Site Info and Member News

• New additions to the website - SZ drugs in development, and the biological basis of insight
• Newspaper editorial from a father with schizophrenia

Medications and Treatment

• Developing SZ Drugs with New Mechanisms
• Memory Pill - moving ahead
• Lamotrigine as an Adjunct Treatment - A Research Review
• Gene Identified That Could Help SZ Treatment
• Updated Guidelines for Evidenced-Based Treatment
• Redefining the Standard of SZ Care

Long Term Management and Prevention of Schizophrenia

• Atypical Meds May Lessen Sleep Problems
• Transition from Hospital a Stressful Time - what to watch for
• Student's Guide to Coping with Mental Illness

Biology and Current Research:

• Study to Examine SZ in Pregnant Women
• Future Clozapine Compatibility Genetics Test
• Sexual Side Effects from Atypical Antipsychotics - A Comparitive Study
• CBT vs. Psychoeducation (research study)

New Site Additions - Developing SZ Meds and the Biology of Poor Insight

Two new reports have recently been added to the schizophrenia.com website.

The first, which can be found under the "Schizophrenia Medications" section, is a comprehensive review of promising schizophrenia medications that are currently in phase II or III clinical trials. The report includes the symptoms that each new drug theoretically targets, any proposed mechanism or site of action in the brain, and links to peer-reviewed research abstracts. There is also a brief introduction explaining the process of FDA drug approval in the United States, as well as what each clinical trial phase means for a medication and the study subjects involved. A direct link is included below:

• Schizophrenia Medications in Development - A Special Report (Dec 2004)

The second report, originally written for an advanced neuroscience research seminar, addresses the possible biological mechanisms that may cause and/or contribute to various aspects of poor insight in schizophrenia patients. It cites recent research on the subject, reviews the current schools of thought concerning the mechanisms of poor insight, and discusses future implications for how this debilitating symptom of schizophrenia might be managed. It can be found under "Schizophrenia Biology and Genetics - Reports on Schizophrenia." A direct link is included below.

• A Neurological Basis for Poor Insight in Schizophrenia - Review of the Research

Newspaper Editorial about Mental Illness

This is a good example of the types of editorials that people can write to Newspapers about their experiences with schizophrenia. The more that people write, the more that people will understand the disease.
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Excerpt from and Editorial in The Vancouver Sun (British Columbia, Canada)

December 18, 2004

Shining light on a dreaded disease: A Vancouver Sun columnist receives a wave of emotion-filled responses to the story of his father and finds that a small army of Canadians is diligently working to shine light on the confusion and fear surrounding people with schizophrenia

By Douglas Todd, Vancouver Sun

All I wanted to do was lie low when I saw the photo of my father, Harold Todd, on the front page of The Vancouver Sun on Saturday, Dec. 4.

My story about my father's struggle with schizophrenia had been, in one sense, my way of coming out of the closet -- to more than half a million people. The feeling of vulnerability was almost overwhelming.

No longer would friendly strangers ask if my father happened to be a retired University of British Columbia professor with the last name of Todd. That pleasant little illusion was over. Now people would learn, at least in the usual sense, my dad hadn't accomplished much at all.

When I emerged from my house on Sunday and went to one of my coffee haunts, Cuppa Joe's on West 4th, the woman behind the counter, Indy, told me I'd been "brave" to write the story about a life of Sunday visits with a father with schizophrenia.

"Brave? Or stupid?" I asked.

"Bravery often includes a bit of stupidity," Indy replied.

Wise barrista.

I've since been flooded with the heartfelt response of colleagues, friends, family and readers. I've heard from police chiefs, psychiatrists, theologians, health officials, researchers, my editor-in-chief and my publisher. Most important of all I've been contacted by scores of people with schizophrenia and other mental illnesses, as well as their often-anguished loved ones.

We are legion.

Health Canada researchers estimate nearly one in five Canadians will suffer mental illness. And fully 80 per cent of Canadians have a direct link to a family member or friend with mental illness, of which schizophrenia is the most common, not to mention one of the strangest and most frightening. Schizophrenia strikes more than 300,000 Canadians. Yet most of us, me included, still find ways to run away from people with the illness.

Where to start with the stories, mostly harrowing but sometimes heartwarming, that people have honoured me with in the past two weeks?

How about in The Sun's newsroom, where one colleague told me about his wife's struggle with the paranoia of schizophrenia, and another told about the pain of having her long-term boyfriend, after being diagnosed with schizophrenia, committing suicide?

The many grateful letters included one from a small-town B.C. mother who valiantly took on London Drugs when a store denied service to someone with a mental illness. Another mother phoned and broke down crying as she wished more people would read such articles so they'd understand her child's disease and counter its stigma.

There were also unexpected letters of admiration for my dad. A classy one came from Paul Glassen of Duncan Mental Health Centre, who said he works for people with schizophrenia and regards my father as "one of the great unsung everyday heroes."

"[Your father] obviously lived quietly and courageously through a dark time in the history of society's treatment of those with this illness. His life exemplified the abiding dignity of those I so admire living under conditions few of us could endure."

People with schizophrenia offered their thanks. And one reader asked if she could create a beadwork version of my father's painting, called Houses, which was printed in The Sun. Douglas College English instructor Susan McCaslin gave me her book of poems, Flying Wounded, about growing up with a mother who had schizophrenic episodes.

There were also words of encouragement from Vancouver educator Susan Inman, who recently had an autobiographical article published titled, So Where's the Gift? "Those who seek the hidden gifts in misfortune would have to look hard if they had a child with schizophrenia."

I heard as well from Marja Bergen of the Mennonite Central Committee in Abbotsford, who said she'd been in Crease Clinic for 10 months in the 1960s, but has "come out" in public and is doing well in part because of advances in modern medicine.

Bergen passed on a book titled No Longer Alone: Mental Health and the Church, by Canadians John Toews and Eleanor Loewen. From a conservative Protestant perspective, the book explores dangerous age-old beliefs that saw mental illness as punishment for sins. Fittingly, the book also devotes a chapter to Jesus' agonized question on the cross: "My God, my God. Why have you forsaken me?"

The correspondence wasn't all supportive, however. A retired psychiatric nurse at what is now called Riverview questioned my childhood memories of the wing known as Crease Clinic, saying it didn't have bars on the windows in the 1950s, nor did it have smoke-filled rooms.

It wasn't my intention to criticize the staff who did what they could to feed, house and help my dad at Riverview more than four decades ago, when psychiatrists had little idea how to treat schizophrenia, beyond electro-shock and lithium treatments.

However, I had more than a few letters from readers who verified my dark recollections. They said they visited parents and children in locked, barred wards in Crease Clinic in the 1950s, with some saying their relatives' experience there was more "abusive" than I had depicted it.

Vancouver Police Chief Jamie Graham also weighed in on a crucial issue. He's been pressing for years to improve the way police interact with people with mental illness -- which is frequently and often disastrously.

My mother remembers with undying sorrow how my dad, whom she always called a "nice man," ran away from police after she called them for help because of his bizarre behavior. Harold ended up institutionalized at Riverview and government boarding homes for the rest of his life.

Separately from Graham, someone sent a chilling 2004 report from the Commission for Public Complaints Against the RCMP, in which commission chair Shirley Heafey wrote that 15 per cent of all police contacts are with someone with mental illness.

With mental health institutions being downsized, Heafey noted Amnesty International is among those worried more people with psychiatric problems are being released onto the streets, often ending up in confrontations with police.

In B.C., people with schizophrenia have been the victims in more than 30 per cent of all fatal police shootings. In her investigation of an accusation police used excessive force in a showdown with an unnamed B.C. man suffering schizophrenic hallucinations, Heafey scathingly noted the RCMP hadn't bothered to set up a training program to help officers defuse situations with mentally ill people.

However, Vancouver's police chief has been working to reduce discrimination against people with mental illness. Not long ago, Graham says wryly, he was the sole member of the B.C. Association of Police Chiefs' mental health committee. Now there are two on the committee.

Graham helped create a small yellow plastic "tips card" police can haul out when confronted by a mentally disturbed person. The card gives advice on how to handle situations involving an unpredictable person in a mental crisis.

The city of Vancouver also has a special patrol vehicle known as "Car 87," in which police and psychiatric nurses together attend emergency calls. The Car 87 teams, Graham says, tell "incredible stories of lives saved and careers turned around" because officers handled troubled mentally ill people with empathy.

The wave of emotion-filled responses to the story of my dad has made clear to me a small army of Canadians is diligently working to shine light on the confusion and fear surrounding people with schizophrenia.

More and more people are willing to put their names and faces to the dreaded disease. And they give the impression they are not going to go away.

Developing SZ Drugs with New Mechanisms

Novasite Pharmaceuticals and the Stanley Medical Research Institute are teaming up to develop a new class of medications for schizophrenia and bipolar disorder.

Called "allosteric modulator drugs", these compounds act at a regulatory site in brain receptors, different from the site that target neurotransmitters use.

According to the press release, allosteric drugs may be a safer option because they mimic the behavior of natural regulatory molecules in the body. This more natural mechanism of action may prevent potential overdose, tolerance, abuse, and dependence problems.

View the press release: "Novasite Pharmaceuticals and the Stanley Medical Research Institute Announce Alliance to Discover Novel Allosteric Modulator Drugs for Schizophrenia" (12/6/04). Available at http://home.businesswire.com

Memory Pill - Moving Ahead

Good news for those with some aspects of cognitive decline that are common for people with schizophrenia.

Newsweek Magazine reports this week in a story titled "Medicine's Next Level" - that "With new insight into the mechanisms that help keep your brain sharp, neurological researchers move closer to improving your recall with a 'memory pill.'

No pill to improve memory, aside from alternative remedies of dubious effectiveness, is currently on the market. But several small biotech companies are launching drugs grounded in the latest research, with a few already in the early stages of clinical trials that could be finished in as little as "two years, if we're lucky," says Kandel, who is now at CUMC and the Howard Hughes Medical Institute.

...

The practical results of this work, as well as extensive follow-up tests in mice and rats, are several new drugs now in early development at Memory Pharmaceuticals, founded in part by Kandel in 1998. MEM1414 is the inheritor of the Aplysia findings. Cyclic AMP, the neurotransmitter that dictates CREB levels, is normally degraded in the brain by enzymes called phosphodiesterases. By inhibiting those enzymes' activity, MEM14 appears to boost CREB levels and enhance the brain's long-term memory functions; researchers hope it will enhance long-term memory in patients with age-related forgetfulness and even ward off the early stages of Alzheimer's disease, even though the two ailments are not related. There's also MEM1917, a drug similar to 1414; MEM1003, which protects neurons from damaging overloads of calcium, and MEM3454, a schizophrenia treatment that targets a receptor also known to respond to nicotine. Researchers think that some schizophrenics ease their symptoms, including loss of memory function, by self-medicating with cigarettes.

For More information:

The Full Article - Medicine's Next Level, Newsweek Magazine

Memory Pharmaceutical's Memory Drug Schedule (for Schizophrenia)
http://www.memorypharma.com/pipeline.html

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Lamotrigine: Adjunct to Schizophrenia Treatment?

1. Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial

Jari Tiihonen, Tero Hallikainen, Olli-Pekka Ryynänen, Eila Repo-Tiihonen, Irma Kotilainen, Markku Eronen, Päivi Toivonen, Kristian Wahlbeck and Anu Putkonen

Biological Psychiatry
Volume 54, Issue 11 , 1 December 2003, Pages 1241-1248

2. Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia

Ilana Kremer, Agnes Vass, Ielena Gorelik, Gali Bar, Monica Blanaru, Daniel C. Javitt, and Uriel Heresco-Levy

Biological Psychiatry Volume 56, Issue 6 , 15 September 2004, Pages 441-446

Lamotrigine (Lamictal) is an anticonvulsant medication (meaning it was originally created to help control seizures) that has been shown to have benefit in patients with bipolar disorder. It has an indication for the long term mood stabilization in bipolar disorder, and has been shown to have a slight anti-depressant effect in bipolar patients who are more prone to periods of depression. Small studies with lamotrigine used to augment clozapine (Clozaril) have shown some improvement in BPRS (Brief Psychotic Rating Scale) scores which indicates a decrease level of symptoms. In one study, symptoms were decreased by up to 75% in chronic treatment-resistant patients. In another study, Lamotrigine works primarily by blocking the neurotransmitter glutamate. Neurotransmitters are the chemicals in the brain that signal brain cells (neurons) to fire and do their job. All antipsychotics work, at varying levels of potency, by blocking the neurotransmitter dopamine. This led to the theory that schizophrenia must be caused in large part by an overabundance of dopamine related activity. However, recent studies have implicated the role of glutamate as also potentially being involved in the problems with schizophrenia.

In the first study, the authors utilized a “crossover” design to try and ascertain the effect of adding lamotrigine to clozapine in severe, treatment-resistant patients that were institutionalized in Finland. The crossover design means that subjects are assigned randomly to either receive a placebo or the active drug for the first half of the study and then are switched halfway through to receive the other. Neither the patient nor the researcher knows which part of the study the patient is on until the end of the trial when the schedule can be revealed. This design is helpful because it allows for patients to be compared with themselves minimizing the risk of bias that can be caused by differences between groups. The authors found that at the end of the study, there was a slight improvement in patients who took the lamotrigine. However, this was an average improvement that while statistically significant, is not very clinically meaningful. In other words, the benefit is measurable in a research setting, but is of overall very little meaning in the outside world. However, they noted that in 20% of the people, when they were on the labotrigine, they showed a very significant benefit (Decrease in the PANSS or Positive and Negative Symptoms in Schizophrenia Scale of 3 points) and in the other 80% of the time, the benefit was negligible. In a population of people who have not responded to medication in the past, improvements in 20% is a meaningful number in terms of benefit to the public.

In the second study, the authors wanted to look at lamotrigine in addition to other antipsychotics besides clozapine. They included patients with severe, treatment-resistant schizophrenia but who were taking antipsychotics other than clozapine. They assigned subjects randomly to either receive a placebo (dummy pill) or to receive lamotrigine at a slowly escalating dose up to 400mg per day (a typical maximum dose.) They assessed the patients after ten weeks and found that among patients that completed the study, those who received the lamotrigine had an improved symptom profile. Generally, it is considered to be a more rigorous research standard to consider all patients enrolled in a study, even if they don’t complete the study, as the reasons for a patient to discontinue the study may be related to a problem with the study medication and therefore should be considered a negative outcome unless there is a specific reason not to believe so. When the authors did that kind of analysis, they found that there was no statistically significant difference between the groups. This does not mean that the medication did not work; rather it implies that further research needs to be done to fully understand the effect.

Based on these data, it may be helpful to add lamotrigine to a patient’s drug regimen if they are not achieving therapeutic success with more conventional treatments. It is a reasonable choice to try as many patients did benefit however there were also several that did not. Research gives answers for overall populations however, and does not necessarily indicate if something will work or not work for a unique individual. There are risks to lamotrigine, not the least of which is a serious and potentially fatal skin rash called Stevens-Johnson syndrome, so the medication must be started and stopped slowly and carefully under guidance from a physician.

Funding notes:
1. The study was supported by funding from Annual EVO Financing (Special government subsidies). No support was provided by any pharmaceutical company.

2. This research was supported by a grant from the National Institute for Psychobiology in Israel (IK, UH-L). DJC and UH-L served as consultants at the GlaxoSmithKline Advisory Meeting on lamotrigine use in schizophrenia held at the American College of Neuropsychopharmacology 42nd Annual Meeting, December 7–11, 2003, San Juan, Puerto Rico.

Click Here for the First article on PubMed
Click here for the Second article on PubMed

(Or go to http://www.pubmed.com and do a search on the full titles of the studies, cited at the beginning of this article)

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Gene Identified That Could Help SZ Treatment

Australian scientists say the discovery of a new gene could significantly improve the treatment of patients with schizophrenia.

Doctors have found a gene which makes patients more susceptible to the side-effects of medication.

Many patients do not like to take the anti-psychotic drugs prescribed for schizophrenia because of severe side-effects, including depression, sexual problems and osteoporosis.

"It is a fundamentally important [discovery] because the way we've used medications until now has been trial and error," Professor Ross Young from Queensland University of Technology said.

Doctors say discovering the gene means they will be able to do a blood test or DNA swab and predict who will do better on certain medications.

"By screening for genetic markers we can give lower doses of medication or give ones that have less side effects," Professor Young said.

Source: ABC News Australia, at:
http://www.abc.net.au/news/newsitems/200412/s1256774.htm

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Updated Guidelines for Evidence-Based Treatment

Magellan Health Services (national managed behavioral health care organization) has adopted, updated, and simplified the American Psychiatric Association (APA) Practice Guidelines for the Treatment of Patients with Schizophrenia. Specifically, they have expanded the guide with a summary of recent research conducted between 2002 and 2004, and added a "consumer summary" for patient and family education.

The result is what senior vice president Dr. Andrew Rudo believes to be "a definitive guide on evidence based treatments in schizophrenia."

The literature-review and treatment-guideline addendum released by Magellan, based on recent research in the area of schizophrenia, includes additional topics such as cultural factors, treatment adherance, suicide prevention, social skills training, and schizophrenia in the elderly. The organization uses this document in addition to the APA Guidelines as their promoted standard of care. The consumer summary is a very brief, two-page general outline including what schizophrenia is, what might cause it, what family members can do, and contact information for helpful organizations (such as NAMI).

The hope is that replacing previous, older treatment guideline documents with this expanded, updated APA-based Guide will improve the standards of care given by network practitioners for patients with schizophrenia.

Download a PDF of the APA Practice Guidelines for Schizophrenia (2nd edition, released in 2004).

Download a PDF of Magellan's updated, evidence-based clinical practice guidelines for schizophrenia.

Download a PDF of Magellan's consumer summary about schizophrenia and available treatments.

Original source articel: 'Magellan Health Services Updates and Enhances Guide for Evidence-Based Schizophrenia Treatment; Resource Helps Practitioners Stay Current on Effective Treatments' (Dec 9, 2004). Available at http://home.businesswire.com

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Redefining the Standard of SZ Care

An expert panel of medical professionals and professors from top research institutions and universities are asking doctors to raise the bar in terms of expectations for schizophrenia treatment.

Atypical antipsychotics have greatly improved the management of positive symptoms, and often with fewer side effects. However, a national survey of schizophrenia patients (the results of which were discussed by the panel) reveals that in addition to hallucinations and delusions, patients feel that it is "very important" that treatments help control depression and the inability to think clearly, concentrate, or remember. 94% of the survey respondants look for improvements in daily functioning - improved ability to work, shop, and engage in normal interests and hobbies - as the ultimate treatment goal.

The expert panel agrees with such goals:

"For decades, psychiatry has focused almost solely on managing a patient's 'positive symptoms,' such as hallucinations and delusions, because for previous treatments, that is pretty much all we had to offer," said Philip D. Harvey, PhD, professor of psychiatry at Mount Sinai School of Medicine and chief psychologist at Mount Sinai Hospital. "Today, patients and physicians should expect that more of the disease symptoms can be controlled, and that people with schizophrenia can have a more meaningful life."

For the full story, see "Expert Panel Calls for Raising the Bar in Treating Schizophrenia", Dec 20 2004. Available at http://biz.yahoo.com/prnews/041220/nym138_1.html

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Atypical Antipsychotics May Lessen Sleep Difficulties

Sleep difficulties are a common problem among people with schizophrenia, either due to disturbing symptoms or as a side effect of the medication used to treat those symptoms. A recent study from the Journal of Clinical Psychiatry suggests that atypical antipsychotics (as opposed to the older versions) may help improve sleep quality in some patients. Adequate and good-quality sleep is especially important for people with illnesses such as schizophrenia or bipolar disorder, as an insufficient amount of sleep can increase stress and exacerbate symptoms, as well as significantly reduce the quality and functionality of waking hours.

The study included 92 people (mean age 60 years, all from Japan) with schizophrenia, each of whom had been previously taking s typical antipsychotic. Each subject was randomly assigned one out of four possible atypical antipsychotics.

After 8 weeks on the new treatment, results (collected by survey) showed that, with the exception of those taking the compound perospirone, patients reported an improvement in sleep quality, latency, and efficiency, as well as reductions in sleep disturbance and daytime dysfunction. However, the actual duration of sleeping time did not change, and patients continued to use sleeping medications with the same frequency as they had on their old medications.

Improvement in sleep quality correlated with an improvement in negative symptoms. Those with poorer quality to begin with showed the greatest level of noticeable improvement with the new medication.

The researchers suggested that the greater serotonin action of atypical antipsychotics may help to improve sleep quality, and suggest that these medications might be helpful for people with schizophrenia who experience sleep problems.

Given the narrow patient demographic, we should be cautious in generalizing these results as applicable to everyone. There are many simple, natural remedies that can alleviate sleep difficulties, as well as over-the-counter medications. For example, getting enough daily exercise, reducing or eliminating caffeine intake, and learning relaxation or guided imagery techniques to use before bedtime can all help. Ask your doctor for recommendations if you are having sleeping problems.

Source: Atypical Antipsychotics Improve Sleep Quality, Dec 15 2004. Available at PsychiatrySource (http://www.psychiatrysource.com).

View the study abstract: J Clin Psychiatry. 2004 Nov;65(11):1525-30. Available at http://www.pubmed.com.

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Transition from Hospital is a Stressful Time

Although returning home from a hospitalization is clearly a stressful experience, very little research exists about what specific stressors might be prevalent during this period, and how they might be avoided. Given the strong link between stress and exacerbation of schizophrenia symptoms, being aware of these transitional stressors could be an important way to reduce future episodes, further hospitalizations, and possible suicide attempts.

A letter to the editor of Psychiatric Services (Dec 2004) suggests that although major life stressors have been a focus in the onset of schizophrenia symptoms, chronic everyday stress may be a better indicator.

The letter then cites a specific study, evaluating the stressors identified by 110 schizophrenia patients within a week of a hospital discharge. Respondants indicated that the most prevalent stressor was psychotic symptoms (identified by 31% of patients). Re-adjusting to residential settings (28%), finding/maintaining employment (33%), various interpersonal stressors such as social activities, relationships with family/friends, and loneliness (43% overall), and health-related concerns (i.e. the possibility of future hospitalization, 31%) were also mentioned as significant stressors.

The researchers conclude their study with the hope that identifying these key stressors shortly following hospital discharge will lead to specific stress management and coping techniques becoming integrated into the discharge treatment and follow-up plan.

Family members who are aware of these potential stresses can also help to create a low-stress living environment for a loved one returning home after a hospital stay. See the following resources for helping to manage life stress:

1) Overcoming stress in the workplace. (http://www.schizophrenia.com/newsletter/697/697stress.htm)
2) Lower levels of family stress to reduce risk of schizophrenia (or relapse): (http://www.schizophrenia.com/prevent2.htm#stress1)
3) Research on how family stress environment can negatively impact schizophrenia symptoms: (Pubmed abstract: "Family Intervention for Schizophrenia")

Research shows that one of the most risky periods for suicide attempts are in the months after someone has begun medication treatment and is "thinking more clearly." Since many people recieve medication treatment for the first time following a hospitalization, family members and caregivers must be especially vigilant in identifying depression and suicidal tendencies immediately following discharge, and encourage the depressed member to find help. See the following pages for more information on how to manage depression and prevent suicide:

1) Preventing suicide in people with schizophrenia. (http://www.schizophrenia.com/suicide.html).
2) Overcoming Depression. (http://www.schizophrenia.com/deprssn.html)

Original Article Source: "Identifying Life Stressors of Patients With Schizophrenia at Hospital Discharge." Psychiatric Services ("Letters" section), Dec 2004. Available at http://psychservices.psychiatryonline.org

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A Student's Guide to Coping with Mental Illness

The Canadian Mental Health Association, a Toronto-based group has just released a comprehensive guide aimed at making student life less harrowing for people with a mental illness.

It is available at: http://www.cmha.ca/youreducation/

It offers practical advice on a wide variety of topics, including selecting programs, managing the workload, getting through the courses and deciding whether to pursue graduate studies.

The guide is posted on the association's website (www.cmha.ca) and will be available at colleges and universities across the country.

"It's a very empowering and necessary document because many individuals with psychiatric disabilities experience mental-health issues," one York University student who has suffered serious anxiety for the past four years said in an interview.

"It's very important to know you can pursue your academic goals in order to pursue your career goals."

The 24-year-old woman, who did not want her name used, praised the guide, entitled Your Education -- Your Future, for its common-sense approach.

"There are a lot of testimonials in the document and that is important because they're real-life stories where individuals who have psychiatric disabilities have been able to pursue their schooling."

Bonnie Pape, who helped develop the guide as the association's director of programs and research, said the project got off the ground when a professor alerted her and other people to the fact students with mental illness were starting to attend university.

For more information See: http://www.cmha.ca/youreducation/

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New Study to Examine SZ in Pregnant Women

A new study to begin in Australia will provide some much needed information about how schizophrenia can be managed during a woman's pregnancy. There have been no past studies on this subject to date, despite the obvious importance of the information to countless women and families.

The study will enroll up to 100 women in Australia, and will look at the best way to clinically manage schizophrenia and other psychosis disorders during pregnancy. Investigators will set up a database of study subjects, and track the woman and her baby during pregnancy and through the first year of the baby's life.

There is little information about the effects of anti-psychotic medication on fetal development, although it is clearly critical for a woman with schizophrenia to continue some form of adequate treatment throughout her pregnancy to ensure her own health and that of her baby.

This will hopefully provide valuable information on how to best prevent schizophrenia and related mental illnesses in such high-risk populations as children born to parents with the disease.

For the full article, see "A new study will research the best way to treat women with psychosis who then become pregnant" (Nov 29 2004), available at http://www.news-medical.net/?id=6522.

Read more about the upcoming study from the sponsoring institution, The Alfred Psychiatry Research Centre (http://www.alfred.org.au/).

See information on what parents can do in the pre- and post-natal periods to help reduce an infant's risk of developing schizophrenia. (http://www.schizophrenia.com/prevent3.htm)

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Future Clozapine Compatibility Genetics Test

It was announced today that Genaissance Pharmaceuticals, Inc. (GNSC) published results from its study, reporting the discovery of genetic markers that the Company believes predict who is at risk of developing clozapine-induced agranulocytosis, a life-threatening decrease of white blood cells that requires frequent blood testing of patients.

A news report suggests that Clozapine ( a drug that has been identified as one of the most effective medications for treating schizophrenia) has had limited utilization due to the risk of inducing agranulocytosis. According to a 1993 study in the New England Journal of Medicine (Volume 329:162-167), clozapine-induced agranulocytosis affects 1-2% of people taking the medication. Normally, the risk is reduced through careful monitoring of the patient's white blood cell count via weekly blood tests.

However, this current research study suggests that there may be alternative approach in the prescribing of clozapine where, a one-time genetic test may someday eliminate the need for continuous blood monitoring.

In the Press Release from the company (published by the company) it states:

"In light of recent drug withdrawals and labeling restrictions due to rare but serious adverse drug events, these results underscore the potential of pharmacogenetics to identify individuals who are at particular risk for developing fatal adverse drug reactions," said Kevin Rakin, President and Chief Executive Officer of Genaissance. "The CARING study is a powerful, cost-effective model for understanding the contribution of genetics to other adverse drug reactions and provides strong evidence of the power of Genaissance 's proprietary platform. We believe an appreciable market exists for a genetic diagnostic test for predicting which patients are at-risk for developing agranulocytosis in response to clozapine and other drugs."

"Our analyses indicate that genetic variation appears to explain a significant portion of the risk of developing clozapine-induced agranulocytosis, " added Carol R. Reed, M.D., Vice President of Medical Affairs of Genaissance. "We believe the sensitivity and selectivity of these markers could support further development of a diagnostic test. Additionally, one of the associations we identified in the HLA (Human Leukocyte Antigen) complex has been previously reported to be associated with clozapine-induced agranulocytosis. Our results confirm this finding, building confidence that our novel findings will be validated in future studies."

"Clozapine has long been accepted as one of the most effective medications for treating schizophrenia but has had limited utilization due to the risk of inducing agranulocytosis," said John Kane, M.D., Chairman of the Department of Psychiatry at The Zucker Hillside Hospital, Professor of Psychiatry at Albert Einstein College of Medicine, and co-Chair of the CARING Steering Committee. "These findings have moved us one step closer to realizing an alternative approach in the prescribing of clozapine where a one-time genetic test may someday alleviate the need for continuous blood monitoring for the majority of clozapine treated patients."

About Genaissance

Genaissance Pharmaceuticals, Inc. is developing products based on its proprietary pharmacogenomic technology and has a revenue-generating business in DNA and pharmacogenomic products and services. For more information on Genaissance, visit the website at: http://www.genaissance.com/ .

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Sexual Side Effects of Antipsychotic Medications

Title: Antipsychotic treatment and sexual functioning in first-time neuroleptic-treated schizophrenic patients

István Bitter, Bruce R. Basson and Martin R. Dossenbach

International Clinical Psychopharmacology 2005, 20:19–21

This small study attempts to determine if particular antipsychotic medications have a more significant impact on sexual functioning. Sexual function is important and a decrease in function can be a reason for discontinuing medication. The authors were particularly interested in understanding the experience of people who were new to antipsychotic medication. They started by asking a simple questionnaire to patients to see what their level of sexual functioning was like before they started medication. They then followed the patients for six months and assessed their sexual functioning at months 3 and 6. They did this by using clinical ratings and by again asking patients for their rating.

The authors found that many patients with schizophrenia (up to 20% of their sample) have a baseline dysfunction sexually. This may be a decreased libido or other forms of sexual dysfunction. However, the numbers mostly stayed the same as patients began antipsychotic treatment. They found a small difference between patients taking risperidone and olanzapine and that olanzapine patients had a slightly better outcome. One might hypothesize that a reason that risperidone and some of the first generation antipsychotics might have a worse effect on sexual functioning could be related to the sometimes seen side effect of an increased prolactin level. Prolactin is a hormone in the blood that helps to produce milk and is involved in breast development. However, increased prolactin can lead to a decrease in libido when it is not needed.

The difference was very small and there were several methodological compromises made in this study that make the result even less impressive. First, the study was sponsored by the manufacturer of olanzapine and the raters generally worked for the company. Additionally, there was no randomization, control group for comparison and the raters were not blinded to treatment condition as they were the primary psychiatrists for the patients. This further leads to possible bias in the ratings.

Overall, sexual function is important consideration in the treatment of any patient, including those with psychiatric illness. Sexual dysfunction is one of the leading causes of treatment nonadherance and can lead to other morbidities as a result. However, this study does not demonstrate a significant negative effect sexually with second generation antipsychotics. Further research, including more rigorous studies, could help to demonstrate a more meaningful difference clinically and one that might prompt a change of medication if indicated. However, this study does not provide such evidence, though the concept is interesting.

Conflict of interest: B.R. Basson and Martin R. Dossenbach are employees and shareholders of Eli Lilly and Company. Eli Lilly and Company funded the study
István Bitter was an employee of Eli Lilly and Company between November 2000 and August 2003. Olanzapine is made by Eli Lilly and Company.

Click here for the abstract on PubMed (Or go to http://www.pubmed.com and do a search on the full title of the study, cited at the beginning of this article)

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CBT vs. Psychoeducation

Title: A randomized comparison of group cognitive-behavioural therapy and group psychoeducation in patients with schizophrenia

A. Bechdolf, B. Knost, C. Kuntermann, S. Schiller, J. Klosterkötter, M. Hambrecht, R. Pukrop

Acta Psychiatrica Scandinavica Volume 110 Issue 1 Page 21 (July 2004)

Cognitive Behavioral Therapy (CBT) is a type of psychotherapy in which the patient is instructed on different possible ways to interpret events and behaviors which can be used to lead to more positive outcomes in his/her life. CBT was originally created for use with depression, but its use has been shown in most mental illness including schizophrenia. Earlier in this blog (see October 4) for two articles that are about using CBT in acute schizophrenia. This study is another that was designed to determine if there was a benefit to the CBT style of training or if Psychoeducation (PE) was more or less effective. Psychoeducation is a method of teaching families and patients about their psychiatric disease.

In this study, the authors conducted a randomized comparison meaning that patients were assigned either to CBT or PE randomly, so as to limit potential biases in group placement for a desired effect. Also, this study utilized psychotherapy groups while the other papers addressed using CBT on an individual basis. Using groups allows for a more practical approach that could be applied in non-research settings in the community. CBT is often limited by the need for an individual therapist per patient which makes it very time consuming and expensive. Utilizing groups would make it more cost effective for more patients.

After six months, the authors report that patients who received CBT had a statistically significant decrease in rehospitalizations compares to the PE group. However, both groups showed improvement over the course of the six month follow-up. In fact, there was not significant difference between the groups with respect to general symptomatology. This might have been because the groups were too small to detect a difference statistically or may relate to the make up of the studied population. It is also possible that the group CBT, while cost effective on the larger scheme, may not work as effectively as originally thought. Despite this equivocal aspect to the results, the overall benefit appears to be promising for CBT and the group effect was ultimately minimal.

Overall, the potential benefits from CBT far outweigh the risks. Patients demonstrated fewer hospitalizations while working in their groups. It is important to note though, that the PE group was similar to the CBT in most other measures. This may be also because simply having a group to be responsible towards may have been helpful for the subjects. Ultimately, CBT would be nice to have for most/all patients (and many people in the non-schizophrenia population.) Its possible effectiveness in the group setting is especially promising for those in heavily populated areas, where it can be difficult to fine, much less afford, a therapist for long enough to do any work. While there is still much more room for research, and this paper did have a few small methodological flaws, it does present a cogent argument for using CBT in conjunction with antipsychotic medication as a way to help people with schizophrenia to improve.

Click here to view the abstract in PubMed. (Or go to http://www.pubmed.com and do a search on the full title of the study, cited at the beginning of this article)

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