Chapter 13

Schizophrenia- Readings

Chapter 13 Chapter 36

Sections 36.18 pages 1043 to 1062 36.30, pages 1091 to 1098

What is Schizophrenia?

Clinical syndrome of variable but profoundly disruptive psychopathology

It involves: Cognition, emotion, perception and other aspects of

behavior

Normally begins before age 25 Persists throughout life Affects persons of all social classes

Epidemiology

Gender and Age Equal prevalence in men and women 1 in 100 persons will develop the condition during

their lifetime, with peak ages 10 to 25 in men and 25 to 35 in women

Women can display bimodal age distribution with a second peak occurring in middle age

3% to 10% of women with schizophrenia present with disease onset after age 40

About 90% of patients in treatment for schizophrenia are between 15 and 55 years of age

Reproductive Factors

Marriage among schizophrenics has led to an increased number of children born to both schizophrenic parents.

Medical Illness

Patients with Schizophrenia have higher incidence of death from accidents and natural causes than the general population.

Studies have shown that up to 80% of patients with schizophrenia have significant concurrent medical illnesses, and up to 50% are undiagnosed.

Other Factors Related to the Development of Schizophrenia

Patients with schizophrenia are more likely to have been born in winter and early spring and less likely to have been born in late spring and summer

Season specific risk-factors may influence the development of the condition Expossure to pathogens

Prenatal malnutrition may play a role in schizophrenia

Substance Abuse

Common in Schizophrenia Lifetime prevalence often greater than 50%

for any drug (other than tobacco) Lifetime prevalence for alcohol abuse, 40% Patients that reported high levels of cannabis

use (more than 50 ocassions) were at sixfold increase risk of schizophrenia compared to non-users

Up to 90% of schizophrenic patients may be dependent on nicotine

Biochemical Basis: Dopamine Hypothesis

Dopamine hyperactivity hypothesis Initially supported by neuroscientists and

clinitians Supported by observing drugs that enhance

dopamine activity Amphetamines- in chronic amounts can induce

symptoms virtually identical to those in paranoid psychosis

This hypothesis failed at explaining many other aspects of schizophrenia such as negative symptoms, cognitive deficits and other neurochemical and pathological findings

Biochemical Basis: Dopamine Hypothesis Antipsychotics neither cure or completely

prevent relapse of symptoms 30% of patients are refractory to treatment with

antipsychotics Conventional antipsychotics have a tendency to

cause Extrapyramidal symptoms Poor efficacy against negative symptoms Inability to reverse or prevent cognitive impairment Inability to permit a normal level of psychosexual

and work function Atypical antipsychotics which are less specific

blockers of dopamine may be superior to Haldol and result in less extrapyramidal symptoms.

Pharmacotherapy of Schizophrenia; The Past, Presnt and Future. Current Drug Therapy, 2006, Vol1, No. 13

Biochemical Basis:Serotonin Hypothesis Hyper-Serotonin hypothesis

First observed in the 1950s when researchers noticed its similarity to LSD, which competes for 5-HT receptors resulting in psychosis-like symptoms

Evidence for action of 5HT lies in observations of brain behavior, neurotransmitter systems, drug mechanisms and postmortem studies.

Some studies found elevated levels of 5-HT in blood platelets

By far the strongest evidence of the role of 5-HT is the mechanism of atypical antipsychotic drugs like clozapine

Pharmacotherapy

Modern treatment primarily relies on somatic drug therapy

Most drugs used to treat schizophrenia antagonize post synaptic dopamine receptors

Antipsychotics are (Atypical)the mainstay of pharmacotherapy of schizophrenia

First-generation antipsychotics Dopamine receptor antagonists

Second-generation antipsychotics Serotonin dopamine antagonists (SDAs)

Families of Antipsychotics Phenothiazines

Aliphatic Chlorpromazine Promazine Triflupromazine

Piperazine Acetophenazine Fluphenazine Perphenazine Proclorphenazine Trifluroperazine Mesoridazine Thioridazine

Families of Antipsychotics Thioxantines

Dibenzoxapine Chlorproxitene Thiothixene

Dihydroindole Molindone

Butyrophenones Droperidol Haloperidol

Families of Antipsychotics Thioxantenes cont.

Dyphenylbutylpiperidine Primozide

Benzamide Sulpiride (not available in the U.S.)

Rauwolfia Alkaloid Reserpine

DRAs

Therapeutic indications Indicated for many types of psychiatric

and neurologic disorders. See table 36.18-2 pg 1045

Pharmacotherapy

Chlorpromazine (Thorazine) Introduced in 1952 Most important single contribution to the

treatment of a psychiatric illness Effective at reducing hallucinations and

delusions as well as excitement Antipsychotics reduce relapse rates Apprx. 70% of patients treated with

antipsychotics achieve remission

Pharmacotherapy

Acute Psychosis Lasts 4-8 weeks Severe agitation as a result of:

Frightening delusions Hallucinations Suspiciousness Other causes:

Stimulant abuse

Pharmacotherapy Therapeutic options

Acute psychosis Antipsychotics (DRAs)

Highly agitated patients: IM antipsychotics offer relatively fast relief

High Potency Haloperidol (Haldol) Acetophenazine (Tindal) Fluphenazine (Prolixin, Permitil) Perphenacin (Trilafon) Thiotixene (Navane)

Pharmacotherapy

Antipsychotics (DRAs) cont. Low Potency

Chlorpromazine (Thorazine) Loxapine (Loxitane) Mesoridazine (Serentil) Molindone (Moban) Pimozide (Orap) Thioridazine (Mellaril)

Possible Adverse Effects of DRAs Seizures

May lower seizure threshold

Sedation Central and peripheral

anticholinergic effects Cardiac effects Sudden death Orthostatic (postural)

hypotension Hematologic effects Endocrine effects Skin and eye

Jaundice Overdoses

Exagerated DRAs effects

Pregnacy and lactation Related to

malformations

Interactions See table 36.18-5

Pharmacotherapy

Atypical Antipsychotics Serotonin Dopamine antagonists (SDAs)

Effective in patients that present aggressive or violent behavior (10% of patients)

Treatment with SDAs decreases suicide risks and water intoxication in patients with schizophrenia

Adverse effects SDAs share similar spectrum of adverse reactions,

but differ in frequency and severity

See table 36.30-1 pg 1093, Kapplan & Sadock

Pharmacotherapy Olanzapine

Effective in psychosis, and in the tratment of agitation in patients with schizophrenia

Clozapine Effective in controlling psychosis but due

to life- threatening adverse effects, appropriate only to non-responsive patients

Also effective in patients that present severe tardive dyskinesia.

Benzisoxazoles Risperidone (Risperdal)

Pharmacotherapy

Benzodiazeoines- Effective for agitation during acute psychosis Lorazepam (Ativan) – may reduce the

amount of antipsychotic needed