Hig hig engi specs rl eet and il sethraweal wind apgrieinaecly 2886 ob opt eres dahon oeepeers fiche fers fees {4 Selah, 201, Milan Poe, Stk, ewan, 2014, volition ‘Avalon isthe inabiliy’ initiate and perio ac teen, Pore ih ie symptom fae elerredl fe amar show bite inaevewe in perforealng even the most Bosc cy: erty cn inching hat sna wt personel vem Alogia ‘Alegin neers 1 the relutie absence of speech. A pense wah alogia a roponal 0 yucrtaees wih brie pli hae Ihave Eile omer ad way app eres! bm she exe ermathon. Such dofleeny a eminem a Bare reflect negative thong disorder raters imadeyemie -tovermunicuti sills Sonne teseurchers, for esas sua rst that peopl wih clogs maw fave trouble first the igh wes tormelae thet thea omiroasem. 2017) Sermetinnen sighs Hans the Farr wf aelayed! exe nin sr shou reapanacs i Questions, Talking sith itn teh nauileat this ssrapenn ca te towel frussrasing, makina you fel an f yom ary “pins tc ext thom enh Anhadonia AA veloc syimptows Is ced seibedoala. the prevemed lack of pleasure experionced by some pope wth seh pleat. Like siare moval dcecrs, wihedhiala vgn tratieverxc 1 aroeivre that wos typwally be cemehfored vicasorabie. inch ath, esa oman ony, amc sex: ud vedios Asociality ‘Pais syonstors may mers sila yeti pelea He anhodonla. Hoseever, aiactaly bas been recopmisod at 9 sequsate srruploen of schivephrenia eect disks ‘This eymptoan copsures a lack of interest Wn social nee actions (APA, 200. Undeuaratsly, this mprmpeoi ca aba result frum ae oe weoreened thy Menitel ppertueliten te tenet wel ther, Foe menetely patie ‘hoakds, Hamar, Cheen, 20181 Affective Flattening Imagine that penyie more wuanks at all hex: You ena “csr wate Bom seta Dat yas ns By ae toner these einotanal racine. Agpwantinalely ste 4Mat- tera the people ih sefieopheoin exhibit whats cated [a aiflest (Lewis «wl, 2004, Buammmsen oi al, 2012), ‘They ate samiler bs peegie weering mine become they 18 nit show emotions when yout worl normaly expect thet ha They dha stare fen sama ypenk (4 et tnd toneleas manner and seem unsfected by rhings wine vm arymunl them. Hboreever, althewgh they sky mi few ‘pew amuaivaal sitaations, choy wnat he regen, thw iid Heard Reteabaismy anit Thasmae Okman (1992) computed people with schisophrenta who bad Aa tor heed) acct wich theme: wth il me. The te prep wert shown clips from corte anal damm sebeceed 1 Cre cematlonal eesetions ia he sewer Becomes andl Glimanns Iso chat the peuple with Hla aff abu lide change in facial expecenin. abhouale they reported femeriencing the appraprate cwsminns. Ye wank cn ledesl that the flat alflest im schivuphrenia yay repre sco datFicats exeenning eration, mot « lack of beeline: Masearehe ine ase conmgusiet atlases f Fabel pressions ta raure obpeclively assess the emutionsl wapeemivenaee of neste wile dbeardeey tach aw schine- liens (King & Elis, 2013), hav suk stty cnodiomaed the fully of prone wich thie Ghonskr to exgeen stem sclsespeuperly ih aul expenate (Hay, Pada Gur, Verma, Ketter 14 eta the schimphremia Ina particulary tnnorntine sods researc fry vibes higher ink chal (hme wih uno sre rats wns had schizophrenia eating ich in 1902 and ica hee salu 30 years Laie Ac hittnas erl 2001) ‘The manerchers wer abr ws sh thot inom br lbter wen i ckvelap x Racer topes lg leas pnd ata! tone opiate alles Una howe hike ‘whe de develop the dasarder. Ths muggesta that em tial expression may Ihe ne way 1 ieily pone nial schlauphransa tn chee Disorganized Symptoms Pestupa Uae Houss studi and therefore Ub bows uae sinod symptoms of schizophrenia are relerred 10-5 the "Ubsaegniced eyaptom” Thevr chase 2 variety a erat Ibcharvioce that uffect weesb. motor behariot. and em Idovnd rewctioma, The penal af thom fatinbors sea those with schlanphrenis uncon eases spars x seo gnemirs sao Rta eset grenhcestres kr ese eevee = dome meet A rotinn teeta ptt meen ren le Ces dg Ache ray wou arctan conten gmat FSntarareR Ser tees patch ne ate secbesenia shy eegmorin pms scm ne ro Pend sotesvnueers ere (ih ee epee pertirieniiciey triiniegiesien pet eile gem meee emt el eaparesOlanzapine Olanzapine is dosed between 5 and 20 mg daily. It is provided in unmarked tablet formulations from Eli Lilly; however, several tablet strengths are available for use. Given its half-life of 30 hours, once-daily dosing has been advocated to facilitate treatment compliance. A sapidly dissolving formulation has recently ‘been marketed (Zyprexa Zydis), which dissolves quickly upon contact with saliva within the mouth “Although more costly than the customary tablet formulations, this quick-dissolving formulation is advocated for patients who experience difficulty swallowing pills, for example, because of dysphagia, and ‘those individuals who may attempt to undermine treatment by “cheeking” and spitting out medications administered to them. This tablet is available only in 5- and 10-mg doses. Generally, patients are initiated at 5 mg/day and the dose is gradually increased up to a maximum of 20 mg/day. Common adverse effects associated with olanzapine use include postural hypetensioa, dizziness, coastipatioa, and weight gain. Of ‘these, weight gain has been the most significant; an average 26-Ib weight gain by the end of 1 year of clinical trials has been reported “2 Certainly, weight gain can be a disincentive to comply with treatment and complicates comorbid medical conditions, such as obesity and heart disease. Olanzapine use has also ‘been linked to disturbances in glucose regulation, hyperglycemia, and diabetic ketoacidosis and increases in trigiyceride levets +227 Consequently. patients with diabetes will need to have more careful ‘monitoring of their blood glucose and hemoglobin AC levels if administered olanzapine. In nondiabetics ‘periodic monitoring of triglycerides, serum glucose level, and weight would be indicated. There have been asymptomatic elevations in haptic enzymes in olanzapine tested patients, bot the significance of such elevations remains uncertain +2 Nonetheless, caution is advised for patients with preexisting hepatic disease including hepatitis, cicrhosis, and significant alcohol abuse histories. Increased olanzapine clearance has been associated with concomitant atiministration of omeprazole, ‘rifampin, and carbamazepine. Decreased olanzapine clearance has been noted among patients coadministered fluvoxamine. Quetiapine The most recent atypical antipsychotic to be approved by the U.S. Food and Drug Administration (FDA) for treatment of psychotic disorders is quetiapine. Dosing is usually begua at 25 mg b.id. or tid. and increased by 25 to 50 mg bid. every 1 to 2 days until a daily dose of 300 mg is achieved by the end of 1 week. Generally, the effective dose ranges between 300 and 500 mg daily in the acutely ill psychiatric patient. Quetiapine is generally well tolerated. The most frequent adverse effects associated with its use include sedation, fatigue, dizziness, and orthostatic hypotension “7 Quetiapine has been noted to have significant blockade of histamine (Hy) receptors, which accounts for both its sedating effect as well as itz effect on weight gain. Similar to other atypical agents, weight gain with quetiapine use can be quite ‘troublesome to patients and can interfere with medication compliance. Unlike risperidone, quetiapine hasRisperidone Risperidone was the second of the atypical antipsychotics marketed in the United States. Similar to clozapine, it has demonstrated clinical efficacy beyond that of conventional antipsychotics in the treatment of refractory illnesses as well as management of negative symptoms. It affords a major advantage over clozapine: without the risk of agranulocytosis, there is no need for weekly blood monitoring. It is available in liquid as well as tablet formulations from Janssen Pharmaceutica, Dosing is generally begun at | mg bid. increased to 2 mg bid. on day 2 then to 3 mg bid. on day 3. While clinical trials assessing the efficacy of risperidone have included doses up to 16 mg/day, the recommended daily dose for most individuals is between 4 and 8 mg/day 2 As compared with conventional antipsychotic use, risperidone use carries with it a decreased risk of Eps LAE 4. noted previously, the propensity toward EPS with risperidone appears to be dose related. At doses exceeding the usual recommended daily doze (16 mg), significantly higher rates of EPS were encountered as compared with placebo 7 The risk of risperidone-associated EPS is reduced if doses are maintained within the recommended dosage range. The most problematic side effects (see Table 2) include sedation, weight gain, and sexual side effects due to alteration of CNS prolactin release. Sedation appears to be common early in the course of treatment and increases with higher doses. As with each of the atypical antipsychotics, weight gain can occur with risperidone use. Patients may need to be advised about altering dietary habits and incorporating exercise into the usual daily regimen to reduce the potential morbidity and medical complications associated with weight gain. Significant weight increases can adversely effect self-image and lead to noncompliance. The risk of weight gain appears to be less for risperidone than either clozapine or olanzapine 112 Hypothalamic dopamine exerts an inhibitory effect on pituitary prolactin release. As with more conventional antipsychotics, risperidone can lead to hyperprolactinemia through its blockade of dopamine seceptors. For women, increase: in serum prolactin can reault in amenorrhea, galactosthea, and decreased libido. For mea, hyperprolactinemia can result in erectile and ejaculatory dysfunction and decreased. ido 22 However, there is no correlation between degree of hyperprolactinemia and side effect rates “1120 Thus, periodic inquiry into sexual side effects associated with risperidone use is warranted, since they can adversely affect patient compliance. Generally, management of sexual side effects is possible with risperidone dose reductions or the use of altemate antipsychotic agents, such as olanzapine. The addition of prolactin-lowering agents, e.g.. bromocriptine, may prove to be hazardous in that these can exacerbate psychosis. Risperidone has been associated with alteration of cardiac conduction, ie., prolongation of the corrected QT interval. While this is of minimal clinical significance, primary care physicians ought to be aware of inert eetan te than itis Hint tho, (A to traafeonetne thn JAnwn ane‘esearch efforts into a clinical problem of a substantial magnitude and importance. Prevalence Goto: Epidemiological data support the notion that patients with the deficit syndrome represent a distinct subgroup within schizophrenia. In clinical samples, patients with the deficit form of schizophrenia or ‘primary negative symptoms represent about 20%-30% of patients, whereas in population-based samples approximating incidence samples, patients with the deficit form of schizophrenia comprise 149%-17% of patients with schizophrenia © Carpenter and colleagues examined the prevalence ofthe deficit syndreme ‘within an cutpatient clinical population 2 They reported a 19% prevalence rate in a nonrandom population of patients. Bottlender and colleagues reported a similar prevalence (26%) in patients who were evaluated 15 years after their first hospitalization ®! The prevalence of the deficit syndrome was substantially higher (G76) im a sample of patients with schizophrenia who were 45 years of older32 However, in a sample of patients with first-episode schizophrenia and followed up through their recovery for at least 6 months, only 4% met all criteria for deficit syndrome, while 19% had deficit symptoms 33 In a retrospective study of 660 consecutively admitted psychiatric inpatients that presented with at least one psychotic symptom and severe negative symptoms, a modified version of the Schedule for the Deficit Syndrome (SDS)"2 was used to identify subjects with persistent primary negative symptoms 4 The symptoms were required to have persisted over the last year, and their association with putative sources of secondary negative symptoms ‘was examined. The subjects were not required to have a diagnosis of schizophrenia. Using the above criteria, the authors identified the presence of persistent primary negative symptoms in 15.5% of all subjects irrespective of the diagnosis, whereas the prevalence was 25.7% in subjects with schizophrenia, 8.1% in those with schizoaffective disorder, 2.3% in mood disorders, and 15.6% in psychotic disorders not otherwise specified. Population-based studies have the advantage of random selection of subjects and may provide more “unbiased estimates of deficit syndrome prevalence. In a study looking at subjects who met criteria for schizophrenia or simple schizophrenia in a population-based psychiatric registry in County Roscommon, Ireland, the lifetime prevalence of the deficit syndrome was 16.5% In the Irish Study of High-Density ‘Schizophrenia Families in subjects who were members of the full sibling pairs concordant for schizophrenia, schizoaffective disorder with poor outcome or simple schizophrenia > the prevalence of the deficit syndrome was 13.9%, Although there is clearly a need for more studies, the available results suggest a prevalence of the deficit syndrome of approximately 15%-20%. There is little epidemiological data pertaining to persistent negative symptoms. In light of the estimated 15%20% prevalence of the deficit syndrome, the prevalence of persistent negative symptoms is probably higher because persistent negative symptoms alzo include unresponsive secondary negative symptoms. The lack of reliable information regarding the prevalence of negative symptoms warranting therapeutic intervention is acknowledged in the recently published NIMH-MATRICS Consensus Statement onDOSING, SIDE EFFECTS, AND DRUG INTERACTIONS Goto: 5) Clozapine Clozapine was the first atypical antipsychotic marketed in the United States. Since its initial use in 1990, it has demonstrated clinical utility for patients with schizophrenia unresponsive to conventional antipsychotics, patients with marked negative symptoms, patients with severe untoward effects om conventional antipsychotics, and patients with tardive dyskinesia. It is available in tablet form from ‘Novartis Pharmaceuticals Corp. Dosing is generally begun at 12.5 mg/day, increased to 25 mg on day 2, then to 25 mg bid. on day 3, then increased an initial 25 mg every 3 days thereafter. The recommended dose range is 300 to 900 mg/day. Some of the side effects associated with clozapine use are summarized in Table 2. Sedation is most common, particularly with the onset of treatment and/or dose increases, although it tends to be mild and transient. Tolerance appears to develop to sedation 1”! Ifthe bulk of the daily dose is administered at bedtime, the sedative effects may enhance sleep. Reduction in doses of, or elimination of, coadministered CNS depressants and sedative-hypnotics may reduce the risk of any additive sedative effects. Another common adverse effect associated with clozapine use is increased salivation. Patients report awakening from sleep with a wet pillow 222 siatorrhea can be reduced by minimizing administered doses of clozapine or by administering a clonidine pateh “> Despite its ability to trigger hypersalivation, clozapine is strongly anticholinergic. Consequently, its use results in nausea, vomiting, constipation, bloating, and abdominal pain 1 Patients should be advised to ensure that they drink adequate amounts of fluids, supplement their diet with highefiber foods, and use ‘bulk-forming agents or stool softeners as needed. Weight gain can be particularly problematic 041 The most serious side effects associated with clozapine use include agranulocytosis, cardiorespiratory arrest, and seizures. The risk of agranulocytosis has been estimated to be between 1% and 2%1°8 From 1990 to 1994, the death rate associated with clozapine-induced agranulocytosis in the United States was approximately 3%, The risk of agranulocytosis appears to be highest in the first 3 months of treatment, increases with age, and appears to be higher in women 101108 Consequently, patients treated with clozapine are required to have weekly complete blood count testing. The WBC count must be maintained at or above 3000 mm!, and the absolute neutrophil count must be maintained at or above 1500/mm*. If patients maintain acceptable WBC and nevtrophil parameters, blood sampling can be reduced to once every 2 weeks after the first 6 months of continuous clozapine therapy. Clozapine availability is, therefore, contingent upon compliance with a distribution system that ensures WBC testing prior to the delivery of the patient's supply of medication for the following week 122 Clearly, patients who are treated with clozapine need to be monitored for signs of infection continuously.ere BETELL Us ABOUT VouRSELF Definition of APATHY 1. slack of feeling or emotion : IMPASSIVENESS + drug abuse leading to apatiy and depression 2 slack of interest or concern ; INDIFFERENCE - political apathy See apathy defined for English-language learners See apathy defined for kids > issra Aa, Adepa (qv), *6, indecl., first letter of the Gr. alphabet: as Numeral, & Avs cis and xgcros, but ‘a = 1,000. Henry George Liddell. Robert Scott. A Greek-English Lexicon. revised and augmented throughout by. Sir Henry Stuart Jones. with the assistance of. Roderick McKenzie. Oxford. Clarendon Press. 1940. ‘The National Endowment for the Huma Do Be ies provided support for entering