Neuroleptics

General

• Neuroleptics and Chronic Mental Illness (research cited in Mad in America).
• Affidavit of Peter C. Gøtzsche, MD
• The "Clickable" Whitaker Affidavit
• Dr. Grace E. Jackson Affidavit
• How the FDA approved an antipsychotic that failed to show a meaningful benefit but raised the risk of death, by Robert Whitaker, August 17, 2023, BMJ 2023;382:p1801 | doi: 10.1136/bmj.p1801.
• Neuroleptics do much more harm than good and should not be used, by Peter C Gøtzsche, Professor and Director Institute for Scientific Freedom, Copenhagen, Denmark, chapter 4 in Psychological Interventions for Psychosis: Towards a Paradigm Shift, edited by Juan Antonio Díaz-Garrido, Raquel Zúñiga, Horus Lafitte and Eric Morris,Springer, 2003.
• Making Sense of the ‘Chemical Revolution’. Patients’ Voices on the Introduction of Neuroleptics in the 1950s.
• Antipsychotic Effects on Longitudinal Cognitive Functioning in First-Episode Psychosis: A randomised, triple-blind, placebo-controlled study, by Kelly Allott1, Hok Pan Yuen1, Lara Baldwin1, Brian O’Donoghue1, Alex Fornito, Sidhant Chopra4 Barnaby Nelson1, Jessica Graham1, Melissa J. Kerr1, Tina Proffitt, Aswin Ratheesh1, Mario Alvarez-Jimenez1, Susy Harrigan, Ellie Brown1, Andrew D. Thompson1, Christos Pantelis, Michael Berk1, Patrick D. McGorry, Shona M. Francey, and Stephen J. Wood, Rxiv preprint, February 21, 2022.  Researchers found that antipsychotics worsened cognitive functioning in people experiencing a first episode of psychosis. The researchers found that, while those taking a placebo found that their cognitive functioning improved over time, those taking antipsychotics found that their memory became significantly more impaired.
• A Guide to Minimal Use of Neuroleptics: Why and How, by Volkmar Aderhold, MD, and Peter Stastny, MD, June 2015.
• Treatment of Young People With Antipsychotic Medications in the United States, by Mark Olfson, Marissa King, and Michael Schoenbaum, JAMA Psychiatry, July 1, 2015.
• Does treatment 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 Psychology.
• 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 ID 247486).
• Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy Long-term Follow-up of a 2-Year Randomized Clinical Trial, by Lex Wunderink, MD, PhD; Roeline M. Nieboer, MA; Durk Wiersma, PhD; Sjoerd Sytema, PhD; Fokko J. Nienhuis, MA,JAMA Psychiatry. 2013;70(9):913-920.
• Antipsychotics and brain shrinkage: an update, by Joanna Moncrieff, MD (2013).
• 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, and Alexander C. Tsai, PLOS Medicine,Vol. 10:3, e1001403 (March, 2013).
• Neuroleptics and 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 (2012).
• 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.
• Mortality 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: 10.1136/bmj.d5422 (2012).
• About the 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.
• Neuroleptics and Violence, by Catherine Clarke SRN, SCM, MSSCH, MBChA. and Jan Evans MCSP. Grad Dip Phys. (2012)
• Editorial: The rise and fall of the atypical antipsychotics, by Tim Kendall, The British Journal of Psychiatry, 199:266-268 (2011)
• 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, 306(5):493-502 (2011).
• 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
• Broadened 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: w770-w781 (2009).
• Effect of 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, 812-817 (2009).
• 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, 2009;302(16):1765-1773.
• 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.
  • The Spurious Advance of Antipsychotic Drug Therapy, by Peter Tyrer, Tim Kendall, The Lancet, January 3, 2009, Vol 373, 4-5.
• 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 promotion of olanzapine in primary care: An examination of internal industry documents, by Glen I. Spielmans, Social Science & Medicine (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.
• Diabetes and 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.
• 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.
• 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, Raul Roncero-Martín, 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) 37-44.
• On the 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): 1090-1096 (2008)
• A 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.
• Oral fluphenazine 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.
• Antipsychotic Drug 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.
•  “Cost-effectiveness 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.
• Efficacy and 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, 2006;63:679-685.
• 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 99(6):417-420.
• 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, 1-9.
• 35 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 http://psychrights.org/Research/Digest/NLPs/FDAFOIAs/.
• 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.
• An 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 Mentally Ill.
• 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.
  • An Update on ADHD Neuroimaging Research, by David Cohen and Jonathan Leo, The Journal of Mind and Behavior, Spring 2004, Volume 25, Number 2, Pages 161–166.
• 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 conventional antipsychotics.
• 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.
• Death From 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
• The 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, 145-152.
• 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 better.
• 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 discontinuation.
• 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).
• Risperidone-Induced Neuroleptic Malignant Syndrome, Iman Bajjoka, PharmD, Tushar Patel, MD, Tami O'Sullivan, PharmD, Annals of Emergency Medicine, 30:5 (1997).
• Cognitive Dysfunction 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, 681-688.
• 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.
• Study of 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)
• Tardive Dyskinesia: 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 (1985) 265-274
• Tardive Dyskinesia and Cognitive Impairment, by James B. Wade, Michael Alan Taylor, Arlene Kasprisin, Samuel Rosenberg, and Denise Fiducia, Biological Psychiatry, 1987;22:393-395.
• 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).
• Brain 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, 1970;116, 271-75.
• 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

•  Is 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 avoided.
• 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, 2000; 157:1824–1828).
• 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.

Unsealed or Otherwise Formerly Confidential Documents

• Risperdal
• Seroquel
• Zyprexa (from Alaska v. Lilly)

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