Creatine Supplements May Speed Up Response to Escitalopram, Improve Brain Connectivity
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.
Cool Head May Help Insomnia
Illustration from Nofzinger’s patent application
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.
In Small Study, High Intensity Light Therapy Boosts Libido in Men
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.
Psilocybin May Improve Treatment-Resistant Depression
Psilocybin mushrooms
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.
Mindfulness-Based Cognitive Therapy May Improve Depression More Than Fitness Intervention
In a study by researcher Stuart Eisendrath and colleagues, people with treatment-resistant unipolar depression responded better to an intervention that combined mindfulness training with cognitive therapy than to one that included exercise, nutrition counseling, and music therapy.
The 173 participants had failed to respond to at least two different antidepressant medications. During the study period, all participants were taking an antidepressant, but none were receiving other types of therapy.
After eight weeks, the mindfulness-based cognitive therapy (MBCT) group showed greater improvement in their depression symptoms than the exercise and nutrition group. Of the MBCT group, 29.58% had a large reduction in symptoms, while 17.19% of the comparison group showed a similarly large reduction in symptoms.
A subgroup of the participants also received functional magnetic resonance imaging (fMRI) as part of the study. While completing a task related to emotional working memory, the MBCT group showed enhanced activation of the dorsal lateral prefrontal cortex (to levels seen in non-depressed people). This area is related to executive control of depression and memory functions. The MBCT group also showed reduced activation of the ventral lateral prefrontal cortex compared to the comparison group. Members of the MBCT whose depression symptoms had improved also showed better regulation of the amygdala during the task compared to the exercise and nutrition group.
The research was presented at the 2016 meeting of the American Psychiatric Association.
Combination of SSRIs and Statins Better than SSRIs Alone
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.
SSRI Use During Pregnancy Linked to Adolescent Depression in Offspring
A 2016 article by Heli Malm and colleagues in the Journal of the American Academy of Child and Adolescent Psychiatry suggests that in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may increase the risk of depression in adolescence. However, the study included potentially confounding factors. It is possible that women who took SSRIs during pregnancy had more severe depression than those who went unmedicated during pregnancy. The mothers in the study who took SSRIs also had more comorbid conditions such as substance abuse.
Editor’s Note: Women should balance the risks and benefits of antidepressant use during pregnancy, since depression itself can have adverse effects on both mother and fetus. It has recently been established that SSRI use during pregnancy does not cause birth defects, so women with depression that has not responded to non-pharmaceutical interventions such as psychotherapy, omega-3 fatty acid supplementation, exercise, mindfulness, and repeated transcranial magnetic stimulation (rTMS) may still want to consider SSRIs.
Antipsychotic Use During Pregnancy Most Likely Safe
A new study suggests that women can continue using antipsychotic medications during the first trimester of pregnancy without meaningfully increasing the risk of birth defects in their offspring.
The study, by Krista F. Huybrechts and colleagues in the journal JAMA Psychiatry, looked at Medicaid users who filled at least one prescription for an antipsychotic medication during their first trimester of pregnancy, when an embryo’s vital organs are formed, and went on to have a live birth. Birth defects, including cardiac malformations, in these children were identified in the first 90 days after delivery and compared to the number of such abnormalities in the children of women on Medicaid who did not receive a prescription for an antipsychotic drug during the first trimester of pregnancy. The number of abnormalities was slightly higher in the children of women who had received atypical antipsychotics than in those who had not, and slightly lower in the children of women who had received a typical antipsychotic than in those who had not.
Huybrechts and colleagues concluded that taking an antipsychotic medication during the first trimester of pregnancy does not meaningfully increase the risk of birth defects in the offspring.
The children of women who took the antipsychotic risperidone did have a small increased risk of birth defects, including cardiac malformations. The researchers called for additional study of risperidone use during pregnancy.
Study Shows FDA Drug Safety Warning on Citalopram Backfired
In August 2011, the US Food and Drug Administration issued a warning that doses of the selective serotonin reuptake inhibitor (SSRI) antidepressant citalopram (Celexa) that exceeded 40mg/day could prolong the QT interval, a measure of heart rate used to diagnose abnormal heart rhythms. A study of records from the Veterans Health Administration showed that 35,848 veterans whose dose of citalopram was reduced from an average of 64mg/day to under 40mg/day faced increased deaths, hospitalizations for any cause, and hospitalizations for depression specifically after the reductions.
The FDA warning meant to prevent heart problems had the unintended consequence of increasing hospitalizations and deaths among the veterans affected. These findings by Thomas S. Rector and colleagues were published in the American Journal of Psychiatry in 2016.
Editor’s Note: There are some similarities between this case and findings by researchers Andrew Nierenberg and Andrew Stoll, who noticed that patients taking 40mg/day of fluoxetine (Prozac) had better long-term outcomes than those taking 20mg/day, even though those taking 40mg were more ill and more likely to relapse at the start of the study.
Researchers Ellen Frank and David Kupfer found that 90% of unipolar depressed patients relapsed when their antidepressant doses were halved, even though they had been stable for 5 years before the change.
These and the findings from Rector and colleagues lead this editor to believe that reducing the dosage of effective treatments should not be done without reason—that is, in the absence of side effects, or simply to achieve the minimal effective dose. Dose reductions without cause not only may increase the risk of relapse, but may also put the patient at increased risk of developing tolerance to the medication, for example hastening the onset of ‘Prozac poop-out.’
When long-term maintenance drug therapy is going well, it may be best to be conservative and stay the course. Conversely, in the absence of a good long-term response, be as active and creative as possible to achieve mood stabilization.
Oral Ketamine Relieves Depression in Patients with Chronic Pain
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.
