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Computer Tool to Link Mental/Physical Health

"Pathways To Wellness", a unique computer software program designed to address some common physical ailments that afflict the mental illness population, was launched today through a collaborative effort of Eli Lilly and The University of Medicine and Dentistry of New Jersey.

The program is aimed at mental health professionals, and is meant to help facilitate positive changes in lifestyle and behavior that might alleviate common co-occuring physical problems in their clients. Says Betty Vreeland, program manager at the UMDNJ University Behavioral Healthcare Center for Excellence in Psychiatry, "Many individuals living with severe mental illness also have co-occurring physical problems that are frequently misdiagnosed, under- diagnosed, or under-treated. Tragically, this population loses between eight and 20 years of life expectancy when compared to a nonpsychiatric population."

In creating their software, developers polled 300 mental health professionals for their opinions on what are the most common and under-addressed physical health and wellness issues for the psychiatric population. Results of the nationwide survey indicated eight top concerns: diabetes, obesity, substance abuse, tobacco use, hypertension, coronary heart disease, sexually transmitted diseases, and hepatitis B and C.

To address these concerns, the software includes features to collect health and wellness lifestyle information on a client, discussions and concerns to help a client stay on track, graphical displays of a clients health behaviors, risk factors, and progress over time, and a library of educational resources from government sources such as the NIH and the Center for Disease Control.

"The Pathways to Wellness program, developed through an alliance between UMDNJ and Eli Lilly and Company, is a wonderful example of how the public and private sectors can work together to improve patient care, with severe and persistent mental illness," said Dr. Edward Kim, medical director of adult services at UMDNJ University Behavioral HealthCare.

For more information, see the press release 'UMDNJ Partners with Eli Lilly and Company to Launch New Software Program to Help Bridge the Gap Between Physical and Mental Health' (Aug 2, 2004) at Yahoo Financial News (http://biz.yahoo.com/).

Substance Abuse Make Mental Illness More Likely

A recently released government report (from the Substance Abuse and Mental Health Services Administration), shows that adults who had a substance abuse disorder in 2002 were about three times as likely to have a serious mental illness as those who were not substance abusers (20.4% of users, vs. 7% of non-users). Within the substance abuse population, the highest prevalence of mental illness occurred in those who used both drugs and alcohol (30.1%), followed closely by drug abusers (29.1%). Alcohol dependants had a 19% rate of mental illness. Overall, an estimated 4 million adults have both a substance abuse problem and a serious mental disorder.

The report also revealed a serious lack of services to address these co-morbid diagnoses; although 47.9% of adults with both disorders had recieved some kind of treatment, only 11.8% had been treated for both mental health and substance abuse problems.

To view the news release, see "New Study Shows Approximately 4 Million Living with Co-Occurring Mental Illness and Substance Abuse" (July 29, 2004) on the SAMHSA website (http://www.samhsa.gov).

To see the results of the report online, go to http://www.oas.samhsa.gov/.

For research showing that substance abuse raises a person's risk for mental illness and/or psychotic episodes, please see Causes and Prevention on the Schizophrenia.com website. (http://www.schizophrenia.com/prevent2.htm#street).

For resources to help deal with these co-occuring diagnoses, see the Dual Diagnosis Website (http://users.erols.com/ksciacca/)

Sz Risks During Pregnancy

Obstetricians in France have identified four complications during pregnancy that may be linked to the development of psychiatric disorders such as schizophrenia:

1) hormone supplementation by diethylstilbestrol
2) severe maternal malnutrition
3) flu exposure
4) repeated psychological stress

Through analysis of numerous psychiatric studies in literature, obstetricians have determined that the risk of schizophrenia is doubled if the pregnancy involves complications such as the ones listed above. Other complications include maternal diabetes, rhesus incompatibility, bleeding, preeclampsia, premature rupture of the membranes, and premature birth. They noted that the appearance of psychosis in children who had complicated births seems to be earlier in adolescence or in early adulthood.

Scientists presented a two-factor model, suggesting that prenatal or delivery complications that result in a lack of adequate oxygen for the fetus (hypoxic events) could exacerbate a genetic predisposition. Thus, the same prenatal complication that causes cerebral palsy in one child might cause psychosis in another.

The research is published in the European Journal of Obstetrics Gynecology and Reproductive Biology ("Obstetrical complications and subsequent schizophrenia in adolescent and young adult offspring: is there a relationship?" Eur J Obstet Gyn Reprod Biol, 2004:114:2:130-136).

For more information on how pregnancy complications increase the risk for certain psychiatric disorders, and what you can do to reduce your own and your child's risk, see Preventing Schizophrenia via Actions Taken During Pregnancy (http://www.schizophrenia.com/prevent3.htm).

Article: "Study suggests link between obstetrical complications and psychiatric
disease" (Aug 15, 2004)
Source: Health Insurance Law Weekly (NewsRx.net), p. 81.

Beneficial Fats May be Added to Plants

Research has shown many possible health benefits of consuming omega-3 fatty acids, from cardiovascular function to cancer protection to improved mental health. Some studies have even specifically targeted schizophrenia patients, and have found that a diet high in omega-3 may help patients derive more symptom control benefits from medication.

Omega-3 acids are produced naturally in fish oils; however, scientists are now looking at bioengineering certain plants to produce them as well.

Plants make natural precursors for the beneficial fats, but don't produce the long acid chains. UK scientists recently inserted three genes into a mouse ear cress plant, allowing it to convert its precursors into the full chains.

Says PUFA (poly-unsaturated fatty acid) Newsletter ditor Joyce A. Nettleton, "Using biotechnology to produce LC-PUFAs in oilseed crops would greatly expand the availability of these beneficial fatty acids in food and feed for human and animal nutrition. This is extremely promising research."

Especially promising given the PUFA newsletter prediction that the largest global health problems in the year 2020 will be cardiovascular disease, perinatal conditions, and mental illness.

For the full news article, see "Health Promoting Omega-3s May be Produced in Biotech Plants" (July 1, 2004) in Life Science News at Biocompare (http://news.biocompare.com).

For more research on the specific benefits of Omega-3 fatty acids for psychiatric health, see "Other Treatments" on the schizophrenia.com website (http://www.schizophrenia.com/treatments.htm#epa)

For a free subscription to the PUFA newsletter, sponsered by DSM Nutritional Products of the Netherlands, please visit http://www.fatsoflife.com/

Meds May Prevent Violence

A recent homicide case in Cincinnati has once again reminded mental illness advocates and the general public that refusal to take medication is the main cause of violent acts from people with mental illness.

Ohio resident Charles A. McCoy, described as "loving and sweet" by family members, was diagnosed with paranoid schizophrenia. He went through long periods without medication, despite his families best efforts. He is currently charged with killing an 85-year-old friend.

The vicious cycle cited by mental health advocates is a familiar one to most affected families: "The delusions convince the person that there is no illness. Worse, doctors and concerned family members recommending treatment could be seen as part of a plot." Because legal options to enforce treatment compliance for people with poor insight are seldom used or don't exist, this cycle all too often escalates into acts of criminal violence or tragic suicide.

"If we had the appropriate resources to bring to bear on treatment, we probably would be able to prevent some of these tragedies," said the board president of NAMI Ohio.

Ohio, along with 42 other states, actually has legislation that allows for court-mandated treatment compliance without hospitalization for the mentally ill. However, since many people (including judges themselves) aren't aware that this legal option exists, it is rarely brought up in court. Moreover, hot debates over patient and personal rights make many judges hesitant to order compliance if a person does not meet the very narrow definition of "a danger to themselves or others."

National advocacy organizations such as NAMI and the Treatment Advocacy Center are active proponents of such "assisted treatment" options for the mentally ill, largely because of the high percentage of patients that aren't able to recognize their sickness.

For more information, please see "Meds May Prevent Violence" in the Cincinnati Post, July 22, 2004. (http://www.cincypost.com/2004/07/22/mental07-22-2004.html)

For more information on assisted treatment and mental illness legislation in different states, see the Treatment Advocacy Center website (http://www.psychlaws.org) or the "Assisted Treatment" section of schizophrenia.com (http://www.schizophrenia.com/invol.html).

Disease-Management Program in TX for Mental Illness

The state of Texas has recently overhauled its mental health care system for the most severely mentally ill. By legislative order, all state-run clinics will implement a disease-management treatment model, beginning Sept. 1 2004.

Disease-management has been used successfully to treat chronic illnesses such as diabetes, but until now has not been implemented much in the treatment of psychiatric disorders. The model helps patients deal with daily life by "using scientifically proven methods and working with patients outside of clinics," says Janet Heimlich of NPR news, who covered the Texas story on a recent All Things Considered segment.

Sam Shore of the Texas Dept. of Mental Health and Mental Retardation, describes the services provided under a disease-management model. "We do things like build natural support systems, work with the families to be better able to help their family member cope with their mental illness, helping those individuals with mental illness get jobs, get stable housing that is safe and affordable."

Critics of the new mandate point out that only a minority of patients in the health care system will recieve this improved treatment. Due to a shortfall in state funding, the legislature limited state disease-management services for patients diagnosed with schizophrenia, bipolar disorder, or severe clinical depression. This potentially leaves many patients with anxiety disorders, eating disorders, obsessive-compulsive disorder, and less severe depression without services. However, officials are saying that alternatives will be provided for those that don't qualify for disease-management treatment. State services will be required to build adequate transition plans, to direct those not covered under disease-management to quality community health programs outside of the public system. However, such community programs appear to be few and far between, and the question is whether they will be able to adequately handle the new crop of incoming patients so that there is no break in care.

Another problem is that state funding does not even cover all the patients who legitimately qualify for disease-management. Some unfortunate mentally ill patients will keep recieving the bare minimum of care.

However, advocates are optimistic that with efficient implementation of disease-management, the program will eventually save the state money. And then, says Joe Lovelace of the National Alliance for the Mentally Ill, "we can go back and convince the Legislature that they won't be wasting money, that they can then add money...to add on for other illnesses."

Other mental health organizations across the country will be measuring the success of Texas's new plan in the near future.

For the full report, listen to the NPR All Things Considered segment (July 20, 2004). See http://www.npr.org/programs/atc/ for the audio file.

For more information about the future of disease management in the treatment of schizophrenia, see a pdf file report published by the National Pharmaceutical Council (available at their website: http://www.npcnow.org/resources/disease/mental.asp)

To read more about the Texas Resiliency and Disease Management program for Mental Health, see the Texas Dept. of Mental Health and Mental Retardation website (http://www.mhmr.state.tx.us). Search for "resiliency and disease management."

Brain Disease Film Wins NAMI Award

The documentary film "People Say I'm Crazy" won the NAMI Outstanding Media Award for best television documentary of 2004. It will be aired on Cinemax at 7pm, August 18. Director John Cadigan, diagnosed with schizophrenia, and producers Katie Cadigan and Ira Wohl jointly accept the honor.

The video-diary talks about director Cadigan's own experiences with schizophrenia, from the onset during his college years to the present day. According to NAMI, it is the first major film directed by someone with schizophrenia.

"People Say I'm Crazy is an extremely important and moving film," said NAMI national board president Margaret Stout. "It will touch millions of people, welcoming them into the mind of a talented artist with a severe mental illness and the love of a family who have stood by him."

The NAMI media awards recognize works that raise awareness, tolerance, and compassion for mental illness issues.

To read the article, see "Cinemax Reel Life 'People Say I'm Crazy' Wins NAMI Award" (Aug 4, 2004), available at http://www.biz.yahoo.com

To visit John Cadigan's website, which has information about his illness, his film, and his artwork, please see http://www.peoplesayimcrazy.com/

Listen to an interview with John and Katie Cadigan about the documentary, aired on WNYC radio (April 26, 2004). Real media file.

Risperdal increases warnings

Janssen Pharmaceutica Products, the maker of the atypical anti-psychotic Risperdal (risperidone), is revising its warnings after FDA claims that the company downplayed potential safety risks.

Although Janssen updated their warning labels in 2003 after a general FDA request to several drug companies, FDA officials maintained that Risperdal labels and promotional material did not accurately portray the risk of strokes, diabetes, and other complications for healthcare consumers. The company also allegedly made claims that their drug was safer than other available anti-psychotics.

In answer, the company recently released a two-page report to health care professionals, re-stating the potential risks for patients taking Risperdal.

In a federal lawsuit earlier this month, a doctor fingered the Janssen company in his general charge that children have been harmed and even killed by drugs that are inappropriately or over-aggresively marketed by pharmaceutical manufacturers.

For the full news story, see "Maker of Schizophrenia Medicine Clarifies Risks" (July 25, 2004) in the Washington Post (http://www.washingtonpost.com/)

For more information on the medication Risperdal and its potential side effects, see the Medications section (Risperdal) on the schizophrenia.com website (http://www.schizophrenia.com/meds.html#risperdal).

Genome affects disease in new ways

Human genome cracked? Not quite.

Scientists in Europe recently launched the "human epigenome project." Epigenome refers to a "hidden" genetic code, not the one that contains information for building protein molecules, but the one that determines when those genes are turned on or off. The epigenetic code is now being implicated as a probable cause for numerous disease, schizophrenia among them.

For example, in a recent twin study, one brother is healthy while the other is diagnosed with schizophrenia. Because they are identical twins, they should have exactly the same genetic code. Well, almost. The surface genomes - the one detectable with standard genetic tests that scan for mutations - were identical. However, the healthy brother had numerous "molecular silencers," molecules that block the genes responsible for making the neurotransmitter dopamine. The brother with schizophrenia had almost none; thus, his dopamine genes were producing much higher levels of neurotransmitter than his brother's.

"Silencer" molecules, that control when a gene is turned on or off, are the products of the epigenome.

Measured by his epigenome, not his genome, the schizophrenic brother appeared more closely related to other schizophrenia patients than to his own twin brother. They also were missing the dopamine silencers.

Epigenetic changes may be behind other diseases as well. For example, the body normally contains tumor-supressing genes that prevent rogue cancer cell growth. However, some patients develop tumors even when these genes contain no mutation. In these cases, it looks like the genes are being silenced at inappropriate times by epigenetic changes. A reverse situation can also happen; sometimes genes can be abnormally turned on by epigenetics, causing uncontrollable cell growth and the appearance of a tumor.

"Epigenetic changes are more clearly associated with the progression of tumors than mutations are," says Dr. Andrew Feinberg, a researcher at Johns Hopkins School of Medicine. "Epigenetics may be as important in certain conditions as the DNA sequence is in other cases."

It also appears that gene silencers normally present in the body begin to disappear with age, providing a possible explanation for why older people are more likely to develop chronic diseases.

To read the full news article, see "How a Second, Secret Genetic Code Turns Genes On and Off" (July 23, 2004) in the Wall Street Journal, p. A9.

To read more about epigenetics and Dr. Feinberg's research at Johns Hopkins, see "The Mystery of Epigenetics" in the Winter 2004 edition of Hopkins Medicine online magazine (http://www.hopkinsmedicine.org/hmn/W04/medrounds.cfm#9)

New Research to Improve Sz Cognition

Acadia Pharmaceutical recently published a research study showing that the compound ACP-104 (N-desmethylclozapine) is similar in its chemical action to the drug clozapine (trade name Clorazil), the only anti-psychotic that partially improves cognition in schizophrenia patients.

ACP-104 (the principal metabolite of clozapine) acts on m1 muscarinic receptors in the brain that affect cognitive abilities. Based on the mechanism of action of the metabolite, researchers hypothesize that it might be responsible for the cognitive benefits of clozapine. The research notes that only ACP-104, not clozapine itself, is responsible for stimulating the muscarinic receptors. They are looking at possibly developing the metabolite compound into a new therapy for schizophrenia.

"By directly administering ACP-104, thereby avoiding the highly variable step of having it metabolized in the body from clozapine, we hope to offer an improved therapy that provides a more consistent cognitive benefit to patients," says Dr. Mark Brann, President and Chief Scientific Officer of Acadia Pharmaceuticals.

The research also included drug blood level analysis of 92 schizophrenia patients taking clozapine. Results noted that patients with higher levels of ACP-104 metabolite (relative to clozapine) in their blood performed better on cognitive performance tests.

For more information, see the following press release: 'Acadia Study Links ACP-104 to Improved Cognition in Schizophrenia Patients' (Aug 3, 2004) from PR Newswire (www.prnewswire.com).

To read the published research abstract, see 'The Role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine' (Psychopharmacology, 2004 Jul 16) at Pubmed (www.pubmed.org).

For more information about the drug clozapine, see the Medications section on the schizophrenia.com website (http://www.schizophrenia.com/meds.html#clorazil).

Sz Gene Defect in Mice

There's a new face in schizophrenia research - assistant professor Jeffrey Eells at the MSU College of Veterinary Medicine recently received $55,000 from NARSAD. He is studying a particular strain of mice that show a gene mutation similar to one seen in humans with schizophrenia.

Mice don't generally share their psychotic symptoms, so Eells is using other techniques to determine the mutant gene's effect. Specifically, he looks at an altered "prepulse inhibition" that is similar to what is observed in schizophrenia patients. "Prepulse Inhibition" is seen when a mild sensory event (the prepulse) is presented a short time interval before a strong, startle-inducing stimulus (such as a loud noise). In normal subjects, once these two events are reliably paired through conditioning, the prepulse will blunt the startle response to the stronger stimuli because the subject is expecting it. An altered prepulse inhibition is present in subjects that do not have reduced startle following the prepulse. In schizophrenia patients, this has been interpreted as indicating a deficit in the early sensory processing networks in the brain.

Eells is also looking at how the gene mutation affects the animals' dopamine system.

“Nobody really knows what causes schizophrenia -- it’s likely that there are a number of different causes that can result in the symptoms of schizophrenia,” Eells said. “This gene mutation may be one of a number of causes or predisposing factors that could signal schizophrenia. The hope is that it will lead to a better understanding of the mechanisms of the disorder and potentially to other avenues of treating schizophrenia.”

According to Associate Dean for Research Jerald Ainsworth, this may be the first time taht anyone at MSU has secured a grant from the NARSAD foundation.

For the full news article, see "Veterinary researcher studies schizophrenia" (July 29, 2004) in the Mississippi State University Office of Agricultural Communications (http://msucares.com/news/print/cvm/cvm04/040729.html).

For more research on altered prepulse inhibition in schizophrenia populations, see the following pubmed abstracts (or do a search on "prepulse inhibition" and schizophrenia at www.pubmed.org):

1. The influence of schizotypy traits on prepulse inhibition in young healthy controls (J Psychopharmacol 2004:18(2):181-88).

2. Preattentional and attentional cognitive deficits as targets for treating schizophrenia. (Psychopharmacology (Berl) 2004:174(1):75-85).

3. Genetic influences on prepulse inhibition of startle reflex in humans. (Neurosci Lett. 2003:15:353(1):45-48).

Salvia Raises Risk of Sz, Other Illnesses

It's not just illegal drugs like marijuana that can raise a person's risk of developing a psychotic disorder such as schizophrenia. Salvia, a natural hallucinogen historically used in the Mazatec indian culture in Mexico, is legally available in the United States as dried leaves or an extract that can be smoked or ingested. However, according to Rusty Payne, a public affairs official with the Washington Bureau of the DEA, salvia and other uncontrolled substances like it are currently under investigation by the scientific and health community. "Just because a drug has not been classified doesn't mean it's healthy or safe. There are legal drugs of concern and salvia is one of them," Payne said.

John Halpern, an associate director of substance abuse research at Mclean Hospital, described the drug as psychoactive, but not physiologically addictive. However, although it doesn't appear to be directlyu toxic to the brain, Halpern cautions that salvia use by young people in their teens and twenties could raise their risk of developing schizophrenia or other severe diseases. Moreover, like anything that is smoked, salvia damages the throat and lungs. At high doses it may induce unconsciousness and memory loss. The drug may also cause high blood pressure or strokes if it is mixed with certain other chemicals, an example of which is antidepressants.

The fact that salvia is unregulated makes it even more unsafe to use. Buyers can never be sure exactly what is in the substance they use, as there are no purification or health regulations.

"There's a false sense of security that if it's legal it must be safe," says Robert Harris, a pharmacist with the Cayuga Medical Center. "That's cause for concern."

As of now, only St. Peters, MO has a local city law that regulates the sale of salvia to people over 17. Salvia remains unregulated anywhere at the state or local level in the United States, although it has been banned in Australia since 2002.

For the full article, please see "Salvia Sparks Curiosity" (July 31, 2004) in the Ithaca Journal (http://www.theithacahournal.com).

For more information about salvia and the health concerns associated with it, see the following:

"A New LSD? Mexican Herb For Sale Online Comes with Divine Claims, Warnings." ABC News, April 1 2004.

Information Bulletin: Salvia divinorum - a factsheet published in April, 2003 by the National Drug Intelligence Center. (http://www.usdoj.gov/ndic/pubs3/3842/)

For more research that implicates substance abuse as a risk factor for schizophrenia and severe mental illness, see the Causes and Prevention section of the schizophrenia.com website (http://www.schizophrenia.com/prevent2.htm#street).

Impact of multiple-family groups for outpatients with schizophrenia on caregivers' distress and resources.

Hazel NA, McDonell MG, Short RA, Berry CM, Voss WD, Rodgers ML, Dyck DG.
Psychiatric Services. 2004 Jan;55(1):35-41.

Family-member caregivers of people with schizophrenia can have substantial demands placed on their personal, financial, social, and/or emotional resources. Multiple-family group family treatment integrates elements of psychoeducation and behavioral family therapy in a group format with two clinicians and six to eight families. This approach provides information and problem-solving experiences to family members and consumers. The treatment begins with a three-session joining phase, where the clinician’s goal is to develop a solid alliance with the family and consumer, gain information about history, impact of illness and resources available for managing it. Next there is a one-day psychoeducational workshop, followed by one year of bimonthly group sessions focusing on relapse prevention. Finally, there is a year of monthly group sessions that focus on social and career rehabilitation.

Research suggests that multiple-family group treatment has a positive effect on consumers' negative symptoms, use of inpatient and outpatient services and relapse. But, the literature is inconclusive about this treatment’s effect on caregivers' well-being. As a result, this study reexamined the impact of multiple-family group treatment on caregivers' outcomes by focusing more specifically on caregivers' distress. They found that over the two-year course of the intervention, caregivers of persons who received multiple-family group treatment experienced greater reductions in distress when compared to caregivers of consumers who received standard psychiatric care.

They also found that contrary to what they expected, there were no significant differences between the multiple-family and standard treatment groups, with respect to increases in caregivers' resources. This could have been because of statistical reasons (low power because people dropped out) or the measures used to assess resources. Also, there is question about whether the baseline for the groups was different to begin with. It is also possible that multiple-family group treatment simply does not have an effect on psychosocial resources of caregivers.

This study suggests that modifications to multiple-family group intervention may be necessary to positively affect the resources of family caregivers. This could include breakout groups designed to address assessment and improvement of caregivers' resources. Also, further research is needed to see whether multiple-family group treatment can also affect caregivers' physical and psychological health, as well as to determine the mechanisms by which this treatment helps caregivers. Nevertheless it is encouraging to see research on more family driven treatments that focus on both the consumer and the caregiver.

This study was supported by grant R01-52259 from the National Institute of Mental Health

Find abstract: 'Impact of multiple-family groups for outpatients with schizophrenia on caregivers' distress and resources' at http://www.pubmed.org

Placebo-Controlled Evaluation of Four Novel Compoundsfor the Treatment of Schizophrenia and Schizoaffective Disorder

Meltzer HY, et al., Placebo-Controlled Evaluation of Four Novel Compoundsfor the Treatment of Schizophrenia and Schizoaffective Disorder. Am J Psychiatry 2004; 161:975–984.

This article is about a trial of 4 new types of antipsychotic medications at the beginning of their testing on people with schizophrenia. As the mechanism of schizophrenia is only partially understood, there is still room to discover new activities in the brain that may contribute to the symptoms that are visible on the outside. Traditionally, antipsychotic medications have focused on the neurotransmitter dopamine which is a chemical in the brain that when too abundant in particular areas can cause hallucinations, delusions and other symptoms. Newer antipsychotics have become more focused in certain dopamine receptors and have also targeted other neurotransmitters receptor sites in order to help minimize side effects. The medications in this study all target new receptors in the brain and work in ways significantly differently than the medications currently on the market. Each of these receptors are like keyholes in which a molecule called a neurotransmitter is the key that helps turn on or turn off various activity in brain cells. They naturally exist in the brain for various purposes but can be altered in schizophrenia and therefore may be targets for new medications. Of the 4 medications in this trial, one targets a cannabinoid receptor, another works on a specific type of serotonin receptor, another works at a neurokinin receptor and the last works as a blocker of the neurotensin receptor.

To study these medications, the authors of the study compared these new compounds to haloperidol (Haldol ®) and to a sugar pill or placebo. Ultimately, 2 of the medicines (the one that worked on the neurokinin receptor and the serotonin receptor drug) worked as well as haloperidol in certain aspects and will warrant further study. Neither drug worked better than Haldol though each may ultimately have subtle benefits that might make them more useful in particular patients. Also, they may have fewer side effects than Haldol, however longer term studies will need to be done in order better estimate side effect profiles. It is encouraging that in this study, none of the drugs studied had any more side effects than placebo.

This study is encouraging because it shows that there are new molecules being tested to treat schizophrenia. While none of these are a magic bullet, two of the four medicines will be further studied and may make contributions to the armamentarium we have to treat schizophrenia. Despite these advances, much more testing will be needed on these medications, both in terms of safety and effectiveness, before they will be ready to come to market.

This trial was sponsored by Sanofi-Synthelabo Research which developed each of these medicines.

Find abstract: 'Placebo-Controlled Evaluation of Four Novel Compoundsfor the Treatment of Schizophrenia and Schizoaffective Disorder' at http://www.pubmed.org

Valproate as an adjunct to antipsychotics for schizophrenia: a systematic review of randomized trials

Valproate as an adjunct to antipsychotics for schizophrenia: a systematic review of randomized trials.
Basan A, Kissling W, Leucht S. Schizophr Res. 2004 Sep 1;70(1):33-7.

This article takes a systematic look at the literature regarding the efficacy of using valproic acid (Depakote) as an adjunctive (additional to an antipsychotic) medication for schizophrenia. This medicine is a mood stabilizer and is typically a first line drug for treating bipolar disorder. However, it has properties that may make it useful in people with schizophrenia. It targets a neurotransmitter (chemical in the brain that turns on or off neurons or brain cells) called GABA which is a neurotransmitter that typically has a turning-off effect on brain cells. Some of these cells are involved in the production of dopamine which is a neurotransmitter that is associated, when in too high of a level, with the positive symptoms of schizophrenia (hallucinations, delusions, paranoia, bizarre thinking) and when in too little concentration, with the movement side effects seen with certain medications, like haloperidol/Haldol.

These authors searched the literature and came up with several articles that seemed relevant. Upon applying certain standards, five articles met the eligibility requirement to be included in the review and meta-analysis. (A meta-analysis is where the data from several studies are compiled together and analyzed as a group.) The results presented in this paper are equivocal at best. There are upsides and downsides to polypharmacy (the use of more than one medication to treat a particular condition.) On the one hand, the more meds you have someone take, the greater risk there is for side effects and drug interactions. Valproic acid has problems with weight gain and liver toxicity and that is true with other antipsychotics which can make for a problem. However, there is some minor evidence that valproic acid may help speed up the initial recovery of someone when starting or restarting them on antipsychotic medication. That can be useful if they only have a short time in the hospital and cannot afford to wait the couple of weeks to get full effect by the antipsychotic alone. However, the benefit wears out and was gone by the end of the study that showed this benefit, so it is unclear whether it means that the valproic acid should be continued or stopped after the acute situation resolves. Small trials have suggested that there may be a general decrease in negative symptoms (flat affect, constricted emotions, low energy, low motivation, poor hygiene) that is sometimes the most debilitating aspect of schizophrenia for many people. It does seem though, that valproic acid is useful in the case of schizoaffective disorder when there is a need for mood stability. It also seems to have a place for the aggressive or violent patient who has frequent outbursts and can benefit from some stabilization of their mood.

Overall, should you ask the doctor to start valproic acid for you or your loved one? Well, if they are already stable on medication, it is not something that they need to have. If they aren’t doing well, it might be worth a try to add it if there are no strong reasons to stay away from it (poor liver function, pregnancy or intent to become pregnant or history of weight gain or nonresponse to valproic acid.) The data currently is inconclusive to the benefit for valproic acid augmentation and therefore it is not possible to give a blanket recommendation one way or the other. However, if things are not working, it might be worth a try if it hasn’t been tried in the past.

Find abstract: 'Valproate as an adjunct to antipsychotics for schizophrenia: a systematic review of randomized trials' at http://www.pubmed.org

Medical decision making in antipsychotic drug choice for schizophrenia

Medical decision making in antipsychotic drug choice for schizophrenia.
Hamann J, Langer B, Leucht S, Busch R, Kissling W
Am J Psychiatry. 2004 Jul;161(7):1301-4.

This article seeks to discern what factors are associated with prescribing patterns amongst physicians in the community. The authors looked at practices in Germany; 50 hospital based and 50 private practice psychiatrists. They conducted survey and followed prescriptions patterns with these doctors to see what their attitudes were towards newer versus older medications and other important treatment decisions. The groups differed in a couple of important ways. The hospital based psychiatrists were on the average 10 years younger and had been in practice less time, though were closer to their training.

The authors report that older patients, patients with more severe positive symptoms (hallucinations, delusions, paranoia, bizarre thinking), and those with a longer duration of illness were more likely to receive the first generation antipsychotics (i.e. haloperidol/Haldol, fluphenazine/Prolixin, etc.) versus the second generation antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, clozapine, aripiprazole.) However, people who requested newer medications or who had a history of a bad reaction with particular med were more likely to receive the newer medications. However, the only statistically significant predictor of receiving an older medication was the age of the physician (by up to 5 fold.) The other factors were important, but did not meet statistical significance. However, there were a small number of physicians polled and a small number of prescriptions written for older antipsychotics regardless of any factor.

While older physicians were more likely to use older drugs, that may be a factor of their being more used to them than the younger doctors. This may not always be a bad thing, new drugs are expensive and not always more effective or with fewer side effects than older meds, however it just brings to light the importance of advocacy for yourself or your loved one when a physician suggests a treatment. Advocacy on your own behalf for a newer medication may make the difference between trying an older one first or just going to the newer medicine right away. This decision is not always totally the doctor’s decision, but when funding is not an impediment to drug choice, appropriate assertiveness by patients and families can help influence the ultimate choice in treatment.

This work was funded by unrestricted grants from Sanofi Synthelabo, Germany, and Astra Zeneca, Germany.

Find abstract: 'Medical decision making in antipsychotic drug choice for schizophrenia' on http://www.pubmed.org