Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 143 No. 2728 (2013)

Age and adverse drug reactions from psychopharmacological treatment

  • Waldemar Greil
  • Anne Häberle
  • Thomas Schuhmann
  • Renate Grohmann
  • Pierre Baumann
DOI
https://doi.org/10.4414/smw.2013.13772
Cite this as:
Swiss Med Wkly. 2013;143:w13772
Published
30.06.2013

Abstract

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years.

METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP.

RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients’ age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions.

CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

References

  1. Alexopoulos GS. Using Antipsychotic Agents in Older Patients: Introduction: Methods, Commentary, and Summary. J Clin Psychiat. 2004;65:5–20.
  2. Consensus Group: Using Antipsychotic Agents in Older Patients: Indication for Using Antipsychotics in Older Patients. J Clin Psychiat. 2004;65:21–41.
  3. Fenn HH, Sommer BR, Ketter TA, Alldredge B. Safety and tolerability of mood-stabilising anticonvulsants in the elderly. Expert Opin Drug Saf. 2006;5:401–16.
  4. Curran S, Turner D, Musa S, Wattis J. Psychotropic drug use in older people with mental illness with particular reference to antipsychotics: a systematic study of tolerability and use in different diagnostic groups. Int J Geriatr Psychiatry. 2005;20:842–7.
  5. Sajatovic M, Gildengers A, Al Jurdi RK, Gyulai L, Cassidy KA, Greenberg RL, et al. Multisite, open-label, prospective trial of lamotrigine for geriatric bipolar depression: a preliminary report. Bipolar Disord. 2011;13:294–302.
  6. Ciudad A, Montes JM, Olivares JM, Gomez JC. Safety and tolerability of olanzapine compared with other antipsychotics in the treatment of elderly patients with schizophrenia: a naturalistic study. Eur Psychiatry. 2004;19:358–65.
  7. Rainer M, Haushofer M, Pfolz H, Struhal C, Wick W. Quetiapine versus risperidone in elderly patients with behavioural and psychological symptoms of dementia: efficacy, safety and cognitive function. Eur Psychiatry. 2007;22:395–403.
  8. Sajatovic M, Coconcea N, Ignacio RV, Blow FC, Hays RW, Cassidy KA, et al. Adjunct extended-release valproate semisodium in late life schizophrenia. Int J Geriatr Psychiatry. 2008;23:142–7.
  9. Grohmann R, Engel RR, Rüther E, Hippius H. The AMSP drug safety program: methods and global results. Pharmacopsychiatry. 2004;37(Suppl 1):S4–S11.
  10. Lange-Asschenfeldt C, Grohmann R, Lange-Asschenfeldt B, Engel RR, Rüther E, Cordes J. Cutaneous adverse reactions to psychotropic drugs: data from a multicenter surveillance program. J Clin Psychiatry. 2009;70:1258–65.
  11. Stübner S, Grohmann R, von Stralendorff I, Rüther E, Möller HJ, Müller-Oerlinghausen B, et al. Suicidality as Rare Adverse Event of Antidepressant Medication: Report from the AMSP Multicenter Drug Safety Surveillance Project. J Clin Psychiat. 2010;71:1293–307.
  12. Moore TJ, Cohen MR, Furberg CD. Serious Adverse Drug Events Reported to the Food and Drug Administration, 1998–2005. Arch Internal Med. 2007;167:1752–9.
  13. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934;26:404–13.
  14. Barr AM, Honer WG, Williams G, Johnson JL, Wu TKY, Procyshyn RM. A comparison of antipsychotic drug-defined daily doses versus chlorpromazine equivalent doses in patients with or without extrapyramidal motor symptoms. J Clin Psychopharmacol. 2010;30:741–3.
  15. Wong IC, Mawer GE, Sander JW. Factors influencing the incidence of lamotrigine-related skin rash. Ann Pharmacother. 1999;33:1037–42.
  16. Malik S, Arif H, Hirsch LJ. Lamotrigine and its applications in the treatment of epilepsy and other neurological and psychiatric disorders. Expert Rev Neurother. 2006;6:1609–27.
  17. Henderson DC, Nguyen DD, Copeland PM, Hayden DL, Borba CP, Louie PM, et al. Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study. J Clin Psychiatry. 2005;66:1116–21.
  18. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry. 1994;151:825–35.
  19. de Leon L, Diaz FJ, Josiassen RC, Cooper TB, Simpson GM. Weight gain during a double-blind multidosage clozapine study. J Clin Psychopharmacol. 2007;27:22–7.
  20. Kinon BJ, Volavka J, Stauffer V, Edwards SE, Liu-Seifert H, Chen L, et al. Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study. J Clin Psychopharmacol. 2008;28:392–400.
  21. Simon GE, Von Korff M, Saunders K, Miglioretti DL, Crane PK, van Belle G, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63:824–30.
  22. Bender S, Grohmann R, Engel RR, Degner D, Dittmann-Balcar A, Rüther E. Severe adverse drug reactions in psychiatric inpatients treated with neuroleptics. Pharmacopsychiatry. 2004;37(Suppl 1):S46–S53.
  23. Gaertner HJ, Fischer E, Hoss J. Side effects of clozapine. Psychopharmacology. (Berl) 1989;99(Suppl):S97–100.
  24. Hummer M, Kurz M, Kurzthaler I, Oberbauer H, Miller C, Fleischhacker WW. Hepatotoxicity of clozapine. J Clin Psychopharmacol. 1997;17:314–7.
  25. Gaertner I, Altendorf K, Batra A, Gaertner HJ. Relevance of liver enzyme elevations with four different neuroleptics: a retrospective review of 7,263 treatment courses. J Clin Psychopharmacol. 2001;21:215–22.
  26. Kelly DL, Conley RR, Richardson CM, Tamminga CA, Carpenter WT, Jr.: Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine in treatment-resistant schizophrenia. Ann Clin Psychiatry. 2003;15:181–6.
  27. Kurz M, Hummer M, Oberbauer H, Fleischhacker WW. Extrapyramidal side effects of clozapine and haloperidol. Psychopharmacology. (Berl) 1995;118:52–6.
  28. Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, et al. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol. 2003;6:325–37.
  29. Crossley NA, Constante M, McGuire P, Power P. Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry. 2010;196:434–9.
  30. Meltzer HY, Bobo WV, Roy A, Jayathilake K, Chen Y, Ertugrul A, et al. A randomized, double-blind comparison of clozapine and high-dose olanzapine in treatment-resistant patients with schizophrenia. J Clin Psychiatry. 2008;69:274–85.
  31. Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F, et al. A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia. Am J Psychiatry. 2009;166:152–63.
  32. Lindenmayer JP, Khan A, Iskander A, Abad MT, Parker B. A randomized controlled trial of olanzapine versus haloperidol in the treatment of primary negative symptoms and neurocognitive deficits in schizophrenia. J Clin Psychiatry. 2007;68:368–79.
  33. Choong E, Bondolfi G, Etter M, Jermann F, Aubry JM, Bartolomei J, et al. Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population. J Psychiatr Res. 2012;46:540–8.
  34. Degner D, Grohmann R, Kropp S, Rüther E, Bender S, Engel RR, et al. Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. Pharmacopsychiatry. 2004;37(Suppl 1):S39–S45.
  35. Preskorn SH, Jerkovich GS. Central nervous system toxicity of tricyclic antidepressants: phenomenology, course, risk factors, and role of therapeutic drug monitoring. J Clin Psychopharmacol. 1990;10:88–95.
  36. Peretti S, Judge R, Hindmarch I. Safety and tolerability considerations: tricyclic antidepressants vs. selective serotonin reuptake inhibitors. Acta Psychiatr Scand Suppl. 2000;403:17-25.
  37. Bezchlibnyk-Butler K, Aleksic I, Kennedy SH. Citalopram – a review of pharmacological and clinical effects. J Psychiatry Neurosci. 2000;25:241–54.
  38. Llorca PM, Fernandez JL. Escitalopram in the treatment of major depressive disorder: clinical efficacy, tolerability and cost-effectiveness vs. venlafaxine extended-release formulation. Int J Clin Pract. 2007;61(4):702–10.
  39. Garnock-Jones KP, McCormack PL. Escitalopram: a review of its use in the management of major depressive disorder in adults. CNS Drugs. 2010;24:769–96.
  40. Arif H, Buchsbaum R, Weintraub D, Koyfman S, Salas-Humara C, Bazil CW, et al. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology. 2007;68:1701–9.
  41. Yang CY, Dao RL, Lee TJ, Lu CW, Yang CH, Hung SI, et al. Severe cutaneous adverse reactions to antiepileptic drugs in Asians. Neurology. 2011;77:2025–33.
  42. Kumra S, Oberstar JV, Sikich L, Findling RL, McClellan JM, Vinogradov S, et al. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull. 2008;34:60–71.
  43. Lewis R. Typical and atypical antipsychotics in adolescent schizophrenia: efficacy, tolerability, and differential sensitivity to extrapyramidal symptoms. Can J Psychiatry. 1998;43:596–604.
  44. Sajatovic M, Ramsay E, Nanry K, Thompson T. Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia. Int J Geriatr Psychiatry. 2007;22:945–50.
  45. Kando JC, Tohen M, Castillo J, Zarate CA, Jr. The use of valproate in an elderly population with affective symptoms. J Clin Psychiatry. 1996;57:238–40.
  46. Arif H, Svoronos A, Resor SR, Jr., Buchsbaum R, Hirsch LJ. The effect of age and comedication on lamotrigine clearance, tolerability, and efficacy. Epilepsia. 2011;52:1905–13.
  47. Madhusoodanan S, Brenner R, Suresh P, Concepcion NM, Florita CD, Menon G, et al. Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study. Ann Clin Psychiatry. 2000;12:11–8.
  48. Kisely S, Cox M, Campbell LA, Cooke C, Gardner D. An epidemiologic study of psychotropic medication and obesity-related chronic illnesses in older psychiatric patients. Can J Psychiatry. 2009;54:269–74.