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52 - References

References

50 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 1 alternative to SGAs where SGAs are poorly tolerated (usually because of metabolic changes) or where FGAs are preferred by patients themselves. Some FGAs may be less effective than some non-­clozapine SGAs (amisulpride, olanzapine and risperidone may be slightly more efficacious)4,5 but any differences in therapeutic efficacy seem to be modest. Two large, independent and pragmatic studies, CATIE6 and CUtLASS,7 found few important differences between SGAs and FGAs (mainly perphenazine and sulpiride, respectively). The main drawbacks of FGAs are acute EPS, hyperprolactinaemia and TD. Hyperprolactinaemia is probably unavoidable in practice because the dose that achieves efficacy is too close to the dose that causes hyperprolactinaemia. Even when not symptomatic, hyperprolactinaemia may grossly affect hypothalamic function.8 Raised prolactin is also associated with sexual dysfunction,9 as are the autonomic effects of some SGAs.10 Notably, some SGAs (risperidone, paliperidone, amisulpride) increase prolactin to a greater extent than FGAs.11 All FGAs are potent dopamine antagonists, which are liable to induce dysphoria.12 Perhaps as a consequence, some FGAs may produce smaller benefits in quality of life than some SGAs.6 Tardive dyskinesia very probably occurs more frequently with FGAs than SGAs13–16 (notwithstanding difficulties in defining what is ‘atypical’), although there remains some uncertainty16–18 and the dose of FGA used is a crucial factor.19 A complicating aspect is the occurrence of TD in untreated schizophrenia,20 which may mean that antipsychotics do not necessarily cause TD but simply fail to suppress it to varying degrees. Among SGAs, partial agonists may have the lowest risk of TD.21 Careful observation of patients and the prescribing of the lowest effective dose are essential to help reduce the risk of this serious adverse event.22,23 Even with these precautions, the risk of TD with some FGAs may be unacceptably high.24 A good example of the relative merits of SGAs and a carefully dosed FGA comes from a trial comparing paliperidone palmitate with low-­dose haloperidol decanoate.25 Paliperidone produced more weight gain and prolactin change but haloperidol was associated with significantly more frequent akathisia and parkinsonism, and, numerically, a higher incidence of TD. Efficacy was identical. References

  1. Blier P, et al. Progress on the Neuroscience-­Based Nomenclature (NbN) for psychotropic medications. Neuropsychopharmacology 2017; 42:1927–1928.
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  3. McCutcheon RA, et  al. Data-­driven taxonomy for antipsychotic medication: a new classification system. Biol Psychiatry 2023; 94:561–568.
  4. Davis JM, et al. A meta-­analysis of the efficacy of second-­generation antipsychotics. Arch Gen Psychiatry 2003; 60:553–564.
  5. Leucht S, et al. Second-­generation versus first-­generation antipsychotic drugs for schizophrenia: a meta-­analysis. Lancet 2009; 373:31–41.
  6. Grunder G, et al. Effects of first-­generation antipsychotics versus second-­generation antipsychotics on quality of life in schizophrenia: a double-­blind, randomised study. Lancet Psychiatry 2016; 3:717–729.
  7. Jones PB, 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; 63:1079–1087.
  8. Smith S, et al. The effects of antipsychotic-­induced hyperprolactinaemia on the hypothalamic-­pituitary-­gonadal axis. J Clin Psychopharmacol 2002; 22:109–114.
  9. Smith SM, et al. Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 2002; 181:49–55.
  10. Aizenberg D, et al. Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapine. J Clin Psychiatry 2001; 62:541–544.
  11. Leucht S, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-­treatments meta-­analysis. Lancet 2013; 382:951–962.

Schizophrenia and related psychoses CHAPTER 1 12. King DJ, et al. Antipsychotic drug-­induced dysphoria. Br J Psychiatry 1995; 167:480–482. 13. Tollefson GD, et al. Blind, controlled, long-­term study of the comparative incidence of treatment-­emergent tardive dyskinesia with olanzapine or haloperidol. Am J Psychiatry 1997; 154:1248–1254. 14. Beasley C, et al. Randomised double-­blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-­term treatment with olanzapine or haloperidol. Br J Psychiatry 1999; 174:23–30. 15. Correll CU, et al. Lower risk for tardive dyskinesia associated with second-­generation antipsychotics: a systematic review of 1-­year studies. Am J Psychiatry 2004; 161:414–425. 16. Novick D, et al. Tolerability of outpatient antipsychotic treatment: 36-­month results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study. Eur Neuropsychopharmacol 2009; 19:542–550. 17. Halliday J, et al. Nithsdale Schizophrenia Surveys 23: movement disorders. 20-­year review. Br J Psychiatry 2002; 181:422–427. 18. Miller DD, et al. Extrapyramidal side-­effects of antipsychotics in a randomised trial. Br J Psychiatry 2008; 193:279–288. 19. Takeuchi H, et al. Pathophysiology, prognosis and treatment of tardive dyskinesia. Ther Adv Psychopharmacol 2022; 12:20451253221117313. 20. Kalniunas A, et  al. Prevalence of spontaneous movement disorders (dyskinesia, parkinsonism, akathisia and dystonia) in never-­treated patients with chronic and first-­episode psychosis: a systematic review and meta-­analysis. BMJ Ment Health 2024; 27:e301184. 21. Carbon M, et al. Tardive dyskinesia prevalence in the period of second-­generation antipsychotic use: a meta-­analysis. J Clin Psychiatry 2017; 78:e264–e278. 22. Jeste DV, et al. Tardive dyskinesia. Schizophr Bull 1993; 19:303–315. 23. Cavallaro R, et al. Recognition, avoidance, and management of antipsychotic-­induced tardive dyskinesia. CNS Drugs 1995; 4:278–293. 24. Oosthuizen P, et al. A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-­episode psychosis. Int J Neuropsychopharmacol 2004; 7:125–131. 25. McEvoy JP, et al. Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial. JAMA 2014; 311:1978–1987.

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