Jay S. Cohen M.D.       http://medicationsense.com      1337 Camino Del Mar   Suite C       Del Mar, CA 92014       Phone: 858.345.1760       Fax: 858.509.8944


Suicides and Homicides in Patients Taking Paxil, Prozac, and Zoloft: Why They Keep Happening -- And Why They Will Continue

Underlying Causes That Continue to Be Ignored by Mainstream Medicine and the Media

From almost the day that they were introduced in the late 1980s and early 1990s, sudden, unexpected suicides and homicides have been reported in patients taking serotonin-enhancing antidepressants such as Prozac, Paxil, and Zoloft. I'm not surprised this problem hasn't disappeared, nor will it unless we look deeper.

I never hesitate to say that these drugs -- selective serotonin reuptake inhibitors (SSRIs) -- help millions of people. But any drug that can cause positive changes in people's brains can also cause negative ones unless care is taken to avoid it. We do not take such care. So it was no surprise to me when, in August 2003, more headlines appeared. These were based on reports by British authorities and the U.S. Food and Drug Administration about unpublished studies showing an increased risk of suicide in children and teenagers taking Paxil (1-3).

Prior reports of suicidal and homicidal acts in adults taking SSRIs have been explained away by drug industry defenders and mainstream doctors, who claim that suicide is common in depression anyway. And that no type of antidepressant helps everyone. Some depressed patients don't get better and choose suicide. That's true sometimes, unfortunately. But these reports describe more impulsive, violent acts than expected. As I said fifteen years ago at the time of the first reports and again in Over Dose in 2001 (4), SSRIs could create a unique combination of side effects that might severely impair judgment and impulse control. This has been described by others as well (5-16).

Psychosis After Three Days of Treatment
One of my first cases with Prozac involved a 35 year-old woman with a job and family, who had a mild depression with no suicidal tendencies. This changed after just three days on Prozac, when she became acutely psychotic. Any psychiatrist will tell you that excessive doses of antidepressants can cause brain dysfunctions including disorientation, confusion, and cognitive disturbances. This was commonly seen with old-time antidepressants like Elavil and Tofranil (17). But more than the older drugs, SSRIs can also cause a severe degree of agitation or restlessness that may become intolerable and reduce impulse control (5-6A). Impulsive behavior, especially if coupled with impaired cognitive functioning, can be dangerous.

Antidepressants can also trigger similar, manic-like symptoms in people whose depression is part of a manic-depressive syndrome, which often gets overlooked when people are given SSRIs. "Some of these individuals may have serious adverse reactions to antidepressants including irritability, aggression, and mania," wrote Dr. Ronald Pies, professor of psychiatry at Tufts University (18).

The Devil Is in the Dosage
My book Over Dose opens with a man whose anxiety and depressive symptoms got much worse rather than better with the standard 20-mg starting dose of Prozac (4). A letter to the editor in the August 11, 2003, issue of the New York Times described a similar reaction to Celexa:


"During the first month, I experienced extreme, almost manic tendencies. My mind raced, I was restless, I couldn't sleep. Eventually that restlessness subsided (18)."


Sometimes the symptoms don't subside. Sometimes the symptoms get out of hand. The writer of the letter made an another important point: "They need new dosing and treatment strategies to counteract the manic effect." Exactly.

These reactions are occurring because the standard starting doses of many antidepressants are excessively strong for many people. One clue is that most of these reactions occur shortly after people have been started on SSRIs or after the dosage has been bumped up. These are called "first-dose" reactions by mainstream medicine, and they almost always indicate a mismatch between the patient and the dosage. With the Paxil study, the New York Times reported:


"Some experts suspect that in the first few weeks of therapy, drugs like Paxil can shove a small number of patients toward a mental precipice, perhaps because they can cause a severe form of restlessness known as akathisia. Patients who make it through the first weeks of drug therapy uneventfully do fine on the medication on the long term, these experts say (3)."


But it doesn't have to be a sink or swim situation. Merely reduce the dose awhile, allow patients to adapt to the medicine, and then increase it again gradually. Sometimes it doesn't need to be increased, because lower doses work for many patients.

When my patient became psychotic in 1988, I researched the problem and found an article that shocked me. This large study, published before Prozac was marketed, showed that 54% of the patients with severe depression improved with just 5 mg -- one-quarter of the standard 20 mg starting dose (19). But Prozac wasn't marketed with a 5 mg recommended dose. 20 mg was the recommended initial dose for everyone -- 400% more than many people needed -- a huge difference pharmacologically. No wonder these reactions were occurring.

I wasn't the only expert to recognize the problem. A 1993 study concluded "that starting fluoxetine [Prozac] at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses (20)." Similar dosing problems have been seen with and other SSRIs.

Informed Consent Means Having Enough Information to Make an Intelligent Choice
Unfortunately, most doctors don't understand that many problems with SSRIs are caused by standard doses that are excessive for substantial numbers of patients. And although Prozac, Zoloft, and other SSRIs now come in lower doses, many doctors still start patients on the stronger, standard doses.

As I've said when invited to speak at the FDA and at other major conferences, drug companies must define the lowest, safest, effective doses of drugs. They must include this information in package inserts and the Physicians' Desk Reference, and they must market pills that make lower dosing possible. And they must do it from the start.

Unfortunately, marketing trends in recent decades have gone in the other direction. Many drugs are marketed one-size-fits-all. Many drugs are dosed exactly the same for big and small, young and old, healthy and frail. The same strong doses are prescribed to people taking no other medications and people taking a dozen. Such methods defy medical sense and common sense.

Shortly after the reports from the British authorities and U.S. FDA about higher incidences of suicide in youngsters taking Paxil, Dr. Richard Friedman, director of the psychopharmacology clinic at Weill Medical College of Cornell University, wrote:


"For too long, drug companies have been allowed to tell us only the good news about their products. Now we're ready for the whole story (21)."


The whole story begins with patients and their doctors knowing about the lowest, safest, effective doses of drugs. Most people don't like taking medications. If they must, they prefer taking as little as possible. But this isn't possible if we aren't given adequate information. Informed consent is denied when information is withheld. We need to know the full range of effective doses, and we need enough pill sizes to make individualized dosing possible. Prevention begins with complete information.

In the meantime, you have to be your own researcher, using books and the Internet, learning enough to choose selectively from the information you see. Since 1996, I have published 15 medical journal articles and Over Dose to help inform you and your doctor about lower, safer, proven-effective drug doses because such information was unavailable to most people. Using all of the resources available today, you can learn a lot, and when you do, tell your doctor -- doctors respect good, scientifically-based information -- so that your doctor can inform others following you.

References
1. Waechter, F. Paroxetine must not be given to patients under 18. BMJ, June 14, 2003;326:1282.
2. FDA statement regarding the antidepressant Paxil for pediatric population. U.S. Food and Drug Administration, June 19, 2003:www.fda.gov -- accessed 9/18/O3.
3. Harris, G. Debate Resumes on the Safety of Depression's Wonder Drugs. New York Times, Aug. 7, 2003:nytimes.com.
4. Cohen, JS. Over Dose: The Case Against The Drug Companies. Prescription Drugs, Side Effects, and Your Health. Tarcher/Putnam, New York: October 2001.
5. Medawar, C, Herxheimer, A, Bell, A, et al. Paroxetine, Panorama, and user reporting of ADRs: consumer intelligence matters in clinical practice and post-marketing drug surveillance. International Journal of Risk & Safety in Medicine 2002;15:161-169.
6. Donovan, S, Clayton, A, Beeharry, M, et al. Deliberate self-harm and antidepressant drugs. Investigation of a possible link. British Journal of Psychiatry, 2000;177:551-6.
6A. Rogers, L, Waterhouse, R. Prozac Makers Told to Warn of Side-Effects. The Sunday Times [Britain], July 8, 2001:www.sunday-times.co.uk/news.
7. Glenmullen, J. Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives. Simon and Schuster, March 2000.
8. Healy, D. The Antidepressant Era. Harvard University Press, Sept. 1997.
9. Hickling, L. Questions Persist concerning Prozac's Role in Suicide Risk. Www.drkoop.com Health News, May 11, 2000: www.drkoop.com/dyncon/article.asp?at=N&id=11009.
10. Teicher, MH, Glod, C, Cole, JO. Emergence of intense suicidal preoccupation during fluoxetine treatment. American Journal of Psychiatry, 1990;147(2):207.
11. Fichter, CG, Jobe, TH, Braun, BG. Does fluoxetine have a therapeutic window? Lancet 1991;338.
12. Anderson GM; Segman RH; King RA. Serotonin and suicidality: the impact of fluoxetine administration. II: Acute neurobiological effects. Israel Journal of Psychiatry and Related Sciences, 1995, 32(1):44-50.
13. Lancon, C, Bernard, D, Bougerol, T. [Fluoxetine, akathisia and suicide]. Encephale, 1997 May-Jun, 23(3):218-23. Abstract.
14. Liu, CY, Yang, YY, et al. Fluoxetine-related suicidality and muscle aches in a patient with poststroke depression [letter]. Journal of Clinical Psychopharmacology, 1996 Dec, 16(6):466-7.
15. Jackson, A. Drug Turned Loving Man into a Killer, Says Judge. Sidney Morning Herald, Fri., May 25, 2001:www.smh.com.au/
16. Donovan, S, Clayton, A, et al. Deliberate self-harm and antidepressant drugs. Investigation of a possible link. British Journal of Psychiatry, 2000;177:551-6.
17. American Society of Hospital Pharmacists. American Hospital Formulary Service, Drug Information 1999. Gerald K. McEvoy, Editor. Bethesda: 1999.
18. The Debate Over Antidepressants (5 Letters). Letters to the Editor. New York Times, 8/11/O3:nytimes.com.
19. Wernicke, JF, Dunlop, SR, Dornseif, BE, et al. Low-dose fluoxetine therapy for depression. Psychopharmacology Bulletin 1988;24(1):183-188.
20. Louie, AK, Lewis, TB, Lannon, MD. Use of low-dose fluoxetine in major depression and panic disorder. Journal of Clinical Psychiatry 1993;54(1):435-438.
21. Richard A. Friedman. What You Do Know Can't Hurt You. New York Times, 8/12/O3:nytimes.com.





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