EMPowerPlus is a nutritional supplement marketed by the company Truehope as a way of correcting nutritional deficiencies that contribute to depression, anxiety, bipolar disorder, and attention-deficit hyperactivity disorder (ADHD). In 2014 Rucklidge et al. published the first controlled study of EMPowerPlus in the British Journal of Psychiatry showing that the supplement was more effective than placebo in adults with untreated ADHD.
EMPowerplus contains 36 ingredients, including 14 vitamins, 16 minerals, 3 amino acids, and 3 antioxidants. Patients were randomized to receive either 15 EMPowerPlus pills per day or 15 placebos per day for 8 weeks, and those patients receiving the supplement were rated as more improved by the end of the study. Effect sizes were moderately robust and side effects did not differ.
Editor’s Note: Multiple uncontrolled studies have suggested the efficacy of EMPowerPlus in childhood mania and related conditions, but this is the first formal placebo-controlled study of the supplement in adults with ADHD. A study in children with ADHD is planned, but it would also be important to study this micronutrient formulation in childhood bipolar disorder, where there is some anecdotal evidence (from Charles Popper at McLean Hospital in Boston and Mary Fristad at the Ohio State University) of excellent responses in children with highly treatment-resistant bipolar illness.
At the US Psychiatric Congress in 2013, researcher T. Ketter reported on two recent studies of armodafinal (Neuvigil), which is approved for the treatment of narcolepsy. Doses of 150mg/day did not perform significantly better than placebo in the treatment of bipolar depression (in contrast to an earlier positive study).
Editor’s Note: It appears that this drug will not play a major role in the treatment of bipolar depression, as some had hoped.
While the reasons why one person develops bipolar disorder and another does not remain mysterious, the current thinking is that genes contribute some risk while immunological abnormalities contribute other risks. Researchers have identified certain antibodies whose levels spike during an episode of mania, as if the patient is having an immune reaction. These are referred to as biomarkers or inflammatory markers.
While various biomarkers for mania have been identified, until recently their effects had only been examined independently. A 2013 article by Dickerson et al. published in the journal PLOS ONE examined four biomarkers in combination. Each was a type of antibody: to the NR peptide of the NMDA receptor, to gliadin (a protein derived from gluten), to Toxoplasma gondii (a parasitic protozoan), and to Mason-Pfizer Monkey Virus. Measures of these four types of antibodies made up a combined inflammation score for participants in the study.
The study compared 57 patients presenting with a manic episode with 207 non-psychiatric controls and 330 patients who had had recent onset of psychosis, schizophrenia, or bipolar depression. The combined inflammation score of the mania group was significantly higher than the other groups at the time of hospital admission and at the time of evaluation several days later. It had returned to normal (i.e. not different from the other groups) at followup six months later, although those with the highest combined inflammation scores were at risk for re-hospitalization during that period.
The findings of this study suggest that hospitalization for mania is associated with immune activation, and the level of this activation predicts subsequent re-hospitalization. Treatments for mania that target this inflammatory response should be investigated.
Metformin, one of the most popular drugs to treat type 2 diabetes, interferes with uptake of vitamin B12, which can in turn lead to some neuronal dysfunction resulting in cognitive dysfunction. Several studies have sought to clarify this link, which may affect up to 30% of patients taking the drug.
Most recently, an Australian analysis of 1354 aging patients found that those with type 2 diabetes performed less well on tests of cognitive abilities, and those diabetic patients with low vitamin B12 levels (below 250 pmol/L) scored lower than those diabetic patients with adequate levels.
Because of the malabsorption problem caused by metformin, patients taking the drug may not be able to get enough B12 from a balanced diet alone and may need supplemental B12. Those who follow a vegetarian diet, have had bowel surgery, have certain complications with the stomach, or who take other medications that depress stomach acid may be at special risk.
Physicians should carefully monitor B12 levels in patients taking metformin, particularly those who have been taking the drug for more than 3 years or those who already suffer from some sort of cognitive impairment.
Omega-3 fatty acids (especially the type known as DHA) are essential for brain development and functioning, but most people eating a modern western diet consume low amounts of these compared to omega-6 fatty acids. Omega-3s are anti-inflammatory while omega-6s are pro-inflammatory. A large UK study published in the journal PLOS One in 2013 reported that healthy 7- to 9-year-olds with lower levels of omega-3 long-chain polyunsaturated fatty acids in their blood (including DHA, DPA, and EPA) had lower reading ability and working memory, and also had more behavior problems.
The oils in fish are the best source of omega-3 fatty acids, and most of the children with poor reading ability in the study fell short of the UK nutritional guideline that recommends eating two portions of fish per week.
Girls in the study had more dramatic deficits in omega-3 levels than boys. In adults, women tend to metabolize long chain polyunsaturated fatty acids more easily than men, but this difference is driven by hormones, and because the girls in the study had not yet reached child-bearing age, they did not reflect this benefit.
Omega-3 deficits in children have been connected with attention deficit hyperactivity disorder (ADHD), and supplementation with extra omega-3 fatty acids in the diet has led to improvements in ADHD.
Cultures where more omega-3 fatty acids (which have anti-inflammatory effects) and fewer omega-6 fatty acids (which have pro-inflammatory effects) are consumed have a lower incidence of depression and bipolar disorder. However, the exact role that each kind of fatty acid plays in the brain and whether dietary changes can improve mood disorders is still being investigated. A 2012 study in the Journal of Psychiatric Research examined the complete lipid profiles of participants with bipolar disorder to collect data on these questions.
The most significant results to come from the study were that levels of the long-chain omega-6 fatty acid dihomo-gamma-linolenic acid (DGLA) were positively correlated with neuroticism, depression severity, and decreased functioning. Depression severity was negatively correlated with the omega-6 fatty acid linolenic acid (LA) and the omega-3 fatty acid alpha-linolenic acid (ALA), and positively correlated with fatty acid desaturase 2 (FADS2), an enzyme that converts LA to the omega-6 fatty acid gamma-linolenic acid GLA.
The data suggest that particular omega-6 fatty acids and the enzymes that lead to their production may be used as biomarkers that can indicate depression.
Editor’s Note: Levels of specific omega-6 fatty acids and their related enzymes were found to correlate with depression severity in this study. Since omega-6 fatty acids are pro-inflammatory, diets higher in omega-6 fatty acids are associated with more cardiovascular problems, and a 2012 article by Chang et al. in the Journal of Psychiatric Research reported that completed suicides in bipolar patients with cardiovascular disorders were significantly higher than in those with bipolar disorder without cardiovascular illness, it seems a healthy diet can have multiple benefits, including potentially reducing depressive burden, cardiovascular risk, and suicide risk.
About a year ago we reported that exercise was recommended for patients with fibromyalgia and chronic fatigue syndrome. The case for exercise has been bolstered by a 2013 analysis published by the Cochrane Collaboration, a nonprofit research network. The authors reviewed five randomized clinical trials that compared resistance training with a control or another type of physical activity in a total of 219 women. Resistance training is exercise that is performed against resistance with the intention of improving muscle strength, and can include weights, resistance machines, or elastic resistance bands. The authors found that in the studies they analyzed, resistance training was both beneficial and safe for women with fibromyalgia, and that aerobic exercise helped reduce pain.
As reported in Medscape Medical News, lead author Angela Busch said, “It appears that people with fibromyalgia can benefit from this form of exercise, but we noted that the programs we examined involved supervised exercise and started low and gradually increased the resistance. There are particular health benefits associated with resistance exercise (e.g. increasing bone strength, which is important for preventing osteoporosis), so it is good to know that clinicians can safely [recommend] this form of exercise.”
Whether patients will widely accept this recommendation remains to be seen since some doctors have advised only rest. The key to avoiding pain exacerbation while adding an exercise regimen may be, like in much of medicine, to start slow.
Editor’s Note: The antidepressant milnacipran (Savella) is the most recent drug to receive Federal Drug Administration approval for the treatment of fibromyalgia. Pregabalin (Lyrica) and duloxetine (Cymbalta) were approved for fibromyalgia in 2007 and 2008, respectively.
Iron deficiency is the most prevalent nutritional deficiency in industrialized countries and can cause problems with cognitive and intellectual development. New research published in the journal BMC Psychiatry shows that it has psychiatric ramifications as well. Children and adolescents with iron deficiency anemia are at greater risk for psychiatric disorders, including depression, bipolar disorder, anxiety, and autism.
Iron supplementation should be implemented in children with iron deficiency anemia in order to prevent any possible psychiatric repercussions, and similarly, psychiatrists should check iron levels in young patients with psychiatric disorders.
Iron provides myelin for white matter in the brain and plays a role in the function of neurotransmitters.
In a 2014 study published by Michael A. Yassa et al. in the journal Nature Neuroscience, a 200mg caffeine pill (about the equivalent of a strong cup of coffee) improved long-term recognition memory. One hundred sixty participants who were not regular coffee drinkers were shown a series of 200 pictures, and 24 hours later they were given a surprise test. Compared to participants who received a placebo, those participants who received 200mg of caffeine were better able to discriminate which pictures they had seen before and which ones were new. Participants who received 100mg of caffeine did not show this effect, while those who received 300mg showed the same improvement in memory but also experienced side effects such as headache and nausea.
As long as a cup of coffee does not make its drinker more anxious, it may help boost memory.
Editor’s Note: Coffee may have other benefits. In research collected by the Bipolar Collaborative Network (in which this editor is an investigator), patients who drank coffee were less likely to be overweight. Yassa also believes based on other research that caffeine is associated with a reduced risk for Alzheimer’s disease and that it increases longevity.
Lithium treatment is associated with a moderate incidence of hyperparathyroidism, usually observed as an elevated concentration of calcium in the blood in addition to elevated parathormone levels, and often associated with the development of a tumor (adenoma) of the parathyroid gland.
In a recent study by Van Melick et al. published in the International Journal of Geriatric Psychiatry, among 111 patients with an average age of 75 years, 24-hour calcium excretion was elevated in only 3% of the patients, but levels of parathormone were elevated in 48%. Duration of lithium treatment was associated with lower vitamin 25OH D. Vitamin D is important for healthy bones and good cognitive functioning.
Editor’s Note: Lithium-induced hyperparathyroid should be investigated in those with elevated calcium levels, and if found, surgical removal of the parathyroid gland may be indicated. Low vitamin D is common in the US population. It is also particularly low in patients with mania and elderly patients on who have been on lithium for more than ten years. (Levels are below normal in 77% of these elderly individuals.) Assessment of vitamin D levels in those on long-term lithium is advisable, in addition to monitoring the thyroid, kidney function, and calcium metabolism.