So much of the research on the newer, much more expensive atypical anti-psychotics is tainted with the biases and dishonesty of academic researchers working for the giant pharmaceutical companies.  This is especially true in the U.S., where the use of traditional anti-psychotics has been totally abandoned by the large majority of psychiatrists.  Many of the small benefits of atypical anti-psychotics can be achieved by adding a low dose of anti-depressants in patients needing them.

I do personally like ziprasidone (Geodon) because of its lower cost and low level of serious side-effects.  However, when it is not effective, I will still often use traditional anti-psychotics especially when patients have a past history of doing well.  Obviously, if tardive dyskinesia starts to appear, I will be more likely to use atypicals.  I do like the preliminary research with melatonin against tardive dyskinesia.

Traditional Anti-Psychotics More Cost-Effective Than Zyprexa or Risperdal: Replacing oral traditional anti-psychotics with risperidone or olanzapine has an incremental cost-effectiveness ratio (ICER) of A$48 000 and A$92 000/DALY respectively. Switching from low-dose traditionals to risperidone has an ICER of A$80 000. Giving risperidone to people experiencing side-effects on typicals is more cost-effective at A$20 000. Giving clozapine to people taking typicals, with the worst course of the disorder and either little or clear deterioration, is cost-effective at A$42 000 or A$23 000/DALY respectively. The least cost-effective intervention is to replace risperidone with olanzapine at A$160 000/DALY. Based on an A$50 000/DALY threshold, low-dose typical neuroleptics are indicated as the treatment of choice for established schizophrenia, with risperidone being reserved for those experiencing moderate to severe side-effects on typicals. The more expensive olanzapine should only be prescribed when risperidone is not clinically indicated. The high cost of risperidone and olanzapine relative to modest health gains underlie this conclusion. Earlier introduction of clozapine however, would be cost-effective. This work is limited by weaknesses in trials (lack of long-term efficacy data, quality of life and consumer satisfaction evidence) and the translation of effect size into a DALY change. Assessing cost-effectiveness of drug interventions for schizophrenia. Magnus A, Carr V, et al. Aust N Z J Psychiatry. 2005 Jan;39(1-2):44-54.

Zyprexa, Seroquel, Geodon, Risperdal, Clozaril: No Difference in CATIE Phase II: In the NIMH CATIE study, patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months. Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy; and all other patients received another second-generation antipsychotic. Overall there were no significant differences in psychosocial functioning between the different agents. Results were similar at 6 and 18 months. Patients treated with clozapine in the efficacy pathway made comparable gains. Early treatment discontinuations, especially among patients most impaired at baseline, limited the ability to achieve more substantial functional gains. Effects of Antipsychotic Medications on Psychosocial Functioning in Patients With Chronic Schizophrenia: Findings From the NIMH CATIE Study. Swartz MS, et alDuke. [email protected]. Am J Psychiatry 2007 Mar;164(3):428-36. Ed: In view of no difference, Geodon seems the first choice based on its lower cost and side-effect profile.

Switch Gradually: Clozapine is the only atypical agent recommended to proceed with a slow dose taper when switching to another atypical drug. Sudden cessation could also precipitate the emergence of motor symptoms, which can include pseudoparkinsonism, dystonia, akathisia, and dyskinesia. A large olanzapine study revealed optimal benefits when the previous agents were gradually withdrawn and olanzapine was initiated at 10 mg/day. In another large study, the ziprasidone switch study demonstrated both reduced adverse side effects from the previous agents and improvements in clinical efficacy with a gradual switch. Psychopharmacol Bull 2002 Summer;36(3):22-41

Diabetes: Atypicals Not Found to Increase: In a retrospective study of outpatients receiving atypical antipsychotics (n = 10,265) compared to those on traditional antipsychotics (n = 4,607), antidepressants (n = 60,856) or antibiotics (n = 59,878), the annual unadjusted new cases of diabetes per 1000 per year were 7.5 for atypical antipsychotics, 11.3 for traditional antipsychotics, 7.8 for antidepressants and 5.1 for antibiotics. In multivariable analyses, age, male sex and Chronic Disease Score were associated with greater odds of diabetes onset. Multivariable analysis showed increased odds of diabetes for clozapine, olanzapine, ziprasidone and thioridazine (relative to risperidone), but these comparisons did not reach statistical significance. Atypical antipsychotic drugs and diabetes mellitus in a large outpatient population: a retrospective cohort study. Ostbye T, Curtis LH, Masselink LE, Hutchison S, Wright A, Dans PE, Schulman KA, Krishnan RR. Duke University. Pharmacoepidemiol Drug Saf. 2004 Sep 16. Ed: This new study is certainly at odds with the new FDA requirement that patients be warned about increased risk of diabetes with atypical anti-psychotics.

Dose Comparisons with Atypical: In randomized, fixed-dose studies of atypical anti-psychotics, the near-maximal efficacy dose for olanzapine may be greater than 16 mg; for risperidone, it is 4 mg; and for ziprasidone, it is 120 mg. Risperidone at 2 mg daily is 50% less efficacious than higher doses. Olanzapine at about 6 mg is approximately 33% less effective than higher doses. Aripiprazole at 10 mg daily was fully efficacious. Doses of clozapine well above 400 mg are necessary for optimal treatment of many schizophrenia patients. Haldol 3.3 to 10 mg is the near-maximal ED range. Dose response and dose equivalence of antipsychotics. Davis JM, Chen N. University of Illinois at Chicago. J Clin Psychopharmacol. 2004 Apr;24(2):192-208

Heart Arrhythmia Appears Very Rare: Reported with Risperidone, Quetiapine, Ziprasidone: Because torsades de pointes is rarely found, QTc interval prolongation serves as a surrogate marker for this potentially life-threatening arrhythmia. Through September, 2002, the author was able to find only nine cases in which drug-induced QTc interval prolongation was associated with atypical antipsychotics. Eight cases were taken from the literature, and the author added one additional report. Agents involved were risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. New Generation Antipsychotic Drugs and QTc Interval Prolongation. Vieweg WV. Medical College of Virginia. 2004

Atypical Side-Effects: All atypical drugs have been shown to cause fewer acute extrapyramidal symptoms (EPS) than a standard typical agent (usually haloperidol) and some (clozapine, sertindole and quetiapine) appear to cause these effects no more often than placebo. In the longer term, clozapine, olanzapine and (less robustly) other atypical antipsychotics are thought to cause less tardive dyskinesia than typical antipsychotics. Problems caused by hyperprolactinaemia occur less often with some atypical antipsychotics than with typical drugs although risperidone and amisulpride appear to have no advantages in this respect. Other adverse effects may occur as frequently with some atypical antipsychotics as with some typical drugs. Clozapine, risperidone and quetiapine are known to cause postural hypotension; clozapine, olanzapine and quetiapine are clearly sedative; and anticholinergic effects are commonly seen with clozapine, and, much less frequently, with olanzapine. Maudsley. London. Tolerability of atypical antipsychotics. Stanniland C, Taylor D. Drug Saf. 2000 Mar;22(3):195-214

Atypicals Mostly Not for Schizophrenia: 70% of prescriptions for atypical antipsychotic medications are being used for conditions other than schizophrenia. In the area of bipolar disorder, in particular. Curr Psychiatry Rep. 2003 Aug;5(4):320-

Atypical Polypharmacy Rampant at West Virginia Hospital: An excellent 2001 study studied 206 patients treated over a 60 day period with anti-psychotics. 41% received more than one simultaneously. Psychiatrists reported that they were doing it primarily to increase the anti-psychotic impact (59%). Psychiatrists reported thinking that the majority of patients so treated were being helped by the polypharmacy. Patients were often receiving sub-optimal doses. There is absolutely no research supporting the very common nationwide practice. The concern is that it needlessly increases side-effects and results in patients taking medicines that are not working well for them. 51% of records did not document why the patients were receiving the polypharmacy. WVU. Multiple antipsychotic medication prescribing patterns. Schumacher JE, Makela EH, Griffin HR. Ann Pharmacother. 2003 Jul-Aug;37(7-8):951-5

Atypicals Better than Depot Anti-Psychotics: readmission in patients discharged from six State of Maryland inpatient mental health facilities on clozapine (N = 41), risperidone (N = 149), and olanzapine (N = 103) compared with those discharged from the two largest state facilities during the same time period on fluphenazine decanoate (N = 59) or haloperidol decanoate (N = 59). One-year readmission risk were 10% for clozapine, 12% for risperidone, and 13% for olanzapine; fluphenazine decanoate (21%)(not significant) but were significantly lower than haloperidol decanoate (35%). Demographic and clinical variables did not predict readmission for any of the medications. Univ Maryland. Rehospitalization risk with second-generation and depot antipsychotics. Conley RR, Kelly DL, Love RC, McMahon RP. Ann Clin Psychiatry. 2003 Mar;15(1):23-31

Possibly Lower Death Rate Than Haldol: Nasrallah reported 2 year mortality for atypicals 4.8% vs 22% for haldol in elderly. Biol Psyc 2001;49:525.

Dosage Equivalents: Doses equivalent to 100 mg/day of chlorpromazine or Haloperidol 2mg/d were 2 mg/day for risperidone, 5 mg/day for olanzapine, 75 mg/day for quetiapine, 60 mg/day for ziprasidone (This disagrees with Harvard report 11/02 reporting 20mg/d), and 7.5 mg/day for aripiprazole. Yale. Chlorpromazine equivalent doses for the newer atypical antipsychotics. Woods SW. : J Clin Psychiatry. 2003 Jun;64(6):663-7

Drug Interactions: No Atypical Inhibitor or Inducer Effect: None of all six atypical antipsychotic drugs are identified as significant inhibitors or inducers to any co-administered medication. clozapine, olanzapine, quetiapine, risperidone, sertindole, and ziprasidone are potent 5-HT2a receptor antagonists and relatively weaker dopamine D2 antagonists.

Prolactin Increases, Risperidone Only Atypical: Current data indicate that conventional antipsychotics, as well as high doses of risperidone (> 6 mg/day), increase prolactin levels to a range associated with sexual dysfunction in nonpsychiatric patients. The lack of prolactin elevation reported with the atypical antipsychotics is believed to be due to their much greater specificity, which results in less blockade of dopamine receptors in the tubero-infundibular pathway. Schizophr Res 1999 Mar 1;35 Suppl:S67-73; Clozapine reductions in hPrl of up to 80%. Risperidone persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have all been found to have little effect or produce decreases in hPrl. Most recently, aripiprazole, in early studies, appears to produce significant reductions in hPrl. Expert Opin Pharmacother. 2002 Oct;3(10):1381-91. Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis.

5-HT2C Gene Polymorphism Less Antipsychotic Weight Gain: Several genotypes involve polymorphism for 5-HT2c receptor gene. One studied in China (-759C/T) and only 15% had substantial weight gain v 51% without the variant allele. Lancet 02;359:2086

Weight Gain High on Olanzapine: f/u of 660 atypical patients = >7% wt gain in olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%) and 0% with quetiapine although 13% on quetiapine showed lesser weight gain. Time period undefined other than at least 4 weeks on the med. Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study. Bobes J, Rejas J, Garcia-Garcia M, Rico-Villademoros F, Garcia-Portilla MP, Fernandez I, Hernandez G. Schizophr Res. 2003 Jul 1;62(1-2):77-88.

BMI in Schizophrenia Shows Obesity Harmful: Body weight was inversely correlated (level p</=0.005) to the SF-36 items: physical functioning (PF, -0.452), role limitations due to physical functioning (-0.279), role limitations due to emotional functioning (-0.256), vitality (-0.200), general health (GH, -0.367) and physical component score (PCS, -0.400). Mental component score (MCS) was not significantly correlated to body weight. When comparing quality of life across BMI categories, obese subjects had worse physical functioning (p</=0.0005) and general health (p</=0.005). U Pitt, Body mass index and quality of life in community-dwelling patients with schizophrenia. Strassnig M, Brar JS, Ganguli R. Schizophr Res. 2003 Jul 1;62(1-2):73-6