At the instigation of the National Mental Health Commission, the Australian Bureau of Statistics (ABS) conducted a study of Mortality of People Using Mental Health Services and Prescription Medications, Analysis of 2011 data.1 They examined the Pharmaceutical Benefits Scheme (PBS) records of 3,190,847 persons, who comprised 14.8% of the Australian population of 21,507,719, who had accessed “mental health-related treatments” in 2011. Then they investigated their death records and suicide records.
The scope of MBS (Medicare Benefits Schedule) and PBS (Pharmaceutical Benefits Scheme) data was restricted to persons who accessed subsidised mental health-related items listed on the MBS or PBS in 2011. The study did not include persons in public hospitals who were given drugs from hospital pharmacies, or drugs prescribed under the Department of Veterans Affairs and Repatriation Pharmaceutical Benefits Scheme. Veterans were counted within the population denominator but those who committed suicide not included in suicide numbers.2 ABS data also excluded persons who accessed services through Aboriginal and Torres Strait Islander Health Programmes that did not use the Medicare processing system. Suicide rates are reportedly high in Aboriginal populations.
Nonetheless, the doubling and trebling of mortality was irrefutable. 153,451 deaths were registered in Australia in the period 10 August 2011 to 27 September 2012. 75,858 of these deaths were registered for persons who had accessed mental health-related treatments. These deaths accounted for 49.4% of all deaths in this period.
The standardised death rate for persons accessing mental health-related treatments in 2011 was almost twice (1.9 times) that of the standardised death rate for the Australian population (11.4 /1,000 vs. 6.1/1,000).
In the 15-74 age group accessing mental health-related treatments the standardised death rate was 2.4 times higher than for the population of the same age (7.4/1,000 vs. 3.0 /1,000.) For males aged 15-74, it was almost three times (2.9) higher (11.2/1,000 v 3.8/1,000). For females aged 15-74 it was 2.2 times, (5.1 v 1,000 v 2.3/1,000) population).
The leading cause of death was ischaemic heart disease, followed by lung cancer. Mental health patients died of lung cancer (12.3% v 14.1%) and heart disease at a greater rate than the general population. Psychiatric patients smoke because the hydrocarbons in cigarettes induce the enzymes that metabolise antidepressants and antipsychotics, and as a result they feel less toxic and more comfortable. The cause of death by intoxication (poisoning) and suicidality is drug toxicity, levels above the therapeutic window of opportunity. Psychiatric drugs affect all organ systems and death can be cardiac, respiratory, endocrine, or multiple organ failure. Damage occurs to brains, now called substance/medication-induced neuroleptic brain injury. It used to be called Neuroleptic Induced Deficit Syndrome, NIDS. Brains are injured by neuroleptics if given in high doses, particularly if the person cannot metabolise them. It appears to be happening much more to the very young.
The outcome is an adult who was normal before getting medication but now appears to be autistic. The clinical presentation is reminiscent of people who were born with early infantile autism, diagnosed at six weeks of age with Kanner’s Syndrome and grew to maturity.
The expectation is that the assessors for Australia’s National Disability Insurance Scheme will be finding scores of these young people who have not surfaced and have not been properly diagnosed. The oldest of them would be in their early 40s now. Indeed these assessors need to be told to look out for the problem.
The standardised death rate by intentional self-harm for persons who accessed mental health-related treatments was more than three times (3.3) higher than the standardised death rate by intentional self-harm amongst the total Australian population (34.4 deaths per 100,000 population compared with 10.5/100,000).
These suicide figures understate the number of medication-induced suicides. Medication-induced and medication withdrawal suicides are 100% preventable, can be predicted from a genotype and can be prevented if compulsory continuing medical education is taken away from the pharmaceutical industry and given to responsible educators. The pharmaceutical industry had the blessing of the Commonwealth government to educate doctors as it wished, and it wished to educate them not in the interests of patients but in their own interests.3 Some members of the medical profession have demonstrated that they are unwilling to learn, read or take on board any information that threatens their current practices and incomes. The regulators of medical practice in Australia have relied on what they believed to be standard psychiatric practice as defined by clinical practice guidelines drafted by the pharmaceutical industry, amended slightly and signed by key opinion leaders who are well remunerated problems. Sometimes the text and graphics are virtually identical to a plethora of clinical practice guidelines ghost written in Canada at the request of the Texas Medication Algorithm Project, TMAP, a consortium of pharmaceutical industry interests which has been sued many times.
In 1993, 68 persons committed suicide while being treated by NSW mental health services, and in 1999, 173 persons committed suicide. Between 1996 and 2002, 1163 persons committed suicide within 28 days of contact with the service. Between 2003 and 2008, 937 more committed suicide, making a total of 2000 suicides.4 However the way those suicides were counted changed, and after 2002, suicides were counted only if they occurred within 7 days of contact with NSW mental health services, which looked better. This means that more patients than were included in the statistics committed suicide and homicide on medication that had been prescribed by NSW mental health services.
Between 1993 and 2001, suicide numbers in those under mental health care trebled, increasing from 9% to 21% of all suicides in New South Wales. Increased suicide numbers in NSW were exactly accounted for by the suicides committed by patients under mental health care.5
Hospitalizations for suicide attempts in NSW increased threefold, from 55/100,000 of the population in 1989-90, to 155/100,000 of the population in 2005-06. These accounted for 9,000 hospitalizations a year, and some hospitals did not count them at all.6
The clinical trial data that was accepted by the FDA for the licensing of antidepressants and atypical antipsychotics provides warnings about these phenomena. Following the signing of the Free Trade Agreement with the United States in 2005, Australia adopted the standard of the FDA.7 The Therapeutic Goods Administration (TGA) did not tell the Australian public that the drugs that it approved as far back as 1990, using the standard of the US FDA, were no longer safe or effective and that they were not independently evaluated in Australia. Darrow investigated the process of drug approval at the FDA and concluded that the public (and physicians and insurers) should not rely on the fact of FDA approval as an indication that medicines, including new and very highly priced ones, possess efficacy that is meaningfully greater than no efficacy at all.8
In order to get a drug approved by the FDA, it needs to surpass placebo in two clinical trials on any criterion that the drug company nominates. The efficacy of antidepressants is tested using the Hamilton Depression Scale (HAM-D), which measures energisation, but not the ability to return to work. Some people become manic and score well on the HAM-D, only to go on to kill themselves and others. Drug companies can do any number of trials before they have two successful trials to present, and in the case of risperidone and sertraline for children, two such trials were eventually conducted some 20 years after the drugs were first approved.
Healy summarised the lines of evidence that demonstrate that the relative risk of suicide on antidepressants is somewhere between two and three times that on sugar pills.9
The “atypical” antipsychotics entered the market with significant warnings and a side effect profile of life threatening conditions. FDA data established that one in every 145 persons enrolled in clinical trials for olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), and ziprasidone (Geodon) died as a result of adverse reactions to the drugs including, but not limited to, suicide, diabetes, convulsions, neuroleptic malignant syndrome, pancreatitis, hyperglycemia, tardive dyskinesia, stroke, hypertension, cardiac arrhythmia, cardiomyopathy, hyper prolactinaemia, and obesity. Persons on atypical antipsychotics committed suicide two to five times more frequently than the schizophrenic population in general. The initial diagnosis is irrelevant, as the side effects occur in people with psychiatric and non-psychiatric disorders. In 1997, when there were five antidepressants on the market and three new atypicals, and they were being prescribed together, the suicide rate in Australia reached record levels. Hanging, the most common form of suicide in akathisia sufferers, accounted for the mode of suicide in 50% whereas it is usually 10%.10
Medications not associated with mental health that are reported to the FDA as causing suicidality include muscle relaxants, analgesics (Tramadol is an SSRI), oxycodone, amphetamines, MDMA (Ecstasy), Ritalin (methylphenidate), and drugs as diverse in structure and function as hypericum (St John’s Wort),11 (Chantix®), oseltamivir (Tamiflu®), isotretinoin (Roaccutaine®), mefloquine (Lariam®), metoclopramide (Maxalon®), zolpidem (Stilnox®), calcium channel blockers, antiepileptic drugs promoted as ‘mood stabilizers,’ allergy medicines,12 reserpine, benzodiazepines, statins, and interferon, all induce suicidal and homicidal thinking as an occasional side effect.13 14 Moore et al. identified 1527 cases of violence including homicides disproportionally reported to the FDA for 31 drugs, including varenicline, 11 antidepressants, sedative/hypnotics, and 3 drugs for attention deficit hyperactivity disorder.15
The harbinger of suicidality and violence is a neurotoxic side effect called akathisia (from the Greek, cannot sit) that comes on in conjunction with other substance/medication-induced disorders that mimic mental illnesses. Akathisia presents as a fluctuating, can’t-sit-down-restlessness, along with thoughts of death and dying, or unwelcome aggression which, turned inwards, becomes suicidality, and turned outwards, becomes violence, right up to homicide and mass homicide.16 17 18 A manifestation of drug sensitivity, akathisia correlates with blood levels that exceed the therapeutic window as well as sudden changes of dose, up or down. This makes starting and stopping a drug the most dangerous, but not the only time for suicide. Both should be done very, very slowly with compounded medication and supervision.
When an obviously medication-induced suicide or homicide is reported in the press, it appears that everyone in the community, except lawmakers and prescribers, asks the question, “What was he taking?” Five minutes of searching on the internet is recommended to see that this is a massive issue whose articulators and whistle blowers are all cruelly silenced by defamation and by medical regulators and their tribunals. Their courts are based on ecclesiastical courts, which were designed to weed out heretics and not to find the truth.
For example, after the Sandy Hook kindergarten massacre by Adam Lanza, a petition to the White House to find out what medication he was taking gained 86,000 signatures in two days. It was shut down by the White House with the words, “Thank you for your interest in gun control.” Lanza had initially been given escitalopram and had a very serious adverse drug reaction to it, which suggests seriously defective metabolising genes. His next treating psychiatrist absconded to New Zealand and destroyed his records. No one thought to ask what had been dispensed or test for post mortem.
The letter from the White House had about the same level of relevance as the “ministerials” (answers to questions prepared by public servants on behalf of the minister) that emerge from both the state and Commonwealth Departments of Health in response to the letters to the Minister. The information relating suicide to drugs and genes has been submitted to countless Senate committees and to state and federal health ministers whose departments’ ministerial writers are hamstrung by policy, even when they know what they should be saying.
The problem demands re-education of all people who write prescriptions for any kind of medication, and willingness and insisting that they get informed consent from the patient for every single drug. This can be most easily done by presenting a consumer information document, which is available for every drug on the website of the TGA. Patients are entitled to this and it should be enforced.
Akathisia has been associated with suicide since the 1950s and with homicide since 1985.19 Shear et al. reported homicides associated with akathisia after treatment with depot fluphenazine.20 Schulte described five cases of murder, suicide and severe violence with akathisia in psychiatric patients.21 22 The same drugs that induce violence also induce suicidality, and akathisia homicides often end in suicide.
Conditions that affect drug metabolism and cause a drug to reach toxic levels include the dose, co-prescribed medications that induce or inhibit the enzymatic pathways, age, nutrition, stress, liver disease, hormones (natural and extraneous), the sequence in which drugs have been prescribed or taken away, the route of administration, the range of the drug’s half-life in any population, potentially multiple metabolic pathways, the size of the therapeutic window above which a drug is both ineffective and toxic, the duration of therapy, and the duration of inhibition.23 24
The population is broadly divided into extensive, intermediate, poor and ultra-rapid metabolisers. Poor metabolisers develop side effects very quickly, but intermediate metabolisers are at higher risk because blood levels build up slowly and toxicity is not recognised. Most at risk of death from suicide and intoxication are ultra-rapid metabolisers. The appear to go in and out of withdrawal over a period of a day with some drugs, and this is problematic emotionally.25 26 With some drugs and prodrugs, ultra rapid metabolism producing an active metabolite can be problematic, particularly in withdrawal.27 28 29
Intermediate metabolizers may metabolize like poor metabolisers and some like extensive metabolizers, and they are vulnerable to inhibition.30 Some extensive metabolizers metabolize drugs like poor metabolizers after taking CYP inhibitors that reduce or eliminate enzyme activity.31 32
The suicide rate in schizophrenia between 1875 and 1924 was 20/100,000 hospital years, a lifetime rate of less than 0.5%. The suicide rate for all psychoses was 16/100,000 hospital years. Current rates of suicide for schizophrenia and other psychoses appear 20-fold higher.33
ABS uses a euphemism “death rate for intentional self-harm” and finds suicide to be more than three times higher in the medicated than in the population. This is an underestimate. ABS did not look at suicides in hospitals or suicide committed on medications prescribed in a hospital, or those that occurred within days of a patient being prescribed an antidepressant or an atypical antipsychotic in a hospital, and who committed suicide shortly after discharge. ABS did not count suicides in the workers compensation stream, particularly among police, because their prescriptions did not show up on the PBS. ABS did not inquire about the number of returned servicemen who committed suicide in 2012. Veterans are also committing suicide at least twice the rate of the general population.34 The mortality report did not count persons whose prescriptions were written under the Repatriation Scheme.
In 2003, the FDA issued a series of public health advisories concerning worsening depression and suicidality on antidepressants.
The Royal Australian and New Zealand College of Psychiatrists (RANZCP) remains “not convinced” in the face of reviews of literally hundreds (373) of clinical trials. That old antidepressants induced suicide in some people was in the 1960 undergraduate psychiatry textbook Clinical Psychiatry written by Mayer-Gross, Slater and Roth. The American Psychiatric Association immediately changed its clinical practice guidelines to include suicide warnings. The RANZCP refused to do so. This is because of fraud in the pharmaceutical sector, which has been documented extensively, country-by-country, and drug-by-drug.35 It is rife in Australia because the country has no way of getting restitution, either for individuals affected or for the Commonwealth and taxpayers. The problem may well be, as it is in the United States, that the pharmaceutical industry and its proxies, Medicines Australia, for example, are generous donors to both political parties. Any changes to this system would require a False Claims Act structured on the American model, so that the Commonwealth and the individuals harmed by pharmaceutical industry fraud can get some kind of restitution. It also would involve making the pharmaceutical industry banned donors.
RANZCP is hugely funded, particularly for its conferences, by the pharmaceutical industry. It is a trade union, not an expert body.
- Australian Bureau of Statistics. 08/09/2017 4329.0.00.006 – Mortality of People Using Mental Health Services and Prescription Medications, Analysis of 2011 data. ↩
- Review into the Suicide and Self-Harm Prevention Services Available to current and former serving ADF members and their families Final report: Findings and Recommendations National Mental Health Commission 28 March 2017.
- Baker Richard. Mental health takes industry pills, The Age. August 8, 2006. http://www.theage.com.au/news/national/mental-health-takes-industry-pills/2006/08/07/1154802820416.html. ↩
- NSW Parliament Question asked on 13 May 2010 (session 54-1) and published in Questions & Answers Paper No. 197 <http://bulletin/prod/la/lapaper.nsf/V3QnBySN/541~197/$file/197-QA-S.pdf> 10218—PSYCHIATRIC DRUGS Mr Daryl Maguire to the Deputy Premier, and Minister for Health. ↩
- NSW Mental Health Sentinel Events Review Committee Tracking Tragedy A systemic look at homicide and non-fatal serious injury by mental health patients, and suicide death of mental health inpatients Fourth Report of the Committee. March 2008. http://pandora.nla.gov.au/pan/40156/20100301-1613/www.health.nsw.gov.au/pubs/2009/pdf/4th_report.pdf (Accessed December 4, 2014) ↩
- The Health of the people of New South Wales – Report of the Chief Health Officer. NSW Department of Health, Sydney, Intentional self-harm hospitalizations by sex, persons of all ages and 15-24 years, NSW 1989-90 to 2006-07 http://www.health.nsw.gov.au/public-health/chorep/men/men_suichos.htm (Accessed December 2007). ↩
- The PBS and the Australia–US Free Trade Agreement. INFORMATION, ANALYSIS AND ADVICE FOR THE PARLIAMENT 2004-5. No 3,21 July 2004. ↩
- Darrow, J. J. (2013). Pharmaceutical Efficacy: The Illusory Legal Standard. Washington and Lee Law Review, 70(4), 2073. http://scholarlycommons.law.wlu.edu/cgi/viewcontent.cgi?article=4358&context=wlulr ↩
- Healy D. Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychother Psychosom. 2003 Mar-Apr;72(2):71-9. Review. PubMed PMID: 12601224. https://www.ncbi.nlm.nih.gov/pubmed/12601224 ↩
- Harrison, JE Steenkamp M. Suicide in Australia: Trends and data for 1998. National Injury Surveillance Unit issue 23, May 2000. ↩
- Nanayakkara PW, Meijboom M, Schouten JA. Suicidal and aggressive thoughts as a result of taking a Hypericum preparation (St. John’s wort). Nederlands tijdschrift voor geneeskunde. 2005 Jun 11;149(24):1347-9. Dutch. PubMed PMID: 16008039.varenicline ↩
- Robertson HT, Allison DB (2009) Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts. PLoS ONE 4(10): e7312. doi:10.1371/journal.pone.0007312. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007312 ↩
- Sachdev P. Akathisia and Restless Legs. Cambridge University Press 1995. ↩
- Marks DH, Breggin PR, Braslow D. Homicidal ideation causally related to therapeutic medications. International Journal of Risk and Safety in Medicine. 2008; 231-240. ↩
- Moore TJ, Glenmullen J, Furberg CD, 2010 Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 5(12): e15337. doi:10.1371/journal.pone.0015337. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015337 (Accessed 01/02/2011) ↩
- SSRI stories antidepressant nightmares. https://ssristories.org (accessed25 September 2017) ↩
- Lucire Y, Crotty C. Antidepressant-induced akathisia-related homicides associated with diminishing mutations in metabolizing genes of the CYP450 family. Pharmacogenomics and Personalized Medicine: 4:1 65-81.2011 http://www.dovepress.com/articles.php?article_id=7993. ↩
- Eikelenboom-Schieveld, S. J., Lucire, Y., & Fogleman, J. C. (2016). The relevance of cytochrome P450 polymorphism in forensic medicine and akathisia-related violence and suicide. Journal of forensic and legal medicine, 41, 65-71. http://www.sciencedirect.com/science/article/pii/S1752928X16300051. ↩
- Healy D, Aldred G. Antidepressant drug use and the risk of suicide. International Review of Psychiatry. 2005;17(3):163-72. ↩
- Shear MK, Frances A, Weiden P. Suicide associated with akathisia and depot fluphenazine treatment. Journal of Clinical Pharmacology1983;(4):235-6. ↩
- Cem Atbasoglu E, Schultz, SK, Andreasen NC. The relationship of akathisia with suicidality and depersonalization among patients with schizophrenia. Journal of Neuropsychiatry and Clinical Neuroscience 2001;13:336-341. ↩
- Schulte JL. Homicide and suicide associated with akathisia and haloperidol. American Journal of Forensic Psychiatry1985;6(2):3-7. ↩
- Cozza K. Armstrong SC, Oesterheld JR. Drug Interaction Principles for Medical Practice. 2003. American Psychiatric Publishing Inc. ↩
- Bauman P et al. The ANGP-TDM Expert group consensus guidelines: Therapeutic Drug Monitoring. Psychiatry. Pharmacopsychiatry 2004;37:243-265. ↩
- Ingelman-Sundberg, M., & Sim, S. C. (2010). Pharmacogenetic biomarkers as tools for improved drug therapy; emphasis on the cytochrome P450 system. Biochemical and biophysical research communications, 396(1), 90-94. ↩
- Zackrisson AL, Lindblom B, Ahlner J. High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases. Clin Pharmacol Ther. 2010 Sep;88(3):354-9. doi: 10.1038/clpt.2009.216. Epub 2009 Nov 11. PubMed PMID: 19907421. ↩
- Gasche Y, Daali Y, Fathi M, Chiappe A, Cottini S, Dayer P, Desmeules J. Codeine intoxication associated with ultrarapid CYP2D6 metabolism. New Engl J Med. 2004;351:2827-31. ↩
- A.L. Zackrisson, B. Lindblom, J. Ahlner, High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases, Clin. Pharmacol. Ther. (2009). ↩
- Ahlner J, Lindblom B, Zackrisson AL, Bertilsson L, Editorial. CYP2D6, serotonin and suicide. Pharmacogenomics (2010) 11(7), 903–905 ↩
- Cytochrome P450 Enzyme Genotyping: optimizing patient care through pharmacogenetics. Mayo Clinic Communiqué. 2005. Mayo Reference Services Publication. http://mayomedicallaboratories.com/media/articles/communique/mc2831-0905.pdf (Accessed 01/02/2011) ↩
- de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for using pharmacogenetic testing of CYP450 2D6 and CYP450 2C19 in psychiatry. Psychosomatics. 2006;47:75–85. ↩
- Zourková A & E, Hadasová E. Paroxetine-induced conversion of cytochrome P450 2D6 phenotype and occurence of adverse effects. Gen Physiol Biophys. 2003;22:103-113. ↩
- Healy, D Harris, R, Tranter, R. Gutting, P Austin, RG. Jones-Edwards G, Roberts AP. Lifetime suicide rates in treated schizophrenia: 1875-1924 and 1994-1998 cohorts compared. BJPsych (2006), 188, 223- 228. ↩
- The Senate Foreign Affairs, Defence and Trade References Committee The Constant Battle: Suicide by Veterans. August 2017 http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Foreign_Affairs_Defence_and_Trade/VeteranSuicide/Report ↩
- Kohler, J., Martinez, M., Petkov, M., & Sale, J. (2016). Corruption in the pharmaceutical sector: diagnosing the challenges. UK: Transparency International. ↩
Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.