Suicidality, violence and mania caused by (SSRIs):

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International Journal of Risk & Safety in Medicine 16 (2003/2004) 31¡V49 31

 

IOS Press

 

Suicidality, violence and mania caused by

 

selective serotonin reuptake inhibitors

 

(SSRIs): A review and analysis .

 

Peter R. Breggin

 

101 East State Street, No. 112, Ithaca, NY 14850, USA

 

Abstract. Evidence from many sources confirms that selective serotonin reuptake

inhibitors (SSRIs) commonly cause or exacerbate

 

a wide range of abnormal mental and behavioral conditions. These adverse drug

reactions include the following

 

overlapping clinical phenomena: a stimulant profile that ranges from mild

agitation to manic psychoses, agitated depression,

 

obsessive preoccupations that are alien or uncharacteristic of the individual,

and akathisia. Each of these reactions can worsen

 

the individual¡¦s mental condition and can result in suicidality, violence, and

other forms of extreme abnormal behavior. Evidence

 

for these reactions is found in clinical reports, controlled clinical trials,

and epidemiological studies in children and

 

adults. Recognition of these adverse drug reactions and withdrawal from the

offending drugs can prevent misdiagnosis and the

 

worsening of potentially severe iatrogenic disorders. These findings also have

forensic application in criminal, malpractice, and

 

product liability cases.

 

1. Introduction

 

Soon after the introduction of the first selective serotonin reuptake inhibitor

(SSRI), fluoxetine (Prozac)

 

into the United States marketplace in January 1988, reports began to appear

describing fluoxetineinduced

 

violence against self and others. In May 1990 the U.S. Food and Drug

Administration required

 

the manufacturer of Prozac, Eli Lilly and Company, to add " suicidal ideation "

and " violent behaviors " to

 

the Postintroduction Reports section of its label.1 In 2003 the British

Committee on the Safety of Medicines

 

and the U.S. Food and Drug Administration issued warnings about increased rates

of self-harm

 

and suicidal behavior in children and youth under the age of 18 exposed to

paroxetine (Paxil) [78]. Most

 

recently, on August 22, 2003, the manufacturer of venlafaxine (Effexor) issued a

similar " Dear Doctor "

 

letter warning about the increased risk of " hostility and suicide-related

adverse events, such as suicidal

 

ideation and self-harm " in children age 6 to seventeen [79].

 

In August 11, 1990, an editorial in The Lancet [53] included " the promotion of

suicidal thoughts and

 

behaviour " (p. 346) among the adverse effects of fluoxetine. The following year,

the British National

 

Formulary, a joint publication of the British Medical Association and the Royal

Pharmaceutical Society

 

(1991), listed suicidal ideation and violent behavior as fluoxetine side

effects. Subsequently, many books

 

and reports have dealt with the subject of SSRI-induced violence and suicide

(e.g., [10,12,14,35,40,72]).

 

This report will provide an extensive review and analyze the literature

concerning SSRI-induced suicide

 

and violence, and identify several clinical syndromes that can cause the

phenomena. It will examine

 

*The present paper appears simultaneously in Ethical Human Sciences, Journal of

the International Center for the Study of

 

Psychiatry and Psychology, and is published with permission of Springer

Publishing Company, New York, NY, USA.

 

1The section that lists violence and suicide as possible adverse drug reactions

begins with a caveat that the reported reactions

 

" may have no causal relationship with the drug. "

 

0924-6479/03/04/$8.00 ÆÉ 2003/2004 ¡V IOS Press. All rights reserved

 

32 P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs)

 

the clinical and forensic implications of these findings, and also examine the

ethical and scientific controversy

 

surrounding the capacity of psychoactive agents to cause " bad behavior. " (The

subject of abnormal

 

behavior induced by withdrawal from SSRIs will be considered in a later

publication. Also see [15]).

 

2. The class of SSRIs

 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine

(Prozac), sertraline (Zoloft),

 

paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most

recently, escitalopram

 

(Lexapro). These drugs block the removal of the neurotransmitter serotonin from

the synaptic cleft.

 

A number of other antidepressants are potent non-selective serotonin reuptake

inhibitors (NSRIs). These

 

include the atypicals venlafaxine (Effexor) and nefazodone (Serzone) and the

tricyclic clomipramine

 

(Anafranil).

 

When observations are made in clinical practice and in the scientific literature

concerning the impact

 

of SSRIs, they are typically treated as a single category or class of

pharmacological agents. It is generally

 

recognized that an adverse mental or behavioral reaction, such as agitation or

mania, that is observed in

 

regard to one SSRI is likely to be found with all the other SSRIs.2 While

usually examined as separate

 

classes of antidepressants, the NSRIs also share many characteristics with the

SSRIs, including the

 

capacity to induce stimulation, anxiety, agitation, and mania.

 

3. SSRI-induced mania and the continuum of stimulation

 

All antidepressants cause mania and mania is an acknowledged adverse effect in

the FDA-approved

 

label of all antidepressants. Preda et al. [66] carried out a retrospective

study of 533 psychiatric hospital

 

admissions over a fourteen month period and found that 43 (8.1%) could be

attributed to antidepressantinduced

 

mania and/or psychosis. The percentages for each antidepressant were as follows:

the SSRIs

 

(70%), the newer atypicals (venlafaxine, nefazodone, and buproprion) (21%), and

the older tricyclic

 

antidepressants (amitryptyline, desipramine, imipramine, nortriptyline) (21%).

The total percentage exceeded

 

100% because of overlapping medications in five cases. Twelve of the cases

represented newonset

 

mania or psychosis. The three illustrative cases were severe, including two with

marked suicidal

 

potential. A 52-year-old married woman with a past history of bipolar disorder

developed " command

 

auditory hallucinations with suicidal content " while taking desipramine and

fluvoxamine, as well as

 

risperidone, zolpidem, and oxazepam (p. 31). A 42-year-old woman with a one-year

history of depression

 

" began to experience derogatory and then command auditory hallucinations to kill

herself " while on

 

fluoxetine as well as lithium and thioridazine (p. 31). Finally, a 49-year-old

woman taking venlafaxine

 

for " low mood and anxiety " developed symptoms of paranoia, feelings of doom, and

a delusion that

 

television messages were being directed at her (p. 31). All three patients

improved rapidly with treatment

 

that included termination of the antidepressants.

 

Mania with psychosis is the extreme end of a stimulant continuum that often

begins with lesser degrees

 

of insomnia, nervousness, anxiety, hyperactivity and irritability and then

progresses toward more severe

 

agitation, aggression, and varying degrees of mania. At the lower end of the

continuum, an ordinarily shy

 

2Marangell, Yudofsky and Silver [58] observed, " All SSRIs have a similar

spectrum of efficacy and a similar side-effect

 

profile " (p. 1035). In the same vein, Borg and Brodin [6] remarked, " There seems

to be little difference between the SSRIs with

 

respect to frequency and severity of adverse effects " (p. 66) and Grimsley and

Jann [37] concluded, " Overall, the adverse-effect

 

profiles of the different SSRIs are comparable " (p. 938).

 

<Article shortened here to space limitations for email message:>

 

(Further parts of article available at web site listed at top.)

 

5.3. Coroner studies

 

Frankenfield et al. [33] conducted a retrospective case review of all deaths in

Maryland where either

 

fluoxetine or tricyclic antidepressants was forensically detected. The study

covered a three and one-half

 

year period of time. They found a statistically significant increase in violent

suicides in association with

 

fluoxetine (65% versus 23%). Violence was defined to include " gunshot or shotgun

wounds, suffocation,

 

stabbing, strangulation, drowning, falls and jumping in front of a moving

vehicle " (p. 109). The

 

evaluation of the suicide attempts were blind to which medications were

involved.

 

Bost and Kemp [7] reviewed a series of coroner¡¦s reports in Dallas, Texas,

involving fifteen suicides

 

associated with fluoxetine treatment. The study covered a nine month period.

While they appreciated that

 

their data was impressionistic, they warned that the proportion taking

fluoxetine and committing suicide

 

was high enough to be of concern to health care providers.

 

6. Studies related to SSRI-induced suicidality, violence, and extreme abnormal

behavior in

 

children

 

Many cases of SSRI-induced violent or suicidal behavior involve children or

young adults. However,

 

even in regard to cases involving older persons, the literature on children and

youth is important. Adverse

 

behavioral effects tend to show up more frequently and severely in children,

providing a magnified view

 

of the same or similar effects that the drugs are causing on adults.

 

6.1. Clinical case studies involving children

 

A single case study involving paroxetine described a sixteen-year-old who became

manic with angry

 

outbursts after three weeks on the drug [62]. In another single case study, a

17-year-old mildly retarded

 

youngster was started on fluvoxamine 50 mg when he became depressed and anxious

[70]. After a single

 

dose, he developed increasing agitation and insomnia, followed in the next 24

hours by auditory and

 

visual hallucinations, a fearful mood, and paranoid delusions about the devil.

He required hospitalization

 

and was treated with an antipsychotic drug. The authors believe that fluvoxamine

caused the acute psychosis.

 

As a third example of single case clinical reports, Wilkinson [76] described a

character change

 

with increased aggression in a fifteen-year-old boy taking fluoxetine.

Uncharacteristically, he struck another

 

youngster in the face. Fluoxetine was stopped and within a week he was no longer

aggressive. The

 

author identified blunting rather than akathisia as the motivational state.

 

Koizumi [52] described a thirteen and one-half year old boy who developed manic

symptoms on 40

 

mg per day of fluoxetine. These side effects disappeared when the dose was

lowered to 15 mg per day.

 

However, after fifteen months of fluoxetine treatment he then developed

" explosive, angry outbursts over

 

P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs) 41

 

minor matters, which was totally unlike him " (p. 695). He then experienced a

" weird " and ego-alien voice

 

telling him to kill himself. He recovered from these symptoms within ten days of

stopping fluoxetine.

 

6.2. Epidemiological studies and clinical trials involving children

 

Numerous epidemiological and clinical study reports confirm that SSRIs cause

suicidal, violent and

 

manic behavior in children and youth.

 

Three controlled clinical trials conducted for the FDA-approval of paroxetine

for children under age

 

eighteen demonstrated a three times increased rate of self-harm and suicidal

behavior in paroxetinetreated

 

children compared to placebo. Based on this data in 2003 the British Committee

on Medicines

 

prohibited the use of paroxetine in children and the U.S. Food and Drug

Administration issued a warning

 

[78].

 

The manufacturer of venlafaxine recently disclosed unpublished data from its

controlled clinical trials

 

for major depressive disorder [79]. Individuals below 18 years of age exposed to

venlafaxine had more

 

than twice the relative risk than those exposed to placebo in regard to the

development of hostility (2%

 

versus <1%) and suicidal ideation (2% versus 0%).

 

According to the FDA-approved label for fluvoxamine (Luvox in the Physicians¡¦

Desk Reference [64]),

 

the SSRI causes a 4% rate of mania in children under age 18, compared to no

cases of mania produced

 

in a similar group of children on placebo. The rate was at least four times

greater than in adults (see

 

Breggin [13] for a more complete analysis of the Luvox label).

 

A controlled clinical trial found that fluoxetine caused a 6% rate of mania in

depressed children and

 

youngsters age 7¡V17 ([27, p. 1003]). The reactions were severe enough to cause

the children to be

 

dropped out of the trials. By contrast, none of the depressed youngsters on

placebo developed mania.

 

Jain et al. [45] made a retrospective examination of the medical charts of

children and young men age

 

8¡V19 who had taken fluoxetine in a university clinic setting. The researchers

found that 23% of fluoxetinetreated

 

young people developed mania or manic-like symptoms. Another 19% developed

drug-induced

 

hostility and aggression, including a grinding anger with short temper and

increasing oppositionalism.

 

Constantino et al. [19] prospectively studied the course of aggressive behavior

in nineteen SSRI-treated

 

psychiatrically hospitalized adolescents who were not pre-selected for potential

aggressiveness. They

 

reported symptoms of aggression toward self or others in 12 of 19 patients on

SSRIs. Of the 19 patients,

 

13 were assessed both on and off SSRIs. On the SSRIs there was increased verbal

aggression (P = 0.04),

 

increased physical aggression toward objects (P = 0.05), and increased physical

aggression toward self

 

(P <0.02). No increase was observed in physical aggression toward others. The

authors warned against

 

using SSRIs to treat aggression in children.

 

Another study of children and youth age 8-16 in a university setting found that

50% developed two or

 

more abnormal behavioral reactions to fluoxetine, including aggression, loss of

impulse control, agitation,

 

and manic-like symptoms [68]. The effects lasted until the fluvoxamine was

stopped.

 

A second research study from the same university setting described a number of

youngsters (6 of

 

42 or 14% in their cohort) who became aggressive and even violent while taking

fluoxetine [51]. The

 

researchers hypothesized that fluoxetine caused aggressive behavior by means of

drug-induced activation

 

(stimulation) or a specific serotonergic-mediated effect.

 

The report [51] provided a clinical window into the development of obsessive

violence and a schoolshooter

 

mentality. A twelve-year-old boy on fluoxetine developed nightmares about

becoming a school

 

shooter and then began to lose track of reality concerning these events. This

case occurred in a controlledclinical

 

trial and the investigators did not know that the child was getting fluoxetine

until they broke the

 

42 P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs)

 

double-blind code. The child¡¦s reaction occurred long before any of the

well-known school shootings

 

had taken place. Therefore, his reaction was not inspired by the school

shootings; it was not a " copycat " :

 

Thirty-eight days after beginning the protocol, F. experienced a violent

nightmare about killing his classmates

 

until he himself was shot. He awakened from it only with difficulty, and the

dream continued to feel " very real. "

 

He reported having had several days of increasingly vivid " bad dreams " before

this episode; these included

 

images of killing himself and his parents dying. When he was seen later that day

he was agitated and anxious,

 

refused to go to school, and reportedmarked suicidal ideation that made him feel

unsafe at home as well (p. 180).

 

The child was hospitalized first for three days and then for 17 days. He

gradually improved. Then

 

three weeks after his last hospitalization, his local physician ¡V not one of

the clinical investigators ¡V put

 

him back on fluoxetine. The child became acutely suicidal until the fluoxetine

was stopped a second

 

time.

 

This individual report is important for a variety of reasons:

 

(1) It took place in a double-blind controlled clinical trial.

 

(2) Entirely new symptoms related to violence developed on the drug (This stage

is called challenge).

 

(3) The symptoms terminated after stopping the drug (called dechallenge).

 

(4) Some of the symptoms resumed on starting the drug again (called

rechallenge).

 

(5) The symptoms cleared for a second time after the drug was again stopped

(demonstrating dechallenge

 

for a second time).

 

7. Antidepressant-induced mania described in two standard sources

 

In a variety of forensic activities including criminal and civil cases, the

courts sometimes rely on " authoritative "

 

or " standard " texts in order to demonstrate that the opinions rendered are

generally accepted

 

by a significant portion of the medical or scientific community.

 

7.1. The Diagnostic and Statistical Manual of Mental Disorders (1994, 2000)

 

The American Psychiatric Association [2] Diagnostic and Statistical Manual of

Mental Disorders,

 

Fourth Edition (DSM-IV) and the Fourth Edition Text Revision (DSM-IV-TR, [3])

are written by committees

 

made up of professionals considered expert by many of their colleagues in their

respective fields.

 

The conclusions therefore provide a professional consensus or body of

conventional wisdom in psychiatry

 

that can at times be useful in clinical practice and in forensics. Many aspects

of the DSM-IV are

 

controversial. However, when such an essentially conservative consensus document

provides evidence

 

for SSRI-induced adverse reactions related to mania, suicide and violence, it

should alert clinicians to the

 

existence of these clinical phenomena and can provide an avenue for

communicating in the courtroom

 

concerning these risks.

 

The DSM-IV was published in 1994, several years after the advent of SSRI

antidepressants and makes

 

clear that all antidepressants can cause mania. The first SSRI, fluoxetine, was

approved by the FDA in

 

December 1987 and was in widespread use when the following observations about

antidepressants were

 

published in the manual.

 

DSM-IV makes multiple references to the fact that antidepressants can cause

mania or manic-like behavior.

 

It states, for example, " Symptoms like those seen in a Manic Episode may be due

to the direct

 

effects of antidepressant medication . . . " [2, p. 329]. Similarly, it

observes, " Symptoms like those seen in

 

aManic Episode may also be precipitated by antidepressant treatment such as

medication . . . " [2, p. 331].

 

P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs) 43

 

References to antidepressant-induced mania and mood disorder can also be found

elsewhere in the manual

 

as well (e.g., pp. 332 [note at bottom of table], 334, 336, 337, 351, 371 and

372). DSM-IV-TR (2000)

 

emphasizes that a diagnosis of mania or bipolar disorder should not be made when

the hypomania or

 

mania first appears while the individual is taking a medication that can cause

these symptoms and " usually

 

disappear when the individual is no longer exposed to the substance. " Of great

clinical importance,

 

it adds, " but resolution of symptoms can take weeks or months and may require

treatment " (p. 191).

 

The association between mania and antisocial behavior, including violence, is

underscored in the DSMIV.

 

Aggression is specifically mentioned as a feature of manic behavior. It is noted

that " antisocial behaviors

 

may accompany the Manic Episode, " " Ethical concerns may be disregarded even by

those who

 

are typically very conscientious, " " The person may become hostile and physically

threatening to others "

 

and " physically assaultive, " and " The mood may shift rapidly to anger or

depression " (p. 330). The very

 

next page in the DSM-IV, repeats the reminder that " Symptoms like those seen in

a Manic Episode may

 

also be precipitated by antidepressant treatment such as medication. . . " (p.

331).

 

Mania is characterized by " increased involvement in goal-directed activities "

(American Psychiatric

 

Association [2, p. 328]). Therefore, the individual is able to plan and carry

out inappropriate or destructive

 

aggressive actions, or to attempt to cover them up once they have been enacted.

Individuals undergoing

 

mania often feel uncontrollably driven to carry out elaborate plans, however

bizarre, destructive,

 

or doomed they may be.

 

According to the DSM-IV, an " elevated, euphoric or irritable mood " is sufficient

to qualify for a diagnosis

 

of Substance-Induced Mood Disorder with Manic Features ([2, pp. 370 and 375];

DSM-IV-TR,

 

2000, [3, pp. 405¡V406]). This descriptor for manic features is sufficiently

broad to encompass some or

 

all symptoms associated with stimulation and aggression. Therefore, an

SSRI-induced stimulant-like or

 

aggressive reaction can often be diagnosed as an SSRI-Induced Mood Disorder with

Manic Features.

 

When drug-induced mood swings occur from mania to depression, sometimes

accompanied by switches

 

from violence to suicidality, the diagnosis can include both depressive and

manic features.

 

Irritability as used in the DSM-IV has a more ominous meaning than irritability

as it is used in ordinary

 

language. During a discussion of depression, the DSM-IV refers to the symptom of

" increased irritability

 

(e.g., persistent anger, a tendency to respond to events with angry outbursts or

blaming others, or an

 

exaggerated sense of frustration over minor matters) " (p. 321). Many individuals

who commit aggression

 

while under the influence of SSRIs will qualify for a Substance-Induced Mood

Disorder with Manic

 

Features on the basis of their obvious increase in irritability while taking the

drug.

 

The capacity for SSRIs to induce akathisia ¡V and for akathisia to cause

suicidality, aggression, and

 

a worsening mental condition ¡V are also recognized in the DSM-IV [2] and the

DSM-IV-TR [3] in the

 

section dealing with neuroleptic-induced akathisia. DSM-IV-TR observes,

" Akathisia may be associated

 

with dysphoria, irritability, aggression, or suicide attempts. " It also mentions

" worsening of psychotic

 

symptoms or behavioral dyscontrol. " It then states, " Serotonin-specific reuptake

inhibitor antidepressant

 

medications may produce akathisia that appears identical in phenomenology and

treatment response to

 

Neuroleptic-Induced Acute Akathisia " (p. 801).

 

7.2. Practice guidelines for major depressive disorder in adults (1993)

 

The American Psychiatric Association [1] practice guideline, like the DSM-IV,

attempts to arrive at a

 

consensus among experts. The emphasis, however, is on treatment rather than

diagnosis. Like the DSMIV,

 

the practice guideline was published after the SSRIs were in use.

 

Using several citations from the literature, the practice guideline states:

 

44 P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs)

 

All antidepressant treatments, including ECT, may provoke manic or hypomanic

episodes. Individuals with a

 

history of mania or hypomania are at particular risk for this untoward effect,

although it may occur even in

 

patients with no such history; this complication is estimated to occur in 5¡V20%

of depressed patients treated

 

with antidepressants (p. 22).

 

Recognition of antidepressant-induced manic-like reactions and akathisia in the

most commonly used

 

manual of psychiatric diagnosis has important implications for clinical practice

and forensics. Practitioners

 

should be aware that these adverse drug reactions occur and that the patient

should be diagnosed with

 

a Substance-Induced Disorder or with akathisia rather than with a primary

psychiatric disorder, such as

 

Bipolar I Disorder or an anxiety disorder. It should alert practitioners to the

need to stop antidepressants

 

at the first sign of initial or recurring hypomanic and manic symptoms, or

akathisia. In forensics,

 

recognition of the existence of these adverse drug reactions can help to

establish causality in malpractice,

 

product liability, and criminal cases when SSRIs induce abnormal mental and

behavioral reactions. The

 

body of literature reviewed in this report and the confirmation found in the

DSM-IV and DSM-IV-TR help

 

to establish a standard requiring that physicians be aware of the potential for

these drugs to cause mania

 

and akathisia with the associated risks of suicidality, violence, and extreme or

bizarre behavior.

 

8. My clinical and forensic experience with similar cases

 

I have been a medical expert in a number of suits in which children and adults

have developed bizarre,

 

irrational, and violent behavior while taking SSRI antidepressants. In one case

in California, a man

 

drowned himself and his two small children in a bathtub a few days after

starting on paroxetine (see

 

www.breggin.com for this and other legal cases). Also while taking paroxetine, a

young adult in South

 

Carolina committed a violent rape and a man in Pennsylvania drove his car into a

policeman in order to

 

obtain the officer¡¦s gun in order to kill himself. In a fourth case involving

paroxetine, in Vermont a 17-

 

year old boy who had missed one or two doses of paroxetine bludgeoned a close

friend for no apparent

 

reason. In Florida a teenage girl taking fluoxetine fired a pistol pointblank at

another younger but the

 

gun fortunately failed to function. None of these individuals had any history of

violence prior to taking

 

SSRIs.

 

When all of the SSRI antidepressants are included, I have direct clinical and

forensic experience with

 

dozens of cases of aggression in association with these drugs.

 

9. Discussion: " The Drug Made Me Do It "

 

There is a natural reluctance to attribute " bad behavior " or loss of ethical

restraint (dyscontrol, loss

 

of impulse control) to a psychoactive substance. Western philosophy, religion,

and tradition tend to hold

 

human beings responsible for their harmful behaviors and eschew " excusing " such

behavior on the basis

 

of " mental illness. " Indeed, the concept of mental illness has been subject to

challenge by this author and

 

many others. Nonetheless, the weight of considered evidence indicates that

psychoactive substances can

 

play a role in causing suicide, violence, and other forms of disinhibited

criminal conduct.

 

First, controlled clinical trials comparing any psychoactive drug to a placebo

will typically produce

 

evidence for a pattern of central nervous system adverse drug effects with

mental symptoms that are

 

specific for the drug and not for the placebo. For example, SSRI-antidepressants

and amphetamine-like

 

agents both tend to produce a continuum of central nervous system stimulation.

This physical stimulation

 

will be associated with mental manifestations that range from mild euphoria and

irritability to depression

 

and mania, and ultimately to increased rates of both aggression and suicidality.

 

P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs) 45

 

Second, patterns of reports made to the FDA spontaneous reporting system also

make apparent that certain

 

drugs are associated with specific patterns of extreme mental and behavioral

reactions (for additional

 

examples and an analysis of methodology, see Breggin [10,11]). Even

non-psychiatric medications have

 

been implicated in causing depression and suicidality. Isotretinoin (Accutane),

a medication used to treat

 

severe acne, has been found to produce depression and suicidality as

demonstrated in numerous clinical

 

reports and in individual case studies. In some clinical cases, " depression

subsided with discontinuation

 

of the therapy and recurred with reinstitution of therapy " [65, p. 2872].

 

Third, many physical disorders also affect mental attitudes and behavior.

Hyperthyroidism as well

 

as overdoses of thyroid hormone can increase anxiety, irritability, and other

emotions that the individual

 

would not ordinarily experience and that can lead to behavioral abnormalities.

There are, of course, many

 

similar examples involving hormones such as testosterone and cortisone. More to

the point, accidental

 

brain injury to the frontal lobes and surgical lobotomy usually impair judgment,

ethical restraint and

 

self-reflection. The character of the individual is often viewed as " changed "

and " worsened. "

 

Fourth, as an expert in criminal and civil cases, I have studied the lives of

many individuals who ¡V

 

under the influence of psychoactive drugs, such as SSRIs, NSRIs, and

benzodiazepines ¡V have committed

 

acts of aggression that were wholly alien to their character and antithetical to

their prior behavior. It is,

 

of course, well-known that the illegal use of stimulant drugs, such as

methamphetamine and cocaine,

 

can be associated with paranoid reactions and violence. As Preda et al. [66]

suggest, the SSRIs and

 

hallucinogens such as lysergic acid diethylamide (LSD) may cause psychosis

through similar effects on

 

serotonin receptors.

 

The example of involuntary intoxication under the law helps elucidate the issue

of responsibility while

 

under the influence of psychoactive substances. Under the law, an individual is

usually held responsible

 

for behavior committed under the influence of alcohol or other non-prescription

intoxicants because it is

 

presumed that the individual knew that he was taking a psychoactive substance

that can impair judgment

 

and self-restraint. However, in most states an individual can claim involuntary

intoxication as a mitigating

 

or exonerating factor in a criminal case. For example, if the individual

unknowingly drank alcohol from

 

" spiked " punch, the involuntary nature of the intoxication might become a

mitigating or exonerating

 

factor under the law. Similarly, when an individual takes an antidepressant

without knowing that it can

 

cause mania, he or she may be exonerated from the consequences of manic-like

behavior.

 

If an individual involuntarily intoxicates another person, the perpetrator may

be guilty of a crime and

 

the victim may be absolved of any contributory responsibility. For example, a

man can be judged guilty

 

of rape if he has impaired the consciousness and self-restraint of his victim by

surreptitiously slipping

 

a sedative into her water glass. The victim, even if physically conscious during

the sexual act, may be

 

exonerated of seeming acquiescence to the assault on the basis of the

involuntary intoxication.

 

The debate over human responsibility will always remain at root ethical and

philosophical, as well as

 

a legal. However, empirical data must be taken into account. A mountain of

experimental and clinical

 

data, some of it reviewed in this report, supports the concept that psychoactive

substances are frequently

 

associated with an increased rate of disturbed mental and behavior reactions,

causing some individuals

 

to act as if they have lost their customary ethical restraint and self-control.

 

It may be argued that some individuals will not lose ethical restraint

regardless of the nature or intensity

 

of an involuntary intoxication. However, even if some individuals are immune to

behaving badly under

 

the influence of drugs, while others seem especially susceptible, this merely

reflects human variation, a

 

factor that complicates most research in medicine and behavioral science. The

reality of human variation

 

does not undermine the validity of the association between certain drugs and the

relatively frequent

 

production of certain kinds of dangerous mental states and behaviors.

 

46 P.R. Breggin / Suicidality, violence and mania caused by selective serotonin

reuptake inhibitors (SSRIs)

 

Drug-induced disturbances in mood or in behavior should be viewed as genuine

neurological disorders

 

rather than as vague " mental illnesses. " The capacity of speculative

" biochemical imbalances " or " genetic

 

factors " to cause or contribute to mania or depression remains unproven. Nor do

we know the specific

 

biochemical or neurological mechanisms whereby psychoactive substances cause

mental disturbances.

 

But the capacity for psychoactive substances to disrupt brain function and hence

mental function is

 

beyond dispute. Furthermore, a great deal of empirical data confirms their

capacity to cause disinhibition,

 

mania, depression and other mental phenomena associated with violence toward

oneself and others, and

 

other destructive behaviors.

 

10. Conclusions

 

There are many reports and studies confirming that SSRI antidepressants can

cause violence, suicide,

 

mania and other forms of psychotic and bizarre behavior. Overall, the SSRIs

produce violence, suicide

 

and extremes of abnormal behavior by a variety of mechanisms. Teicher et al.

[72] suggest nine possible

 

mechanisms: (1) energizing the depressed and suicidal patient, (2) paradoxically

worsening the

 

individual¡¦s depression, (3) causing akathisia, (4) causing panic and anxiety,

(5) causing manic or mixed

 

manic-depressive states, (6) causing insomnia or disturbances in the sleep

architecture, (7) causing obsessive

 

suicidal preoccupations, (8) causing borderline states with hostility, and (9)

causing alterations in

 

EEG activity. Teicher et al. document each of these phenomena in their review of

the literature and, as

 

this paper indicates, the scientific evidence has grown considerably stronger in

the intervening decade.

 

With the exception of the alteration in EEG activity, my clinical and forensic

work has confirmed that

 

each of above SSRI- and NSRI-induced phenomena can cause violent and suicidal

behavior. However,

 

my clinical and forensic experiences and reviews of the literature indicate that

four syndromes encompass

 

most of the phenomena and describe most of the individual cases:

 

(1) The production of a stimulant continuum that often begins with lesser

degrees of insomnia, nervousness,

 

anxiety, hyperactivity and irritability and then progresses toward more severe

agitation,

 

aggression, and varying degrees of mania. Mania or manic-like symptoms include

disinhibition,

 

grandiosity, sleep disturbances, and out-of-control aggressive behavior,

including cycling into depression

 

and suicidality.

 

(2) The production of a combined state of stimulation and depression ¡V an

agitated depression ¡V with

 

a high risk of suicide and violence. Often the overall depression is markedly

worsened.

 

(3) The production of obsessive preoccupations with aggression against self or

others, often accompanied

 

by a worsening of any pre-existing depression.

 

(4) The production of akathisia, an inner agitation or jitteriness that is

usually (but not always) accompanied

 

by an inability to stop moving. It is sometimes described as psychomotor

agitation

 

or restless leg syndrome. The state causes heightened irritability and

frustration with aggression

 

against self or others, and often a generally worsening of the mental condition.

 

The above syndromes often appear in combination with each other. Often the

syndromes will abate

 

within days after stopping the SSRI but sometimes they persist, leading to

hospitalization and additional

 

treatment over subsequent weeks or months. Reported rates for these syndromes

very widely but each

 

of them appears to be relatively common. They frequently occur in individuals

with no prior history of

 

violence, suicidality, psychomotor agitation, or manic-like symptoms.

 

 

 

(References available at web siteof article.)

 

 

 

 

 

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