but the occupancy of the d2 receptor falls off within 24 hours with atypical antipsychotics, while lasting over 24 hours for the typical antipsychotics. this may explain why relapse into psychosis happens quicker with atypical antipsychotics than with typical antipsychotics, as the drug is excreted faster and is no longer working in the brain. physical dependence with these drugs is very rare. however, if the drug is abruptly discontinued, psychotic symptoms, movement disorders, and sleep difficulty may be observed. it is possible that withdrawal is rarely seen because the aap are stored in body fat tissues and slowly released. pharmacokinetic parameters of available atypical antipsychotics drugroute(s) of administrationhalf-life (t1/2 in hours)volume of distribution (vd in l/kg)protein bindingexcretionenzymes involved in metabolismbioavailabilitypeak plasma time (h)cmax (ng/ml) amisulprideoral125.816%urine (50%), faeces (20%; 70% of this is as unchanged drug) ?48%two peaks: 1 hr & 3-4 hrs post-oral dosing39±3 (1 hr), 54±4 (3-4 hrs) aripiprazoleoral, intramuscular (including depot)75 (94 for active metabolite)4.999%faeces (55%), urine (25%)cyp2d6 & cyp3a487% (oral), 100% (im)3-5 ? asenapinesublingual2420-2595%urine (50%), faeces (40%)cyp1a2 & ugt1a435% (sublingual), <2% (oral)0.5-1.54 blonanserinoral10.7 (single 4 mg dose), 12 (single 8 mg dose), 16.2 (single 12 mg dose), 67.9 (repeated bid dosing) ?>99.7%urine (59%), faeces (30%)cyp3a484% (oral)<20.14 (single 4 mg dose), 0.45 (single 8 mg dose), 0.76 (single 12 mg dose), 0.57 (bid dosing) clozapineoral8 hours (single dosing), 12 (twice daily dosing)4.6797%urine (50%), faeces (30%)cyp1a2, cyp3a4, cyp2d650-60%1.5-2.5102-771 iloperidoneoral ?1340-280095%urine (45-58%), faeces (20-22%)cyp2d6 & cyp3a496%2-4 ? lurasidoneoral18617399%faeces (80%), urine (9%)cyp3a49-19%1-3 ? melperoneoral, intramuscular3–4 (oral), 6 (im)7–9.950%urine (70% as metabolites; 5–10.4% unchanged drug) ?65% (tablet), 87% (im), 54% (oral syrup)0.5–375–324 (repeated dosing) olanzapineoral, intramuscular (including depot)30100093%urine (57%), faeces (30%)cyp1a2, cyp2d6>60%6 (oral) ? paliperidoneoral, intramuscular (including depot)23 (oral)390-48774%urine (80%), faeces (11%)cyp2d6, cyp3a428%24 (oral) ? perospironeoral ? ?92%urine (0.4% as unchanged drug) ? ?1.51.9-5.7 quetiapineoral6 (ir), 7 (xr)6-1483%urine (73%), faeces (20%)cyp3a4100%1.5 (ir), 6 (xr) ? risperidoneoral, intramuscular (including depot)3 (em) (oral), 20 (pm) (oral)1-290%, 77% (metabolite)urine (70%), faeces (14%)cyp2d670%3 (em), 17 (pm) ? sertindoleoral72 (55-90)2099.5%urine (4%), faeces (46-56%)cyp2d674%10 ? ziprasidoneoral, intramuscular7 (oral)1.599%faeces (66%), urine (20%)cyp3a4 & cyp1a260% (oral), 100% (im)6-8 ? zotepineoral13.7-15.910-10997%urine (17%) ?7-13% ? ? acronyms used: ir - immediate release formulation. xr - extended release formulation. em - extensive metabolisers. pm - poor metabolisers. cmax - maximum plasma concentrations of the drug. pharmacokinetics of long-acting injectable antipsychotics medicationbrand nameclassvehicledosagetmaxt1/2 singlet1/2 multiplelogpcref aripiprazole lauroxilaristadaatypicalwatera441–1064 mg/4–8 weeks24–35 days ?54–57 days7.9–10.0 aripiprazole monohydrateabilify maintenaatypicalwatera300–400 mg/4 weeks7 days ?30–47 days4.9–5.2 bromperidol decanoateimpromen decanoastypicalsesame oil40–300 mg/4 weeks3–9 days ?21–25 days7.9 clopentixol decanoatesordinol depottypicalviscoleob50–600 mg/1–4 weeks4–7 days ?19 days9.0 flupentixol decanoatedepixoltypicalviscoleob10–200 mg/2–4 weeks4–10 days8 days17 days7.2–9.2 fluphenazine decanoateprolixin decanoatetypicalsesame oil12.5–100 mg/2–5 weeks1–2 days1–10 days14–100 days7.2–9.0 fluphenazine enanthateprolixin enanthatetypicalsesame oil12.5–100 mg/1–4 weeks2–3 days4 days ?6.4–7.4 fluspirileneimap, redeptintypicalwatera2–12 mg/1 week1–8 days7 days ?5.2–5.8 haloperidol decanoatehaldol decanoatetypicalsesame oil20–400 mg/2–4 weeks3–9 days18–21 days7.2–7.9 olanzapine pamoatezyprexa relprevvatypicalwatera150–405 mg/2–4 weeks7 days ?30 days– oxyprothepin decanoatemeclopintypical ? ? ? ? ?8.5–8.7 paliperidone palmitateinvega sustennaatypicalwatera39–819 mg/4–12 weeks13–33 days25–139 days ?8.1–10.1 perphenazine decanoatetrilafon dekanoattypicalsesame oil50–200 mg/2–4 weeks ? ?27 days8.9 perphenazine enanthatetrilafon enanthatetypicalsesame oil25–200 mg/2 weeks2–3 days ?4–7 days6.4–7.2 pipotiazine palmitatepiportil longumtypicalviscoleob25–400 mg/4 weeks9–10 days ?14–21 days8.5–11.6 pipotiazine undecylenatepiportil mediumtypicalsesame oil100–200 mg/2 weeks ? ? ?8.4 risperidonerisperdal constaatypicalmicrospheres12.5–75 mg/2 weeks21 days ?3–6 days– zuclopentixol acetateclopixol acuphasetypicalviscoleob50–200 mg/1–3 days1–2 days1–2 days4.7–4.9 zuclopentixol decanoateclopixol depottypicalviscoleob50–800 mg/2–4 weeks4–9 days ?11–21 days7.5–9.0 note: all by intramuscular injection. footnotes: a = microcrystalline or nanocrystalline aqueous suspension. b = low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). c = predicted, from pubchem and drugbank. sources: main: see template. history the first major tranquilizer or antipsychotic medication, chlorpromazine (thorazine), a typical antipsychotic, was discovered in 1951 and introduced into clinical practice shortly thereafter. clozapine (clozaril), an atypical antipsychotic, fell out of favor due to concerns over drug-induced agranulocytosis. following research indicating its effectiveness in treatment-resistant schizophrenia and the development of an adverse event monitoring system, clozapine re-emerged as a viable antipsychotic. according to barker (2003), the three most-accepted atypical drugs are clozapine, risperidone, and olanzapine. however, he goes on to explain that clozapine is usually the last resort when other drugs fail. clozapine can cause agranulocytosis (a decreased number of white blood cells), requiring blood monitoring for the patient. despite the effectiveness of clozapine for treatment-resistant schizophrenia, agents with a more favorable side-effect profile were sought for widespread use. during the 1990s, olanzapine, risperidone, and quetiapine were introduced, with ziprasidone and aripiprazole following in the early 2000s. the atypical antipsychotic paliperidone was approved by the fda in late 2006. the atypical antipsychotics have found favor among clinicians and are now considered to be first-line treatments for schizophrenia and are gradually replacing the typical antipsychotics. in the past, most researchers have agreed that the defining characteristics of atypical antipsychotics are the decreased incidence of extrapyramidal side effects (eps) and an absence of sustained prolactin elevation. the terminology can still be imprecise. the definition of "atypicality" was based upon the absence of extrapyramidal side effects, but there is now a clear understanding that atypical antipsychotics can still induce these effects (though to a lesser degree than typical antipsychotics). recent literature focuses more upon specific pharmacological actions and less upon categorization of an agent as "typical" or "atypical". there is no clear dividing line between the typical and atypical antipsychotics therefore categorization based on the action is difficult. more recent research is questioning the notion that second-generation antipsychotics are superior to first generation typical antipsychotics. using a number of parameters to assess quality of life, manchester university researchers found that typical antipsychotics were no worse than atypical antipsychotics. the research was funded by the national health service (nhs) of the uk. because each medication (whether first or second generation) has its own profile of desirable and adverse effects, a neuropsychopharmacologist may recommend one of the older ("typical" or first generation) or newer ("atypical" or second generation) antipsychotics alone or in combination with other medications, based on the symptom profile, response pattern, and adverse effects history of the individual patient. society and culture between may 2007 and april 2008, 5.5 million americans filled at least one prescription for an atypical antipsychotic. in patients under the age of 65, 71% of patients were prescribed an atypical antipsychotic to treat schizophrenia or bipolar disorder where this dropped to 38% in patients aged 65 or above. regulatory status regulatory status of second-generation antipsychotics (sgas) as of july 2013 generic nameunited statesfda approvedcanadahpfb approvedaustraliatga approvedeuropeema approvedjapanpmda approvedunited kingdommhra approved amisulpridenonoyes(some members)noyes aripiprazoleyesyesyesyesyesyes asenapineyesyesyesyesyesyes blonanserinnonononoyesno carpipraminenonononoyesno clocapraminenonononoyesno clozapineyesyesyesyesyesyes iloperidoneyesnonorefusednono lurasidoneyesyesyesyesnoyes melperonenononononono mosapraminenonononoyesno olanzapineyesyesyesyesyesyes paliperidoneyesyesyesyesyesyes perospironenonononoyesno pimavanserinyesnonoinvestigationalno(no) quetiapineyesyesyesyesyesyes remoxipridenononowithdrawnnono risperidoneyesyesyesyesyesyes sertindolenononoyesnoyes sulpiridenononoyesyesyes ziprasidoneyesyesyes(some members)noyes zotepinenonononoyesno notes the route of administration in this category refers to the standard means of administration when the drug is being used in its capacity as an atypical antipsychotic, not for other purposes. for example, amisulpride can be administered intravenously as an antiemetic drug but this is not its standard route of administration when being used as an antipsychotic note these values are from a study in of which amisulpride was intravenously administered stahl: ap explained 1 p. 329-336. p. 346-352. p. 355-360.