Nasal spray delivers new type of depression treatment -- ScienceDaily

Nasal spray delivers new type of depression treatment

Some drug combinations may be more effective than others for schizophrenic patients

  Patients with schizophrenia are often treated with more than one type of psychiatric medication, but a new study suggests that some combinations may be more effective than others.

The findings were published in JAMA Psychiatry.

Antipsychotic drugs are usually the first line of treatment for individuals with schizophrenia. But because these drugs often fail to control symptoms adequately on their own, doctors often prescribe additional psychiatric medications, such as another antipsychotic, an antidepressant, a benzodiazepine, or a mood stabilizer.

"Antipsychotic medications are used to treat psychotic symptoms such as delusions and hallucinations but there is little guidance on what to do for other types of symptoms like depression, anxiety or excitement. Additional medications are often prescribed, but we know little about how different psychiatric drug combinations affect people with schizophrenia," says T. Scott Stroup, MD, MPH, professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons and lead author of the paper. "Until now we have known virtually nothing about how these strategies compare to each other."

To find out, the researchers conducted a comparative effectiveness study using Medicaid records of 81,921 adults with schizophrenia who had been taking only an antipsychotic drug for at least 3 months before starting either an antidepressant, benzodiazepine, mood stabilizer, or another antipsychotic drug.

The researchers found that individuals with schizophrenia who added an antidepressant were less likely to land in the emergency room or hospital for a mental health issue than those who started another antipsychotic or a benzodiazepine. Antidepressants reduced the risk of hospitalization by 16% compared to antipsychotics and by 22% compared to benzodiazepines. For emergency room visits, antidepressants reduced the risk by 8% compared to antipsychotics and by 18% compared to benzodiazepines.

"Our study adds more evidence that benzodiazepine use should be limited and that combining antidepressants with antipsychotic drugs for individuals with schizophrenia may have benefits," says Stroup. "We still need to know more about when to use antidepressants, which may be useful for conditions other than depression."

Combining medications is often referred to as polypharmacy. "The results of our study should promote rational polypharmacy," added Stroup. He thinks that clinicians will find the results believable and hopes that they will lead to practice changes and improved patient outcomes.

The study is titled, "Comparative Effectiveness of Adjunctive Psychotropic Medications in Patients with Schizophrenia."

https://www.cuimc.columbia.edu/

Some drug combinations may be more effective than others for schizophrenic patients

Vraylar (cariprazine) capsules now approved by FDA to treat schizophrenia, bipolar disorder in adults

We know that, Cariprazine (trade name Vraylar, previously known as RGH-188) is an antipsychotic drug developed by Gedeon Richter. It acts as a D2 and D3 receptor partial agonist, with high selectivity towards the D3 receptor.  Positive Phase III study results were published for schizophrenia and mania early 2012, while Phase II studies in bipolar disorder I, and for bipolar depression are in progress.  Action on the dopaminergic systems makes it also potentially useful as an add-on therapy in major depressive disorder  

Rights are currently owned by Gedeon Richter and Actavis. The drug received FDA approval on September 17, 2015.

Now The U.S. Food and Drug Administration today approved Vraylar (cariprazine) capsules to treat schizophrenia and bipolar disorder in adults.

"Schizophrenia and bipolar disorder can be disabling and can greatly interfere with day-to-day activities," said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. "It is important to have a variety of treatment options available to patients with mental illnesses so that treatment plans can be tailored to meet a patient's individual needs."

Schizophrenia is a chronic, severe and disabling brain disorder affecting about one percent of Americans. Typically, symptoms are first seen in adults younger than 30 years of age and include hearing voices or seeing things that are not there, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn.

Bipolar disorder, also known as manic-depressive illness, is another brain disorder that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. The symptoms of bipolar disorder include alternating periods of depression and high, irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior and a decreased need for sleep.

The efficacy of Vraylar in treating schizophrenia was demonstrated in 1,754 participants in three six-week clinical trials. In each of the trials, Vraylar was shown to reduce the symptoms of schizophrenia compared to placebo.

The efficacy of Vraylar in treating bipolar disorder was shown in three three-week clinical trials of 1,037 participants. Vraylar was shown to reduce symptoms of bipolar disorder in each of the trials.

More info video 

Vraylar (cariprazine) capsules now approved by FDA to treat schizophrenia, bipolar disorder in adults

Drugs designed to target nervous system could control inflammation in the gut, study shows

There's a reason it's called a gut feeling. The brain and the gut are connected by intricate neural networks that signal hunger and satiety, love and fear, even safety and danger. These networks employ myriad chemical signals that include dopamine, a powerful neurotransmitter most famous for its role in reward and addiction.

Duke University researchers have shown that manipulating dopamine signaling in the nervous system of the nematode worm C. elegans can control inflammation in the gut.

The study, which appears Aug. 12 in Current Biology, provides a proof of principle that the immune system can be controlled using drugs originally designed to target the nervous system, such as antipsychotics.

"We are talking about an existing set of drugs and drug targets that could open up the spectrum of potential therapeutic applications by targeting pathways that fine-tune the inflammatory response," said Alejandro Aballay, Ph.D., a professor of molecular genetics and microbiology at Duke School of Medicine.

"It is a big leap from worms to humans, but the idea of targeting the nervous system to control the immune system could potentially be used to treat conditions such as rheumatoid arthritis, autoimmune disease, cancer, inflammatory bowel disease, and Crohn's disease," Aballay said.

Recent research suggests that the wiring between the gut and the brain is involved in many other maladies, including autism, anxiety, depression, Alzheimer's disease, and Parkinson's disease.

Aballay believes that C. elegans provides an excellent model for dissecting this complex cross-talk between the nervous system and the immune system. This tiny, transparent worm has a simple nervous system, consisting of only 302 neurons compared to the roughly 100 billion neurons in the human brain. Yet the worm also has a very basic, rudimentary immune system.

Aballay and his team first stumbled upon the gut-brain connection a few years ago when they were studying the immune system of C. elegans. The worms were subjected to a barrage of chemicals in search of immune activators that could protect against bacterial infections. Out of more than a thousand different chemical compounds, they identified 45 that turned on an immune pathway. Curiously, half of those were involved in the nervous system, and a handful blocked the activity of dopamine.

In this study, Aballay decided to examine the effects of dopamine and dopamine signaling pathways on immunity.

Graduate student Xiou Cao blocked dopamine by treating animals with chlorpromazine, a dopamine antagonist drug used to treat schizophrenia and manic depression in humans. He found that these worms were more resistant to infection by the common pathogen Pseudomonas aeruginosa than counterparts that hadn't received the drug.

When Cao then treated the animals with dopamine, it generated the opposite effect, rendering them more susceptible to infection.

The researchers believe their findings indicate that dopamine signaling acts by putting the brakes on the body's inflammatory response so it doesn't go too far.

"Worms have evolved mechanisms to deal with colonizing bacteria," Aballay said. "That is true for us as well. Humans have trillions of microorganisms in our guts, and we have to be careful when activating antimicrobial defenses so that we mainly target potentially harmful microbes, without damaging our good bacteria -- or even our own cells -- in the process."

"The nervous system appears to be the perfect system for integrating all these different physiological cues to keep the amount of damage in check," Aballay said.

Aballay plans continue his studies in C. elegans to identify the different cues involved in fine-tuning the immune response. He also thinks it is worth looking at different analogues or different doses of dopamine antagonists to see if their effects on psychosis can be separated from their effects on immunity.

Drugs designed to target nervous system could control inflammation in the gut, study shows

Add-on lamotrigine enhances bipolar depression treatment

Combining lamotrigine with quetiapine improves the treatment of depressive symptoms in patients with bipolar disorder, with the benefits maintained for at least a year, show findings from the CEQUEL trial.

Scores on the Quick Inventory of Depressive Symptomatology–self report version 16 (QIDS-SR16) at 12 weeks were, on average, 1.73 points lower among 101 moderately depressed bipolar patients randomly assigned to receive lamotrigine (25 mg/day titrated to 200 mg/day) in addition to quetiapine, compared with 101 assigned to receive add-on placebo.

By 52 weeks, the difference was significant at an average of 2.69 points lower for those taking add-on lamotrigine, after taking into account age, bipolar disorder type and dose of quetiapine (< or ≥300 mg/day), the researchers led by John Geddes (University of Oxford, UK) report in The Lancet Psychiatry.

They also found that significantly more patients taking lamotrigine plus quetiapine were in remission at 12 weeks (31 vs 16%) and 52 weeks (36 vs 13%), with relative risks of 2.11 and 3.73, respectively.

Discussing the findings in a related comment, Gin Malhi (University of Sydney, New South Wales, Australia) says: “[T]he investigators skillfully take advantage of the synergy between quetiapine and lamotrigine that arises from their differing, but complementary, mechanisms of action and the separate timescales over which they exert their effects.”

He explains that quetiapine is often given in the short term to ameliorate acute symptoms, whereas lamotrigine is more effective over the longer term. The drug is therefore able to “achieve a therapeutic level and exert its actions under the initial cover of the antipsychotic, which can then be gradually tapered and withdrawn”, he writes.

Add-on lamotrigine enhances bipolar depression treatment

Kratom Seems Safe for Pain, Anxiety, Opioid Withdrawal

We know that, Mitragyna speciosa (commonly known as kratom is a tropical evergreen tree in the coffee family native to Southeast Asia. It is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where it has been used in traditional medicines since at least the nineteenth century. Kratom has opioid properties and some stimulant-like effects.

Kratom is used for symptoms of pain, anxiety, depression, and opioid withdrawal, and serious adverse events are uncommon, according to a the results of a survey published online Feb. 3 in Drug and Alcohol Dependence.

Albert Garcia-Romeu, Ph.D., from the Johns Hopkins University School of Medicine in Baltimore, and colleagues conducted a cross-sectional online survey in 2017 involving 2,798 kratom users.

The researchers found that kratom was mainly taken orally in doses of 1 to 3 g (49 percent) and was most commonly used daily (59 percent). Kratom was used for pain, anxiety, and depression (91, 67, and 65 percent, respectively); effectiveness was highly rated. Overall, 41 percent (1,144 individuals) used kratom to stop or reduce prescription or illicit opioid use, with reports of decreased opioid withdrawal and craving in relation to use; continuous abstinence from opioids for more than one year was attributed to kratom use by 411 individuals. Adverse effects of kratom were reported by about one-third of respondents; these adverse effects were mainly rated as mild in severity and lasted ≤24 hours. Only 0.6 percent of participants sought treatment for adverse events. Two percent of participants met criteria for past-year moderate or severe kratom-related substance use disorder.

"Although our findings show kratom to be relatively safe according to these self-reports, unregulated medicinal supplements raise concerns with respect to contamination or higher doses of the active chemicals, which could increase negative side effects and harmful responses," Garcia-Romeu said in a statement.

Kratom Seems Safe for Pain, Anxiety, Opioid Withdrawal 

https://www.sciencedirect.com/science/article/abs/pii/S0376871620300144

https://en.wikipedia.org/wiki/Mitragyna_speciosa

Omega-3 fatty acids may prevent some forms of depression

Omega-3 fatty acids may prevent some forms of depression 

Serotonin-Specific Reuptake Inhibitor (SSRIs) as antiinflammatory agents?

We know that Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia.  Now researchers from Brighton and Sussex Medical School (BSMS) in the UK, lead by Dr. Sandra Sacre have come up with an interesting findings, i.e., two SSRIs fluoxetine &  citalopram significantly inhibited disease progression of collagen-induced arthritis (CIA) in mice. As per the claim by the researchers both SSRIs exhibited antiinflammatory effects and may provide drug development opportunities for arthritic conditions such as rheumatoid arthritis (RA).

Prior studies (of SSRIs)  have shown that patients with depression,  who respond to treatment with SSRIs display a reduction in cytokine levels (signals that can induce inflammation), suggesting a connection between SSRIs and the immune system. 

In the current study, researchers used a CIA mouse model due to the similarities to human RA, including synovitis, bone erosion and pannus formation. At the onset of arthritis, mice were treated daily for 7 days with a dose of 10 or 25 mg/kg of fluoxetine and 25 mg/kg of citalopram. At the lower dose of fluoxetine the mice showed a small reduction in the clinical score (a combined measure of redness, swelling and joint mobility/deformity) and a slower increase in paw swelling. At a dose of 25 mg/kg, fluoxetine halted disease progression and no further elevation was noted in the clinical score or paw swelling.

Researchers observed reduced inflammation, reduced cartilage and bone erosion, and a preservation of the joint structure in the mice treated with a higher dose of fluoxetine.  Citalopram was not as effective as fluoxetine at inhibiting disease progression in this model. 

They  also observed a decrease in cytokine production from cultures of human RA synovial joint tissues that were treated with SSRIs.  Toll-like receptors (TLRs) are strong activators of immune cells leading to the production of cytokines that can induce inflammation. Fluoxetine was found to inhibit the activation of TLRs more effectively than citalopram. 

Researchers conclude that SSRIs effectively target TLRs contributing to inflammation and could provide therapeutic benefit in RA, they are not ideal candidates to progress into clinical trials (from the data, the  effective inhibition of RA requires levels of the drugs higher than the safe therapeutic dosages.) The authors suggest further study of the role of TLRs in chronic inflammation may uncover drugs that offer an effective treatment of RA in the future..... 

Ref : http://www3.interscience.wiley.com/journal/123235497/abstract

FDA Approves Abilify MyCite (aripiprazole) Pill with Sensor to Digitally Track if Patients Have Ingested Their Medication

In continuation of my update on  aripiprazole 

The U.S. Food and Drug Administration today approved the first drug in the U.S. with a digital ingestion tracking system. Abilify MyCite (aripiprazole tablets with sensor) has an ingestible sensor embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder and for use as an add-on treatment for depression in adults.

The system works by sending a message from the pill’s sensor to a wearable patch. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smart phone. Patients can also permit their caregivers and physician to access the information through a web-based portal.

“Being able to track ingestion of medications prescribed for mental illness may be useful for some patients,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”

It is important to note that Abilify MyCite’s prescribing information (labeling) notes that the ability of the product to improve patient compliance with their treatment regimen has not been shown. Abilify MyCite should not be used to track drug ingestion in “real-time” or during an emergency because detection may be delayed or may not occur.

Schizophrenia is a chronic, severe and disabling brain disorder. About 1 percent of Americans have this illness. Typically, symptoms are first seen in adults younger than 30 years of age. Symptoms of those with schizophrenia include hearing voices, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn. Bipolar disorder, also known as manic-depressive illness, is another brain disorder that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. The symptoms of bipolar disorder include alternating periods of depression and high or irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior and a decreased need for sleep.

Abilify MyCite contains a Boxed Warning alerting health care professionals that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Abilify MyCite is not approved to treat patients with dementia-related psychosis. The Boxed Warning also warns about an increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants. The safety and effectiveness of Abilify MyCite have not been established in pediatric patients. Patients should be monitored for worsening and emergence of suicidal thoughts and behaviors. Abilify MyCite must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

In the clinical trials for Abilify, the most common side effects reported by adults taking Abilify were nausea, vomiting, constipation, headache, dizziness, uncontrollable limb and body movements (akathisia), anxiety, insomnia, and restlessness. Skin irritation at the site of the MyCite patch placement may occur in some patients.

Prior to initial patient use of the product, the patient’s health care professional should facilitate use of the drug, patch and app to ensure the patient is capable and willing to use the system.

Abilify was first approved by the FDA in 2002 to treat schizophrenia. The ingestible sensor used in Abilify MyCite was first permitted for marketing by the FDA in 2012.

FDA Approves Abilify MyCite (aripiprazole) Pill with Sensor to Digitally Track if Patients Have Ingested Their Medication

Top-line results from Vanda's tasimelteon Phase IIb/III study on major depressive disorder

We know that, Tasimelteon (BMS-214,778) is a drug which is under development for the treatment of insomnia and other sleep disorders. It is a selective agonist for the melatonin receptors MT₁ and MT₂ in the suprachiasmatic nucleus of the brain, similar to older drugs such as ramelteon. It has been through Phase III trials successfully and was shown to improve both onset and maintenance of sleep, with few side effects.

A year-long (2011-2012) study at Harvard is testing the use of tasimelteon in blind subjects with non-24-hour sleep-wake disorder.

Now Vanda Pharmaceuticals Inc. (NASDAQ: VNDA),  announced top-line results of the Phase IIb/III clinical study (MAGELLAN) in Major Depressive Disorder (MDD), investigating the efficacy and safety of tasimelteon as a monotherapy in the treatment of patients with MDD.  The clinical study did not meet the primary endpoint of change from baseline in the Hamilton Depression Scale (HAMD-17) after 8 weeks of treatment as compared to placebo.  Both tasimelteon and placebo treated patients had an approximately 40% reduction of their MDD symptoms from baseline.  Tasimelteon was shown to be safe and well-tolerated, consistent with observations in prior studies.  Given these current proof of concept clinical study results, Vanda has decided to discontinue all activities in this indication.

"These results are disappointing, as there is still a significant unmet medical need for patients with Major Depression," said Mihael H. Polymeropoulos , M.D., President and CEO of Vanda.  "Tasimelteon's application in the treatment of blind individuals with Non-24 remains our top priority as we pursue our planned NDA submission this year."     

Vanda has recently reported positive results in two phase III clinical studies of tasimelteon in Non-24-Hour Disorder (Non-24) and plans to submit a New Drug Application to the U.S. Food and Drug Administration in mid-2013......

Top-line results from Vanda's tasimelteon Phase IIb/III study on major depressive disorder

Drug commonly used as antidepressant helps fight cancer in mice

A class of drug called monoamine oxidase inhibitors is commonly prescribed to treat depression; the medications work by boosting levels of serotonin, the brain's "happiness hormone."

A new study by UCLA researchers suggests that those drugs, commonly known as MAOIs, might have another health benefit: helping the immune system attack cancer. Their findings are reported in two papers, which are published in the journals Science Immunology and Nature Communications.

"MAOIs had not been linked to the immune system's response to cancer before," said Lili Yang, senior author of the study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "What's especially exciting is that this is a very well-studied and safe class of drug, so repurposing it for cancer isn't as challenging as developing a completely new drug would be."

Recent advances in understanding how the human immune system naturally seeks out and destroys cancer cells, as well as how tumors try to evade that response, has led to new cancer immunotherapies—drugs that boost the immune system's activity to try to fight cancer.

In an effort to develop new cancer immunotherapies, Yang and her colleagues compared immune cells from melanoma tumors in mice to immune cells from cancer-free animals. Immune cells that had infiltrated tumors had much higher activity of a gene called monoamine oxidase A, or MAOA. MAOA's corresponding protein, called MAO-A, controls levels of serotonin and is targeted by MAOI drugs.

"For a long time, people have theorized about the cross-talk between the nervous system and the immune system and the similarities between the two," said Yang, who is also a UCLA associate professor of microbiology, immunology and molecular genetics and a member of the UCLA Jonsson Comprehensive Cancer Center. "So it was exciting to find that MAOA was so active in these tumor-infiltrating immune cells."

Next, the researchers studied mice that didn't produce MAO-A protein in immune cells. The scientists found that those mice were better at controlling the growth of melanoma and colon tumors. They also found that normal mice became more capable of fighting those cancers when treated with MAOIs.

Digging in to the effects of MAO-A on the immune system, the researchers discovered that T cells—the immune cells that target cancer cells for destruction—produce MAO-A when they recognize tumors, which diminishes their ability to fight cancer.

That discovery places MAO-A among a growing list of molecules known as immune checkpoints, which are molecules produced as part of a normal immune response to prevent T cells from overreacting or attacking healthy tissue in the body. Cancer has been known to exploit the activity of other previously identified immune checkpoints to evade attack by the immune system.

In the Science Immunology paper, the scientists report that MAOIs help block the function of MAO-A, which helps T cells overcome the immune checkpoint and more effectively fight the cancer.

But the drugs also have a second role in the immune system, Yang found. Rogue immune cells known as tumor-associated macrophages often help tumors evade the immune system by preventing anti-tumor cells including T cells from mounting an effective attack. High levels of those immunosuppressive tumor-associated macrophages in a tumor have been associated with poorer prognoses for people with some types of cancer.

But the researchers discovered that MAOIs block immunosuppressive tumor-associated macrophages, effectively breaking down one line of defense that tumors have against the human immune system. That finding is reported in the Nature Communications paper.

"It turns out that MAOIs seem to both directly help T cells do their job, and stop tumor-associated macrophages from putting the brakes on T cells," Yang said.

Combining MAOIs with existing immunotherapies

Yang said she suspects that MAOIs may work well in concert with a type of cancer immunotherapies called immune checkpoint blockade therapies, most of which work by targeting immune checkpoint molecules on the surface of immune cells. That's because MAOIs work on MAO-A proteins, which are inside cells and function differently from other known immune checkpoint molecules.

Studies in mice showed that any of three existing MAOIs—phenelzine, clorgyline or mocolobemide—either on their own or in combination with a form of immune checkpoint blockade therapy known as PD-1 blockers, could stop or slow the growth of colon cancer and melanoma.

Although they haven't tested the drugs in humans, the researchers analyzed clinical data from people with melanoma, colon, lung, cervical and pancreatic cancer; they found that people with higher levels of MAOA gene expression in their tumors had, on average, shorter survival times. That suggests that targeting MAOA with MAOIs could potentially help treat a broad range of cancers.

Yang and her collaborators are already planning additional studies to test the effectiveness of MAOIs in boosting human immune cells' response to various cancers.

Yang said MAOIs could potentially act on both the brain and immune cells in patients with cancer, who are up to four times as likely as the general population to experience depression.

"We suspect that repurposing MAOIs for cancer immunotherapy may provide patients with dual antidepressant and antitumor benefits," she said.

The experimental combination therapy in the study was used in preclinical tests only and has not been studied in humans or approved by the Food and Drug Administration as safe and effective for use in humans. The newly identified therapeutic strategy is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California, with Yang, Xi Wang and Yu-Chen Wang as co-inventors.

Drug commonly used as antidepressant helps fight cancer in mice

Clinical Data completes NDA submission for vilazodone.......

         Vilazodone (structure) is an antidepressant and anxiolytic of  the piperazine chemical class.

Clinical Data, Inc.   recently announced that the Company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for vilazodone for the treatment of major depressive disorder (MDD). Vilazodone is a dual-acting potent and selective serotonin reuptake inhibitor and a 5-HT_1A receptor partial agonist. The Company expects that the NDA submission, if accepted, will be subject to a standard review. 

This is a major milestone in the development of vilazodone and, if approved, its dual mechanism of action and safety profile will offer a new alternative for patients suffering from depression,” said Carol R. Reed, M.D..more...

FDA Approves Juluca, First Two-Drug Regimen for HIV Patients

In continuation of my updates on dolutegravir and rilpivirine,

The FDA has approved the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of the three or more drugs included in standard HIV treatment.

Juluca (dolutegravir/rilpivirine, ViiV Healthcare) is a fixed-dose tablet approved to treat adults with HIV-1 infections whose virus is currently suppressed (HIV-1 RNA less than 50 copies per mL) on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of the new combination. Dolutegravir 50 mg (ViiV Healthcare) is an integrase strand transfer inhibitor, and rilpivirine 25 mg (Janssen Therapeutics) is a non-nucleoside reverse transcriptase inhibitor.

 rilpivirine     Dolutegravir

 “Limiting the number of drugs in any HIV treatment regimen can help reduce toxicity for patients,” said Debra Birnkrant, MD, director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research.

HIV weakens a person’s immune system by destroying important cells that fight disease and infection. According to the Centers for Disease Control and Prevention, an estimated 1.1 million people in the United States are living with HIV, and the disease remains a significant cause of death for certain populations.

This FDA approval is based primarily on data from two pivotal phase 3 clinical trials, SWORD-12 and SWORD-2,2 which showed the two-drug regimen achieved non-inferior viral suppression (HIV-1 RNA less than 50 copies per mL) at 48 weeks compared with patients’ three- or four-drug current antiretroviral regimen (CAR) in both pooled and individual analyses of the SWORD-1 and SWORD-2 studies (dolutegravir/rilpivirine 486/513 [95%], CAR 485/511 [95%]; adjusted difference, –0.2%; 95% confidence interval, –3.0% to  2.5%, pooled analysis). Virological suppression rates were similar between treatment arms. Drug related adverse events and adverse events leading to withdrawal occurred in low frequencies in both arms of the study, but more frequently in the investigational arm.

The most common side effects in patients taking Juluca were diarrhea and headache. Serious side effects include skin rash and allergic reactions, liver problems, and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.

Ref : https://www.viivhealthcare.com/media/press-releases/2017/november/viiv-healthcare-announces-us-fda-approval-for-juluca.aspx

FDA Approves Juluca, First Two-Drug Regimen for HIV Patients

Scientists develop obesity drug without neurological side effects....

We know the side effects of Rimonabant, (see structure) the first selective CB1 receptor blocker to be approved for use anywhere in the world. In Europe, it was indicated for use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m², or patients with a BMI greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia. In the UK, it was available beginning in July 2006. As of 2008, the drug was available in 56 countries. On October 23, 2008, the European Medicines Agency (EMEA) issued a press release stating that its Committee for Medical Products for Human Use (CHMP) had concluded that the benefits of Acomplia no longer outweighed its risks and subsequently recommended that the product be suspended from the UK market. Sanofi-Aventis later released a press statement stating that the drug had been suspended. Approval of the drug was officially withdrawn by the EMEA on January 16, 2009. But never approved for use in the US because of serious neurological side effects including depression and anxiety.

Now researchers from National Institutes of Health, Bethesda, and Alexandros Makriyannis, at Northeastern University, Boston lead by Dr. George Kunos, have developed a drug (see structure AM6545)  that has the same positive effects in mice on levels of glucose and fats in the blood as rimonabant but none of the neurological side effects.

As per researchers claim AM6545 is a non-brain-penetrant neutral CB1R antagonist. First-generationCB1R antagonists, such as rimonabant, are highly lipid soluble and readily penetrate the blood-brain barrier. In order to reduce brain penetrance, we introduced several modifications into the structure of rimonabant. AM6545 is less lipid soluble than rimonabant (estimated partition coefficient [log P], 3.3 vs. 6.4 for rimonabant) but retains high affinity and selectivity for CB1R. In radioligand displacement assays, AM6545 has a KI of 3.3 nM for CB1R, which is similar to that of rimonabant and greater than 100-fold CB1/CB2 selectivity. Unlike rimonabant, AM6545 does not reduce GTPγS binding in mouse brain membranes and is therefore a neutral antagonist.

As per the claim by the researchers, this drug did not cause weight loss or neurological side effects, which rimonabant does, but did have effects on levels of glucose and fats in the blood that should reduce the risk of the serious health consequences of obesity.

The authors therefore hope that this approach of targeting only peripheral CB1R can be translated into the clinic to reduce health risks in obese patients..

Ref : http://www.jci.org/articles/view/42551/pdf

Veggies, Fruits and Grains Keep Your Heart Pumping

  

As if you needed any more proof that fruits, vegetables and whole grains are good for you, a new study finds they may cut your chances of heart As if you needed any more proof that fruits, vegetables and whole grains are good for you, a new study finds they may cut your chances of heart failure by 41%.

Conversely, the so-called Southern diet, which focuses on meats, fried and processed foods and lots of sweet tea, was tied to a 72% increased risk of heart failure.

"Eat more plants, limit red and processed meat," said lead researcher Dr. Kyla Lara, a cardiology fellow at the Mayo Clinic in Rochester, Minn.

Lara cautioned that this study cannot prove different diets cause or prevent heart failure, only that they are linked.

Nearly 6 million American adults suffer from heart failure, and that number is expected to rise with the aging population. The condition occurs when the heart does not pump blood sufficiently to meet the body's needs.

Steps to prevent heart failure include not smoking, keeping blood pressure under control, maintaining a healthy weight and eating healthy foods.

Getting people to eat healthier requires that they be educated about the benefits of plant-based diets and have access to low-cost healthy foods, Lara said.

"Animal meat is not necessary for a nutritious diet, in terms of health promotion and quality of life," she said. "Now is the time to get on board with a plant-based diet -- it's going to be the future of health."

In the study, Lara and her colleagues collected data on more than 16,000 men and women, 45 and older, who took part in a large U.S. stroke study. None of the participants had heart disease at the start of the study. Participants completed a questionnaire that asked them about their diet.

The diets were classified into five types:

Convenience, which was heavy on meats, pasta, Mexican food, pizza and fast food.

Plant-based, which included vegetables, fruits, beans and fish.

Sweets and fats, which was heavy on desserts, bread, sweet breakfast foods, chocolate and other sugars.

Southern, which was heavy on fried foods, processed meats, eggs, added fats, and sugar-sweetened drinks.

Alcohol and salads, which was heavy on wine, liquor, beer, leafy greens and salad dressing.

After nearly nine years of follow-up, 363 participants developed heart failure.

The benefit of the plant-based diet was significant, but after taking into account factors such as weight, waist size, high blood pressure and high cholesterol, the negative effect of the Southern diet was no longer statistically significant, Lara said.

It might be that the increased risk for heart failure in this group was due to obesity and excess belly fat or other factors, she said.

None of the other diets showed a statistically significant association with heart failure, and no association was seen between any diet and the type of heart failure people developed, the researchers noted.

The findings were published April 22 in the Journal of the American College of Cardiology.

"Our lifestyle, such as what we eat, if we are physically active and smoking or vaping, can contribute significantly to a poorly functioning heart, which in turn affects our quality of life and ultimately how soon we die," said Samantha Heller, a senior clinical nutritionist at New York University Medical Center in New York City.

Plant-based diets have been shown to reduce the risk of cardiovascular disease, cognitive [thinking] decline, type 2 diabetes, several cancers, depression and obesity," said Heller, who wasn't involved with the study.

For optimal health, people need to cut back on fried foods, cheese, fast food and junk foods, and processed and red meats, she said.

"It is sad and frustrating when I see patients who could quite literally save their lives by making healthier choices, but instead opt for a burger and fries," Heller said.

A cheeseburger, fries and milkshake meal sounds innocent enough, but it can add up to more than 2,600 calories, 65 grams of saturated fat and 3,400 milligrams of salt, she said.

Heller advises people to include a minimum of one high-fiber food to every meal. "Dietary fiber is only found in plant foods, such as spinach, oranges, quinoa and lentils."

Also try having meatless dinners two or three nights a week, like a grilled vegetable and black bean burrito, pasta primavera or an edamame and fresh vegetable stir fry, she suggested.failure by 41%.

Conversely, the so-called Southern diet, which focuses on meats, fried and processed foods and lots of sweet tea, was tied to a 72% increased risk of heart failure.

"Eat more plants, limit red and processed meat," said lead researcher Dr. Kyla Lara, a cardiology fellow at the Mayo Clinic in Rochester, Minn.

Lara cautioned that this study cannot prove different diets cause or prevent heart failure, only that they are linked.

Nearly 6 million American adults suffer from heart failure, and that number is expected to rise with the aging population. The condition occurs when the heart does not pump blood sufficiently to meet the body's needs.

Steps to prevent heart failure include not smoking, keeping blood pressure under control, maintaining a healthy weight and eating healthy foods.

Getting people to eat healthier requires that they be educated about the benefits of plant-based diets and have access to low-cost healthy foods, Lara said.

"Animal meat is not necessary for a nutritious diet, in terms of health promotion and quality of life," she said. "Now is the time to get on board with a plant-based diet -- it's going to be the future of health."

In the study, Lara and her colleagues collected data on more than 16,000 men and women, 45 and older, who took part in a large U.S. stroke study. None of the participants had heart disease at the start of the study. Participants completed a questionnaire that asked them about their diet.

The diets were classified into five types:

• Convenience, which was heavy on meats, pasta, Mexican food, pizza and fast food.

• Plant-based, which included vegetables, fruits, beans and fish.

• Sweets and fats, which was heavy on desserts, bread, sweet breakfast foods, chocolate and other sugars.

• Southern, which was heavy on fried foods, processed meats, eggs, added fats, and sugar-sweetened drinks.

• Alcohol and salads, which was heavy on wine, liquor, beer, leafy greens and salad dressing.

After nearly nine years of follow-up, 363 participants developed heart failure.

The benefit of the plant-based diet was significant, but after taking into account factors such as weight, waist size, high blood pressure and high cholesterol, the negative effect of the Southern diet was no longer statistically significant, Lara said.

It might be that the increased risk for heart failure in this group was due to obesity and excess belly fat or other factors, she said.

None of the other diets showed a statistically significant association with heart failure, and no association was seen between any diet and the type of heart failure people developed, the researchers noted.

The findings were published April 22 in the Journal of the American College of Cardiology.

"Our lifestyle, such as what we eat, if we are physically active and smoking or vaping, can contribute significantly to a poorly functioning heart, which in turn affects our quality of life and ultimately how soon we die," said Samantha Heller, a senior clinical nutritionist at New York University Medical Center in New York City.

Plant-based diets have been shown to reduce the risk of cardiovascular disease, cognitive [thinking] decline, type 2 diabetes, several cancers, depression and obesity," said Heller, who wasn't involved with the study.

For optimal health, people need to cut back on fried foods, cheese, fast food and junk foods, and processed and red meats, she said.

"It is sad and frustrating when I see patients who could quite literally save their lives by making healthier choices, but instead opt for a burger and fries," Heller said.

A cheeseburger, fries and milkshake meal sounds innocent enough, but it can add up to more than 2,600 calories, 65 grams of saturated fat and 3,400 milligrams of salt, she said.

Heller advises people to include a minimum of one high-fiber food to every meal. "Dietary fiber is only found in plant foods, such as spinach, oranges, quinoa and lentils."

Also try having meatless dinners two or three nights a week, like a grilled vegetable and black bean burrito, pasta primavera or an edamame and fresh vegetable stir fry, she suggested.

Veggies, Fruits and Grains Keep Your Heart Pumping