Antipsychotics
Antipsychotics
Indications for use: schizophrenia, schizoaffective disorder, bipolar disorder- for mood stabilization and/or when psychotic features are present, delirium, psychotic depression, dementia, trichotillomania, augmenting agent in treatment resistant anxiety disorders.
Key pathways affected by dopamine in the Brain
Key pathways affected by dopamine in the Brain
MESOCORTICAL
- MESOCORTICAL- projects from the ventral tegmentum (brain stem) to the cerebral cortex. This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise. Problem here for a psychotic patient, is too little dopamine.
MESOLIMBIC
- MESOLIMBIC-projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system. This pathway is where the positive symptoms come from (hallucinations, delusions, and thought disorders). Problem here in a psychotic patient is there is too much dopamine.
NIGROSTRIATAL
- NIGROSTRIATAL- projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia. This pathway is involved in movement regulation. Remember that dopamine suppresses acetylcholine activity. Dopamine hypoactivity can cause Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia and dystonia.
TUBEROINFUNDIBULAR
- TUBEROINFUNDIBULAR-projects from the hypothalamus to the anterior pituitary. Remember that dopamine release inhibits/regulates prolactin release. Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia (gynecomastia/galactorrhea/decreased libido/menstrual dysfunction).
Antipsychotics as mood stabilizers
FDA approved indications in Bipolar disorder
| Generic name | Trade name | Manic | Mixed | Maintenance | Depressed |
|---|---|---|---|---|---|
| Aripiprazole | Abilify | x | x | x | |
| Ziprasidone | Geodon | x | x | X* | |
| Risperdone | Risperdal | x | x | ||
| Asenapine | Saphris | x | x | ||
| Quetiapine | Seroquel | x | X* | ||
| Quetiapine XR | Seroquel XR | x | X* | x | |
| Chlorpromazine | Thorazine | x | |||
| Olanzapine | Zyprexa | x | x | x | |
| Olanzapine/fluoxetine comb | Symbyax | x |
*denotes FDA approval for adjunct therapy not mono-therapy
Antipsychotics: Typicals
Antipsychotics: Typicals
- Are D2 dopamine receptor antagonists
- High potency typical antipsychotics bind to the D2 receptor with high affinity. As a result they have higher risk of extrapyramidal side effects. Examples include Fluphenazine, Haloperidol, Pimozide.
- tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects including sedation, hypotension. Examples include chlorpromazine and Thioridazine.
Antipsychotics: Atypicals
Antipsychotics: Atypicals
- The Atypical Antipsychotics - atypical agents are serotonin-dopamine 2 antagonists (SDAs)
- They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.
- Examples (respiridone ,olanzapine quetiapine ,aripiprazole)
Antipsychotic adverse effects
Antipsychotic adverse effects
- Tardive Dyskinesia (TD)-involuntary muscle movements that may not resolve with drug discontinuation- risk approx. 5% per year
- Neuroleptic Malignant Syndrome (NMS): Characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts. Potentially fatal.
- Extrapyramidal side effects (EPS): Acute dystonia, Parkinson syndrome, Akathisia
Clozapine (Clozaril)
Clozapine (Clozaril)
- Is reserved for treatment resistant patients because of side effect profile but this stuff works!
- Associated with agranulocytosis (0.5-2%) and therefore requires weekly blood draws x 6 months, then Q 2weeks x 6 months)
- Increased risk of seizures (especially if lithium is also on board)
- Associated with the most sedation, weight gain and transaminitis
- Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain