Antipsychotics metabolic effects

Many compounds have been evaluated for their effects on brain metabolism (London, 1993). A surprisingly limited number of common regional metabolic effects have been seen within drug classes. Antipsychot ics, especially the older typical antipsychotics, tend to be associated with changes in striatal metabolism consistent with the high density of D2 dopamine receptors in those brain structures (Cohen et al.. 1999). On the other hand, quite different patterns of metabolic effects have been seen following acute doses with paroxetine and fluoxetine, both of which are selective serotonin... 

Newcomer JW, Haupt DW The metabolic effects of antipsychotic medications. Can J Psychiatry 2006 51 480. [PMID 16933585]... 

Extra-pyramidal side effects - abnormalities of movement due antipsychotic side effect First pass metabolism - metabolism on first passage through the liver Fungicidal - kills fungi Fungistatic - inhibits fungal growth... 

Patients who use atypical antipsychotic drugs may have secondary metabolic effects, such as weight gain and changes in lipid and glucose metabolism [SEDA-33, 94]. The EIDOS and DoTS descriptions of these effects are shown in Figure 1. 

Roy G, Bedard A, Desmarais PA, Jourdain F, Allen S, Michaud D, Ben Amor L. Age-dependent metabolic effects of second-generation antipsychotics in second-generation antipsychotic-naive French Canadian patients. J Child Adolesc Psychopharmacol 2010 20 479-87. 

Moreno C, Merch n-Naranjo J, Alvarez M, Baeza I, Alda JA, Martfnez-Cantarero C, Parellada M, Sanchez B, de la Serna E, Gir ldez M, Arango C. Metabolic effects of second-generation antipsychotics in bipolar youth comparison with other psychotic and nonpsychotic diagnoses. Bipolar Disord 2010 12 172-84. 

Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects a comprehensive literature review. CNS Drugs 2005 19(Suppl 1) 1-93. 

Boden R, Lundgren M, Brandt L, Reutfors J, Kieler H. Antipsychotics during pregnancy relation to fetal and maternal metabolic effects. Arch Gen Psychiatry 2012 69(7) 715-21. 

One approach to formulating potential differences in ethnic response is to examine the metabolic pathways of the common antipsychotics and determine whether the known ethnic variations in metabolizing enzymes or other effects on absorption, distribution, and excretion can be applied a priori to predict potential clinical effects. In this section we will consider some of the commonly prescribed SGAs, and only briefly touch on the FGAs. 

Meyer, J. M., Nasrallah, H. A., McEvoy, J. P., Goff, D. C. et al. (2005). The clinical antipsychotic trials of intervention effectiveness trial clinical comparison of subgroups with and without metabolic syndrome. Schizophr. Res., 80, 9-18. 

Shin, J.G., Soukhova, N. and Flockhart, D.A. (1999) Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro preferential inhibition of CYP2 D6. Drug Metabolism and Disposition, 27 (9), 1078-1084. 

Other sleep-inducing benzodiazepines should be avoided. They are more difficult to metabolize and can accumulate in elderly, demented patients. Sedating, low potency antipsychotics should also be avoided. Their strong anticholinergic (acetylcholine-blocking) effects can worsen dementia or cause delirium. 

---