|
|
|
Nefazodone (Serzone): A Deadly Antidepressant A fairly new patented anti-depressant, nefazodone costs $100-$200 per month for 300-600mg/day. It has a good safety index on overdose, doesn't cause weight gain or sexual difficulties, and is claimed to work as well as most other anti-depressants. It is in the same family as trazodone, an inexpensive and much safer generic to which it has never been compared. Nefazodone causes its own side-effects including 55 cases of liver failure and 20 deaths. It does not appear to be widely used in the U.S. and has been banned in both Canada and Europe. Nefazodone is still legal in the U.S. only because the Bush Food and Drug Administration has been all but taken over by the pharmaceutical industry. For instance, FDA actions under President Bush against inappropriate advertising have fallen by 85% since 1998 under President Clinton. In other words, the Clinton FDA took seven times more legal actions each year against false and deceptive advertising than has the Bush administration! In the Bristol-Myers Squibb studies of 3,496 patients, the drug company reports that 16% had to discontinue the medication due to side-effects. Dropout was caused by nausea (3.5%), dizziness (2%), insomnia (2%), asthenia (1%), and agitation (1%). Side-effects occurring more often than with placebo include asthenia (11%), dizziness (17%), dry mouth (25%), nausea (22%), constipation (14%), lightheadedness (10%), confusion (7%), blurred vision (9%), and abnormal vision (7%). Of course, some patients on placebos also had these side-effects, but the rates were definitely lower. Do Not Take Serzone. There is no reason for such a dangerous medication to still be on the market. If you do take Serzone, you should be alert for signs or symptoms of liver dysfunction including jaundice, loss of appetite, stomach or bowel problems, not feeling well, etc. Medication Helped Depression Psychotherapy Failures and Vice-Versa: In a 12-week randomized crossover study of 140 outpatients with chronic major depression, the rates of response and remission after 12 weeks of nefazodone (Serzone) 100-600 mg/d vs. cognitive-behavioral psychotherapy (CBP) were the same. Both the switch from nefazodone to CBP and the switch from from CBP to nefazodone resulted in clinically and statistically significant improvements in symptoms. Neither the rates of response nor the rates of remission were significantly different when the groups of completers were compared. However, the switch to CBASP following nefazodone therapy was associated with fewer dropouts due to side-effects, which may explain the higher intent-to-treat response rate among those crossed over to CBP (57% vs 42%). Chronic Depression: Medication (Nefazodone) or Psychotherapy (CBP) Is Effective When the Other Is Not. Schatzberg AF, Rush AJ, et al. Stanford University. Arch Gen Psychiatry. 2005 May;62(5):513-20. Nefazodone Reduced Relapse a Little: In a DB PC 52-week follow-up study of 160 chronic Major Depression or MDD with dysthmia patients who had responded in an acute and continuation study of nefazodone, nefazodone was used up to 600 mg/d. Relapse rates were 30% vs. 47% with placebo meaning 6 patients had to be treated to prevent one relapse. 15% of patients reported somnolence. Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Gelenberg AJ, Trivedi MH, et al. Biol Psychiatry. 2003 Oct 15;54(8):806-17 Nefazodone (Serzone) Helps: Drug company ad says in 6 comparative DB studies vs SSRIs, nefazodone did as well as SSRIs in treating depression with minimal activating side effects, sexual dysfunction, or wt gain. Side-effects were dry mouth, somnolence, nausea, dizziness, constipation, asthenia, blurred vision, and confusion. Not to be given with Seldane, Hismanal, Propulsid, or MAOIs and usually not with triazolam, in the latter case because of a 4-fold increase in half-life and doubling of blood level of the nefazodone due to both metabolized by CYP3A4. With alprazolam the effect was a doubling. No reports of priapism. 16% discontinued due to side-effects. No deaths in 7 intentional suicidal overdoses of up to 11,200 mg. Combo Psychotherapy and Nefazodone Better for Chronic Depression: Controlled study 622 patients for 12 weeks MDD >2yr or MDD on Dysthymic Disorder or incomplete remission. Nefaz 200-600mg/d. >50% response in 85% combo v 55% or 52% with meds or therapy only. Keller, NEJM 00;342:1462 Amitriptyline Much Better than Nefazodone: DB PC inpatient 106 MDD 6 weeks. Average dose 242mg/d nefazodone and 124mg/d amitriptyline. Authors speculate nefazodone dosage needs to be higher. Dry mouth 39% on amitriptyline vs 11%. Controlled comparison of nefazodone and amitriptyline in major depressive inpatients. Ansseau M, Darimont P, Lecoq A, De Nayer A, Evrard JL, Kremer P, Devoitille JM, Dierick M, Mertens C, Mesotten F, et al. Imipramine = Nefazodone: DB PC 123 pt 8 weeks. Equal response tho author tries to say nefazodone did better based on very small percentage difference. More imipramine side-effect dropouts stressed by author. Cohn Center. Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression. Cohn CK, Robinson DS, Roberts DL, Schwiderski UE, O'Brien K, Ieni JR. J Clin Psychiatry 1996;57 Suppl 2:15-8 Imipramine = Nefazodone in 6 Studies: Meta-analysis of 6 DB PC studies 345 placebo pt, 288 imipramine, 184 nefazodone pt found equal benefit. However, authors tease out two HAM-D items in which nefazodone at some point did better. They note the greater imipramine drop out rate of 17% vs 5% for nefazodone or placebo. Response of anxiety and agitation symptoms during nefazodone treatment of major depression. Rush-Presbyterian: Fawcett J, Marcus RN, Anton SF, O'Brien K, Schwiderski U. J Clin Psychiatry 1995;56 Suppl 6:37-42 Imipramine = Nefazodone at U Penn: DB PC 283 MDD 8 weeks. Nefazodone better tolerated. Nefazodone and imipramine in major depression: a placebo-controlled trial. Rickels K, Schweizer E, Clary C, Fox I, Weise C. Br J Psychiatry 1994 Jun;164(6):802-5 Nefazodone Never Compared to Trazodone: Although nefazodone is an analog of trazodone, it is somewhat different. While it is considered to be equivalent to imipramine in efficacy, it has never been compared to trazodone. Supposedly Helps Sex Desire Disorders: 49 pts (35 males!) with depression and sex desire disorders were treated in a very poor quality open study with 300-600mg 12 wk and 85% CGI much improved and 85% objective improvement in sex desire disorder. Juan Romi, Buenos Aires, APA 5/99. Less Weight Gain Than SSRI or Imipramine: Using 7% or greater weight change as the measure of clinical significance, 4.3% of SSRI-treated patients had lost weight at any point in the acute phase versus 1.7% of those treated with nefazodone (p = .017). However, at any point during the long-term phase, significantly more SSRI-treated patients than nefazodone-treated patients showed a significant increase in body weight (17.9% vs. 8.3%; p = .003). At any point in the acute phase, significantly more imipramine-treated patients than nefazodone-treated patients had a 7% or greater increase in body weight (4.9% vs. 0.9%; p = .027), and for the long-term phase the comparison yielded 24.5% versus 9.5%. Sussman, NYU, J Clin Psychiatry 2001 Apr;62(4):256-60 Three Cases Liver Failure: 3 women, aged 16, 54, 57, within 14-28 weeks of starting for depression. Early symptoms jaundice, fatigue, nausea. Progressed to encephalopathy in 2.5-6 weeks despite stopping of nefazonone. Two liver transplants, one of whom died. Annals Internal Med 99;130:285. Nefazodone Benefits Accumulates Over 12 Weeks: Study of 993 out-pt MDD for 12 weeks with 77% remitting and 60% sustained remission or 44%? Average dose 376 mg/d with benefit slightly faster through 3rd and 6th weeks but still improving through end of study. Week 2 20% had 50% improvement, week 3 40% had, week 6 70% had 50% and 50% had remitted. J Rush, J Clin Psyc 3/01 62:158-63 Supposedly Helped Four on Methadone: Four opiate addicts on 90-180 mg/d methadone with MDD not responding to at least one of sertraline, risperidone, or bupropion did well on nefazonone in non-scientific report. Potent cytochrome P450 enzyme 3A4 inhibition may increase methadone. Amer J Addictions 98;7:309 Nefazodone Increase in Carbamazepine Level Potentially Fatal: Psyc Drug Alert 8/02 Liver Failure Deaths: Ralph Nader, has petitioned the FDA to remove Serzone from the market. The petition cites 28 reports of liver failure leading to necrosis or death, involving 18 deaths worldwide. Bristol-Myers Squibb withdrew Serzone from Sweden when regulators there demanded a liver enzyme monitoring requirement be added to the product's labeling, and very soon after from the rest of Europe when other countries were considering the same requirement. Serzone is metabolized by the enzyme CYP3A4, which results in raised toxicity for other drugs administered simultaneously, including a 50-fold increase for Buspar. Other drugs affected include Xanax, Halcion, desipramine, Tegretol, Prozac, and the MAOIs. 3/15/03 |