Second-generation antipsychotics comprise a wide variety of drugs that in many instances do not have better efficacy against schizophrenia or a better side-effect profile than do first generation antipsychotics, according to findings from the broadest-sweeping meta-analysis of randomized trials of the drugs to date.
Many of the supposed improvements of second-generation drugs over their first-generation counterparts may have been the result of biases introduced into industry-funded randomized trials that used high-dose haloperidol or other inappropriate comparator drugs, Dr. Stefan Leucht of the Technical University of Munich and his coinvestigators reported in the Lancet (doi:10.1016/S0140-6736[08]61764-X).
Dr. Leucht and his colleagues wrote that the “improper generalisation” of the second-generation antipsychotics into a homogenous class “creates confusion” and suggests that the classification “might be abandoned.”
Dr. Peter Tyrer of Imperial College London and Dr. Tim Kendall of the Royal College of Psychiatrists’ research and training unit, London, agreed with this assessment, calling their naming and classification “inaccurate.” They said in an editorial that “the time has come to abandon the terms first-generation and second-generation antipsychotics, as they do not merit this distinction” (Lancet 2008;[doi:10.1016/
S0140-6736(08)61765-1]).
“The spurious invention of the atypicals can now be regarded as invention only, cleverly manipulated by the drug industry for marketing purposes and now only being exposed,” Dr. Tyrer and Dr. Kendall wrote.
“On present evidence from all sources, it is difficult not to conclude that the trials of the second-generation antipsychotics seem to be driven more by marketing strategy than to clarify their role for clinicians and patients.”
The investigators criticized previous literature reviews and meta-analyses that compared second- and first-generation antipsychotics, aside from Cochrane Reviews, for not assessing side effects thoroughly, even though they are important criteria in drug choice.
They also faulted previous attempts at distilling the results of trials for analyzing only one global efficacy outcome, despite claims that the main advantage of second-generation antipsychotics is their broad efficacy spectrum, especially for negative symptoms, depression, and quality of life.
In 2005-2006, the researchers searched Medline, as well as previous reviews, the register of the Cochrane Schizophrenia Group, and the Food and Drug Administration Web site.
Their meta-analysis included 150 double-blind studies of nine second-generation antipsychotics, identifying 21,533 patients with schizophrenia or related disorders.
Of the nine second-generation drugs that were evaluated, only four—amisulpride (which has not been approved by the FDA), clozapine (Clozaril), olanzapine (Zyprexa), and risperidone (Risperdal)—had significantly larger effect sizes on overall symptoms than did first-generation antipsychotics. For these
four drugs, the number of patients that would need to be treated to have one additional responder ranged between 6 for amisulpride and 15 for risperidone.
The study was funded by the National Institute of Mental Health. Dr. Leucht disclosed receiving speaker and consultancy honoraria from Sanofi-Aventis, Bristol-Myers Squibb Co., Eli Lilly & Co., Janssen-Cilag, H. Lundbeck A/S, and Pfizer Inc. The other authors declared that they had no conflicts of interest.
via Current Psychiatry November 2009
"Clinical trials support new algorithm for treating pediatric bipolar mania"
a few excerpts:
"Five recent randomized controlled trials (RCTs) have demonstrated the eficacy of atypical antipsychotics for treating bipolar disorder in children and adolescents, but 4 of these 5 trials remain unpublished."
"Change in Young Mania Rating Scale (YMRS) score was the primary outcome measure in these 5 trials, and each compound was more effective than placebo. The trials demonstrated statistically significant and clinically relevant differences between each antipsychotic and placebo. The number needed to treat (NNT)—how many patients need to be treated for 1 to benefit in a controlled clinical trial—ranged from 2 to 4."
"Bottom Line
Studies of 5 atypical antipsychotics’ efficacy and tolerability support their use for treating acute mania in children and adolescents. Four of these agents can be justified as first-line treatments, before lithium or divalproex. At the same time, antipsychotics’ potentially serious side effects—extrapyramidal symptoms, tardive dyskinesia, weight gain, hyperlipidemia, hyperprolactinemia, and QTc changes—must be recognized, monitored, and managed."
Four of the drugs trialed did not have final drug trial results published by the time this marketing tool disguised as Continuing Medical Education was published in November of 2009. The professional conferences where the data were presented in support of this pseudo-medical 'evidence-based treatment algorithm' had all taken place by the summer of 2008. The last paper utilized was presented at the Annual Meeting of the American Psychiatric Association, May 3-8, 2008; in Washington, DC.
Why there are no final reports of trial results available in November 2009, is never explained. It is also not even mentioned how much more efficacious these drugs are for pediatric bipolar mania than they are for schizophrenia by the authors of this algorithm for pediatric bipolar mania. "Robert A. Kowatch, MD, PhD Professor of psychiatry and pediatrics, Director of psychiatry research; Jeffrey R. Strawn, MD, Clinical fellow; Michael T. Sorter, MD Associate professor of psychiatry and pediatrics, Director, division of psychiatry Cincinnati Children’s Hospital Medical Center Cincinnati, OH."
"*Each trial included a 6-month open extension phase; results are pending;" the article states. Apparently results are still pending...for the ziprasidone Checking the lead author's CV, there is no article listed reporting the results of the "Safety and efficacy of ziprasidone in pediatric bipolar disorder" to date. But this author is also the lead listed for another one of the four drugs that had pending results: "DelBello M, Findling RL, Earley W, et al. Efficacy of quetiapine in children and adolescents with bipolar mania: a 3-week, double-blind, randomized, placebo-controlled trial. Paper presented at: Annual Meeting of the American Academy of Child and Adolescent Psychiatry, October 23-28, 2007; Boston, MA"
The following manuscript makes this algorithm even more strange, "Atypical Antipsychotics for Acute Manic and Mixed Episodes in Children and Adolescents with Bipolar Disorder A Review of Efficacy and Tolerability" published in final edited form in: Drugs. 2010 March 5; 70(4): 433–442.
a couple of excerpts:
In addition, two smaller controlled studies suggest that quetiapine is a useful medication for the treatment of adolescent mania. In a double-blind, placebo-controlled, adjunctive study in children and adolescents with BD, DelBello and colleagues reported that valproate and quetiapine reduced manic symptoms significantly more than valproate and placebo.[24] In another double-blind study, this same group found that adolescent patients with BD receiving quetiapine monotherapy had faster resolution of their manic symptoms and higher rates of remission than those treated with valproate monotherapy, and quetiapine was well tolerated.[25]
"Ziprasidone was approved by the FDA for the treatment of acute manic episodes in adults in 2006, but it has not been approved for use in paediatric mania."
Summary:
Why is the NIMH not using the information it has available?
Specifically: “The spurious invention of the atypicals can now be regarded as invention only, cleverly manipulated by the drug industry for marketing purposes and now only being exposed," “On present evidence from all sources, it is difficult not to conclude that the trials of the second-generation antipsychotics seem to be driven more by marketing strategy than to clarify their role for clinicians and patients.”
Given the very serious deleterious direct adverse effects of neuroleptic drugs, why are they still being used on children "off-label"? Why are teratogenic drugs prescribed for non-FDA approved conditions in infants, children and teenagers? The drugs are not only prescribed off-lablel, but are openly MARKETED by psychiatrists; the academic researchers who are "Key Opinion Leaders" who appear to put a lot of effort into encouraging the prescription of dangerous drugs off label; acting more like as marketeers for pharma, than healers with a duty to their patients.
The vast majority of off label prescriptions are then paid for by submitting fraudulent claims for prescriptions that are not approved for payment; but are paid anyway. It's become a standard practice to defraud the American people through publicly-funded medical programs and it is done as part of a "marketing strategy" while the American people are funding the KOLs "research," i.e. the drug trials conducted to support pharma's "marketing strategy."
The secret has been exposed for years now---yet we still have Tommy Insel blowing smoke up our proverbial skirts---and we still have psychiatry draining the taxpayer's wallets through Medicaid, Medicare, and Tri-Care paying for teratogenic drugs that cause psychiatric patients iatrogenic diseases and disabilities and increase their need for additional medical care and social services...
I am painfully aware of what these teratogenic drugs do to children, adults, wounded veterans, and the elderly. I am painfully aware that Informed Consent is not happening in Real World 'standard clinical practice;' at least it has not ever happened in my experience as a parent who once upon a time, trusted psychiatrists. I've not been struck willfully blind; I'm wide awake.
My adult son was Court Ordered to Involuntary Treatment with perjured testimony and a forged affidavit by a psychiatrist and a 'designated mental health professional' Under Color of Law. The deputy prosecutor knew for a fact he was submitting perjured testimony; my son's defense attorney should have known. (since she was not in a coma) This was supposedly done to, "Maintain the ethical integrity of the medical profession." In the moment I first read that sentence on the Court Order, I knew without a doubt that 'psycho' pharmacology was never a medical specialty in the Hippocratic tradition--The best interests of the patient are ALWAYS the primary focus for any person who claims to be a healer. Psychiatry is the only "medical" specialty that 'successful treatment' is not defined or quantified by the patient's real world outcome.
'Psycho' pharmacology has redefined successful treatment.
Successful treatment now means 'treatment compliance.'
Common direct adverse effects include dependence,
iatrogenic injuries, diseases, disabilities, and fatalities.
The Department of Social and Health Services and Children's Administration were motivated by fraud; It is a violation of Federal Law to require parents to place a child in State Custody in order to qualify for social services and/or Medicaid---Isaac was already on Medicaid due to being disabled by a violent assault perpetrated by a foster parent when he was 3 years old. I was told that the only way that Medicaid would continue to pay for his medical care was if he became a ward of the state---this was, I later found out, an outright lie. He had Medicaid as an identified disabled child who was on SSI for Left Temporal Lobe Epilepsy caused by a brain trauma sustained in the assault and severe PTSD from being traumatized by violent assault. There were no restrictions; his Medicaid eligibility was not at risk.
I am grateful he is alive, knows who he is and where he lives.
photo credit
