The antioxidant N-acetylcysteine (NAC) has been found to reduce many types of habitual behavior, from gambling to drug use to compulsive hair-pulling. A recent study by researcher Gihyun Yoon and colleagues, which was presented at a 2015 scientific meeting, found that while NAC and placebo reduced days of heavy drinking by about the same rates, NAC significantly reduced alcohol cravings and quality of life compared to placebo among participants with alcohol dependence.
In the 8-week study, 44 participants aged 18–65 received either 3600mg/day of NAC or a placebo. This dose of NAC was higher than the 600mg–2400mg doses that have typically been used in research settings, and there were few side effects, confirming that NAC is a safe treatment.
The authors are not sure how NAC produces this effect, but it may be by regulating the neurotransmitter glutamate.
Glia are brain cells that surround neurons and synapses, protecting and insulating them. Chronic cocaine use and withdrawal changes the way certain glial cells, called astrocytes, interact with neurons. In particular, chronic cocaine use and withdrawal can shrink astrocytes and cause them to pull away from neurons. Cocaine use and withdrawal also interfere with the way the neurotransmitter glutamate is cleared from synapses and transported into astrocytes.
New research shows that certain medications that regulate and increase the movement of glutamate from the synapse into glial cells can reduce cravings for cocaine.
In studies of rats chronically exposed to cocaine and then denied access to it, treatment with these glutamate-targeting medications reduces the rats’ cocaine-seeking behaviors. The medications include N-acetylcysteine (NAC), an antioxidant that can reduce habitual behaviors, including addictive behaviors; riluzole, a treatment for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease; the antibiotic ceftriaxone; and propentofylline, which has been explored as a possible treatment for dementia and stroke.
The antioxidant N-acetylcysteine (NAC) has been found to be an effective treatment for a variety of habit-based behaviors—substance abuse, including cocaine, alcohol, marijuana, and nicotine; gambling; obsessive-compulsive behaviors; trichotillomania (compulsive hair-pulling), and repetitive behaviors among people with autism. Recent research by researcher Jon Grant and colleagues revealed that NAC can also treat skin-picking disorder.
At a 2015 scientific meeting, Grant reported that 1200–3000mg of NAC per day led to improvement in 47.1% of patients with a skin-picking disorder, compared to 19.2% improvement in patients who received placebo.
In addition to its positive effects in people with addictions and habit-based behaviors, NAC has also improved mood and anxiety in bipolar disorder and treated negative symptoms of schizophrenia, such as withdrawal and lack of motivation.
Editor’s Note: Given NAC’s effectiveness in such a wide range of disorders and behaviors, it could be a particularly useful treatment for people with major psychiatric disorders, such as bipolar disorder or schizophrenia, with co-occurring substance abuse.
Post-partum depression affects 13% of new mothers, but little is known about how to prevent it. Doctors are researching ways of reducing post-partum blues, which can occur 4–6 days after delivery, when levels of the enzyme monoamine oxidase-A are high. At a 2015 scientific meeting, researchers led by Yekta Dowlati of the Centre for Addiction and Mental Health at the University of Toronto reported that a nutritional supplement designed to counteract the high levels of monoamine oxidase-A improved depression among 17 healthy women who had recently given birth, compared to 16 new mothers who did not receive the supplement. The supplement contained 2g of tryptophan and 10g of tyrosine, both amino acids found in protein-rich foods, plus blueberry juice and a blueberry extract.
Repeated transcranial magnetic stimulation, or rTMS, is a non-invasive treatment in which a magnetic coil placed near the skull transmits electrical signals to the brain. It is an effective treatment for depression, and now it appears it may also be useful in the treatment of addictions.
A pilot study by Alberto Terraneo and colleagues published in European Neuropsychopharmacology in 2016 compared rTMS treatment delivered to the dorsolateral prefrontal cortex to pharmacological treatment in 32 patients who wanted to stop using cocaine. Those in the rTMS group received one session of the treatment per day for five days, followed by one session per week for three weeks. Those who received rTMS had a higher number of cocaine-free urine tests than those who had been treated with pharmacological treatments. Among those who received rTMS, 69% had a positive outcome, compared to 19% of the control group. RTMS also reduced cravings for cocaine. Both treatments improved depression.
Antonello Bonci, another author of the study who is also scientific director at the US National Institute on Drug Abuse, suggested that rTMS may work by “scrambling” the pattern of neural activity that leads to cocaine craving.
Now that there is some evidence suggesting that rTMS may be useful in the treatment of addictions, the researchers are planning a placebo-controlled study of rTMS treatment for cocaine use, in which they will give some patients a sham treatment instead of real rTMS.
Other studies are examining whether rTMS can be used to treat smoking and alcohol use disorders in addition to depression.
Research continues on pioglitazone, a drug typically used to treat diabetes but with other positive effects on depression and stroke risk. Some researchers are working on determining whether the drug increases the risk of developing certain cancers, including bladder, prostate, and pancreatic cancers. A recent study by James D. Lewis and colleagues in the journal JAMA found no statistically significant increase in risk of bladder cancer among patients taking the drug, but the researchers said they also couldn’t rule out that the drug may increase this risk, as has been seen in previous studies. The study by Lewis did show an increase in pancreatic and prostate cancers in patients taking pioglitazone, but the researchers did not determine whether this was caused by the drug.
Another recent study by Walter N. Kernan and colleagues in the New England Journal of Medicine reported that pioglitazone reduced the incidence of stroke and heart attack in patients with a history of stroke or blocked blood vessels in the brain but without a diagnosis of diabetes. Patients who received pioglitazone also experienced side effects including weight gain, edema (an increase in fluids in the body’s tissues) and serious bone fractures.
Pioglitazone has had positive effects in bipolar depression and may one day be used as a treatment for bipolar disorder. For now, it may be worthy of consideration for the treatment of diabetes in patients who also have bipolar depression.
There is no perfect treatment to reduce the risk of suicide in someone who is considering it. Antidepressants can reduce suicidal ideation, but they take several weeks to start working. Intravenous ketamine is used at higher doses as an anesthetic, but in low doses works quickly to reduce suicidal thoughts. However, it requires repeated infusions to keep working. Researchers led by Yoram Yovell are exploring another option: ultra-low doses of the opioid buprenorphine.
In a study published in the American Journal of Psychiatry in 2015, Yovell and colleagues compared low-dose buprenorphine to placebo in 62 patients with no history of substance abuse who had been contemplating suicide for a week or more. Many had attempted suicide before, and more than half met the criteria for borderline personality disorder.
Buprenorphine was administered under the tongue, in doses of 0.1 mg once or twice a day. The researchers used these low doses to minimize the side effects of a drug that could potentially be addictive. Those randomized to receive buprenorphine saw greater reductions in suicidal ideation compared to those who received placebo, both after two weeks and after four weeks.
Use of antidepressants did not affect the likelihood that patients would respond to buprenorphine. The researchers suggest that buprenorphine specifically treats suicidal thoughts, rather than improving depression in general.
Patients with borderline personality disorder, who are often unresponsive to medication, also saw improvement in suicidal ideation after taking buprenorphine, suggesting that the opioid treated a particular symptom of their disorder—sensitivity to feelings of separation from the people with whom they are close.
Patients did not experience withdrawal when they discontinued buprenorphine. Side effects included fatigue, nausea, dry mouth, and constipation. Patients who started out taking 0.2 mg per day were much more likely to drop out than those who started at 0.1 mg per day.
There is another reason the researchers used very low doses. A potential benefit to ultra-low–dose buprenorphine is that even a week’s supply of the drug would not produce a dangerous overdose, so patients could potentially be prescribed a week’s worth of medication to take at home instead of in an inpatient setting.
Buprenorphine is not recommended for patients with a history of substance abuse. The study only explored short-term use of the drug, and replication studies are needed to clarify its effects.
The hormone oxytocin, best known for creating feelings of love and bonding, may help treat post-traumatic stress disorder, since it also reduces anxiety. A study by Saskia B.J. Koch and colleagues that will soon be published in the journal Neuropsychopharmacology reports that a single intranasal administration of oxytocin (at a dose of 40 IU) reduced anxiety and nervousness more than did placebo among police officers with PTSD.
Oxytocin also improved abnormalities in connectivity of the amygdala. Male participants with PTSD showed reduced connectivity between the right centromedial amygdala and the left ventromedial prefrontal cortex compared to other male participants who had also experienced trauma but did not have PTSD. This deficit was corrected in the men with PTSD after they received a dose of oxytocin. Female participants with PTSD showed greater connectivity between the right basolateral amygdala and the bilateral dorsal anterior cingulate cortex than female participants who had experienced trauma but did not have PTSD. This was also restored to normal following a dose of oxytocin.
These findings suggest that oxytocin can not only reduce subjective feelings of anxiety in people with PTSD, but may also normalize the way fear is expressed in the amygdala.
Vitamin D3 tends to be low in children and adolescents with mania, but supplements may help. In a small open study published in the Journal of Child and Adolescent Psychopharmacology in 2015, Elif M. Sikoglu and colleagues administered 2000 IU of vitamin D3 per day to youth aged 6–17 for eight weeks. Sixteen of the participants had bipolar spectrum disorders (including subthreshold symptoms) and were exhibiting symptoms of mania. Nineteen participants were typically developing youth.
At the beginning of the study, the youth with bipolar spectrum disorders had lower levels of the neurotransmitter GABA in the anterior cingulate cortex than did the typically developing youth. Following the eight weeks of vitamin D3 supplementation, mania and depression symptoms both decreased in the youth with bipolar spectrum disorders, and GABA in the anterior cingulate cortex increased in these participants.
Editor’s Note: GABA dysfunction has been implicated in the manic phase of bipolar disorder. While larger controlled studies of vitamin D supplementation are needed, given the high incidence of vitamin D deficiency in youth in the US, testing and treating these deficiencies is important, especially among kids with symptoms of bipolar illness.
Chronic fatigue syndrome, or Systemic Exertion Intolerance Disease (SEID), as it is now known, is characterized by extreme fatigue that cannot be explained by any underlying illness. Doctors have long disagreed over how it should be treated, particularly about whether or not exercise should be encouraged. A new small study of adolescents suggests that anti-viral medications can reduce fatigue.
The 2014 article by Theodore A. Henderson in Advanced Mind Body Medicine reports that among 15 adolescents who reported chronic fatigue symptoms, 1000 mg/day of the antiviral valacyclovir (trade name Valtrex) led to improvement in 86% of the patients by 3 months, and 92% of the patients by 5 months. One patient dropped out due to nausea. Symptoms of fatigue, exertion-induced malaise, excessive sleep, napping, unrefreshing sleep, headaches, cognitive symptoms, and emotional symptoms all improved after treatment with the antiviral. Several previous studies have also shown positive effects of antiviral treatments in patients with chronic fatigue.