Issues

Antidepressants - The Dark Side

The dangers may be remote, but they are real.

Early in 2000, in a non-jury trial, a Connecticut judge acquitted Christopher DeAngelo, an insurance agent, of robbing a bank after his lawyer successfully argued that his client's state of mind was due to the Prozac he had been taking at the time. Listed in the manufacturer's warning as an "infrequent" adverse reaction is "akathisia," which may cause an unsuspecting victim to become mentally restless and lose all inhibitions about his actions.

In October 1999, Pfizer, makers of Zoloft, settled for an undisclosed sum with the estate of Brynn Hartman, who had shot her husband comedian Phil Hartman dead, and then killed herself. Ms Hartman had been taking Zoloft at the time of the murder/suicide. According to the lawsuit, Ms Hartman had complained to friends that she felt as if she were going to "jump out of her skin."

Until recently, Eli Lilly, makers of Prozac, had managed to settle all of its 200 or so civil claims out of court. But that changed in 2000:

In 1992, Bill Forsyth, a retiree living in Hawaii, was prescribed Prozac for his anxiety and depression. The next day, he called his doctor to say he felt 200 percent better. The day after, however, he requested to be taken to a psychiatric hospital, where doctors continued giving him the drug. Eleven days later, he returned home, stabbed to death his wife of 37 years, then impaled himself on a kitchen knife.

Eli Lilly won the case, but possibly lost a long-term war, for the company was obliged to make public incriminating internal documents dating back to 1978.

According to company minutes, Eli Lilly had full knowledge of what its top-selling drug could do to some people. In the company's own words, back in 1978: "There have been a fairly large number of reports of adverse reactions ... Another depressed patient developed psychosis ... Akathisia and restlessness were reported in some patients."

In another meeting, it was noted that, "some patients have converted from severe depression to agitation within a few days; in one case the agitation was marked and the patient had to be taken off [the] drug."

The minutes also revealed that during the approval process, Eli Lilly's trial subjects were put on tranquilizers to counter the akathisia (and presumably skew the drug trial findings in their favor), though no warning was given when the drug came on the market in the US. In Germany, however, Eli Lilly was obliged to put this caveat on its package insert:

"For his/her own safety, the patient must be sufficiently observed, until the antidepressive effect of Fluctin [Prozac] sets in. Taking an additional sedative may be necessary."

The documents also reveal that Eli Lilly excluded from scrutiny at-risk subjects in a so-called suicide study requested by the FDA, as well as 76 out of 97 suicides.

Meanwhile, in 2001, a Wyoming jury has returned a verdict in a wrongful death suit against GlaxoSmithKline (formerly SmithKline Beecham), makers of Paxil, with damages amounting to $6.4 million. On Feb 13, 1998, Donald Schell, 60, took two Paxil tablets, then shot to death his wife, daughter, and grand-daughter before killing himself. Unpublished data from SmithKline revealed that its own investigators had attributed a variety of side effects to the drug, including akathisia (turmoil), mania, psychosis, aggression, and attempted suicides. Dr David Healy, who has published studies on Prozac (but not Paxil) side effects, testified as an expert witness, along with Harvard psychiatrist Terry Maltsberger.

This is the first successful wrongful death suit in the US involving SSRIs. The plaintiffs in the Forsyth and Tobin cases were represented by the same legal team, Vickery and Waldner of Houston, Texas. Andrew Vickery told this writer what was different about taking a drug company to court this time around:

"We had additional experts in Tobin. We tried SKB on a ‘failure to test’ theory in addition to failure to warn. In Tobin we wised up and emphasized that homicide and suicide are ‘multifactorial’ and ‘biological’ phenomena.’ These and other tactical changes made a big difference."

In October 2002, BBC aired on its flagship current affairs program, Panorama, a no-holds barred documentary on Paxil (marketed as Seroxat in the UK). Right off, with reporter Shelley Joffre's allusion to the medication's "darker side," you knew this was no industry-sponsored symposium:

In quick succession, we hear from two patients, one who cannot get off the drug and the other who mutilated himself while on the drug, followed by David Healy MD who testified in a successful wrongful death suit brought against the drug's manufacturer, and attorney Andrew Vickery who brought that wrongful death suit. Then Joffre cuts to the chase:

"The Maudsley Hospital in London runs a national information service for people taking psychiatric medicines. Trouble coming off Seroxat is the number one complaint from callers. Doctors too report far more withdrawal problems from patients on Seroxat than on any other drug."

Paxil Side Effects

According to Davis Taylor, Chief Pharmacist at the Maudsley Hospital: "If a patient is to stop taking Seroxat suddenly, then usually they would quite soon become quite anxious. They may feel very dizzy and unsteady on their feet. Often people experience electric shock sensations. They may also have a fever and feel generally unwell and they also may experience mood changes or very vivid nightmares for example."

Thanks to the wrongful death suit brought against manufacturer GlaxoSmithKline, Dr Healy gained access to some quarter million documents in the company's archives. He told Panorama that according to GSK's own studies, often on healthy volunteers, that one in four experienced mental agitation while on the drug, and in some instances up to 85 percent had withdrawal problems when they halted.

More on Paxil

At about the same time the documentary aired, the Prescription Medicines Code of Practice Authority in the UK ruled that GSK had breached the industry's of the code of practice by playing down Paxil's side effects. Meanwhile, in the US, Paxil's most recent TV ad leaves out its previous
claim about the drug not being habit-forming.

Number One

According to the World Health Organization reported in The Guardian, Paxil tops the list for drugs in terms of difficulty to quit followed by Effexor at number two, Zoloft at number four, and Prozac at number seven. The benzodiazepines Ativan and Valium come 11th and 13th.

Walk, Don't Run

If you are on Paxil, please do not panic. Mental agitation or anxiety from SSRIs usually occurs in the first few days, if at all, then recedes. If the agitation or anxiety persists, it is advisable to notify your doctor or psychiatrist. If the drug is working for you, it is sensible to stay on it. If the drug is being prescribed to you for the first time, it is advisable,
as with any medication, to express any concerns to your doctor or psychiatrist. Should you no longer need to stay on the drug, following is a "reprint" from a recent Newsletter:

In December 2001, GSK changed Paxil's label, encouraging physicians to recommend "a gradual reduction in the dose rather than abrupt cessation." Paxil washes out of the system more quickly than other SSRIs when stopped. In recent clinical trials, GSK decreased the daily dose by 10 mgs a week (doses can range from 10 to 60 mg a day), then stopped treatment after reducing the dose to 20 mgs. The Washington Post reports Frederick Goodwin MD, former head of the NIMH, as in favor of an even more gradual taper, "dropping the dose every four or five days by as little as possible, even if that means cutting pills in half."

On The Paxil Label

According to the manufacturer's product information, of patients who gradually weaned off Paxil 2.3 percent experienced abnormal dreams, two percent experienced a tingling sensation (paresthesia), and 7.1 percent experienced dizziness. According to GSK, the majority of cases were mild and did not require medical intervention.

Paxil Lawsuits

Not since the tobacco lawsuits have law firms been so eagerly licking their litigious chops. A Google search turns up dozens of law firms in the US, Canada, and the UK that have already been filed on behalf of individuals or classes of individuals or are touting for business. The claims generally
allege withdrawal symptoms or suicidal gestures and the failure of GSK to issue appropriate warnings.

In (July 2003, the FDA has advised that no one under age 18 should be prescribed Paxil for depression, owing to the risk of suicide. Three studies found the drug did not help for pediatric depression, and an analysis of the data showed a three times greater risk of suicidal thoughts and attempts among mostly teens taking the drug vs those on a placebo. There were no deaths in the studies.

The warning follows similar action by the Medicines and Healthcare Products Regulatory Authority in the UK, where the drug is marketed as Seroxat.

Children and teens already on the drug should not suddenly stop the drug, the FDA cautioned, as a long tapering period is required to avoid withdrawal effects.

Prozac is the only antidepressant FDA approved to treat depression in children.

Final Word

If soon after beginning antidepressant treatment you start feeling uncharacteristically hyper, call your doctor at once and stop taking the medication while you still have your wits about you. Your doctor may adjust your dose or switch medications to get you on something that works for you. If you are experiencing anxiety or agitation in the early going, the effect is usually temporary, but it won't hurt to keep your doctor informed.

If, after reading this, you feel you are ready to flush your pills down the toilet - hold on. If you have been taking antidepressants for some time, then you will need to be gradually weaned off of them under a doctor's supervision over a period of weeks or months.

If an antidepressant has harmed you or your family, you may have cause for a legal action, but this is something you would need to take up with a lawyer who specializes in these kinds of cases.

Updated Feb 11, 2008