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Dr. Toby Watson, PsyD

"Not all answers are found in a prescription pad...    

it's elementary Dr. Watson!"

I have outlined below, in three parts, research related to psychiatric medications causing violence.  The first part is a letter, edited now, that has been submitted to multiple government agencies here in the US and Mexico.  It highlights research on the causal relationship of these medications and suicide-violence.  The second part is a summary on why the body may react with aggression by the introduction of some psychiatric medications.  The third part is a summary of research on these medications not lowering violence.

 


Section 1
Despite the US spending approximately 200 Billion dollars per year on mental health,[5] and 1 in 6 Americans are taking at least one psychiatric drug.[6] The US spends more than any country on the planet for mental health, and more on mental health than any other true medical speciality[7]. Researchers found that 9 out of 10 people who come into a doctor’s office for any mental issue is given a psychiatric drug prescription, and only 10% of discharged patients get in front of a mental health specialist. [8]  In 2006, psychiatrists 60% of the time prescribed two psychiatric drugs, and 33% of the time they prescribed 3 psychiatric drugs. [9]  This initial visit to a doctors office comes following the dozens of screening days, events and measures used today.

Dr. Allen Frances, the Chairperson of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), once called the most important psychiatrist in the world, stated in his new book, “Saving Normal”: Screening devices used scare tactics in order to increase profits, and that it is often not good for people...Screening in general does not improve outcomes, but it burdens people financially with aggressive, expensive unnecessary medical treatments, whereby, billions of dollars are being spent…Mental illness is a “terribly misleading because the diagnosis is no more than descriptions of what we observe people do or say, not established diseases.”

Dr. Thomas Insel, the Director of the National Institute of Mental Health (NIMH), the largest funding agency for research in the world, made it clear they would no longer use the DSM, because the DSM is at best, a “dictionary” simply defining things, and the mental disorder labels “lack validity because they do not have any objective laboratory measure.”

Research has consistently shown that people suffering with mental disorders in general are not more violent than the general public, but there are certain things that cause people to become more violent and suicidal.[10]

We all know poverty and unemployment[11], physical punishment[12] [13], verbal abuse[14], sexual abuse, childhood trauma[15], and exposure to violence are can increase future violence and suicide, but, until recently people have pretty much ignored psychiatric medications as a causal factor for causing an increase in violence, homicide and suicide. 

My colleague Professor Gotzsche, the Director of the Nordic Cochrane Center in Copenhagen, reviewed 70 controlled trials, with more than 18,000 people, and found that if your under 18 years old, taking an antidepressant increased the rate of suicide violence by 200%.[16] 

Researchers Moore and Glenmullen in 2010 found a disproportionate number of violent acts reported to the FDA for psychiatric medications.[17]  In the approximate year and a half sample where doctors reported to the FDA negative effects from drugs, the researchers identified 484 drugs causing severe violence, 31 drugs accounted for the vast majority of all of the cases.

Of the 31, eleven were the most widely used antidepressants, 6 were sleep aids and antianxiety drugs, and 3 were the common stimulants given to children for ADHD. Over 67% of the 400 homicides, 400 assaults, 223 cases of “other violence” and the nearly 900 reports of homicidal ideation where the patient felt they wanted to kill someone, all of these were linked to starting a psychiatric medication.

Keep in mind, this did not include the actual completed suicides, a violence-homicide to oneself. The researchers noted these cases only represented a few percent of the actual cases out there.

If you multiply the numbers, there are hundreds of thousands of acts of violence, suicide, and thousands of homicides, linked to taking psychiatric drugs.

In 1979, 3 different researchers published articles noting how psychiatric medications were increasing violence and aggression. The first researchers noticing psychiatric drugs increasing violence was performed at Queen’s University in Kingston Canada. 

They tracked 375 prison inmates who began taking a psychiatric medication, and found a 250% to 1,000% increase in violence that was “clearly tied to the taking of psychotropic drugs”.[18]

Another researcher noted to their surprise that discharged patients prior the access and use of psychiatric drugs, in 1955, they had lower aggression than patients discharged after having psychiatric medications available.[19] 

Lastly in 1979, a third researcher conducted a controlled study over an eleven month period, whereby they randomized people into typical drug treatment group and a pure psychotherapy group.  The pure psychotherapy group had no suicides or significant acts of aggression, but the psychiatric drug group had 3 suicides and more acts of aggression.[20]

Other controlled studies showing an increase in suicide includes when Prozac was introduced to the market in the 1980s.  Eli Lilly’s own controlled clinical trials showed that Prozac increased the rate of suicidal ideation and actual suicide homicide by a 600-1,200%.[21]   Prozac alone carries 8 drug regulatory agency warnings and studies citing side effects of violence, aggression, mania, or hostility.  Eli Lilly never made this public, and it only became really publicly known after Harvard psychiatrist Dr. Peter Breggin wrote a book called Talk Back to Prozac and appeared before the US Veterans Affairs Committee in 2010.

As a result of the FDA becoming aware of many psychiatric medications causing suicidal ideation and suicide, they added something called Black Box Warning Label to certain psychiatric medications.  The Black Box Warning Labels are a very serious and special warning label that basically states in the label, it has been found that the psychiatric medication causes:

Anxiety, agitation, panic attacks, hostility, irritability, insomnia, aggressiveness, impulsivity, mania and hypomania and akathisia.  Akathisia is a horrible inner agitation and you feel like you want to crawl out of your skin.

The DSM and researchers have stated akathisia causes suicide violence[22] and was formally recognized in the late 1970’s[23] and later supported in the 1980’s with the introduction of the first SSRI (e.g. Prozac).[24] 

 These warnings are often not highlighted to patients and their families, and risks are minimized. 

The violence and suicide increase by taking psychiatric medications has been known for decades and the FDA label demonstrates a known causal relationship. To highlight this point, please consider the following:

 Researcher Aursnes, in 2005, looked at 16 placebo clinical trials, where Paxil was randomized and compared to placebo. They found increase in suicide.

Fergussen in 2005 looked at 702 randomized clinical trials with 87,000 patients, and found psychiatric medication increased suicide thoughts and behavior.[25]

Donovan in 1999 found 229 completed suicides, and higher rates of suicide with antidepressant usage.[26]

Donivan that next year found 2,776 consecutive cases of deliberate harm and violence in 17 year olds to adults, whereby they were seen at the emergency room.  They found the suicide rate increased when they took anti-depressants. [27]

Jick in 1995 did an epidemiological study with 172,000 participants, and found that Prozac resulted in more suicides than older antidepressants.[28]

Researcher Frankenfield looked at corners reports in Maryland, and he found that people taking Prozac and the newer SSRI antidepressants had more violent suicides than before their introduction to the market.[29]

GlaxoSmithKline was asked by the FDA to do a meta-analysis of the studies on Paxil, and in 2006 they noted an increase in suicides by all people taking Paxil.  As a result, they had to send a letter to all the doctors in the US letting them know it caused people to become suicidal and violent.[30]

Valenstein in 2009 did a retrospective study in the veterans administration and looked at 887,000 patients treated with antidepressants, and found a 200% increase in completed suicides with the start of using those psychiatric medication.[31] 

Jururink in 2006 reviewed over 1000 cases of suicide in the elderly, and when given an antidepressant, there was a 500% increase in suicide after starting the psychiatric medication.[32]

Preda in 2001 found that 8.1% of psychiatric admissions were due to antidepressant induced mania.[33]  Please note that mania is whereby a person does not sleep or only sleeps for a few hours.  Mania is huge bouts of energy, whereby, the person does not think clearly, might engage in high risk taking behaviors and can become delusional and psychotic.  Mania is well known to play a causal role to suicide and violence. 

Morishita in 2003 conducted a retrospective review of 79 patients treated for depression with Paxil.  Morishita found that 8.6% developed hypomania or mania.[34]

Howland in 1996 found 6% had psychiatric drug induced mania.[35] 

Ebert in 1997 found 17% of the patients developed hypomania and became suicidal and dangerous.[36]

A Harvard Medical School study by Wilens in 2003 found that 22% of the participants developed severe adverse psychiatric events and disturbances of their mood.[37]

To again show causality, another researcher conducted a “Rechallenge” study.  This type of study is where the researcher adds a drug, sees a problem so they take the drug away, sees the problem go away, but then reintroduces they drug again to see if the negative result happens again. This type of study is very good for showing causality.  Re-exposure to antidepressant drugs lead to 44% of the people again becoming disturbed with irritability, anxiety, mania and insomnia, and 4% became aggressive and violent.  Healy in 2006 evaluated controlled clinical trial data for Paxil (GlaxoSmithKline), and found an increased rate of aggression.[38]

This causation is leading the courts, researchers and governments to recognize the dangers to these medications.  In 2016, a California court decided to drop attempted murder charges when the court heard psychiatric testimony on how medications cause an elderly man to use a meat cleaver upon his wife.[39]   In 2011, a Winnipeg Canadian judge agreed that Prozac made an individual become murderous due to the manic, suicidal and violent effects of the drug. This was in result to a 16 year old violently stabbing his friend to death.[40]

Sanji Gupta noted a few years ago on CNN, and in response to a mass shooting: “it's worth pointing out, over a seven-year period, there were 11,000 episodes of violence related to drug side effects.”

In 2015, researchers showed that young adults up to age 24 were nearly 50 percent more likely to be convicted of a homicide, assault, robbery, arson, kidnapping, sexual offense and other violent crime when taking antidepressants than when they weren’t taking the psychiatric drug.[41]

US Secretary of Homeland Security, Tom Ridge, publicly stated that psychiatric drugs probably contributed to the Columbine school Mass shootings and murder.  Such research and mainstream comments have now led to several documentary movies, such as the United Kingdom movie “Prescription for Murder”, whereby they note the link between psychiatric medications causing murder. 

In conclusion, there are a host of controlled clinical trials, epidemiological studies and overwhelming clinical reports mounting and showing how psychiatric medications are leading to an increase in suicide, violence homicide, and overall aggression.  There are 27 international drug regulatory warnings on psychiatric drugs, citing effects of mania, hostility, violence and homicidal ideation.[42]  Despite warning labels, from 1999-2013, psychiatric medications increased by over 117%, concurrent with a 240% increase in death rates from those medications.[43] 

Whereas blaming medications for suicide and violence would have been like saying umbrellas cause rain, we now have the above controlled data, and 3 large meta-analysis studies showing that more psychiatric treatment equates with more suicide-violence[44] [45] [46], even if a healthy volunteer without a psychiatric disorder takes these psychiatric medications.[47] [48]


[5]https://www.huffingtonpost.com/entry/highest-health-costs-mental_us_574302b8e4b045cc9a716371 Accessed 11-18-17.

[6]Moore TJ, Mattison DR. (2016). Adult utilization of psychiatric drugs and differences by sex, age, and race. JAMA Internal Medicine, 177(2), 274-275 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2592697. Accessed 11-18-17

[7] http://www.latimes.com/nation/la-na-healthcare-comparison-20170715-htmlstory.html

[8] Carnahan, 2002; Cummings, 2006.

[9] https://www.jhsph.edu/news/news-releases/2010/mojtabai-psych-drugs.html. Accessed 11-19-17

[10] http://www.drtobywatson.com/violence-prediction.html. Accessed 11-19-17

[11] Gilligan, J. (1996). Violence: Reflections on a National Epidemic. New York: Vintage Books.

[12] Corporal Punishment and other formative experiences associated with violent crimes. The Journal of Psychohistory, 35(1), pp. 71-82.

[13] Lansford J.E., Chang, L., Dodge, K.A., Malone, P.S., Oburu, P., Palmacrus, K., Bacchini, D., Pastorelli, C., Bombi, A.S., Zelli, A., Tapanya, S., Chaudhary, N., Deater-Deckard, K., Manke, B., & Quinn, N. (2005). Physical discipline and children's adjustment: Cultural normativeness as a moderator. Child Development, 76 (6), pp. 1234-1246

[14] Choi, J., Jeong, B., Rohan, M.L., Polcari, A.M., & Teicher, M.H. (2009). Preliminary evidence of white tract matter abnormalities in young adults exposed to parental verbal abuse. Biological Psychiatry 65(3), 227-234

[15] Anda, R.F., Felitti, V.J., Bremner, D.J., Walker,J.D., Whitefield, C., Perry, B.D., Dube, S.R., & Giles, W. (2006). The enduring effects of abuse and related adverse experiences in childhood: A convergence of evidence from neurobiology and epidemiology. European Archives of Psychiatry and Clinical Neuroscience, 256, pp.174-186.

[16] http://www.bmj.com/content/352/bmj.i65. Accessed 11-19-17

[17] Moore TJ, Glenmullen J, Furberg CD (2010) Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 5(12): e15337. doi:10.1371/journal.pone.0015337

[18] Workman, D.G., Cunningham, D.G., (1975). “Psychotropic Drugs on Aggression in a Prison Setting” In Canadian Family Physician, pp. 63-64.  Queen's University, Kingston.

[19] Rabkin, J.1979, Criminal Behavior of Discharged Mental Patients, Psychological Bulletin, 86, 1-27. 

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

[21] https://www.youtube.com/watch?v=SBJfZtB_3cc

[22] Crowner ML, et al (1990)  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/1973544" http://www.ncbi.nlm.nih.gov/pubmed/1973544

[23] GB. Leong, M.D. and JA Silva, M.D. (2003)
HYPERLINK "http://library-resources.cqu.edu.au/JFS/PDF/vol_48/iss_1/JFS2002173_481.pdf" http://library-resources.cqu.edu.au/JFS/PDF/vol_48/iss_1/JFS2002173_481.pdf

[24] Talking back to prozac: What doctors aren't telling you about today's most controversial drug. Von P. R. Breggin und G. Ross Breggin. St. Martin's Press, New York, 1994. 273 S., geb. 19.95 $. – ISBN 0-312-11486-9

[25] Fergusson, D., Doucette, S., Glass, K., Shapiro, S., Healy, D., Hebert, P., et al. (2005). Association between suicide attempts and selective serotonin reuptake inhibitors: A systematic review of randomized controlled clinical trials. British Medical Journal, 330, 396 – 403.

[26] Donovan, S., Kelleher, M., Lambourn, J., & Foster, T. (1999). The occurrence of suicide following the prescription of antidepressant drugs. Archives of Suicide Research, 5, 181–192.

[27] Donovan, S., Clayton, A., Beeharry, M., Jones, S., Kirk, C., Waters, K., et al. (2000). Deliberate self-harm and antidepressant drugs: Investigation of a possible link. British Journal of Psychiatry, 177, 551–556.

[28] Jick, S., Dean, A., & Jick, H. (1995). Antidepressants and suicide. British Medical Journal, 310, 215 – 218.

[29] Frankenfi eld, D., Baker, S. Lange, W., Caplan, Y., & Smialek, J. (1994). Fluoxetine and violent death in Maryland. Forensic Science International, 64, 107–117.

[30] GlaxoSmithKline. (2006, May). Dear Healthcare Professional: Important prescribing information [regarding Paxil-induced suicidality]. Philadelphia: Author.

[31] Valenstein, M., Kim, H., Ganoczy, D., McCarthy, J., Zivin, K., Austin, K., et al. (2009). Higher Risk periods of suicide among VA patients receiving depression treatment: Prioritizing suicide prevention efforts. Journal of Affective Disorders, 112, 50 – 58

[32] Jurrlink, D., Mamdani, M., Kopp, A., & Redeimeier, D. (2006). The risk of suicide with selective serotonin reuptake inhibitors in the elderly. American Journal of Psychiatry, 163, 813– 821.

[33] Preda, A., MacLean, R., Mazure, C., & Bowers, M. (2001). Antidepressant-associated mania and psychosis resulting in psychiatric admission. Journal of Clinical Psychiatry, 62, 30 – 33.

[34] Morishita, S., & Arita, S. (2003). Induction of mania in depression by paroxetine. Human Psychopharmacology, 18, 565 –568

[35] Howland, R. (1996). Induction of mania with serotonin reuptake inhibitors. Journal of Clinical Psychopharmacology, 16, 425– 427.

[36] Ebert, D., Albert, R., May, A., Merz, A., Murata, H., Stosiek, I., et al. (1997). The serotonin syndrome and psychosis-like side effects of fluvoxamine in clinical use —An estimation of incidence. European Neuropharmacology, 7, 71–74.

[37] Wilens, T., Biederman, J., Kwon, A., Chase R., Greenberg, L., Mick, E., et al. (2003). A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors. Journal of Child and Adolescent Psychopharmacology, 13, 143–152.

[38] Healy, D., Herxheimer, A., & Menkes, D. (2006). Antidepressants and violence: Problems at the interface of medicine and law. PLoS Medicine, 3, 1478 –1487.

[39] https://breggin.com/attempted-murder-charges-dropped-due-to-medication-toxicity/

[40] https://breggin.com/judge-prozac-turned-teen-into-murderer/

[41] https://www.cchrint.org/2016/09/30/are-psychiatric-drugs-fueling-increase-in-murders/#_edn4

[42] https://www.cchrint.org/psychiatric-drugs/drug_warnings_on_violence/

[43]https://meps.ahrq.gov/mepsweb/data_stats/download_data_files_results.jsp?cboDataYear=All&cboDataTypeY=2%2CHousehold+Event+File&buttonYearandDataType=Search&cboPufNumber=All&SearchTitle=Prescribed+Medicines

[44] http://content.iospress.com/articles/international-journal-of-risk-and-safety-in-medicine/jrs0645 [9] http://archpsyc.jamanetwork.com/article.aspx?articleid=210055

[45] http://www.ncbi.nlm.nih.gov/pubmed/15555028

[46]https://www.researchgate.net/publication/26713983_The_Relationship_Between_General_Population_Suicide_Rates_and_Mental_Health_Funding_Service_Provision_and_National_Policy_a_Cross-National_Study

[47] http://www.sciencedirect.com/science/article/pii/S0160252713000587

[48] https://www.ncbi.nlm.nih.gov/pubmed/2301661/

Section 2

Neuroleptic and Anti-Depressant Induced Violence

The purpose of this document is to provide a referenced explanation of how some psychiatric medications can cause of violence in otherwise non-violent individuals.  Some of this information has been adapted from reference material.[1]  Additional research below demonstrates other research showing psychiatric medications not reducing violence.

In 2010, researchers Moore and Glenmullen highlighted there was a disproportionate number of violent acts reported to the Federal Drug Associations (FDA) adverse reporting system.[2]  They found that violent “adverse events” are associated with anti-depressant and several other types of psychotropic medications. In reviewing 2004 to 2009 data, they found that of the 484 drugs identified as trigging violence, 31 drugs accounted for the vast majority of all of the cases of violence. These drugs were 11 of the most widely used anti-depressants, 6 of the sleep aids and anti-anxiety (hypnotics and sedatives) drugs, and 3 of the stimulant drugs often given for concentration issues or fatigue. It means that over 67% of the 400 homicides, 400 assaults, 223 cases of “other violence” and the nearly 900 reports of homicidal ideation were all linked to the psychiatric medications. This did not include the actual completed suicides to one’s self or other violent acts against one’s self. The researchers noted the reported cases represent only represented a few percent of the actual cases out there.

Both government agencies, departments and private researchers have been identifying the dangers of how psychiatric medications can negatively impair outcomes and cause suicides and violence:     

Neuroleptic and Anti-depressant medications causing disruption of neurotransmitter circuits (e.g.
dopamine, serotonin, norepinephrine/ noradrenaline and acetylcholine).

Pharmacogenetics – the issue of inefficient metabolising.

Psychological Locus of Control being externalized and creating a “Spell Binding Effect”.

Adverse Effects on Behaviour of Neuroleptics
 
Neuroleptic and Selective Serotonin Reuptake Inhibitor (SSRI) toxic adverse reactions are related to behavioural changes such as akathesia, which is known to be a predisposing factor to violence[3] and was formally recognized in the late 1970’s[4] and later supported in the 1980’s with the introduction of the first SSRI (e.g. Prozac).[5]  The symptoms of akathisia, an extreme, involuntary internal physical and emotional restlessness, includes restlessness, agitation and irritability, has been linked to suicides and aggression, and is acknowledged by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 

A marked increase of violence has occurred with patients prescribed moderately high-doses of haloperidol,7  and regular doses of clozapine.[6] Both the older ‘typical’ and the newer ‘atypical’ neuroleptics are associated with adverse behavioural reactions, noting that “the newer antipsychotics did not reduce violence more than” older drugs.[7] 

Observations in prisons have also noted neuroleptics and increased aggressive behaviour. Inmates are better able to control their aggression until they were prescribed neuroleptics, whereby,  the aggression rate almost tripled.[8]

 
Neuroleptic Withdrawal Adverse Effects on Behaviour

There is also the issue of violence experienced during withdrawal. Irritability and agitation is reported in association with neuroleptic withdrawal,[9] and akathisia has been noted to be a withdrawal effect.

Neurotransmitter Functioning and Behaviour

Fundamentally, human behaviour is determined by neurotransmitter functioning and “A rich literature exists to support the notion that monoamine (i.e. serotonin, dopamine, and norepinephrine) neurotransmitter functioning is related to human aggressive behaviour.”[10]

Dopamine, serotonin and all other neurotransmitter circuits are interdependent and any disturbance in one will result in an imbalance in them all, disrupting normal functioning. Jackson's First Law of Biopsychiatry states:  “For every action, there is an unequal and frequently unpredictable reaction.”[11]

Chronic neuroleptic treatment causes unpredictable behavioural reactions due to dysregulation and disruptions between dopamine, serotonin and acetylcholine neurotransmitters.

Despite patients being told they suffer from too much dopamine or serotonin in the brain, researchers who investigated this hypothesis during the 1970s and 1980s were unable to find evidence that people with psychosis had, in fact, overactive dopamine systems[12]. In fact, attempts to quantify D2 receptor density in vivo with PET scans have also proved inconclusive results.[13] Within the psychiatric research community, this was widely acknowledged in the late 1980s and early 1990s. As Pierre Deniker, who was one of the founding fathers of psychopharmacology, confessed in 1990: The dopaminergic theory…retains little credibility for psychiatrists.[14] With regards to Serotonin, Dr. Steven Rose, a Professor and neuroscientist at Open University, UK, reported a study of serotonin levels in psychiatric patients compared with psychiatric nursing staff. Both groups had the same levels, but only the patients reported feeling depressed. [15]

Since people struggling with psychosis have no known “chemical imbalance” in the brain, antipsychotic drugs cannot be said to work by “balancing” brain chemistry. These drugs are not like “insulin for diabetes.” They do not serve as a corrective to a known biological abnormality.  Instead, standard antipsychotics (also known as older neuroleptics) work by powerfully blocking dopamine transmission in the brain. Specifically, these drugs block 70% to 90% of a particular group of dopamine receptors known as D2 receptors.[16] This thwarting of normal dopamine transmission is what causes the drugs to be so problematic in terms of their side effects.

In the 1970s, two physicians at McGill University, Guy Chouinard and Barry Jones, offered a biological explanation for why this is so. The brain responds to neuroleptics and their blocking of dopamine receptors as though they are a pathological insult. To compensate, dopaminergic brain cells increase the density of their D2 receptors by 40%  to 90%.[17] The brain is now “supersensitive” to dopamine, and as a result, the person has become more biologically vulnerable to psychosis than he or she would be naturally. The two Canadian researchers wrote: “Neuroleptics can produce a dopamine supersensitivity that leads to both dyskinetic and psychotic symptoms. An implication is that the tendency toward psychotic relapse in a patient who had developed such a supersensitivity is determined by more than just the normal course of the illness. [18]

MRI-imaging studies have powerfully confirmed this hypothesis. During the 1990s, several research teams reported that antipsychotic drugs cause atrophy of the cerebral cortex and an enlargement of the basal ganglia.[19], [20], [21]  In 1998, investigators at the University of Pennsylvania reported that the drug-induced enlargement of the basal ganglia is “associated with greater severity of both negative and positive symptoms.” In other words, they found that the drugs cause morphological changes in the brain that are associated with a worsening of the very symptoms the drugs are supposed to alleviate.[22]

This is analogous to what happens in tardive dyskinesia (TD), in which dopaminergic (DA) receptors in the nigro neostriatal pathway are up-regulated (i.e. the DA receptors become more numerous and sensitive) secondary to chronic DA blockade, thereby causing the random purposeless movements seen in TD, the Dopaminergic receptors in the meso limbic pathway (thought to mediate the positive symptomatology, such as voices and delusions) become more sensitized and numerous (i.e. up-regulated).

When the person removes the anti-psychotic-Dopaminergic blocking agent, particularly abruptly, it 'unmasks' the now up-regulated Dopaminergic receptors resulting in a 'tardive’ or ‘rebound’ or ‘supersensivity’ psychosis.[23]

Researchers have found the same is true for anti-depressant medications, such as SSRI’s[24],[25], whereby they call this upregulation of the serotonergic system “Tardive dysphoria”[26] and “oppositional tolerance”[27],[28].  Researchers note “in the era prior to pharmacotherapy, poor outcome in mania was considered a relatively rare occurrence, however, modern outcome studies have found that a majority of bipolar patients evidence high rates of functional impairment.” In their discussion of this deterioration in outcomes, they concluded that “medication-induced changes” may be at least partly responsible. Antidepressants may cause a “worsening of the course of illness,” while the antipsychotics may lead to more “depressive episodes” and “lower functional recovery rates.” Drug side effects, they added, may “explain the cognitive deficits in bipolar disorder patients.”[29] 

Harvard researchers observe that “prognosis for bipolar disorder was once considered relatively favourable, but contemporary findings suggest that disability and poor outcomes are prevalent.” They note that “neuropharmacological-neurotoxic factors” might be causing “cognitive deficits in bipolar disorder patients.”[30]

Neuroleptics and Serotonin Disruption

Some neuroleptics are known as serotomimetic drugs, affecting serotonin receptors – some block the receptors and some make them more active. "There are 14 different types of serotonin receptors that may be targeted by neuroleptics, with risperidone, clozapine, olanzapine, quetiapine and clopixol especially affecting the serotonin 5-HT2 receptor.”[31] 

Mental status changes occur in Serotonin Syndrome. This is caused by neuroleptic drugs due to serotonin toxicity. Animal research indicates that serotonin disruption is associated with increased violence. Reduced levels of a specific serotonin metabolite (5-HIAA) in cerebrospinal fluid has been linked with increased aggression in both dogs and male rhesus macaques[32] [33], and low concentrations of 5-HIAA in different cultures have been consistently reported to be associated with impulsive destructive behaviours, aggression and violence.[34]

Since “Impulsive violence is closely linked to serotonergic function and to several brain regions”[35] and since impulsivity is also linked with both low and high serotonin levels it is difficult to know which of these changes play the most important role in treatment emergent violence.”[36] 

The reciprocal interaction between the dopaminergic and serotonergic systems disturbed by either dopaminergic blockers or serotonergic enhancers leads to the disruption of homeostasis.[37] Although the serotonin system and its interactions with other neurotransmitters are complex and full information is difficult to find, there are clear research papers, which show that serotonin and aggression are related.

Neuroleptics and Noradrenaline/Norepinephrine Disruption
Neuroleptics affect the norepinephrine neurotransmitter and akathisia induction with haloperidol is known to be associated with increased noradrenaline turnover.[38] [39]

Neuroleptics and Acetylcholine Disruption

An important function of the acetylcholine neurotransmitter is the control of psychological defence mechanisms including fight or flight responses.  Such responses are impulsive and naturally include aggression and violence.

In varying degrees, all neuroleptic drugs have anticholinergic properties. This means that they block and cause disruption to the acetylcholine neurotransmitters. The body compensates and responds by making and releasing more acetylcholine.[40]

Acetylcholine Disruption and Increased Violence

Aggressive responses such as defensive rage and violence have been linked with excessive acetylcholine in animals [41] [42]  [43] and a relative acetylcholine increase is associated with neuroleptic drugs due to the disruption of the dopamine-acetylcholine equilibrium.[44] [45]   

Since excessive acetylcholine is linked with aggression and violence in animals, it is likely that neuroleptic induced acetylcholine abundance triggers aggression and violence in humans.

Neuroleptic → Disrupted dopamine-acetylcholine equilibrium → Relative acetylcholine increase → Aggression/Violence.

Neuroleptic Malignant Syndrome and Organophosphate Exposure

Neuroleptic Malignant Syndrome (NMS) is an adverse effect of neuroleptics, a potentially fatal condition with up to 76% mortality rate.  Symptoms of NMS include aggression, agitation and violence.[46] [47]  New research associates NMS with elevated acetylcholine.[48]

Organophosphate chemicals form the basis of many insecticides, herbicides and nerve gases. They block the action of the body’s acetylcholinesterase enzyme, which breaks down acetylcholine so it may be processed and recycled. Excessive acetylcholine accumulates in the nervous system if the action of this enzyme is blocked. 

Prolonged and repeated exposure to Organophosphates results in Chronic Organophosphate-Induced Neuropsychiatric Disorder (COPIND) e.g. in farmers who handle pesticides, due to chronic Organophosphate Poisoning (OP). COPIND behavioural symptom changes include: Hostility, Anger, Aggression and Violence.[49] [50]  Since OP results in excessive acetylcholine, which is linked with aggression and violence in animals, the behavioural changes in COPIND are highly likely caused by excessive acetylcholine.

The link between Neuroleptic Malignant Syndrome and Organophosphate Poisoning

The symptoms of NMS and OP are similar. In both NMS and OP the replication of symptoms is due to autonomic instability and stems from disruption of the acetylcholine circuits and transmitters of the Autonomic Nervous System, involved with vital involuntary functions.

Autonomic Instability includes profuse sweating, high blood pressure, low blood pressure, respiratory distress, drooling, urinary or faecal incontinence, increased and decreased heart rate.[51]

Conclusion: Organophosphates, Neuroleptics and Violence

Organophosphate Poisoning results in over stimulated acetylcholine neuro-circuits and systems. The action of neuroleptics is similar.  It is generally accepted that Organophosphate Poisoning results in behavioural changes including violence.                                     

Despite research to show that neuroleptics are associated with disrupted acetylcholine, it is not yet generally accepted that neuroleptics are a potential cause of violence.

Antipsychotic/neuroleptic drugs have strong anti-cholinergic properties and long-term use causes behavioural changes, which replicate the same behavioural changes occurring in chronic Organophosphate Poisoning:  

“This adaptation (to psychiatric drugs - author input) replicates the effect of organophosphate poisoning whether by nerve gas, by insecticide, or by anti-Alzheimers pharmaceuticals by over stimulating acetylcholine circuits of the brain.”[52]  

 
Increased Prescribing of Neuroleptics

There has been a distinct increase in neuroleptic medications, prescribed as part of treatment for mental health issues.

Increased Prescribing as a Risk for Increased Violence

As outlined above, neuroleptics are a possible cause of violence. With ever increased prescribing of neuroleptic medications, it is reasonable to expect an increased amount of violent behaviour amongst those with a severe mental health diagnosis.

Since anti-psychotic medication usage is increasing by a staggering rate each year, it has now become one of the two best selling prescription drugs on the entire market in the Untied States, despite it’s very limited FDA approval use, the rise in violence for neuroleptic-treated patients will escalate.[53]

Conclusion

Those treated with neuroleptic medication and or SSRI medications are at a higher risk of causing violence towards others and themselves, as their psychiatric medications disrupt neurotransmitter functions in the brain that decides or does not decide to hit, shoot or kill someone. It creates a “super-sensitivity” to the very problem they may be dealing with and or create an medication induced aggressive behaviour.

Of the most recent years of mass shootings, every one of the patients were taking or just stop taking a psychiatric medication known to cause suicidal ideation, suicide attempts and or aggression.[54] It is almost without question at this point, that anyone who is well versed in the research does not acknowledge the link that the pharmaceutical companies themselves acknowledge, that taking psychiatric medications can increase the rate of violence to self and other.

[1] Clarke, C. and Evans, J., Grad Dip Phys. August 19th, 2012. http://domenicofargnoli.com/tag/selective-serotonin-reuptake-inhibitor/

[2] Moore TJ, Glenmullen J, Furberg CD (2010) Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 5(12): e15337. doi:10.1371/journal.pone.0015337

[3] Crowner ML, et al (1990) http://www.ncbi.nlm.nih.gov/pubmed/1973544

[4] GB. Leong, M.D. and JA Silva, M.D. (2003)

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[5] Talking back to prozac: What doctors aren't telling you about today's most controversial drug. Von P. R. Breggin und G. Ross Breggin. St. Martin's Press, New York, 1994. 273 S., geb. 19.95 $. – ISBN 0-312-11486-9

[6] KA.Mansour, C.Willan and J.Follansbee (2003)  http://bapauk.com/doc/Deteriorationofpsychosisinducedbyclozapine_41.doc

[7] Jeffrey W. Swanson et al, (2008) http://bjp.rcpsych.org/content/193/1/37.full

[8] D.G. Workman and D.G. Cunningham (1975) page 65

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2274756/pdf/canfamphys00332-0065.pdf

[9] MIND,  http://www.mind.org.uk/help/medical_and_alternative_care/making_sense_of_coming_off_psychiatric_drugs

[10] Theodore Van Putten, (1975)

http://psychrights.org/research/Digest/NLPs/RWhitakerAffidavit/VanPuttenManyFacesofAkathisia.PDF

[11] Jackson, Grace E. MD, Appendix D, Transcript of “What Doctors May Not Tell You About Psychiatric Drugs”    Public Lecture, Centre for Community Mental Health – UCE Birmingham June 2004

[12] Knable, M. B., Kleinman, J. E., & Weinberger, D. R. (1998). Neurobiology of schizophrenia. In A. F. Schatzberg & C. B. Nemeroff (Eds.), Textbook of Psychopharmacology, 2nd ed., (pp.595-596). Washington, DC: American Psychiatric Press.

[13] Knable, M. B., Kleinman, J. E., & Weinberger, D. R. (1998). Neurobiology of schizophrenia. In A. F. Schatzberg & C. B. Nemeroff (Eds.), Textbook of Psychopharmacology, 2nd ed., (pp.595-596). Washington, DC: American Psychiatric Press.

[14] Deniker, P. “The neuroleptics: a historical survey.” Acta Psychiatrica Scandinavica 82, supplement 358 (1990):83-87.

[15] Biological Citizenship, in Aihwa Ong and Stephen Collier, eds., Global Assemblages: Technology, Politics and Ethics as Anthropological Problems, pp. 439-463. Oxford: Blackwell, 2005.

[16] Wysong, P., PET Brain Scans Best to Determine Schizophrenics’ drug dosages, In Washington Post, April 12, 2000, Vol. 36, Issue 14.

[17] Silvestri S, Seeman MV, Negrete JC et al. (October 2000). "Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study". Psychopharmacology 152 (2): 174–80. doi:10.1007/s002130000532. PMID 11057521.

[18] Chouinard, G, et al. “Neuroleptic-induced supersensitivity psychosis.” American Journal of Psychiatry 135 (1978):1409-10. Also see Chouinard, G, et al. “Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics.”  American Journal of Psychiatry 137(1980):16-20.

[19] Gur, R, et al. “A follow-up magnetic resonance imaging study of schizophrenia.” Archives of General Psychiatry 55 (1998):142-152.

[20] Chakos M, et al. “Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.” American Journal of Psychiatry 151 (1994):1430-6.

[21] Madsen A, et al. “Neuroleptics in progressive structural brain abnormalities in psychiatric illness.” The Lancet 352 (1998): 784-5.

[22] Gur, R, et al.  “Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia.” American Journal of Psychiatry 155 (1998):1711-17.

[23] Samaha, A., Seeman, P., et al, “Breakthrough Dopamine Supersensitivity during Ongoing Antipsychotic Treatment Leads to Treatment Failure over Time.”  Journal of Neuroscience 27 (11) 2007: 2979-2986.

[24] E. Richelson, “Biological basis of depression and therapeutic relevance,” Journal of Clinical Psychiatry, vol. 52, no. 6, supplement, pp. 4–10, 1991.

[25] J. R. Cooper, F. E. Bloom, and R. H. Roth, The Biochemical Basis of Neuropharmacology, Oxford University Press, New York, NY, USA, 1996.

[26] R. S. El-Mallakh, Y. Gao, and R. Jeannie Roberts, “Tardive dysphoria: The role of long term antidepressant use in-inducing chronic depression,” Medical Hypotheses, vol. 76, no. 6, pp. 769–773, 2011.

[27] P. W. Andrews, S. G. Kornstein, L. J. Halberstadt, C. O. Gardner, and M. C. Neale, “Blue again: perturbational effects of antidepressants suggest monoaminergic homeostasis in major depression,” Frontiers in Psychology, vol. 2, article 159, 2011.

[28] G. A. Fava and E. Offidani, “The mechanisms of tolerance in antidepressant action,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 35, no. 7, pp. 1593–1602, 2011.

[29] Functional impairment and cognition in bipolar disorder . Zarate, C. Psychiatric Quarterly 71 (2000):309-29.

[30] Disability and its treatment in bipolar disorders. Huxley, N. Bipolar Disorders 9 (2007):183-96.

[31] Jackson Grace E. (2005)  Rethinking Psychiatric Drugs: A Guide for Informed Consent.  Bloomington, IN: Author House.

[32] Reisner I, et al, (1996) http://www.ncbi.nlm.nih.gov/pubmed/8861609

[33] Mehlman P, et al (1990) http://www.ncbi.nlm.nih.gov/pubmed/7522411

[34] Brown GL & Linnoila MI (1990) http://www.ncbi.nlm.nih.gov/pubmed/1691169

[35] Muller JL et al (2004) http://www.ncbi.nlm.nih.gov/pubmed/15570500

[36] Jackson Grace E. (2005)  Rethinking Psychiatric Drugs: A Guide for Informed Consent.  Bloomington, IN: Author House.

[37] Odagaki (2009) http://www.benthamscience.com/cds/samples/cds4-1/0013CDS.pdf

[38] Naveed Iqbal, MD, et al, (2007) http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1262

[39] Hall LM et al (1995) http://www.ncbi.nlm.nih.gov/pubmed/7543647

[40] Grace Jackson MD (2009) Drug Induced Dementia. A Perfect Crime Bloomington, IN: Author House.

[41] Siegel A, Bhatt S. (2007) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435345/

[42] Stefan M. Brudzynski, et al (1990) http://www.ncbi.nlm.nih.gov/pubmed/2293258

[43] Graeff FG. (1994) http://www.ncbi.nlm.nih.gov/pubmed/7916235

[44] Imperato A. et al, (1993) “Evidence that neuroleptics increase striatal acetylcholine release through stimulation of dopamine D1 receptors” http://jpet.aspetjournals.org/content/266/2/557.abstract 

[45] Donald W. Black, Nancy C. Andreasen - Introductory Textbook of Psychiatry - (2011) 5th Edition p.544 American Psychiatric Publishing Inc.

[46] Grace Jackson MD (2009) Drug Induced Dementia. A Perfect Crime Bloomington, IN: Author House.

[47] Kasantikul D, Kanchanatawan B, (2006)  http://www.ncbi.nlm.nih.gov/pubmed/17214072

[48] Tanya C. Warwick, et al, (2008)

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[49] Davies et al, (2000) http://www.national-toxic-encephalopathy-foundation.org/oppest.pdf

[50] Singh S, Sharma N. Neurological syndromes following organophosphate poisoning. Neurol India 2000;48:308. http://www.neurologyindia.com/text.asp?2000/48/4/308/1510

[51] Grace Jackson MD (2009) Drug Induced Dementia. A Perfect Crime Bloomington, IN: Author House.

[52] Grace Jackson MD (2009) Drug Induced Dementia. A Perfect Crime Bloomington, IN: Author House.

[53] http://www.medscape.com/viewarticle/803986

[54] http://www.psychintegrity.org/isepp_statement_on_the_connection_between_psychotropic_drugs_and_mass_murder.php

Evidence Revealing No Reduction in Violence With Anti-Psychotics.

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27.       The first research noticing antipsychotic drugs did not lower crime and aggression was performed by researchers at Queen’s University in Kingston Canada, whereby they tracked 375 prison inmates who began taking neuroleptic or atypical psychotropic medications while in prison.  They stated “violent aggressive incidents occurred significantly more frequently (250% to 1,000% more often) in inmates who were taking psychotropic medications than those who did not get the psychotropic medications [and the increase was] clearly tied to the taking of psychotropic drugs”, accounting for differences in behaviors, symptoms and other factors.  For those taking solely neuroleptic or atypical drugs, the rate of aggression over the term rose by 280%.[1]

28.        This led researchers then in 1979 to reviewed psychiatric discharged patients prior the inclusion of psychiatric drugs (prior to 1955), and compared the rate to those from 1965 to 1979, post neuroleptic administration.  Prior to the use of such intervention, psychiatric patients committed crimes equal to and or less than the general population; however, when they assessed the crime rates following neuroleptic medication, to their surprise, the rate had increased and exceeded the general public.[2]  Researchers likewise then performed a controlled study of schizophrenic patients over an eleven month period, whereby they randomized them into typical hospital drug treatment group and a pure psychotherapy group.  The results were that in the pure psychotherapy group, they had no elopements, suicides or significant acts of aggression, whereas, the typical antipsychotic drug had 3 suicides and more acts of aggression. [3]

29.      The conventional thought used to be that patients who are psychotic are a much greater risk of committing violence, and thus, need to be medicated to reduce this risk.  This hypothesis led researchers to conduct the largest meta-analysis study to date, assessing the risk for a psychotic patient to become violent.  Researchers Fazel, et al, assessed 20 studies spanning from 1970 to 2009, with over 18,400 patients, and determined the risk of committing an act of violence was not statistically greater than the general public, and was not at all greater than if a person simply had a substance abuse disorder. [4] 

30.     In fact, this led the United States NIMH researcher to further assess this phenomena in what is now known as the MacArthur study, whereby, they found recently discharged psychiatric patients were not statistically more dangerous than people in the communities they were discharged to, and those same patients were not more dangerous “even if they had threat/control delusions.”  “The presumed risk of violence associated with delusions per se does not justify hospitalization of a patient.”[5] [6] [7] 

However, patients diagnosed with schizophrenia that have co-occurring substance abuse disorders, are younger, are male, and have prior acts of significant violence tend to be more violent in general than the general population. [8] [9] [10]  Despite the low rate of violence, psychotic patients are routinely given neuroleptic or atypical medications to reduce possible violence, often being told at certain medications are better for such reductions. 

31.      This led researchers Swanson and others to randomly assign 1,445 patient’s diagnosed with Schizophrenia into one of five antipsychotic treatment groups or an “intent to treat” group, whereby they were not given any antipsychotic medications.  They found that there was no significant difference for reducing violence between the different medications, and importantly only 2% reduction between the medication groups and the no medication groups, leading researchers to conclude that neuroleptic or atypicals may not actually reduce violence other than for “acute behaviors.” [11]

32.     Lastly and to address “acute behaviors”, psychiatrists and researchers at the Arkansas State Hospital assessed late 1999 through early 2000 when the hospital banned P.R.N. orders for inpatient psychiatric patients (i.e. meaning not allowing staff and nurses to administer a psychiatric medication that was not on a set schedule, but rather as the nurse or other felt the patient “needed” the medication due to problem behaviors).[12]

Dr. Thapa, assistant professor of psychiatry- University of Arkansas Medical Sciences and staff psychiatrist at the hospital noted:

"The underlying concern at the time-among the psychiatrists and the staff-was that the delay caused by having to contact one of the physicians for a 'now' order might result in patients getting a bit out of hand or too agitated…[and that]… it would result in an increase in the use of seclusion and restraint for incidents of aggression."

However, they found:

"…clearly a dramatic reduction in the use of unscheduled psychotropic medications… [and] … we did not see any increase in adverse events when staff lost the option of PRN orders… [but rather] …the use of seclusion and restraint actually decreased"

The researchers noted that despite a 47% reduction in PRN’s being administered:
* the use of seclusion was reduced by 15%
* the use of restraints were reduced by 50%, cut in half.
* “…one could argue whether the PRN orders are really necessary.”* “The results of our study thus raise the uncomfortable question of whether PRN orders are for the benefit of the patient or the staff."


[1] Workman, D.G., Cunningham, D.G., (1975). “Psychotropic Drugs on Aggression in a Prison Setting” In Canadian Family  Physician, pp. 63-64.  Queens University, Kingston.

[2] Rabkin, J.1979, Criminal Behavior of Discharged Mental Patients, Psychological Bulletin, 86, 1-27.  Patients

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

[4] Fazel S, Gulati G, Linsell L, Geddes JR, Grann M (2009) Schizophrenia and Violence: Systematic Review and Meta-Analysis. PLoS Med 6(8): e1000120. doi:10.1371/journal.pmed.1000120

[5] Applebaum P, Robbins P, and Monahan (2000). Violence and Delusions: Data from the MacArthur Violence Risk Assessment Study. American Journal of Psychiatry; 157:566-572

[6] Monahan, J., Steadman, H.J., Silver, E., Appelbaum, P.S., Robbins, P.C., et al. (2001). Rethinking risk assessment: The MacArthur Study of Mental Disorder and Violence. New York: Oxford University Press.

[7] Monahan, J, Steadman, H., Robbins, et al. (2005). An actuarial model of violence risk assessment for persons with mental disorders. Psychiatric Services, 56, 810-815.

[8] Monahan, J. and Shah, S.(1991). Dangerousness and commitment of the mentally disordered in the United States. Schizophrenia Bulletin, 15: 541-553. Reprinted in: Social and Clinical Psychiatry, 1: 56-70 [in Russian].               

[9] Elbogen, E.B. & Johnson, S.C. (2009). The intricate link between violence and mental disorder. Archives of General Psychiatry, 66, 152-161. 

[10] Monahan, J, Steadman, H., Robbins, et al. (2005). An actuarial model of violence risk assessment for persons with mental disorders. Psychiatric Services, 56, 810-815.

[11]  Swanson, J., Swartz, M, et al. (2008). Comparison of antipsychotic medication effects on reducing violence in people with schizophrenia.  British Journal of Psychiatry, 931(1): 37-43.  doi:  10.1192/bjp.bp.107.042630

[12] Thapa, P., Palmer, S., et al., P.R.N. (as needed) orders and exposure of psychiatric inpatients to unnecessary psychotropic medications, Psych Serv, Vo. 54, 9, Sept. 2003, pp. 1282-1286.  http://ps.psychiatryonline.org/doi/full/10.1176/appi.ps.54.9.1282#citart1