Pharmacology of antipsychotics
(dopamine blockers)

Haloperidol, a typical antipsychotic



Major side effects

There are two major side effect problems with atypical neuroleptics: metabolic syndrome and extrapyramidal syndrome (EPS).  We have discussed the main EPS here.

Regarding metabolic syndrome, the agents most associated with this outcome are clozapine, olanzapine, and quetiapine, with a smaller risk for risperidone.  Ziprasidone and aripiprazole do not appear to have this risk, nor do any of the three newest agents (lurasidone, Latuda; iloperidone, Fanapt; and asenapine, Saphris).  Nonetheless, despite the scientific inaccuracy of stating that they all are similar in risk, the FDA has put a black box warning on all drugs in this class for potential risk of diabetes and lipid abnormalities.  

Weight gain is not the same as metabolic syndrome

It is important to note that the risk of metabolic syndrome is independent of weight gain, although obviously if there is weight gain,  there will also be an even higher risk of metabolic syndrome. Thus, for instance, divalproex causes weight gain, but does NOT directly cause metabolic syndrome: in fact, it improves cholesterol and lipid profiles.  

Other side effects

Antipsychotics (dopamine blockers) differ in other side effects besides EPS and weight gain and metabolic syndrome. Clozapine has a serious risk of seizures and agranulocytosis, requiring weekly or biweekly blood monitoring.  Risperidone is associated with prolactin elevation; while this effect is common at the laboratory level, clinically-associated side effects are infrequent (5-10% of patients; mainly galactorrhea, amenorrhea, or sexual dysfunction).  This effect is most relevant to postmenopausal or dysmenorrheic women, where prolactin elevation is associated with increased risk of osteoporosis.  Ziprasidone is associated with prolongation of the QT interval on the EKG to a greater extent than other atypical neuroleptics, though less so than some traditional neuroleptics. In cases where cardiac history is present, baseline EKGs are prudent.

Dosing

Typical effective doses of newer agents for schizophrenia is provided here. For bipolar illness or depression, about half these doses should be used.

  • Clozapine (Clozaril) and Quetiapine (Seroquel) 300-400 mg/d
  • Olanzapine (Zyprexa) 10-20 mg/d
  • Risperidone (Risperdal) 3-6 mg/d
  • Aripiprazole (Abilify) 10-30 mg/d
  • Ziprasidone (Geodon) 80-160 mg/d
  • Asenapine (Saphris) 10-30 mg/d
  • Iloperidone (Fanapt) 3-12 mg/d
  • Lurasidone (Latuda) 40-80 mg/d

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