Curcumin Improves Memory and Depression

October 2, 2018 · Posted in Potential Treatments · Comment 

curcumin

Recent studies suggest that curcumin, the micronutrient in turmeric that gives Indian curry its bright color, may reduce depression and improve memory.

A 2018 study published in the American Journal of Geriatric Psychiatry by Gary Small, director of geriatric psychiatry at UCLA’s Longevity Center, and colleagues found that a curcumin supplement improved mild, age-related memory loss in people without dementia.

Forty adults between the ages of 50 and 90 received either placebo or 90 mg of Theracumin, a bioavailable form of curcumin, twice daily for 18 months. The participants took cognitive tests at the beginning of the study and every 6 months during the study. Thirty of the participants also received positron emission tomography (PET) scans upon beginning and ending the study to evaluate the appearance of plaques and tangles in their brains.

Participants who received curcumin saw improvements in verbal and visual memory and attention over the course of the study compared to those who received placebo. The curcumin participants also saw mild improvements in mood, and less accumulation of amyloid plaques and tau tangles in the amygdala and hypothalamus, brain areas that play a role in memory and emotion. A few participants had mild gastrointestinal effects after taking Theracumin.

In India, where diets are high in curcumin, there is a lower incidence of Alzheimer’s than in the west, and older people also have better cognitive performance than in the west.

Curcumin has anti-inflammatory, antioxidant, and neuroprotective properties. Researchers speculate that curcumin may reduce brain inflammation, which has been implicated in both depression and Alzheimer’s disease.

A 2017 meta-analysis by Qin Xiang Ng and colleagues of 6 studies of curcumin including a total of 377 patients found that the substance has significant antidepressant effects compared to placebo. Half of the studies also reported improvements in anxiety. No adverse events were reported. Ng’s meta-analysis was published in the Journal of the American Medical Directors Association.

Mixed Findings for Intranasal Ketamine

September 13, 2018 · Posted in Potential Treatments · Comment 

intranasal ketamine

The drug ketamine can rapidly and temporarily improve depression when delivered intravenously. Researchers have been working on extending ketamine’s effects and finding easier ways of delivering the medication. One new delivery method under investigation is nasal spray, which could be used repeatedly to extend ketamine’s effects.

Unfortunately, researcher Colleen Loo reported in the Journal of Psychopharmacology in 2018 that a pilot study of self-administered intranasal ketamine for severe depression was suspended when 5 of the 10 participants had side effects that included high blood pressure, psychotic symptoms, and motor incoordination that made them unable to keep using the spray. Early in the four-week study, dosage was adjusted to leave more time between sprays, but this was not enough to prevent the problems with side effects.

Loo said that the nasal spray version of ketamine has complications including variations in absorption among different people and on different days, depending on factors like mucus in the nose and exact application techniques. Its rapid absorption into the bloodstream could lead to high peak levels in certain people.

Loo and colleagues had previously found that elderly patients receiving injections of ketamine under the skin required highly individualized dosing to avoid side effects. This may also be the case with nasal spray.

While Loo’s study found intranasal ketamine infeasible for the moment, Janssen Research and Development, a pharmaceutical company owned by Johnson & Johnson, reported positive results in phase 3 clinical trials of intranasal esketamine (a component of ketamine) at the annual meeting of the American Psychiatric Association in May. Researchers for Janssen reported that intranasal esketamine was highly effective for depression and well-tolerated both in acute treatment and over a year-long period. Janssen is now pursing approval for the drug from the US Food and Drug Administration.

 

Repeated Ketamine Reduces PTSD and Depression in the Short Term

September 11, 2018 · Posted in Comorbidities, Potential Treatments · Comment 

iv ketamine

In a 2018 open study by C. Sophia Albott and colleagues in the Journal of Clinical Psychiatry, veterans with post-traumatic stress disorder (PTSD) and a simultaneous diagnosis of major depression were treated with six infusions of intravenous ketamine over a 12-day period (Mondays, Wednesdays, and Fridays for two weeks).

Ketamine produced large improvements in both conditions. The remission rate was 80.0% for PTSD and 93.3% for depression. The median time to first relapse after the treatment was 41 days for PTSD and 20 days for depression.

One side effect of ketamine was that dissociative symptoms increased temporarily with repeated infusions. PTSD symptoms did not worsen among those participants taking ketamine.

The study was intended to evaluate the efficacy, safety, and durability of repeated ketamine infusions. Ketamine has been used in emergency rooms to rapidly treat depression and suicidality, but the effects of a single infusion fade within days.  Albott and colleagues reported that this treatment scenario with multiple ketamine infusions produced rapid results that lasted longer than single ketamine infusions.

Editor’s Note: While this study found that repeated ketamine infusions were safe, it is possible that long-term use may lead to addiction. Researcher Nolan R. Williams and colleagues reported in a 2018 article in the American Journal of Psychiatry that ketamine works via activation of the opiate receptor.  The drug naloxone, which rapidly reverses opiate overdose, completely blocked ketamine’s antidepressant effects.

 

Nutritional Supplement ALC Improves Depression

March 26, 2018 · Posted in Potential Treatments · Comment 

vitamin

A meta-analysis of 12 studies suggests that the nutrient acetyl-l-carnitine (ALC), when taken as a nutritional supplement, has antidepressant effects. The meta-analysis by researcher Nicola Veronese and colleagues appeared in the journal Psychosomatic Medicine in 2017. Veronese and colleagues found that in nine randomized controlled trials, ALC reduced depressive symptoms significantly compared to placebo. In three randomized controlled trials that compared ALC with established antidepressants, ALC showed similar effectiveness at reducing depressive symptoms while producing 79% fewer side effects. Doses of ALC ranged from 1 to 4 grams per day, and higher doses led to greater improvement.

In the comparisons with antidepressants, the other treatments included fluoxetine (Prozac), duloxetine (Cymbalta), and amisulpride (which is not approved by the US Food and Drug Administration).

Low ALC has been linked to depression. According to Veronese and colleagues, ALC deficiency can dysregulate the transport of fatty acids across the inner membrane of mitochondria. The researchers suggest several ways that ALC might contribute to an improvement in depression. One is that is seems to promote neuroplasticity in cerebral regions implicated in depression, such as the hippocampus. It could also work by increasing brain-derived neurotrophic factor (BDNF), which protects neurons and is important for learning and memory. ALC decreases release of the neurotransmitter glutamate by increasing the production of the inhibitory metabotrophic glutamate receptor (mGluR-2) on presynaptic glutamate neurons . Another way ALC might work is by normalizing lipid metabolism. Or it could modulate neurotransmitters, increasing serotonin and dopamine and protecting against stress.

In the meta-analysis, ALC produced more improvement in older patients than in younger ones. The researchers stressed the need for better treatments for older people, which may experience falls, cardiovascular disease, or increased mortality from antidepressants.

ALC also seems to improve pain syndromes, making it a good option for patients with both depression and pain symptoms.

Veronese and colleagues cited another meta-analysis that found that taking ALC in addition to an antidepressant led to lower rates of adverse events than the antidepressants alone, which helped patients adhere to their drug regimen.

Taking SSRI Antidepressants May Increase Stroke Risk

December 6, 2017 · Posted in Current Treatments · Comment 

pill bottleA Taiwanese study published in the Journal of Clinical Psychiatry in 2017 finds that taking selective serotonin reuptake inhibitor (SSRI) antidepressants can increase risk of stroke. The study by Chin-Hong Chan and colleagues analyzed eight years of data from Taiwan’s National Health Insurance Research Database, comparing people who had taken SSRIs for at least two consecutive months to those who had not. First onset strokes were more common among people who had taken SSRIs, and the higher stroke rates in this group persisted for three years after exposure.

Ischemic strokes (which occur when a blood vessel carrying blood to the brain is obstructed) were more common than hemorrhagic strokes (which occur when a weak blood vessel ruptures). Younger adult participants exposed to SSRIs were more likely to have strokes, while people older than 65 saw only a slight increase in stroke risk from taking SSRIs. More strokes occurred during the first three years of SSRI treatment than later in treatment.

Chan and colleagues suggest that these strokes are caused by cerebral microbleeding or by overcorrection of hemostasis, the process by which the body slows or stops bleeding by constricting blood vessels and coagulating blood.

Best Antidepressants for Post-Stroke Depression

December 4, 2017 · Posted in Current Treatments · Comment 

strokeA recent meta-analysis in the journal BMJ Open analyzes the efficacy and tolerability of 10 different antidepressants given to treat depression following a stroke. The meta-analysis incorporated data from 12 trials and a total of 707 participants. Reboxetine was the most effective antidepressant, followed by paroxetine, doxepin, and duloxetine. Sertraline, fluoxetine, and nefiracetam failed to outperform placebo in the treatment of post-stroke depression.

In terms of tolerability, paroxetine had the least side effects and led to significantly fewer discontinuations than doxepin, citalopram, and fluoxetine. After paroxetine, the most tolerable drugs were sertraline and nortriptyline. The least tolerable drug was citalopram.
Researchers led by Yefei Sun suggested that paroxetine might be the best antidepressant to prescribe after a stroke due to its efficacy and good tolerability. Fluoxetine might be the worst due to its poor efficacy and poor side effects profile.

Editor’s Note: Multiple randomized controlled trials suggest that antidepressants can be helpful for anyone who has a stroke, both to decrease depression and to improve neurological and functional outcomes.  

One Night of Sleep Deprivation Can Rapidly Improve Depression

November 22, 2017 · Posted in Current Treatments · Comment 

sleepy womanOne night of sleep deprivation can bring about rapid improvement in depression symptoms the following day. A 2017 meta-analysis by Elaine M. Boland and colleagues in the Journal of Clinical Psychiatry summarizes the findings from 66 studies of sleep deprivation for unipolar and bipolar depression and finds that the technique produced a response rate of 45% in randomized controlled studies.

It did not seem to matter whether patients experienced full or partial sleep deprivation, whether they had unipolar or bipolar depression, or whether or not they were taking medication at the time. Age and gender also did not affect the results of the sleep deprivation.

Extending the Effects

While sleep deprivation can rapidly improve depression, the patient often relapses after the next full night of sleep. There are a few things that can prevent relapse or extend the efficacy of the sleep deprivation. The first is lithium, which has extended the antidepressant effects of sleep deprivation in people with bipolar disorder.

The second strategy to prevent relapse is a phase change. This means going to sleep early in the evening the day after sleep deprivation and gradually shifting the sleep schedule back to normal. For example, after an effective night of sleep deprivation, one might go to sleep at 6pm and set their alarm for 2am. Then the next night, they would aim to sleep from 7pm to 3am, the following night 8pm to 4am, etc. until the sleep wake cycle returns to a normal schedule.

A 2002 article by P. Eichhammer and colleagues in the journal Life Sciences suggested that repetitive transcranial magnetic stimulation (rTMS), electromagnetic stimulation of the scalp over the prefrontal cortex, could help maintain improvement in depression following a night of partial sleep deprivation for up to four days.

Bright light therapy may also help. Read more

Inflammation Linked to Non-Response to Antidepressants

November 17, 2016 · Posted in Current Treatments · Comment 

antidepressant non-response and inflammation

In a symposium on inflammation’s role in psychiatric disorders at the 2016 meeting of the Society of Biological Psychiatry, researcher Carmine Pariante reviewed the considerable literature indicating that major depression is often associated with measures of inflammation. Depression has been linked to elevated blood levels of the inflammatory proteins interleukin-1, interleukin-6, TNF alpha, and c-reactive protein, with about one-third of depressed patients having an elevated level of at least one of these proteins. People with elevated inflammatory markers are also less likely to respond to traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs).

Pariante reported that in depressed people, interleukin-6 is also elevated in cerebrospinal fluid in addition to blood, suggesting that inflammation in depression extends to the central nervous system. Increased secretion of interleukin-6 has been linked to depressive behaviors in mice exposed to stress.

There is some hope that anti-inflammatory treatments can help patients who do not respond to traditional antidepressant treatment. Some anti-inflammatory medications that may eventually be used to treat depression with inflammation include the COX-1 inhibitor aspirin, the COX-2 inhibitor celecoxib (Celebrex), or the antibiotic minocycline. Each of these approaches gained some support in preliminary clinical trials, but it has not yet been established that these anti-inflammatory treatments produce a better response in people with elevated inflammatory markers.

Methylene Blue May Help Bipolar Depression

November 16, 2016 · Posted in Potential Treatments · Comment 

methylene blueWe 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.

IV Ketamine 2 or 3 Times Per Week Improves Depression

October 12, 2016 · Posted in Potential Treatments · Comment 

intravenous ketamine for 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.

Next Page »