Psychotic Disorders

Psychotic Disorder Definition: Disorder characterized by loss of contact with reality, marked disturbances of thought & perception & bizarre behavior. Types : 1) Schizophrenia -Psychotic symptoms ( P ! usually lasts for up to " months 2) Schizophreniform disorder - P lasts for # $ month but %" months &! Schizoaffective disorder - 'istory of (DD ) now P at least for * weeks +! Drug abuse disorders - Drug induced psychosis ,! Ma or depression !ith Psychotic features. - imultaneous occurrence of depressive symptoms ) Psychotic symptoms "! Dementia. - loss of cognitive functions. Schizophrenia Def : Psychiatric disorder with delusional beliefs & 'allucinations Preva"ence : - -round $-& . of the population - (en ( early */0s ! & 1omen ( late */0s! e2ually affected. #ause : - 3enetic abnormalities - $iochemica" factors %&'cessive Dopamine ( D)) - 4rain tructural abnormalities - Psychological stress & lower social class - 5amilial relationship Types: $! Paranoid schizophrenia. -eg: Patients think that somebody is going to kill him. *! 6atatonic schizophrenia -eg: Patients motion is disturbed &! Disorganised chizophrenia -eg: Patients thoughts & language is changes. +! 7ndifferentiated chizophrenia -eg: Mix of above 4 types . ,! 8esidual chizophrenia -eg: Symptoms !hich remain after the treatment.

Symptoms : 1) Positive Symptoms - -ddition of e9tra behavior to the patient0s present personality - eg 'allucinations , delusions etc 2) *egative Symptoms - 8emoval of some e9isting behavior from the patient0s personality. - eg: ;motional flatness or lack of e9pression, +) #ognitive symptoms - Cognition is the act or process of thinking, perceiving, and learning ,) )ggressive symptoms - <his is not really a symptom of schizophrenia but when it does occur, it tends to occur in con=unction with hallucinations, delusions, preoccupations and =umbled thoughts -) )n'iety . Depressive symptoms/ Dopamine Theory - Dopamine levels increased in mesolimbic portion - Drugs that block D- reduce psychotic symptoms. Dopamine Path!ays Path!ay $!(esolimbic *!(esocortical &!?igrostriatal +!<uberoinfundibular D) activity >veractivity 7nderactivity 4alanced with -6' 4alanced #onse0uences Positive symptoms ?egative symptoms ?ormal movement @nhibits P8A inhibition 1e0d Drug effect 8educe D@ncrease D?o change -----B------

1eceptor )ctivity . #"inica" effects/ 1eceptor activity D* receptor antagonist , '<$- agonist , '<$D antagonist , '<*- antagonist , '<*- , D* binding (i9ed ,'<)?; reuptake inhibition )ntipsychotic Drugs $. <ypical antipsychotics *. -typical antipsychotics Typica" )ntipsychotics -ll typical antipsychotics block all the + D- pathways. - D* receptor blocking capacity ( primary effect ! - >ther 8eceptor blocking capacity ( secondary effect! ( -6' , adrenergic , 'istaminic receptor blocker! #"inica" effects/ -ntipsychotic ( positive ! benefits , ;P -ntidepressant activity, less ;P , improved cognition -ntidepressant effects. -ntipsychotic (negative ! benefits, reduced ;P . @mproved antipsychotic activity, lower ;P . -ntidepressant C an9iolytic benefits, less weight gain.

Path!ay $! (esolimbic *! (esocortical &! ?igrostriatal +! <uberoinfundibular 1eceptor -cetylcholine -drenergic 'istaminergic

Drug &ffect 4locked 4locked 4locked 4locked Drug &ffect 4locked 4locked 4locked

#onse0uences Positive symptoms ?egative symptoms (ovement disorder(;P ! prolactin levels #onse0uences -nticholinergic -D8 ) Aow ;P Aow 4P edation ) weight gain.

&'amp"es of Typica" )ntipsychotics/ $. 'aloperidol. *. 6hlorpromazine &. <rifluoperazine +. <hioridazine ,. Pimozide ". <rifluopromazine.

2a"operido" ( S&*31M ) - 'aloperidol is a butyropherone derivative - -ntipsychotic properties are particularly effective in the management of hyperactivity, agitation, and mania. - ;ffective neuroleptic also possesses antiemetic properties - 'as a marked tendency to provoke e9trapyramidal effects M3) <he mechanism of action of haloperidol has not been entirely elucidated, but has been attributed to the inhibition of the transport mechanism of cerebral monoamines, particularly by blocking the impulse transmission in dopaminergic neurons. 4ndication: -(anagement of manifestations of acute and chronic psychosis, including schizophrenia and manic states. - -lso in the management of aggressive and agitated behavior in patients with chronic brain syndrome and mental retardation and in the symptomatic control of 3illes de la <ouretteDs syndrome.

)T5P4#)6 )*T4PS5#23T4#S
$. *. &. +. ,. ". >lanzapine. 8isperidone. 6lozapine. Euetiapine. Fiprasydone -ripiprazole

)T5P4#)6 D178S erotonin Dopamine -ntagonist (ore effective on negative symptoms Aess risk of causing ;9trapyramidal symptoms ( ;P ! Aess risk of causing <ardive Dyskinesia (<D! G Permanent movement disorder, it starts after +-, years of the therapy Aess risk of causing high protactin levels

)T5P4#)6 D178S D* receptor blocking capacity ,'< *- receptor blocking capacity (primary effect! (Aead to D* thus reduces negative symptoms!. D* blocker

<-PH

D* blocker

,'<*- blocker

-<-PI
H <-P I -<-P <ypical antipsychotics. -typcal -ntipsychotics

D3P)M4*& P)T29)5S (esolimbic <ract ((A<! (esocortical <ract((6<! ?igrostriatal <ract (? <! <uberoinfundibular <ract(<@<! D- overactivity J positive symptoms D- underactivity J negative symptoms D- balanced with -6' J normal movement modulation D- balanced activity J normal P8A inhibition

239 )T5P4#)6 D178S 931: (A< (6< ? < <@< reduce D- overactivity J reduce positive symptoms increase D- underactivity J improve negative symptoms D- balanced with -6' J normal movement modulation D- balanced activity J normal P8A inhibition

Dopamine and -2T interactions , '< can modulate & reduce D- neuronal activity. <hus improves Positive symptoms effectively. $. *. M6T D2 receptors more than -2T2) receptors >verall effect D* blockade & reduction of positive symptoms M#T -2T2) receptors more than D2 receptors >verall effect ,'<*a blockade with increase of D- activity and improvement in negative symptoms -2T2) receptors same as D2 receptors >verall effect ,'<*a blockade with sufficient increase of D- activity of prevent C reduce ;P risk -2T2) receptors same as D2 receptors >verall effect ,'<*a blockade with sufficient increase of D- activity of prevent C reduce hP8A risk

&.

+.

36&)*;
#ategory : )ntipsychotic M3): >leanz is a thienbenozodiazepine atypical antipsychotic >leanz demonstrates a broad pharmacological profile across a number of receptor systems. >leanz has affinity for : -Dopamine (D$, D*, and D+!, - erotonin (,'< *-C*6!, -'istamine ('$!, --drenergic ($! receptors. 4ndications: >leanz is indicated for the treatment of schizophrenia. >leanz is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. Dosage and )dministration: >lanzapine should be administered on a once-a day schedule without regard to meals, generally beginning with , to $/ mg initially, with a target dose of $/ mgCday within several days. 5urther dosage ad=ustments, if indicated, should generally occur at intervals of not less than $ week. Daily dosage may subse2uently be ad=usted on the basis of individual clinical status within the range of ,-*/ mg daily. -n increase to a dose greater than the routine therapeutic dose of $/ mgCday, i.e. to a dose of $, mgCday or greater, is recommended only after appropriate clinical reassessment. Elderly patients: - lower starting dose (, mgCday! is not routinely indicated but should be considered for those ", and over when clinical factors warrant. Patients with hepatic and/or renal impairment: - lower starting dose (, mg! may be considered for such patients.

# marc 2igh"ights/
Indication dependance ( Psychiatrist ) Rank 1 2 3 3 4 5 6 # Indications Schizophrenia Psychosis Depression Manic Depression Bipolar Depression Bipolar mood disorder. Bipolar a ec!i"e disorder. $!hers Preference 39% 22% 21% 5% 6% 2% 2% 4% Indication Schizophrenia Depression Bipolar Disorder $!her co e%is!in& condi!ions Oleanz 60% 26% 10% 4%

"he #ommunication for $lean% !ill be based on the above & indication. "he thrust for each indication !ill be as per the se'uence #ommunication 3b ective : @st Aine therapy in chizophrenia. )s an essentia" choice in Psychotic depression/ -lso the drug of choice in acute & maintenance treatment of 4ipolar disorder

S4;3D3*
#"ass: -ntipsychotic M3): 8isperidone is a benziso9azole derivative 8isperidone0s antipsychotic activity is attributed to its antagonist activity at both - Dopamine (D* subtype! and - erotonin (,'<* subtype! receptors. 8isperidone is also an antagonist of alpha$ and alpha* and '$ receptor subtypes which mediate non antipsychotic effects of the drug. 4ndications $. -cute schizophrenia. *. 6hronic schizophrenia. &. >ther psychoses. +. -ffective symptomatology Dosage and )dministration Adults 8isperidone $ mg bid on day oneK * mg bid on day two and & mg bid on day three. tabilise for one week. 5urther dose ad=ustment to be done only after one week at increments of $ mg bid with ma9imum dose not to e9ceed L mg per day. @f tardive dyskinesia occurs discontinue risperidone. Elderly /., mg bid on day oneK increase by /., mg to achieve $-* mg bid. Patients may be prone to profound hypotension in the presence of hepatic or renal disease.

S4;3P4* #"ass : )ntipsychotic/

M3)/

6lozapine is a novel atypical antipsychotic drug. Differs from other antipsychotic medications by its profile of binding to dopamine receptors and its effects on various dopamine mediated behaviours. @t does interfere with the binding of dopamine at D$, D*, D& and D, 'as a high affinity for the D+ receptor. @t is also preferentially more active at limbic than at striatal dopaminergic receptors. <hus, clozapine does not produce catalepsy or e9trapyramidal side effects. 6lozapine produces little or no prolactin elevations. 6lozapine also has an antiadrenergic, anticholinergic, antihistaminic and antiserotonergic action.
4ndications: 6lozapine is indicated for the management of severe"y i"" schizophrenic patients !ho fai" to respond ade0uate"y to standard psychotic treatment (either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable side effects from these drugs). i/e Treatment risitant . Treatment 4nto"erant Schizophrenia/ Dosage and administration

<he initial recommended dose is one-half of a *, mg tablet ($*., mg! once or twice daily 6ontinue with daily dosage increments of *,-,/ mgCday, if well-tolerated to achieve a target dose of &//-+,/ mgCday at the end of * weeks. ubse2uent dosage increments may be made once or twice weekly in increments not e9ceeding $// mg.
"o minimise risk of hypotension sei%ures and sedation divided dosage schedule is advised. Ma*ority of patients respond !ell bet!een &++-,++ mg-day dose. .o not exceed doses beyond /++ mg-day.

Elderly: Dose selection for the elderly should be cautious reflecting the greater fre2uency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. <he initial recommended dose should be $*., mg on the first day with the subse2uent dose increments being restricted to *,mgCday.

Special patient groups: @n patients with a history of seizures, those suffering from cardiovascular, renal or hepatic disorders, the initial dose should be $*., mg given on the first day and dosage increase should be slow and in small increments.
# M)1# 2igh"ights: SIZOPIN
Indication dependance ( Psychiatrist ) Rank Indications Preference Indication 1 Schizophrenia '3% Schizophrenia 1#% 2 Psychosis Oleanz 100%

6lozapine has a well - defined & role in the mangement of chizophrenia. >nly reason for the restricted use of 6lozapine is the problem of -granulocytosis. <hus sizopin becomes the drug of choice in treatment -resistant & treatment -intolerant cases. #ommunication 3b ective: Drug of 6hoice in <reatment G8esistant & <reatment G @ntolerant chizophrenia. -lso in chizophrenia to control uicidal 4ehaviour.