SNRI Viloxazine May Be Reintroduced as ADHD Treatment
The pharmaceutical company Supernus identifies older drugs that may be repurposed to treat other disorders. The company believes it may have found a new use for the discontinued antidepressant viloxazine, as a treatment for attention deficit hyperactivity disorder (ADHD).
Viloxazine is a selective norepinephrine reuptake inhibitor, or SNRI, that was approved in Europe but not in the US and was eventually removed from the market due to competition from other drugs. Its structure and mechanism of action resemble those of the ADHD treatment atomoxetine, so Supernus has begun trials of viloxazine for ADHD in adults.
At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, the researchers reported that compared to placebo, viloxazine was about twice as likely to reduce ADHD symptoms. Side effects included nausea, decreased appetite, headache, and insomnia. Supernus hopes to create an extended release form of the drug for both adults and children.
Inflammation Linked to Post-Stroke Depression
A 2016 study in the journal Psychoneuroendocrinology confirms that high levels of inflammatory cytokines in the blood are linked to higher risk of depression following a stroke.
The study, by Hee-Ju Kang and colleagues, followed 222 stroke sufferers for one year. Two weeks following the stroke, their levels of inflammatory cytokines IL-6 and IL-18 were measured. They were also assessed for depression both at the two-week point and one year later. The researchers also observed whether or not the participants were treated with statins, which are often prescribed to lower stroke risk and also have anti-inflammatory effects.
Those participants who had depression following their strokes (either at two weeks or at one year) tended to be older, to have a history of depression or stroke, to have a more severe stroke, and to have a stroke location toward the front of the brain.
Having any depression following the stroke was associated with higher levels of IL-6 and IL-18. This was particularly true of those participants who were not taking a statin. Among those taking statins, the statins may have interfered with the link between inflammatory cytokines and post-stroke depression. In the statin group, the only significant finding was a link between levels of IL-6 and depression at the two-week mark.
Depression Elevates Stroke Risk
Depression has been linked to increases in medical problems such as cardiovascular disease. A new study shows that depression is linked to increased risk of stroke, even when symptoms of depression are in remission.
The 2015 study, by Paola Gilsanz and colleagues in the Journal of the American Heart Association, focused on health and retirement. It included over 16,000 adults aged 50 and up who were interviewed every two years about their health history.
Previous studies have shown a link between depression and stroke risk. Like those studies, the study by Gilsanz and colleagues found that people who were depressed during two consecutive interviews were more than twice as likely to have a stroke in the subsequent two-year period than those who reported few depressive symptoms in the first two visits.
What is new is that in this study, people who were depressed in the first interview but not in the second interview were still at 66% greater risk for a stroke than those with no depression. Those who were depressed only during the second interview not at greater risk for a stroke, implying that depression takes more than two years to affect stroke risk.
Gilsanz and colleagues suggest that they don’t know how depression, remission, and stroke risk interact over the longer term. It is possible that stroke risk diminishes the longer a patient’s depression stays in remission.
It is not clear why depression increases strokes, though some have speculated that depression causes irregular heartbeats. There is not as yet any support for that theory, but high blood pressure, rigid veins, or sticky platelets may be other explanations.
Smoking Ban in New Jersey Jails Drastically Reduced Deaths of Inmates with Mental Illness
Policy changes by the New Jersey Department of Corrections drastically reduced the availability of tobacco products in New Jersey jails between 2005 and 2014. Prison commissaries reduced their stock of tobacco, prices increased, sales to minors were banned, and facilities were designated tobacco-free (including for staff and visitors).
Along with this reduction in the availability of tobacco products, the Department of Corrections also introduced smoking cessation programs, began offering nicotine replacement lozenges in commissaries, and increased treatment for tobacco use.
A surprise consequence of the decision to go tobacco-free was a drastic reduction of deaths among prison inmates with mental illness. The mortality rate for these inmates dropped by 48%. In contrast, the mortality rate for inmates without mental illness remained flat before and after the tobacco ban.
People with mental illness are at increased risk of mortality, particularly from cardiovascular illnesses. Now it seems that eliminating tobacco use can go a long way toward improving health and reducing mortality for these people.
Metabolized Form of B Vitamin Improves Depression in People with MTHFR Deficiency
MTHFR is an enzyme needed for the body to break down vitamin B9, also known as folate or folic acid. It also helps convert the toxic amino acid homocysteine into the antidepressant amino acid s-adenysl-methionine. However, a significant segment of the population (some estimate 40%) have a genetic mutation in the MTHFR gene that interferes with the body’s ability to break down B vitamins and is linked to higher levels of homocysteine. MTHFR mutations are also linked to depression.
A 2016 study by Arnold W. Mech and Andrew Farah in the Journal of Clinical Psychiatry found that treating people with major depression and a MTHFR deficiency using a combination of micronutrients and already-broken-down B vitamins improved their depression and reduced their homocysteine levels compared to placebo.
The study included 330 adult patients with major depression and one of two genetic variants in the MTHFR gene—C677T or A1298C. Of those who received the metabolized vitamins, 82.4% showed reduced homocysteine levels. Those who received placebo showed a small average increase in homocysteine. The vitamin group also saw a large drop in depression symptoms on average after 8 weeks, with 42% achieving full remission. There were no side effects.
These findings suggest that homocysteine levels play a role in depression and that metabolized B vitamins can be an effective treatment for depression, particularly in those with a MTHFR deficiency. A metabolized form of folate that is commercially available is called L-methylfolate.
Mouse Study Shows That Ketamine Metabolite May Treat Depression with Fewer Side Effects
The drug ketamine has been used intravenously for years to rapidly treat depression, because it can take effect within hours. Unfortunately, its antidepressant effects fade in 3–5 days, and it has some unpleasant side effects. In larger doses ketamine is used as an anesthetic and sometimes as a club drug, for its ability to induce hallucinations and dissociation. It can be addictive as well.
A 2016 animal study by Todd Gould and colleagues published in the journal Nature identified a byproduct of ketamine that may be able to provide the drug’s benefits without its side effects.
When the body breaks down ketamine, it produces several chemicals that are known as ketamine metabolites. The researchers found that one of these, called hydroxynorketamine, reversed a depression-like state in mice, without producing the side effects that would be expected of ketamine.
Gould and colleagues also determined that blocking the transformation of ketamine into hydroxynorketamine prevented ketamine’s antidepressant effects.
Ketamine’s unpleasant anesthetic and dissociative effects result from the blockade of a particular receptor for the neurotransmitter glutamate (the NMDA glutamate receptor). Researchers originally thought that the NMDA blockade was linked to ketamine’s antidepressant effects, but this appears not to be the case. Instead, hydroxynorketamine seems to activate a different type of glutamate receptor, the AMPA receptor.
Gould and colleagues plan to test hydroxynorketamine in humans soon. Because it has already been present in the human body following ketamine administration, they expect it to be safe.
IV Ketamine 2 or 3 Times Per Week Improves Depression
We have written many times before about intravenous ketamine as a fast-acting antidepressant treatment that can produce results within hours. Unfortunately, these quick results tend to fade within a few days. Current research is focused on possible ways of extending ketamine’s antidepressant effects.
A 2016 article by Jaskaran B. Singh and colleagues in the American Journal of Psychiatry reported that giving depressed patients infusions of ketamine (0.5mg/kg of body weight) twice or three times per week improved their depression compared to placebo over a period of up to 2 weeks.
Side effects included headache, anxiety, dissociation, nausea, and dizziness. The dissociation was temporary and improved with repeated dosing.
In Rats, Mother’s Exercise Habits Affect Those of Offspring
A recent study suggests that when a mother rat exercises during pregnancy, her offspring will exercise more too.
In the study, published by Jesse D. Eclarinel and colleagues in The FASEB Journal, pregnant mother rats were placed in cages that each contained an exercise wheel. One group had access to a working wheel on which they could run. The other group had the same wheel, but it was locked so that they couldn’t use it for running. Daughters of the rats who ran during pregnancy ran more in adulthood (both at 60 days and 300 days after birth) than daughters of the rats who couldn’t run during pregnancy.
While it is a mystery why this occurs, it is consistent with other data about the ways that a parent’s experiences can influence the next generation, even when the offspring don’t grow up with the parents.
For example, father rats conditioned to associate a specific smell with fear of an electric shock have offspring that also fear that smell (but not other smells).
Drug use is another example. Father rats given access to cocaine have offspring that are less interested in cocaine. Interestingly, father rats exposed to marijuana have offspring that are more interested in opiates.
Experiences with drugs or stress are thought to affect the next generation via ‘epigenetic’ marks on ova or sperm. These marks change the way DNA is packaged, with long-lasting effects on behavior and chemistry. Most marks from a mother’s or father’s experiences are erased at the time of conception, but some persist and affect the next generation.
The nature versus nurture debate is getting more and more complicated. Parents can influence offspring in a number of ways: 1) genetics; 2) epigenetics in the absence of contact between parent and offspring after birth; 3) epigenetic effects of behavioral contact—that is, parents’ caring and warmth versus abuse and neglect can affect offspring’s DNA expression too. All these are in addition to any purely behavioral influence a parent may have on their offspring via discipline, teaching, being a role model, etc.
Editor’s Note: The moral of the story is, choose your parents wisely, or behave wisely if you yourself become a parent.
TDCS Can Change Sleep Duration
A German study published in 2016 suggests that transcranial direct current stimulation (tDCS) can affect the duration of a person’s nightly sleep. Lukas Frase and colleagues compared the effects of two different tDCS parameters and a sham stimulation on the sleep patterns of 19 healthy volunteers.
TDCS is a treatment in which an anode and a cathode electrode placed on the skull are used to apply a steady, low-level current of electricity to the brain.
Bi-frontal anodal stimulation, intended to increase arousal, significantly decreased total sleep time compared to the other two interventions.
Bi-frontal cathodal stimulation, intended to decrease arousal, did not increase total sleep time, possibly because there is a ‘ceiling’ beyond which good sleepers do not sleep longer.
EEG analysis showed that the anodal stimulation did increase arousal, while cathodal stimulation decreased it.
The research increases what is currently known about sleep-wake regulation by showing that total sleep time can be decreased using anodal tDCS. The researchers hope this knowledge can contribute to future treatments for disturbed arousal and sleep.
Antidepressant Brintellix Renamed Trintellix
A new label: Brintellix is now Trintellix.
You may notice the label on your prescription bottle changing. As of June, the antidepressant vortioxetine (formerly Brintellix) is now called Trintellix. The US Food and Drug Administration approved the change to reduce any possible confusion of the antidepressant with a blood-thinning medication called Brilinta.
