First-generation antipsychotics

Meet the patient

A 19-year-old man, first episode of psychosis, was given intramuscular haloperidol twice overnight in the emergency department. At the 8am ward round his head is pulled hard to the left and his eyes are locked upward. He is terrified and he cannot tell you why, because his jaw will not close.^[13][3]

The intern has written "bizarre posturing, query catatonia" in the notes and asked for a psychiatry opinion later that morning.^[13]

Two questions are live and both are timed: what is this and what do you give in the next five minutes?, and why was a high-potency FGA the first choice in a drug-naive teenager at all? Everything below answers those two.^[13][3]

FGAs are a high-yield fellowship monograph because examiners test class literacy, landmark comparative effectiveness, receptor-to-side-effect mapping, and emergency EPS and NMS management in a single station. CATIE and CUtLASS dismantled the myth that every SGA is always superior; EUFEST shows first-episode patients tolerate low-dose high-potency FGA poorly; Carbon's meta-analyses quantify the tardive differential; TRRIP stops endless FGA switches in treatment resistance.^{[1][2][3][8][9][12]}

References16ShowHide

1. [1]Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia N Engl J Med, 2005.PMID 16172203
2. [2]Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1) Arch Gen Psychiatry, 2006.PMID 17015810
3. [3]Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial Lancet, 2008.PMID 18374841
4. [4]Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis Lancet, 2013.PMID 23810019
5. [5]Howes OD, Kapur S The dopamine hypothesis of schizophrenia: version III--the final common pathway Schizophr Bull, 2009.PMID 19325164
6. [6]Kapur S, Seeman P Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis Am J Psychiatry, 2001.PMID 11229973
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8. [8]Carbon M, Hsieh CH, Kane JM, Correll CU Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use: A Meta-Analysis J Clin Psychiatry, 2017.PMID 28146614
9. [9]Carbon M, Kane JM, Leucht S, Correll CU Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis World Psychiatry, 2018.PMID 30192088
10. [10]Barnes TR A rating scale for drug-induced akathisia Br J Psychiatry, 1989.PMID 2574607
11. [11]Solmi M, Pigato G, Kane JM, Correll CU Clinical risk factors for the development of tardive dyskinesia J Neurol Sci, 2018.PMID 29439776
12. [12]Howes OD, McCutcheon R, Agid O, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology Am J Psychiatry, 2017.PMID 27919182
13. [13]Ward KM, Citrome L Antipsychotic-Related Movement Disorders: Drug-Induced Parkinsonism vs. Tardive Dyskinesia-Key Differences in Pathophysiology and Clinical Management Neurol Ther, 2018.PMID 30027457
14. [14]Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia Am J Psychiatry, 2011.PMID 21362741
15. [15]Schooler NR, Kane JM Research diagnoses for tardive dyskinesia Arch Gen Psychiatry, 1982.PMID 6121550
16. [16]Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 Pharmacopsychiatry, 2018.PMID 29390205