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Updated: Jan 1 2022


  • Snapshot
    • A 23-year-old male is brought into the inpatient psychiatric hospital after a suicide attempt. When talking with the patient he seemed to be responding to internal stimuli at times. He states that he heard voices telling him to kill himself. He said he has heard these voices for over a year now but within the past month they have become louder, more persistent and convincing.
  • Overview
    • 2 classes
      • typical
        • older
        • stronger D2 receptor antagonism 
          • ↑ [cAMP]
      • atypical
        • newer
        • weaker D2 receptor antagonism and stronger 5-HT2, α, and H1 antagonism 
    • Targets
      • dopaminergic neurons
        • specific pathways affected include:
          • nigrostriatal (extrapyramidal motor)
          • mesolimbic (mood and reward)
          • tuberoinfundibular (prolactin release) 
  • Typical Antipsychotics Overview
    • Typical Antipsychotics
      High Potency Antipsychotics (in Descending Order)
      AdvantagesDisadvantagesUnique Features
      Haloperidol •Fewer side effects of sedation and hypotension
        •High association with extrapyramidal symptoms
          •Able to use as long-acting depot injections

          •Can be given IM in acute situations
            Chlorpromazine •Lower frequency of extrapyramidal side effects
              •Greater incidence of anticholinergic side-effects, hypotension, sedation
                •Corneal deposits
                  Thioridazine •Retinal deposits
                  QT prolongation
                • Introduction
                  • Overview
                    • also known as neuroleptics
                    • highly fat soluble results in storage for long time in body fat
                  • Drugs ("haloperidol + -azines")
                    • high potency - low dose needed
                      • haloperidol
                      • trifluoperazine
                      • fluphenazine low potency - high dose needed
                        • thioridazine
                        • chlorpromazine
                  • Clinical uses
                    • schizophrenia
                      • primarily positive symptoms
                    • acute mania
                    • psychosis
                      • temporary treatment because lithium has slow onset
                    • Tourette syndrome
                    • hiccups (persistent > 48 hours and intractable > 1 month)
                      • haloperidol
                      • chlorpromazine 
                  • Toxicity
                    • high potency
                      • ↑ extrapyramidal system (EPS) side effects
                        • due to high affinity for D2 receptor
                        • has characteristic time course
                          • early onset/reversible symptoms
                            • 4 hours = acute dystonia  
                              • spasm of face, neck, tongue, and extraocular muscles
                              • treat with benztropine or diphenhydramine 
                            • 4 days = Parkinsonism
                              • muscle rigidity, ankinesia, tremor, shuffling gait
                            • 4 days to 4 weeks = akathisia 
                              • urge to move
                          • late onset/irreversible symptoms
                            • 4 months = tardive dyskinesia 
                              • involuntary, repetitive movements of facial, tongue, neck muscles
                              • anticholinergics worsen!
                              • must reduce dose or switch to an atypical antipsychotic
                              • can be treated with valbenazine
                                • a vesicular monoamine transporter 2 inhibitor
                      • ↓ non-specific side effects
                      • fluphenazine has been implicated in causing hypothermia in select cases 
                    • low potency
                      • ↓ EPS side effects
                      • ↑ non-specific side effects
                        • due to low affinity to D2 receptors and high concentrations needed to achieve effect
                        • muscarinic receptor antagonism
                          • dry mouth and constipation
                          • vision problems
                        • α receptor antagonism
                          • orthostatic hypotension
                          • sexual dysfunction
                        • histamine receptor antagonism
                          • sedation
                        • chlorpromazine can cause corneal deposits
                        • thioridazine can cause retinal deposits
                    • endocrine side effects
                      • dopamine normally inhibits prolactin secretion
                        • antagonism of receptor may result in hyperprolactinemia can cause galactorrhea 
                    • neuroleptic malignant syndrome (NMS)
                      • presentation
                        • high fever, hypertension, tachycardia, “lead pipe” rigidity, elevated CPK, leukocytosis, metabolic acidosis
                      • treatment 
                        • discontinue offending agent
                        • use of muscle relaxant (e.g., dantrolene)
                • Side Effects of High Potency Antipsychotics
                  • Extrapyramidal Side Effects of High Potency D2 Blockers (Haloperidol, Fluphenazine, Perphenazine)
                    3 Hours: Acute Dystonia
                    3 Days - Weeks: Bradykinesia (Pseudo-Parkinsonism)
                    3 Months: Akathisia
                    3 Years: Tardive Dyskinesia
                    Emergency: Neuroleptic Malignant Syndrome
                    •Muscle spams (neck, eye, diffuse)
                    •Trouble swallowing
                      •Symptoms of Parkinson's disease: tremors, bradykinesia, rigidity
                        •Sustained feeling of motion/restlessness
                          •Uncontrollable repetitive, stereotypical writhing movements, usually of the tongue
                            •High fever
                            •Muscle rigidity
                            •Unstable vitals
                            •Increased CK, K+, and WBC's
                              Treatment of Side Effects
                              •Anticholinergic medications:(benztropine, diphenhydramine, trihexyphenidyl)

                                  •Stop high potency D2 blockers and switch to atypicals (clozapine preferred)
                                  •Can be treated with valbenazine

                                    •Stop antipsychotic
                                    •IV fluids
                                      NOTE: You can always decrease the dose or switch to a different antipsychotic – choose the drug with the side-effect profile that the patient can tolerate.
                                  • Atypical Antipsychotics Overview
                                    • Atypical Antipsychotics
                                      MedicationUnique features and side effects
                                      Risperidone •High potency
                                      •Usually first line
                                      •Weight gain
                                      •Severe weight gain 
                                      •Very sedating
                                      Ziprasidone •Minimal to no weight gain
                                      •Increased QTc
                                      Quetiapine •Low potency
                                      •Weight gain
                                      •Useful in bipolar depression and augmentation of major depression therapy
                                      Lurasidone •Minimal weight gain
                                      •Useful in biploar depression
                                      Clozapine •Weight gain
                                      •Most effective anti-psychotic
                                      •Decreased suicide risk
                                      •Orthostatic hypotension
                                      •Increased seizures
                                      Aripiprazole •D2 partial agonist
                                      •Augmentation of major depression therapy
                                  • Introduction
                                    • Drugs
                                      • olanzapine
                                      • quetiapine
                                      • risperidone
                                      • aripiprazole
                                      • ziprasidone
                                    • Mechanism
                                      • antagonist at 5-HT2, α, H1, and dopamine receptors
                                    • Clinical use
                                      • schizophrenia 
                                        • both positive and negative symptoms
                                      • olanzapine
                                        • OCD
                                        • anxiety disorder
                                        • depression
                                        • mania
                                        • Tourette's syndrome
                                    • Toxicity 
                                      • less EPS and anticholinergic side effects as compared to traditional antipsychotics
                                      • olanzipine
                                        • weight gain
                                          • monitor weight, blood lipids, blood glucose, and HbA1C
                                      • clozapine 
                                        • agranulocytosis 
                                          • requires patients to have weekly WBC monitoring 
                                          • treat with drug cessation, neutropenic protocol, possibily filgrastim
                                        • weight gain
                                      • ziprasidone
                                        • prolonged QT and possible resultant torsades
                                      • risperidone
                                        • EPS
                                        • tardive dyskinesia 
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