Neuroleptic malignant syndrome can occur with any antipsychotic

I. "First-generation"

  1. Specific drugs
    1. Chlorpromazine (Thorazine)
    2. Fluphenazine (Prolixin)
    3. Haloperidol (Haldol)
    4. Perphenazine (Trilafon)
    5. Thioridazine (Mellaril)
    6. Thiothixene (Navane)
    7. Trifluoperazine (Stelazine)

II. "Second-generation"

  1. Less likely to cause extrapyramidal effects than first-generation:
    1. Dystonia
    2. Akasthisia
    3. Parksinonism
  2. Less likely to cause tardive dyskinesia than first-generation
    1. In elderly pts, tardive dyskinesia more common in pts with depression than with primary degenerative dementia or delusional disorder; age doesn't seem to predispose to TD (Am. J. Psych, 149:1206, 9/92)
  3. Less likely to cause hyperprolactinemia than first-generation (except for risperdone
  4. Other adverse effects of 2nd-generation antipsychotics
    1. Clozapine causes agranulocytosis in 1% of pts and weekly WBC monitoring is suggested
    2. Use of clozapine or olanzapine ass'd with HR 1.57 (sig.) for Diabetes Mellitus vs. first-generation antipsychotics one a retrospective study (Am. J. Psychiat. 161:1709, 2004--JW)
  5. More effective at treating "negative" sx of schizophrenia than first-generation:
    1. Apathy
    2. Social withdrawal
    3. Flat affect
    4. Impoverished speech
  6. Specific drugs
    1. Aripiprazole (Abilify)-Little to no effect on weight; can cause insomnia, constipation, dizziness, and akasthisia
    2. Clozapine (Clozaril)-Can cause agranulocytosis, requires Q1-2wk CBC's; also dose-related sz in 1-4% of pts; also sedation, weight gain, DM,  dyslipidemia, increased salivation, and bedwetting; rarely, myocarditis
    3. Olanzapine (Zyprexa)-Can cause sedation, weight gain, DM, dyslipidemia, dizziness, and constipation
    4. Quetiapine (Seroquel)-Can cause sedation, dizziness, constipation, and DM; less weight gain than clozapine or olanzapine
    5. Risperidone (Risperdal)-Can cause weight gain, dizziness, and constipation, and hyperprolactinemia; less likely than Olanzapine or Clozapine to cause DM but more likely to cause extrapyramidal sx than olanzapine.
    6. Ziprasidone (Geodon)-Weight gain is rare; can cause sedation, QT interval prolongation (but no reports of torsades), and extrapyramidal sx in 5%
    7. Lurasidone (Latuda) 40-80mg QD with food (max 40mg if renal or hepatic impairment)
III. Comparisons among antipsychotic drugs
  1. In a meta-analysis, clozapine found to be sig. more efficacious than other 2nd-generation drugs; risperdone & olanzapine were not as efficacious but better than the other 3; the other 3 were not sig. more efficacious than first-generation drugs (Arch. Gen. Psychiat. 60:553, 2003, cited in Med. Lett. 45:102, 2003)
  2. In a study in 1,493 pts with schizophrenia randomized to perphenazine vs. olanzapine, quetiapine, risperidone, or ziprasidone x 18mos, the incidence of drug discontinuation was sig. lower in olanzapine group (64%) than in the other groups (74-82%) (NEJM 353:1209, 2005--JW)