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
poster:zeugma
thread:561772
URL: http://www.dr-bob.org/babble/20050927/msgs/561993.html