Journal09-01b.cdr

Selective SerotoninReuptake Inhibitor (SSRI) Drugs:More Risks Than Benefits? Benefits of SSRIs
Joel M. Kauffman, Ph.D.
A prominent recent meta-analysis of Bridge et al.2 included 27
ABSTRACT
trials of SSRIs for three defined mental conditions: majordepressive disorder (MDD), OCD, and non-OCD anxiety disorders.
Anecdotal reports have suggested that selective serotonin Benefits, compared with placebo, were found to be highly reuptake inhibitors (SSRIs) may cause suicidal or violent behavior statistically significant. For MDD, data from 13 trials showed in some patients. Because of the publicity surrounding certain benefit in 61% vs. 50% on placebo, a gain of 11% absolute events, and the numerous lawsuits that have been filed, a review of for all ages of participants. For OCD, data from six trials showed benefit in 52% vs. 32% on placebo, a gain of At most 30% of patients receive a benefit from SSRIs beyond the large placebo effect in certain mental conditions, especially anxiety, data from 6 trials showed benefit in 69% vs. 39% on place- depression, according to a recent meta-analysis of published trials.
bo, a gain of 30% absolute (NNT=3), <0.001 An equally recent meta-analysis of all SSRI trials submitted to the results represent the maximum expectation of benefit from SSRIs FDA showed a small benefit for the severely depressed patients since 22 of the 27 trials were financially supported by SSRI makers, only. Many early unpublished trials did not show any benefit.
and thus subject to the routinely positive bias of industry-sponsored Adverse effects are common, occurring in up to 75% of clinical trials.3
subjects. Severe adverse effects may be underreported. Meta- Jay S. Cohen, M.D., author of the 2001 book Over Dose: the Case analyses of controlled trials did not include any actual suicides or Companies wrote that half his patients did well on murders, but only suicidality, some finding, in 1991 and 2007, no fluoxetine, but he noted a high incidence (50%) with side-effects.
evidence even of suicidality. Other meta-analyses using many of Cohen also cited a pre-approval study showing that the standard 20 mg the same trials found that suicidality doubled to 1 in 500 on SSRIs per day starting dose helped 65% of patients, while 5 mg helped 54%, compared with placebo or non-SSRI antidepressants, but did not so Cohen became one of the pioneers in using lower doses before Lilly include any actual suicides or murders. The trial designs were devised by SSRI makers to prevent reports of suicides, by made them available. The 1996 Physicians Desk Reference (PDR) eliminating subjects with the slightest trace of suicidal tendencies.
entry for paroxetine, at least, confirmed that the 17 most common Retrospective studies by others showed actual suicides on SSRIs with a relative risk (RR) of 2–3 compared with non-SSRI In four observational cohort studies of four common SSRIs antidepressants, with an increased incidence of 123/100,000.
reported by physicians as part of the prescription-event monitoring Lower doses than the smallest available ones were found to program in the UK, with more than 10,000 patients in each drug maintain benefits in a majority of patients while reducing risks.
group, only 36% of the physicians reported fluvoxamine as effective, No causal connection between SSRIs and suicide and/or compared with 60% for fluoxetine, sertraline, and paroxetine. These violence has been proved; neither has it been ruled out. Physicians possible benefit rates, which include the placebo effect, parallel the need to be vigilant, and aware of legal precedents that may subject percentage of patients remaining on the drug for 2 months.
them to enhanced liability when prescribing these drugs.
The Genesis of SSRIs
Table 1. Commonly Prescribed SSRIs and Other Antidepressants
Fluoxetine (Prozac in the U.S., see Table 1), introduced in 1988 to combat depression, was the fourth selective serotonin reuptake inhibitor (SSRI) on the U.S. market, after being seriously considered by Eli Lilly as an antihypertensive drug. Unlike the earlier “tricyclics” (amitripyline, clomipramine, dothiepin, imipramine, etc.) and other drug classes, SSRIs acted on the brain to raise levels of the neurotransmitter serotonin without raising thelevels of norepinephrine. This was thought to be a benefit in treatment of depression, and later anxiety, panic, social phobia, obsessive-compulsive disorder (OCD), and many other conditions.1 The SSRIs listed in Table 1 are among the most
frequently prescribed in the U.S., and compete with the five non- Journal of American Physicians and Surgeons
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An old trial of placebo for anxious and depressed subjects Perhaps such considerations led David Healy, M.D., an SSRI reduced distress in 43%.6 Three meta-analyses of the antidepressant
expert, to his conclusion that “.these drugs do not convincingly literature that appeared in the 1990s independently concluded that work….”10 His evidence came from early unpublished clinical trials
two-thirds of the effectiveness attributed to SSRIs is actually whose results were revealed to him at FDA hearings. For fluoxetine, placebo effect.1 In a series of nine controlled studies on hospitalized
Healy noted four trials with a positive result and four without. For patients with depression, 57% of those given placebo showed sertraline, only one of five early studies showed benefit.11,12
improvement in 2–6 weeks.7
Because of the huge placebo effect, 32–75%, most physicians A 1998 meta-analysis of 47 trials on antidepressant medication unfamiliar with the studies revealing this effect are likely, in my including SSRIs indicated that 75% of the response to them was opinion, to say that one-third to two-thirds of their patients are duplicated by placebo. This meta-analysis was criticized on several improved on SSRIs. This would also explain Dr. Jay S. Cohen’s grounds. Therefore, Irving Kirsch, Ph.D., of the University of findings on lower doses of fluoxetine.
Connecticut, with other authors, obtained data submitted to the Adverse Effects of SSRIs
FDA on every placebo-controlled clinical trial on the six mostwidely used SSRIs, and published a meta-analysis on 47 trials, SSRIs reportedly interact with 40 other drugs to cause finding a small, clinically insignificant effect.8 This work was
“serotonin syndrome.” This presents as twitching, tremors, rigidity, fever, confusion, or agitation. Serotonin/norepinephrine reuptake Analyses of datasets including unpublished as well as inhibitors (SNRIs) also may cause serotonin syndrome by published clinical trials reveal smaller effects that fall well interactions. Most tricyclic depressants do not have these below recommended criteria for clinical effectiveness.
interactions, with the exception of amitriptyline.13
Specifically, a meta-analysis of clinical trial data submitted In a controlled trial of paroxetine vs. clomipramine sponsored to the U.S. Food and Drug Administration (FDA) revealed a by GlaxoSmithKline, 75% of the subjects had an adverse effect on mean drug–placebo difference in improvement scores of paroxetine, 21% had a severe adverse effect, and 13% committed a 1.80 points on the Hamilton Rating Scale of Depression suicidal act (1 in 8).14 The 1996 Physicians Desk Reference (
(HRSD), whereas the National Institute for Clinical entry for paroxetine lists 17 side-effects with an incidence of ≥5% Excellence (NICE) used a drug–placebo difference of three for approved doses. They are: asthenia, sweating, constipation, points as a criterion for clinical significance when decreased appetite, diarrhea (up to 15%), dry mouth (up to 21%), establishing guidelines for the treatment of depression in the nausea (up to 36%), anxiety, dizziness, nervousness, paresthesia, United Kingdom.9
somnolence (up to 22%), tremor (up to 15%), blurred vision, Kirsch et al. concluded that the updated findings from 35 abnormal ejaculation, impotence, and other male genital disorders.
carefully vetted trials suggest that, compared with placebo, the four Fully 31 additional side effects with an incidence at least 1% greater new-generation antidepressants (fluoxetine, venlafaxine, than placebo were listed, including uncontrollable yawning.
nefazodone, and paroxetine) do not produce clinically significant Murder, suicide, and suicidality were not included. Nor were they improvements in depression in patients who initially have on comparable lists for fluvoxamine, or sertraline.
moderate or even severe depression. They show statistically For fluvoxamine, suicide attempts were separately listed as significant but clinically minor effects only in the most severely “infrequent.” For fluoxetine, suicidal ideation was listed as a depressed patients. Moreover, the significance of the effect voluntary report not proved to be drug related. For sertraline, probably is based on a decreased responsiveness to placebo, rather suicidal ideation and attempt were listed separately as “infrequent.” than increased responsiveness to medication. Given these results, The entry for venlafaxine was: “…the possibility of a suicide the researchers conclude that there is little reason to prescribe new- generation antidepressant medications to any but the most severely Not found in the PDR was weight gain, which Cohen lists as a depressed patients unless alternative treatments have been serious side effect.4
ineffective. In addition, they write that the decreased placebo Typical dropout rates in recent trials are claimed to be 5% (see response in extremely depressed patients, combined with a below), but these must be short trials, or trials with a run-in period. In response to antidepressants comparable to that of less severely a meta-analysis of 62 earlier trials with a total of 6,000 subjects, the depressed patients, is a potentially important insight that should be mean total dropout rate and the proportion of dropouts due to side effects appear comparable to results in general practice: total dropout Even these unimpressive findings exaggerated the benefits of rates of between 30% and 70% have been reported by 6 weeks, of antidepressants. In three fluoxetine trials and in the three sertraline which some 30%–40% are attributed to side effects and the rest to trials for which data were reported, the protocol allowed failure of treatment.15
replacement of patients who, in the investigators’ judgment, were Early findings of severe adverse effects by SSRI makers came not improving after 2 weeks. The trials also included a 1–2 week to light only after the class was established. Of 53 healthy volunteer washout period, during which patients were given a placebo prior to studies on fluoxetine, the results of only 12 were openly reported.
randomization. Those whose scores improved 20% or more were From 35 healthy volunteer studies on paroxetine, pre-launch, the excluded from the study. In 25 trials, the use of other psychoactive results of only 14 appeared. From 35 pre-launch healthy volunteer medication was reported. In most trials, a chloral hydrate sedative studies on sertraline, only seven appeared. Among the unpublished was permitted in doses ranging from 500 mg to 2,000 mg per day.
trials, there was one in which all volunteers dropped out because of Other psychoactive medication was usually prohibited but still agitation (akathisia). In published work on sertraline, data excluded reported as having been taken in several trials.9
material on behavioral toxicity, including at least one suicide of a Journal of American Physicians and Surgeons
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Spring 2009
healthy volunteer, and in a different trial, 2 of 20 volunteers became SSRIs in general have long lifetimes in the body. Fluoxetine and intensely suicidal. This last is consistent with the dropout rate of 5% its active metabolite in particular have a half-life of 16 days, for agitation alone in actual trials.16 It is also consistent with Lilly’s
PDR In a reexamination of trials in which animal studies, in which previously friendly cats treated with suicides or attempts during the inadequate washout period were not fluoxetine started growling and hissing—an unheeded warning.1
blamed on the drug, it was shown that the relative risk (RR) of Just a year after fluoxetine was introduced, Bill Forsyth of suicidal acts ranged from 3 for sertraline to 10 for fluoxetine.
Maui, Hawaii, had taken it for only 12 days when he committed one A concurrent meta-analysis of 24 trials by Kaizar et al.22 utilized
of the first murder/suicides attributed to any SSRI. In the same year Bayesian statistics, a valid choice, in my opinion, because data do not Joseph Wesbecker killed eight others and himself in a Louisville, have to follow a Gaussian or normal curve to yield valid results, and Ky., printing plant where he worked, after 4 weeks on fluoxetine.
this method can be used to revise probabilities to determine whether a Yet as early as 1986, clinical trials showed a rate of 12.5 suicides per specific effect was due to a specific cause.23 They found an
1,000 subjects on fluoxetine vs. 3.8 on older non-SSRIs vs. 2.5 on association between SSRI use and suicidality with odds ratios of 2.3 placebo! An internal 1985 Lilly document found even worse results (95% confidence interval [CI] 1.3-3.8), when the diagnosis was and said that benefits were less than risks. Such documents were MDD, not OCD, anxiety, nor ADHD. Non-SSRI antidepressants released into the public domain by Lilly as part of the settlement in were said to have no association with suicide. This supports the the Wesbecker case.17 Fifteen more “anecdotes” of murder/suicide,
FDA’s findings and requirement, as of October, 2004, for a Black three with sertraline, were listed by DeGrandpre.1
Box warning for all SSRIs, to monitor children and adolescents for Lilly’s denials of a link to murder/suicide on national television suicidality. Kaizar et al. were concerned that there were no completed and elsewhere cited a sponsored meta-analysis in BMJ in 1991, suicides among 4,487 subjects in the trials; that the trial times were which exonerated fluoxetine as a cause of suicidal acts or thoughts too short at median length of 8 weeks; and that in 10 of the 12 MDD without even mentioning actual murder or suicide.18 This study
studies, children and adolescents with an elevated baseline risk of included only 3,067 patients of the 26,000 in the clinical trials it suicide were excluded. Again, there was no citation of actual suicides 16,17,24
utilized. None of the trials had a declared endpoint of suicidality.
associated with SSRIs and no citation of Healy’s work.
Some of the trials had been rejected by the FDA. No mention was Healy reviewed epidemiologic studies that have been cited to made that Lilly had had benzodiazepines co-prescribed to minimize exonerate SSRIs.16 One was analyzed by Healy to show a threefold
the agitation that had been recognized with fluoxetine alone. The increase in suicidality compared with other antidepressants.
5% dropout rate for anxiety and agitation (akathisia) would have While “treatment-related activation” has been considered taken out the most likely candidates for suicide.16 Nevertheless, the
primarily with regard to suicidality, it can lead to harm to others as 1991 study had its intended effect. For example, in 2006 a 900-page well as to self. Healy17 summarized data on “hostile episodes”
Injury which was aimed at attorneys, cited only provided by GlaxoSmithKline from placebo-controlled trials with this study, and only failed lawsuits concerning SSRIs.19
paroxetine in subjects of all ages: 9,219 on paroxetine and 6,455 on The 2007 meta-analysis by Bridge et al.2 may be influenced by
placebo. The rubric of “hostility” was used in the trial to code for indirect conflicts of interest that are hard to prove based on the aggression and violence, including homicide, homicidal acts, and financial disclosures. Their paper pooled excess risk above placebo homicidal ideation, as well as aggressive events and “conduct for “suicidal ideation/suicide attempt” from 27 trials. The excess disorders.” No homicides were reported from these trials. Overall, risk was said to be 0.7% and statistically significant across all during both therapy and withdrawal, the RR was 2.1 for hostile indications, but not significant within each indication. Of the 27 events. In children with OCD the RR was 17. Separately, in healthy trials, only five were not sponsored by the drug maker, and one of volunteer studies, hostile events occurred in 3 of 271 subjects on these, the 2004 Treatment for Adolescents with Depression (TADS) paroxetine vs. none of 138 on placebo. In trials of sertraline on study of fluoxetine, had the highest rate of suicidality—7% above depressed children submitted by Pfizer, 8 of 189 subjects placebo. Most of the same trials were used in a meta-analysis by the discontinued for aggression, agitation, or hyperkinesis (a coding FDA, which found a statistically significant excess risk of 2% (4% term for akathisia), compared with 0 of 184 on placebo. In clinical vs. 2% on placebo, 1 in 50 more). Bridge et al. used a random- practice, the term akathisia has been restricted to demonstrable effects calculation, while the FDA used a fixed-effects calculation.
motor restlessness, but if that is the only effect, it would have been In commenting on the negative findings, Bridge et al. write: “No called dyskinesia according to Healy, who cites four studies linking study [in our meta-analysis] was designed to examine suicidal akathisia to both suicide and homicide.17
ideation/suicide attempt as a study outcome, and in fact most trials Actual suicides were combined with suicide attempts in a 2005 were conducted in patients who had been carefully screened to meta-analysis of 702 trials of SSRIs vs. either placebo or an active exclude youths at risk.” No actual murders or suicides associated non-SSRI control.25 Studies were rejected if the citation was a
with SSRI use were reported. Did the designs of the studies review, a result of duplicate publication, too short, crossover, or had no reporting of actual or attempted suicide. The studies meeting the The Bridge meta-analysis was not just a vindication of SSRIs, criteria included 88,000 patients. For attempted suicide, the RR was as communicated to the Wall Street Journal by Gilbert Ross, M.D., 2.3 for SSRIs vs. placebo (95% CI, 1.14-4.55). The number needed Medical Director of the American Council on Science & Health.
to treat to harm (sometimes called the “reverse NNT”) was 1 in 684.2
Ross went further, commenting that the FDA “Black Box warning” There was no difference in actual suicide. Of the 702 trials, 104 (see below) was counterproductive because it was discouraging the failed to report adverse events below a certain pre-set limit of 3%, use of antidepressants! Ross speculated that the lethal rampage of 5%, or 10% of patients. Only 493 trials reported dropout rates, with the Virginia Tech shooter might have resulted from premature a mean of 29%, and the mean follow-up time was only 11 weeks.
cessation of medications.20
Thus, there was clearly gross underreporting of adverse effects.
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Table 2. Suicides Related to SSRIs or Mirtazapine
SSRI use (Rosie Meysenburg, personal communication, 2008). As
the number of “anecdotes” exceeds 1,600—hardly a small Incidence/100,000
Patients
Suicides
number—the association of SSRIs with murder/suicide, often The SSRI website was searched to find combined murder/suicide incidents attributed to a specific SSRI. There were three for fluvoxamine, four for citalopram, 10 each for paroxetine and sertraline, and 31 for fluoxetine. Where the studies abovesubstantiated suicide from SSRI use, the total on the SSRI website Source: British Drug Safety Research Unit, adapted from Healy, 200316
of 48 simultaneous murder/suicide incidents associated with SSRIuse ties together SSRIs and murder. Since there were about two More importantly, because actual suicides are involved, Healy murders per suicide, we may infer that the murder rate on SSRIs cited a study by Donovan et al.26 that demonstrated a RR=3.4
could be about 250/100,000. Since no clinical trial involving for SSRIs compared with all non-SSRI antidepressants involving 222 actual suicides, of which 41 were among patients multiple homicides is ever likely to be run, no firmer evidence is who had an SSRI within a month of their suicide.26 Also the British
likely to be found. Healy noted that much of the evidence for suicide Drug Safety Research Unit recorded more than 110 suicides in and murder came from the efforts of journalists and lawyers.
50,000 patients taking an SSRI, an incidence of 219/100,000 Note that the website carries a prominent warning that “withdrawal compared with 96/100,000 for the non-SSRI mirtazepine can often be more dangerous than continuing on a medication.” (Remeron), an increase of 123/100,000, or 1 in 813 (Table 2). Thus Nine violent events cited elsewhere—seven court cases of the RR for actual suicide in patients taking SSRIs was 2.3 (or 2.8 for homicide (one attempted) and two assaults—were associated with paroxetine). Even here, though, no murders were listed.16
specific SSRIs: three with paroxetine, three with sertraline, two In another study cited by Healy, Jick et al.27 reported 143 actual
with fluoxetine, and one with venlafaxine.17
suicides among 172,598 patients taking antidepressants. The Skeptics have cast doubt on whether the prescribed SSRIs were relative risk of suicide in patients taking fluoxetine was 2.1, actually taken, especially since many medical records of juveniles compared with those taking the tricyclic antidepressant dothiepin.
were sealed. In the Columbine, Colo., shootings the toxicology report showed “therapeutic” levels of fluvoxamine in one of the SSRI makers keep insisting that there will be more suicides if shooters. The Red Lake, Minn., shooter had fluoxetine found, SSRIs are not used as frequently as now. But the RR of 2–3 shown in according to news items referenced on the website.
studies is a net number that includes the number of suicides that may A 2004 editorial in JAMA by Simon Wessely, M.D., a spokes- have been prevented, so SSRI use is associated with more suicides, man for Eli Lilly, and Robert Kerwin, Ph.D,28 cited only a single
paper by Healy24 as a source of claims of suicidality that have found a
receptive media audience. Tellingly, the only study described at
SSRIs Provide 1,600 Anecdotes of Violence
length is by Jick et al.29 on the correlation of SSRI use and “attempted
The International Coalition for Drug Awareness in cooperation suicide,” in which the rates on dothiepin, amitriptyline, fluoxetine with the Prozac Survivors Support Group has produced a website on and paroxetine were not statistically different. Actual suicides in this which about 1,600 violent incidents associated with SSRI use are study (seven on SSRIs) were not mentioned by Wessely and Kerwin, described (www.ssristories.com/index.php). The first column on the nor were the 143 suicides in Jick’s earlier paper. Jick et al. have type of incident (murder, school shooting, etc.) is a hot link to a publicly been supported partially by GlaxoSmithKline and Pfizer. No study available description of the incident, typically a local newspaper article.
that reported actual suicides on SSRIs was described in detail, let A selection of 10 entries (rows) is presented here as Table 3.
alone refuted. Wessely and Kerwin wrote: “The problem is that About 360 suicides are tallied as well as about 400 murder depression is unequivocally and substantially associated with incidents, many of which were multiple murders, each linked to suicide and self-harm.” True, but this not the whole truth.
Table 3. Selected Violent Incidents Associated with SSRI Use
INCIDENT TYPE
LOCATION
ADDITIONAL INFORMATION
10 dead, 7 wounded: dosage increased one week before rampage 15 year old shoots two teachers, killing one: then kills himself Columbine High School: 15 dead, 24 wounded Four dead, twenty injured after Prozac withdrawal Teen shoots at two students: kills his father Jury finds Paxil was cause of murder-suicide Man cleared of charges due to Paxil withdrawal defense Not guilty by reason of Prozac induced insanity: mother kills daughter Nine dead, 12 wounded in workplace shooting Source: List of 1,600 violent incidents found at www.ssristories.com/index.php. Accessed Feb 21, 2009.
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The legal defense by Lilly, repeated by the media and others, is The Black Box warning of 2004 about possible suicide in that any suicides are caused by the condition, depression, not by children under 18 years of age did not cover adults or murder at any their drug—whether the violence is associated with short-term drug age, so potential liability for the SSRI makers still exists. In 2007 use, long-term drug use, increased doses, withdrawal, or the warning was extended to persons under age 25 years. David rechallenge. There is no website, as far as I know, for violent acts Healy was quoted as saying that the warning was overdue, and that committed by persons who never received SSRIs, or for total the risk was not likely to disappear above age 25. This was shown violent acts; hence the denominator for violent acts is not known.
by the trials from GlaxoSmithKline on paroxetine cited above.
Also unknown is the fraction of potentially violent persons who aretreated with SSRIs, or of persons treated with SSRIs who are Conclusions
potentially violent. The published studies on actual suicide,however, compare patients on SSRIs with similar patients on non- Antidepressants are extraordinarily difficult to assess for risks SSRI antidepressants or placebo. Children diagnosed with OCD, At most, 11%–30% of patients with depression or related not depression, also became suicidal on SSRIs, as did healthy conditions who take SSRIs actually benefited beyond the placebo volunteers. Actual two- to threefold increases in suicide rates have effect on normal doses. Of the perceived benefit, 32%–67% can be been demonstrated as well as they could be.1,11,17 How else could
such effects be demonstrated? Who would submit, and what Adverse effects, mostly dose-dependent, will appear in up to institutional review board or human subjects committee would 75% of patients on normal doses. Of these, studies suggest that approve a study explicitly designed to show whether assaultive, suicidality will be observed in an additional 2%–13% (1 in 50 to 1 in homicidal, or other violent behavior increases in subjects 8) of patients on normal doses, beyond what is seen on placebo or many non-SSRI antidepressant drugs. This is sufficiently frequent Denial by SSRI makers of culpability for these risks continues that a typical prescribing physician should observe examples in to this day. Whether physicians’ acting on the Black Box warnings of 2004 and 2007 for all SSRIs will diminish the incidence of The actual suicide rate could be about 123/100,000 (1 in 813) murders and suicides is not yet known.
higher in patients on SSRIs than in those on tricyclics or placebo.
Studies show that many more suicides are attempted on normal 200 SSRI-related Lawsuits
doses of SSRIs beyond what is seen on placebo or many non-SSRIantidepressant drugs.
Following the introduction of fluoxetine in 1988, only a year Available data suggest that actual murders may be committed at passed before an early user committed multiple murders and suicide; about the rate of 250/100,000 (1 in 400) SSRI-treated patients many other examples followed. More than 200 lawsuits have been beyond what is seen on placebo or many non-SSRI antidepressant begun by users of SSRIs and victims’ families charging wrongful drugs, and that many more murders will be attempted on normal death or failure to warn; these have had mixed outcomes. There is now doses as well. While correlation does not prove causation, and legal precedent for SSRIs as a cause of murder, and the maker of the results of court trials are not medical science, the data for suicide aresolid, and the association of murder with simultaneous suicide is SSRI is potentially liable for damages, according to David Healy.10-12
Eli Lilly responded with total denial to the lawsuits claiming a Now that there is a stronger Black Box warning, physicians who link between fluoxetine and violence. Several claims were settled ignore it may be liable for damages; the warning primarily protects out of court with secret details and no admission of guilt. The Australian David Hawkins was freed from a murder charge by a There is obviously great peril in drawing conclusions about finding of temporary insanity caused by using sertraline. Tim Tobin causation from press reports or court decisions. While of Wyoming won $6.4 million from SmithKline Beecham when a manufacturers have a vested interest in exonerating their drugs, jury found that a murder/suicide committed by Donald Schell was plaintiffs have an interest in blaming it, and defendants in attributable to use of paroxetine.1 There are four other homicide
exonerating themselves. We need careful, independent analysis of cases in which the SSRI was deemed to have contributed, resulting in existing study data. In addition to randomized controlled trials, a suspended sentence in one case and an insanity verdict in another.
evidence from basic science (neuropharmacology) and One case of homicide, with a guilty verdict and a life sentence, challenge/dechallenge/rechallenge investigations needs to be followed a judicial ruling that akathisia was associated with SSRI sought. Both the public and individual patients are imperiled by an use, but that a causal relationship with homicide could not be argued; incorrect answer to the pressing questions about these widely thus the link of an SSRI with homicide was disallowed. This was in direct conflict with the findings of the four trials cited above.17
Future studies may show lower levels of murder and suicide The SSRI website was searched to find murders related to a with close supervision, and with better matching of this drug type to specific SSRI whose perpetrators were acquitted based on temporary SSRI-induced insanity. There were two cases with Joel M. Kauffman, Ph.D., is professor of chemistry emeritus at the
sertraline, four cases with paroxetine, and four cases with University of the Sciences, 600 S. 43rd St., Philadelphia, PA 19104-4495, fluoxetine. So a precedent has been established for legal recognition that an SSRI can be a cause for murder, and that the Acknowledgements: Frances E. H. Pane edited the manuscript. David
drug maker can be found liable for damages. The notices of Moncrief piqued my interest by providing a review copy of The Cult of suicidality for the SSRIs found in the PDR or package inserts before Pharmacology: How America Became the World’s Most Troubled Drug 2004 did not really warn of actual suicide or murder.
Culture by Richard DeGrandpre.
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Potential conflicts of interest: The author has neither a financial interest in
14 Braconnier A, Le Coent R, Cohen D. Paroxetine versus clomipramine in
any drug mentioned, nor in any alternate treatments for treating any mental adolescents with severe major depression: a double-blind, randomized, multicenter trial. J Am Acad Child Psychiatry 2003;42:22-29.
15 Anderson IM, Tomenson BM. Treatment discontinuation with
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29 Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal
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Journal of American Physicians and Surgeons
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Spring 2009

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