SSRI-Induced Akathisia
SSRI-Induced Akathisia's Link To Suicide and Violence
Washington, DC: Medical
experts have long known that the side effect associated with the class
of antidepressants known as the selective serotonin reuptake inhibitors
most likely to drive people to suicide or violence against others is
"akathisia".
Akathisia is but one in a long list of side effects that SSRI makers
were able to keep hidden, as they settled thousands of lawsuits out of
court, by obtaining court orders to seal documents produced in
litigation. For instance, a 1984 Eli Lilly document showed akathisia
occurred in at least 1% of patients long before Prozac was approved.
In
a paper entitled, "Suicides and Homicides in Patients Taking Paxil,
Prozac, and Zoloft: Why They Keep Happening - And Why They Will
Continue," Dr Jay Cohen points out that, as soon SSRI's arrived on the
market in the late 1980s, reports of sudden, unexpected suicides and
homicides by patients taking the drugs began to come in.
The DSM-IV acknowledges the association of akathisia with suicidality
and states: "Akathisia may be associated with dysphoria, irritability,
aggression, or suicide attempts."
According to Dr Cohen, SSRI's can create a combination of side effects
that reduce impulse control and cause severe agitation or restlessness
that may become intolerable. He says, impulsive behavior coupled with
impaired cognitive functioning can be dangerous.
A 1998 article on akathisia associated with Prozac and its link to
suicidal ideation in the Journal of Psychopharmacology, by Roger Lane,
who was working for Pfizer at the time, states in part:
"It may be less of a question of patients experiencing
fluoxetine-induced suicidal ideation than patients feeling that 'death
is a welcome result' when the acutely discomforting symptoms of
akathisia are experienced on top of already distressing disorders.
"Hamilton and Opler (1992) stated that the term 'suicidal ideation' to
describe the apparent suicidality associated with akathisia was
misleading, as the 'suicidal ideation' reported in patients receiving
fluoxetine was a reaction to the side-effect of akathisia (i.e.,
unbearable discomfort and restlessness) and not true suicidal ideation
as is typically described by depressed patients experiencing suicidal
ideation."
Dr Joseph Glenmullen, author of "Prozac Backlash" and "The
Antidepressant Solution," obtained a Lilly document dated November 13,
1990, from Claude Bouchy, a Lilly employee in Germany, to three
executives at Lilly's Indianapolis headquarters, complaining about
directions to change the identification of events as they are reported
to doctors from "suicide attempt" to "overdose" and "suicidal ideation"
to "depression".
"I do not think I could explain to the BGA, to a judge, to a reporter or
even to my family," Mr Bouchy wrote, "why we would do this especially
on the sensitive issue of suicide and suicide ideation."
Dr Glenmullen says akathisia makes people profoundly agitated,
uncomfortable in their own skin and impulsive. It erodes judgment and
can lower their threshold to become violent toward themselves or others,
he states.
Dr Martin Teicher, an associate professor at Harvard Medical School and
McLean Hospital researcher at the time, co-authored a paper with
psychiatrist and psychopharmacologist Jonathan Cole on the link between
Prozac and suicide back in 1990, which found that 3.5% of patients on
Prozac either attempted or committed suicide due to severe agitation
from akathisia.
In the paper, the authors discussed 6 cases of patients who became
intensely preoccupied with suicide after taking Prozac. Dr Cole said, in
an affidavit submitted in litigation on April 20, 2000, "Our purpose in
writing this article was to alert the profession to an alarming,
probable drug side effect which we had observed."
"There was a very clear association," he said, "not merely temporal,
between the ingestion of Prozac and the patients' suicidality."
"I have also seen patients and reviewed cases," Dr Cole stated, "where
an SSRI unmistakably precipitated a driven preoccupation with suicide."
"The SSRI drugs, as a class," he advised, "clearly have the potential to
cause, and in reasonable medical probability or certainty do cause,
akathisia in some patients."
"Although in 1997," Dr Cole notes, "practicing physicians undoubtedly
varied in their level of sophistication and knowledge about the
phenomenon, the potential to cause akathisia and its potential, in turn,
to trigger suicidal behavior."
Additional evidence showing Lilly knew about the akathisia-induced
suicide surfaced in an application for a patent for a second-generation
Prozac pill which claimed that the new-and-improved Prozac would
decrease the side effects of, "inner restlessness (akathisia), suicidal
thoughts and self-mutilation."
Besides the concealment of this adverse effect by the drug companies,
another major problem in getting the word out, according to Vince Boehm,
who tracks all studies and research published on SSRI's, is that the
FDA refuses to fully acknowledge the role of drug-induced akathisia in
what he refers to as "this hideous equation."
"Akathisia is up to 6 times more likely to trigger a suicide," he
states, "than any form of depression caused by life's circumstances
alone."
"The minds inner turmoil is so intense that a person will do anything to escape it," he says.
"The Brits, the Aussies, Canada, and the European Union," he points out,
"have all gone on record recognizing this phenomenon for all age
groups."
Judging by internal FDA documents which have surfaced in litigation, Mr
Boehm appears to be correct. For instance, in a September 11, 1990,
memo, FDA scientist Dr David Graham found that Lilly's data on Prozac
was insufficient to prove the drug was safe, stating: "Because of
apparent large-scale underreporting, the firm's analysis cannot be
considered as proving that fluoxetine and violent behavior are
unrelated."
A more recent study in the September 2006 journal Public Library of
Science (PLoS) has further verified the warnings made by many other
experts, when it reported that, in addition to self-harm, SSRI's cause
some patients to become violent and homicidal.
Dr David Healy, described as "one of the three most eminent academic
clinical psychiatrists in the UK," professor David Menkes, from Cardiff
University in Britain, and Andrew Herxheimer, from the Cochrane Centre,
did the study to determine the risk of violent behavior in people taking
SSRI's.
As part of their investigation, the researchers reviewed all available
clinical data on SSRI's and summarized a series of "medico-legal" court
cases involving patients who had became violent on SSRI's.
One case discussed dated back to 2001, when Dr Healy testified at a
wrongful death trial in Wyoming, after a 60-year-old man on Paxil shot
and killed his wife, daughter and infant granddaughter before turning
the gun on himself in 1998.
At trial, the jury returned a verdict for the man's son-in-law after Dr
Healy presented the jury with a summary of an unpublished company study
that found incidents of serious aggression in 80 patients on Paxil,
including 25 that involved homicide, and proved that the drug maker knew
about the violence and suicide risks before the 1998 shootings.
Dr Healy points out a rechallenge study by Rothschild and Locke in
McLean Hospital where the authors found Prozac-induced emergent
suicidality associated with akathisia in several patients. In order to
test whether suicidality was coincidental or associated with Prozac,
they withdrew Prozac, then re-administered it, and in all three cases,
the patients experienced the exact same effect. "All three patients
developed severe akathisia during treatment with fluoxetine and stated
that the development of the akathisia made them feel suicidal and that
it had precipitated their prior suicide attempts."
However, even more alarming, one set of patients who became suicidal on
Prozac were described as follows: "[n]one had a history of significant
suicidal behavior; all described their distress as an intense and novel
somatic-emotional state; all reported an urge to pace that paralleled
the intensity of the distress; all experienced suicidal thoughts at the
peak of their restless agitation; and all experienced a remission of
their agitation, restlessness, pacing urge, and suicidality after the
fluoxetine was discontinued."
Source: Lawyers and Settlements.com
Akathisia, or
acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless (hence the word's origin in
Ancient Greek: from καθίζειν - kathízein - "to sit" with a privative a as prefix expressing negation or absence; literally meaning inability to sit). It can be a side effect of medications, or it can, to a lesser extent, be caused by Parkinson's disease and related syndromes,[1] and likely other neurological diseases. However, this may be due more to the drugs used in treatment such as sinemet (l-dopa) and less with the Parkinson's disease itself.[2] Another major cause is withdrawal from almost any physical addiction, for example, in benzodiazepine withdrawal syndrome.[3] It was discovered that akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal.[4] Though no further research has been done as of yet, it may also be involved with disrupted NMDA channels in the brain, which have both synergistic and regulatory effects on norepinephrine.
Description
Akathisia may range in intensity from a sense of disquiet or
anxiety,
to severe discomfort, particularly in the knees. Patients typically
pace for hours because the pressure on the knees reduces the discomfort
somewhat; once their knees and legs become fatigued and they are unable
to continue pacing, they sit or lie down, although this does not relieve
the akathisia. At high doses or with potent drugs such as
haloperidol (Haldol) or
chlorpromazine (Thorazine/Largactil), the feeling can last all day from awakening to sleep. The
anticholinergic procyclidine
reduces neuroleptic-induced akathisia to a certain degree, in addition
to preventing and sometimes eliminating the muscle stiffness that can
occur alongside akathisia.
Some doctors report an anti-anxiety drug such
as
clonazepam helps to reduce the anxiety which occurs along with the akathisia.
[citation needed].
When misdiagnosis occurs in antipsychotic neuroleptic-induced
akathisia, more antipsychotic neuroleptics may be prescribed,
potentially worsening the symptoms.
[1]
High-functioning patients have described the feeling as a sense of
inner tension and torment or chemical torture. Many patients describe
symptoms of
neuropathic pain akin to
fibromyalgia and
restless legs syndrome.
[5]
Although these side effects disappear quickly and remarkably when the
medication is stopped, tardive, or late-persisting akathisia may go on
long after the offending drug is discontinued, sometimes for a period of
years—unlike the related
tardive dyskinesia,
which can be permanent. Considering that this is rare, it must also be
noted that it is not unheard of that patients are medicated or given
higher doses without their knowledge.
Causes
Akathisia is most often seen as a side effect of
antipsychotic medications, but has other causes as well:
- Antipsychotics[13] such as haloperidol (Haldol), droperidol, pimozide, trifluoperazine, amisulpride, risperidone, aripiprazole (Abilify), ziprasidone and asenapine (Saphris). Less common in sedating antipsychotics such as zuclopenthixol (Cisordinol) or chlorpromazine where anticholinergic and antihistaminergic effects counteract akathisia to a degree.
- SSRIs, such as fluoxetine (Prozac).[14] It has also been documented with the use of paroxetine (Paxil).[11] Akathisia has been studied as the mechanism by which SSRI-induced suicidality occurs.[14]
- Other antidepressants, such as venlafaxine (Effexor)[citation needed], the tricyclics and trazodone (Desyrel).
- Certain anti-emetic drugs, particularly the dopamine blockers, such as metoclopramide (Reglan), prochlorperazine (Compazine), and promethazine.
- Antihistamines, such as cyproheptadine or diphenhydramine.
- Opioid withdrawal.
- Barbiturates withdrawal.
- Cocaine withdrawal (Mostly in heavy and long-term users).
- Amphetamines[15] and any stimulant (including coffee, tea, tobacco, etc.).
- Benzodiazepine, and alcohol withdrawal.
- GHB- gamma hydroxy butyric acid.
- Chondromalacia patellae, resulting in discomfort when knees are bent.
- Serotonin syndrome.
The 2006 UK study by Healy, Herxheimer, and Menkes observed that
akathisia is often miscoded in antidepressant clinical trials as
"agitation, emotional lability, and hyperkinesis (overactivity)".
[11]
The study further points out that misdiagnosis of akathisia as simple
motor restlessness occurs, but that this is more properly classed as
dyskinesia.
Healy, et al., further show links between antidepressant-induced
akathisia and violence, including suicide, as akathisia can "exacerbate
psychopathology." The study goes on to state that there is extensive clinical evidence correlating akathisia with
SSRI use, showing that approximately ten times as many patients on SSRIs as those on
placebos showed symptoms severe enough to drop out of a trial (5.0% compared to 0.5%).
Source and FULL Article at:
Wikipedia
