Psychosis

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Psychosis Classification and external resources

ICD-9 OMIM

290-299 60 !2 60"92 60 #$% #92! 0

MedlinePlus 00#%% MeSH F03.700.67

Psychosis &from the 'reek ()*+ ,psyche,, for mind or soul, and --./0 ,-osis,, for a1normal condition2, 3ith ad4ective psychotic, literally means a1normal condition of the mind, and is a generic psychiatric term for a mental state often descri1ed as involving a ,loss of contact 3ith reality,5 6eople suffering from psychosis are said to 1e !sychotic. 6eople e7periencing psychosis may report hallucinations or delusional 1eliefs, and may e7hi1it personality changes and disorgani8ed thinking5 9his may 1e accompanied 1y unusual or 1i8arre 1ehavior, as 3ell as difficulty 3ith social interaction and impairment in carrying out the activities of daily living5 : 3ide variety of central nervous system diseases, from 1oth e7ternal to7ins, and from internal physiologic illness, can produce symptoms of psychosis5 9his disease link has led to the metaphor of psychosis as the ;fever; of <=> illness?a serious 1ut nonspecific indicator5@#A@2A Bo3ever, many people have unusual and distinct &unshared2 e7periences of different realities at some point in their lives, 3ithout 1eing impaired or even distressed 1y these e7periences5 For e7ample, many people have e7perienced visions of some kind, and some have even found inspiration or religious revelation in them5@ A :s a result, it has 1een argued that psychosis is not fundamentally separate from normal consciousness, 1ut rather, is on a continuum 3ith normal consciousness5@!A Cn this vie3, people 3ho are clinically found to 1e psychotic may simply 1e having particularly intense or distressing e7periences &see schi8otypy25

Cn contemporary culture, the term ,psychotic, is often incorrectly used interchangea1ly 3ith ,psychopathic or sociopathic,, 3hich actually descri1e a propensity to engage in violently antisocial 1ehaviors, not usually involving hallucinations or delusions5

[edit] Signs and symptoms

6eople 3ith psychosis may have one or more of the follo3ing: hallucinations, delusions, thought disorder, or lack of insight &each descri1ed 1elo325 9he symptoms are similar in nature to mental confusion and delirium5 @%A

[edit] Hallucinations
Ballucinations are defined as sensory perception in the a1sence of e7ternal stimuli5 9hey are different from illusions, or perceptual distortions, 3hich are the misperception of e7ternal stimuli5@6A Ballucinations may occur in any of the five senses and take on almost any form, 3hich may include simple sensations &such as lights, colors, tastes, and smells2 to more meaningful e7periences such as seeing and interacting 3ith fully formed animals and people, hearing voices and comple7 tactile sensations5 :uditory hallucinations, particularly the e7perience of hearing voices, are a common and often prominent feature of psychosis5 Ballucinated voices may talk a1out, or to the person, and may involve several speakers 3ith distinct personas5 :uditory hallucinations tend to 1e particularly distressing 3hen they are derogatory, commanding or preoccupying5 Bo3ever, the e7perience of hearing voices need not al3ays 1e a negative one5 Desearch has sho3n that the ma4ority of people 3ho hear voices are not in need of psychiatric help5@$A 9he Bearing Eoices Fovement has su1seGuently 1een created to support voice hearers, regardless of 3hether they are considered to have a mental illness or not5

[edit] Delusions
6sychosis may involve delusional 1eliefs, some of 3hich are paranoid in nature5 Harl Jaspers classified psychotic delusions into !rimary and secondary types5 6rimary delusions are defined as arising suddenly and not 1eing comprehensi1le in terms of normal mental processes, 3hereas secondary delusions may 1e understood as 1eing

influenced 1y the person;s 1ackground or current situation &e5g5, ethnic or se7ual orientation, religious 1eliefs, superstitious 1elief25@"A

[edit] Thought disorder

Ct descri1es an underlying distur1ance to conscious thought and is classified largely 1y its effects on speech and 3riting5 :ffected persons sho3 loosening of associations, that is, a disconnection and disorganisation of the semantic content of speech and 3riting5 Cn the severe form speech 1ecomes incomprehensi1le and it is kno3n as ,3ord-salad,5

[edit] ac! o" insight

Ine important and pu88ling feature of psychosis is usually an accompanying lack of insight into the unusual, strange, or 1i8arre nature of the person;s e7perience or 1ehavior5 @9A Jven in the case of an acute psychosis, people may 1e completely una3are that their vivid hallucinations and delusions are in any 3ay ,unrealistic,5 9his is not an a1solute, ho3everK insight can vary 1et3een individuals and throughout the duration of the psychotic episode5 Ct 3as previously 1elieved that lack of insight 3as related to general cognitive dysfunction@#0A or to avoidant coping style5@##A Later studies have found no statistical relationship 1et3een insight and cognitive function, either in groups of people 3ho only have schi8ophrenia,@#2A or in groups of psychotic people from various diagnostic categories5@# A

[edit] Classi"ication
Cn medical practice today, a descriptive approach to psychosis &and to all mental illness2 is used, 1ased on 1ehavioral and clinical o1servations5 9his approach is adopted in the standard guide to psychiatric diagnoses employed in the Mnited >tates, the Niagnostic and >tatistical Fanual of Fental Nisorders &N>F25 >ince the N>F provides a 3idelyused standard of reference, the description presented here 3ill largely reflect that point of vie35 :ccording to the N>F-CE-9D, the term psychosis has had many definitions in the past, 1oth 1road and narro35 9he 1roadest 3as not 1eing a1le to meet the demands of everyday life5 9he narro3est 3as delusions or hallucinations 3ithout insight5 : middle ground may 1e delusions, hallucinations 3ith or 3ithout insight, as 3ell as disorgani8ed 1ehavior or speech5 9hus, psychosis can 1e a symptom of mental illness, 1ut it is not a mental illness in its o3n right5 For e7ample, people 3ith schi8ophrenia often e7perience psychosis, 1ut so can people 3ith 1ipolar disorder &manic depression2, unipolar depression, delirium, or drug 3ithdra3al5@#!A@#A 6eople diagnosed 3ith these conditions can also have long periods "ithout psychosis, and some may never e7perience them again5 <onversely, psychosis can occur in people 3ho do not have chronic mental illness &e5g5 due to an adverse drug reaction or e7treme stress25@#%A

6sychosis should 1e distinguished from:

insanity, 3hich is a legal term denoting that a person is not criminally responsi1le for his or her actions5@#6A ,Cnsanity is no longer considered a medical diagnosis555,
@#$A

!sycho!athy, a general term for a range of personality disorders characteri8ed 1y lack of empathy, socially manipulative 1ehavior, and occasionally criminality or violence5@#"A Nespite 1oth 1eing a11reviated to the slang 3ord ,psycho,, psychosis 1ears little similarity to the core features of psychopathy, particularly 3ith regard to violence, 3hich rarely occurs in psychosis,@#9A@20A and distorted perception of reality, 3hich rarely occurs in psychopathy5@2#A delirium: a psychotic individual may 1e a1le to perform actions that reGuire a high level of intellectual effort in clear consciousness, 3hereas a delirious individual 3ill have impaired memory and cognitive function5

9he N>F-CE-9D lists 9 formal psychotic disorders, 1ut many other disorders may have psychotic symptoms5 9he formal psychotic disorders are: #5 25 5 !5 %5 65 $5 "5 95 >chi8ophrenia >chi8oaffective disorder >chi8ophreniform disorder Orief psychotic disorder Nelusional disorder >hared psychotic disorder &Folie P deu72 >u1stance induced psychosis 6sychosis due to a general medical condition 6sychosis - =ot other3ise specified

[edit] Causes
<auses of symptoms of mental illness 3ere customarily classified as ,organic, or ,functional,5 Irganic conditions 3ere primarily medical or pathophysiological, 3hereas, functional conditions are primarily psychiatric or psychological5 9he N>F-CE-9D no longer classifies psychotic disorders as functional or organic5 Dather it lists traditional psychotic illnesses, psychosis due to 'eneral Fedical conditions, and >u1stance induced psychosis5

[edit] Psychiatric
Functional causes of psychosis include the follo3ing:

1rain tumors drug a1use amphetamines, cocaine, alcohol among others schi8ophrenia 1ipolar disorder &manic depression2 severe clinical depression

severe psychosocial stress sleep deprivation some focal epileptic disorders especially if the temporal lo1e is affected e7posure to some traumatic event &violent death, terrorist activity, etc52

: psychotic episode can 1e significantly affected 1y mood5 For e7ample, people e7periencing a psychotic episode in the conte7t of depression may e7perience persecutory or self-1laming delusions or hallucinations, 3hile people e7periencing a psychotic episode in the conte7t of mania may form grandiose delusions5 >tress is kno3n to contri1ute to and trigger psychotic states5 : history of psychologically traumatic events, and the recent e7perience of a stressful event, can 1oth contri1ute to the development of psychosis5 >hort-lived psychosis triggered 1y stress is kno3n as 1rief reactive psychosis, and patients may spontaneously recover normal functioning 3ithin t3o 3eeks5@#%A Cn some rare cases, individuals may remain in a state of full-1lo3n psychosis for many years, or perhaps have attenuated psychotic symptoms &such as lo3 intensity hallucinations2 present at most times5 >leep deprivation has 1een linked to psychosis5@22A@2 A@2!A Bo3ever, this is not a risk for most people, 3ho merely e7perience hypnagogic or hypnopompic hallucinations, i5e5 unusual sensory e7periences or thoughts that appear during 3aking or drifting off to sleep5 9hese are normal sleep phenomena and are not considered signs of psychosis5@2%A Eitamin O#2 deficiency can also cause symptoms of mania and psychosis5@26A@2$A

[edit] #eneral medical

6sychosis arising from ,organic, &non-psychological2 conditions is sometimes kno3n as secondary psychosis5 Ct can 1e associated 3ith the follo3ing pathologies:

neurological disorders, including: o 1rain tumour@2"A o dementia 3ith Le3y 1odies@29A o multiple sclerosis@ 0A o sarcoidosis@ #A o Lyme Nisease@ 2A@ A@ !A o syphilis @ %A@ 6A o :l8heimer;s Nisease@ $A o 6arkinson;s Nisease@ "A electrolyte disorders such as: o hypocalcemia@ 9A o hypernatremia@!0A o hyponatremia@!#A o hypokalemia@!2A o hypomagnesemia@! A

hypermagnesemia@!!A hypercalcemia@!%A hypophosphatemia@!6A hypoglycemia@!$A lupus@!"A :CN>@!9A leprosy@%0A@%#A malaria@%2A :dult-onset vanishing 3hite matter leukoencephalopathy@% A Late-onset metachromatic leukodystrophy@%!A@%%A@%6A <ere1ral involvement of scleroderma &a single case report25@%$A Bashimoto;s encephalopathy, an e7tremely rare condition &a1out #00 reported cases25@%"A@%9A@60A
o o o

6sychosis can even 1e caused 1y apparently innocuous ailments such as flu@6#A@62A or mumps5@6 A

[edit] Psychoacti$e drug use

6sychotic states may occur after ingesting a variety of su1stances 1oth legal and illegal and 1oth prescription and non prescription5 Nrugs 3hose use, a1use or 3ithdra3al are implicated include:

alcohol@6!A@6%A@66A I9< drugs, such as: o Ne7tromethorphan o <ertain antihistamines at high doses5@6$A@6"A@69A@$0A o <old Fedications@$#A &ie5 containing 6henylpropanolamine, or 66:2 prescription drugs: o 1ar1iturates@$2A@$ A o 1en8odia8epines@$!A@$%A@$6A o Csotretinoin o :nticholinergic drugs atropine@$$A@$"A scopolamine@$9A Jimson 3eed@"0A o antidepressants o L-dopa o antiepileptics@"#A o amphetamines@"2A o methamphetamine@"2A o methylphenidate@"2A Cllegal drugs, including: o >timulants

cocaine@" A amphetamines@"2A methamphetamine@"2A methylphenidate@"2A FNF: &ecstasy2 <anna1is@"!A

Cnto7ication 3ith drugs that have general depressant effects on the central nervous system &especially alcohol and 1ar1iturates2 tend not to cause psychosis during use, and can actually decrease or lessen the impact of symptoms in some people5 Bo3ever, "ithdra"al from 1ar1iturates and alcohol can 1e particularly dangerous, leading to psychosis or delirium and other, potentially lethal, 3ithdra3al effects5 >ome studies indicate that canna1is use may lo3er the threshold for psychosis, and thus help to trigger full-1lo3n psychosis in some people5@"%A Jarly studies have 1een critici8ed for failing to consider other drugs &such as L>N2 that the participants may have used 1efore or during the study, as 3ell as other factors such as pre-e7isting &,comor1id,2 mental illness5 Bo3ever, more recent studies 3ith 1etter controls have still found a small increase in risk for psychosis in canna1is users5@"6A Ct is not clear 3hether this is a causal link, and it is possi1le that canna1is use only increases the chance of psychosis in people already predisposed to itK or that people 3ith developing psychosis use canna1is to provide temporary relief of their mental discomfort5 : fact is that canna1is use has increased over past fe3 decades 1ut declined in the last decade, 3hereas the rate of psychosis has not increased5 9his suggests that a direct causal link is unlikely for all users5@"$A Ct is also important to this topic to understand the parado7ical effects of some sedative drugs5@""A5>erious complications can occur in con4unction 3ith the use of sedatives creating the opposite effect as to that intended5 Falcolm Lader at the Cnstitute of 6sychiatry in London estimates the incidence of these adverse reactions at a1out %Q, even in short-term use of the drugs5@"9A 9he parado7ical reactions may consist of depression, 3ith or 3ithout suicidal tendencies, pho1ias, aggressiveness, violent 1ehavior and symptoms sometimes misdiagnosed as !sychosis5 @90A@9#A

[edit] Prescription medication

>ome medications such as 1romocriptine and phenylpropanolamine may also cause or 3orsen psychotic symptoms5@92A@9 A @9!A

[edit] Pathophysiology
Orain imaging studies of psychosis, investigating 1oth changes in 1rain structure and changes in 1rain function of people undergoing psychotic episodes, have sho3n mi7ed results5

9he first 1rain image of an individual 3ith psychosis 3as completed as far 1ack as #9 % using a techniGue called pneumoencephalography@9%A &a painful and no3 o1solete procedure 3here cere1rospinal fluid is drained from around the 1rain and replaced 3ith air to allo3 the structure of the 1rain to sho3 up more clearly on an R-ray picture25 Fore recently, a 200 study investigating structural changes in the 1rains of people 3ith psychosis sho3ed there 3as significant grey matter reduction in the corte7 of people 1efore and after they 1ecame psychotic5@96A Findings such as these have led to de1ate a1out 3hether psychosis is itself neuroto7ic and 3hether potentially damaging changes to the 1rain are related to the length of psychotic episode5 Decent research has suggested that this is not the case@9$A although further investigation is still ongoing5 Functional 1rain scans have revealed that the areas of the 1rain that react to sensory perceptions are active during psychosis5 For e7ample, a 6J9 or fFDC scan of a person 3ho claims to 1e hearing voices may sho3 activation in the auditory corte7, or parts of the 1rain involved in the perception and understanding of speech5@9"A In the other hand, there is not a clear enough psychological definition of 1elief to make a comparison 1et3een different people particularly valid5 Orain imaging studies on delusions have typically relied on correlations of 1rain activation patterns 3ith the presence of delusional 1eliefs5@99A Ine clear finding is that persons 3ith a tendency to have psychotic e7periences seem to sho3 increased activation in the right hemisphere of the 1rain5@#00A 9his increased level of right hemisphere activation has also 1een found in healthy people 3ho have high levels of paranormal 1eliefs@#0#A and in people 3ho report mystical e7periences5@#02A Ct also seems to 1e the case that people 3ho are more creative are also more likely to sho3 a similar pattern of 1rain activation5@#0 A >ome researchers have 1een Guick to point out that this in no 3ay suggests that paranormal, mystical or creative e7periences are in any 3ay by themsel#es a symptom of mental illness, as it is still not clear 3hat makes some such e7periences 1eneficial 3hilst others lead to the impairment or distress of diagnosa1le mental pathology5 Bo3ever, people 3ho have profoundly different e7periences of reality or hold unusual vie3s or opinions have traditionally held a comple7 role in society, 3ith some 1eing vie3ed as kooks, 3hilst others are lauded as prophets or visionaries5 6sychosis has 1een traditionally linked to the neurotransmitter dopamine5 Cn particular, the dopamine hypothesis of psychosis has 1een influential and states that psychosis results from an overactivity of dopamine function in the 1rain, particularly in the mesolim1ic path3ay5 9he t3o ma4or sources of evidence given to support this theory are that dopamine-1locking drugs &i5e5 antipsychotics2 tend to reduce the intensity of psychotic symptoms, and that drugs 3hich 1oost dopamine activity &such as amphetamine and cocaine2 can trigger psychosis in some people &see amphetamine psychosis25@#0!A Bo3ever, increasing evidence in recent times has pointed to a possi1le dysfunction of the e7citory neurotransmitter glutamate, in particular, 3ith the activity of the =FN: receptor5 9his theory is reinforced 1y the fact that dissociative =FN: receptor antagonists such as ketamine, 6<6 and de7tromethorphanSdetrorphan &at large

overdoses2 induce a psychotic state more readily than dopinergic stimulants, even at ,normal, recreational doses5 9he symptoms of dissociative into7ication are also considered to mirror the symptoms of schi8ophrenia more closely, including negative psychotic symptoms than amphetamine psychosis5 Nissociative induced psychosis happens on a more relia1le and predicta1le 1asis than amphetamine psychosis, 3hich usually only occurs in cases of overdose, prolonged use or 3ith sleep deprivation, 3hich can independently produce psychosis5 =e3 antipsychotic drugs 3hich act on glutamate and its receptors are currently undergoing clinical trials5 &>ee glutamate hypothesis of psychosis2 9he connection 1et3een dopamine and psychosis is generally 1elieved to 1e comple75 While antipsychotic drugs immediately 1lock dopamine receptors, they usually take a 3eek or t3o to reduce the symptoms of psychosis5 Foreover, ne3er and eGually effective antipsychotic drugs actually 1lock slightly less dopamine in the 1rain than older drugs 3hilst also affecting serotonin function, suggesting the ;dopamine hypothesis; may 1e oversimplified5@#0%A >oyka and colleagues found no evidence of dopaminergic dysfunction in people 3ith alcohol-induced psychosis@#06A and Toldan et al5 reported moderately successful use of ondansetron, a %-B9 receptor antagonist, in the treatment of levodopa psychosis in 6arkinson;s disease patients5@#0$A 6sychiatrist Navid Bealy has criticised pharmaceutical companies for promoting simplified 1iological theories of mental illness that seem to imply the primacy of pharmaceutical treatments 3hile ignoring social and developmental factors 3hich are kno3n to 1e important influences in the aetiology of psychosis5@#0"A >ome theories regard many psychotic symptoms to 1e a pro1lem 3ith the perception of o3nership of internally generated thoughts and e7periences5@#09A For e7ample, the e7perience of hearing voices may arise from internally generated speech that is misla1eled 1y the psychotic person as coming from an e7ternal source5

[edit] Treatment
9he treatment of psychosis depends on the cause or diagnosis or diagnoses &such as schi8ophrenia, 1ipolar disorder andS or su1stance into7ication25 9he first line treatment for many psychotic disorders is antipsychotic medication &oral or intramuscular in4ection2, and sometimes hospitalisation is needed5 9here is gro3ing evidence that cognitive 1ehavior therapy@##0A and family therapy@###A can 1e effective in managing psychotic symptoms5 When other treatments for psychosis are ineffective, electroconvulsive therapy &J<92 &aka shock treatment2 is sometimes utili8ed to relieve the underlying symptoms of psychosis due to depression5 9here is also increasing research suggesting that :nimal-:ssisted 9herapy can contri1ute to the improvement in general 3ell-1eing of people 3ith schi8ophrenia5@##2A

[edit] %arly inter$ention in psychosis

$ain article% &arly inter#ention in !sychosis Jarly intervention in psychosis is a relatively ne3 concept 1ased on the o1servation that identifying and treating someone in the early stages of a psychosis can significantly improve their longer term outcome5@## A 9his approach advocates the use of an intensive multi-disciplinary approach during 3hat is kno3n as the critical period, 3here intervention is the most effective, and prevents the long term mor1idity associated 3ith chronic psychotic illness5 =e3er research into the effectiveness of cognitive 1ehavioural therapy during the early pre-cursory stages of psychosis &also kno3n as the ,prodrome, or ,at risk mental state,2 suggests that such input can prevent or delay the onset of psychosis5 Bo3ever further research in this area is needed5 @##!A

[edit] History
9he 3ord !sychosis 3as first used 1y Jrnst von Feuchtersle1en in #"!%@##%A as an alternative to insanity and mania and stems from the 'reek '()*+,- &!sychosis2, ,a giving soul or life to, animating, Guickening, and that from '.)/ &!syche2, ,soul, and the suffi7 0*+,- &0osis2, in this case ,a1normal condition,5@##6A@##$A 9he 3ord 3as used to distinguish disorders 3hich 3ere thought to 1e disorders of the mind, as opposed to ,neurosis,, 3hich 3as thought to stem from a disorder of the nervous system5 9he division of the ma4or psychoses into manic depressive illness &no3 called 1ipolar disorder2 and dementia praeco7 &no3 called schi8ophrenia2 3as made 1y Jmil Hraepelin, 3ho attempted to create a synthesis of the various mental disorders identified 1y #9th century psychiatrists, 1y grouping diseases together 1ased on classification of common symptoms5 Hraepelin used the term ;manic depressive insanity; to descri1e the 3hole spectrum of mood disorders, in a far 3ider sense than it is usually used today5 Cn Hraepelin;s classification this 3ould include ;unipolar; clinical depression, as 3ell as 1ipolar disorder and other mood disorders such as cyclothymia5 9hese are characterised 1y pro1lems 3ith mood control and the psychotic episodes appear associated 3ith distur1ances in mood, and patients 3ill often have periods of normal functioning 1et3een psychotic episodes even 3ithout medication5 >chi8ophrenia is characteri8ed 1y psychotic episodes 3hich appear to 1e unrelated to distur1ances in mood, and most non-medicated patients 3ill sho3 signs of distur1ance 1et3een psychotic episodes5 Nuring the #960s and #9$0s, psychosis 3as of particular interest to counterculture critics of mainstream psychiatric practice, 3ho argued that it may simply 1e another 3ay of constructing reality and is not necessarily a sign of illness5 For e7ample, D5 N5 Laing argued that psychosis is a sym1olic 3ay of e7pressing concerns in situations 3here such vie3s may 1e un3elcome or uncomforta1le to the recipients5 Be 3ent on to say that psychosis could 1e also seen as a transcendental e7perience 3ith healing and spiritual aspects5 9homas >8as8 focused on the social implications of la1eling people as psychotic, a la1el he argues un4ustly medicalises different vie3s of reality so such unorthodo7 people can 1e controlled 1y society5 6sychoanalysis has a detailed account of psychosis

3hich differs markedly from that of psychiatry5 Freud and Lacan outlined their perspective on the structure of psychosis in a num1er of 3orks5 >ince the #9$0s, the introduction of a Decovery approach to mental health, 3hich has 1een driven mainly 1y people 3ho have e7perienced psychosis &or 3hatever name is used to descri1e their e7periences2, has led to a greater a3areness that mental illness is not a lifelong disa1ility, and that there is an e7pectation that recovery is possi1le, and pro1a1le 3ith effective support5@citation neededA

&ntipsychotic Medications &nti-psychotic Drugs &ntipsychotic Medications &nti-psychotic Drugs Introduction

: person 3ho is psychotic is out of touch 3ith reality5 Be may ,hear voices, or have strange and untrue ideas &for e7ample, thinking that others can hear his thoughts, or are trying to harm him, or that he is the 6resident of the Mnited >tates or some other famous person25U Be may get e7cited or angry for no apparent reason, or spend a lot of time off 1y himself, or in 1ed,sleeping during the day and staying a3ake at night5 Be may neglect his appearance, not 1athing or changing clothes, and may 1ecome difficult to communicate 3ith saying things that make no sense, or 1arely talking at all5 9hese kinds of 1ehaviors are symptoms of psychotic illness the principal form of 3hich is schi'ophrenia5 :ll of the symptoms may not 1e present 3hen someone is psychotic, 1ut some of them al3ays are5 :ntipsychotic medications, as their name suggests, act against these symptoms5 9hese medications cannot ,cure, the illness, 1ut they can take a3ay many of the symptoms or make them milder5 Cn some cases, they can shorten the course of the illness as 3ell5 9here are a num1er of antipsychotic &neuroleptic2 medications availa1le5 9hey all 3orkK the main differences are in the potency that is, the dosage &amount2 prescri1ed to produce therapeutic effects and the side effects5 >ome people might think that the higher the dose of medication, the more serious the illness, 1ut this is not al3ays true5 : doctor 3ill consider several factors 3hen prescri1ing an antipsychotic medication, 1esides ho3 ,ill, someone is5 9hese include the patient;s age, 1ody 3eight, and type of medication5 6ast history is important, too5 Cf a person took a particular medication 1efore and it 3orked, the doctor is likely to prescri1e the same one again5 >ome less potent drugs, like chlorproma8ine &9hora8ine2, are prescri1ed in higher num1ers of milligrams than others of high potency, like haloperidol &Baldol25 Cf a person has to take a large amount of a ,high-dose, antipsychotic medication, such as chlorproma8ine, to get the same effect as a small amount of a ,lo3-dose, medication, such as haloperidol, 3hy doesn;t the doctor 4ust prescri1e ,lo3-dose, medicationsV 9he main reason is the difference in their side effects &actions of the medication other than the one intended for the illness25

9hese medications vary in their side effects, and some people have more trou1le 3ith certain side effects than others5 : side effect may sometimes 1e desira1le5For instance, the sedative effect of some antipsychotic medications is useful for patients 3ho have trou1le sleeping or 3ho 1ecome agitated during the day5 Mnlikesome prescription drugs, 3hich must 1e taken several times during the day, antipsychotic medications can usually 1e taken 4ust once a day5 9hus, patients can reduce daytime side effects 1y taking the medications once, 1efore 1ed5 >ome antipsychotic medications are availa1le in forms that can 1e in4ected once or t3ice a month, thus assuring that the medicine is 1eing taken relia1ly5 Fost side effects of antipsychotic medications are mild5 Fany common ones disappear after the first fe3 3eeks of treatment5 9hese include dro3siness, rapid heart1eat, and di88iness 3hen changing position5 >ome people gain 3eight 3hile taking antipsychotic medications and may have to change their diet to control their 3eight5 Ither side effects that may 1e caused 1y some antipsychotic medications include decrease in se7ual a1ility or interest, pro1lems 3ith menstrual periods, sun1urn, or skin rashes5 Cf a side effect is especially trou1lesome, it should 1e discussed 3ith the doctor 3ho may prescri1e a different medication, change the dosage level or schedule, or prescri1e an additional medication to control the side effects5 Fovement difficulties may occur 3ith the use of antipsychotic medications, although most of them can 1e controlled 3ith an anticholinergic medication5 9hese movement pro1lems include muscle spasms of the neck, eye, 1ack, or other musclesK restlessness and pacingK a general slo3ing-do3n of movement and speechK and a shuffling 3alk5 >ome of these side effects may look like psychotic or neurologic &6arkinson;s disease2 symptoms, 1ut aren;t5 Cf they are severe, or persist 3ith continued treatment 3ith an antipsychotic, it is important to notify the doctor, 3ho might either change the medication or prescri1e an additional one to control the side effects5 Just as people vary in their responses to antipsychotic medications, they also vary in their speed of improvement5 >ome symptoms diminish in days, 3hile others take 3eeks or months5 For many patients, su1stantial improvement is seen 1y the si7th 3eek of treatment, although this is not true in every case5 Cf someone does not seem to 1e improving, a different type of medication may 1e tried5 Jven if a person is feeling 1etter or completely 3ell, he should not 4ust stop taking the medication5 <ontinuing to see the doctor 3hile tapering off medication is important5 >ome people may need to take medication for an e7tended period of time, or even indefinitely5 9hese people usually have chronic &long-term, continuous2 schi8ophrenic disorders, or have a history of repeated schi8ophrenic episodes, and are likely to 1ecome ill again5 :lso, in some cases a person 3ho has e7perienced one or t3o severe episodes may need medication indefinitely5 Cn these cases, medication may 1e continued in as lo3 a dosage as possi1le to maintain control of symptoms5 9his approach, called maintenance treatment, prevents relapse in many people and removes or reduces symptoms for others5 While maintenance treatment is helpful for

many people, a dra31ack for some is the possi1ility of developing long-term side effects, particularly a condition called 9ardive Nyskinesia5 9his condition is characteri8ed 1y involuntary movements5 9hese a1normal movements most often occur around the mouth, 1ut are sometimes seen in other muscle areas such as the trunk, pelvis, or diaphragm5 9he disorder may range from mild to severe5 For some people, it cannot 1e reversed, 3hile others recover partially or completely5 9ardive dyskinesia is seen most often after longterm treatment 3ith antipsychotic medications5 9here is a higher incidence in 3omen, 3ith the risk rising 3ith age5 9here is no 3ay to determine 3hether someone 3ill develop this condition, and if it develops, 3hether the patient 3ill recover5 :t present, there is no effective treatment for tardive dyskinesia5 9he possi1le risks of long-term treatment 3ith antipsychotic medications must 1e 3eighed against the 1enefits in each individual case 1y patient, family, and doctor5 :ntipsychotic medications can produce un3anted effects 3hen taken in com1ination 3ith other medications5 9herefore, the doctor should 1e told a1out all medicine 1eing taken, including over-the-counter preparations, and the e7tent of the use of alcohol5 >ome antipsychotic medications interfere 3ith the action of antihypertensive medications &taken for high 1lood pressure2, anticonvulsants &taken for epilepsy2, and medications used for 6arkinson;s disease5 >ome :ntipsychotic medications add to the effects of alcohol and other central nervous system depressants, such as antihistamines, antidepressants, 1ar1iturates, some sleeping and pain medications, and narcotics5 :typical neuroleptics Cn #990, clo8apine &<lo8aril2, an ,atypical neuroleptic,, 3as introduced in the Mnited >tates5 Cn clinical trials, this medication 3as found to 1e more effective than traditional antipsychotic medications in individuals 3ith treatment-resistant schi8ophrenia, and the risk of tardive dyskinesia is lo3er5 Bo3ever, 1ecause of the potential side effect of a serious 1lood disorder, agranulocytosis, patients 3ho are on clo8apine must have a 1lood test each 3eek5 9he e7pense involved in this monitoring, together 3ith the cost of the medication, has made maintenance on clo8apine difficult for many persons 3ith schi8ophrenia5 Bo3ever, % years after its introduction in the Mnited >tates, appro7imately %",000 persons 3ere 1eing treated 3ith clo8apine5 >ince clo8apine;s approval in the Mnited >tates, other atypical neuroleptics &also called atypical antipsychotics2 have 1een introduced5 Disperidone &Disperdal2 3as released in #99!, olan8apine &Typre7a2 in #996, and Guetiapine &>eroGuel2 in #99$5 >everal other atypical neuroleptics are in development5 While they have some side effects, these ne3er medications are generally 1etter tolerated than either clo8apine or the the traditional antipsychotics, and they do not cause agranulocytosis5 Like clo8apine, they have sho3n little tendency to give rise to tardive dyskinesia or other movement difficulties5 9heir main disadvantages compared to the older medications are a greater tendency to produce 3eight gain, and much higher cost5

&ntipsychotic
From Wikipedia, the free encyclopedia

Jump to: navigation, search &ntipsychotics are a group of psychoactive drugs commonly 1ut not e7clusively used to treat psychosis,@#A 3hich is typified 1y schi8ophrenia5 Iver time a 3ide range of antipsychotics have 1een developed5 : first generation of antipsychotics, kno3n as typical antipsychotics, 3as discovered in the #9%0s5 Fost of the drugs in the second generation, kno3n as atypical antipsychotics, have more recently 1een developed5 Ooth classes of medication tend to 1lock receptors in the 1rain;s dopamine path3ays, 1ut antipsychotic drugs encompass a 3ide range of receptor targets5 : num1er of side effects have 1een o1served in relation to specific medications, including 3eight gain, agranulocytosis, tardive dyskinesia, tardive akathisia and tardive psychoses5 9he development of ne3 antipsychotics, and the relative efficacy of different ones, is an important ongoing field of research5 :ntipsychotic medication is not generally regarded as a good treatment, 4ust the 1est availa1le5 9he most appropriate drug for an individual patient reGuires careful consideration5

Contents
@hideA

# 9erminology 2 Msage Bistory ! <ommon antipsychotics o !5# First generation antipsychotics !5#5# Outyrophenones !5#52 6henothia8ines !5#5 9hio7anthenes o !52 >econd generation antipsychotics o !5 9hird generation antipsychotics o !5! Ither options % Nrug action 6 >ide effects $ >tructural effects " Jfficacy 9 9ypical versus atypical #0 Iver-prescri1ing ## Deferences #2 J7ternal links

[edit] Terminology
:ntipsychotics are also referred to as neuroleptic drugs 5@2A 9he 3ord neurole!tic is derived from 'reek: ,WXYZ-W, &originally meaning sine3 1ut today referring to the nerves2 and ,[\]^_W`, &meaning ta1e hold of25 9hus, the 3ord means ta1ing hold of one2s ner#es5 9his term reflects the drugs; a1ility to make movement more difficult and sluggish, 3hich clinicians previously 1elieved indicated that a dose 3as high enough5 @citation neededA 9he lo3er doses used currently have resulted in reduced incidence of motor side effects and sedation, and the term is less commonly used than in the past55 :ntipsychotics are 1roadly divided into t3o groups, the typical or first-generation antipsychotics and the atypical or second-generation antipsychotics5 9here are also dopamine partial agonists, 3hich are often categori8ed as atypicals5 9ypical antipsychotics are also sometimes referred to as tran(uili'ers,@ A 1ecause some of them can tranGuili8e and sedate5 9his term is increasingly disused, as the terminology implies a connection 3ith 1en8odia8epines &,minor, tranGuili8ers2 3hen none e7ists5

[edit] )sage
<ommon conditions 3ith 3hich antipsychotics might 1e used include schi8ophrenia, mania, and delusional disorder5 9hey might 1e used to counter psychosis associated 3ith a 3ide range of other diagnoses, such as psychotic depression5 Cn addition, these drugs are used to treat non-psychotic disorders5 For e7ample, some antipsychotics &haloperidol, pimo8ide2 are used off-la1el to treat 9ourette syndrome, 3hereas :ripipra8ole is prescri1ed in some cases of :sperger;s syndrome5

[edit] History
9he original antipsychotic drugs 3ere happened upon largely 1y chance and 3ere tested empirically for their effectiveness5 9he first antipsychotic 3as chlorproma8ine, 3hich 3as developed as a surgical anesthetic5 Ct 3as first used on psychiatric patients 1ecause of its po3erful calming effectK at the time it 3as regarded as a ,chemical lo1otomy,5 Lo1otomy 3as used to treat many 1ehavioral disorders, including psychosis, although its ,effectiveness, 3as &from a modern vie3point2 due to its tendency to markedly reduce 1ehavior of all types5 Bo3ever, chlorproma8ine Guickly proved to reduce the effects of psychosis in a more effective and specific manner than the e7treme lo1otomy-like sedation it 3as kno3n for5 9he underlying neurochemistry involved has since 1een studied in detail, and su1seGuent anti-psychotic drugs have 1een discovered 1y an approach that incorporates this sort of information5

[edit] Common antipsychotics

<hlorproma8ine5 Baloperidol5 auetiapine5 <ommonly used antipsychotic medications are listed 1elo3 1y drug group5 9rade names appear in parentheses5

[edit] *irst generation antipsychotics

[edit] +utyrophenones

Baloperidol &Baldol2

[edit] Phenothia'ines

<hlorproma8ine &9hora8ine2 Fluphena8ine &6roli7in2 - :vaila1le in decanoate &long-acting2 form 6erphena8ine &9rilafon2 6rochlorpera8ine &<ompa8ine2 9hiorida8ine &Fellaril2 9rifluopera8ine &>tela8ine2 Fesorida8ine 6roma8ine 9rifluproma8ine &Eesprin2 Levomeproma8ine &=o8inan2 6rometha8ine &6henergan2

[edit] Thio,anthenes

<hlorprothi7ene Flupenthi7ol &Nepi7ol and Fluan7ol2 9hiothi7ene &=avane2 Tuclopenthi7ol &<lopi7ol b :cuphase2

[edit] Second generation antipsychotics

<lo8apine &<lo8aril2 - DeGuires 3eekly to 1i3eekly <O< &FO<2 1ecause of risk of agranulocytosis &a severe decrease of 3hite 1lood cells25 Ilan8apine &Typre7a2 - Msed to treat psychotic disorders including schi8ophrenia, acute manic episodes, and maintenance of 1ipolar disorder5 Nosing 25% to 20 mg

per day5 <omes in a form that Guickly dissolves in the mouth &Typre7a Tydis25 Fay cause appetite increase, 3eight gain, and altered glucose meta1olism leading to an increased risk of dia1etes mellitus5 Disperidone &Disperdal2 - Nosing 052% to 6 mg per day and is titrated up3ardK divided dosing is recommended until initial titration is completed, at 3hich time the drug can 1e administered once daily5 :vaila1le in long-acting form &Disperdal <onsta that is administered every 2 3eeksK usual dose is 2% mg25 <omes in a form that Guickly dissovles in the mouth &Disperdal F-9a125 Msed off-la1el to treat 9ourette >yndrome or :n7iety Nisorder5 auetiapine &>eroGuel2 - Msed primarily to treat 1ipolar disorder and schi8ophrenia, and ,off-la1el, to treat chronic insomnia and restless legs syndromeK it is a po3erful sedative &if it is used to treat sleep disorders and is not effective at 200 mg, it is not going to 1e effective in this regard25 Nosing starts at 2% mg and continues up to "00 mg ma7imum per day, depending on the severity of the symptom&s2 1eing treated5 Msers typically take smaller doses during the day for the neuroleptic properties and larger dose at 1edtime for the sedative effects, or divided in t3o eGual high doses every #2 hours &$% - !00 mg 1id25 Tiprasidone &'eodon2 - =o3 &20062 approved to treat 1ipolar disorder5 Nosing 20 mg t3ice daily initially up to "0 mg t3ice daily5 6rolonged a9 interval a concernK 3atch closely 3ith patients that have heart diseaseK 3hen used 3ith other drugs that prolong a9 interval potentially life-threatening5 :misulpride &>olian2 - >elective dopamine antagonist5 Bigher doses &greater than !00 mg2 act upon post-synaptic dopamine receptors resulting in a reduction in the positive symptoms of schi8ophrenia, such as psychosis5 Lo3er doses, ho3ever, act upon dopamine autoreceptors, resulting in increased dopamine transmission, improving the negative symptoms of schi8ophrenia5 Lo3er doses of amisulpride have also 1een sho3n to have anti-depressant and an7iolytic effects in nonschi8ophrenic patients, leading to its use in dysthymia and social an7iety disorder5 Cn one particular study, amisulpride 3as found to have greater efficacy than fluo7etine in decreasing an7iety5 :t present, amisulpride is approved in Jurope, :ustralia, and other countries for use in schi8ophrenia, and is approved and marketed in lo3er dosages in some countries for treating dysthymia &such as in Ctaly as Neni1an25 :misulpride has not 1een approved 1y the FN: for use in the Mnited >tates5 :senapine is a %-B92:- and N2-receptor antagonist under development for the treatment of schi8ophrenia and acute mania associated 3ith 1ipolar disorder5 6aliperidone &Cnvega2 - Nerivative of risperidone5 :pproved in Necem1er 20065

[edit] Third generation antipsychotics

:ripipra8ole &:1ilify2 - Nosing # mg up to ma7imum of 0 mg has 1een used5 Fechanism of action is thought to reduce suscepti1ility to meta1olic symptoms seen in some other atypical antipsychotics5@!A Nopamine partial agonists: Mnder clinical development - Oifepruno7K norclo8apine &:<6-#0!25

[edit] Other options

9etra1ena8ine &=itoman in <anada and Rena8ine in =e3 Tealand and some parts of Jurope2 is similar in function to antipsychotic drugs, though is not, in general, considered an antipsychotic itself5 9his is likely due to its main usefulness 1eing the treatment of hyperkinetic movement disorders such as Buntington;s Nisease and 9ourette syndrome, rather than for conditions such as schi8ophrenia5 :lso, rather than having the potential to cause tardive dyskinesia, 3hich most antipsychotics have, tetra1ena8ine can actually 1e an effective treatment for the condition5 <anna1idiol Ine of the main psychoactive components of canna1is5 : recent study has sho3n canna1idiol to 1e as effective as atypical antipsychotics in treating schi8ophrenia5 @%A

9he most common typical antipsychotic drugs are no3 off-patent, meaning any pharmaceutical company is legally allo3ed to produce generic versions of these medications5 While this makes them cheaper than the atypical drugs that are still manufactured under patent constraints, atypical drugs are preferred as a first-line treatment 1ecause they are 1elieved to have fe3er side effects and seem to have additional 1enefits for the ;negative symptoms; of schi8ophrenia, a typical condition for 3hich they might 1e prescri1ed5 Feta1otropic glutamate receptor 2 agonism has 1een seen as a promising strategy in the development of novel antipsychotics5@6A When tested in patients, the research su1stance 345670053 yielded promising results and had fe3 side effects5 9he active meta1olite of this prodrug targets the 1rain glutamate receptors m'luD2S rather than dopamine receptors5@$A Ct is currently in phase-2 clinical testing &200$25

[edit] Drug action

:ll antipsychotic drugs tend to 1lock N2 receptors in the dopamine path3ays of the 1rain5 9his means that dopamine released in these path3ays has less effect5 J7cess release of dopamine in the mesolim1ic path3ay has 1een linked to psychotic e7periences5 Ct is the 1lockade of dopamine receptors in this path3ay that is thought to control psychotic e7periences5 9ypical antipsychotics are not particularly selective and also 1lock Nopamine receptors in the mesocortical path3ay, tu1eroinfundi1ular path3ay, and the nigrostriatal path3ay5 Olocking N2 receptors in these other path3ays is thought to produce some of the un3anted side effects that the typical antipsychotics can produce &see 1elo325 9hey 3ere commonly classified on a spectrum of lo3 potency to high potency, 3here potency referred to the a1ility of the drug to 1ind to dopamine receptors, and not to the effectiveness of the drug5 Bigh-potency antipsychotics such as haloperidol, in general, have doses of a fe3 milligrams and cause less sleepiness and calming effects than lo3potency antipsychotics such as chlorproma8ine and thiorida8ine, 3hich have dosages of

several hundred milligrams5 9he latter have a greater degree of anticholinergic and antihistaminergic activity, 3hich can counteract dopamine-related side effects5 :typical antipsychotic drugs have a similar 1locking effect on N2 receptors5 >ome also 1lock or partially 1lock serotonin receptors &particularly %B92:, < and %B9#: receptors2:ranging from risperidone, 3hich acts over3helmingly on serotonin receptors, to amisulpride, 3hich has no serotonergic activity5 9he additional effects on serotonin receptors may 1e 3hy some of them can 1enefit the ;negative symptoms; of schi8ophrenia5@"A

[edit] Side e""ects

:ntipsychotics are associated 3ith a range of side effects5 Ct is 3ell-recogni8ed that many stop taking them &around t3o-thirds of people in controlled drug trials2 due in part to adverse effects5@9A J7trapyramidal reactions include tardive psychosis, acute dystonias, akathisia, parkinsonism &rigidity and tremor2, tardive dyskinesia, tachycardia, hypotension, impotence, lethargy, sei8ures, intense dreams or nightmares, and hyperprolactinaemia5 From a su14ective perspective, antipsychotics heavily influence one;s perceptions of pleasura1le sensations, causing a severe reduction in feelings of desire, motivation, pensive thought, and a3e5 9his does not coincide 3ith the apathy and lack of motivation e7perienced 1y the negative symptoms of schi8ophrenia5 Netrimental effects on short term memory, 3hich affect the 3ay one figures and calculates &although this also may 1e purely su14ective2, may also 1e o1served on high enough dosages5 9hese are all the reasons 3hy they are thought to affect ,creativity,5 :lso, for some individuals 3ith schi8ophrenia, too much stress may cause ,relapse,5 Follo3ing are details concerning some of the side effects of antipsychotics:

:ntipsychotics, particularly atypicals, appear to cause dia1etes mellitus and fatal dia1etic ketoacidosis, especially &in M> studies2 in :frican :mericans5@#A@2A :ntipsychotics may cause pancreatitis5@#0A 9he atypical antipsychotics &especially olan8apine2 seem to cause 3eight gain more commonly than the typical antipsychotics5 9he 3ell-documented meta1olic side effects associated 3ith 3eight gain include dia1etes, 3hich can 1e lifethreatening5 <lo8apine also has a risk of inducing agranulocytosis, a potentially dangerous reduction in the num1er of 3hite 1lood cells in the 1ody5 Oecause of this risk, patients prescri1ed clo8apine may need to have regular 1lood checks to catch the condition early if it does occur, so the patient is in no danger5@citation neededA Ine of the more serious of these side effects is tardive dyskinesia, in 3hich the sufferer may sho3 repetitive, involuntary, purposeless movements often of the lips, face, legs, or torso5 Ct is 1elieved that there is a greater risk of developing tardive dyskinesia 3ith the older, typical antipsychotic drugs, although the ne3er antipsychotics are no3 also kno3n to cause this disorder5

: potentially serious side effect of many antipsychotics is that they tend to lo3er an individual;s sei8ure threshold5 <hlorproma8ine and clo8apine, in particular, have a relatively high sei8urogenic potential5 Fluphena8ine, haloperidol, pimo8ide and risperidone e7hi1it a relatively lo3 risk5 <aution should 1e e7ercised in individuals that have a history of sei8urogenic conditions such as epilepsy, or 1rain damage5 :nother antipsychotic side effect is deterioration of teeth due to a lack of saliva5
@citation neededA

:nother serious side effect is neuroleptic malignant syndrome, in 3hich the drugs appear to cause the temperature regulation centers to fail, resulting in a medical emergency, as the patient;s temperature suddenly increases to dangerous levels5 :nother pro1lematic side effect of antipsychotics is dysphoria5 Follo3ing controversy over possi1le increased mortality &death2 related to antipsychotics in indivdiuals 3ith dementia, 3arnings have 1een added to packaging5@##A

>ome people suffer fe3 apparent side effects from taking antipsychotic medication, 3hereas others may have serious adverse effects5 >ome side effects, such as su1tle cognitive pro1lems, may go unnoticed5 9here is a possi1ility that the risk of tardive dyskinesia can 1e reduced 1y com1ining the anti-psychotics 3ith diphenhydramine or 1en8tropine, although this remains to 1e esta1lished5 <entral nervous system damage is also associated 3ith irreversi1le tardive akathisia andSor tardive dysphrenia5

[edit] Structural e""ects

Fany studies no3 indicate that chronic treatment 3ith antipsychotics affects the 1rain at a structural level, for e7ample increasing the volume of the 1asal ganglia &especially the caudate nucleus2, and reducing cortical grey matter volume in different 1rain areas5 9he effects may differ for typical versus atypical antipsychotics and may interact 3ith different stages of disorders5@#2A Neath of neurons in the cere1ral corte7, especially in 3omen, has 1een linked to the use of 1oth typical and atypical antipsychotics for individuals 3ith :l8heimers5@# A Decent studies on macaGue monkeys have found that administration of haloperidol or olan8apine for a1out t3o years led to a significant overall shrinkage in 1rain tissue,@#!A in 1oth gray and 3hite matter across several 1rain areas, 3ith lo3er glial cell counts,@#%A due to a decrease in astrocytes and oligodendrocytes,@#6A and increased neuronal density5 Ct has 1een said that these studies reGuire serious attention and that such effects 3ere not clearly tested for 1y pharmaceutical companies prior to o1taining approval for placing the drugs on the market5@#$A

[edit] %""icacy

9here have 1een a large num1er of studies of the efficacy of typical antipsychotics, and an increasing num1er on the more recent atypical antipsychotics5 9he :merican 6sychiatric :ssociation and the MH =ational Cnstitute for Bealth and <linical J7cellence recommend antipsychotics for managing acute psychotic episodes and for preventing relapse5@#"A@#9A 9hey state that response to any given antipsychotic can 1e varia1le so that trials may 1e necessary, and that lo3er doses are to 1e preferred 3here possi1le5 :ntipsychotic polypharmacy?prescri1ing t3o or more antipsychotics at the same time for an individual?is said to 1e a freGuent practice 1ut not necessarily evidence-1ased5@20A >ome dou1ts have 1een raised a1out the long-term effectiveness of antipsychotics 1ecause t3o large international World Bealth Irgani8ation studies found individuals diagnosed 3ith schi8ophrenia tend to have 1etter long-term outcomes in developing countries &3here there is lo3er availa1ility and use of antipsychotics2 than in developed countries5@2#A@22A 9he reasons for the differences are not clear, ho3ever, and various e7planations have 1een suggested5 >ome argue that the evidence for antipsychotics from 3ithdra3al-relapse studies may 1e fla3ed, 1ecause they do not take into account that antipsychotics may sensiti8e the 1rain and provoke psychosis if discontinued5@2 A Jvidence from comparison studies indicates that at least some individuals recover from psychosis 3ithout taking antipsychotics, and may do 1etter than those that do take antipsychotics5@2!A >ome argue that, overall, the evidence suggests that antipsychotics only help if they are used selectively and are gradually 3ithdra3n as soon as possi1le5@2%A : dose response effect has 1een found in one study from #9$# 1et3een increasing neuroleptic dose and increasing num1er of psychotic 1reaks5@26A@#erification neededA

[edit] Typical $ersus atypical

While the atypical, second-generation medications 3ere marketed as offering greater efficacy in reducing psychotic symptoms 3hile reducing side effects &and e7trapyramidal symptoms in particular2 than typical medications, the results sho3ing these effects often lack ro1ustness5 9o remediate this pro1lem, the =CFB conducted a recent multi-site, dou1le-1lind study &the <:9CJ pro4ect2, 3hich 3as pu1lished in 200%5@2$A 9his study compared several atypical antipsychotics to an older typical antipsychotic, perphena8ine, among #!9 persons 3ith schi8ophrenia5 6erphena8ine 3as chosen 1ecause of its lo3er potency and moderate side effect profile5 9he study found that only olan8apine outperformed perphena8ine in the researchers; principal outcome, the discontinuation rate5 9he authors also noted the apparent superior efficacy of olan8apine to the other drugs for greater reduction in psychopathology, longer duration of successful treatment, and lo3er rate of hospitali8ations for an e7acer1ation of schi8ophrenia5 Cn contrast, no other atypical studied &risperidone, Guetiapine, and 8iprasidone2 did 1etter than the typical perphena8ine on those measures5 Ilan8apine, ho3ever, 3as associated

3ith relatively severe meta1olic effects: >u14ects 3ith olan8apine sho3ed a ma4or 3eight gain pro1lem and increases in glucose, cholesterol, and triglycerides5 9he average 3eight gain &#5# kgSmonth, or !! pounds for the #" months that the study lasted2 casts serious dou1t on the potentiality of long-term use of this drug5 6erphena8ine did not create more e7trapyramidal side effects as measured 1y rating scales &a result supported 1y a metaanalysis 1y Nr5 Leucht pu1lished in Lancet2, although more patients discontinued perphena8ine o3ing to e7trapyramidal effects compared to the atypical agents &" percent vs5 2 percent to ! percent, 6c0500225 : phase 2 part of this study roughly replicated these findings5@2"A 9his phase consisted of a second randomi8ation of the patients that discontinued taking medication in the first phase5 Ilan8apine 3as again the only medication to stand out in the outcome measures, although the results did not al3ays reach statistical significance, due in part to the decrease of po3er5 6erphena8ine again did not create more e7trapyramidal effects5 : su1seGuent phase 3as conducted5 @29A 9his phase allo3ed clinicians to offer clo8apine 3hich 3as more effective at reducing medication drop-outs than other neuroleptic agents5 Bo3ever, the potential for clo8apine to cause to7ic side effects, including agranulocytosis, limits its usefulness5

[edit] O$er-prescri-ing
Mse of this class drugs has a history of criticism in residential care5 :s the drugs use can make patients calmer and more compliant, critics claim that the drugs can 1e overused5 Iutside doctors can feel under pressure from care home staff@ 0

&ntipsychotic Medications
From About.com Updated: May 30, 2006 About.com Health's Disease and Condition content is e!ie"ed by ou Medical #e!ie" $oa d

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1. Mental Health

Antipsychotic medications have been available since the mid-1950s. They have greatly improved the outloo !or individual patients. These medications reduce the psychotic symptoms o! schi"ophrenia and usually allo# the patient to !unction more e!!ectively and appropriately. Antipsychotic drugs are the best treatment no# available$ but they do not cure schi"ophrenia or ensure that there #ill be no !urther psychotic episodes. The choice and dosage o! medication can be made only by a %uali!ied physician #ho is #ell trained in the medical treatment o! mental disorders. The dosage o! medication is individuali"ed !or each patient$ since people may vary a great deal in the amount o! drug needed to reduce symptoms #ithout producing troublesome side e!!ects. The large ma&ority o! people #ith schi"ophrenia sho# substantial improvement #hen treated #ith antipsychotic drugs. 'ome patients$ ho#ever$ are not helped very much by the medications and a !e# do not seem to need them. (t is di!!icult to predict #hich patients #ill !all into these t#o groups and to distinguish them !rom the large ma&ority o! patients #ho do bene!it !rom treatment #ith antipsychotic drugs. A number o! ne# antipsychotic drugs )the so-called *atypical antipsychotics+, have been introduced since 1990. The !irst o! these$ clo"apine )-lo"aril,$ has been sho#n to be more e!!ective than other antipsychotics$ although the possibility o! severe side e!!ects . in particular$ a condition called agranulocytosis )loss o! the #hite blood cells that !ight in!ection, . re%uires that patients be monitored #ith blood tests every one or t#o #ee s. /ven ne#er antipsychotic drugs$ such as risperidone )0isperdal,$ aripipra"ole )Abili!y,$ %uetiapine )'ero%uel,$ and olan"apine )1ypre2a,$ are sa!er than the older drugs or clo"apine$ and they also may be better tolerated. 'everal additional antipsychotics are currently under development. Antipsychotic drugs are o!ten very e!!ective in treating certain symptoms o! schi"ophrenia$ particularly hallucinations and delusions. The drugs may not be as help!ul #ith other symptoms$ such as reduced motivation and emotional e2pressiveness. The older antipsychotics$ medicines li e haloperidol )Haldol, or chlorproma"ine )Thora"ine,$ may even produce side e!!ects that resemble the more di!!icult to treat symptoms. 3o#ering the dose or s#itching to a di!!erent medicine may reduce these side e!!ects4 the ne#er medicines$ including olan"apine )1ypre2a,$ %uetiapine )'ero%uel,$ risperidone )0isperdal,$ and aripipra"ole )Abili!y, appear less li ely to have this problem. 'ometimes #hen people #ith

schi"ophrenia become depressed$ other symptoms can appear to #orsen. The symptoms may improve #ith the addition o! an antidepressant medication. 5atients and !amilies sometimes become #orried about the antipsychotic medications used to treat schi"ophrenia. (n addition to concern about side e!!ects$ they may #orry that such drugs could lead to addiction. Ho#ever$ antipsychotic medications do not produce a 6high6 or addictive behavior in people #ho ta e them. Another misconception about antipsychotic drugs is that they act as a ind o! mind control$ or a 6chemical strait&ac et.6 Antipsychotic drugs used at the appropriate dosage do not noc out people or ta e a#ay their !ree #ill. 7hile these medications can be sedating$ these drugs are not used because o! the sedation but because o! their ability to diminish the hallucinations$ agitation$ con!usion$ and delusions o! a psychotic episode. Antipsychotic medications should eventually help an individual #ith schi"ophrenia to deal #ith the #orld more rationally. 'ource8 9ational (nstitutes o! Mental Health articles and brochures on Antipsychotic How Long Should People With Schizophrenia Take Antipsychotic Drugs Antipsychotic medications reduce the !re%uency and intensity o! !uture psychotic episodes in patients #ho have recovered !rom an episode. /ven #ith continued drug treatment$ some people #ho have recovered #ill su!!er relapses. Higher relapse rates are seen #hen medication is discontinued. The treatment o! severe psychotic symptoms can re%uire a higher dosages than those used !or maintenance treatment. (! symptoms reappear on a lo#er dosage$ a temporary increase in dosage may prevent a !ull-blo#n relapse. (t is important that people #ith schi"ophrenia #or #ith their doctors and !amily members to adhere to their treatment plan. Adhe ence to treatment re!ers to the degree to #hich patients !ollo# the treatment plans recommended by their doctors. :ood adherence involves ta ing prescribed medication at the correct dose and proper times each day$ eeping all appointments$ and care!ully !ollo#ing other treatment procedures. Treatment adherence is o!ten di!!icult !or people #ith schi"ophrenia$ but it can be made easier #ith the help o! several strategies and can lead to improved %uality o! li!e. There are a variety o! reasons #hy people #ith schi"ophrenia may not adhere to treatment. 5atients may not believe they are ill and may deny the need !or medication$ or they may have such disorgani"ed thin ing that they cannot remember to ta e their daily doses. Family members or !riends may not understand schi"ophrenia and may inappropriately advise the person #ith schi"ophrenia to stop treatment #hen he or she is !eeling better. 5hysicians$ #ho play an important role in helping their patients adhere to treatment$ may neglect to as patients ho# o!ten they are ta ing their medications$ or may be un#illing to accommodate a patient;s re%uest to change dosages or try a ne# treatment. 'ome patients report that side e!!ects o! the medications seem #orse than the illness itsel!. Further$ substance abuse can inter!ere #ith the e!!ectiveness o! treatment$ leading patients to discontinue medications. 7hen a complicated treatment plan is added to any o! these !actors$ good adherence may become even more challenging. There are many strategies that patients$ doctors$ and !amilies can use to improve adherence and prevent #orsening o! the illness. 'ome antipsychotic medications are available in longacting in&ectable !orms that eliminate the need to ta e pills every day. A ma&or goal o! current research on treatments !or schi"ophrenia is to develop a #ider variety o! long-acting antipsychotics$ especially the ne#er agents #ith milder side e!!ects$ #hich can be delivered through in&ection. Medication calendars or pill bo2es labeled #ith the days o! the #ee can help patients and caregivers no# #hen medications have or have not been ta en. <sing

electronic timers that beep #hen medications should be ta en$ or pairing medication ta ing #ith routine daily events li e meals$ can help patients remember and adhere to their dosing schedule. /ngaging !amily members in observing oral medication ta ing by patients can help ensure adherence. (n addition$ through a variety o! other methods o! adherence monitoring$ doctors can identi!y #hen pill ta ing is a problem !or their patients and can #or #ith them to ma e adherence easier. (t is important to help motivate patients to continue ta ing their medications properly. (n addition to any o! these adherence strategies$ patient and !amily education about schi"ophrenia is an important part o! the treatment process and helps support the rationale !or good adherence. What A!out Side "##ects Antipsychotic drugs$ li e virtually all medications$ have un#anted e!!ects along #ith their bene!icial e!!ects. =uring early treatment patients may be troubled by side e!!ects such as dro#siness$ restlessness$ muscle spasms$ tremor$ dry mouth$ or blurring o! vision. Most o! these can be corrected by lo#ering the dosage or can be controlled by other medications. =i!!erent patients have di!!erent treatment responses and side e!!ects to various antipsychotic drugs. A patient may do better #ith one drug than another. The long-term side e!!ects o! antipsychotic drugs may pose a considerably more serious problem. Tardive dys inesia )T=, is a disorder characteri"ed by involuntary movements most o!ten a!!ecting the mouth$ lips$ and tongue$ and sometimes the trun or other parts o! the body such as arms and legs. (t occurs in about 15 to >0 percent o! patients #ho have been receiving the older$ 6typical6 antipsychotic drugs !or many years$ but T= can also develop in patients #ho have been treated #ith these drugs !or shorter periods o! time. (n most cases$ the symptoms o! T= are mild$ and the patient may be una#are o! the movements. Antipsychotic medications developed in recent years all appear to have a much lo#er ris o! producing T= than the older$ traditional antipsychotics. The ris is not "ero$ ho#ever$ and they can produce side e!!ects o! their o#n such as #eight gain. (n addition$ i! given at too high o! a dose$ the ne#er medications may lead to problems such as social #ithdra#al and symptoms resembling 5ar inson;s disease$ a disorder that a!!ects movement. 9evertheless$ the ne#er antipsychotics are a signi!icant advance in treatment$ and their optimal use in people #ith schi"ophrenia is a sub&ect o! much current research.