Hope in Treatment-Refractory Depression

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Editor’s Note: Severe, treatment-refractory depression is one of the most challenging conditions facing psychiatrists. And, unfortunately, it’s very common. Now, an old drug — ketamine — is having a renaissance in psychiatry and is offering hope to patients unresponsive to standard antidepressant therapies. Medscape recently spoke with David Feifel, MD, PhD, Professor in the Department of Psychiatry at the University of California, San Diego, about his experience with using ketamine in the treatment of depression.

Medscape: We’ve been hearing a lot about ketamine’s potential as a psychiatric medication lately. Can you give us some background on the medical and cultural history of the drug?

Dr. Feifel: Ketaminehasbeen approved for veterinary and human use as an anesthetic agent for decades. It produces a type of anesthesia called a “dissociative anesthesia,” meaning that it tends to dissociate or cut off the physical sensation of the body from the mind. Ketamine is used every day in medical centers around the world, including my institution, UCSD Medical Center, as an anesthetic and as an analgesic for intractable pain. However, the latter use is somewhat controversial, in terms of the potential long-term benefits. Ketamine is also used illicitly for recreational purposes, typically as part of the club scene, and in this capacity it goes by various names, such as “Special K.” Pharmacologically, ketamine is related to other known street drugs such as phencyclidine (PCP), also known as “angel dust.”

Medscape: How is ketamine being used in psychiatry? And is this a relatively recent approach?

Dr. Feifel: Psychiatric use of ketamine is very recent and stems from research findings in patients with treatment resistant depression. In such patients, infusional ketamine at a dose that is significantly lower than the anesthetic dose can produce a strong antidepressant response. Not only do these challenging depressed patients respond, but the response is very rapid. Ketamine differs from anything we have with which to treat depression. The efficacy rate is higher than traditional antidepressant medications, and the onset of the antidepressant effect is almost immediate compared with conventional antidepressants, which have a latent efficacy that can take several weeks to fully manifest. This novel therapeutic profile is what has garnered so much attention for ketamine.

by Bret Stetka, MD, David Feifel, MD, PhD

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Strong Dose-Dependent Effect With Meth and Psychosis

The risk of developing psychotic symptoms increases during periods of methamphetamine use among long-term users, new research suggests.

Investigators from Australian National University in Canberra found that among long-term users, there was a 5-fold increased likelihood of psychotic symptoms during periods of meth use vs periods of abstinence. Such symptoms included suspiciousness (71%), delusions or unusual thought content (35%), and hallucinations (51%).

This risk was strongly related with how often they used the drug, with the odds increasing from 4.0 (95% confidence interval [CI], 2.5 – 6.5) with 1 to 15 days’ use in the past month to 11.2 (95% CI, 5.9 – 21.1) when people were using for 16 or more days in the past month.

“This translated into an increase of around 10% having psychotic symptoms in the past month when they were not using methamphetamine up to 48% when they were using it heavily, that is, for more than 16 days,” lead author Rebecca McKetin, PhD, from Australian National University, told Medscape Medical News.

The risk was compounded by heavy cannabis and alcohol use, which increased the risk for psychotic symptoms up to 69%.

by Fran Lowry, Medscape

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Dietary Supplement Offers Hope for Schizophrenia Prevention

Perinatal supplementation of the essential nutrient choline may lead to a lower risk of children developing schizophrenia, new research suggests.

The randomized controlled trial included 93 healthy pregnant women, half of whom received choline supplementation during their last 2 trimesters of pregnancy. Their newborns also received choline soon after delivery. Results showed that the offspring who received choline perinatally had a significantly lower rate of a physiologic risk factor for schizophrenia at the age of 33 days compared with their counterparts who had received matching placebo.

In addition, the supplements were found to be safely tolerated by all mothers and infants.

“We thought that if we could get a good intervention prenatally or early postnatally, we could decrease risk for the disorder,” lead author Randy Ross, MD, professor of psychiatry at the University of Colorado Denver School of Medicine, told Medscape Medical News. “This is really a first step towards trying to develop a prevention strategy,” explained Dr. Ross. He added that his takeaway message from the study is that finding ways to prevent a disease “may be much more effective than treating it after it comes on.”

by Deborah Brauser, Medscape

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Cognitive Decline in Youth May Predict Adult Psychosis

A relative decline in cognitive performance in adolescence and young adulthood, particularly in verbal ability, may be an independent predictor of psychosis in adulthood, new research shows.

Further, the longitudinal cohort study also reveals that a relative decline in verbal ability between the ages 13 and 18 years is a stronger predictor of psychosis than verbal ability at age 18 alone.

“We found a relative decline in verbal ability between ages 13 and 18 years that predicts later psychosis more strongly than the absolute score at age 18 years and that this decline is associated independently with the development of schizophrenia and other nonaffective and affective psychoses,” the authors, led by James H. MacCabe, MRCPsych, PhD, from the Institute of Psychiatry, King’s College London in the United Kingdom, write. The study was published online January 16, 2013, in JAMA Psychiatry.

According to investigators, there is clear evidence from a large number of prospective, population-based studies that individuals who develop psychosis in adulthood experience cognitive deficits during childhood and adolescence. However, they note, it is not clear whether these deficits become more severe during adolescence. They also point out that, to date, no prospective studies have measured changes in cognitive functioning during adolescence and early adulthood.

by Caroline Cassels, Medscape

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More Evidence Brain’s Emotion Circuitry Disrupted in Bipolar Disorder

New research provides more evidence that the brain’s emotion circuitry is dysregulated in individuals with bipolar disorder and that this may result in impairment of patients’ ability to control emotion, leading to mood swings. Specifically, the study suggests that distinct circuit dysfunctions may contribute to different features of emotion dysregulation in bipolar disorder.

“This study provides important information regarding brain areas that may be important in controlling response to emotional material and the functional abnormalities in these areas in mood disorders,” senior author Amit Anand, MD, Indiana University School of Medicine in Indianapolis, said in a statement. The investigators say that it will be important to replicate these findings because, to their knowledge, no prior reports have implicated these prefrontal cortical regions as trait-related neural markers of emotional inhibition in bipolar disorder.

“These findings may have implications for the refinement of circuit-based treatments for bipolar disorder, including neurostimulation and psychotherapy,” John Krystal, MD, editor of Biological Psychiatry, who was not involved in the study, commented in a statement. “It is interesting that subtly different circuits distinguish symptomatic and nonsymptomatic patients with bipolar disorder when they are suppressing their happy and sad reactions,” Dr. Krystal added. Commenting on the study for Medscape Medical News, Stephen M. Strakowski, MD, professor and chairman, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine in Ohio, noted, “There have been relatively few studies comparing individuals with bipolar disorder across mood states, so this manuscript does improve the existing literature in that regard.”

by Megan Brooks, Medscape

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Lance’s Story Continues…

February 2, 2013

One day I went away for a long time and I thought there was no turning back. I left my family, my friends my job, my support. I moved my business all the way to rehab. It was like an angel was calling me but didn’t leave a message. So I walked, talked, ate, and just kept going on with my own business. Whatever the business was caused me to become delirious. After causing me to become delirious I found my way in the brinks of hospitals, institutions, jails and death in the midst of my journey. I was broke and I lost all my self-respect. I lost it somewhere between Florida and Pittsburgh. With nothing left, all I really had was my broken soul.  I had people who liked me but I couldn’t be their friend. I swore to myself that one day I would get back to those people – so many different people, so many walks of life, attitudes, friends, so-called friends and interesting people.  Everywhere I go I manage to find a way to be all right. I swore to myself there would never be a day when I couldn’t spend 10 dollars. When that day came and I was about to check myself into the hospital – there was my friend waiting for me with a bag of bud and some pills. I chose the hospital over my friend. Shortly before, this friend went through a terrible tragedy. He lost someone he loved to drugs. When the death came I found myself on my last drug run. Death after death, I finally moved on and only the strong survive. When they put their guns down, I cried. That’s when I found myself bowing to evil spirits. I didn’t want to leave but somebody came and let me out of the dark hell I was in. Instead of that last bag of crack, I had lunch. I made a lot of new connections but they were dark and devious. Just before I left the angel sent me a message. He said: “Get out of here and don’t ever come back”. My family culture, which was once ruined, came back to life and helped me out of the grips of my hell. I found myself again walking in the street alone but this time I had ten bucks. I saved it for a pack of cigarettes.  I walked and walked and walked and one day I just cried.  My broken soul began to heal.

Asenapine in Bipolar I Disorder

Asenapine is a new second-generation antipsychotic approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder.

It demonstrated significant efficacy compared with placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was noted at day 2 and was strongly associated with response and remission at week 3. Asenapine also appeared effective in treating acute mania in older patients with bipolar disorder. Posthoc analyses of asenapine showed efficacy in treating depressive symptoms during manic or mixed episodes compared with placebo. The efficacy of asenapine in patients with acute mania appeared to remain constant during maintenance treatment.

Asenapine was reasonably well tolerated, especially with regard to metabolic effects. There were minimal signs of glucose elevation or lipid changes and the risk of weight gain appeared limited. The prolactin elevation was smaller than other antipsychotic comparators. Only oral hypoesthesia occurred as a new adverse event compared with other second-generation antipsychotics. Asenapine presents several advantages over other second-generation antipsychotics, such as sublingual formulation, early efficacy and good metabolic tolerability. This tolerability profile confirms the heterogeneity of the second-generation antipsychotic class and supports the view of some authors for the need to re-evaluate the boundaries of this group.

by Ludovic Samalin, MD, Thomas Charpeaud, MD, Pierre-Michel Llorca, MD, PhD

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Some Kids ‘Age Out’ of Autism

Some children with an accurate diagnosis of an autism spectrum disorder (ASD) may eventually “outgrow” the diagnosis and have normal levels of overall functioning that are within normal testing limits, new research suggests.
The study compared 34 school-age children and young adults with a prior diagnosis of ASD who had achieved “optimal outcome” (no current symptoms of the disorder) with 44 matched individuals with high-functioning autism (HFA) and 34 typically developing peers.
Results showed that the first and third groups did not differ significantly on mean test scores of communication, social interaction, face recognition, and most language subscales. Although the optimal outcome group had milder symptoms of social dysfunction than the HFA group during their early developmental years, difficulties with communication and repetitive behaviors were equally severe.
“I wasn’t too surprised by the overall findings, but it was surprising just how indistinguishable from typically developing most of these kids were on virtually every measure,” lead author Deborah Fein, PhD, professor in the Department of Psychology and the Department of Pediatrics at the University of Connecticut in Storrs, told Medscape Medical News.

by Deborah Brauser, Medscape News

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