Antidepressants May Be Missing the Mark By Rick Nauert PhD

A new study suggests most antidepressants do not target a key brain protein believed to be of importance in maintaining mood.

The protein is monoamine oxidase A (MAO-A), a substance that is highly elevated during clinical depression. The new study suggests this chemical is unaffected by treatment with commonly used antidepressants.

According to experts, the study has important implications for understanding why antidepressants don’t always work.

Researchers at the Centre for Addiction and Mental Health (CAMH) used an advanced brain imaging method to measure levels of the brain protein MAO-A. MAO-A digests multiple brain chemicals, including serotonin, that help maintain healthy mood.

High MAO-A levels excessively remove these brain chemicals.

Antidepressant medications are the most commonly prescribed treatments in North America, yet 50 percent of people do not respond adequately to antidepressant treatment.

Dr. Jeffrey Meyer, the lead investigator, explains, “Mismatches between treatment and disease are important for understanding why treatments don’t always work. Rather than reversing the problem of MAO-A breaking down several chemicals, most antidepressants only raise serotonin.”

Understanding the Problem of a Persistent Illness

Depression ranks as the fourth leading cause of disability and premature death worldwide, according to the World Health Organization. Recurrent illness is a major problem. Even under the most optimal treatment circumstances, recurrence rates for clinical depression are at least 20 percent over two years.

The new study also focused upon people who had fully recovered from past episodes of clinical depression. Some people who appeared to be in recovery actually had high levels of MAO-A. Those with high levels of MAO-A then had subsequent recurrence of their depressive episodes.

This new idea of high levels of MAO-A lowering brain chemicals (called monoamines), then falling into a clinical depression is consistent with the historical finding that medications which artificially lower monoamines can lead to clinical depression as a side effect.

In the 1950’s some medications to treat high blood pressure also lowered monoamines and people began to experience depressive episodes. When the medications were removed, people recovered.

From Technology to Treatment

VP of Research Dr. Bruce Pollock highlights the study’s use of advanced brain imaging technology. “CAMH has the only positron emission tomography (PET) centre in the world that is dedicated solely to mental health and addiction treatment and research. As a consequence, we were able to develop this new technology to measure MAO-A levels.”

According to Dr. Meyer, “Since most antidepressants miss MAO-A, we are counting on the brain to heal this process of making too much MAO-A, and that doesn’t always happen. The future is to make treatments that tell the brain to make less MAO-A, even after the antidepressant treatment is over, to create better opportunities for sustained recovery.”

Monoamine oxidase inhibitors (MAOIs) are an older class of antidepressants used for the treatment of depression. While more commonly prescribed in Europe and other places, they are not commonly prescribed in the U.S. due to the potential for serious dietary and drug interactions. People who take a MAOI antidepressant must eat a restricted diet to ensure they don’t suffer from serious side effects.

The study is found in the current issue of the Archives of General Psychiatry.

Source: Centre for Addiction and Mental Health

New Program Helps Mental Health Patients Stop Smoking By Rick Nauert PhD

Experts say that tobacco use among mental health patients account for nearly half of all cigarettes consumed in the United States.

A program developed by the division of addiction psychiatry at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School to address this addiction has received national recognition by the American Psychiatric Association (APA).

The program, called CHOICES – Consumers Helping Others Improve Their Condition by Ending Smoking – utilizes peer counselors to promote smoking cessation in mentally ill patients.

The counselors, who receive 30 hours of intensive training, are nonsmokers or former smokers who are moderately impaired or disabled by mental illness.

Their goal is not to provide treatment, but to assist smoking patients who are in mental health centers, psychiatric hospitals, group homes and self-help centers, by linking them to treatment, referrals, advocacy and support for smoking cessation in New Jersey.

“Peers are less threatening than professionals,” said Jill Williams, MD, associate professor of psychiatry at Robert Wood Johnson Medical School and co-founder and medical director of the program.

“CHOICES symbolizes empowerment and personal choice in recovery by involving persons with mental illness talking with peers with mental illness who smoke, and who may have low motivation to address their tobacco use.”

A salient feature of the CHOICES program is the unique peer-to-peer approach to promoting tobacco cessation.

In the October issue of its journal Psychiatric Services, the APA said, “The CHOICES program exemplifies many aspects of a successful wellness and recovery initiative. For example, it targets a group with a vital health care need; seeks to reduce tobacco’s harm in a vulnerable group; focuses its efforts in the community, which best accommodates the target population; employs peers to reduce educational and cultural barriers; and develops successful partnerships with key stakeholders for sustainability.”

According to Dr. Williams and co-founder Marie Verna, the program’s advocacy director and senior training and consultation specialist at UMDNJ-University Behavioral HealthCare’s Center for Excellence in Psychiatry, the CHOICES team has conducted more than 280 community visits, reaching more than 9,600 smokers with mental illness, since the program’s inception in 2005. The team also visits consumer conferences and health-related fairs.

An outcome study of the program showed success at reducing the number of cigarettes smoked by consumers each day and an increase in the number of quit attempts following individualized intervention.

Program participants reported that within six months after meeting with a peer counselor, they had talked to their mental health provider about getting help with quitting smoking. Patients also reported that peer counselors were extremely knowledgeable about tobacco and interested in their smoking. Seventy percent of those surveyed said that talking to a peer about their smoking was much easier than talking to a mental health professional.

Peer counselors also reported improvements of their own recoveries from mental illness as a result of participating in CHOICES. They reported on the achievement of personal milestones including participation in publications and conferences on wellness and recovery, and pursuing additional formal education.

Source: >Robert Wood Johnson Medical School

Brain Scans Clarify Borderline Personality Disorder

By Rick Nauert PhD Senior News Editor
Reviewed by John M. Grohol, Psy.D.

Using real-time brain imaging, a team of researchers have discovered that patients with Borderline Personality Disorder (BPD) are physically unable to regulate emotion.

The findings, by Harold W. Koenigsberg, MD, professor of psychiatry at Mount Sinai School of Medicine suggest individuals with BPD are unable activate neurological networks that would help to control feelings.

The research will be published in the journal Biological Psychiatry.

Using functional magnetic resonance imaging (fMRI), researchers viewed how the brains of people with BPD reacted to social and emotional stimuli.

Koenigsberg found that when people with BPD attempted to control and reduce their reactions to disturbing emotional scenes, the anterior cingulate cortex and intraparetical sulci areas of the brain that are active in healthy people under the same conditions remained inactive in the BPD patients.

“This research shows that BPD patients are not able to use those parts of the brain that healthy people use to help regulate their emotions,” said Dr. Koenigsberg.

“This may explain why their emotional reactions are so extreme. The biological underpinnings of the disordered emotional control systems are central to borderline pathology. Studying which areas of the brain function differently in patients with borderline personality disorder can lead to more targeted uses of psychotherapy and medications, and also provide a link to connect the genetic basis of the disorder.”

According to background information in the article, borderline personality disorder is a common condition, affecting up to two percent of all adults in the United States, mostly women.

Characteristics of BPD include being so emotionally overreactive that they suffer alternating bouts of depression, anxiety and anger, are interpersonally hypersensitive, and are impelled to self-destructive and even suicidal behavior.

Patients with BPD often exhibit other types of impulsive behaviors, including excessive spending, binge eating and risky sex. BPD often occurs together with other psychiatric problems, particularly bipolar disorder, depression, anxiety disorders, substance abuse, and other personality disorders.

The disorder is found in 10 to 20 percent of people in psychiatric care, and about 10 percent of people with this condition ultimately die of suicide. Only recently have researchers begun to identify underlying biological factors associated with the condition.

Source: The Mount Sinai Medical Center

New Grant To Study Depression Treatments

By Rick Nauert PhD Senior News Editor
Reviewed by John M. Grohol, Psy.D.

Depression affects more than 20 million people in the United States. The federal government recognizes the pervasive nature of the disease and has awarded the University of Illinois at Chicago a five-year, $4.8 million grant to develop new therapies to treat depression.

Currently, the most common treatment approach is a combination of antidepressant medication and psychotherapy.

Symptoms can include sadness, loss of interest in activities that were once enjoyed, weight change, difficulty in sleeping (or oversleeping), loss of energy, feelings of worthlessness and thoughts of death or suicide.

The illness can run in families, and it occurs more often in women than men.

What’s needed are antidepressants that work faster, have fewer side effects and that act pharmacologically in new ways, says Alan Kozikowski, UIC professor of medicinal chemistry and pharmacognosy (the study of medicines derived from natural sources) and the grant’s principal investigator.

Kozikowski and his research team had been designing and synthesizing novel nicotine-like compounds that target certain receptors in the brain, in hopes that they would improve cognition in Alzheimer’s disease. Studies in animal models revealed that some of these compounds had antidepressant activity.

“We thus chose to focus our program on depression, as this offered a very different target that might lead to something better, with a faster onset of action,” Kozikowski said.

While the main focus of the research now is to develop medications for depression, Kozikowski said it’s likely some candidate compounds may have other clinical applications, including the treatment of schizophrenia, pain and nicotine dependence.

In fact, the UIC drug discovery group — which also includes investigators from the Barrow Neurological Institute in Phoenix and from PsychoGenics Inc. in Tarrytown, N.Y. — has already found that some of these novel agents do work for pain in animal models.

Prior research has also shown that many smokers smoke to improve their mood, supporting the notion that nicotine itself has antidepressant properties. This would explain, Kozikowski said, why cigarette smoking is much more common among depressed individuals. A recent study found that smokers are 41 percent more likely than nonsmokers to suffer from depression.

Such studies suggest that nicotinic compounds that have been modified to reduce their addictive potential while retaining the ability to balance mood could provide a new family of antidepressant drugs, he said.

This new drug class could have greater efficacy and fewer side effects than antidepressant medications currently on the market that work by inhibiting monoamine reuptake, Kozikowski said. Side effects of current antidepressants include headache, nausea, insomnia, dry mouth, constipation and agitation.

In spite of the intensive efforts that have gone into the design and study of nicotinic drugs, very few of the compounds have reached clinical trials, Kozikowski said.

The new grant is part of the National Cooperative for Drug Discovery and Development Groups and is funded by the National Institute of Mental Health, one of the National Institutes of Health.

Source: University of Illinois at Chicago

PTSD and Problems with Alcohol Use

PTSD does not automatically cause problems with alcohol use; there are many people with PTSD who do not have problems with alcohol. However, PTSD and alcohol together can be serious trouble for the trauma survivor and his or her family.

How do PTSD and alcohol use affect each other and make problems worse?

PTSD and alcohol problems often occur together.

People with PTSD are more likely than others with similar backgrounds to have alcohol use disorders both before and after being diagnosed with PTSD, and people with alcohol use disorders often also have PTSD.
Being diagnosed with PTSD increases the risk of developing an alcohol use disorder.
Women exposed to trauma show an increased risk for an alcohol use disorder even if they are not experiencing PTSD. Women with problematic alcohol use are more likely than other women to have been sexually abused at some point in their lives.
Men and women reporting sexual abuse have higher rates of alcohol and drug use disorders than other men and women.
Twenty-five to seventy-five percent of those who have survived abusive or violent trauma also report problems with alcohol use.
Ten to thirty-three percent of survivors of accidental, illness, or disaster trauma report problematic alcohol use, especially if they are troubled by persistent health problems or pain.
Sixty to eighty percent of Vietnam veterans seeking PTSD treatment have alcohol use disorders. Veterans over the age of 65 with PTSD are at increased risk for attempted suicide if they also experience problematic alcohol use or depression. War veterans diagnosed with PTSD and alcohol use tend to be binge drinkers. Binges may be in reaction to memories or reminders of trauma.

Alcohol problems often lead to trauma and disrupt relationships.

Persons with alcohol use disorders are more likely than others with similar backgrounds to experience psychological trauma. They also experience problems with conflict and intimacy in relationships.
Problematic alcohol use is associated with a chaotic lifestyle, which reduces family emotional closeness, increases family conflict, and reduces parenting abilities.

PTSD symptoms often are worsened by alcohol use.

Although alcohol can provide a temporary feeling of distraction and relief, it also reduces the ability to concentrate, enjoy life, and be productive.
Excessive alcohol use can impair one's ability to sleep restfully and to cope with trauma memories and stress.
Alcohol use and intoxication also increase emotional numbing, social isolation, anger and irritability, depression, and the feeling of needing to be on guard (hyper-vigilance).
Alcohol use disorders reduce the effectiveness of PTSD treatment.
Many individuals with PTSD experience sleep disturbances (trouble falling asleep or problems with waking up frequently after falling asleep). When a person with PTSD experiences sleep disturbances, using alcohol as a way to self-medicate becomes a double-edged sword. Alcohol use may appear to help symptoms of PTSD because the alcohol may decrease the severity and number of frightening nightmares commonly experienced in PTSD. However, alcohol use may, on the other hand, continue the cycle of avoidance found in PTSD, making it ultimately much more difficult to treat PTSD because the client's avoidance behavior prolongs the problems being addressed in treatment. Also, when a person withdraws from alcohol, nightmares often increase.

Additional Mental Health Issues

Individuals with a combination of PTSD and alcohol use problems often have additional mental or physical health problems. As many as 10-50% of adults with alcohol use disorders and PTSD also have one or more of the following serious disorders:

• Anxiety disorders (such as panic attacks, phobias, incapacitating worry, or compulsions)
• Mood disorders (such as major depression or a dysthymic disorder)
• Disruptive behavior disorders (such as attention deficit or antisocial personality disorder)
• Addictive disorders (such as addiction to or abuse of street or prescription drugs)
• Chronic physical illness (such as diabetes, heart disease, or liver disease)
• Chronic physical pain due to physical injury/illness or due to no clear physical cause

What are the most effective treatment patterns?

Because the existence of both PTSD and an alcohol use disorder in an individual makes both problems worse, alcohol use problems often must be addressed in PTSD treatment. When alcohol use is (or has been) a problem in addition to PTSD, it is best to seek treatment from a PTSD specialist who also has expertise in treating alcohol (addictive) disorders. In any PTSD treatment, several precautions related to alcohol use and alcohol disorders are advised:
The initial interview and questionnaire assessment should include questions that sensitively and thoroughly identify patterns of past and current alcohol and drug use.
Treatment planning should include a discussion between the professional and the client about the possible effects of alcohol use problems on PTSD, sleep, anger and irritability, anxiety, depression, and work or relationship difficulties.
Treatment should include education, therapy, and support groups that help the client address alcohol use problems in a manner acceptable to the client.
Treatment for PTSD and alcohol use problems should be designed as a single consistent plan that addresses both sources of difficulty together. Although there may be separate meetings or clinicians devoted primarily to PTSD or to alcohol problems, PTSD issues should be included in alcohol treatment, and alcohol use ("addiction" or "sobriety") issues should be included in PTSD treatment.
Relapse prevention must prepare the newly sober individual to cope with PTSD symptoms, which often seem to worsen or become more pronounced with abstinence.

Where can you get help?

For a listing of professionals in the USA and Canada who treat alcohol disorders and PTSD, we suggest consulting the membership directories of the International Society for Traumatic Stress Studies or the Association of Traumatic Stress Specialists. For veterans experiencing problems with PTSD and alcohol use, the Department of Veterans Affairs has a network of specialized PTSD and substance use treatment programs. For information on these programs, contact the local VA Vet Center or the Psychiatry Service at a VA Medical Center. (For addresses and telephone numbers, look under the "United States Government" listings in the telephone directory.)
FOR MORE INFORMATION:
EMAIL - ncptsd@va.gov
CALL - THE PTSD Information Line at (802) 296-6300