Neuroleptics and Chronic Mental Illness
(research cited in Mad in America).
Affidavit of Peter
C. Gøtzsche, MD
Dr. Grace E. Jackson Affidavit
A Guide to Minimal Use of Neuroleptics: Why and How,
by Volkmar Aderhold, MD, and Peter Stastny, MD, June
Treatment of Young People With Antipsychotic Medications
in the United States, by Mark Olfson, Marissa King,
and Michael Schoenbaum, JAMA Psychiatry, July 1, 2015.
of schizophrenia with antipsychotic medications
eliminate or reduce psychosis? A 20-year multi-follow-up
study, by M. Harrow, T. H. Jobe and R. N. Faull,
Psychological Medicine, 2014.
Antipsychotics and Brain Shrinkage: an Update, by
Joanna Moncrief, M.D., June 19, 2013, Free
Adjunctive Atypical Antipsychotic Treatment for Major
Depressive Disorder: A Meta-Analysis of Depression,
Quality of Life, and Safety Outcomes, by Glen I.
Spielmans, Margit I. Berman, Eftihia Linardatos,
Nicholas Z. Rosenlicht, Angela Perry, Alexander C. Tsai,
PLOS Medicine, Vol 10, Issue 3 (2013)
Risk of Mortality (Including Sudden Cardiac Death) and
Major Cardiovascular Events in Atypical and Typical
Antipsychotic Users: A Study with the General Practice
Research Database, by Tarita Murray-Thomas, Meghan
E. Jones, Deven Patel, Elizabeth Brunner, Chetan C.
Shatapathy, Stephen Motsko, and Tjeerd P. Van Staa1,
Cardiovascular Psychiatry and Neurology (2013, Article
Antipsychotics and brain shrinkage: an update, by
Joanna Moncrieff, MD (2013).
Atypical Antipsychotic Treatment for Major Depressive Disorder: A
Meta-Analysis of Depression, Quality of Life, and Safety Outcomes,
by Glen I. Spielmans, Margit I. Berman, Eftihia Linardatos, Nicholas Z.
Rosenlicht, Angela Perry, and Alexander C. Tsai, PLOS Medicine,Vol.
10:3, e1001403 (March, 2013).
Violence, by Catherine Clarke SRN, SCM, MSSCH,
MBChA. and Jan Evans MCSP. Grad Dip Phys. (2012)
Extrapyramidal motor side-effects of firstand
second-generation antipsychotic drugs, by Michael J.
Peluso, Shon W. Lewis, Thomas R. E. Barnes and Peter B.
Jones, British Journal of Psychiatry, 200, 387-392
Risperdal and Brain Shrinkage: A Warning for Autism
Families, by William J. Walsh, Ph.D, Autism
Science Digest, December, 2012.
Antipsychotics during pregnancy: relation to fetal and
maternal metabolic effects, by Robert Bode´n, MD,
PhD; Maria Lundgren, MD, PhD; Lena Brandt, BSc; Johan
Reutfors, MD, PhD; Helle Kieler, MD, PhD, Arch Gen
Psychiatry 2012; 69: 715-721.
after hospital discharge for people with schizophrenia
or bipolar disorder: retrospective study of linked
English hospital episode statistics, 1999-2006, Uy
Hoang, Robert Stewart, Michael J Goldacre, British
Medical Journal, BMJ 2011;343:d5422 doi:
Intrinsic Suicidal Effects of Neuroleptics: Towards
breaking the taboo and fighting therapeutic recklessness,
by Peter Lehmann, International Journal of
Psychotherapy, Vol. 16, No. 1 (2012).
Second-generation antipsychotics and cardiometabolic
adverse reactions in children and adolescents,
Canadian Adverse REaction Newsletter, Vol 22; Iss.
1, January 2012.
Violence, by Catherine Clarke SRN, SCM, MSSCH,
MBChA. and Jan Evans MCSP. Grad Dip Phys. (2012)
rise and fall of the atypical antipsychotics, by Tim
Kendall, The British Journal of Psychiatry,
Adjunctive Risperidone Treatment for
Antidepressant-Resistant Symptoms of Chronic Military
Service–Related PTSD A Randomized Trial, by John H.
Krystal, MD; Robert A. Rosenheck, MD; Joyce A. Cramer,
BS; Jennifer C. Vessicchio, MSW; Karen M. Jones, MS;
Julia E. Vertrees, PharmD; Rebecca A. Horney, BA; Grant
D. Huang, MPH, PhD; and Christopher Stock, PharmD,
Journal of the American Medical Association,
Questionable Antipsychotic Prescribing Remains Common,
Despite Serious Risks, Bridget M. Kuehn, Journal
of the American Medical Association, vol. 303, No.
16 1582-1584 (2010)
Do antipsychotic medications reduce or increase
mortality in schizophrenia? A critical appraisal of the
FIN-11 study, by Marc De Hert Christoph U. Correll,
and Dan Cohen, Schizophrenia Research 117 (2010) 68–74.
Antipsychotic Medication Use in Medicaid Children and
Adolescents: Report and Resource Guide from a 16-State
Study, from the Medicaid Directors Learning Network and
the Rutgers Center for Education and Research on Mental
Health Therapeutics (CERTs), June 2010.
Pharmacotherapy and the risk for community-acquired
pneumonia, by Jen-Tzer Gau, Utkarsh Acharya, Salman
Khan, Victor Heh, Lona Mody and Tzu-Cheg Kao, MBC
Geriatrics 10:45 (2010)
Letter to Editor from Adam B. Lwein, Phd., Eric A.
Storch, PhD, & Henry D. Storch, MD, re:
Risks from Antipsychotic Medications in Children and
Adolescents, Journal of the American Medical
Association, Vol. 303, No. 8:729 (2010)
Incidence of Tardive Dyskinesia With Atypical Versus Conventional Antipsychotic Medications: A
Prospective Cohort Study, by Scott W. Woods, MD; Hal
Morgenstern, PhD; John R. Saksa, PsyD; Barbara C. Walsh,
PhD; Michelle C. Sullivan, RN; Roy Money, MS; Keith A.
Hawkins, PsyD; RaIitza V. Gueorguieva, PhD; and William
M. Glazer, MD, Journal of Clinical Psychiatry
Use Of Atypical Antipsychotics: Safety, Effectiveness, And Policy
Challenges, by Stephen Crystal, Mark Olfson, Cecilia Huang, Harold
Pincus and Tobias Gerhard, Health Affairs, Vol. 28, No.5:
treatment on weight gain and metabolic abnormalities in patients with
first-episode psychosis, by Swapna Verma, Alvin Liew, Mythily
Subramaniam, Lye Yin Poon,
Australian and New Zealand Journal of Psychiatry, 43,
Cardiometabolic Risk of Second-Generation Antipsychotic
Medications During First-Time Use in Children and
Adolescents, by Christoph U. Correll, MD; Peter
Manu, MD; Vladimir Olshanskiy, MD; Barbara Napolitano,
MA; John M. Kane, MD; Anil K. Malhotra, MD, Journal
of the American Medical Association,
Second-Generation versus First-Generation Antipsychotic
Drugs for Schizophrenia: a Meta-Analysis, by Stefan
Leucht, Caroline Corves, Dieter Arbter, Rolf R Enge,
Chunbo Li, John M Davis, The Lancet, January 3,
2009, Vol 373: 31-41.
Atypical Antipsychotic Drugs and the Risk of Sudden
Cardiac Death (with supplement), by Death Wayne A.
Ray, Ph.D., Cecilia P. Chung, M.D., M.P.H., Katherine T.
Murray, M.D., Kathi Hall, B.S., and C. Michael Stein,
M.B., Ch.B., New England Journal of Medicine,
3603: 225-235 (2009)
The Use of Antipsychotic Medication for People with
Dementia: Time for Action, A Report for the
(English) Minister of State for Care Services, by
Professor Sube Banerjee.
Antipsychotic effects on estimated 10-year coronary
heart disease risk in the CATIE schizophrenia study,
by Gail L. Daumit, Donald C. Goff, Jonathan M. Meyer,
Vicki G. Davis, Henry A. Nasrallah, Joseph P. McEvoy,
Robert Rosenheck, Sonia M. Davis, John K. Hsiao, T.
Scott Stroup, and Jeffrey A. Liebelman, Schizophrenia
Research, 105 (2008) 175-187.
Chronic administration of anti psychotics impede
behavioral recovery after experimental traumatic brain
injury, by Anthony E. Kline, Ann N. Hoffman, Jeffrey
P. Cheng, Ross D. Zafonte, and Jaime L. Massucci,
Neuroscience Letters, 448 (2008) 263-267.
schizophrenia - effect of disease or drug? Results from
a randomized, double-blind, controlled prospective study
in first-episode schizophrenia, by S Saddicha, N
Manjunathaa, S. Ameen, S. akhtar, Acta Psychiatrie
Scandinavia, 2008: 117: 342-347.
administration of anti psychotics impede behavioral
recovery after experimental traumatic brain injury,
by Anthony E. Kline, Ann N. Hoffman,Jeffrey P. Cheng,
Ross D. Zafonte, and Jaime L. Massucci, Neuroscience
Letters, 448 (2008) 263-267.
Double-Blind Comparison of First- and Second-Generation
Antipsychotics in Early-Onset Schizophrenia and
Schizoaffective Disorder: Findings From the Treatment of
Early Onset Schizophrenia Spectrum Disorders (TEOSS)
Study, by Linmarie Sikich, M.D.; jJan A. Frazier,
M.D.; Jon McClellan, M.D.; Robert L. Findling, M.D.;
Benedetto Vitiello, M.D.; louise Ritz, M.B.A.; Denisse
Ambler, M.D.; Madeline Puglia, B.A.; Ann E. Maloney,
M.D.; Emily Michael, B.A.; Sandra De jong, M.D.; Karen
Slifka, R.N.; C.S., Nancy Noyes, C.P.N.P., C.S.;
Stefanie Hlastala, Ph.D.;Leslie Pierson, M.P.H.;Nora K.
McNamara, M.D.; Denise Delporto-Bedoya, M.A.; Robert
Anderson, B.S.; Robert M. Hamer, Ph.D.; Jeffrey A.
lieberman, M.D., American Journal of Psychiatry,
2008 0: appi.ajp.2008.08050756.
Ultrasound Bone Mass in Schizophrenic Patients on
Antipsychotic Therapy, by Purificación
Rey-Sanchez, Jesus M Lavado-García,
Maríia L Canal-Macíias,
Maria A Gómez-Zubeldia,
and Juan D Pedrera-Zamorano, Human Psychopharmacology,
24: 49-54 (2008).
Metabolic and Hormonal Side Effects in Children and
Adolescents Treated With Second-Generation
Antipsychotics, by David Fraguas, M.D.;
Jessica Merchan-Naranjo, M.S.; Paula Laita, M.D.; Mara
Parellada, M.D., Ph.D.; Dolores Moreno, M.D., Ph.D.; Ana
Ruiz-Sancho, M.D.; Alicia Cifuentes, M.S.; Marisa
Giraldez, N.P; and Celso Arango, M.D., Ph.D. Clinical
Psychiatry 69:7 1166-1175 (2005).
Atypical antipsychotic agents for the schizophrenia
prodrome: Not a clear first choice, by Stefan P.
Kruszewski, and Richard P. Paczynski, International
Journal of Risk & Safety in Medicine, 20 (2008)
Necessity and Possibility on Minimal Use of Neuroleptics,
Volkmar Aderhold, Institute For Social Psychiatry,
University of Greifswald.
Medication-induced mitochondrial damage and disease,
by John Neustadt and Steve R. Pieczenik, Mol. Nutr. Food
Res. 2008, 52, 780 – 788.
Antipsychotic Therapy and Short-term Serious Events in
Older Adults With Dementia, by Paula A. Rochon, MD,
MPH, FRCPC; Sharon-Lise Normand, PhD; Tara Gomes, MHSc;
Sudeep S. Gill, MD, MSc; Geoffrey M. Anderson, MD, PhD;
Magda Melo, MSc; Kathy Sykora, MSc; Lorraine Lipscombe,
MD, MSc; Chaim M. Bell, MD, PhD; and Jerry H. Gurwitz,
MD, Archives of Internal Medicine, 168(10):
Randomised, Blinded, Placebo-Controlled Trial in
Dementia Patients Continuing or Stopping Neuroleptics
(The DART-AD Trial), by Clive Ballard, Marisa
Margallo Lana, Megan Theodoulou, Simon Douglas, Rupert
McShane, Robin Jacoby, Katja Kossakowski1, Ly-Mee Yu,
Edmund Juszczak, on behalf of the Investigators DART AD
(PLOS 2008): Vol 5, Iss4, e76; 1-13. The found no
benefit of continuing neuroleptic therapies in older
patients on either cognitive or neuropsychiatric
outcomes, concluding that neuroleptics, with their known
safety issues, including causing death, should not be
used as first-line treatment to manage problems such as
agitation or aggression.
versus placebo for schizophrenia: a Cochrane systematic
review of 40 years of randomised controlled trials,
by Hosam El-Din Matar, Muhammad Qutayba Almerie, Ana
María Giraldo & Clive E. Adams, Cochrane Review (2007).
Factors Involved in Outcome and Recovery in
Schizophrenia Patients Not on Antipsychotic Medications: A 15-Year
Multifollow-Up Study, A longitudinal study of 145 patients found a 40%
recovery rate for those who did not take antipsychotics, versus a 5% rate
for those who did, Journal of Nervous and Mental Disease, Vol 195, May,
2007, No. 5: 407-414.
Use and Mortality in Older Adults with Dementia, by Sudeep S. Gill, MD, MSc;
Susan E. Bronskill, PhD; Sharon-Lise T. Normand, PhD; Geoffrey M. Anderson, MD,
PhD; Kathy Sykora, MSc; Kelvin Lam, MSc; Chaim M. Bell, MD, PhD; Philip E. Lee,
MD; Hadas D. Fischer, MD; Nathan Herrmann, MD; Jerry H. Gurwitz, MD; and Paula
A. Rochon, MD, MPH, Annals of Internal Medicine, 2007;146:775-786.
of first- v. second-generation antipsychotic drugs,” by Davies, L, et
al., L.M.Davies, S. Lewis, P. B. Jones, T. R. E. Barnes, F.Gaughran, K.
Hayhurst, A. Markwick And H. Lloyd On Behalf Of The Cutlass Team, The British
Journal of Psychiatry 191 (2007):14-22 (Cutlass II). This British
government funded study found quality of life is worse on the "atypical"
neuroleptics, such as Risperdal, Seroquel, Zyprexa and Abilify than the older
ones, such as Thorazine and Haldol and came to the overall conclusion that
patients given the older drugs do better than those given the new drugs, which
was the opposite of what they expected.
Full Disclosure: Toward a
Participatory and Risk-Limiting Approach to Neuroleptic Drugs, by Volkmar
Aderhold, MD, and Peter Stastny, MD, Ethical Human Psychology & Psychiatry,
Vol 9, No. 1: 35-61, 2007.
Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics, by
Southern California/RAND Evidence-based Practice Center fro the Agency for
Healthcare Research and Quality, AHRQ Publication No. 07-EHC003-EF, January
2007, including Executive Summary and Appendices. This report found there
was insufficient evidence supporting most of the off label use of "atypical"
neuroleptics, saripiprazole (sold as Abilify), olanzapine (Zyprexa), quetiapine
(Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
Seroquel (quetiapine) in
2007 Physicians Desk Reference (PDR)
Lifetime suicide rates in
treated schizophrenia: 1875-1924 and 1994-1998 cohorts compared, by D.
Healy, M. Harris, R. Tranter, P. Gutting, R. Austin, G. Jones-Edwards, and A.P.
Roberts, British Journal of Psychiatry, (2006), 188 , 223 -228.
This study found a 20 fold increase in the suicide rate for people
diagnosed with schizophrenia since the introduction of the neuroleptics. This
study documents how the suicide rate went from one half of one percent before
the advent of neuroleptics (and deinstitutionalization) to four percent in the
modern era where neuroleptics are the standard treatment.
The study indicated this was probably a result of both deinstitutionalization
and the neuroleptics.
Outcomes, Costs, and Policy Caution A
Commentary on the Cost Utility of the Latest Antipsychotic Drugs in
Schizophrenia Study (CUtLASS 1), by Robert A. Rosenheck, MD, Archives of
General Psychiatry, Vol 63, October, 2006, 1074-6.
National Trends in the Use of Psychotropic Medications by Children,
by Mark Olfson, MD, Steven C. Marcus PhD, Myrna M. Weissman, PhD, and
Peter S. Jensen, MD, Archives of General Psychiatry,
The Effect of
Atypical versus Typical antipsychotics on Tardive Dyskinesia: A Naturalistic
Study, by Jose de Leon, European Archives of Psychiatry/Clinical
Neuroscience, Vol. 257, No. 3:169-172 (2007).
Randomized Controlled Trial of the
Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in
Schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia
Study (CUtLASS 1), by Peter B. Jones, MD, PhD; Thomas R. E. Barnes, MD, DSc;
Linda Davies, MSc; Graham Dunn, PhD; Helen Lloyd, BA; Karen P. Hayhurst, MSc;
Robin M. Murray, MD, DSc; Alison Markwick, BA; Shoˆn W. Lewis, MD, Archives
of General Psychiatry, 2006;63:1079-1087. Measuring quality of life,
symptoms, adverse effects, participant satisfaction, and costs of care,
this study found people tended to do no better, if not a little worse on the
newer "atypical" neuroleptics, such as Zyprexa, Risperdal and Seroquel than the
older ones such as Thorazine and Haldol.
Symbyax (combination Zyprexa and Prozac) Label.
Schizophrenia, neuroleptic medication and mortality,
by Matti Joukamaa, Markku Helovaara, Paul Knekt, Helio Vaara, Arpo Aromaa, Raimo
Ratasalo and Ville Lehtinen, British Journal of Psychiatry (2006), 188, 122-127
found that that in a given time period the relative risk of dying was 2.50
times per increment of one neuroleptic.
Endocrine and Metabolic Adverse
Effects of Psychotropic Medications in Children and Adolescents, by
Christoph U. Correll, M.D., and Harld E. Carlson, M.D, Journal of the
American Academy of Child and Adolescent Psychiatry, 45:7 771-891 (2006).
Commentary: Why Are
Doctors Still Prescribing Neuroleptics?, by B.G. Charlton, QJM, 2006
Effect of Chronic Exposure to Antipsychotic
Medication on Cell Numbers in the Parietal Cortex of Macaque Monkeys, by
Glenn T Konopaske, Karl-Anton Dorph-Petersen, Joseph N Pierri, Qiang Wu, Allan R
Sampson and David A Lewis, Neuropsychopharmacology, 2006, 1-8.
Acute Effects of Atypical Antipsychotics on
Whole-Body Insulin Resistance in Rats: Implications for Adverse Metabolic
Effects, by Karen L Houseknecht, Alan S Robertson, William Zavadosk, E
Michael Gibbs, David E Johnson, and Hans Roilema, Neuropsychopharmacology, 2006,
megabyte Adverse Events Access Database of the so-called "atypical"
neuroleptics Zyprexa, Risperdal, Seroquel, Clozapine, Geodon and Abilify created
by PsychRights from Freedom of Information Act response. This looks to be a
pretty clean database, but there are a few entries that seem not quite right.
The original, flat, text files can be accessed from
Effectiveness of Antipsychotic Drugs in
Patients with Chronic Schizophrenia, by Jeffrey A. Lieberman, M.D., T. Scott
Stroup, M.D., M.P.H., Joseph P. McEvoy, M.D., Marvin S. Swartz, M.D., Robert A.
Rosenheck, M.D., Diana O. Perkins, M.D., M.P.H., Richard S.E. Keefe, Ph.D.,
Sonia M. Davis, Dr.P.H., Clarence E. Davis, Ph.D., Barry D. Lebowitz, Ph.D.,
Joanne Severe, M.S., and John K. Hsiao, M.D., for the Clinical Antipsychotic
Trials of Intervention Effectiveness (CATIE) Investigators, New England
Journal of Medicine, N Engl J Med 2005;353:1209-23. This
government-financed study compared drugs used to treat schizophrenia finding the
newer drugs that are highly promoted and widely prescribed offer few - if any -
benefits over older medicines that sell for a fraction of the cost.
- CATIE II, published in the April, 2006, issue of the American Journal
of Psychiatry, basically gives up on the idea that these drugs
help people to recover and measures success by how long people can stand to
be on them.
- Effectiveness of Clozapine Versus
Olanzapine, Quetiapine, and Risperidone in Patients With Chronic
Schizophrenia Who Did Not Respond to Prior Atypical Antipsychotic Treatment,
by Joseph P. McEvoy, M.D., Jeffrey A. Lieberman, M.D., T. Scott Stroup,
M.D., M.P.H., Sonia M. Davis, Dr.P.H., Herbert Y. Meltzer, M.D., Robert A.
Rosenheck, M.D., Marvin S. Swartz, M.D., Diana O. Perkins, M.D., M.P.H.,
Richard S.E. Keefe, Ph.D., Clarence E. Davis, Ph.D., Joanne Severe, M.S.,
John K. Hsiao, M.D. for the CATIE Investigators American Journal of
Psychiatry 163:600-610, April 2006, doi: 10.1176/appi.ajp.163.4.600
- Effectiveness of
Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients With
Chronic Schizophrenia Following Discontinuation of a Previous Atypical
Antipsychotic, by T. Scott Stroup, M.D., M.P.H., Jeffrey A. Lieberman,
M.D., Joseph P. McEvoy, M.D., Marvin S. Swartz, M.D., Sonia M. Davis, Dr.P.H.,
Robert A. Rosenheck, M.D., Diana O. Perkins, M.D., M.P.H., Richard S.E.
Keefe, Ph.D., Clarence E. Davis, Ph.D., Joanne Severe, M.S., John K. Hsiao,
M.D. for the CATIE Investigators, American Journal of Psychiatry
163:611-622, April 2006, doi: 10.1176/appi.ajp.163.4.611
Does antipsychotic withdrawal provoke psychosis?
Review of the literature on rapid onset psychosis (supersensitivity psychosis)
and withdrawal-related relapse, by J. Moncrief, Acta Psychiatrica
Scandinavica, 2006: 1–11
Ciozapine, Diabetes Mellitus,
Hyperlipidemia, and Cardiovascular Risks and Mortality: Results of a 10-Year
Naturalistic Study, by David C. Henderson, M.D.; Dana D. Nguyen,
Ph.D.; Paul M. Copeland, M.D.; Doug L. Hayden, MA.; Christina P. Borba, frLP.H.;
Pearl M. Louie, M.D.; Oliver Freudenreich, M.D.; A. Eden Evins, M.D.; Corrine
Cather, Ph.D.; and Donald C. Golf, M.D., Journal of Clinical Psychiatry,
65:9, September 2005
Prospective analysis of premature mortality in
schizophrenia in relation to health service engagement: a 7.5-year study within
an epidemiologically complete, homogeneous population in rural Ireland, by
Maria G. Morgan , Paul J. Scully , Hanafy A. Youssef, Anthony Kinsellac, John M. Owensa,
and John L. Waddington, Psychiatry Research 117
(2003) 127–135. This study concluded: "On long-term prospective
evaluation, risk for death in schizophrenia was doubled on a background of
enduring engagement in psychiatric care with increasing provision of
community-based services and introduction of second-generation antipsychotics."
The influence of psychotropic drugs on
cerebral cell female neurovulnerability to antipsychotics, by Raphael M.
Bonelli a, Peter Hofmann a, Andreas Aschoffb, Gerald Niederwieserc, Clemens
Heubergerd, Gustaf Jirikowskib and Hans-Peter Kapfhammera, International
Clinical Psychopharmacology 2005, 20:145-149
The Influence of Chronic Exposure
to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A
Comparison of Haloperidol and Olanzapine in Macaque Monkeys, by Karl-Anton
Dorph-Petersen, Joseph N Pierri, James M Perel, Zhuoxin Sun, Allan R Sampson,
and David A Lewis, Neuropsychopharmacology (2005) 30, 1649–1661.
This study found here was an 8 to 11% reduction in mean fresh brain weights as
well as left cerebrum fresh weights and volumes in both drug-treated groups
compared to the control and found a number of the monkeys became aggressive.
Atypical antipsychotics in the treatment of schizophrenia:
systematic overview and meta-regression analysis by Geddes J, Freemantle N,
Harrison P, Bebbington P., BMJ (British Medical Journal) 2000 Dec
2;321(7273):1371-6 After a systematic and rigorous statistical analysis it was
found that "There is no clear evidence that atypical antipsychotics are more
effective or are better tolerated than conventional antipsychotics."
Happy birthday neuroleptics! 50 year later: la folie
du doute, by Emmanuel Stip, European Psychiatry 2002 ; 17 : 1-5. In this
paper, Dr. Stip asks the following questions: "After 50 year of neuroleptic
drugs, are we able to answer the following simple questions: Are neuroleptics
effective in treating schizophrenia? Is there a difference between atypical and
conventional neuroleptics? How do the efficacy and safety of newer antipsychotic
drugs compare with that of clozapine?" There are a lot of interesting
comments Dr. Stip makes about the lack of answers to these and other questions,
but perhaps the most interesting is: "At this point in time,
responsibility and honesty suggest we accept that a large number of our
therapeutic tools have yet to be proven effective in treating patients with
schizophrenia." He also notes: "One thing is certain: if we wish to base
psychiatry on EBM [Evidence Based Medicine], we run the genuine risk of taking a
closer look at what has long been considered fact."
Effectiveness and Cost of
Olanzapine and Haloperidol in the Treatment of Schizophrenia: A Randomized
Controlled Trial, by Robert Rosenheck, MD; Deborah Perlick, PhD; Stephen
Bingham, PhD; Wen Liu-Mares, PhD; Joseph Collins, ScD; Stuart Warren, JD, PharmD;
Douglas Leslie, PhD; Edward Allan, MD; E. Cabrina Campbell, MD; Stanley Caroff,
MD; June Corwin, PhD; Lori Davis, MD; Richard Douyon, MD; Lawrence Dunn, MD;
Denise Evans, MD; Ede Frecska, MD; John Grabowski, MD; David Graeber, MD;
Lawrence Herz, MD; Kong Kwon, MD; William Lawson, MD; Felicitas Mena, MD; Javaid
Sheikh, MD; David Smelson, PhD; Valerie Smith-Gamble, MD; for the Department of
Veterans Affairs Cooperative Study Group on the Cost-Effectiveness of Olanzapine,
JAMA. 2003;290:2693-2702. Conclusion Olanzapine does not demonstrate advantages
compared with haloperidol (in combination with prophylactic
benztropine) in compliance, symptoms, extrapyramidal symptoms, or
overall quality of life, and its benefits in reducing akathisia and
improving cognition must be balanced with the problems of weight gain
and higher cost.
Analysis of the Olanzapine Clinical Trials – Dangerous Drug, Dubious Efficacy,
an affidavit submitted by Grace E. Jackson in In re: Myers, Anchorage
Superior Court, 3AN 03-277 P/S, March 3, 2003, in which Dr. Jackson
analyzes the drug trials submitted to the FDA for approval of Olanzapine
(Zyprexa). Dr. Jackson had available to her, the Freedom of Information
Act material writer Robert Whitaker obtained in researching
Mad in America: Bad Science, Bad Medicine and the Enduring Mistreatment of the
Persistence of Haloperidol in Human Brain
Tissue, Johannes Kornhuber, M.D., Andreas Schultz, Jens Wiltfang, M.D.,
Ingolf Meineke, Ph.D., Christoph H. Gleiter, M.D., Robert Zöchling, M.D.,
Karl-Werner Boissl, M.D., Friedrich Leblhuber, M.D., and Peter Riederer, Ph.D.,
American Journal of Psychiatry, June 1999, 156:6, 885-890.
Antipsychotics and the Risk of Sudden Cardiac
Death, by Sabine M. J.M. Straus, MD; Gysele S. Bleumink, MD; Jeanne P.
Dielman, PhD; Johan van der Lei, MD, PhD; Geert W. 'tJong, PhD; J. Herre Kingma,
MD, PhD; Miriam C.J.M. Surgenboom, PhD; Bruno H.C. Stricker, PhD, Archives of
Internal Medicine, Vol 164; 1293-1297, June 28, 2004.
Broken Brains or Flawed Studies? A
Critical Review of ADHD Neuroimaging Research, by Jonathon Leo and David
Cohen, The Journal of Mind and Behavior, Winter 2003, Volume 24, Number
1, pp 29-56. This review of studies on ADHD and neuroimaging finds that
most of them can not rule out that the differences observed are medication
caused and the others "inexplicably avoided making straightforward comparisons"
that could have given information on this issue.
Incidence of Tardive Dyskinesia in
First-Episode Psychosis Patients Treated with Low-Dose Haloperidol, by Piet
P. Oosthuizen, M.B,; Robin A. Emsley, M.D.; J. Stephanus Maritz, D.Sc.; Jadri A.
Turner, M.B,; and N. Keyter, R.N., Journal of Clinical Psychiatry, 64:9,
1075-1080, September, 2003, concluded the incidence of tardive dyskinesia was at
least as high for low doses of Haloperidol (Haldol) as for standard doses of
Neuroleptics and Chronic Mental Illness.
This webpage cites and links to a large number of studies that cumulatively show
the widespread use of neuroleptics is resulting in many more chronic mental
health patients than if other strategies were also available. Basically,
this page has all of the studies cited by Robert Whitaker in
Mad in America.
Association of Anticholinergic Load With
Impairment of Complex Attention and Memory in Schizophrenia, by Michael J.
Minzenberg, M.D., John H. Poole, Ph.D., Cynthia Benton, M.D., Sophia Vinogradov,
M.D. in the American Journal of Psychiatry 2004; 161:116–124).
This study found that people given medications for schizophrenia had reduced
functioning in attention and declarative memory, including auditory and visual
memory and complex attention. It concluded that doses of psychiatric medication
within the range of routine pharmacotherapy practice may have clinically
significant effects on memory and complex attention in patients with
schizophrenia and these effects may contribute as much as one-third to
two-thirds of the memory deficit typically seen in patients with schizophrenia.
Do Clozapine and
Risperidone Affect Social Competence and Problem Solving? by Alan S. Bellack,
Ph.D., Nina R. Schooler, Ph.D., Stephen R. Marder, M.D., John M. Kane, M.D.,
Clayton H. Brown, Ph.D., Ye Yang, M.S. in American Journal of
Psychiatry, 2004, 161:364–367). This study found that despite evidence of
clinical improvement with both medications, there was virtually no medication
effect on either social competence or problem solving. The study's conclusions
were that its findings underscore the circumscribed nature of symptomatic
improvement in the broader spectrum of clinical outcomes and suggest that
new-generation medications may not be expected to produce substantial changes in
social role functioning or social problem-solving capacity in the community.
The case against antipsychotic drugs:
a 50-year record of doing more harm than good, by Robert Whitaker,
Medical Hypotheses, Volume 62, Issue 1 , 2004, Pages 5-13 is the
academically written presentation of the information in Mad in America: Bad
Science, Bad Medicine and the Enduring Mistreatment of the Mentally Ill.
The research papers analyzed in both of these publications can be found at
Neuroleptics and Chronic Mental Illness.
The Emperor's New Drugs: An Analysis of
Antidepressant Medication Data Submitted to the U.S. Food and Drug
Administration, by Irving Kirsch, University of Connecticut, Thomas J.
Moore, The George Washington University School of Public Health and Health
Services, Alan Scoboria and Sarah S. Nicholls, University of Connecticut,
Prevention & Treatment, Volume 5, Article 23, posted July 15, 2002.
Clozapine-Induced Constipation Case Report and Literature Review, by Tomer
T. Levin, MBBS, Jonathon Barrett, MBBS, and Alan Medelowitz, M.D., in
Psychosomatics, 43:1, January-February 2002
- Research on the Drug
Treatment of Schizophrenia: A Critical Appraisal and Implications for Social
Work Education by David Cohen, Ph.D., Social Work Education, volume
38, issue 2 (Spring 2002). This article analyzes the systematic flaws and
biases pervading the published research on neuroleptics, including the "atypicals,"
concluding: "These flaws raise serious doubts about the scientific
justifications for the widespread use of neuroleptics." This article was
made available as a public service by the Council on Social Work Education,
publisher of the Journal of Social Work Education."
- Neuroleptics and mortality in
schizophrenia: prospective analysis of deaths in a French cohort of
schizophrenic patients, by Christine Montout, Francoise Casadebaig,
Rajaa Lagnaoui, Helene Verdoux, Alain Philippe, Bernard Begaud, and Nicholas
Moore, Schizophrenia Research 57 (2002) /47-156.
Antipsychotics and the
Risk of Sudden Cardiac Death, Wayne A Ray, PhD; Sarah Meredith, MBBS,
MSc,; Parushottam B. Thapa, MBBS, MPH; Keith G. Meador, MD, MPH;
Kathi Hall, BS; Katerine T. Murray,, MD., Archives of General Psychiatry,
Vol. 58; 1161-1167 (2002).
Content and quality of 2000 controlled trials in
schizophrenia over 50 years, Ben Thornley, Clive Adam, BMJ (British
Medical Journal), Vol. 317, October 1998.
Subcortical MRI Volumes in Neuroleptic-Naive
and Treated Patients With Schizophrenia, by Raquel E. Gur, M.D., Ph.D., Veda
Maany, B.A., P. David Mozley, M.D., Charlie Swanson, M.D., Warren Bilker, Ph.D.,
and Ruben C. Gur, Ph.D, Am J Psychiatry 155:12, December 1998
neuropathological effects of antipsychotic drugs, by Paul J. Harrison,
Schizophrenna Research, 40 1999 87-99, reviews the studies showing the brain
damage caused by neuroleptics.
Follow-up Magnetic Resonance Imaging Study of
Schizophrenia: Relationship of Neuroanatomical Changes to Clinical and
Neurobehavioral Measures, by Raquel E. Gur, MD, PhD; Patricia Cowell, PhD;
Bruce Il Turetsky, MD; Fiona Gallacher, MS; Tyrone Cannon, PhD; Warren Bilker,
PhD; Ruben C. Gur, PhD, Archives of General Psychiatry, 1998, Vol 55,
Striatal Enlargement in Rats Chronically Treated
with Neuroleptic, by Miranda H. Chakos, Osamu Shirakawa, Jeffrey Liebermaii,
Heidi Lee, Robert Bilder, and Carol A. Tamminga, Biological Psychiatry,
1998: 44:675- 684. This study was designed to find out if the striatal
enlargement found in many patients diagnosed with schizophrenia was caused by
the "mental illness" or by the drugs. The drugs caused enlargement in the
rats, which strongly indicates the same is true for people.
A Critique of the Use of
Neuroleptic Drugs by David Cohen, Ph.D., in From Placebo to Panacea,
edited by Seymour Fisher and Roger Greenburg, John Wiley and Sons, 1997 (3.5 mb
file). This is a comprehensive look at what the research really shows about the
use of neuroleptics, including the myth that the newer "atypicals" are any
Clinical Risk Following Abrupt and Gradual Withdrawal,
by Adele C. Viguera, MD, Ross J. Baldessarini, MD, James D. Hegarty, MD, MPH,
Daniel P. van Kammen, MD, PhD, Maricio Tohen, MD, DrPH, Archives of
General Psychiatry, 1997, 54: 49-55, quantified how much the abrupt
discontinuation of long-term neuroleptic use increased relapse rates. This
study concluded that the relapse risk was relatively high within six months;
most patients who remained stable for 6 months continued to do so for long
periods without medication; and the risk of relapse was lower when the
medication withdrawal was gradually discontinued as compared to abrupt
Do neuroleptic drugs
hasten cognitive decline in dementia? Prospective study with necropsy follow up,
by Rupert McShane, Janet Keene, Kathy Gedling, Christopher Fairburn, Robin
Jacoby, Tony Hope, BMJ 1997;314:266 (25 January).
Malignant Syndrome, Iman Bajjoka, PharmD, Tushar Patel, MD, Tami O'Sullivan,
PharmD, Annals of Emergency Medicine, 30:5 (1997).
in Chronic Schizophrenia Followed Prospectively Over 10 Years and its
Longitudinal Relationship to the Emergence of Tardive Dyskinesia, by John L.
Waddington and Hanafy A. Youssef, Psychological Medicine, 1996; 26,
Clozapine, Negative Symptoms, and Extrapyramidal Side Effects, by John M. Kane,
M.D., Allan Z. Safferman, M.D., Simcha Pollack, Ph.D., Celeste Johns, M.D.,
Sally Szymanski, D.O., Michael Kronig, M.D., and Jeffrey A. Lieberman, M.D.,
Journal of Clinical Psychiatry 1994; 55(9, suppl B]: 74-77, found
that the persistence of drug induced parkinsonism can confound the assessment of
therapeutic drug effects on negative symptoms.
FDA approval letter from Robert Temple to
Janssen Research Foundation, dated December 21, 1993, in which the FDA
states it would consider any presentation of data by Janssen that Risperdal® is
superior to Haldol or any other neuroleptic with regard to safety or
effectiveness false, misleading, or lacking fair balance.
Neuropathological Changes in teh Striatum Following 4, 8, and 12 Months of
Treatment with Fluphenazine in Rats, by Dilip V. Jeste, James B. Lohr, and
Michael Manley, Psychopharmacology, 1992; 106, 154-160.
Sustained Remission in Drug-Free
Schizophrenic Patients, by Wayne S. Fenton, M.D., and Thomas H. McGlashan,
M.D., American Journal of Psychiatry, 144:1306-1309 (1987)
Barriers to the Professional Recognition of an Iatrogenic Disease, by
Phil Brown and Steven C. Funk, Journal of Health and Social Behavior,
Vol. 27, No. 2 (Jun., 1986), pp. 116-132
The Effects of Haloperidol on
Synaptic Patterns in the Rat Striatum, by Francine M. Benes, Peter A.
Paskevich, Jessica Davidson and Valerie B. Domesick, Brain Research, 329
Tardive Dyskinesia and
Cognitive Impairment, by James B. Wade, Michael Alan Taylor, Arlene
Kasprisin, Samuel Rosenberg, and Denise Fiducia, Biological Psychiatry,
Tardive Dyskenesia and Dementia,
by O.O. Famuyiwa, D. Eccleston, A.A. Donaldson and R.F. Garside, British
Journal of Psychiatry, 1979; 135, 500-504.
Evidence for Cell Loss in
Corpus Striatum After Long-Term Treatment With a Neuroleptic Drug
(Flupenthixol) in Rats, by Erik B. Nielsen and Melvin Lyon,
Psychopharmacology, 1978; 59, 85-89.
Antischizophrenic Drugs: Chronic Treatment Elevates Dopamine Receptor Binding in
Brain, by David R. Burt, Ian Creese, and Solomon H Snyder, Science,
Vol 196: 326-328 (1977).
Neurotransmitter Receptors After Long-Term Haloperidol: Dopamine, Acetylcholine,
Serotonin, a-Noradrenergic and Naloxone Receptors, by P . Mauer and P .
Seepan, Life Sciences, 1977; Vol. 21, pp . 1751-1758 (1986).
The Significance of Brain Damage in
Persistent Oral Dyskinesia, by H. Edwards, British Journal of Psychiatry,
Treatment of Persistent
Phenothiazine-Induced Oral Dyskinesia, by Peter A. Roxburgh, British
Journal of Psychiatry, 1970; 116, 277-80
Failure to Medicate Does Not Harm Patients
active psychosis neurotoxic? by T. H. McGlashan, Schizophrenia
Bulletin, vol. 32 no. 4 pp. 609–613, 2006
- Untreated Initial Psychosis: Relation to Cognitive
Deficits and Brain Morphology in First-Episode Schizophrenia, by Ho,
Alicata, Ward, Moser, O'Leary, Arndt, and Andreasen, American Journal of
Psychiatry 2003; 160:142-148. This studies' "results suggest that
large-scale initiatives designed to prevent neural injury through early
intervention in the prepsychotic or early psychosis phase may be based on
incorrect assumptions that neurotoxicity or cognitive deterioration may be
- Is There an
Association Between Duration of Untreated Psychosis and 24-Month Clinical
Outcome in a First-Admission Series? by Thomas J. Craig, M.D., Evelyn J.
Bromet, Ph.D., Shmuel Fennig, M.D., Marsha Tanenberg-Karant, M.D., Janet
Lavelle, M.S., and Nora Galambos, Ph.D., American Journal of Psychiatry
157:1, January 2000, 157:60–66.
- Lack of Association Between
Duration of Untreated Illness and Severity of Cognitive and Structural Brain
Deficits at the First Episode of Schizophrenia, by Anne L. Hoff,
Ph.D. Michael Sakuma, Ph.D. Kamran Razi, M.D. Gitry Heydebrand, Ph.D. John
G. Csernansky, M.D. Lynn E. DeLisi, M.D., American Journal of Psychiatry,
- Duration of untreated psychosis and the
long-term, course of schizophrenia, by L. de Haan, and M. van der Gaag,
J. Wolthaus, in Eur Psychiatry 2000 ; 19 : 264-7. Conclusion: "The
results of this study do not support antipsychotic intervention at the
earliest sign of psychosis in order to 'protect the brain'."
- Medication-Free Research in Early
Episode Schizophrenia: Evidence of Long-Term Harm?, by John R. Bola,
Schizophrenia Bulletin vol. 32 no. 2 pp. 288–296, 2006 doi:10.1093/schbul/sbj019,
concludes in this meta- study that good-quality evidence is inadequate to
support a conclusion of long-term harm resulting from short-term
postponement of medication in early episode schizophrenia research.
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