For two decades, medical professionals, the public, and public health policy officials who determine the allocation of public funds for healthcare, have been misled about the safety and benefits of psychiatric drugs–in particular, the newer, expensive drugs, the so-called SSRI antidepressants, and the new neuroleptics, marketed as ‘atypical antipsychotics’.

Pharmaceutical industry marketing hype, deceptively packaged as "scientific study findings," gained the appearance of legitimacy when they were accepted by the FDA for licensure, and accepted for publication in medical journals. Those reported "findings" were fraudulent, concocted and aggressively disseminated by manufacturers of these drugs.

The deception has seriously undermined the integrity of the scientific literature, and misled physicians who unwittingly prescribed hazardous drugs causing patients irreparable harm. 

Thanks to years of litigation during which company documents have been uncovered, the truth has been revealed. We now know that SSRI antidepressants and the ‘atypical’ antipsychotics have failed decisively to demonstrate therapeutic benefits in clinical trials and in clinical practice Instead, these drugs have triggered debilitating, chronic illness and even life-threatening risks: antidepressants increase the suicide risk and trigger serotonin syndrome, which is potentially fatal. Antipsychotics undermine normal metabolic, cardiovascular, hormonal function, resulting in cardiac arrest, obesity, metabolic syndrome and diabetes.

1. A groundbreaking pharmaco-genetic study by Australian psychopharmacology experts–Dr. Yolande Lucire, a forensic psychiatrist, and Christopher Crotty, a pharmacogeneticist–report in the peer reviewed journal, Pharmacogenomics and Personalized Medicine , (abstract below) an alarming finding. They report a significant association among  genetic variants, metabolism of psychiatric drugs, and severe, homicidal akathisia. 

The authors examined the relationship between genetic variants in the CYP450 family, the interaction of antidepressant-induced akathisia, and violence, including homicide in 129 forensic patients who had referred to Dr. Lucire by lawyers.

 Of 138 persons tested for CYP450 genes, 129 had experienced adverse events, "mainly akathisia, due to psychiatric drugs, and nine were first degree relatives of those treated who also had a history of adversity on other drugs." 

 Of the 129 persons who experienced drug-induced adverse effects, 8 had committed homicide, 3 had committed suicide,  and one had sleepwalked to her death.

 The authors report that:

" In all of the cases presented here, the subjects were prescribed  antidepressants that failed to mitigate distress  emerging from their predicaments, which encompassed psychosocial stressors such as bereavement, marital and relationship difficulties, and work-related stress. Every subject’s emotional reaction worsened while their  prescribing physicians continued the “trial and error” approach, increasing from standard to higher dose and/or switching to other antidepressants, with disastrous consequences. In some cases the violence ensued from changes occasioned by withdrawal and polypharmacy.

 In all of these cases, the subjects were put into a state of drug induced toxicity manifesting as akathisia, which resolved only upon discontinuation of the antidepressant drugs."

 " This paper has detailed and substantiated in specific terms how the metabolism of each of the antidepressant drugs used by the subjects would have been seriously impaired both before and at the time they committed or attempted homicide. They were experiencing severe reported side effects, adverse drug reactions due to impaired metabolism complicated by drug–drug interactions against a background of variant CYP450 alleles."

The authors further state:

"The results presented here concerning a sample of persons given antidepressants for psychosocial distress demonstrate the extent to which the psychopharmacology industry has expanded its influence beyond its ability to cure. The roles of both regulatory agencies and drug safety “pharmacovigilantes” in ensuring quality and transparency of industry information is highlighted."

Two other recently published studies, one in the British Medical Journal (BMJ), the other in the Journal of the American Medical Association, also challenge the validity of psychiatry’s prescribing practices whose rationale is mostly commercially propagated.

2. The authors of the BMJ report, "Antidepressant Use and Risk of Adverse Outcomes in Older People: Population Based Cohort Study," analyzed data for 60,746 persons in the UK who were over 65 and diagnosed with depression between 1996 and 2007. The authors followed the subjects until December, 2008.

The authors of this  study found that those prescribed SSRI antidepressants are at increased risk of death and heart attack, stroke, falls and seizures than those who were prescribed the older, cheaper, tricyclic antidepressants. 

 During those 10 years, patients not taking any antidepressants had a 7% risk of dying from any cause. But the risk rose to 8.1% for those taking the older antidepressants and increased to 10.6% for patients prescribed SSRIs.

  " All classes of antidepressant drug were associated with significantly increased risks of all cause mortality, attempted suicide/self harm, falls, fractures, and upper gastrointestinal bleeding compared with when these drugs were not being used. Selective serotonin reuptake inhibitors and the group of other antidepressant drugs were associated with increased risks of stroke/transient ischaemic attack and epilepsy/seizures; selective serotonin reuptake inhibitors were also associated with increased risks of myocardial infarction and hyponatraemia."

 3. According to government data, 10% to 20% of soldiers who see heavy combat develop lasting symptoms of Post Traumatic Stress Disorder (PTSD), and about a fifth of those who are treated are prescribed an antipsychotic drug. The JAMA report, by prominent psychiatrists on the faculty of Yale University, examines the treatment outcome for veterans suffering from PTSD, whose treatment with SSRI antidepressants failed, who were then prescribed antipsychotics. See, "Adjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service–Related PTSD A Randomized Trial."

 The finding: after six months of treatment, the veterans who were prescribed Risperdal were doing no better than a similar group of 124 veterans, who were given a placebo. About 5% in both groups recovered, and 10% to 20% reported at least some improvement, based on standardized measures.

 “We didn’t find any suggestion that the drug treatment was having an overall benefit on their lives,” said Dr. John H. Krystal, the director of the clinical neurosciences division of the Department of Veterans Affairs’ National Center for PTSD and the lead author of the study.

 The New York Times reports: "The surprising finding, from the largest study of its kind in veterans, challenges current treatment standards so directly that it could alter practice soon, some experts said."

 In an accompanying editorial, Dr. Charles Hoge, a senior scientist at the Walter Reed Army Institute of Research, who was not involved in the study, stated: “I think it’s a very important study given how frequently the drugs have been prescribed. It definitely calls into question the use of antipsychotics in general for PTSD.”

 Although the study focused on one antipsychotic, Johnson & Johnson’s Risperdal, experts agree that the results most likely extend to the entire class, including the drugs, Seroquel, Geodon and Abilify.

These three reports are the latest in a string of scientific reports, untainted by industry influence, that examined the evidence and found that current psychiatric drug prescribing practices are of little, if any, therapeutic value. But since the drugs pose serious risks of harm by triggering drug-induced (iatrogenic) illness–which significantly increases healthcare costs–why does the U.S. government waste billions of taxpayer dollars to subsidize their cost?.

Posted by Vera Hassner Sharav 

   
 1. Pharmacogenomics and Personalized Medicine
A ntidepressant-induced akathisia-related homicides associated with diminishing mutations in metabolizing genes of the CYP450 family, by Yolande Lucire, Christopher Crotty

Edgecliff Centre, Edgecliff, NSW, Australia

 ABSTRACT

Purpose: To examine the relation between variant alleles in 3 CYP450 genes (CYP2D6, CYP2C9 and CYP2C19), interacting drugs and akathisia in subjects referred to a forensic psychiatry practice in Sydney, Australia.

Patients and methods: This paper concerns 10/129 subjects who had been referred to the first author’s practice for expert opinion or treatment. More than 120 subjects were diagnosed with akathisia/serotonin toxicity after taking psychiatric medication that had been prescribed for psychosocial distress. They were tested for variant  alleles in CYP450 genes, which play a major role in Phase I metabolism of all antidepressant and many other medications.

Eight had committed homicide and many more became extremely violent while on antidepressants. Ten representative case histories involving serious violence are presented in detail.

Results: Variant CYP450 allele frequencies were higher in akathisia subjects compared with random primary care patients tested at the same facility. Ten subjects described in detail had variant alleles for one or more of their tested CYP450 genes. All but two were also on interacting drugs, herbals or illicit substances, impairing metabolism further. All those described were able to stop taking antidepressants and return to their previously normal personalities.

Conclusion: The personal, medical, and legal problems arising from overuse of antidepressant medications and resulting toxicity raise the question: how can such toxicity events be understood and prevented?

The authors suggest that the key lies in understanding the interplay between the subject’s CYP450 genotype, substrate drugs and doses, co-prescribed inhibitors and inducers and the age of the subject.

 The results presented here concerning a sample of persons given antidepressants for psychosocial distress demonstrate the extent to which the psychopharmacology industry has expanded its influence beyond its ability to cure. The roles of both regulatory agencies and drug safety “pharmacovigilantes” in ensuring quality and transparency of industry information is highlighted.

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THE INDEPENDENT 
Warning over newer antidepressants pills
By Jane Kirby
Wednesday, 3 August 2011

  Newer antidepressants may increase the risk of serious health problems in older people compared to older pills, researchers say.

  Selective serotonin reuptake inhibitors (SSRIs) are more likely to cause death and issues such as heart attack, stroke, falls and seizures than older tricyclic antidepressants (TCAs), according to a study published in the British Medical Journal (BMJ).

  Researchers from the universities of Nottingham and East Anglia analyzed data for more than 60,000 people diagnosed with depression between 1996 and 2007. All were aged 65 and over.

  Those patients not taking any antidepressants had a 7% risk of dying from any cause but this rose to 8.1% for those taking TCAs and 10.6% for SSRIs.

The risk was even higher for other types of antidepressants, at 11.4%.

 The risks of stroke and fracture were noticeably higher in those taking SSRIs compared to TCAs and SSRIs were linked to the most falls of any drugs.

 The risk to the patient was highest in the first 28 days after starting an antidepressant, and in the first 28 days after stopping taking the drugs.

The findings held true even when other factors were taken into account, including age, sex, severity of depression, other illnesses and use of other medications.

One theory put forward by the researchers is that TCAs tended to be prescribed at lower doses than SSRIs and other antidepressants, which may partly explain the findings.

 They warn that the risks and benefits of different antidepressants should be carefully evaluated when they are prescribed to older people.

In an accompanying editorial, Professor Ian Hickie from the University of Sydney said: "Given the potential harms, the decision to prescribe for an older person with depression should not be taken lightly."

Michelle Mitchell, charity director of Age UK, said: "Depression is the most common mental health problem in later life, affecting around a quarter of people aged 65 and over, yet it is often overlooked and wrongly seen as part of growing old.

 "Older people are often reluctant to discuss their feelings and GPs often overlook signs and symptoms of depression, meaning the condition often goes undiagnosed and untreated. "Any older person that has been feeling down … for some time should speak to their GP and discuss suitable treatment options."

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http://jama.ama-assn.org/content/306/5/493

JAMA, 2011;306(5):493-502.

Adjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service–Related PTSD A Randomized Trial

   1. John H. Krystal, MD;   2. Robert A. Rosenheck, MD;   3. Joyce A. Cramer, BS;   4. Jennifer C. Vessicchio, MSW;   5. Karen M. Jones, MS;

   6. Julia E. Vertrees, PharmD;   7. Rebecca A. Horney, BA;   8. Grant D. Huang, MPH, PhD;   9. Christopher Stock, PharmD  10. for the Veterans Affairs Cooperative Study No. 504 Group

  Abstract

  Context Serotonin reuptake-inhibiting (SRI) antidepressants are the only FDA-approved pharmacotherapies for the treatment of posttraumatic stress disorder (PTSD).

  Objective To determine efficacy of the second-generation antipsychotic risperidone as an adjunct to ongoing pharmacologic and psychosocial treatments for veterans with chronic military-related PTSD.

  Design, Setting, and Participants A 6-month, randomized, double-blind, placebo-controlled multicenter trial conducted between February 2007 and February 2010 at 23 Veterans Administration outpatient medical centers. Of the 367 patients screened, 296 were diagnosed with military-related PTSD and had ongoing symptoms despite at least 2 adequate SRI treatments, and 247 contributed to analysis of the primary outcome measure.

  Intervention Risperidone (up to 4 mg once daily) or placebo.

  Main Outcome Measures The Clinician-Administered PTSD Scale (CAPS) (range, 0-136). Other measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAMA), Clinical Global Impression scale (CGI), and Veterans RAND 36-Item Health Survey (SF-36V).

Results Change in CAPS scores from baseline to 24 weeks in the risperidone group was −16.3 (95% CI, −19.7 to −12.9) and in the placebo group, −12.5 (95% CI, −15.7 to −9.4); the mean difference was 3.74 (95% CI, −0.86 to 8.35; t = 1.6; P = .11). Mixed model analysis of all time points also showed no significant difference in CAPS score (risperidone: mean, 64.43; 95% CI, 61.98 to 66.89, vs placebo: mean, 67.16; 95% CI, 64.71 to 69.62; mean difference, 2.73; 95% CI, −0.74 to 6.20; P = .12). Risperidone did not reduce symptoms of depression (MADRS mean difference, 1.19; 95% CI, −0.29 to 2.68; P = .11) or anxiety (HAMA mean difference, 1.16; 95% CI, −0.18 to 2.51; P = .09; patient-rated CGI mean difference, 0.20; 95% CI, −0.06 to 0.45; P = .14; observer-rated CGI mean difference, 0.18; 95% CI, 0.01 to 0.34; P = .04), or increase quality of life (SF-36V physical component mean difference, −1.13, 95% CI, −2.58 to 0.32; P = .13; SF-36V mental component mean difference, −0.26; 95% CI, −2.13 to 1.61; P = .79). Adverse events were more common with risperidone vs placebo, including self-reported weight gain (15.3% vs 2.3%), fatigue (13.7% vs 0.0%), somnolence (9.9% vs 1.5%), and hypersalivation (9.9% vs 0.8%), respectively.

  Conclusion Among patients with military-related PTSD with SRI-resistant symptoms, 6-month treatment with risperidone compared with placebo did not reduce PTSD symptoms.

  Trial Registration clinicaltrials.gov Identifier: NCT00099983