psychopharmacology

antipsychotics

aka neuroleptics

categorized as first, second, or third generation

first-generation antipsychotics (FGAs) (names, uses, how it works)

aka typical antipsychotics

includes: chlorpromazine (Thorazine), haloperidol (Haldol) thiordazine (Mellaril), and fluphenazine (Prolixin)

used to treat schizophrenia and other disorders with psychotic symptoms, more effective for treating positive than negative symptoms

how it works: FGAs are dopamine antagonists that exert their effects by blocking dopamine (D2) receptors

3 categories of FGA side effects (names only)

1. anticholinergic side effects

2. extrapyramidal side effects

3. neuroleptic malignant syndrome (NMS)

anticholinergic side effects

side effects from low potency FGAs (e.g., chlorpromazine and thioridazine)

• dry mouth

• blurred vision

• urinary retention

• constipation

• tachycardia

extrapyramidal side effects

side effects of high potency FGAs (e.g., haloperidol and fluphenazine)

• parkinsonism (resting tremor, muscle rigidity, slowed movement)

• dystonia (uncontrollable muscle contractions)

• akathisia (a sense of inner restlessness)

• tardive dyskinesia

tardive dyskinesia

related to side effects from long-term high potency FGA use

can be life threatening

more common in women and older adults

starts with involuntary, rhythmic movements of the tongue, face, jaw, and over time, the limbs and trunk

irreversible for some patients

treated by gradually withdrawing the drug, administering a benzodiazepine, or switching to a SGA

neuroleptic malignant syndrome (NMS)

a rare, life-threatening side effects of FGAs

• muscle rigidity

• high fever

• autonomic dysfunction (e.g., unstable blood pressure, tachycardia, excessive sweating)

• altered mental state (e.g., confusion, combativeness)

treatmeant involves having the person stop taking the drug at the first side of symptoms and providing them with supportive therapy (e.g., hydration, cooling)

second-generation antipsychotics (SGAs) (names, uses, how it works)

aka “atypical antipsychotics”

includes: clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel)

like FGAs, they are used to treat schizophrenia and other disorders with psychotic symptoms, and some are FDA-approved as adjunctive treatment for MDD and bipolar disorder

how SGAs work: they are dopamine-serotonin antagonists, which alleviate positive symptoms primarily by blocking dopamine (especially D2, D3, and D4) receptors, and alleviate negative and cognitive symptoms primarily by blocking serotonin (5-HT2A) receptors

benefits of SGAs

there is some evidence that SGAs are as effective or more effective than FGAs in treating positive symptoms of schizophrenia, and that some SGAs may also reduce negative symptoms

SGAs may be effective for patients who can’t tolerate or do not respond to FGAs, with clozapine being the only FDA-approved antipsychotic for treatment-resistant schizophrenia

side effects of SGAs

less likely to cause extrapyramidal side effects, however, they can cause:

• anticholinergic effects

• neuroleptic malignant syndrome

• metabolic syndrome

clozapine and, to a lesser extent, other SGAs can also cause neutropenia and agranulocytosis (a severe form of neutropenia).

metabolic syndrome

sometimes caused by SGAs

involves substantial weight gain, high blood pressure, insulin resistance, hyperglycemia, and increased risk for diabetes and heart disease

side effects of clozapine

clozapine and, to a lesser extent, other SGAs can also cause neutropenia and agranulocytosis (a severe form of neutropenia).

both are life-threatening and involve dangerously low levels of neutrophils, a type of white blood cell that is an essential part of the body’s immune system.

treatment/prevention: for patient’s taking clozapine, regular blood testing and, when neutrophil levels are too low, treatment may include discontinuing the drug and prescribing an antibiotic for infections and medications to improve the body’s ability to produce neutrophils more quickly.

third-generation antipsychotics (TGAs) (names, uses, how they work)

aka dopamine-sertotonin stabilizers

includes: aripiprazole (Abilify), brexpiprazole (Rexulti), and cariprazine (Vraylar)

used to treat schizophrenia and as an adjunctive treatment for bipolar and MDD

how they work: TGAs are partial agonists even though they have both antagonist and agonist effects

• dopamine: TGAs exert their effects primarily at D2 receptors where they a) act as antagonists by reducing dopamine levels in areas of the brain where dopamine levels are too high and thereby reduce positive symptoms, and b) act as partial agonists by increasing dopamine levels in areas of the brain where dopamine levels are too low and thereby reduce negative and cognitive symptoms

• serotonin: TGAs act as antagonists at 5-HT2A receptors and partial agonists at 5-HT1A receptors, which reduces depression, anxiety, and cognitive symptoms

benefits of TGAs

there is evidence that TGAs are similar to SGAs in terms of effectiveness but have fewer side effects. for example, they are less likely to cause extrapyramidal side effects, tardive dyskinesia, anticholinergic effects, and metabolic syndrome

side effects of TGAs

although they have less side effects than SGAs, they can cause:

• akathisia (restlessness)

• fatigue

• headache

• nausea

• anxiety

there is also some evidence that aripiprazole can cause addicted gambling and other impulse control disorders