. The file’s answer is prescriber control and the short course.

Clinician-only. Do not combine it with alcohol or opioids. Do not use someone else’s prescription.

Amber glasses in the hospital trial were worn from 6 p.m. to 8 a.m. for 7 days, added to usual treatment.

A fixed wake time, 7–9 hours in bed, no all-nighters, and amber (blue-blocking) glasses after dark when sleep starts to slip. Treat two short nights in a row as an early warning and call the prescriber. Added rules on this order: good deep and REM sleep, and never three nights in a row under 6 hours.

Sleep loss is a common trigger, not a small one, in a large survey. Protecting the rhythm is the cheapest high-yield step in the file. It is still not a substitute for the medicines at the top.

Nights stay long enough, and a short night is treated as a signal rather than pushed through. The file does not define a lab test for “passed.”

Deliberate sleep deprivation can help bipolar depression in the short term (SMD −0.58 at 1 week) without more switching in that analysis. For bipolar I the file says to do that only under a clinician, because of the trigger data above.

Pooled melatonin and ramelteon on mania was g = −0.44, not significant. Two acute-mania trials favored added melatonin.

In the glasses trial: one headache, and two people had depressive symptoms that reversed easily.

Haloperidol 5 mg, lorazepam 2 mg, and diphenhydramine. The TREC trial used promethazine, a different antihistamine, with haloperidol.

In a monitored emergency or hospital setting: haloperidol 5 mg, lorazepam 2 mg, and diphenhydramine, given as a shot for acute agitation. The names on this order are Benadryl, 2 mg Ativan, and 5 mg Haldol.

The antihistamine is there to prevent haloperidol dystonia and to add sedation. In the TREC trial, all 10 acute dystonias were in the haloperidol-only group.

The person is calm or asleep within minutes, in a place that can watch breathing and blood pressure. This is not a maintenance treatment.

It can feel coercive, and it carries breathing and blood-pressure risks. The file’s answer is a monitored setting, which is why the rung is hospital-only.

B52 had more hypotension, more oxygen desaturation, more restraints, and longer stays than the shot without diphenhydramine. The group without diphenhydramine needed an antimuscarinic more often. None of those had documented extrapyramidal symptoms.

Hospital-only. Benzodiazepines alone have poor evidence for agitation. Cochrane says that evidence “is not good.”

The file does not set a target dose. One published patient took 250 mg for five years.

A prescriber uses quetiapine for mania, bipolar depression, or to stay well. Dose is theirs, not a number from this page.

It is one of the few options in this file with evidence on both poles and on staying well.

The episode settles and a maintenance plan is in place. Sedation and appetite are watched, not ignored.

Sedation, morning fog, and appetite or weight gain are real. A man in the Parker 2022 case took 250 mg for five years and described dependence, feeling clouded the next morning for several hours, severe food cravings, and distinct weight gain. He judged that the benefits outweighed these. Weight can be addressed with the prescriber. See the weight page for add-on options. It is not fully solved.

Clinician-only. Do not stop it on your own. The weight and sedation stay on this card. They do not move the rung down.

A prescriber uses olanzapine for mania and, in some plans, to prevent relapse. Track weight and labs from the start.

The acute mania effect is one of the larger medicine effects in the file, and maintenance data show fewer relapses than placebo.

The mania score falls and a plan exists for weight and metabolic labs. Passing the episode is not the same as the weight being solved.

Weight gain and metabolic harm are why CANMAT ranks it second-line. Partly addressed by tracking weight and labs, and by metformin or a GLP-1 drug if the prescriber adds one. Not fully solved. The weight risk is real.

Clinician-only. Do not stop it without the prescriber. See the weight ladder for the add-on numbers in schizophrenia-spectrum trials, which are not bipolar trials.

“Therapeutic” in Bloomfield 2026: 0.6–0.8 mmol/L, about 112–250 mg elemental per day. “Low-dose”: 0.2–0.6 mmol/L, about 20–100 mg elemental per day. Toxicity is a concern from 1.2 mmol/L. 300 mg lithium carbonate is about 56 mg elemental (18.8 mg per 100 mg).

A prescriber starts lithium carbonate and sets the dose from the blood level, not from a fixed capsule count. “300 mg and up” on this order is the usual capsule. 300 mg of lithium carbonate contains about 56 mg of elemental lithium.

It reduces mania, reduces relapse, and is the rung with a large effect on suicide. The leading mechanism in the file is blocking GSK-3β and the enzyme that recycles inositol, plus neurotrophic and anti-inflammatory effects.

The blood level is in the range you and the prescriber aimed for, the episode has settled, and kidney, thyroid, and calcium checks are on the calendar.

Kidney and thyroid risk is real and depends on dose and time. The file’s answer is monitoring: lithium level, kidney, thyroid, and calcium.

The range is narrow. Avoid dehydration and NSAIDs, and tell the prescriber about diarrhea, vomiting, a new diet such as keto, or a GLP-1 drug. In a real-world cohort starting tirzepatide, lithium rose by 0.08 mmol/L at 12 weeks, and two patients went above 1.2, one with symptoms.

Feeling flat is real for some people. A lower target or a combination can be discussed with the prescriber. It is not fully solved for everyone.

Clinician-only. Never stop lithium abruptly. The IGSLi guide links abrupt or rapid stopping to faster, more severe relapse and higher suicide risk.

Do not add lithium orotate on top unless the prescriber is measuring the level.