FDA Approves New Higher Dose of Valbenazine for Tardive Dyskinesia

December 15, 2017 · Posted in Current Treatments · Comment 

tardive dyskinesia

The US Food and Drug Administration has approved an 80 mg capsule dose of valbenazine (Ingrezza) for tardive dyskinesia (jerky, involuntary movements of the face, especially the mouth and tongue, fingers and body that can be a side effect of antipsychotic medication). Valbenazine, a selective vesicular monoamine transporter 2 inhibitor, was the first drug FDA-approved for tardive dyskinesia. The FDA initially approved a dosage of 40 mg/day in April 2017. The 80 mg/day dose was approved in October 2017.

The new approval was based on a 6-week clinical trial in which 80 mg of valbenazine improved tardive dyskinesia significantly compared to placebo. Improvement continued over 48 weeks of treatment.

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

Safety of Atypical Antipsychotics in Pregnancy

August 31, 2017 · Posted in Current Treatments · Comment 

pregnant woman

A 2017 article in the Journal of Clinical Psychiatry systematically reviewed data on the risks related to schizophrenia, bipolar disorder, and treatment with atypical antipsychotic medication during pregnancy. The article by researcher Sarah Tosato and colleagues suggests that a mother’s illness may be more harmful to a fetus than treatment for that illness is.

The review analyzed 49 articles about illness-related and atypical antipsychotic–related risks in bipolar disorder and schizophrenia. Tosato and colleagues found that abrupt discontinuation of treatment led to a high risk of relapse in pregnant women with bipolar disorder or schizophrenia.

Schizophrenia was linked to a slight increase in obstetric complications for mothers, while both bipolar disorder and schizophrenia were linked to a slight increase in complications for newborns. Mothers ill with schizophrenia had the highest risk for serious complications, including stillbirth, neonatal or infant death, and intellectual disability in the child.

The researchers reported that untreated bipolar disorder and schizophrenia are risk factors for birth defects, but use of atypical antipsychotics is not. Children’s neurodevelopment also does not seem to be affected by mothers’ use of atypical antipsychotics during pregnancy.

The authors suggest that, given parents agree and understand any risks involved, the least harmful choice of action is to maintain treatment of women with bipolar disorder and schizophrenia during pregnancy at the safest minimum dosage to keep their illness at bay.

Dutch Study Links Low Vitamin D to Bipolar Disorder

August 15, 2017 · Posted in Risk Factors · Comment 

Vitamin D sources

A 2016 study in the Netherlands found that people with bipolar disorder are more likely to have vitamin D deficiency than the general population. Vitamin D deficiency has been linked to other psychiatric disorders including schizophrenia and unipolar depression. Poor diet and lack of exposure to sunlight can put someone at risk for vitamin D deficiency.

The study, led by Remco Boerman and published in the Journal of Clinical Psychopharmacology, included 118 adults with bipolar disorder, 149 with schizophrenia, and 53 with schizoaffective disorder. More than 30% of these participants had deficient levels of vitamin D. Only 15% had optimum levels of the vitamin. More than 22% of the participants with bipolar disorder were deficient in vitamin D, while close to 35% of those with schizophrenia and schizoaffective disorder were deficient.

Study participants had vitamin D levels that were 25% lower than those of the white Dutch population, and vitamin D deficiency was 4.7 times more common in those with psychiatric disorders than the general Dutch population.

The authors suggested screening people with bipolar disorder, schizophrenia, and schizoaffective disorder for low levels of vitamin D.

FDA Approves Treatment for Tardive Dyskinesia

May 26, 2017 · Posted in Current Treatments · Comment 

facesA new drug valbenazine (trade name Ingrezza) has been approved by the US Food and Drug Administration for the treatment of tardive dyskinesia. Tardive dyskinesia, a side effect of long-term use of antipsychotic medication, consists of involuntary movements of the tongue, face, torso, arms, and legs. It can interfere with walking, talking, and breathing.

The approval followed 20 clinical trials of valbenazine that included a total of more than 1000 participants who had symptoms of tardive dyskinesia in addition to schizophrenia, schizoaffective disorder, or bipolar disorder.

In a 2017 article in the American Journal of Psychiatry, researcher Robert A. Hauser and colleagues reported that patients who received 80 mg/day of valbenazine had a significant reduction in tardive dyskinesia symptoms after six weeks compared to those who received placebo. Participants who received 40 mg/day of valbenazine also had reductions in symptoms, although not as dramatic as with the higher dose.

Serious side effects of valbenazine include sleepiness and lengthening of the QT interval, which can increase heart arrhythmias. The FDA notes that people who already have abnormal heartbeats due to a long QT interval should not take valbenazine. In addition, people taking the drug should avoid driving or operating heavy machinery until they know how valbenazine affects them.

Levels of Amino Acid Proline Interact with COMT Genotype to Affect Negative Symptoms

May 24, 2017 · Posted in Course of Illness, Genetics, Neurobiology · Comment 

DNAIn a 2016 article, researcher Catherine L. Clelland and colleagues reported that a patient’s levels of the amino acid proline interact with their genetic profile to influence the seriousness of their negative symptoms. Negative symptoms of schizophrenia and bipolar disorder include flat affect and lack of volition and can be some of the hardest symptoms to treat.

High levels of proline in the central nervous system have been linked to schizophrenia. Proline is a precursor to the neurotransmitter glutamate, and high proline levels have been found to alter glutamate and dopamine signaling in mice. This is one of the factors affecting negative symptoms.

The other factor affecting negative symptoms is the COMT gene. The enzyme catechol-o-methlyl transferase (COMT) metabolizes dopamine in the prefrontal cortex. There are several common versions of the gene for COMT. The most efficient is known as val-158-val, identifying that the gene has two valine amino acids at position 158. People with high proline levels and the val-158-val version of the COMT gene had fewer negative symptoms than people with high proline levels and another version of the gene, val-158-met (indicating one valine and one methionine amino acid at position 158).

Clelland and colleagues hypothesized that high proline levels may actually counteract the dopamine shortages common in the prefrontal cortex in people with the val-158-val genotype of COMT, which is more efficient at breaking down dopamine in this region.

The mood stabilizer valproate increases proline levels. In the study, which was published in Translational Psychiatry, people with schizophrenia and the val-val genotype had fewer negative symptoms when treated with valproate than those with the val-met genotype who received the same treatment.

Continuing Marijuana Use After a First Episode of Psychosis Increases Risk of Relapse

May 5, 2017 · Posted in Risk Factors · Comment 

marijuanaA 2016 article in the journal JAMA Psychiatry reports that continuing to use cannabis after a first episode of psychosis increases risk of relapse. The study by Sagnik Bhattacharyya and colleagues employed longitudinal modeling to determine the role of cannabis use in psychotic relapse. The researchers followed 90 women and 130 men for two years after a first episode of psychosis, and found that the more marijuana they used, the more likely they were to have a relapse of psychosis.

Relapse rates were highest (59.1%) for participants who used pot continuously following their first episode of psychosis. Relapse rates were lower (36.0%) for those who used cannabis intermittently thereafter, and lowest (28.5%) among those who discontinued cannabis use after their first episode of psychosis.

A statistical test known as a cross-lagged analysis was used to establish that cannabis use affected later relapse, rather than relapse of psychosis leading to further cannabis use.

Another statistical strategy using fixed-effect models revealed that risk of psychotic relapse was 13% higher during times of cannabis use than during periods of no cannabis use.

These findings offer some hope that the likelihood of psychosis relapse can be reduced, since ongoing cannabis use is a risk factor that can be modified, unlike family history or genetics. Bhattacharyya and colleagues called for research into interventions that can help discourage cannabis use in people who have had a first episode of psychosis.

Editor’s Note: N-acetylcysteine, a nutritional supplement sold in health food stores, can reduce cannabis use compared to placebo in teen users.

Cannabis Use May Cause Schizophrenia

May 1, 2017 · Posted in Risk Factors · Comment 

marijuanaCannabis use has been linked to schizophrenia risk, and new genetic research suggests a causal relationship between the two. In a 2017 article in the journal Molecular Psychiatry, researcher Julian Vaucher and colleagues reported that lifetime cannabis use was linked to schizophrenia even when the researchers controlled for 10 genotypes weakly associated with lifetime cannabis use. This makes it unlikely that the schizophrenia caused the cannabis use, suggesting instead that it is the cannabis use that leads to a schizophrenia diagnosis.

Vaucher and colleageus also controlled for genetic associations between cigarette smoking and cannabis use to eliminate cigarette use as a third variable causing the association between cannabis and schizophrenia.

The study by Vaucher and colleagues included 34,241 people with schizophrenia and 45,604 healthy controls.

Omega-3 Fatty Acids May Be Helpful Early in Schizophrenia, But Not Later

January 24, 2017 · Posted in Potential Treatments · Comment 

sources of omega-3 fatty acidsSome studies have suggested that omega-3 fatty acids may be helpful in the treatment of schizophrenia, but data to support this idea have been inconsistent. A recent meta-analysis of research on omega-3s and schizophrenia suggests that this nutritional supplement might be more useful in early-stage schizophrenia than in later illness.

At the 2016 meeting of the Society of Biological Psychiatry, researchers led by Alexander T. Chen presented the findings of their meta-analysis. First they analyzed six studies that shared a common scale for measuring schizophrenia symptoms. In these studies, omega-3 fatty acids did not outperform placebo when used as an add-on treatment to antipsychotics for people with schizophrenia.

In four remaining studies of omega-3 fatty acids and schizophrenia, the omega-3s were associated with improvement only in patients in the early stages of schizophrenia. Compared to placebo, the supplements decreased non-psychotic symptoms, decreased the dosage of antipsychotic medication patients required, and improved early treatment response (but not late treatment response) in patients in their first episode of schizophrenia.

In the same study, omega-3 fatty acids also reduced conversion to full-blown schizophrenia and psychotic symptom severity in patients at high risk for schizophrenia who were having preliminary symptoms of the illness.

Editor’s Note: Researcher Paul E. Keck has also found that omega-3 fatty acids may be more effective early in bipolar disorder rather than later. He reported that younger patients with bipolar depression and rapid cycling showed more improvement when taking the omega-3 fatty acid EPA than when taking placebo. In contrast, patients with bipolar depression who were over the age of 45 did worse on EPA than on placebo.

Part of the ambiguity about whether omega-3 fatty acids can help treat or prevent mental illness may be explained by the supplements working better in younger people or earlier in the course of an illness.

Kynurenine Pathway Suggests How Inflammation is Linked to Schizophrenia

December 20, 2016 · Posted in Neurochemistry · Comment 

schizophrenia

The kynurenine pathway describes the steps that turn the amino acid tryptophan (the ingredient in turkey that might make you sleepy) into nicotinamide adenine dinucleotide. This pathway might be a connection between the immune system and neurotransmitters involved in schizophrenia.

A recent autopsy study by researcher Thomas Weickert and colleagues explored this link by determining that in the brains of people with schizophrenia and high levels of inflammation, messenger RNA for Kynurenine Aminotransferase II (KATII, a step on the kynurenine pathway) was elevated in the dorsolateral prefrontal cortex compared to the brains of people who died healthy and those with schizophrenia but low levels of inflammation.

The KATII mRNA levels also correlated with mRNA levels of inflammatory markers such as glial fibrillary acidic protein and interleukin-6.

Blood measures related to the kynurenine pathway also differentiated people with schizophrenia from healthy controls. People with schizophrenia had lower levels of tryptophan, kynurenine, and kynurenic acid in their blood. The low levels of kynurenic acid in the blood were correlated with deficits in working memory and smaller volume of the dorsolateral prefrontal cortex.

Weickert and colleagues suggest that blood levels of kynurenic acid might provide a measurable indicator of the degree to which people with schizophrenia are experiencing problems with executive functioning (planning and decision-making) and loss of brain volume.

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