Showing posts with label pharmaceuticals. Show all posts
Showing posts with label pharmaceuticals. Show all posts

Thursday, July 1, 2010

Class action settlement in drug for schizophrenia


An article published in the June 30th edition of The Toronto Star:
Some users of antipsychotic drug say they were not warned of risk of diabetes

By Theresa Boyle, Health Reporter

Canadian courts have approved a $17.6 million settlement in a class-action lawsuit launched by individuals who became diabetic after taking an antipsychotic drug.

The settlement with Eli Lilly, manufacturer of Zyprexa, was announced Wednesday. It stems from allegations that the drug giant failed to warn about risks of severe weight gain, diabetes, hyperglycemia and pancreatitis.

Zyprexa is used for treatment of schizophrenia and bipolar disorder.

Eli Lilly denies any wrongdoing and the allegations have not been proved in court.

“While we believe the allegations are without merit, Lilly is taking this difficult step because we believe it is in the best interest of the company as well as the Canadian health care professionals who depend on this important medication,” John Rudolph, legal counsel for Eli Lilly, said in a written statement.

The drug continues to be used, but changes have since been made to its label to include warnings of diabetes.

The class action was filed on behalf of 11 people from Ontario, British Columbia and Quebec and approved by the superior courts of those provinces.

“We acknowledge that Eli Lilly has done the right thing,” said Harvin Pitch, counsel for Stevensons LLP, which represented some of the plaintiffs. “We encourage all users of Zyprexa who qualify to apply for their benefits.”

To receive a settlement payment, an individual must have started taking the drug prior to June 6, 2007 and then been diagnosed with diabetes, hyperglycemia, ketoacidosis or pancreatitis. The size of each payment will depend upon severity of illness and the total number of approved claims.

The settlement was based on an estimate that there would be 1,450 claims, though it is possible that the actual number may be higher, Pitch said.

The total number of prescriptions filled in 2009 in Canadian retail pharmacies for Zyprexa and its generic equivalents was 2,493,081. It is the third most prescribed antipsychotic on the Canadian market.

Further information is available at classaction.ca, from lawyer Daniel McConville at Stevensons LLP: (866) 940-8329, or from lawyer Matthew Baer at Siskinds LLP: (800) 461-6166 x 7782.

Note:

The claims deadline is October 28th, 2010.

Also see:

Notice of Settlement Approval (long version) [PDF Document]

Claim form [PDF Document]

Press Release – June 30, 2010 [PDF Document]

Wednesday, May 26, 2010

A national settlement has been proposed in the Zyprexa class action




Please click on the images to magnify them.

To view a high resolution version of the second document, please click here.


Also see:

ZYPREXA (OLANZAPINE) CLASS ACTION: NOTICE OF SETTLEMENT APPROVAL HEARING


From Poyner Baxter LLP:
Zyprexa

May 21, 2010

A national settlement has been proposed in the Zyprexa class action. This settlement cannot proceed until it has received court approval. The dates scheduled for the court settlement approval hearings are June 8, 2010 in Ontario, June 14, 2010 in Quebec and June 15, 2010 in British Columbia.

IF YOU OR SOMEONE CLOSE TO YOU TOOK ZYPREXA (OLANZAPINE) PRIOR TO JUNE 6, 2007, PLEASE CLICK HERE TO READ THIS NOTICE CAREFULLY AS IT MAY AFFECT YOUR LEGAL RIGHTS AND YOU MAY BE ELIGIBLE FOR COMPENSATION.

To view the full legal notice, click here.

To view the proposed settlement agreement, click here.

A further notice will be published once the settlement has been approved by the courts which will explain how individuals can make a claim.

For further information email classaction@poynerbaxter.com or phone 604 988-6321.

This Web site is offered for information only and is not legal advice. Use of the site and sending or receiving information through it does not establish an attorney-client relationship. No one should act, or refrain from acting, based solely upon this information without seeking appropriate legal or other professional advice. In particular, you should obtain advice about limitation periods as it may affect your right to bring a legal action on your own behalf. Links to and from from this Web site do not state or imply a relationship between Poyner Baxter LLP and the linked entity.


From Siskinds LLP:
UPDATE (May 21, 2010): We are pleased to announce that a settlement has been reached in this action:
The next step is to have the settlement approved by the courts. Settlement approval hearings have been scheduled for Ontario on June 8 , 2010, Quebec on June 14, 2010, and British Columbia on June 15, 2010.
Once the settlement has been approved by each of the courts, a further notice will be published which will explain the steps for making a claim.

Friday, December 11, 2009

Phase III Study Demonstrates INVEGA® SUSTENNA(TM) Statistically Similar to RISPERDAL® CONSTA® Long-Acting Injection


A December 10th news release from PR Newswire:
TITUSVILLE, N.J., Dec. 10 /PRNewswire/ -- Treatment with once-monthly INVEGA® SUSTENNA(TM) is not inferior to treatment with bi-weekly RISPERDAL® CONSTA®, according to new data from a comparative study of both treatments in patients with schizophrenia. Results of the 13-week clinical trial were released this week.

To read the entire news release, please click here

Friday, July 31, 2009

Schering-Plough Wins Panel’s Backing on Antipsychotic (Update 2)


An article posted on July 30th by Bloomburg.com:
By Catherine Larkin

Schering-Plough Corp. won a U.S. panel’s backing to introduce a new antipsychotic drug that would compete with Eli Lilly & Co.’s Zyprexa and AstraZeneca Plc’s Seroquel.

Outside advisers to the Food and Drug Administration voted 9-1, with two abstentions, that the drug’s benefits outweighed its risks for adults with schizophrenia, and 12-0 in favor of its use in treating manic or mixed episodes of bipolar disorder. The FDA usually follows the recommendations of its advisers, though it isn’t required to do so.

Asenapine [molecular structure shown], a fast-acting tablet that dissolves under the tongue, would help patients who can’t swallow pills or have side effects such as weight gain on other treatments, the advisers said. Merck & Co. offered to buy Schering-Plough on March 9 to get asenapine, to be marketed as Saphris, and six other drugs targeted for sale by 2012.

“We believe that the opportunity for Saphris is underappreciated, as we think an antipsychotic with little to no weight gain and no cardiovascular safety issues is a lay-up blockbuster,” Jon LeCroy, an analyst at Natixis Bleichroeder in New York, said today in a note to clients. “We are modeling 2013 sales of $650 million.”

Positive Expectations

Investors anticipated a positive recommendation from the advisory panel meeting in Silver Spring, Maryland, after FDA staff voiced their support for Schering-Plough’s data in briefing documents released this week. The agency delayed asenapine last year and is now scheduled to make a decision on approval by Aug. 20.

To read the complete article, please click here.

Also see:

FDA Approves Saphris to Treat Schizophrenia and Bipolar Disorder (August 14th, 2009)

Monday, July 13, 2009

11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study)


An article published online today by The Lancet:

By Jari Tiihonen, Jouko Lönnqvist, Kristian Wahlbeck, Timo Klaukka, Leo Niskanen, Antti Tanskanen, and Jari Haukka

Background
The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.

Methods
Nationwide registers in Finland were used to compare the cause-specific mortality in 66,881 patients versus the total population (5.2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.

Findings
Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22·5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1·41, 95% CI 1·09–1·82), and the lowest risk for clozapine (0·74, 0·60–0·91; p=0·0045 for the difference between clozapine vs perphenazine, and p<0·0001 for all other antipsychotic drugs). Long-term cumulative exposure (7–11 years) to any antipsychotic treatment was associated with lower mortality than was no drug use (0·81, 0·77–0·84). In patients with one or more filled prescription for an antipsychotic drug, an inverse relation between mortality and duration of cumulative use was noted (HR for trend per exposure year 0·991; 0·985–0·997).

Interpretation
Long-term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use. Second-generation drugs are a highly heterogeneous group, and clozapine seems to be associated with a substantially lower mortality than any other antipsychotics. Restrictions on the use of clozapine should be reassessed.

Funding
Annual EVO Financing (Special government subsidies from the Ministry of Health and Welfare, Finland).

To download the entire article, please click here (PDF).

Posting of this abstract is for the purposes of research into schizophrenia.

Monday, June 1, 2009

APA meeting 2009: new schizophrenia products and depot formulations


An article posted on May 31st by PipelineReview.com:
The annual meeting of the American Psychiatric Association is the year's largest psychiatry event. This year's conference in San Francisco indicated that long-acting depot versions of atypical antipsychotics continue to prove useful tools in the treatment of schizophrenia. In addition, new potential market entrants reported mixed data from new oral antipsychotics.

Although the majority of antipsychotics are now broadly used across most psychiatric conditions, the schizophrenia market continues to attract attention from developers of both novel antipsychotics and new formulations aimed at addressing the major unmet need of compliance.

The long-dosing regimen and intramuscular administration of long-acting injectable depot formulations of atypical antipsychotics results in a greater transparency of compliance. Eli Lilly presented new data for Zypadhera (olanzapine long-acting injection), as it continues to seek US approval and enter the market that Johnson & Johnson (J&J) has pioneered through Risperdal Consta (risperidone long-acting injection).

Data from new oral atypical antipsychotics were also presented. Vanda followed up the recent surprise approval of oral Fanapt (iloperidone) by presenting two posters detailing comparative data. Dainippon Sumitomo, meanwhile, provided delegates the first chance to see Phase III data for lurasidone.
To read the entire article, please click here.

Also see:

Newer Treatments for Schizophrenia: Benefits and Drawbacks

Schering asks EU to approve schizophrenia drug


Saturday, May 23, 2009

Novel Antipsychotic Promising for Schizophrenia


An article posted May 22nd on MedPage Today:
By Crystal Phend, Staff Writer

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

SAN FRANCISCO, May 22 -- The experimental psychotropic agent lurasidone [molecular structure shown] appeared effective in acute schizophrenia, according to the first phase III data on the drug.

The intermediate 80-mg dose of the novel compound significantly improved total scores on the Positive and Negative Syndrome Scale (PANSS) by about eight points more than placebo over six weeks of treatment in the randomized controlled trial.

However, the 40- and 120-mg per day doses did not appear better than placebo for either the primary or secondary endpoints in the trial, Antony Loebel, Ph.D., of Dainippon Sumitomo Pharma America in Fort Lee, N.J., and colleagues found.

All doses appeared to be well tolerated with little impact on weight and lipids, they reported here at the American Psychiatric Association meeting.

Lurasidone is part of the pipeline of psychotropics that have been called the "me-too" medications. It has high affinity for dopamine (D2) and serotonin 5-HT2A receptors.

But Dr. Loebel highlighted its uniqueness among psychotropics in affinity for serotonin receptors implicated in the enhancement of cognition, mood, and negative symptoms (5-HT7, 5-HT1A and alpha-2c).

He also noted that the compound's low attraction to noradrenaline alpha-1, histamine H1, and cholinergic M1 receptors may minimize weight gain and other problems seen with psychotropics currently on the market.

Action Points
  • Explain to interested patients that lurasidone is not FDA approved for any indication.
  • Note that this study was published as an abstract and presented as a poster at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
To read the entire article, please click here.

Thursday, January 15, 2009

Clozaril® (clozapine)


For Nova Scotia Residents Only

To the very best of my knowledge and effective today, many individuals currently taking Clozaril® (clozapine) produced by Novartis Canada Inc. will be switched to a generic version of Clozaril® called Gen-Clozapine produced by Genpharm. Again, to the very best of my knowledge, this only applies to all individuals receiving income assistance form the Nova Scotia Department of Community Services or enrolled in the Nova Scotia Family Pharmacare Program and currently taking Clozaril®. Blood monitoring will now be conducted by a program called GenCAN instead of Novartis’ CSAN® program. A patient’s prior blood work information will be transferred, and from what I understand without the individual’s permission, from the CSAN® program (Novartis) to the GenCAN program (Genpharm).

If you have any questions or concerns about the above, please feel free to contact the Schizophrenia Society of Nova Scotia.

Also see:

Evaluation of an interchangeability switch in patients treated with clozapine: A retrospective review.

Generic clozapine: a cost-saving alternative to brand name clozapine?

Branded versus generic clozapine: bioavailability comparison and interchangeability issues.

Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis.


Clozaril® graphic courtesy of Novartis.

Friday, January 2, 2009

Eric Kandel on the Year in Neuroscience


An article posted by The Dana Foundation on December 29th:
What were the most significant neuroscience discoveries of 2008? Eric Kandel, a professor of biochemistry and biophysics at Columbia University, weighed in on the topic at an event at the Dana Center in Washington, D.C., in November. Kandel was a co-recipient of the 2000 Nobel Prize in Physiology or Medicine for his work on the physiological basis of memory. Here is an edited transcript of his remarks during a reception for members and guests of the Dana Alliance for Brain Initiatives.
To read the entire article, click here.

I thank David Whitehorn for bringing this article to my attention.

Monday, December 1, 2008

New drug for schizophrenia offers relief from weight gain


Posted on December 1st by 3news.co.nz:
An alternative antipsychotic drug which causes less weight gain than older treatments has been funded for those with schizophrenic disorders by New Zealand’s drug buying agency Pharmac.

Patients would be able to get the drug, amisulpride (Solian) [molecular structure illustrated], from today, which has been funded without restrictions.

Pharmac’s medical director Peter Moodie said increasing the range of treatments [for schizophrenia] had benefits for a condition that was difficult to treat.

"Over recent years some of the older antipsychotic treatments have been discontinued and so increasing the choice of medicines is an advantage," he said.

He also confirmed amisulpride was less likely to cause weight gain than other antipsychotics.

The agreement also saw injection and suppository formulations of the antinausea treatment prochlorperazine (Stemetil) becoming fully funded.

Antipsychotic drugs cost Pharmac more than $60 million a year, one of the agency’s highest expenditure groups.

Tuesday, September 16, 2008

Rethinking Schizophrenia

From the September 15th edition of Chemical and Engineering News (C&EN):
Advances could spur treatments for more symptoms than current drugs address

By Carmen Drahl

WHEN ACCOUNTS of schizophrenia began to emerge in the 1800s, institutionalization was the most common treatment for patients suffering from the disease. Despite significant advances in therapy, many of today's patients still find fitting into society a big challenge. Although iconoclastic 1960s psychiatrist Ronald D. Laing once wrote "Schizophrenia cannot be understood without understanding despair," the prevailing sentiment at last month's American Chemical Society national meeting in Philadelphia was one of hope. Researchers have learned more about the pathways that underpin schizophrenia, and those advances have led to drugs in clinical trials that reflect new approaches to treating the disease.

Session organizer John E. Macor, executive director of neuroscience discovery chemistry at Bristol-Myers Squibb (BMS), in Wallingford, Conn., told C&EN that existing medications for schizophrenia, known as antipsychotics, do not remedy all of the disease's symptoms. Speakers at the Division of Medicinal Chemistry-sponsored symposium advocated moving beyond established drugs, which are all aimed at dopamine neurotransmission. They argued that focusing on new targets, such as the glutamate neurotransmitter system, a nicotinic acetylcholine receptor, or a signaling pathway mediated by cyclic nucleotides, might tackle a wider range of symptoms.

In her stage-setting overview for the session, Judith A. Siuciak, principal scientist for neuroscience biology at BMS, characterized schizophrenia by what she described as positive, negative, and cognitive symptoms. Commonly prescribed drugs ease positive symptoms, which include hallucinations and disorganized speech. However, she said, the drugs are less effective at eliminating negative symptoms, such as lack of motivation and inability to experience pleasure, and cognitive symptoms, which include impairments to memory and decision-making.

"The medications that we have are only partially effective," concurs Robert K. Heinssen, deputy director of the National Institute of Mental Health's (NIMH's) Division of Services & Intervention Research, who did not attend the symposium but spoke with C&EN beforehand. What's more, he adds, not all patients respond equally well to the drugs. Even with medication, schizophrenia sufferers can be withdrawn and have trouble processing information, so "these patients are overwhelmed by the competing demands of our environment," he says.
Bold emphasis within the article is mine. To read the entire article, click here.


Selective Drug Pfizer's drug candidate for schizophrenia (stick model) blocks a specific phosphodiesterase enzyme. Protein surfaces contacting the drug are shown in a space-filling format. Amino acids and a water molecule that make contact with the drug are shown in ball-and-stick form.

Image courtesy of Eric Marr, Jayvardhan Pandit & Xinjun Hou/Pfizer.



New drug candidates for the treatment of schizophrenia.
Click on the image to enlarge it.


Sunday, June 8, 2008

Schizophrenia therapy: beyond atypical antipsychotics

From Nature Reviews Drug Discovery 7, 471-472 (June 2008) | doi:10.1038/nrd2571:
By Eric M. Snyder & Melanie R. Murphy

Antipsychotics remain the current standard of care for mental disorders including schizophrenia (1% prevalence) and bipolar mania (3% prevalence), and generate over US$16 billion worldwide in annual sales (Fig. 1; Table 1). However, a large trial known as CATIE, sponsored by the US National Institutes of Health, found that 74% of patients discontinue use within 18 months of therapy due to either poor tolerability or incomplete efficacy (1), indicating a need for novel therapies.


Figure 1. The schizophrenia drug market has grown from less than $1 billion annually in 1993 to more than $10 billion. This rapid growth has followed the introduction of Risperdal in 1993, followed by Zyprexa, Seroquel, Geodon [Zeldox in Canada] (ziprasidone; Pfizer) and Abilify (aripiprazole; Bristol–Myers Squibb). Annual prescriptions have increased from approximately 20 million to more than 40 million in this time. Source: IMS. (Click on the figure to magnify it.)


Table 1. Currently marketed antipsychotics. (Click on the table to magnify it.)


The first generation of antipsychotics — termed conventional or 'typical' antipsychotics — such as haloperidol, inhibit dopamine D2 receptors and are moderately effective in treating positive symptoms of schizophrenia (for example, hallucinations), but may cause extrapyramidal movement disorders. Second-generation 'atypical' antipsychotics — such as Lilly's Zyprexa (olanzapine), Johnson & Johnson's Risperdal (risperidone) and AstraZeneca's Seroquel (quetiapine) — inhibit D2 receptors in conjunction with other receptors (notably 5-hydroxytryptamine 2A (5-HT2A) receptors) (Table 1). Atypical antipsychotics have proved less likely to cause movement disorders, but are associated with weight gain, prolactin and glucose elevation, and sedation.

Zyprexa is widely regarded as being the most effective atypical antipsychotic on the market, but in the past 3 years, issues related to side effects have led to the drug losing nearly half its market share, as well as over 28,000 lawsuits, again indicating the need for drugs with better side-effect profiles. Furthermore, with all of the currently marketed atypicals facing generic competition within 5 years, there is a considerable market opportunity for new branded antipsychotics.

A new approach: mGluRs

In September 2007, Eli Lilly announced results of a 4-week Phase II trial of their metabotropic glutamate receptor 2/3 (mGluR2/3) agonist LY2140023 for schizophrenia. Although LY2140023 exhibited slightly less efficacy than Zyprexa in reducing positive symptoms, it nonetheless delivered significant improvement (2). Importantly, while treatment with Zyprexa was associated with weight gain, patients who received LY2140023 actually lost an average of 0.5 kg. These data indicate that mGluR agonists could represent a breakthrough in the search for a better-tolerated antipsychotic.

Indeed, this mechanism appears so promising that Eli Lilly, Merck, Johnson & Johnson and Pfizer (as well as partners Addex and Taisho) are all racing to develop mGluR-targeted drugs for schizophrenia. For example, early this year, Merck expanded their commitment to develop a new antipsychotic by entering into an exclusive worldwide license agreement with Addex for their preclinical, positive allosteric mGluR5 modulator ADX63365. This is Merck's second deal for an mGluR modulator for schizophrenia, having previously partnered with Taisho for another preclinical compound.

Eli Lilly clearly holds the lead in the mGluR race, with proof-of-concept data in hand and Phase III trials anticipated to begin later this year, whereas other competitors are not yet in the clinic. However, it remains to be seen whether Eli Lilly's LY2140023 will prove superior in the long run. This compound is a traditional, orthosteric agonist that provides continual activity as long as it is bound to the receptor. Conversely, allosteric modulators such as those being developed by Addex provide activity only when the endogenous agonist is present. This might provide a more normal pattern of signalling and be more attractive for long-term use.

The precise mechanism by which LY2140023 and other mGluR-targeted agents have efficacy in schizophrenia is not understood, although there may be some overlap with previously established mechanisms. Glutamate and dopamine axons converge on the medium spiny neurons of the striatum (3), 4 (Fig. 2). In addition, mGluR2/3 agonists have been shown to inhibit dopamine release, demonstrating functional interconnectivity of these two neurotransmitter pathways. It remains possible that mGluR2/3 agonists may in fact target the conventional pathway of dopamine D2 antagonism. Alternatively, mGluR2/3 may form a complex with 5-HT2A receptors, suggesting that mGluR activation can regulate 5-HT signalling5.


Figure 2. Metabotropic glutamate receptors (mGluRs) in the synapse. (Click on the figure to magnify it.)


Addex and Merck's ADX63365 targets mGluR5, which has no known effect on dopamine signalling, but which can modulate the signalling of the ionotropic NMDA (N-methyl-D-aspartate) glutamate receptor, another receptor that has long been thought to be associated with schizophrenia. This pathway may have additional benefits: while Merck and Addex still await human clinical data for ADX63365, animal studies suggest that this compound can improve cognition as well as positive symptoms. Thus, in addition to being safer than atypicals, mGluR agonists might offer improved efficacy in the cognitive domains of schizophrenia.

Outstanding issues


Long-term studies of mGluR-targeted agents have yet to be conducted and it remains to be seen whether the efficacy seen in Eli Lilly's 4-week study can be maintained. Further-more, although mGluRs appear to offer good tolerability, longer-term trials are needed to gauge safety. If mGluR-targeted drugs can mimic the profile seen so far with Eli Lilly's LY2140023, it will be interesting to see how physicians would use mGluR agonists. Would they be prescribed independently, even though they may not have the efficacy of their atypical predecessors? Would they be used as adjunctive therapies, in combination with lower doses of atypicals? This cocktail therapy model is being pursued by Acadia with their 5-HT2 inverse agonist primavanserin, which improves the efficacy of low doses of risperidone without causing weight gain. A third possibility is that mGluR-targeted agents could be used in conjunction with primavanserin, creating a selective, targeted therapy with few side effects.

Overall, the development of mGluR-targeted drugs for schizophrenia represents an opportunity for a new class of drugs that might represent a superior treatment option to that of currently available antipsychotics, as well as an advance in the understanding of the molecular basis for therapies for psychiatric disorders.

Beyond atypicals

The market for drugs for schizophrenia has grown tenfold in the past decade (Fig. 1, Table 1). In 2007, Risperdal and Zyprexa led the worldwide market with $4.7 billion in sales each. Zyprexa sales have grown, despite continuing concerns with side effects. In addition to the need for novel antipsychotics with improved safety and efficacy profiles, the approaching patent expirations of leading products is creating a challenge for the pharmaceutical industry. Recent data indicate that agents that target mGluRs could represent a promising new class of antipsychotics, and such agents are now being developed by several companies (Table 2).

Table 2. Next-generation antipsychotics. (Click on the table to magnify it.)


References


1. Lieberman, J. A. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353, 1209–1223 (2005).

2. Patil, S. et al. Activation of mGluR2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nature Med. 13, 1102–1107 (2007).

3. Sesasck, S. et al. Anatomical substrates for glutamate–dopamine interactions: evidence for specificity of connections and extrasynaptic actions. Ann. NY Acad. Sci. 1003, 36–52 (2003).

4. Moghaddam, B. Bringing order to the glutamate chaos in schizophrenia. Neuron 40, 881–884 (2003).

5. Gonzalez-Maeso, J. et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452, 93–97 (2008).

Author affiliations

Eric M. Snyder and Melanie R. Murphy are at Mehta Partners Global BioPharmaceutical Investments, 276 Fifth Avenue Suite 1100, New York 10001, USA. Email: snyder@mpglobal.com

Competing interests statement

The authors declare competing financial interests.

To download a PDF of this article, click here.

Thursday, May 22, 2008

Report highlights impact of future brain drugs on society


From the University of Cambridge:
22 May 2008

A report by the Academy of Medical Sciences which was led by Sir Gabriel Horn FRS FRCP, Emeritus Professor of Zoology at the University states that an increasing number and variety of psychoactive drugs - drugs that act on the brain - will emerge over the next few decades.

Some drugs could bring new treatments for addiction and mental ill health, but others could also increase the burden of drug misuse.
To read the entire article, click here.

Thanks go to John Devlin for bringing this article to my attention.

Monday, April 14, 2008

Which drugs best for schizophrenia?


An article from The Gazette (Cedar Rapids - Iowa City - Eastern Iowa). To read the entire article, click here.


Saturday, April 5, 2008

Restrictive drug policies often cause patients with schizophrenia to discontinue medication, study finds

NEWS ALERT
Harvard Medical School Office of Public Affairs

FINDINGS:
{Patients with schizophrenia] in Maine’s Medicaid program experienced more frequent interruptions in treatment when the state began requiring physicians to seek prior authorization for medications not on the programs’ preferred drug list.

RELEVANCE: Schizophrenia is a devastating psychiatric illness that affects roughly three million Americans. Disruptions in medication compliance can be devastating for the patient. Despite this, prior authorization policies for antipsychotic drugs are used in about forty percent of state Medicaid programs and in one-third of the Medicaid Part D drug benefit in attempts to save costs.

BOSTON, Mass. (April 1, 2008)—Policies requiring authorization before physicians can prescribe newer medications to [patients with schizophrenia] may be counter-productive. According to a new study, patients in Maine’s Medicaid program who found themselves in this situation were 29% more likely to stop or disrupt medication use than patients not subject to the policy. In addition, although the policy was originally designed to cut costs, government savings were minimal at best.

These findings are reported online in Health Affairs [click here to download the entire article (PDF)].

The study, led by investigators from Harvard Medical School’s Department of Ambulatory Care and Prevention, looked at Maine Medicaid beneficiaries with schizophrenia on antipsychotic drugs before, during, and after a policy that required patients to use an authorized medication (step treatment) before they were allowed to use drugs not on the preferred list. They were compared to similar beneficiaries in New Hampshire, where there was no prior authorization regulation. The Maine policy was replaced by a provider education program after less than a year.

Study data indicated that the original Maine policy disrupted essential antipsychotic treatment for vulnerable patients with schizophrenia, with minimal or no cost savings.

“This study calls into question the effectiveness of many similar policies throughout the country,” says Stephen Soumerai (pictured), Harvard Medical School professor and senior author on the study. “Getting prior authorization requires paperwork and is time-consuming, so physicians may tend to switch to prescribing preferred medications even if they have concerns about the appropriateness of the medication for a specific patient.” However, as medication choice is restricted, more patients discontinue treatment.

Previous studies have shown that gaps in antipsychotic medication use are likely to result in recurrence of psychotic episodes and higher hospitalization rates and costs for these patients.

Schizophrenia is a disabling and costly illness that afflicts approximately one percent of the US population, or three million people. Without antipsychotic treatment, about 80% of patients will have a serious recurrence of their illness within a year. The study investigators believe that while there is a legitimate place for prior authorization and step treatment policies for some medications, patients with chronic mental illness are put at particular risk of receiving inadequate treatment.

“Given the tremendous variation in individual responses to these drugs as well as the devastating impact of treatment disruptions on schizophrenic patients, a policy that pushes all patients toward a limited number of preferred drugs may do more harm than good,” says Dr. Soumerai. “It would be much better to focus on ensuring that antipsychotic drugs are prescribed for evidence-based reasons and that preferred drugs are prescribed only to patients who can benefit from them.”

This study was supported by the Agency for Healthcare Research and Quality (AHRQ), Centers for Education and Research in Therapeutics (CERT) Public/Private Partnership Program and the HMO Research Network CERT, Eli Lilly and Company, and the Harvard Pilgrim Health Care Foundation.

Written by Ann Plasso


CITATION:
Health Affairs, April 1, 2008
“Use of atypical antipsychotic drugs for schizophrenia in Maine Medicaid following a policy change”
Stephen Soumerai(1), Fang Zhang(1), Dennis Ross-Degnan(1), Daniel Erik Ball(2), Robert LeCates(1), Michael Robert Law(1), Tom Hughes(2), Daniel Chapman(3), and Alyce Adams(1)

1-Harvard Medical School, Department of Ambulatory Care and Prevention, Boston MA
2-Eli Lilly and Company, Indianapolis, IN
3-Centers for Disease Control and Prevention, Atlanta GA

CONTACT:
David Cameron
public_affairs@hms.harvard.edu
617.432.0442

Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School's Boston campus or in one of 47 hospital-based clinical departments at 18 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center, Judge Baker Children's Center, Immune Disease Institute, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Saturday, January 12, 2008

Potential New Treatments Being Researched for Schizophrenia

A January 10th posting by Psych Central:
Schizophrenia remains one of the most challenging mental disorders to treat. New research published this month examines a number of possible treatments that hold promise in the treatment of schizophrenia. While these drugs are still in their infancy and far from being approved for human use for schizophrenia, the research suggests future schizophrenia treatment directions.
To read the remainder of this article, click here.


All of the research papers referred to in the above news story are available for free download from the January 1st issue of Biological Psychiatry, the theme of which is Schizophrenia: From Genetics to Treatment. Click here to view the Table of Contents of this issue and to download the papers.



Saturday, January 5, 2008

FDA Evaluating New Drugs for Schizophrenia Treatment


"Despite an earlier setback with bifeprunox, three new antipsychotic drugs — asenapine [molecular structure illustrated on right], paliperidone palmitate injection, and iloperidone — have been submitted to the FDA for review."

To read this article written by Jun Yan and published in the January 4th issue of Psychiatric News, click here.

Sunday, September 2, 2007

Eli Lilly drug lessens schizophrenia symptoms in trial


An article published in the September 2nd edition of the International Herald Tribune:
By Alex Berenson

In a clinical trial of about 200 patients, an experimental drug from Eli Lilly lessened schizophrenia symptoms without the serious side effects of current treatments, according to a paper published Sunday in the journal Nature.

The drug must still be tested on many more patients and is at least three to four years from completing regulatory review. But schizophrenia researchers said the trial's results were surprising and impressive, especially since the drug works in a different way from existing antipsychotic medicines, all of which have serious side effects including weight gain and tremors.

Lilly will begin a new and larger clinical trial for the drug this month. If that trial confirms the results seen so far, the new drug could mark a breakthrough in the treatment of schizophrenia - and open the way to a broad new class of treatments for the disease. Schizophrenia, a devastating mental illness that affects 1 percent of adults and usually begins in the late teens or 20s, is marked by psychotic delusions as well as social withdrawal and cognitive impairment.

"This is potentially one giant step forward for patients," said Dr. Jeffrey Lieberman, chairman of the psychiatry department at Columbia and the lead investigator on a federally sponsored clinical trial of schizophrenia medicines.

Lieberman has not been involved with the development of the Lilly medicine and does not receive any payments or consulting fees from Lilly.

The new drug also has the potential to be a blockbuster for Lilly. Medicines for schizophrenia and bipolar disorder had sales of $12 billion in the United States and $18 billion worldwide last year.

The troubled history of Zyprexa, another antipsychotic medicine from Lilly, will lead regulators and psychiatrists to scrutinize the new medicine closely for hidden dangers, Lieberman said. When it introduced Zyprexa in 1996, Lilly hailed it as a breakthrough with fewer side effects than older drugs. But Zyprexa causes severe weight gain, and the American Diabetes Association has linked it to diabetes. Internal Lilly documents show that the company played down Zyprexa's side effects, worrying that they would hurt sales.

Despite that history, psychiatrists will be eager to see whether the new Lilly medicine works, since the existing drugs are of limited help for many patients. Existing schizophrenia medicines, whether older drugs such as Thorazine or newer medicines like Zyprexa, all work the same way, by blocking the brain's dopamine receptors.

But the new Lilly drug does not directly affect dopamine. Instead, it modulates brain activity through a different set of receptors. As a result, it has the potential to be the first truly novel treatment for schizophrenia since Thorazine was introduced 1954, Lieberman and other researchers said.

Lilly's new drug - which does not have a name yet and is referred to only as LY2140023 - emerged from almost two decades of research into the similarities between symptoms of users of PCP, a street drug sometimes called angel dust, and schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain receptors that are triggered by an amino acid called glutamate.

The Lilly clinical trial validated the theory that modulating glutamate receptors may control the symptoms of schizophrenia, said Dr. Joseph Coyle, a professor of psychiatry and neuroscience at Harvard Medical School.
Click here for a related story from BBC News.

Click here for more information from the Schizophrenia Research Forum.

Click here for a Psychiatric News article entitled Drug Bypassing Dopamine Could Broaden Antipsychotic Arsenal.

Saturday, August 18, 2007

Novel targets for drugs in schizophrenia


The abstract of a paper by J.M. Stone and L.S. Pilowsky published in the August 1st issue of CNS & Neurological Disorders - Drug Targets:
Since the discovery of the first antipsychotic drug, chlorpromazine, in the early 1950s, all effective antipsychotic drugs have been found to share the common property of dopamine D2 receptor antagonism. There has been some suggestion that simple D2 receptor antagonism may not confer optimal antipsychotic efficacy. Currently available antipsychotic drugs leave many symptoms of the illness untreated and cause unacceptable side effects. Recent research in schizophrenia suggests a number of potential new non-D2 targets for pharmacotherapy including glutamate, acetylcholine and serotonin neurotransmitter systems. This review summarises the main neurochemical theories of schizophrenia, and, in the light of these, examines possible therapeutic targets for new antipsychotic drugs.

D2 receptor binding of typical and atypical antipsychotic drugs. (Source: ABPI via drugdevelopment-technology.com.) Click on the figure to magnify it.