antipsychotic drugs

-10-20% of all prescriptions in US

ANTIPSYCHOTICS  (severe psychiatric illnesses)

ANTIDEPRESSANTS  (mood elevators)

LITHIUM SALTS  (mood stabilizers)

ANXIOLYTICS  (most are sedatives)

• Schizophrenia
• Schizoaffective   disorder
• Mood Disorder with psychosis
• Dementia with psychosis
• Delirium
• Delusional disorder
• Psychosis secondary to a non-psychiatric medical disorder 
• Developmental disability with psychosis and/or aggression
• Tourette’s disorder, Huntington’s ,chorea, intractable hiccups
• Acute Mania
• Augmentation in Major Depression and Bipolar disorder

• severely disordered thought and emotion
• 2 kinds
• --organic: memory and orientation are affected
• --Idiopathic: memory and orientation are intact (schizophrenia)

•Positive Symptoms: Hallucinations, Delusions

•Negative Symptoms: Blunted affect, Anhedonia, Social withdrawal, Avolition, Alogia

–

Lifetime prevalence: 1%

Age of onset: 18-35 (mean=20)

Typical Antipsychotics (neuroleptics): block postsynaptic D2 dopamine receptors

Efficacy?: reduce positive symptoms

• •Schizophrenia
• – caused by excessive amounts of dopamine

• •Problems?
• –Typical antipsychotics are unable to
• reduce negative symptoms

• •Conclusions
• –Dopamine is undeniably involved
• –However, mechanism of Schizophrenia is
• much more complex (e.g. structural changes)

???

• Atypical Antipsychotics (e.g. clozapine, risperidone)
• –block 5-HT2A serotonin receptors

–weakly block D2 receptors

•Efficacy

–reduce positive symptoms

–some are able to mildly attenuate negative symptoms

•Conclusions

–further evidence of dopamine involvement

–evidence that other neurotransmitters are involved

• proven clinical efficacy, but all share important side effects. Due to the highly
• variable therapeutic response and variable tolerance to side effects, treatment
• is highly individualized, and dosages can differ as high as 20- to 30-fold
• between patients.

Antipsychotic effect: dec emotional, display, hallucinations, output of RF in response to sensory stimuli

Antiemetic effect: at low doses, action on CTZ

Hypothalamic effect:- loss of thermoregulation, dec cortitropin levels, inc prolactin lvl and appetite, weight gain

Early: dystonia, akathisia, parkinsonism, neuroleptic malignant syndrome (rare)

Late: Perioral tremor, tardive dyskinesia 405)

•postural hypotension

•reflex tachycardia

•pressor effects of epinephrine

•suppression of some dyskinesias

•blurred vision

•dec salivation, inc incidence of caries

•constipation

inc in incidence with inc in neuroleptic exposure

Haloperiol has higher incidence than Risperidone.

Risperidone's incidence plateau after 3 month of txn

is to use novel antipsychotics in preference to conventional neuroleptics

Diminished extrapyramidal side effects (EPS)

Minimized risk for tardive  dyskinesia (TD)

No hyperprolactinemia

Beneficial for treatment of refractory patients

Improved negative symptoms

Improved cognitive/mood symptoms

Advantages: txn of refractory pt, negative symptoms, minimal risk of eps or TD, no prolatin inc

Disadvantage: agranulocytosis, seizures, weight gain, orthostasis, tachycardia, sedation, sialorrhea, constipation

Weight gain after 10 weeks

Most common with:

Clozapine, Olanzapine, Quetiapine, Low-potency neuroleptics

anti-serotonin (5HT2)

anti-dopamine (impaired erection, inhibited orgasms)

anti-norepinephrine (reduced intensity of orgasm)

anti-cholinergic (impaired erection)

anti-histamine (loss of libido, impaired erection)

• fewer
• greatly reduce adverse effects burden
• Clozapine is an exception

major dec

inc

a problem and varies across atypical class