Subjective response to neuroleptics in patients with schizophrenia is reviewed in terms of its validity and measurement. Evidence is presented to support a correlation between altered subjective state on neuroleptics, and therapeutic outcome and medication compliance. Factors that have been implicated in the genesis of such altered subjective states include demographics, psychiatric characteristics, type and dose of neuroleptic, extrapyramidal symptoms (particularly akathisia), depressive states, and patients' values and attitudes toward health and illness. Factors that may contribute to lack of interest in researching subjective experiences of schizophrenia patients on medications are reviewed, and methodological improvements in study design are proposed to enhance our understanding of this phenomenon. Such understanding may help us to better appreciate the many factors that contribute to variability of responses to neuroleptic therapy in patients with schizophrenia and also help us to develop more effective treatment strategies.

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Objective: Bipolar disorder is frequently misdiagnosed as major depressive disorder (MDD). We aim to quantify the prevalence of misdiagnosed bipolar disorder among the depression population and evaluate the quality-of-life (QOL) impact of misdiagnoses.Method: Data were collected from 2 selfadministered, cross-sectional studies in 2003. Patients participating in The Bipolar Disorder Misdiagnosis Study (N = 1156) were previously diagnosed with depression, experienced a depressive episode within the past year, and had no previous diagnosis of bipolar disorder or schizophrenia. Patients who experienced a manic episode in the past year, based on DSM-IV criteria, were classified as misdiagnosed. Patients participating in The Bipolar Disorder Project (N = 1214) selfreported a diagnosis of bipolar disorder and were recruited through community mental health centers and support groups. Quality of life was assessed via the Psychological General Well-Being (PGWB) Index and Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8). Demographic differences between groups were controlled using linear regression models.Results: Of the diagnosed MDD sample, 14.3% met criteria for misdiagnosed bipolar disorder. When controlling for demographic differences, the PGWB overall score for the misdiagnosed averaged 12.77 (p < .001) points lower than that of MDD patients and 9.55 (p < .001) points lower than that of diagnosed bipolar disorder patients. The average SF-8 mental component summary score for the misdiagnosed was 5.85 (p < .001) points lower than that of MDD patients and 3.18 (p = .002) points lower than that of diagnosed bipolar disorder patients.Conclusion: Misdiagnosis is associated with poorer QOL than MDD or diagnosed bipolar disorder, which are recognized as having a considerable impact on QOL.(Prim Care Companion J Clin Psychiatry 2007;9:195-202) ipolar disorder, a chronic affective disorder characterized by depression and at least 1 manic episode,

The utility of quality of life (QOL) as an evaluative tool in clinical psychiatric research and drug trials could be enhanced by developing appropriate conceptual models of QOL, specific for psychiatric disorders. In our proposed model, QOL of individuals maintained on antipsychotic drug therapy for schizophrenia, is viewed as the subject's perception of the outcome of an interaction between severity of psychotic symptoms, side-effects including subjective responses to antipsychotic drugs, and the level of psychosocial performance. In order to test the validity of the model in clinical setting, we selected a sample of 62 schizophrenic patients clinically stabilized on antipsychotic drug therapy, and measured their subjective QOL and other potentially relevant clinical and psychosocial factors. Standardized scales including the positive and negative syndromes scale (PANSS), abnormal involuntary movements scale (AIMS), Hillside Akathisia scale (HAI), and the social performance schedule (SPS) were used for this purpose. Results of a multiple regression analysis using subjective quality of life as the outcome variable, indicated that severity of schizophrenic symptoms (partial R2 = 0.32, p < 0.0001) and subjective distress caused by akathisia (partial R2 = 0.11, p < 0.01) and neuroleptic dysphoria (partial R2 = 0.06, p < 0.05), accounted for nearly half of the variance, while the contribution from the psychosocial indicators was negligible. These results broadly endorse key aspects of the proposed model, and suggest further studies in this direction. These results experiences during antipsychotic therapy can enhance patients' QOL. This conceptual model has been developed with particular focus on the impact of antipsychotic medications on the QOL of persons with schizophrenia. As such, it is more applicable to clinical trials of new antipsychotic medications but may not be broad enough to be applicable for other social or vocational interventions.

The recent development of new neuroleptics that differ from the conventional neuroleptics in both mechanism of action and side-effects profile has introduced problems in their clinical assessment, and highlighted ongoing issues in the design and methodology of clinical trials. These issues are broadly grouped and discussed as follows: sampling problems and selection of patients; design issues; problems in measurement; ensuring compliance; recognition of extrapharmacological issues; and statistical models. For patients to benefit from the development of new neuroleptics, clinical settings have to be prepared for testing their efficacy and safety without too much delay in well designed clinical trials.