Tired of industry-funded antipsychotic trials? The NIMH comes to the rescue with the “CATIE” project (Clinical Antipsychotic Trials of Intervention Effectiveness). Blissfully unindustry-funded researchers have enrolled 1500 schizophrenic patients at 50 different sites, and have randomly assigned them to Zyprexa, Seroquel, Risperdal, Geodon, or Trilafon (perphenazine). This will allow us to compare the effectiveness of different atypicals, and will also evaluate whether atypicals are truly better than conventionals. The first results are due in a year or so; Big Pharma is holding its breath.
The Zyprexa juggernaut rolls on. A psychopharmacologic overachiever, it excels at everything, with a new FDA indication for maintenance treatment of bipolar disorder as well as treatment of acute mania….Meanwhile, Symbyax, a combination of Zyprexa and Prozac, was just approved for the treatment of bipolar depression. It’s supplied as 6/25 (6 mg Zyprexa/25 mg Prozac), 6/50, 12/25, and 12/50 capsules. The mean dose used in the major published trial was 7 mg Zyprexa and 40 mg Prozac (Arch Gen Psychiatry 2003;60:1079). The 8 week 48% remission rate was twice that of placebo, but Symbyax also outperformed placebo in those typically unpleasant Zyprexoid ways–weight gain (20% of patients gained significant weight) and metabolic havoc (a 10 point increase in cholesterol and a 6 point increase in random blood glucose).
Risperdal Consta is getting rave reviews in the field. It’s the first atypical depot neuroleptic. Dose it at 25 mg to 50 mg IM Q 2 weeks. Especially at the 25 mg dose, EPS are no different from placebo and weight gain is negligible (Am J Psychiatry 2003;160:1125). No more shaky, shuffling Haldol decanoate-niks.
Good old oral Risperdal got a big boost recently from “The Expert Consensus Guideline Series” published by The Journal of Clinical Psychiatry (2003, vol. 16, suppl 12). Risperdal was voted the “treatment of choice” for both first-episode patients and multi-episode patients. Of course, Janssen Pharmaceutica paid for the survey and the supplement, and they got good opinions for their cash.
Seroquel is causing so many people to sleep for so many hours that savvy psychopharmacologists are reserving it for the seriously over-stimulated insomniac patient group. Keep it at HS, and warn your patients of that “knocked off your feet” kind of feeling. To be fair, tolerance develops after a week or two, and the risk of akathisia on Seroquel is practically nil.
Geodon is being used increasingly as a first line agent even though the Mount Sinai Conference Schizophrenia experts say it should only be used second line (Schiz Bull 2002;28:5). Basically, with no verified cases of torsade de pointes yet reported in post-marketing surveillance, clinicians are feeling more comfortable prescribing it, as long as they have their list of contraindicated agents at their side (see Geodon Fact Sheet in www.thecarlatreport.com).
Nonetheless, Pfizer had its hand slapped by the FDA in September of 2002 because of “misleading” promotional material. The journal ads implied that Geodon does not cause torsade; the FDA countered that post-marketing experience hasn’t been sufficient to definitively rule out Geodon’s role in causing several reported cases of sudden death….When using Geodon for psychosis, experts have found that higher doses are necessary, and that sedation is a common limiting side effect. Start at 40 mg BID for one or two days, then bump up to 40 mg AM/80 mg HS, and you may need to ratchet up to the FDA max of 160 mg QD (40/120)…Also, look for an FDA bipolar mania indication soon; Pfizer submitted impressive efficacy data in October 2003.
Abilify (see TCR 1:2) is one of the more stimulating antipsychotics and should not be given at night. Start at 5 mg QAM for the first day or two (BMS just introduced a 5 mg tablet), primarily to minimize nausea and insomnia, and then bump it up to 10 to 20 mg QAM. Most patients will need a dusting of trazodone or Ambien as an adjunct. It and Geodon are still the cleanest in terms of weight gain and hyperglycemia.