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Anti-psychotic Usage Appears to Increases Mortality and Dementia

People diagnosed with a mental illness tend to have shortened life spans, often dying decades prior to people undiagnosed, and researchers have offered numerous reasons why this may be true.[1] [2] [3] [4]

However, more recently researchers followed 99 people for 17 years, and usage of even one neuroleptic drug increased the risk of dying by 3 fold (35% actually died within the 17 years), 2 neuroleptic drugs caused 44% of them to die, and 3 neuroleptics increased the risk of dying in 17 years by 7 fold, whereby, 57% died.  The relative risk of mortality, relative to normal healthy controls was:
             zero neuroleptic (NL) at baseline      1.29 (small increase for patient Vs non-patient)
             1 NL                                                   2.97 times more likely to die if you take 1 NL drug
             2 NL                                                   3.21 times more likely to die if you take 2 NL drugs
             3 NL                                                   6.83 time more likely to die if you take 3 NL drugs

So if you have 1,000 people who do not take an anti-psychotic drug, and you track them over 17 years, and lets say 10 people die, then you can predict that if you had another 1,000 people taking a neuroleptic anti-psychotic drug, like the ones now being often used for sleep disorders, dementia and to curb agitation/aggression, one could generalize that about 30 people will die (2.97 times more) due to the psychiatric medication. If they took three over the course of the years, you would almost 70 people die as a result of the medication. ([5])

Additionally, researchers conducted the largest study ever to address suicide in treated psychotic patients with and without the usage of psychotropic medications, and indicated there was approximately a 20 fold increase in suicide rates for patients treated in modern period where there were psychiatric medications were used. ([6])

Further, an eleven month study compared typical hospital treatment with pure psychological treatment, noting the most severe cases went to the psychological treatment without medication group, and found that there were no suicide attempts, elopements or other significant acts of violence in the psycho-social treatment group; however, typical hospital psychiatric drug group with a higher staffed ward had 3 suicides. ([7])

Overall mortality occurs highest as a partial result of anti-psychotic drug induced Tardive Dyskinesia, and sudden death has been reported as a serious adverse effect of taking anti-psychotic medications. ([8], [9]) 

Other studies that have also found patients who take anti-psychotic medications dying at an earlier age than their counterparts who choose not to use psychiatric medications include:

a) A survey of 49 sudden death cases associated with the use of antipsychotic or antidepressant drugs, whereby the antipsychotic class of drugs phenothiazines caused disturbances of the cardiac rhythm. This study showed that in 46 of the 49 cases of sudden death reported in users of antipsychotic or antidepressant drugs, individuals were taking therapeutic doses of phenothiazines, which consisted of the drug thioridazine in over half the cases. The high representation of this class of drugs in individuals with sudden death is indicative of a causal association.[10]

b) In a study of Irish patients, 25 of 72 patients (35%) died over a period of 7.5 years, leading the researchers to conclude that the risk of death for these patients had “doubled” since the introduction of the atypical antipsychotics. [11]

c) Researchers who followed a cohort of 88 patients, ages 25 to 89, over a 10-year period, and noted that 39 of them died over the period. Reduced survival was associated with the administration of two or more anti-psychotics at the same time. The researchers further indicated that patients who were kept on the psychiatric drugs became so burdened with chronic physical illnesses, these replaced the "psychiatric disorder as the primary focus of medical care." The final pathway to early death was global medical decline and death from respiratory illness.[12]

d) Researchers working with the Veteran’s Administration in Ann Arbor, MI, did a retrospective study, reviewing records from 2001 to 2005, and found that patients given anti-psychotic medications following a dementia diagnosis (N=10,615) had a significantly greater likelihood of dying over a 12 month period than other diagnosed patients that did not use anti-psychotic medications (23-29% dying).  When patients were given alternative psychiatric medications, this rate of mortality dropped to 15%. 

Historically, neuropsychiatric symptoms are present in more than 80% of persons with dementia[13], and they are associated with more hospitalizations, nursing home placement, caregiver stress, and depression and with less caregiver employment and income [14] [15] [16] [17] [18] [19]. Such symptoms may be more critical to institutionalization than cognitive symptoms [20], accounting for up to one-third of the costs for care of Alzheimer’s dementia [21].  Research examining treatment of neuropsychiatric symptoms of dementia is modest, and no medication is approved by the Food and Drug Administration (FDA) for this indication. Nevertheless, conventional antipsychotics have long been used to treat neuropsychiatric symptoms. Following the introduction of atypical antipsychotics, with lower reported rates of causing parkinsonism and tardive dyskinesia presentations, there was a significant shift from the use of conventionals to atypicals [22] [23].

That research has more recently now come into question, as researchers in 2015 found that people with Parkinson disease psychosis that were treated with antipsychotics were four times (400% increase) more likely to have died following three to six months of treatment than those who did not receive any antipsychotic medication[24]. They were also more likely to experience serious health issues including cognitive decline, worsening of Parkinson's symptoms, stroke, infections and falls.  The lead researcher indicated “Our findings clearly indicate serious risks associated with antipsychotics…” , noted doctors need to use greater caution, and indicated these findings are similar in that “antipsychotics are known to be linked to serious harm in people with Alzheimer's Disease…”[25].

Modest reductions of neuropsychiatric symptoms of dementia had been reported with risperidone and olanzapine [26] [27] [28] [29] [30], although results from the recently published Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer’s Disease (CATIE-AD), one of the largest studies ever conducted, indicate that response rates with olanzapine, risperidone, and quetiapine are not significantly different from the rates with placebo [31].

In 2005, the FDA issued a warning [32] that, among elderly patients with dementia, the treatment of behavioral disorders with atypical antipsychotics was associated with a higher mortality rate. Of 17 placebo-controlled trials with olanzapine, aripiprazole, risperidone, or quetiapine in patients with neuropsychiatric symptoms of dementia, 15 showed greater mortality (approximately 1.7-fold). Specific causes of deaths were mostly cardiac related or infections. The FDA noted that a warning for conventional antipsychotics was being considered because the limited available data suggested a similarly higher mortality risk. This concern was confirmed by a meta-analysis by Schneider et al. of data from trials of atypicals that included ad hoc haloperidol analyses showing a relative mortality risk of 2.07 [33] and by a study [34] demonstrating that mortality risks with conventional antipsychotics were higher than with atypicals in elderly patients. A recent reanalysis of olanzapine trial data found no significant differences in mortality between olanzapine and risperidone and between olanzapine and conventionals [35].

In Conclusion

There is growing evidence that anti-psychotic and other psychiatric medication usage causes severe and persistent general decline, which often can lead to premature death.  In turn, researchers have documented how such medication usage has directly increased rates of mental health disability, with a direct causal relationship between number of medications, doses of medication and future impairment and mental health decline and disability.[36]  Analysis of the neurological research on the brain can and does account for why this general decline occurs, and I would be happy to further explain why we see such an increase in mortality and mental health disability with the use of these medicines.

[1] Goldman LS. (1999). Medical illness in patients with schizophrenia. Journal of Clinical Psychiatry, 60: 10-15

[2] Babidge N, Buhrich N, Butler T. (2001). Mortality among homeless people with schizophrenia in Sydney, Australia: a 10-year follow-up. Acta Psychiatr Scand; 103: 105-110.

[3] Brown S, Inskip H, Barraclough B. (2000).  Causes of the excess mortality of schizophrenia.  British Journal of Psychiatr, 177: 212-217.

[4] Lawrence D, Jablensky A, Holman C, Pinder T. (2000). Mortality in Western Australian psychiatric patients. Psychiatry Epidemiology, 35: 341-347.

[5] Joukamaa, M., Heliova, M., Knekt, P. at el. (2006). Schizophrenia, neuroleptic medication and mortality, British Journal of Psychiatry, 188: 22-127.

[6] Healy, D. Harris, M. at el. (2006) Lifetime suicide rates in treated schizophrenia: 1875-1924 and 1994-1998, British Journal of Psychiatry, 18, 8, p. 223-228. http://bjp.rcpsych.org/cgi/content/abstract/188/3/223

[7] Diekman, A., and Whitaker, L. (1979). "Humanizing the Psychotherapy ward: Changing from drugs to psychotherapy."  Psychotherapy: Theory, Research, and Practice. 16 (2):204-214.

[8] Ballesteroa J, Gonzales-Pinto A, & Bulbena (2000). Tardive Dyskinesia Associated with Higher Mortality in Psychiatric Patients: Results of a Meta- analysis. American Journal of Clinical Psychopharmacology, 20:188-98

[9] Appleby L, Thomas S, Ferrier N, et. al. (2000).  Sudden unexplained deaths in psychiatric in-patients. British Journal of Psychiatry, 176:405-6

[10] Mehtonen OP; Aranko K; Malkonen L; Vapaatalo H. (1991).  A survey of sudden death associated with the use of antipsychotic or antidepressant druge: 49 cases in Finland. Acta Psychiatr Scand, 84(1):58-64.

[11] Morgan, M, et al. (2003). Prospective analysis of premature morbidity in schizophrenia in relation to health service engagement. Psychiatry Research 117:127-35.

[12]  Waddington, J.. (1998). Mortality in Schizophrenia.  British Journal of Psychiatry, 173 :325-329. 

[13] Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S: Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the Cardiovascular Health Study. JAMA 2002; 288:1475–1483.

[14] Coen RF, Swanick GR, O’Boyle CA, Coakley D: Behavioral disturbance and other predictors of carer burden in Alzheimer’s disease. Int J Geriatr Psychiatry 1997; 12:331–336

[15] Devanand DP, Marder K, Michaels KS, Sackeim HA, Bell K, Sullivan MA, Cooper TB, Pelton GH, Mayeux R: A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer’s disease. Am J Psychiatry 1998; 155:1512–1520

[16] Covinsky KE, Eng C, Lui LY, Sands LP, Sehgal AR, Walter LC, Wieland D, Eleazer GP, Yaffe K: Reduced employment in caregivers of frail elders: impact of ethnicity, patient clinical characteristics, and caregiver characteristics. J Gerontol A Biol Sci Med Sci 2001; 56:M707–M713

[17] Wancata J, Windhaber J, Krautgartner M, Alexandrowicz R: The consequences of non-cognitive symptoms of dementia in medical hospital departments. Int J Psychiatr Med 2003; 33:257–271

[18] Steele C, Rovner B, Chase GA, Folstein M: Psychiatric symptoms and nursing home placement of patients with Alzheimer’s disease. Am J Psychiatry 1990; 147:1049–1051

[19] Kales HC, Chen PJ, Blow FC, Welsh DE, Mellow AM: Rates of clinical depression diagnosis, functional impairment and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry 2005; 13:441–449

[20] Kales HC, Chen PJ, Blow FC, Welsh DE, Mellow AM: Rates of clinical depression diagnosis, functional impairment and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry 2005; 13:441–449

[21] Beeri MS, Werner P, Davidson M, Noy S: The cost of behavioral and psychological symptoms of dementia in community dwelling Alzheimer’s disease patients. Int J Geriatr Psychiatry 2002; 17:403–408

[22] Lopez OL, Becker JT, Sweet RA, Klunk W, Kaufer DI, Saxton J, DeKosky ST: Patterns of change in the treatment of psychiatric symptoms in patients with probable Alzheimer’s disease from 1983 to 2000. J Neuropsychiatry Clin Neurosci 2003; 15:67–73

[23] Rapoport M, Mamdani M, Shulman KI, Herrmann N, Rochon PA: Antipsychotic use in the elderly: shifting trends and increasing costs. Int J Geriatr Psychiatry 2005; 20:749–753

[24] Clive Ballard, Stuart Isaacson, Roger Mills, Hilde Williams, Anne Corbett, Bruce Coate, Rajesh Pahwa, Olivier

Rascol, David J. Burn. Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.Journal of the American Medical Directors Association, 2015; DOI:10.1016/j.jamda.2015.06.021

[25]King's College London. "Antipsychotics increase risk of death in people with Parkinson's disease psychosis." ScienceDaily. ScienceDaily, 30 September 2015. <www.sciencedaily.com/releases/2015/09/150930140141.htm>.

[26] Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M: Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized double-blind trial: Risperidone Study Group. J Clin Psychiatry 1999; 60:107–115

[27] De Deyn PP, Rabheru K, Rasmussen A, Bocksberger JP, Dautzenberg PL, Eriksson S, Lawlor BA: A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999; 53:946–955

[28] Street JS, Clark WS, Gannon KS, Cummings JL, Bymaster FP, Tamura RN, Mitan SJ, Kadam DL, Sanger TM, Feldman PD, Tollefson GD, Breier A: Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing home care facilities: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2000; 57:968–976

[29] Brodaty H, Ames D, Snowdon J, Woodward M, Kirwan J, Clarnette R, Lee E, Lyons B, Grossman F: A randomized, placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003; 64:134–143

[30] De Deyn PP, Carrasco MM, Deberdt W, Jeandel C, Hay DP, Feldman PD, Young CA, Lehman DL, Breier A: Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 2004; 19:115–126

[31] Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA: Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006; 355:1525–1538

[32] Food and Drug Administration: FDA Public Health Advisory: Deaths With Antipsychotics in Elderly Patients With Behavioral Disturbances. Washington, DC, FDA, April 11, 2005 (http://www.fda.gov/cder/drug/advisory/antipsychotics.htm)

[33] Schneider LS, Dagerman KS, Insel P: Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294:1934–1943

[34] Wang PS, Schneeweiss S, Avorn J, Fischer MA, Mogun H, Solomon DH, Brookhart MA: Risk of death in elderly users of conventional vs atypical antipsychotic medications. N Engl J Med 2005; 353:2335–2341

[35] Lopez OL, Becker JT, Sweet RA, Klunk W, Kaufer DI, Saxton J, DeKosky ST: Patterns of change in the treatment of psychiatric symptoms in patients with probable Alzheimer’s disease from 1983 to 2000. J Neuropsychiatry Clin Neurosci 2003; 15:67–73

[36] Whitaker, R. (2010). Anatomy of an epidemic: Magic bullets, psychiatric drugs, and the astonishing rise of mental illness in America. New York: Crown Publishers.