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.
The same type of high-intensity light therapy used to treat seasonal affective disorder (SAD) and as an adjunctive treatment for non-seasonal depression has been found to boost testosterone and improve sexual satisfaction in men with low libido.
In a study by Andrea Fagiolini and colleagues, men with low sexual desire or trouble getting aroused were exposed to the high intensity light (10,000 Lux) for a half hour upon waking. Compared to men who used a lightbox that filtered the light to only 100 Lux, men exposed to the high-intensity light for two weeks showed increased testosterone in the blood and reported greater sexual satisfaction. Testosterone levels increased from around 2.1 ng/ml to 3.6 ng/ml in the high-intensity light group. (There were no significant changes in the comparison group.) Light therapy is quite safe for people without eye problems.
Fagiolini explained that in the Northern hemisphere, testosterone production declines from November to April and then rises again through the spring and summer, peaking in October. He suggests that the light therapy mimics the effect of summer light on the body, perhaps by inhibiting the pineal gland, which secretes hormones.
Fagiolini and colleagues hope to replicate the study with a greater number of participants and to determine how long the results may last.The study of 38 participants was presented at the 29th Congress of the European College of Neuropsychopharmacology in 2016.
A small, uncontrolled study in the journal Lancet Psychiatry suggests that psilocybin, an ingredient in hallucinogenic mushrooms, relieved depression symptoms for up to three months in seven of 12 participants with unipolar depression that had not responded to at least two antidepressant medications.
Psilocybin has a different mechanism of action than typical treatments for depression. It activates 5HT2A serotonin receptors.
The participants, who had moderate to severe depression, were given two oral doses of psilocybin, a low dose (10mg) to establish the safety of the intervention, and a higher dose (25mg) seven days later. Psychedelic effects (anxiety, confusion, nausea, and headache) peaked within two to three hours and had dissipated by six hours after the intervention.
Depression began to improve within 24 hours after the 25mg dose. Depression symptoms were significantly improved by one week after the intervention. Eight of the 12 participants had a complete remission of their depression after one week, and this lasted the full three months in five participants. By the end of the three months, a total of seven of the 12 participants met the criteria for response to psilocybin.
The study’s authors, led by Robin L. Carhart-Harris, suggest that their preliminary results warrant more systematic investigation of psilocybin, but because there was no comparison group in this study, a large placebo effect cannot be ruled out.
A large study in Denmark suggests that taking selective serotonin reuptake inhibitor (SSRI) antidepressants alongside cholesterol-lowering statin drugs improved depression more than SSRIs alone. The findings, by Ole Köhler and colleagues were reported in the American Journal of Psychiatry in 2016.
The study included 872,216 people in Denmark’s national health care database who took SSRIs between 1997 and 2012. The most common SSRIs were citalopram, sertraline, and escitalopram. Of these people taking SSRIs, 13.0% also took a statin drug, typically simvastatin. Those patients who were taking both an SSRI and a statin were less likely than those taking an SSRI alone to be hospitalized for any psychiatric problem, or for depression specifically.
Depression is known to be correlated with inflammation throughout the body. Statins reduce this inflammation as well as lowering cholesterol. A 2013 study by Ahmad Ghanizadeh and Arvin Hedayati in the journal Depression and Anxiety showed that the SSRI fluoxetine and the statin lovastatin reduced depression severity compared to fluoxetine alone.
The combination of SSRIs and statins did not seem to reduce deaths or suicidal behavior compared to SSRIs alone. Statins have some side effects, but combining them with antidepressants did not increase the risks associated with their use.
Ketamine, which is used as an anesthetic at higher doses, can also relieve depression within hours when delivered intravenously. A 2016 study by Morteza Jafarinia and colleagues in the Journal of Affective Disorders suggests that oral ketamine may be helpful in the treatment of mild to moderate depression in people with chronic pain.
The study compared 150mg daily doses of oral ketamine to 150mg daily doses of the anti-inflammatory pain reliever diclofenac over 6 weeks. When interviewed at week 3 and week 6, the ketamine group reported significantly fewer symptoms of depression than the diclofenac group.