schizophrenia

SCH

IZO

PH

REN

IA

Summarized by :

Mona NasrYasmin Elmesallamy

Outlines : Historical overview Definition of

Schizophrenia Epidemiology Etiology Pathophysiology Subtypes Risk factors Symptoms Clinical presentation

Complications Diagnostic criteria Differential diagnosis Prognosis Desired outcome Management Algorithm of

pharmacotherapy of schizophrenia

Stor

ies

of

Schi

zoph

reni

a

HistoryEmil Kraepelin original term-dementia praecox-early age, chronic deteriorating course.

Eugen Bleulercoined the term schizophrenia (split mind) affective blunting, loosening of associations, autism (withdrawal) and ambivalence (coexisting conflicting ideas) - 4 As- earned acceptance in USA

Kurt Schneider first rank symptom

Definition

Psychotic mental disorder of unknown etiology characterized by disturbances in:

Thinking (e.g. distortion of reality, delusions and hallucinations)

Mood (e.g. ambivalence, inappropriate affect)

Behavior (e.g. Apathetic withdrawal, bizarre activity)

EpidemiologyAge-related demographics

• According to DSM5, the onset of schizophreniausually occurs between the late teens and the mid 30sSex-related demographics• The prevalence of schizophrenia

is about the same in men & women • The onset is later in women than un men• The clinical course is less severe in women than in

men Race-related demographics• No racial differences in the prevalence of

schizophrenia have been positively identified

Etiology Genetic factors

Psychosocial factors

Pathophysiology

PathophysiologyInflammation & immune

function

Neurotransmitter system

abnormality

Anatomic abnormaliti

es

•Dopaminergic system hypothesis

•Glutaminergic dysfunction

•Serotonin abnormalities

•Increased Ventricular size

•Decreased brain volume in medial temporal areas

•Changes in the hippocampus

•Overactivation of immune system Alteration in brain structure & function

•Metabolic disturbance (Insulin resistance)

SubtypesDSM (Diagnostic & Statistical Manual) of Mental Disorders Published by APA ( American Psychiatry Association)

DSM I 1952DSM II 1968DSM III 1980DSM IV 1994 Classified Schizophrenia to 5 Subtypes DSM V 2013 Proposed the deletion of subtypes

ICD ( International Classification of diseases)

Published by WHO

ICD 10 Classified Schizophrenia to 7 Subtypes

Schizophrenia

iParanoid

iiCatatonic

iiiDisorganiz

ed

IVUndifferentiate

d V

Residual

ViPost-

Schizophrenic

ViiSimple

Schizophrenia

A-preoccupation with 1 or more delusions or frequently auditory hallucinationsB-Non of the following is prominent: -Disorganized speech -Disorganized or catatonic behavior- Flat affect

paranoid

-At least 2 of the following:i-Motoric immobility evidenced by catalepsy or stuporii-excessive motor activity (purposeless& without stimulus)iii-Echolaliaiv-Excessive negatism Catato

nic

A- All of the following are prominent : - Disorganized speech -Disorganized behavior - Flat affectB- the criteria are not met for catatonic type

Disorganized

- Psychotic symptoms are present but criteria for paranoid, catatonic or disorganized have not been met Undiff

er-entiat

ed

-The general criteria for schizophrenia have been met at sometime in the past but are not met in the present time

Residual- - Depressive

episodes arising in the aftermath of schizophrenic illness where some low-level symptoms may still be present

Post-schizophrenic

- Insidious & progressive

development of negative symptoms

with no history of psychotic episodes

Simple-schizophrenia

Risk factors• Family history of Schizophrenia• Any potential cause of fetal hypoxic

brain damage• History of brain complications• Advanced age of mother during

pregnancy• Birth during winter months !! • Substance abuse • Single marital status• Low socioeconomic class• Urban environment• Environmental stress

Symptoms

Symptoms Positive symptoms Hallucination DelusionsIllusionsDisorganized speechBehavioral disturbances

Negative symptoms Absence of normal cognitionAllogiaAvolitionAnhedoniaSocial isolation

Cognitive dysfunction

Impaired - attention - Working memory - Executive functions

Seems cheerful or sad

without obvious reasons

Mood Symptoms

Clinical

PresentationParodro

mal

phase

• Gradual development of symptoms

• Precedes 1st psychotic episode

• Includes:- Isolation-Deterioration of hygiene- loss of interest in work

Acute

phase

• Out of reality

• Hallucination

• Delusion

• Ambivalence

• Autism

• Disturbed sleep &appetite

• Impaired self care skills

• Flat affect

• Disconnected thoughts

• Aggression

Resi

dual

phase

• Occurs between episodes of psychosis

• Includes:- Anxiety- Avolition- poor insight- social withdrawal- lack of

motivation- impaired judgment

ComplicationsSubstance abuse

Depression

AnxietyViolence

Diagnostic criteria of

schizophrenia

DSM-IV ICD-10

DSM-IV Diagnostic CriteriaA. Characteristic symptoms. At

least 2 of the following; each for 1- month period

a. Delusions b. Hallucinations c. Disorganized speech d. Grossly disorganized or

catatonic behavior e. Negative symptoms, i.e.

avolition, flattening of affect, alogia (poverty of speech)

B. Social/occupational dysfunction

C. Continuous signs of the disturbance persists for at least six months

D. Schizoaffective and mood disorder exclusion

E. Substance/medical condition exclusion

F. Relationship to pervasive developmental disorder :

the additional diagnosis of Schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month

ICD-10 Diagnostic Criteria

At least one of the symptoms :

a. Thought echo, insertion, or withdrawal and thought broadcasting

b. Delusions of control, influence, or passivity; delusional perception

c. Hallucinatory voices-running commentary or other < part of body

d. Persistent delusions of other kinds

At least one of the symptoms :

a. Persistent hallucinations in any modality occurring everyday for weeks or months

b. Breaks or interpolation in the train of thought > incoherence or irrelevant speech, or neologism

c. Catatonic behavior, such as excitement, posturing, or waxy flexibility, negativism, mutism, stupor

d. Negative symptoms: apathy, paucity of speech, blunting of emotional response

OR

Persistent dysfunction lasting longer than 6 months 2 or more symptoms for at least

1 month ( at least 1 of i, ii or iii)

i- Hallucination ii- Delusions

iii- Disorganized speechiv- Grossly disorganized or

catatonic behavior

v- Negative symptoms Significantly impaired functioning ( work, self care , interpersonal )

Diagnosis

Differential Diagnosis

• Alcohol-related psychosis

• Bipolar affective disorder• Brief psychotic disorder• Cocaine-related psychiatric

disorders• Delusional disorder• Depression• Mental disorders secondary

to general medical conditions

• Schizoaffective disorder• Schizophreniform disorder

Prognosis• Complete recovery 25%

• Much improved 35%• Improved but require

extensive therapy15%• Hospitalized

(unimproved )10%

• Dead ( mostly Suicide )15%

Desired outcome1.Alleviation of target symptoms

2.Avoidance of side effects

3. Importance of Psychosocial functioning and proactively

4.Compliance with the prescribed regimen

5. Involvement of the patient inthe treatment plan

6.Not to be hospitalized

Before treatment 1.Mental status examination

2.Physical & neurological examination3.Complete family & social history (take in consideration

family history of response to drugs)4.Psychiatric diagnostic interview5.Laboratory work up ( CBC, electrolytes, hepatic &

renal functions, ECG, FBG, lipid profile, thyroid functions and urine drug screening )

Antipsychotic pharmacotherapy

Other pharmacotherapy

Psychosocial intervention

Diet and activity

Managemen

t

AntipsychoticsAtypical APs.Second generation

Typical APs.first generation


Typical APs. traditional, conventional, first generation

antipsychotics, classical neuroleptics, major tranquilizers

Low potency Chlorobromazine: Neurazine ® Thioridazine: Mellcril ®

Medium potencyMolindone: Moban ®

Thiothixene: Navane®

Pimozide: Orape forte ®

High potencyTrifluperazine: Stellazine ®

Haloperidol: Haldol ®Fluphenazine: Modecate ®

Zuclopenthixol: Clopexol ®

Aripiprazole: Apilify ®

Clozapine: leponex ®

Olanzapine: Zyprexa ®

Quetiapine: Seroquil ®

Resperidone: Resperidal ®

Sulpiride: Dogmatil ®

Ziprasidone: Zeldox ®



Mechanism of action :- DA receptor blocker-Have activity on histamine, muscarinic & α-receptors ( not responsible for the therapeutic activity )

Superior action in positive symptoms

Mechanism of action :- DA antagonist and 5-HT2A –

receptor blocker EXCEPT Aripiprazole Partial DA & 5-HT1A-

agonist 5-HT2A- antagonist- Have activity on histamine,

muscarinic & α-receptors ( not responsible for the therapeutic activity )

Superior action in negative

& cognition symptoms



Major side effects : Major side effects :Sed. EPS A.Ch O.HoTN

CPZ +++ ++ ++ +++

Thioridazine +++ + +++ +++

Molindone ++ ++ + +

Thiothixene + +++ + ++

Trifluperazine + +++ + +

Haloperidol + +++ + +

Fluphenazine + +++ + +

Sed. EPS A.Ch O.HoTN Wt.G

clozapine +++ 0 +++ +++ +++

Resperidone + + 0 + ++

Olanzapine ++ + ++ + +++

Quetiapine ++ + 0 ++ ++

Ziprasidone 0 + 0 0 0

Aripeprazole + + 0 0 0

Sed : sedation, EXP: extrapyramidal side effects , A.Ch anticholinergic side effects , O.HoTN: orthostatic hypotension wt.G : weight gain

Side effects of antipsychotics1-Autonomic nervous system S.Es :

- Dry mouth ( ttt: fluid intake, oral lubricant, sugarless gum)- Constipation (ttt: Exercise , fluid and dietary fibers intake)- Blurred vision- Tachycardia- Inhibition of Ejaculation- Urinary retention- Impaired memory

2- CNS Side effects : a. Extrapyramidal S.Es

i- Dystonia :Definition : Prolonged tonic muscle contraction, Risk : life threatening (pharyngeal –laryngeal dystoniaRisk factors : young patient , male gender, high potency agent, high doses Treatment : IV or IM anticholenergic or BDZ Prophylaxis : Anticholinergic in : high potent 1st generation APs, young men or history of dystonia

ii- Akathesia :Definition : Subjective complain : feeling of inner restlesnessObjective symptoms: pacing, shuffling or tapping feet Treatment : decrease the dose of FGAPs or switch to SGAPs

iii-Pseudoparkinsonism:

Symptoms : - Akinesia, brdykinesia or decreased motor activity including

micrographia, slowed speech, decreased arm swing - Tremors

- Cogwheel rigidity- Postural abnormalities

Risk factors :- FGAPs specially in high dose - High doses - Old age

Onset : 1-2 weeks after initiation or increment of APs dose

Treatment : - Anti cholinergic s: - Benzotropine, Diphene hydramine, Biperidine)- Amantadine

Iv-Tardive dyskinesia: Definition : abnormal involuntary movement with chronic use of APs e.g: Oro facial movement , Risk : life threatening (pharyngeal –laryngeal dystoniaRisk factors : Old age , long duration of ttt, high doses , diagnosis of organic mental disorder , DM or mood disorder Treatment : Decrease dose or switch to SGAPs Prophylaxis : Use SGAPs as first line

b. Seizures : - Highest risk of drug including seizures are chloropromazine& clozapine- Likely in initiation of ttt, high doses or rapid dose increment Treatment :- Decrease the FGAPs dose & switch to SGAPs - Anticonvulsant not recommended

- 0.5% - 1 % of patients taking FGAPs Risk factors :

- High potency FGAPs, - Injectable or depot FGAPs - Dehydrated patient - Organic mental disorderSymptoms :- Temp. < 38°C - Altered level of consciousness- Rigidity - Autonomic dysfunction

( tachycardia, tachypnea , urinary & fecal incontinence )

Lab. Findings :- Leukocytosis- High CK, AST, ALT, LDH, - Myoglobin uria

c. Neuroleptic Malignant syndrome :

Treatment : - Discontinue AP drug - Supportive care - Bromocriptin ( reduce DA

blockade, rigidity, fever & CK level)

- Amantadine - Dabtrolone ( skeletal muscle

relaxant with favourable effect on Temp.& respiratory rate )

- Lowest effective dose of SGAPs after 2 ws without AP & monitor closely

3-Endocrine System : a- Prolactin : - APs stimulate prolactin production which is

associated with galactorhea & menstrual irregularities

- Dose related - Frequently with FGAPs & risperidone- Management : switch to SGAPs aripiprazole or

ziprasidone

b- Weight gain :- Frequently with SGAPsOlanazapine , clozapine , risperidone & quetiapine more than ziprasidone & aripiprazole )

c- Glucose level : - New onset of diabetes reported with SGAPs

4- CNS side effects :Orthostatic hypotension :- < 20 mmHG drop in systolic pressure upon

standing

- Frequently with :• low potency APs• APs combination • DM• Cardio vascular disease • Elderly patient

- Tolerance occurs within 2-3ms

- If not tolerated ; change AP drug or decease the dose

- Some SGAPs & phenothiazines cause elevation in serum TGs & cholesterol- Risk decreases with ; risperidone,ziprasidone & aripiprazole

5- Lipid effects :

6- Ophthalmic effects : - Impaired visual accommodation- Photophobia- Narrow angle glaucoma exacerbation- Opaque deposit in cornea & lens (frequently with chronic use of

phenothiazines specially chloropromazine )- Cataract : with quetiapine ( periodic slit lamp examination is

recommended ) - Retinitis pigmentosa : with thioridazine < 800 mg daily

Other pharmacotherapy

- Mainly to Control APs side effectse.g : anticholinergic agents and amantadine are often used in conjunction with the conventional APs to treat extrapyramidal symptoms.

41

Need rapid tranquilization Urgent

No

Combination of parenteral treatment

Yes

Yes

No

Identify Phases of Illness

No

Adequate dose & duration

Oral medication is preferred When parenteral needed use single agent

• Provide comprehensive plan (pharmacological, psychosocial & service level interventions)

• Offer conventional APs (300-1000mg CPZ equivalent) or AMS or OLZ• Monitor clinical response, side effects & treatment adherence

Poor response

Optimize APs usage

• Exclude substance abuse, treatment non-adherence & concurrent other general medical conditions

• Optimize psychosocial interventions• Refer to psychiatrist for trial of

clozapine

Yes

No

• Plan for recovery (ACT, family intervention, psychoeducation, social skills training & supported employment)

• APs usage to continue with single oral agent from acute phase; use depot when non-adherent• Monitor for clinical response, side effects & treatment adherence

Acute phase

Relapse prevention

ALGORITHM FOR MANAGEMENT OF SCHIZOPHRENIA Diagnosis of

Schizophrenia

Stable phase

Follow-up at primary care Follow manual on Garispanduan

Perkhidmatan Rawatan Susulan Pesakit Mental di Klinik Kesihatan

Prevention & management of side effects of APs at all phases Monitor EPS/akathisia/weight gain/diabetes/heart

disease/sexual dysfunction Follow schedule of physical care as per follow-up manual

Psychosocial interventions

Cognitive remediationCognitive remediation is a treatment modality derived from principles of neuropsychological rehabilitation. It is based, in part, on the ideas that the brain has some plasticity and that brain exercises can encourage neurons to grow and can develop the neurocircuitry underlying many mental activities. Vocational rehabilitationMost patients with schizophrenia would like to work; employment can improve income, self-esteem, and social status. However, few people with the disorder are able to maintain competitive employment. Supported employment programs currently thought to be most effective are those that offer individualized, supported, and rapid job assignments and that are integrated with other services

Family interventionSchizophrenia affects the person’s whole family, and the family’s responses can affect the trajectory of the person’s illness. Familial “high expressed emotion” (hostile overinvolvement and intrusiveness) leads to more frequent relapses. Some studies have found that family therapy or family interventions may prevent relapse, reduce hospital admission, and improve medication compliance

Smoking cessation : Most patients with schizophrenia smokethis may be a result of previous conventional antipsychotic treatment . Smoking may also be related to the boredom associated with hospitalizations, the peer pressure from other patients to smoke, or the anomie associated with unemployment. Whatever the cause of the high incidence of smoking, the health risks from smoking are well known, and all schizophrenic patients should be encouraged to stop smoking.

Diet & Activity Many psychotropic medications can cause weight gain and changes in glucose or lipid metabolism. Occasionally, a person with schizophrenia develops odd food preferences. Finally, many persons with schizophrenia have limited funds, do not cook for themselves, and live in areas where fast food outlets are abundant. Therefore, nutritional counseling is difficult but important. Because many psychotropic medications are associated with weight gain, persons with schizophrenia should be encouraged to be as physically active as possible.

References:

Medscape websitePharmacotherapyComprehensive pharmacy reviewAPA website

Thank you