Posts tagged treatment

The vast majority of people with addiction have suffered significant previous trauma, and many people who struggle with addiction suffer from post-traumatic stress disorder (PTSD) simultaneously. But the treatment of these patients has posed a conundrum: experts have believed that PTSD treatment should not begin until the addicted person achieves lasting abstinence, because of the risk that PTSD treatment may trigger relapse, yet addicted people with untreated PTSD are rarely able to abstain for long.

Now, a new study suggests that there may be no need to wait. Researchers found that using exposure therapy — the gold-standard treatment for PTSD, which involves exposure to memories and reminders of patients’ past trauma — can successfully reduce symptoms of PTSD, even when people with addiction continue to use drugs. And, although exposure therapy requires patients to face some of their worst fears, it does not increase their drug use or prompt them to drop out of treatment more than ordinary addiction therapy, the study found.

“The exciting thing in my view is that [the study] supports people with drug and alcohol problems having access to other forms of psychological interventions, rather than being fobbed off and told to sort out their alcohol or drug problem first,” says Michael Farrell, director of the National Drug and Alcohol Research Center at the University of New South Wales in Sydney, Australia, where the research was conducted.

The finding could potentially help the majority of those who suffer from addiction or PTSD: one-half to two-thirds of people with addictions suffer from PTSD concurrently, or have in the past, and about the same proportion of people with PTSD also have substance use disorders.

The new study involved 103 people with both conditions. Most were addicted to multiple drugs, primarily heroin, marijuana and alcohol. More than two-thirds of the participants had been traumatized during childhood, with almost half reporting a history of sexual abuse.

Researchers randomly assigned half of the participants to simply continue the addiction treatment of their choice, whether it was detoxification leading to abstinence, residential treatment or maintenance on medications like methadone and buprenorphine (Suboxone, Subutex).

The other half received their usual treatment, plus exposure therapy for PTSD, which consisted of 13 one-on-one sessions with a clinical psychologist, meeting about once a week for 90 minutes at a time. The therapy began with education about PTSD and addiction, including instruction on cognitive techniques to address distressing thoughts that could lead to relapse. Then, when patients were ready, they were exposed to reminders of their traumatic experience, which they usually avoided out of fear of triggering flashbacks and intense anxiety. Exposure therapy works to reduce or eliminate these PTSD symptoms by breaking patients’ cycle of fear and avoidance.

Indeed, participants in the exposure treatment “demonstrated significantly greater reductions in PTSD symptom severity compared with participants randomized to receive usual treatment alone,” the authors wrote. However, drug use in the exposure therapy group didn’t decline any more than it did in the usual treatment group. Both groups saw a reduction in the severity of addiction but in each case, the majority of participants continued to use drugs. Notably, however, drug use did not increase due to exposure therapy.

“These findings challenge the widely held view that patients need to be abstinent before any trauma work, let alone prolonged exposure therapy, is commenced,” the authors wrote. “[F]indings from the present study demonstrate that abstinence is not required.”

Importantly, however, while the findings showed that carefully delivered exposure therapy can help, they did not support the practice of forcing addicts to confront trauma in settings where they do not feel safe or in control. Exposure therapy is calibrated so that patients do not become overwhelmed or feel helpless; in contrast, coercion by the therapist can re-traumatize patients and worsen both PTSD and addiction symptoms, previous studies have shown.

In other words, it’s not clear that treating people with addiction by compelling them to recall or re-enact traumatic experiences — a commonly used tactic in group settings — actually helps. What the current study shows is that when trained clinical psychologists carefully deliver exposure therapy in a tightly monitored trial, they can help ease PTSD symptoms in people with addiction.

By Maia Szalavitz | August 15, 2012

Source: TIME

August 13, 2012

Researchers at Mount Sinai School of Medicine may have discovered why certain drugs to treat schizophrenia are ineffective in some patients. Published online in Nature Neuroscience, the research will pave the way for a new class of drugs to help treat this devastating mental illness, which impacts one percent of the world’s population, 30 percent of whom do not respond to currently available treatments.

A team of researchers at Mount Sinai School of Medicine set out to discover what epigenetic factors, or external factors that influence gene expression, are involved in this treatment-resistance to atypical antipsychotic drugs, the standard of care for schizophrenia. They discovered that, over time, an enzyme in the brains of schizophrenic patients analyzed at autopsy begins to compensate for the prolonged chemical changes caused by antipsychotics, resulting in reduced efficacy of the drugs.

"These results are groundbreaking because they show that drug resistance may be caused by the very medications prescribed to treat schizophrenia, when administered chronically," said Javier Gonzalez-Maeso, PhD, Assistant Professor of Psychiatry and Neurology at Mount Sinai School of Medicine and lead investigator on the study.

They found that an enzyme called HDAC2 was highly expressed in the brain of mice chronically treated with antipsychotic drugs, resulting in lower expression of the receptor called mGlu2, and a recurrence of psychotic symptoms. A similar finding was observed in the postmortem brains of schizophrenic patients. The research team administered a chemical called suberoylanilide hydroxamic acid (SAHA), which inhibits the entire family of HDACs. They found that this treatment prevented the detrimental effect of the antipsychotic called clozapine on mGlu2 expression, and also improved the therapeutic effects of atypical antipsychotics in mouse models.

Previous research conducted by the team showed that chronic treatment with the antipsychotic clozapine causes repression of mGlu2 expression in the frontal cortex of mice, a brain area key to cognition and perception. The researchers hypothesized that this effect of clozapine on mGlu2 may play a crucial role in restraining the therapeutic effects of antipsychotic drugs.

"We had previously found that chronic antipsychotic drug administration causes biochemical changes in the brain that may limit the therapeutic effects of these drugs,"said Dr. Gonzalez-Maeso. "We wanted to identify the molecular mechanism responsible for this biochemical change, and explore it as a new target for new drugs that enhance the therapeutic efficacy of antipsychotic drugs."

Mitsumasa Kurita, PhD, a postdoctoral fellow at Mount Sinai and the lead author of the study, said, “We found that atypical antipsychotic drugs trigger an increase of HDAC2 in frontal cortex of individuals with schizophrenia, which then reduces the presence of mGlu2, and thereby limits the efficacy of these drugs,” said

Dr. Gonzalez-Maeso’s team is now developing compounds that specifically inhibit HDAC2 as adjunctive treatments to antipsychotics. The study was funded by the National Institutes of Health.

Source: The Mount Sinai Hospital

6-Aug-2012

Treatment with growth hormone-releasing hormone appears to be associated with favorable cognitive effects among both adults with mild cognitive impairment and healthy older adults, according to a randomized clinical trial published Online First by Archives of Neurology, a JAMA Network publication.

"Growth hormone-releasing hormone (GHRH), growth hormone and insulinlike growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease," the authors write as background information in the study.

To examine the effects of GHRH on cognitive function in healthy older adults and in adults with mild cognitive impairment (MCI), Laura D. Baker, Ph.D., of the University of Washington School of Medicine and Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues, conducted a randomized, double-blind, placebo-controlled trial in which participants self-administered daily injections of a form of human GHRH (tesamorelin), or placebo.

The authors enrolled 152 adults ranging in age from 55 to 87 years (average age, 68 years) and 137 participants (76 healthy patients and 61 patients with MCI) successfully completed the study. At baseline, at 10 and 20 weeks of treatment, and after a 10-week washout (30 weeks total), the authors collected blood samples and administered parallel versions of cognitive tests.

Among the original 152 patients enrolled in the study, analysis indicated a favorable effect of GHRH on cognition, which was comparable in adults with MCI and healthy older adults. Analysis among the 137 patients who successfully completed the trial also showed that treatment with GHRH had a favorable effect on cognition among both groups of patients. Although the healthy adults outperformed those with MCI overall, the cognitive benefits relative to placebo was comparable among both groups.

Treatment with GHRH also increased insulin like growth factor 1 levels by 117 percent, which remained within the physiological range, and increased fasting insulin levels within the normal range by 35 percent in adults with MCI but not in healthy adults.

"Our results replicate and expand our earlier positive findings, demonstrating that GHRH administration has favorable effects on cognitive function not only in healthy older adults but also in adults at increased risk of cognitive decline and dementia," the authors conclude. "Larger and longer-duration treatment trials are needed to firmly establish the therapeutic potential of GHRH administration to promote brain health in normal aging and ‘pathological aging.’"

Source: EurekAlert!

August 3, 2012

Scientists have discovered a biological marker that may help to identify which depressed patients will respond to an experimental, rapid-acting antidepressant. The brain signal, detectable by noninvasive imaging, also holds clues to the agent’s underlying mechanism, which are vital for drug development, say National Institutes of Health researchers. 

Dr. Zarate views subject in MEG scanner from scanner control room.

The signal is among the latest of several such markers, including factors detectable in blood, genetic markers, and a sleep-specific brain wave, recently uncovered by the NIH team and grantee collaborators. They illuminate the workings of the agent, called ketamine, and may hold promise for more personalized treatment.

"These clues help focus the search for the molecular targets of a future generation of medications that will lift depression within hours instead of weeks," explained Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health (NIMH). "The more precisely we understand how this mechanism works, the more narrowly treatment can be targeted to achieve rapid antidepressant effects and avoid undesirable side effects."

Zarate, Brian Cornwell, Ph.D., and NIMH colleagues report on their brain imaging study online in the journal Biological Psychiatry.

Previous research had shown that ketamine can lift symptoms of depression within hours in many patients. But side effects hamper its use as a first-line medication. So researchers are studying its mechanism of action in hopes of developing a safer agent that works similarly.

Ketamine works through a different brain chemical system than conventional antidepressants. It initially blocks a protein on brain neurons, called the NMDA receptor, to which the chemical messenger glutamate binds. However, it is not known if the drug’s rapid antidepressant effects are a direct result of this blockage or of downstream effects triggered by the blockage, as suggested by animal studies.

To tease apart ketamine’s workings, the NIMH team imaged depressed patients’ brain electrical activity with magnetoencephalography (MEG). They monitored spontaneous activity while subjects were at rest, and activity evoked by gentle stimulation of a finger, before and 6.5 hours after an infusion of ketamine.

It was known that by blocking NMDA receptors, ketamine causes an increase in spontaneous electrical signals, or waves, in a particular frequency range in the brain’s cortex, or outer mantle. Hours after ketamine administration— in the timeframe in which ketamine relieves depression — spontaneous electrical activity in people at rest was the same whether or not the drug lifted their depression.

Electrical activity evoked by stimulating a finger, however, was different in the two groups. MEG imaging made it possible to monitor excitability of the somatosensory cortex, the part of the cortex that registers sensory stimulation. Those who responded to ketamine showed an increased response to the finger stimulation, a greater excitability of the neurons in this part of the cortex.

Such a change in excitability is likely to result, not from the immediate effects of blocking the receptor, but from other processes downstream, in the cascade of effects set in motion by NMDA blockade, say the researchers. Evidence points to changes in another type of glutamate receptor, the AMPA receptor, raising questions about whether the blocking of NMDA receptors is even necessary for ketamine’s antidepressant effect. If NMDA blockade is just a trigger, then targeting AMPA receptors may prove a more direct way to effect a lifting of depression.

Read more …

July 31, 2012

Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.

B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.

In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.

The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.

The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can “leak” and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons. 

The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.

"We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage," Lisak said.

The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.

Provided by Wayne State University

Source: medicalxpress.com