Subjective Well-being and Initial Dysphoric Reaction under Antipsychotic Drugs - Concepts, Measurement and Clinical Relevance

Since the introduction of neuroleptics in 1952, many studies have examined objective aspects of efficacy and tolerability. Despite the fact that neuroleptic treatment should also improve the patient’s subjective experiences, this outcome criterion has been neglected in the past. This is unfortunate, as subjective well-being with treatment appears to be strongly related to patients’ readiness to take their medication. The few existing studies differ in methodology and are difficult to compare due to a number of weaknesses, including varying underlying concepts, used assessment scales, or small sample sizes. Negative subjective well-being may manifest itself throughout the entire neuroleptic treatment, even as early as in the first 48 hours after neuroleptic treatment starts (initial dysphoric reaction, IDR). The aetiology of reduced subjective well-being or IDR is not fully explained; neuroleptic side effects, especially affective, cognitive and motor adverse events, differential effects of varying psychopathology or biopsychosocial are factors in discussion. The clinical impression is characterised by symptoms as dysphoria/anhedonia, reduced vitality, and emotional indifference, which could have a negative impact on relevant clinical factors such as response or medication adherence, and therefore on outcome. With regard to pharmacological treatment, evidence suggests that atypical antipsychotics induce less negative subjective effects than conventional neuroleptics, and that various new-generation antipsychotics could be evaluated differently by patients. This article reviews existing literature in order to approach relevant questions for pharmacotherapy.

Key words

Schizophrenia - subjective well-being - initial dysphoric reaction - typical and atypical antipsychotics

References

• 1 Agarwal M R, Sharma V K, Kishore Kumar K V, Lowe D. Non-compliance with treatment in patients suffering from schizophrenia: a study to evaluate possible contributing factors.  Int J Soc Psychiatry.. 1998;  44(2) 92-106
• 2 Allan E R, Sison C E, Alpert M, Connolly B, Crichton J. The relationship between negative symptoms of schizophrenia and extrapyramidal side effects with haloperidol and olanzapine.  Psychopharmacol Bull. 1998;  34(1) 71-74
• 3 Allison D B, Mackell J A, McDonnell D D. The impact of weight gain on quality of life among persons with schizophrenia.  Psychiatr Serv. 2003;  54(4) 565-7
• 4 Awad A G. Subjective response to neuroleptics in schizophrenia.  Schizophr Bull. 1993;  19 609-618
• 5 Awad A G, Hogan T P. Subjective response to neuroleptics and the quality of life: implications for treatment outcome.  Acta Psychiatr Scand. 1994;  89 (suppl 380) 27-32
• 6 Awad A G, Hogan T P, Voruganti L N, Heslegrave R J. Patients’ subjective experiences on antipsychotic medications: implications for outcome and quality of life.  Int Clin Psychopharmacol. 1995;  10 Suppl 3 123-32
• 7 Awad A G. Antipsychotic medications in schizophrenia: How satisfies are our patients? Management Issues in Schizophrenia: Patient satisfaction, compliance and outcomes in schizophrenia.  Clear Perspectives. 1999;  2(3) 1-6
• 8 Ayers T, Liberman R P, Wallace C J. Subjective response to antipsychotic drugs: failure to replicate predictions of outcome.  J Clin Psychopharmacol. 1984;  4(2) 89-93
• 9 Bartko G, Herczeg I, Bekesy M. Predicting outcome of neuroleptic treatment on the basis of subjective response and early clinical improvement.  J Clin Psychiatry. 1987;  48(9) 363-5
• 10 Belmaker R, Wald D. Haloperidol in normals.  Br J Psychiatry. 1977;  131 222-223
• 11 Bergner M, Bobbitt R A, Carter W B, Gilson B S. The Sickness Impact Profile: development and final revision of a health status measure.  Med Care. 1981;  19(8) 787-805
• 12 Bilder R M. Neurocognitive impairment in schizophrenia and how it affects treatment options.  Can J Psychiatry. 1997;  42 255-264
• 13 Bressan R A, Costa D C, Jones H M, Ell P J, Pilowsky L S. Typical antipsychotic drugs - D(2) receptor occupancy and depressive symptoms in schizophrenia.  Schizophr Res. 2002;  56(1 - 2) 31-6
• 14 Browne S, Roe M, Lane A, Gervin M, Kinsella A, Larkin C, O’Callaghan E. Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.  Acta Psychiatr Scand. 1996;  94 118-124
• 15 Browne S, Garavan J, Gervin M, Roe M, Larkin C, O’Callaghan E. Quality of life in schizophrenia: insight and subjective response to neuroleptics.  J Nerv Ment Dis.. 1998;  186 74-8
• 16 Bullinger-Naber M, Naber D. Assessing the quality of life in mental illness. In: Henn FA, Sartorius N, Helmchen H, Lauter H (eds.) Contemporary Psychiatry. 2001 Vol 1: pp. 135-150 Foundation of Psychiatry
• 17 Cabeza I G, Amador M S, Lopez C A, Gonzalez de Chavez M. Subjective response to antipsychotics in schizophrenic patients: clinical implications and related factors.  Schizophr Res 2000;. 21;  41(2) 349-55
• 18 Carpenter W T, Heinrichs D W, Wagman A. Deficit and Nondeficit Forms of Schizophrenia: The Concept.  Am J Psychiatry. 1988;  145 578-583
• 19 Craig T J, Richardson M A, Pass R and Bregman Z. Measurement of mood and effect in schizophrenic inpatients.  Am J Psychiatry. 1985;  142 1272-1277
• 20 Day J C, Kinderman P, Bentall R. A comparison of patients’ and prescribers’ beliefs about neuroleptic side effects: prevalence, distress and causation.  Acta Psychiatr Scand. 1998;  97(1) 93-7
• 21 De Haan L, Lavalaye J, Linszen D, Dingemans P, Booji J. Subjective Experience and Striatal Dopamine D(2) Receptor Occupancy in Patients With Schizophrenia Stabilized by Olanzapine or Risperidone.  Am J Psychiatry. 2000;  157(6) 1019-1020
• 22 De Haan L. Subjective experiences of patients with schizophrenia related to antipsychotic medication. In: de Haan L Patients’ perspectives, subjective experiences and attitudes of patients with recent onset schizophrenia. Thesis. University of Amsterdam 2001: pp. 105-114
• 23 De Haan L, Weisfelt M, Dingemans P M, Linszen D H, Wouters L. Psychometric properties of the Subjective Well-Being Under Neuroleptics scale and the Subjective Deficit Syndrome Scale.  Psychopharmacology (Berl). 2002;  162(1) 24-8
• 24 Donohoe G, Owens N, O’Donnell C, Burke T, Moore L, Tobin A, O’Callaghan E. Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: a discriminant function analysis.  Eur Psychiatry. 1997;  16(5) 293-298
• 25 Doyle M, Flanagan S, Browne S, Clarke M, Lydon D, Larkin C, O’Callaghan E. Subjective and external assessments of quality of life in schizophrenia: relationship to insight.  Acta Psychiatr Scand. 1999;  99(6) 466-72
• 26 Emerich D, Sanberg P. Neuroleptic dysphoria.  Biol Psychiatry. 1991;  29 201-203
• 27 Gaebel W, Pietzcker A, Ulrich G, Schley J, Müller-Oerlinghausen B. Predictors of neuroleptic treatment response in acute schizophrenia: Results of a treatment study with perazine.  Pharmacopsychiat. 1988;  21 384-386
• 28 Garavan J, Browne S, Gervin M, Lane A, Larkin C, O’Callaghan E. Compliance with neuroleptic medication in outpatients with schizophrenia; relationship to subjective response to neuroleptics; attitudes to medication and insight.  Compr Psychiatry.. 1998;  39(4) 215-9
• 29 Gebhardt R. Veränderungen der subjektiven Befindlichkeit psychotischer Patienten unter neuroleptischer Therapie.  Pharmacopsychiatry. 1972;  5 295-300
• 30 Gerlach J, Larsen E B. Subjective experience and mental side effects of antipsychotic treatment.  Acta Psychiatr Scand. 1999;  99(suppl 395) 113-117
• 31 Gervin M, Browne J, Garavan M, Roe C, Larkin C, Callaghan O. Dysphoric subjective response to neuroleptics in schizophrenia: relationship to extrapyramidal side effects and symptomatology.  Eur Psychiatry. 1999;  14 405-409
• 32 Giner J, Ibanez E, Cervera S, Sanmartin A, Caballero R. Subjective experience and quality of life in schizophrenia.  Actas Esp Psiquiatr. 2001;  29(4) 233-42
• 33 Gruber O, Northoff G, Pflug B. Subjective experiences of patients with acute neuroleptic-induced akathisia.  Fortschr Neurol Psychiatr.. 1998;  66(12) 531-8
• 34 Heinrichs D W, Hanlon T E, Carpenter WT J r. The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome.  Schizophr Bull. 1984;  10(3) 388-98
• 35 Hellewell J S. Patients’ subjective experiences of antipsychotics: clinical relevance.  CNS Drugs.. 2002;  16(7) 457-71
• 36 Hofer A, Kemmler G, Eder U, Honeder M, Hummer M, Fleischhacker W W. Attitudes toward antipsychotics among outpatient clinic attendees with schizophrenia.  J Clin Psychiatry. 2002;  63(1) 49-53
• 37 Hogan T, Awad A, Eastwood R. A self-report scale predictive of drug compliance in schizophrenics: Reliability and discriminative validity.  Psychol Med. 1983;  13 177-183
• 38 Hogan T P, Awad A G, Eastwood R. Early subjective response and prediction of outcome to neuroleptic drug therapy in schizophrenia.  Can J Psychiatry. 1985;  30 246-248
• 39 Hogan T, Awad A. Subjective response to neuroleptics and outcome in schizophrenia: a re-examination comparing two measures.  Psychol Med. 1992;  22 347-352
• 40 Jaeger J, Bitter I, Czobor P, Volovka J. The maesurement of subjective experience in schizophrenia: The subjective deficit syndrome scale.  Compr Psych. 1990;  31 216-226
• 41 Jarema M, Murawiec S, Szafranski T, Szaniawska A, Konieczynska Z. Subjective and objective evaluation of treating schizophrenia with classic or atypical drugs.  Psychiatr Pol.. 2001;  35(1) 5-19
• 42 Kampman O, Lehtinen K, Lassila V, Leinonen E, Poutanen O, Koivisto A. Attitudes towards neuroleptic treatment: reliability and validity of the attitudes towards neuroleptic treatment (ANT) questionnaire.  Schizophr Res. 2000;  45 223-34
• 43 Kaneda Y. The impact of prolactin elevation with antipsychotic medications on subjective quality of life in patients with schizophrenia.  Clin Neuropharmacol. 2003;  26(4) 182-4
• 44 Karow A, Naber D. Subjective well-being and quality of life under atypical antipsychotic treatment.  Psychopharmacology (Berl).. 2002;  162(1) 3-10
• 45 Karow A, Moritz S, Lambert M, Krausz M. The influence of psychopathology on subjective quality of life in acute and stabilized schizophrenic patients. Compr Psychiatry, submitted
• 46 Knudstorp T B, Gerlach J. Quality of Life (QoL) in chronic schizophrenic patients related to symptoms, side effects and subjective distress. Poster presented XI World Congress of Psychiatry 1999 Hamburg Germany;
• 47 Lacro J P, Dunn L B, Dolder C R, Leckband S G, Jeste D V. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature.  J Clin Psychiatry. 2002;  63(10) 892-909
• 48 Lader M. Neuroleptic induced deficit syndrome: old problem, new challenge.  J Psychopharmacol. 1993;  7 392-393
• 49 Lambert M, Graf Schimmelmann B, Haasen C, Naber D. Subjective well being under neuroleptic treatment - relevant for the psychopharmacotherapy of schizophrenic patients?.  Psychopharmakotherapie. 2002;  2 53-59, Review, German
• 50 Lambert M, Conus P, Eide P, Karow A, Krausz M, Naber D. Impact of present and past side effects on the attitude towards typical antipsychotic treatment. Eur Psychiatry, submitted
• 51 Lewander T. Neuroleptics and the neuroleptic-induced deficit syndrome.  Acta Psychiatr Scand. 1994;  suppl 380 8-13
• 52 Lindström L H. Long-term clinical and social outcome studies in schizophrenia in relation to the cognitive and emotional side effects of antipsychotic drugs.  Acta Psychiatr Scand. 1994;  suppl 380 74-76
• 53 May P RA, Van Putten T, Yale C, Potepan P, Jenden D J, Fairchild M D, Goldstein M J, Dixon W J. Predicting individuel responses to drug treatment in schizophrenia: A test dose model.  J Nerv Ment Dis. 1976;  162 177-183
• 54 Meltzer H Y, Burnett S, Bastani B, Ramirez L F. Effects of six months of clozapine treatment on the quality of life of chronic schizophrenic patients.  Hospital Community Psychiatry. 1990;  41 892-897
• 55 Mitchell R, Connell J, Van F, Elliott R, Woodruff P WR, Deakin J FW. The effects of haloperidol on cognitive processes in healthy volunteers.  Schizophr Res. 2000;  41(1) B115
• 56 Naber D. A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables.  International Clinical Psychopharmacology. 1995;  10 (suppl 3) 133-138
• 57 Naber D, Moritz S, Lambert M, Pajonk F G, Holzbach R, Mass R, Andresen B, Rajonk F. Improvement of schizophrenic patients’ subjective well-being under atypical antipsychotic drugs.  Schizophr Res. 2001;  50(1 - 2) 79-88
• 58 Naber D, Riedel M, Klimke A, Vorbach E U, Lambert M, Kühn K U, Bender S, Bandelow B, Lemmer W, Moritz S, Dittmann R W. Randomized Double Blind Comparison of Olanzapine and Clozapine on Subjective Well-Being and Clinical Outcome in Patients with Schizophrenia. Arch Gen Psychiatry submitted
• 59 Noll R L, Hoenkamp E, Nolen W A. Subjectieve bijwerkingen van neuroleptics.  Nederlands Tijdschrift voor Geneeskunde. 1991;  135 2113-2116
• 60 Norman R M, Malla A K, McLean T, Voruganti L P, Cortese L, McIntosh E, Cheng S, Rickwood A. The relationship of symptoms and level of functioning in schizophrenia to general wellbeing and the Quality of Life Scale.  Acta Psychiatr Scand. 2000;  102(4) 303-9
• 61 Pi E, Sramek J, Johnson T, Herrera J, Heh C, Costa J, Cutler N, Ananth J. Subjective neuroleptic response and treatment outcome under open and double-blind conditions - a preliminary report.  Prog Neuropsychopharmacol Biol Psychiatry. 1990;  14(6) 921-8
• 62 Priebe S. Die Bedeutung der Patientenmeinung. Initiale Bewertung und Verlauf psychiatrischer Therapie. Hogrefe 1992 Göttingen;
• 63 Prosser E S, Csernansky J F, Kaplan J, Thiemann S, Becker T J, Hollister L E. Depression, parkinsonian symptoms and negative symptoms in schizophrenic treated with neuroleptics.  J Nerv Ment Disease. 1987;  175 100-105
• 64 Ramaekers J G, Louwerens J W, Muntjewerff N D, Milius H, de Bie A, Rosenzweig P, Patat A, O’Hanlon J F. Psychomotor, Cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic.  J Clin Psychopharmacol. 1999;  19(3) 209-21
• 65 Ritsner M, Modai I, Endicott J, Rivkin O, Nechamkin Y, Barak P, Goldin V, Ponizovsky A. Differences in quality of life domains and psychopathologic and psychosocial factors in psychiatric patients.  J Clin Psychiatry. 2000;  61(11) 880-9
• 66 Ritsner M, Ponizovsky A, Endicott J, Nechamkin Y, Rauchverger B, Silver H, Modai I. The impact of side effects of antipsychotic agents on life satisfaction of schizophrenia patients: a naturalistic study.  Eur Neuropsychopharmacol. 2002;  12(1) 31-8
• 67 Ritsner M. Predicting changes in domain-specific quality of life of schizophrenia patients.  J Nerv Ment Dis. 2003;  191(5) 287-94
• 68 Rossi A, Arduini L, Stratta P, Pallanti S. Subjective experience and subjective response to neuroleptics in schizophrenia.  Compr Psychiatry. 2000;  41(6) 446-9
• 69 Graf Schimmelmann B, Schacht M, Perro C, Lambert M. The initial dysphoric reaction (IDR) followed the first neuroleptic dosage. Nervenarzt 2003. Review. German
• 70 Graf Schimmelmann B, Paulus S, Tilgner C, Schacht M, Lambert M. Side Effects, Subjective Distress and Subjective Well-Being in first admitted Adolescents with Early Onset Psychosis treated with Atypical Antipsychotics. Int Clin Psychopharmacology, submitted
• 71 Singh M M. Dysphoric response to neuroleptic treatment in schizophrenia and its prognostic significance.  Diseases of Nerv Syst. 1976;  37 191-196
• 72 Singh M M, Kay S R. Dysphoric response to neuroleptic treatment in schizophrenia: Its relationship to automatic arousal and prognosis.  Biol Psychiatry. 1979;  79 277-294
• 73 Skantze K, Malm U, Dencker S J, May P R, Corrigan P. Comparison of quality of life with standard of living in schizophrenic out-patients.  Br J Psychiatry. 1992;  161 797-801
• 74 Spohn H E, Strauss M E. Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia.  Journal of Abnormal Psychology. 1989;  98 367-380
• 75 Van Putten T. Why do schizophrenic patients refuse to take their drugs?.  Arch Gen Psychiatry. 1974;  31 67-72
• 76 Van Putten T, Crumpton E, Yale C. Drug refusal in schizophrenia and wish to be crazy.  Arch Gen Psychiatry. 1976;  33 1443-1446
• 77 Van Putten T, May P. Akinetic depression in schizophrenia.  Arch Gen Psychiatry. 1978;  35 1101-1107
• 78 Van Putten T, May P. Subjective response as a predictor of outcome in pharmacotherapy: the consumer has a point.  Arch Gen Psychiatry. 1978;  35 477-480
• 79 Van Putten T, May P, Marder S R, Wittmann L. Subjective response to antipsychotic drugs.  Arch Gen Psychiatry. 1981;  38 187-190
• 80 Van Putten T, May P RA, Marder S R. Response to antipsychotic medication: The doctor's and the consumer's view.  Am J Psychiatry. 1984;  141 16-19
• 81 Van Putten T, Marder S R. Behavioral toxicity of antipsychotic drugs.  J Clin Psychiatry. 1987;  48 13-19
• 82 Voruganti L NP, Heslegrave R J, Awad A G. Neuroleptic dysphoria may be the missing link between schizophrenia and substance abuse.  J Nerv Ment Dis.. 1997;  185(7) 463-5
• 83 Voruganti L NP, Heslegrave R J, Awad A G, Seeman M V. Quality of life measurement in schizophrenia: reconciling the quest for subjectivity with the question of reliability.  Psychol Med. 1998;  28 165-172
• 84 Vorugante L, Cortese L, Oyewumi L, Cernovsky Z, Zirul S, Award A. Comparative evaluation of conventional and novel antipsychotic drugs with reference to their subjective tolerability, side effect profile and impact on quality of life.  Schizophr Res. 2000;  43(2 - 3) 135-45
• 85 Voruganti L NP, Cortese L, Owyeumi L, Kotteda V, Cernovsky Z, Zirul S, Awad A. Switching from conventional to novel antipsychotic drugs: results of a prospective naturalistic study.  Schizophr Res. 2002;  57(2 - 3) 201-8
• 86 Voruganti L NP, Awad A G. Personal evaluation of transitions in treatment (PETiT): a scale to measure subjective aspects of antipsychotic drug therapy in schizophrenia.  Schizophr Res. 2002;  56(1 - 2) 37-46
• 87 Ware JE J r, Sherbourne C D. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.  Med Care. 1992;  30(6) 473-83
• 88 Weiden P J, Mann J J, Dixon L. et al . Is neuroleptic dysphoria a healthy response?.  Compr Psychiatry. 1989;  30 546-552
• 89 Weiden P, Rapkin B, Mott T, Zygmunt A, Goldman D, Horvitz-Lennon M, Frances A. Rating of medication influences (ROMI) scale in schizophrenia.  Schizophr Bull.. 1994;  20(2) 297-310
• 90 Weiden P J, Mackell J. Differing side effect burdens with newer antipsychotics. Poster presented at the International Congress on Schizophrenia Research 1999 Santa Fe, USA;
• 91 White K, Busk J, Eaton E, Gomez G, Razani J, Sloane R B. Dysphoric response to neuroleptics as a predictor of treatment outcome with schizophrenics. A comparative study of Haloperidol versus Mesoridazine.  Int Pharmacopsychiat. 1981;  16 34-38
• 92 Wise R A. Neuroleptic-induced anhedonia. Recent studies. In Advances in Neuropsychiatry and Psychopharmacology, Volume 1: Schizophrenia Research (Eds CA Tamminga and SC Schulz). 1991: pp. 323-331 Raven Press New York;