Antipsychotic Medications

used to treat psychoses;

aka “neuroleptics”, “major tranquilizers”, or “anti-schizophrenics”

Schizophrenia Symptoms

n Hallucinations

n Delusions

n Disordered thought

n Inappropriate emotion

n Often bizarre behavior & speech

n “positive (+) symptoms”

n Normal emotion lost

n Decreased social interaction

n Speech often decreased

n “negative (-) symptoms”

Typical/Traditional Antipsychotics

Phenothiazines

n *chlorpromazine (Thorazine) was 1st used in the 1950’s

n became the prototypic antipsychotic

n chemically complex - blocks the action of DA, NE, 5HT, ACh and histamine

n Others: Mellaril (thioridazine), Stelazine (trifluoperazine), Prolixin (fluphenazine) & ~6 others (all the generics end in “azine”)

n Differ in potency & degree of side effects

Main Side Effects

n *Extrapyramidal Motor Disorders

n Dry mouth, blurred vision, constipation

n Sedation, decreased response to stimuli& low blood pressure

n Disturbed hypothalamic functions; skin photosensitivity

n Risk of Neuroleptic Malignant Syndrome (NMS)

“Extrapyramidal” Motor Effects

n drug-induced Parkinson’s-like decreased movement (akinesia) in over 30%

n sometimes compulsive restlessness (akathesia)

n sometimes strong involuntary muscle spasms (dystonias)

n sometimes involuntary movements of face & limbs (dyskinesias)

n often must take drugs like Artane, Cogentin to treat side-effects

Tardive Dyskinesia (TD)

n Neurological symptom that may appear in 15-25% after 2+ yrs of use, more common the longer you use meds or the older you get.

n Involuntary movements of lips, tongue, jaw, face, eyelids &, less often, the body .

n Unlike other extrapyramidal symptoms, TD may increase if drug is discontinued (may be long-lasting or permanent in some)

Neuroleptic Malignant Syndrome

n possibly life-threatening event in 1-2%; may not be recognized

n severe rigidity, may not be able to swallow or speak or move eyes

n confusion, agitation, delirium, catatonia, or coma possible

n autonomic effects, high fever; possible cardiac, respiratory or kidney arrest

Typical Antipsychotics:

n primarily reduce the “positive symptoms” of schizophrenia

n low potency drugs produce more sedation, more autonomic and fewer motor effects

n high potency drugs produce more motor effects, less sedation and autonomic effects

Dopamine Hypothesis

n Schizophrenia is associated with excessive response to DA

n Schizophrenics do not seem to have more DA, but may have more receptors or over-responsive receptors

n All DA areas of brain are not over-responsive - just the limbic & cortical DA neurons

Support for the DA Hypothesis

n effectiveness of typical antipsychotics almost perfectly correlated with DA blockade

n drugs which increase DA can cause paranoid schizophrenic states (e.g. amphetamine)

n drugs which ONLY block DA (1967) are highly effective: *butyrophenones (*Haldol (haloperidol), Inapsine (droperidol)

n brains of schizophrenics do show some abnormalities in DA activity

Atypical Antipsychotics

n Prototype: Clozaril (clozapine)

n Blocks DA4 and 5HT2 receptors

n few extrapyramidal side effects

n helps previously unresponsive patients

n improves “negative” symptoms; disorganization; decreases suicides

n BUT can cause agranulocytosis in 1-2% so requires monitoring of blood

Newer Atypical Antipsychotics

n risperidone (Risperdal)

n olanzapine (Zyprexa)

n quetiapine (Seroquel)

n ziprosidone (Zeldox)

n block narrower categories of receptors (DA2 & 5HT2)

n These show less agranulocytosis

Other Uses for Antipsychotics

n other psychotic conditions; some bipolar cases

n decrease symptoms of Huntington’s Disease & Tourette’s syndrome

n anti-emetic (anti-vomiting), anti-itching

n treat intractable hiccups: slow premature ejaculation

n preanesthetic calming

n Anti-aggression, agitation

n Some developmental disorders