Psychotic Disorders

Muhammad Junaid Farrukh

Pharm D, M Clin Pharm

Hamdard Institute of Pharmaceutical Sciences

Islamabad Campus

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Psychosis

• Psychosis is a loss of contact with reality, usually including false beliefs about what is taking place or who one is (delusions) and seeing or hearing things that aren't there (hallucinations).

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Psychosis is also part of a number of psychiatric disorders, including:

• Bipolar disorder (manic or depressed)

• Delusional disorder

• Depression with psychotic features

• Personality disorders (schizotypal, shizoid, paranoid, and sometimes borderline)

• Schizoaffective disorder

• Schizophrenia

Definition

Schizophrenia is a serious mental illness characterized by illogical thoughts, bizarre behavior and speech, and delusions or hallucinations, such as hearing voice (American psychiatry association)

Pathophysiology

Diagnostic criteria for Schizophrenia(DSM IV) diagnostic and statistical manual of mental disorders

A. Characteristic symptoms  (1) delusions(2) hallucinations(3) disorganized speech (e.g., frequent derailment or incoherence) (4) grossly disorganized or catatonic behavior(5) negative symptoms, i.e., affective flattening

B. Social/occupational dysfunction: Failure to achieve expected level of interpersonal, academic, or occupational achievement).C. Duration: Continuous signs of the disturbance persist for at least 6 months

Positive and negative symptoms scoringTo assess a patient using PANSS, an approximately 45-minute clinical interview is conducted. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers

Positive scale7 Items, (minimum score = 7, maximum score = 49)• Delusions• Conceptual disorganization• Hallucinations• Hyperactivity• Grandiosity• Suspiciousness/persecution• Hostility

Negative scale7 Items, (minimum score = 7, maximum score = 49)• Blunted affect• Emotional withdrawal• Poor rapport• Passive/apathetic social withdrawal• Difficulty in abstract thinking• Lack of spontaneity and flow of conversation• Stereotyped thinking

Positive and negative symptoms scoringGeneral Psychopathology scale16 Items, (minimum score = 16, maximum score = 112)• Somatic concern• Anxiety• Guilt feelings• Tension• Mannerisms and posturing• Depression• Motor retardation• Uncooperativeness• Unusual thought content• Disorientation• Poor attention• Lack of judgment and insight• Disturbance of volition• Poor impulse control• Preoccupation• Active social avoidance

PANSS Total score minimum = 30, maximum = 210

Positive and negative symptoms scoring

CGI Severity of Illness

Corresponding PANSS score

Mildly ill 58

Moderately ill 75

Markedly ill 95

Severely ill 116

Treatment of schizophrenia

Typical• Chlorpromazine

(Largactil®)• Flupenthixol

(Fluanxol®)• Haloperidol

(Serenace® Haldol®)• Sulpiride (Dogmatil®)• Thioridazine

(Melleril®)• Trifluoperazine

(Stelazine®)

Atypical• Amisulpiride (Solian®)• Quetiapine (Seroquel®)• Ziprasidone (Zeldox®)• Risperidone

(Risperdal®)• Olanzapine (Zyprexa®)• Clozapine (Clozaril®)• Aripiprazole (Abilify®)

Typical antipsychotics - MOA

Blocks receptors for dopamine, acetylcholine, histamine and norepinephrine

Current theory suggests dopamine2 (D2) receptors suppresses psychotic symptoms

All typical antipsychotics block D2 receptors

Typical antipsychotics Ex: Haloperidol

Typical antipsychotics - cont

• Properties• Effective in reducing positive symptoms during acute

episodes and in preventing their recurrence

• Less effective in treating negative symptoms• Some concern that they may exacerbate negative

symptoms

• Higher incidence of EPS

EPS

Early reactionCan be managed with drugs

Late reactionDrug treatment unsatisfactory

Dystonias • Develops within a few hours to 5 days after first dose• Muscle spasm of tongue, face, neck and back

• Oculogyric crisis (involuntary upward deviation of eyeballs)• Opisthotonus (tetanic spasm of back muscles, causing trunk

to arch forward, while head and lower limbs are thrust backwards)

• Laryngeal dystonia can impair respiration

• Management• Anticholinergics (Benztropine, diphenhydramine IM/IV)

• Add scheduled benztropine / diphenhydramine with antipsychotic

Parkinsonism

• Occurs within first month of therapy

• Management• Centrally acting anticholinergics (scheduled benztropine /

diphenhydramine / benzhexol with antipsychotics) and amantadine

• Avoid levodopa as it may counteract antipsychotic effects

• Switch to atypical antipsychotics

Akathisia

• Develop within first 2 months of therapy• Compulsive, restless movement• Symptoms of anxiety, agitation

• Management• Benzodiazepines (e.g. lorazepam)• Anticholinergics (e.g. benztropine, benzhexol)• Reduce antipsychotic dosage or switch to low potency

agent

Tardive dyskinesia (TD)

• Develops months to years after therapy• Involuntary movements of tongue and face

• Can interfere with chewing, swallowing and speaking

• Symptoms are usually irreversible• Management:

• Mild: Use milder atypical • Severe: Clozapine• Gradual drug withdrawal

Atypical antipsychotics

Ex: Risperidone

Atypical antipsychotics

• Properties

• Available evidence to show advantage for some (clozapine, risperidone, olanzapine) but not all atypicals when compared with typicals

• At least as effective as typicals for positive symptoms

• May be more efficacious for negative symptoms (still under debate)

Atypical antipsychotics

• Properties – cont

• Less frequently associated with EPS

• More risk of weight gain, new onset diabetes, hyperlipidemia

• Novel agents, more expensive

Atypical antipsychotics

• All atypical antipsychotics are equally effective at therapeutic doses

• Except clozapine• Most effective antipsychotic• For resistant schizophrenia• 2nd line due to life-threatening side effect

Atypical antipsychotics

Drug Advantages DisadvantagesClozapine For treatment-resistant

cases, little EPSRisk of fatal agranulocytosis

Risperidone

Broad efficacy, little or no EPS at low doses

EPS and hypotension at high doses

Olanzapine

Effective with positive and negative symptoms, little or no EPS

Weight gain

Quetiapine Similar to risperidone, maybe less weight gain

Dose adjustment with associated hypotension, BD dosing

Ziprasidone

Perhaps less weight gain than clozapine, Inj A/V

QT prolongation

Aripiprazole

Less weight gain, novel mechanism potential

Uncertain

Atypical antipsychotics

• 1st line atypical antipsychotics• All atypicals except clozapine

• NICE recommendations

• Atypical antipsychotics considered when choosing 1st line treatment of newly diagnosed schizophrenia

• Treatment option of choice for managing acute schizophrenic episode

• Considered when suffering unacceptable Adverse effects from a conventional antipsychotic

• Changing to an atypical not necessary if typical controls symptoms adequately and no unacceptable Adverse effects

Atypical antipsychotics

• 2nd line atypical antipsychotic• Clozapine

• Most effective antipsychotic for reducing symptoms and preventing relapse

• Use of clozapine effectively reduce suicide risk

• 1% risk of potentially fatal agranulocytosis• Acute pronounced leukopenia with great reduction

in number of neutrophil

• NICE recommendations• Clozapine should be introduced if schizophrenia is

inadequately controlled despite sequential use of 2 or more antipsychotic (one of which should be an atypical) each for at least 6-8 weeks)

Depot antipsychotics

• Depot APs • Fluphenazine decanoate

• Flupenthixol decanoate • Risperidone

• Depot APs may confer an advantage over conventional oral APs by improving adherence to drug treatment.

• Depot preparations could ensure continuous drug delivery, overcome bioavailability problems and avoid the risk of overdose with oral medications.

• However, depot preparations do not allow flexibility in administration and dose adjustment.

• Patients may also complain of side effects at site of injection e.g. pain, oedema, pruritus and sometimes a palpable mass.

Common side effects of atypical antipsychotics

Patient counselling and Family education

Patient should be counseled to follow the prescribed medications.

Family member are advised

to monitor patients routine

To check if he is taking medicine in time or any family member take self responsibility to administer medicine

To ensure monthly administration of i/m depot to minimize risk of relapse

If patient shows any signs or symptoms of relapse or ineffective treatment report the doctor immediately

References https://ww1.cpa-apc.org/Publications/Clinical_Guidelines/schizophrenia/november2005/

Pharmacotherapy.asp

http://www.ncbi.nlm.nih.gov/pubmed/16086618

http://bjp.rcpsych.org/content/195/52/S13.full.pdf

http://www.ingentaconnect.com/content/apl/pcp/2001/00000005/00000003/art00005

Conley RR, Mahmoud R. Am J Psychiatry 2001; 158: 765-774.

Zhong KX et al. Poster presented at the 16th European College of Neuropsychopharmacology Congress, Prague, Czech Republic, 2003

http://www.ncbi.nlm.nih.gov/pubmed/15231461

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