Schizophrenia & Antipsychotics

Discuss the incidence of schizophrenia & the genetic influence.

General incidence in US is about 1%. Has a genetic/biological component. Incidence increases to 3% in persons with a second degree relative with schizophrenia, & 10% in those with a first degree relative. If both parents have schizophrenia, the incidence is 40%.

What are the Extrapyramidal Side Effects?

1) Acute dystonia (10%) 2) Akathisia (20%) 3) Parkinson-like movement disorders (30-60%) 4) Tardive Dyskinesia (20%)

What are the main differences between 1st & 2nd generation antipsychotics?

2nd generation antipsychotics generally block serotonin receptors to a higher degree than they block D2 receptors, thus they have a much lower risk of EPSEs. 2nd generation antipsychotics relieve both positive & negative symptoms of psychosis, may also improve some cognitive symptoms. 2nd generation = drugs of choice due to lower incidence of adverse effects, especially EPSE, & possible improved efficacy.

Explain the % of pts that will respond well to antipsychotics, partially respond, & minimally respond.

30% of pts respond well to antipsychotics. 30% of pts partially respond. 30% of pts only minimally respond. Positive symptoms generally resolve first; negative symptoms may be more difficult to treat.

Explain Tardive Dyskinesia.

Associated with long-term therapy. Incidence estimated at 5% per year of treatment with 1st generation agents & 1% per year with 2nd generation. Exact mechanism unclear. Involuntary movement of tongue or fact. Include rapid blinking, facial tics, lip-smacking, tongue twisting, tongue flicking out of mouth. Can interfere with chewing, swallowing, & speech. may progress to the limbs.

Name the off-label uses & less well studied therapeutic uses of antipsychotics.

Behvaioral disorders in dementia & delusion disorders. Management of personality disorders. Suppression of severe Tourette's symptoms.

What is the mechanism of action for the 1st generation antipsychotics?

Block dopamine receptors (maily D2) in certain areas of the brain. Effective for positive symptoms - not very effective for negative symptoms or cognitive symptoms.

What is the mechanism of action of the 2nd generation antipsychotics?

Block serotonin & various dopamine receptors. They also have varying degrees of a1-blocking, histamine blocking, & muscarinic blocking properties.

Explain the general principles of pt & family education.

Continuously discuss important of compliance!!!! Be clear that there is no cure for schizophrenia & that medications only help to decrease the symptoms. Discuss managment of common SE (orthostatic hypotension, anticholinergic SE, sedation). Discuss the rare but dangerous SE that may occur. Withdrawal of medication in chronic schizophrenia is highly associated with relapse.

Explain the clinical features of an acute schizophrenic episode.

During an acute schizophrenic episode, delusions & hallucinations are common. Delusions are typically religious, grandiose, or persecutory. Auditory hallucinations may consist of voices arguing or commenting on one's behavior. The pt may feel controlled by external influences. Disordered thinking may make rational conversation impossible.

What is the Black Box Warning associated with antipsychotics?

Elderly pts with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

What is the etiology of schizophrenia?

Exact etiology is unknown. The simplest hypothesis involves hyperdopaminergic activity. More recent hypothesis is DOPAMINE DYSREGULATION (areas of hyperdopaminergic activity & areas of hypodopaminergic activity). Other neurotransmitters implicated in schizophrenia include glutamate & serotonin.

Name the Positive symptoms (Psychotic symptoms.

Hallucinations (auditory more common than visual), delusions (fixed false beliefs), agitation, tension, paranoia, hostility, excitement, grandiosity, illogical thought & speech

What is unique to know about Risperidone?

Highest rate of EPSE among 2nd generation agents. (Not as much as 1st generation) Similar risk of hyperprolactinemia as seen in the 1st generation agents.

What is unique to know about Clozapine?

Life threatening adverse effect of AGRANULOCYTOSIS (1-2%) accounts for the required weekly monitoring of CBC. If WBC falls too much, the drug should be stopped. Warn pts of signs of infection like fever, sore throat, & fatigue. Seizures may occur in 1-4% of pts. Only antipsychotic clinically superior for treatment-resistant pts.

Explain acute dystonia & how to treat it.

May develop within the first days of therapy. Includes severe spasms of muscles of tongue, face, neck, or back. Considered a medical emergency! Treat with anticholinergic drugs. Ex: diphenhydramine IV for acute treatment, oral benztropine or trihexyphenidyl for prevention.

Explain the monitoring process of EPSE.

Monitor for EPSE using appropriate scales. The most common scale for TD is the Abnormal Involuntary Movement Scale (AIMS) which should be done annually for pts taking 2nd generation antipsychotics & at every visit for pts taking 1st generation antipsychotics.

Explain the monitoring process of adverse effects.

Perform orthostatic BP measurements before & throughout treatment. Ask about impaired menstruation, libido, sexual performance regularly. Encourage annual eye exams (cataracts). Check body wt, fasting glucose, HgbA1c, & lipid profile at baseline, at 4 months, & then annually. (If high risk for DM, check more frequently.) Baseline EKG for pts with pre-existing CVD.

When do symptoms of schizophrenia usually present?

late adolescence or early adulthood

What are the treatment goals for schizophrenia?

Receive early, comprehensive treatment designed to achieve functional outcomes. Treat positive, negative, depression, & anxious symptoms, as well as preserve cognition. Reduce symptomatology & psychotic relapses. Improve functional & social outcomes. Antipsychotics medications are the cornerstone of therapy & often life-long treatment is required.

Explain the therapeutic uses of antipsychotics.

Schizophrenia, schizoaffective disorder. Bipolar disease (acute mania or mixed episodes & maintenance). Treatment-resistant depression (olanzepine, aripiprazole, quetiapine). Agitation, irritability & aggression in Autism (risperidone).

What are the adverse effects of 1st generation antipsychotics?

Similar list of adverse effects to the 2nd generation. Generally higher rates of EPSE, anticholinergic side effects, hyperprolactinemia.

What are the therapeutic uses of 1st generation antipsychotics?

Similar to the therapeutic uses of the 2nd generation antipsychotics, but less commonly used overall. Antiemetic: chlorpromazine, blocks dopamine receptors in the chemoreceptor trigger zone. Fluphenazine IM or SQ may be an attractive option in non-compliant pts (lasts 7-28 days).

What is unique to know about Aripiprazole?

Sometimes regerred to as a 3rd generation antipsychotic due to its unique mechanism of action as a dopamine system stabilizer.

Is tardive dyskinesia reversible? How do you treat it?

TD is reversible in only 30-50% of cases; early recognition is helpful. Treat by switching to an antipsychotic with less EPSE. TD may initially worsen when the switch is made. Anticholinergic & anti-parkinson drugs are generally NOT effective to reverse these symptoms.

Explain the clinical features of vivid residual symptoms that remain after acute episodes.

These symptoms may include suspiciousness, anxiety, & diminished judgement. These pts may find it difficult to maintain close relationships & employment. Symptoms are classified as positive, negative or cognitive.

Explain Parkinson-like movement disorders & how to treat it.

Usually occurs within the first few months of therapy. Bradykinesia, drooling, tremor, rigidity, shuffling gait, cogwheeling, stooped posture. Best treated with anticholinergic drugs, amantadine or in some cases propranolol. (Anti-parkinson drugs like levodopa will counteract EPSE, but may worsen schizophrenia)

Explain akathisia & how to treat it.

Usually occurs within the first few months of therapy. Includes pacing, squirming, & the need to constantly be in motion. Frequently mistaken for anxiety or exacerbation of psychoses. May also respond to anticholinergic drugs.

Name the 2nd generation antipsychotics (atypical).

aripiprazole asenapine clozapine olanzepine quetiapine iloperidone risperidone ziprasidone

Name the 1st generation antipsychotic we need to know.

haloperidol

Name the Cognitive symptoms.

impaired attention, impaired short-term memory, impaired executive function, impaired verbal fluency, reduced IQ

Name the Negative symptoms.

lack of motivation, uncooperativeness, blunted affect, poor self-care, social withdrawal, little speech, poor abstract thinking (pull back from society)

Psychosis may occur in __________.

schizophrenia, schizoaffective disorder, bipolar disorder, major depression, & the dementias

What are the general adverse effects of antipsychotics. (1st & 2nd generation)

sedation, sexual dysfunction hyperprolactinemia (esp. risperidone) wt gain, glucose dysregulation anticholinergic SE orthostatic hypotension QT prolongation EPSE