Several researchers have found that lithium has some value in fighting dementia. The researcher Lars Kessing has published several studies showing that people taking clinical doses of lithium for bipolar disorder have a lower incidence of dementia in old age.
In 2011, another researcher, Oreste Vicentes Forlenza, reported that a year of low-dose lithium (typically around 300mg/day) slowed deterioration in people with mild cognitive impairment compared to placebo.
In an article published in the journal Current Alzheimer Research in 2013, researchers led by Marielza Andrade Nunes reported that very small doses of lithium (more than a thousand times lower than doses used to treat mood disorders) also improved mild cognitive impairment in people with Alzheimer’s disease.
In Nunes’ study, participants with Alzheimer’s disease were randomly assigned to receive either 300 micrograms of lithium daily or a placebo. Beginning at three months of treatment, those receiving the microdoses of lithium showed stable performance on a common Alzheimer’s evaluation tool that measures how well patients remember, recall information, and follow directions; while those taking placebo got worse.
This continued over the 15 months of the study, with the difference between the two groups intensifying over time—those taking placebo got worse, while those getting the microdoses of lithium remained stable.
There were no complaints of side effects from the microdoses of lithium, and participants showed no sign of impairment to their kidney or thyroid function (a risk with the higher doses of lithium used to treat bipolar disorder).
In 2015, Nunes and colleagues reported in the journal PLOS ONE that in a mouse model of Alzheimer’s disease, mice treated with chronic low doses of lithium in their water had less memory disruption, fewer plaques in the brain, and fewer reductions in cortex and hippocampus size compared to mice given plain water.
These studies suggest that low or micro doses of lithium may be a promising treatment for Alzheimer’s disease. Much more research is needed to determine appropriate lithium dosing for the treatment of dementia or cognition problems.
People with unipolar depression and bipolar disorder may experience cognitive difficulties, even when they’re not currently depressed. In a study published in the journal European Neuropsychopharmacology in 2016, researchers led by Caroline Vintergaard Ott determined that treatment with the hormone erythropoietin (EPO) may help. EPO is produced in the kidney and increases the production of hemoglobin and red cells.
Seventy-nine participants with unipolar or bipolar disorder were randomized to receive infusions of either EPO or a saline solution once a week for eight weeks. By the end of the study, those who received EPO showed significant improvements in the speed of their complex cognitive processing compared to those who received saline. EPO is known to induce the production of red blood cells. The improvements in processing speed lasted for at least another six weeks after red blood cell production would have normalized.
Those participants who received EPO not only had improved scores on tests of processing speed, they also reported fewer cognitive complaints. The EPO treatment was most likely to be effective in participants who had more impaired cognition at the beginning of the study.
In previous research by the same research group presented by Kamilla W. Miskowiak at the 2014 meeting of the International Society of Bipolar Disorders, EPO also improved sustained attention and recognition of happy faces.
Oxytocin, a hormone that promotes emotional bonding, also benefits people having trouble dealing with stress. A new study suggests that giving oxytocin for a week shortly following a traumatic experience reduces the risk that the recipient will develop post-traumatic stress disorder (PTSD).
In the study by researcher Mirjam van Zuiden and colleagues, people who visited an emergency room following some kind of trauma were randomized to receive either a placebo nasal spray or intranasal oxytocin twice daily for 7.5 days beginning within 12 days after the trauma. The dosage was 40 IU twice daily.
For those participants with severe PTSD symptoms at baseline, repeated oxytocin administration prevented worsening PTSD. The research was presented at the 2016 meeting of the Society of Biological Psychiatry.
In a new study by Keiho Owada and colleagues, 18 people with autism spectrum disorders had more neutral facial expressions and fewer surprised expressions than 17 typically developing people while interacting socially. Oxytocin, a hormone that promotes social bonding, was delivered to the autism group via a nasal spray for six weeks, and made the faces of the people with autism more expressive. Oxytocin also improved their reciprocity in social interactions and increased activity in the dorsomedial prefrontal cortex, as observed via functional magnetic resonance imaging (fMRI).
The study suggests not only that oxytocin can normalize facial expressions, but also that the counting of facial expressions on videos of social interactions can be used as a measure of social symptoms of autism. The research was presented at the 2016 meeting of the Society of Biological Psychiatry.
Oxytocin, the hormone that promotes emotional bonding, also regulates a variety of behaviors. Two recent studies suggest that in rats, an injection of oxytocin can prevent drug-seeking behavior.
In the first study, researcher Gary Aston-Jones found that oxytocin reduced the rats’ interest in methamphetamine. The effect was strongest in the rats that started out with the strongest interest in the methamphetamine.
In the second study, researcher Luyi Zhou and colleagues determined that oxytocin also reduced cocaine-seeking behavior in rats. In addition, the oxytocin reversed changes in the brain’s glutamate signaling pathway that were caused by cocaine use.
Both studies, which were presented at the 2016 meeting of the Society of Biological Psychiatry, suggest that oxytocin is a promising potential treatment for drug addictions.
PANS is a neuropsychiatric syndrome characterized by the acute onset of obsessive compulsive and other abnormal behaviors, tics, and mood changes that appear in a child following a bacterial or viral infection. PANS refers to any pediatric acute-onset neuropsychiatric syndrome of this type, while PANDAS refers more specifically to such a syndrome that occurs after exposure to streptococcal infections.
New research suggests that treatment with the antibiotic azithromycin can treat PANS. In a study presented at the 2016 meeting of the Society of Biological Psychiatry, Tanya K. Murphy and colleagues found that among 32 children aged 4–14 who showed obsessive compulsive symptoms following an infection, those who were given a 4-week course of azithromycin (10mg/kg of body weight, up to 500 mg/day) saw a 26% drop in symptoms, compared to a 1% drop in symptoms in those who received placebo instead.
At the end of the four weeks, 38.9% of the azithromycin group were classified as much improved or very much improved, while no one in the placebo group achieved this level of improvement. Azithromycin treatment increased the QTc interval (a measure of heart rate) and pulse in the study participants, but did not have any other notable side effects.
PANS is thought to arise from an immune response to infection that goes awry and begins attacking neurons in the brain, particularly in the thalamus. For a more complete review of PANS, see several of our earlier articles about PANS and an excellent review article by researcher Kiki Chang and colleagues in the Journal of Child and Adolescent Psychopharmacology in 2015.
It is important to work up a child suspected of having PANS, as the syndrome does not usually respond to conventional psychiatric treatment and often requires anti-inflammatory drugs (steroids or immunosuppressants), intravenous immunoglobulin (IVIG), plasma exchange, the TNF alpha blocker infliximab, or antibiotics.
In a small proof-of-concept study, researcher Stephen J. Kanes and colleagues showed that injections of allopregnanolone could nearly eliminate symptoms of post-partum depression.
Allopregnanolone is the main metabolite of the hormone progesterone. Rapid changes in hormone levels following delivery are thought to cause post-partum depression.
In the study, four women with post-partum depression were given injections of SAGE-547, a proprietary solution of allopregnanolone. The dose was adjusted over 12 hours until it approximated prenatal levels of allopregnanolone. This level was maintained for 36 hours, and then the women were weaned off the SAGE-547 over another 12 hours. As soon as the women began injections of SAGE-547, their depression began to improve, and this lasted after they stopped receiving the injections. By 84 hours after beginning treatment, depression scores had improved by 81%.
Kanes and colleagues, who presented this research at the 2016 meeting of the Society of Biological Psychiatry, will follow up this study with placebo-controlled trials of SAGE-547.
We have previously reported on the research by Martin Alda and colleagues that the chemical compound methylene blue had positive effects in patients with bipolar depression. The research was published in the British Journal of Psychiatry in 2016.
Now a new article by Ashley M. Feen and colleagues in the Journal of Neurotrauma reports that methylene blue has an antidepressant-like effect in mice with traumatic brain injury (TBI). Methylene blue reduced inflammation and microglia activation in the animals. Methylene blue reduced levels of the pro-inflammatory cytokine Il-1b and increased levels of the anti-inflammatory cytokine Il-10.
These findings are of particular interest as many patients with classical depression (and no brain injury) have abnormal levels of these inflammatory markers. It remains to be seen whether methylene blue is more helpful in those patients with elevated inflammatory markers and if levels of the markers can predict treatment response or not.
Methylene blue causes urine to turn blue, so low doses of the compound are used as a placebo. Alda and colleagues reported that the active dose 195mg reduced depression and anxiety significantly more than the placebo dose (15mg) in a 13-week crossover study. In that study, methylene blue was added to lamotrigine which had not had a complete enough effect.
In a 1986 study by G.J. Naylor and colleagues in the journal Biological Psychiatry, patients were treated with either 15mg/day or 300mg/day of methylene blue for one year and crossed over to the other dose in the second year. Participants had significantly less depression during the year of taking the active 300mg/day dose.
The FDA has issued a warning about the danger of a serotonin syndrome if methylene blue is combined with serotonin active agents (presumably because it inhibits MAO-A). Symptoms of the serotonin syndrome can include lethargy, confusion, delirium, agitation, aggression, decreased alertness, and coma. Neurological symptoms, such as jerky muscle contractions, loss of speech, muscle tension, and seizures; or autonomic symptoms, such as fever and elevated blood pressure, are also common. Patients should call their doctor if they are taking a serotonergic psychiatric medication and develop any of the above symptoms.
Antidepressants can take weeks to begin working, and researchers have been investigating ways to speed up this process. A 2012 study by In Kyoon Lyoo and colleagues in the American Journal of Psychiatry found that among 52 women taking the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram (Lexapro) for unipolar depression, those who were prescribed an additional creatine supplement had earlier and greater decreases in depression symptoms than those who received a placebo in addition to the escitalopram.
The difference between the two groups was evident by the second week of treatment. At the end of the 8-week study, 52% of those who received creatine had achieved remission, compared to 26% of those in the placebo group.
Creatine, a supplement sometimes used by weightlifters, increases cellular energy. The women received 3g/day of creatine for the first week of the study, and 5g/day thereafter.
The same research group recently published more data from their creatine study. The new article by Sujung Yoon and colleagues in the journal Biological Psychiatry shows that following the creatine supplementation, the women in the creatine group had greater levels of N-acetylaspartate (a sign of healthy neurons) in their prefrontal cortex and also had greater levels of brain connectivity than women in the placebo group.
The US Food and Drug Administration recently approved a device that improves sleep by cooling the forehead. People with insomnia often have an active frontal cortex that keeps their thoughts racing as they try to fall asleep, preventing deeper, more restorative sleep. Through conducting functional brain imaging studies, researcher Eric Nofzinger found that cooling participants’ foreheads to a precise level during the night improved the quality of their sleep.
The sleep studies included more than 230 patients observed over 3800 research nights. One such study found that participants reached stage 1 and stage 2 sleep faster when they used the device.
Nofzinger founded the company Cerêve to produce the new bedside device, which pumps cooled fluid to a pad worn on the forehead. The company expects to release the device in 2017.
Insomnia may affect as many as 55 million Americans, frustrating them at night and leading to decreased alertness the following day. Sleeping pills are the most common treatment, but they can also cause impairment the following day.