Augmentation Strategies for Negative Symptoms of Schizophrenia

December 13, 2017 · Posted in Potential Treatments · Comment 

 teen

In a 2017 article in the journal JAMA Psychiatry, Christoph U. Correll and colleagues reviewed 42 secondary strategies to treat schizophrenia when the primary antipsychotic treatment has an incomplete effect. Many people with schizophrenia show only a limited response to antipsychotic drugs, so additional treatments are often necessary, but currently there are no US Food and Drug Administration guidelines for combination treatment.

Correll and colleagues compiled data from 29 meta-analyses covering 381 individual trials. They found that while the meta-analyses were well done, the quality of the data in the original studies was lacking.

Focusing on Negative Symptoms

However, since the negative symptoms of the illness such as apathy, withdrawal, and blunted emotional response are the hardest to treat, any amount of improvement in this area could be particularly helpful. Read more

Probiotics May Improve Depression As Well As IBS

December 11, 2017 · Posted in Potential Treatments · Comment 

vitamin DA pilot study of people with irritable bowel syndrome (IBS) suggests that taking a probiotic nutritional supplement can improve depression as well as gastrointestinal upset.
In the 2017 study published in the journal Gastroenterology, researcher Maria Pinto Sanchez and colleagues at the Farncombe Family Digestive Health Research Institute found that when those with IBS took a probiotic, their co-occurring depression improved more than it did in people with IBS who took a placebo.

Senior author Premysl Bercik suggested the study confirms that the microbiota environment in the gut affects what goes on in the brain, opening new avenues for the treatment of psychiatric diseases.

The study included 44 adults with IBS who also had mild to moderate anxiety and depression. For 10 weeks, half received a daily dose of the probiotic Bifidobacterium longum NCC3001, while the others received placebo.

After 6 weeks, 64% of the probiotic group saw improvement in their depression, compared to 32% of the placebo group. Functional magnetic resonance imaging (fMRI) showed brain changes associated with the improvement in mood.

The researchers are planning larger trials of probiotics.

TDCS Better Than Placebo But Not as Good as Escitalopram at Improving Unipolar Depression

December 8, 2017 · Posted in Potential Treatments · Comment 

An article by André R. Brunoni and colleagues in the New England Journal of Medicine reports that transcranial direct current stimulation (tDCS) can treat unipolar depression more effectively than placebo, but not quite as effectively as the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram. TDCS consists of a constant, low direct current applied to the scalp via electrodes.

The study included 245 patients with moderate to severe depressive symptoms, many of whom also had anxiety disorders. To minimize the placebo effect, patients all participated in sessions wearing tDCS gear and received a daily pill. However, one group received real tDCS treatment but placebo pills, a second group received sham tDCS but real escitalopram pills, and the third group received both sham tDCS and placebo pills.

The real tDCS treatment consisted of 30-minute sessions of tDCS every day for 15 consecutive weekdays, then seven once-a-week treatments. The escitalopram dosage was 10 mg/day for three weeks, then 20 mg daily.

Ten weeks into treatment, those who received escitalopram showed the greatest improvement in depression. Those who received tDCS showed slightly less improvement, but still significantly more than those who received neither treatment. Cognitive performance either improved or stayed the same in all the groups.

In terms of side effects, those who received escitalopram were more likely to report sleepiness or severe constipation. Those who received tDCS reported more skin redness/tingling, itching, tinnitus, and nervousness. Two patients in the tDCS group had new-onset mania during treatment. There were no suicides, hospitalizations, or other serious side effects.

Botox for Depression

December 1, 2017 · Posted in Potential Treatments · Comment 

botox injectionSeveral recent clinical trials have suggested that Botox injections between the eyebrows may improve depression. The theory is that decreasing muscle tension could reduce feelings of depression, instead of depression causing muscle tension. In a phase 2 double blind multicenter trial of 258 women with depression, participants were randomized to receive 30 units of Botox, 50 units of Botox, or placebo. Those who received the 30-unit injections showed significantly greater improvement in depression at three weeks and nine weeks compared to those who received placebo. However, it was not superior to placebo at the primary endpoint of the study, six weeks, and the 50-unit dosage was not superior to placebo. Both doses were well tolerated.

Botox is derived from botulinum toxin, which can relax tense muscles. It is also being explored as a treatment for migraine headaches. The manufacturer, Allergan, expects to move forward with phase 3 trials of Botox for depression.

Intranasal Ketamine for Bipolar Disorder

November 29, 2017 · Posted in Potential Treatments · Comment 

nasal sprayAn in-press article due out in January 2018 by Demitri F. Papolos and colleagues in the Journal of Affective Disorders reports that intranasal ketamine delivered every three to four days reduced symptoms of bipolar disorder in 45 teens (aged 16 years on average). The teens treated in one private practice had the ‘fear-of-harm’ subtype, which in addition to bipolar symptoms is characterized by treatment resistance, separation anxiety, aggressive obsessions, disordered sleep, and poor temperature regulation.

The repeated administration of ketamine produced long-lasting positive results, improving bipolar symptoms as well as social function and academic performance. Many participants reported via survey that they were much or very much improved after being treated for durations ranging from 3 months to 6.5 years. Side effects were minimal and included sensory problems, urination problems, torso acne, dizziness, and wobbly gait.

The ketamine was delivered to alternating nostrils via 0.1 ml sprays that included 50–200 mg/ml of ketamine in 0.01% benzalkonium chloride. Patients were instructed to increase the dosage just up until it became intolerable and then repeat the last tolerable dose every three to four days. Final doses ranged from 20–360 mg. The mean dose was 165 mg (plus or minus 75 mg) delivered every 3 days.

Papolos and colleagues called for placebo-controlled clinical trials based on the positive results from this open study.

An Overview of Ketamine for Treatment-Resistant Depression

November 27, 2017 · Posted in Potential Treatments · Comment 

ketamineA 2017 series of articles by researcher Chittaranjan Andrade in the Journal of Clinical Psychiatry reviews the last 10 years of research on ketamine, the anesthetic drug that in smaller doses (0.5 mg/kg of body weight) can bring about rapid antidepressant effects. Ketamine is typically delivered intravenously (though it can also be delivered via inhaler, injected under the skin or into muscles, and least effectively by mouth). Ketamine can improve depression in less than an hour, but its effects usually fade within 3 to 5 days. Repeating infusions every few days can extend ketamine’s efficacy for weeks or months.

Andrade cited a 2016 meta-analysis of nine ketamine studies by T. Kishimoto and colleagues in the journal Psychological Research. The meta-analysis found that compared to placebo, ketamine improved depression beginning 40 minutes after IV administration. Its effects peaked at day 1 and were gone 10–12 days later. Remission rates were better than placebo starting after 80 minutes and lasting 3–5 days.

Several studies have found that ketamine also reduces suicidality.

Andrade reported that both effectiveness and side effects seem to be dose-dependent within a range from 0.1 mg/kg to 0.75 mg/kg.

Side effects of ketamine are typically mild and transient. A 2015 study by Le-Ben Wan and colleagues (also in the Journal of Clinical Psychiatry) that Andrade cited reported that in 205 sessions of ketamine administration, the most common side effects were drowsiness, dizziness, poor coordination, blurred vision, and feelings of strangeness or unreality. The feelings of unreality (dissociative effects) diminish with repeated infusions. Heart and blood pressure may also temporarily increase as a result of ketamine administration.

One study found that ketamine could speed up and add to the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram (Lexapro). A meta-analysis of 10 randomized controlled trials found that ketamine did not improve the effects of electroconvulsive therapy.

Ketamine has some history as a recreational club drug (sometimes known as ‘K’ or ‘special K’), and can be misused or abused.

While there have been many studies of ketamine’s antidepressant effects, Andrade concludes that none is of a standard to justify US Food and Drug Administration approval for the drug. It is hoped that larger, more rigorous trials will be completed in the next few years. However, ketamine is already being used widely to treat treatment-resistant unipolar and bipolar depression.

Study Suggests Magnesium Could Improve Mild to Moderate Depression as Much as SSRIs

November 13, 2017 · Posted in Potential Treatments · Comment 

foods with magnesium

Researcher Emily Tarleton and colleagues report in a 2017 article in the journal PLoS One that over-the-counter magnesium may improve mild to moderate unipolar depression with efficacy similar to that of selective serotonin reuptake inhibitor (SSRI) antidepressants. Magnesium is a mineral that can fight inflammation.

The 126 participants in the open study had an average age of 52. Compared to not taking magnesium, taking 248 mg/day of magnesium produced statistically significant improvement in depression and anxiety symptoms after only two weeks.

The magnesium was well-tolerated by participants. Tarleton and colleagues hope to replicate their findings with a larger and more diverse population.

IVIG Produces Long-Term Results in PANDAS

November 3, 2017 · Posted in Potential Treatments · Comment 

PANDAS diagnosis

PANDAS, or pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection, is an autoimmune condition that produces psychiatric symptoms that appear suddenly following a case of strep throat in children. These symptoms can include obsessive-compulsive symptoms, tics, and behavioral dyscontrol and regression. Treatments are still experimental, but those that target the immune system are expected to be most successful at improving PANDAS.

In 2015, Miro Kovacevic and colleagues published a case series describing the use of intravenous immunoglobulin treatment (IVIG) in twelve children with PANDAS in the Journal of Child and Adolescent Psychopharmacology. One or in some cases two injections of IVIG brought about long-term remission in the children with PANDAS.

IVIG consists of a wide range of antibodies from multiple individuals delivered via injection. This increase in the quality or quantity of antibodies in the recipient is thought to suppress the production of antibodies that attack brain cells, causing PANDAS. The case series was based on patients at a large clinical practice that specializes in the treatment of PANDAS. The practice used a dosage of 1.5g/kg divided into two daily doses of 750 mg/kg, meant to match twice the volume of the patients’ own immunoglobulin G.

IVIG and other anti-inflammatory approaches are also effective in PANS, a more general variation on PANDAS in which psychiatric symptoms occur following an infection other than strep.

Diuretic Looks Promising for Autism

October 27, 2017 · Posted in Potential Treatments · Comment 

bumetanidePhase 2 clinical trials showed that the diuretic bumetanide can reduce the severity of autism spectrum disorders in children aged 3 to 11. A 2017 phase 2B trial assessed side effects and determined the dosage that maximizes benefits and minimizes side effects. Bumetanide will now move on to year-long phase 3 trials in five European countries and may be on the market by late 2021. Bumetanide is an unusually potent ‘loop diuretic’ (a diuretic that works at the loop of Henle in the kidney). In preliminary studies, it has also been used to prevent seizures in newborns.

The phase 2B study included 88 mostly male participants with autism spectrum disorder between the ages of 2 and 18. The participants were randomly assigned to receive 0.5 mg, 1.0 mg, or 2.0 mg twice daily of bumetanide or a placebo for three months.

Bumetanide improved core symptoms of autism such as social communication and restricted interest across all ages. Side effects were worse at higher doses, and included hypokalemia (low potassium), increased urine production, loss of appetite, dehydration, and weakness or lack of energy.

Researchers led by Eric Lemonnier determined that doses of 1.0 mg twice/day produces the most benefits while controlling side effects.

Dietary Supplements for Autism: Up-to-Date Research

October 20, 2017 · Posted in Potential Treatments · Comment 

supplements

A 2017 review article by Yong-Jiang Li and colleagues in the journal Frontiers in Psychiatry describes the current research on dietary supplements that may help improve symptoms of autism spectrum disorder.

Some of the most promising research was on vitamin D, folinic acid, and sulforaphane. Methyl B12 and digestive enzyme therapy had some positive effects, while gluten- and casein-free diets and omega-3 fatty acids did not seem to help improve autism symptoms.

Vitamin D

Li and colleagues described a randomized, controlled trial of vitamin D in 109 children with autism aged 3 to 10 years. The experimental group received doses of 300 IU/kg of body weight/day, not exceeding 5000 IU/day. By the end of the four-month study, vitamin D levels had significantly increased in the experimental group compared to the control group. Those who received vitamin D also showed significant improvement on all ratings of autism symptoms, which included general scales of autism symptoms and more specialized checklists that capture aberrant behavior and social responsiveness.

Folinic Acid

The review article also described a randomized double-blind placebo-controlled trial of folinic acid in 48 children with autism spectrum disorder and language impairment. Participants received high-dose folinic acid (2 mg/kg/day) or placebo for 12 weeks. Those who received folinic acid, a form of folic acid that can readily be used by the body, showed significant improvements in verbal communication and core autism symptoms compared to those who received placebo. Participants who tested positive for folate receptor alpha autoantibodies (FRAA), which disrupt the transportation of folate across the blood-brain barrier and are common in autism, showed greater improvements from taking folinic acid than those without this abnormality.

Sulforaphane

Sulforaphane is a phytochemical derived from cruciferous vegetables. It can create metabolic effects that resemble those of a fever, which can improve behavioral symptoms of autism. Sulforaphane also fights oxidative stress, inflammation, and DNA damage, which may play roles in autism. Li and colleagues described the first double-blind, placebo-controlled trial of sulforaphane treatment in 29 boys aged 13 to 17 years. The boys who received sulforaphane showed significant improvement in autism-related behavior, especially social interaction and communication, after 18 weeks compared to those who received placebo. Sulforaphane has low toxicity and is well tolerated. Read more

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