Prazosin Effective and Well-Tolerated for PTSD in Young People

March 2, 2020 · Posted in Potential Treatments · Comment 

young woman sleeping

In a poster session at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), three posters highlighted the efficacy and tolerability of prazosin, a drug typically used to treat high blood pressure, for the treatment of childhood-onset post-traumatic stress disorder (PTSD).

Researchers Samira Khan and Taniya Pradhan of West Virginia University reviewed cases in which 39 patients aged 8–19 received 1–5 mg of prazosin at bedtime. The mean dose was 1.72 mg. Sleep (including nightmares) improved in 92.3% of the youths, and mood improved in 33.3%. Sleep improved more in patients who received lower doses (1–2 mg) than those who received higher doses. About 70% of the patients whose data were included in the case series were also receiving psychotherapy while being treated with prazosin.

In another poster, researcher Vladimir Ferrafiat and colleagues from University Hospital of Rouen in France reported on a prospective study of 18 participants under age 15 with severe PTSD who were unresponsive to other medications. The participants were given 1 mg of prazosin at bedtime, which was increased to 3 mg in 20% of the participants. The youth were assessed weekly over a one-month period. Improvement was seen in all domains, including sleep, nightmares and daytime intrusive symptoms. Prazosin was well tolerated, with only one patient experiencing low blood pressure, which did not necessitate withdrawal from the study.

In the final poster, researcher Fatima Motiwala and colleagues reviewed the literature on the treatment of PTSD in children. Motiwala indicated that among the options, prazosin was widely used in her hospital, at doses starting at 1 mg given at bedtime and increasing to a mean of 4 mg at bedtime with excellent results and tolerability.

Editor’s Note: Although these were not double-blind controlled studies, the findings are noteworthy in that they provide consistent data on the effectiveness and tolerability of prazosin in low doses in children with PTSD, essentially mirroring controlled data in adults, where higher doses are typically required.

Lurasidone Highly Effective in Open Continuation in Youth with Schizophrenia

February 27, 2020 · Posted in Potential Treatments · Comment 

teen girlResearcher Michael Tocco and colleagues reported at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) that in adolescents between the ages of 13 and 17 with schizophrenia, taking lurasidone for two years following a double-blind, placebo-controlled study led to steady improvement. There was a remarkably high 91% response rate and a 66% remission rate. Out of all the participants, 51.3% were rated as recovered.

Improvement in Bipolar Depression on Open-Label Lurasidone

February 10, 2020 · Posted in Potential Treatments · Comment 

healthy teen

Researcher Katherine Burdick and colleagues of Brigham and Women’s Faulkner Hospital and Harvard University reported in a poster at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) that youth between the ages of 10 and 17 with bipolar depression who continued taking lurasidone on a non-blind basis following a double-blind placebo-controlled six-week trial of the drug, or those who began taking lurasidone (for those who had been in the placebo group during the trial) saw improvement over a period of one to two years. All of the patients began the extension portion of the study at a dose of 20 mg/day.

Lurasidone appeared to be effective and well-tolerated. In addition, Burdick and colleagues reported a lack of cognitive difficulties in the youth taking lurasidone. Interestingly, a measure of visual learning substantially and progressively improved over the course of the study.

Infliximab Helps the Subgroup of Bipolar Depressed Patients Who Faced Adversity in Childhood

October 11, 2019 · Posted in Potential Treatments · Comment 

child with bruised face

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Mike Cosgrove and colleagues described a study of the immune-suppressing drug infliximab in adults with bipolar disorder. The researchers found persistent significant improvements on infliximab only in those with bipolar disorder who also had a history of childhood adversity. Childhood adversity is consistently associated with elevated levels of inflammatory cytokines, and baseline inflammation may be a prerequisite for a positive effect from infliximab, which works by blocking the inflammatory cytokine TNF alpha.

Links Between Mixed Depression, Insulin Resistance, Inflammation, and Cognitive Deficits

August 1, 2019 · Posted in Potential Treatments · Comment 

depressed man with woman

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Roger McIntyre discussed links between obesity, diabetes, and cardiovascular problems; increased inflammation; and decreased functioning of the neural networks involved in cognition. 

He and his colleagues analyzed 121 studies that included empirical research and meta-analyses. McIntyre and colleagues found that patients with higher levels of inflammatory markers have more insulin resistance and cognitive dysfunction. A meta-analysis revealed that the inflammatory markers IL-6, TNF alpha, and CRP were significantly elevated in people with bipolar disorder compared to normal controls, while IL-1B was not.

People with depression who had a few manic traits (mixed depression) were particularly likely to have insulin resistance and elevated levels of pro-inflammatory markers.

People with mixed depression have increases in inflammation and increased incidence of cardiovascular disorder. People experiencing a first episode of mixed depression who are overweight show increased signs of brain aging.

In studies McIntyre and colleagues analyzed, diabetes or pre-diabetes occurred in 50% of depressed patients, and these patients had the greatest amount of cognitive dysfunction.

Treatment

McIntyre noted that taking the antipsychotic drug lurasidone for bipolar depression worked best in both adults and children who had elevated levels of CRP at baseline. The fast-acting antidepressant ketamine also works well in those who show baseline inflammation .

The anti-diabetes drug liraglutide (Victoza, Saxenda) improves mixed depression symptoms and cognition in obesity, diabetes, and mixed depression. Liraglutide belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists or incretin mimetics. They work by increasing insulin release from the pancreas and decreasing excessive glucagon release.

McIntyre now routinely uses liraglutide for cognitive deficits in patients with obesity or diabetes, including patients with mixed depression. It is injected under the skin at 0.6 mg daily, then the dosage is increased to 1.2 mg and then 1.8 mg. Victoza reduces major cardiovascular events in those with type 2 diabetes. The higher-dose Saxenda (3mg) can be used for weight control.

Another anti-diabetes drug, pioglitazine, has also been reported to be helpful in bipolar depression.

McIntyre found that the antibody infliximab, which can be used as an intravenous treatment for chronic inflammation and works by blocking the effects of TNF-alpha, did not improve depression, but did improve cognition.

McIntyre also supports the use of acetyl-L-carnitine, a potential adjunctive treatment that can reverse the insulin resistance that often occurs with obesity and thus could theoretically improve cognition.

McIntyre described preliminary literature suggesting the effectiveness of drugs such as statins, calcium channel blockers, and biguanides such as the diabetes treatment metformin in reducing inflammation.

Bariatric surgery to reduce the size of the stomach was another option discussed by McIntyre. He said the intervention is safe for patients with bipolar disorder and can help them recover cognitive function.

McIntyre noted that offspring of a mother with obesity have decreased response to sensory cues, reward preference, cognitive control, and motor control. Obesity and the inflammation that goes along with it apparently affect offspring via epigenetic mechanisms, meaning obesity may change the structure of inherited DNA (without changing its sequence).

Treating Bipolar Depression in an Adolescent

July 9, 2019 · Posted in Potential Treatments · Comment 

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Ben Goldstein discussed a case of a 15-year-old with bipolar depression and his recommended treatments for the adolescent. Goldstein endorsed the use of an atypical antipsychotic such as lurasidone, and perhaps also quetiapine. Goldstein noted 2015 findings from researcher Robert Findling that lamotrigine was significantly more effective than placebo in adolescents 13–18 years old, but was not effective in those aged 10–12.

(In adults, researcher John Geddes and colleagues found that in patients with an inadequate antidepressant response to quetiapine, the addition of lamotrigine was more effective than adding a placebo, both acutely and in long-term follow-up. The only caveat was that lamotrigine was less effective in those who were also being treated with folate.)

Editor’s Note: Some other treatments could augment the effects of the regimen proposed by Goldstein, including lithium and the antioxidant N-acetylcysteine, which, it should be noted, takes more than eight weeks to become effective. Vitamin D3 could also be considered, as it is often low in children with psychiatric disorders. One treatment that went unmentioned at the meeting was repeated transcranial magnetic stimulation, or rTMS, which is effective and well-tolerated in adolescents with depression.

For patients with more rapidly cycling bipolar disorder and only partial response to medications, the combination of the ‘three Ls’ (lurasidone, lamotrigine, and lithium) could have considerable appeal, given that each drug is from a different class of medications, has a different mechanism of action, targets a different mood phase, and is relatively well-tolerated both alone and in combination with other drugs.

Newly Identified Effects of N-Acetylcysteine

July 5, 2019 · Posted in Potential Treatments · Comment 

NACIn a talk at the 2019 meeting of the International Society for Bipolar Disorders, researcher Michael Berk, who was responsible for some of the initial findings on the effects of the antioxidant N-acetylcysteine (NAC), summarized some of the newer findings about the treatment.

NAC has been found to be effective in bipolar depression and in the treatment of both positive and negative symptoms of schizophrenia. It also helps in the avoidance of cocaine, alcohol, tobacco, and marijuana. It can reduce habitual behaviors such as gambling, obsessive compulsive disorder (OCD), and trichotillomania (compulsive hair-pulling) and irritability and motor stereotypy (repeated movements) in autism.

A 2016 study by researcher Sudie E. Back and colleagues in the Journal of Clinical Psychiatry found that NAC improved symptoms of post-traumatic stress disorder (PTSD) in veterans who also had depression and substance use disorders at a dosage of 2.4 grams/day.

According to Berk, NAC also reduces the incidence of lithium-related renal failure and reduces mitochrondrial toxicity. One study reported that it improved working memory in patients with schizophrenia.

In his talk, Berk also noted that statins offer an interesting new avenue for treatment. Several studies have suggested statins can improve mood or reduce the likelihood of a depressive recurrence. Angiotension-active drugs (inhibitors) have also been reported to decrease the incidence of depression and to improve cognition.

Study in Mice Suggests that Compound in Turmeric May Reduce Anxiety and Promote Resilience to Stress

June 12, 2019 · Posted in Potential Treatments · Comment 

turmericChronic stress is a risk factor for the development of mood and anxiety disorders. Researchers have begun to focus on how to promote resilience to stress. Curcumin is a micronutrient found in turmeric that has anti-inflammatory and antidepressant effects and may promote such resilience.

Researchers studying human depression often design studies to see how mice with chronic social defeat stress respond to various interventions. Mice who are repeatedly menaced by a larger mouse begin to show symptoms that resemble human depression, such as social avoidance, lack of interest in saccharin compared to plain water (a stand-in for loss of enjoyment or anhedonia in humans), and anxiety.

In a 2018 article in the journal Neuropsychopharmacology, researcher Antonio V. Aubry and colleagues described the effects of curcumin on mice undergoing chronic social defeat stress. Mice who were given a diet that consisted of 1.5% curcumin showed a 4.5-fold increase in resilience to social defeat stress, measured by their performance during a test of social interaction. Among the 129 mice in the study, 64% showed the increase in resilience, the remaining 36% did not respond to the curcumin diet and had the normal ‘depressed’ response. The mice who responded well to curcumin released less of the stress hormone corticosterone, and they also had lower levels of the inflammatory marker IL-6.

All of the mice on the curcumin diet showed reduced anxiety during tests that forced them to travel through open spaces (when they prefer to stay in more enclosed spaces or move along the edges of an enclosure).

Vitamin Methyl B12 Improved Autism Symptoms in Randomized, Placebo-Controlled Study

May 23, 2019 · Posted in Potential Treatments · Comment 

group of kids

In a 2016 article in the Journal of the American Academy of Child and Adolescent Psychiatry, Robert L. Hendren and colleagues described an 8-week study in which the vitamin methyl B12 improved symptoms of autism spectrum disorders in children.

Fifty-seven children were randomized to receive either 75??g/kg of methyl B12 injected under the skin every three days or saline injections as a placebo instead. Methyl B12 improved the children’s autism symptoms compared to placebo. The improvements correlated with increases in levels of the amino acid methionine in the blood and improvements in cellular methylation capacity. Children with autism spectrum disorders have reduced ability to methylate (i.e. add methyl groups to) DNA. The methylation process helps convert the toxic amino acid homocysteine into beneficial methionine. The children who received methyl B12 showed a reduction in homocysteine and a better ratio of methionine to homocysteine.

Homocysteine is bad for the heart, for cognition, and for fetal development, while methionine can help improve depression and is important to many cellular reactions. Converting homocysteine to methionine requires vitamin B12 and folate, another B vitamin found in foods such as green vegetables and beans.

Taking folate supplements can help make antidepressants more effective by aiding the methylation process. However, some people have a common variation in the MTHFR gene that makes it difficult for the body to make use of folate. These people would need to take the nutritional supplement L-methylfolate instead of regular folate to help in the conversion of homocysteine to s-adenosylmethionine (SAMe, which acts as an antidepressant).

Vitamin D Has More Benefits Than Previously Thought

May 17, 2019 · Posted in Potential Treatments · Comment 

supplementsVitamin D has long been known as an important vitamin for bone health, preventing conditions such as osteoporosis and rickets. More recently, research suggests that vitamin D may also protect against conditions such as cancer, heart failure, diabetes, respiratory tract infections, and autoimmune disease.

Many Americans have low vitamin D or a vitamin D deficiency. The human body produces vitamin D in large amounts when the skin is exposed to ultraviolet B rays in sunlight. Vitamin D can also be absorbed from vitamin D–fortified foods such as dairy products, some orange juice, and cereals. Some foods such as fatty fish, beef liver, and egg yolks naturally contain some vitamin D, but it is difficult to get enough vitamin D just from consuming these foods.

Low mood or seasonal affective disorder (SAD), in which people feel depressed during winter periods of limited exposure to sunshine, have been linked to low vitamin D.

Other symptoms of low vitamin D vary but can include pain in the joints, bones, or muscles; fatigue; and breathing problems.

Editor’s Note: A few small studies have suggested that 1,500 IU per day of vitamin D supplements can help depressed mood, even in those with normal vitamin D levels. Several studies have indicated that children or adolescents with psychiatric disorders are especially likely to be vitamin D–deficient. Another study found that higher amounts of vitamin D (4,000 IU) could improve cognition in healthy volunteers more than lower doses could. Vitamin D also improved cognition in people with multiple sclerosis and in those with the autoimmune disease Hashimoto’s thyroiditis.

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