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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by Phillipa on October 1, 2005, at 22:25:37
Trilafon is listed in this week's US News and World Report as being just as effective as newer antipsychotics in schizophrenia. Anyone else read this. I haven't heard of it being used in a very long time. Fondly, Phillipa
Posted by Phillipa on October 1, 2005, at 22:52:07
In reply to Perphenazine, Trilafon for Antipsychotic, posted by Phillipa on October 1, 2005, at 22:25:37
Here it is the articleUSNews.com: Health and Medicine (10/3/05)
... a goodie A landmark study of schizophrenia drugs in last week's New England Journal
of Medicine found that an older, generic pill, perphenazine, works just as ...
www.usnews.com/usnews/health/articles/051003/3healthwatch.lede.htm
Fondly, Phillipa
Posted by med_empowered on October 2, 2005, at 12:54:31
In reply to Re: Perphenazine, Trilafon for Antipsychotic, posted by Phillipa on October 1, 2005, at 22:52:07
yup. Apparently, they chose this drug as the "conventional" comparison med...interestingly enough, in an interview I read, one of the study researchers said initially they weren't even going to include an old drug; they just assumed that it would come up very substandard, and the side-effects would throw off the double-blind set up. Wow...scary stuff; since when has it become OK to just "assume" stuff like that in modern medicine? (Remember the old saying about assuming: makes an *SS out of U and ME). Anyway, somebody got the brilliant idea to use perphenazine/Trilafon as the comparator drug b/c it's medium potency (fewer obvious EPS than, say, Haldol, but much less sedation than Thorazine) and it apparently has a rep. for being milder than some of the other old drugs (which runs against the current line that "all the old drugs are the same"). From what I understand, perphenazine used to be pretty popular as an augmenting agent for antidepressants in Triavil/Etrafon, where it was mixed with Elavil (that was in the early 60s; interesting how almost 40years later, symbyax comes out and is "the first drug of its kind"). Low-dose Triavil was considered good for "agitated depression" (probably a bipolar mixed-state), psychotic depression, and depression with high-grade anxiety...it was also used in depression in schizophrenia (which has been historically under-recognized; also, lots of people DX'd as schizophrenic back then would be considered bipolar under today's diagnostic criteria, so it really was the Symbyax of yesteryear). Anyway, I'm discouraged that today's new, fancy, heavily-advertised and incredibly expensive drugs can't even outperform perphenazine, which has been around since 1958 or 1959...its a sad statement on the pharmaceutical industry that they'd milk desperate patients and families for $$$ while delivering drugs that aren't any better than the old ones. I think it's also a damning indictment of the psychiatric profession that they'd buy into all the hooplah and take over a decade to demand some solid, substantial evidence of the superiority of these new drugs. **sigh** Oh well. BTW- I haven't actually seen the study; I've only read about it...did they analyse the rates of tardive dyskinesia? I'd be really interested to know how perphenazine did in that area compared with the new drugs.
Posted by zeugma on October 2, 2005, at 16:16:33
In reply to Re: Perphenazine, Trilafon for Antipsychotic, posted by med_empowered on October 2, 2005, at 12:54:31
The big problem with the newer AP's is their heightened propensity for weight gain. Someone, using thinking analogous to SSRI/TCA combinations for depression, combined two drugs not well thought of these days (one of which is perphenazine) to get the same effect as an atypical without the weight gain:
Nord J Psychiatry. 2005;59(3):205-8. Links
Switching patients from olanzapine or risperidone to a combination treatment using perphenazine plus buspirone: Evaluation of antipsychotic efficacy and side-effects, including extrapyramidal effects and weight loss.Andersen TH, Bech P, Larsen NE.
In this pilot study, we have investigated the effects of switching from olanzapine or risperidone treatment to low-dose perphenazine combined with buspirone in six schizophrenic patients who had experienced weight gain. We found no relapse as to psychotic symptoms measured by the CGI-S scale and no exacerbation of extrapyramidal side-effects as measured by the Simpson-Angus Scale. In addition, we observed a medium weight reduction of 10.5 kg (range 1-20 kg).>
Furthermore, some have argued that perphenazine itself possesses atypical properties via a metabolite or two:
J Clin Psychopharmacol. 2000 Apr;20(2):181-7. Related Articles, Links
Pharmacologic profile of perphenazine's metabolites.Sweet RA, Pollock BG, Mulsant BH, Rosen J, Sorisio D, Kirshner M, Henteleff R, DeMichele MA.
Geriatric Psychopharmacology, Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania, USA. SweetRA@msx.upmc.edu
The authors have previously reported that in elderly patients treated with low doses of perphenazine, few extrapyramidal symptoms (EPS) developed in those who were not poor CYP2D6 metabolizers. The authors hypothesized that this atypical side effect profile is due to perphenazine's principal metabolite, n-dealkylperphenazine (DAPZ), which is usually present in vivo at concentrations 1.5 to 2 times that of the parent drug. Perphenazine, DAPZ, and 7-hydroxyperphenazine affinities were examined in vitro by competition-binding analysis to isolated human receptors expressed in transfected cell lines. Perphenazine and metabolite effects were examined in vivo in 54 older patients who were treated with perphenazine, at a target dose of 0.1 mg/kg, for 10 to 17 days. Drug concentrations were determined by high-performance liquid chromatography with electrochemical detection. In in vitro binding studies, DAPZ demonstrated a higher affinity for serotonin-2A receptors than for dopamine-2 receptors to an extent comparable to that of some atypical neuroleptic agents. In contrast, perphenazine and 7-hydroxyperphenazine demonstrated a higher affinity for dopamine-2 receptors than for serotonin-2A receptors. The mean +/- SD concentrations in the 54 subjects were the following: perphenazine, 1.5 +/- 1.4 ng/mL; DAPZ, 2.0 +/-1.6 ng/mL; and 7-hydroxyperphenazine, 0.8 +/- 1.9 ng/mL. The mean +/- SD quotient for the DAPZ/perphenazine concentration was 1.7 +/- 1.1 and for the 7-hydroxyperphenazine/perphenazine was 0.54 +/-1.6. EPS onset was not correlated with the perphenazine concentration, the metabolite concentrations, the DAPZ/perphenazine quotient, or the 7-hydroxyperphenazine/perphenazine quotient. Despite a moderately atypical receptor-binding profile, DAPZ does not seem to moderate perphenazine effects in vivo in older patients. This outcome likely reflects the low potency of DAPZ for dopamine-2 and serotonin-2A receptors relative to the potency of perphenazine for these receptors. Further exploration of atypical properties of DAPZ should include de novo administration of this metabolite in animal models.>
I cannot say that my experience with perphenazine (many years ago) was a pleasant one. However, high doses were used (up to 48 mg) which I believe reflect clinical mismanagement of AP's in the era before the introduction of atypicals.
It's interesting that low-dose perphenazine was used in conjunction with buspirone. Buspirone started life as a potential AP and was found useless for this indication. It's now an 'anxiolytic' although clinical mismanagement of this drug has resulted in its getting nearly as bad a name as the older AP's. I wish an extended release formulation of this, or gepirone, would be marketed, since IMO its primary drawback is its short half-life. It's a useful drug to combine with others, although it does not seem to do much as monotherapy.
-z
Posted by med_empowered on October 2, 2005, at 21:30:04
In reply to well, this is interesting » med_empowered, posted by zeugma on October 2, 2005, at 16:16:33
You were given 48mgs of perphenazne?!?! That's ridiculous. I'm not a fan of **any** neuroleptics--they're all based more or less either on Thorazine or on Clozapine (which is itself based loosely on Thorazine, although its profile is somewhat different)...with all the focus on D2 stuff, its no wonder schizophrenia "treatment" still leaves people developing EPS and leading largely un-fulfilling lives...Thorazine was (and is) a *tranquilizer* in the truest since of the word; its effects on mental illness occur primarily through behavior control and reduction of arousal and expression of emotion...other effects are, at most, secondary. Anyway, since antipsychotics do help some people...it would be nice to use cheaper drugs that (apparently) are just as effective as new ones. The buspirone+perphenazine combo interests me; even after it was introduced as an anxiolytic, buspar was being considered as a treatment for EPS and tardive dyskinesia, and lots of docs were recommending it for use with long-term antipsychotics. But...that obviously didn't go very far, lol. One combo that would interest me...using Triavil in low doses (possibly with an RX for plain old elavil along with Triavli) along with Buspar...it seems like there would be some pretty potent anti-anxiety and anti-depressant properties to a combo like that but...who knows. It also seems that adding things like Remeron or the newer dopamine agonists could be interesting, too...with this new study, I imagine (and hope) we'll see more research into creative combos of low-dose old drugs with newer medications...maybe then there will be some substantial progress in the treatment of schizophrenia.
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