Menopause depression: Under recognised and poorly treated.

Menopause is a biological process experienced by all people assigned female at birth. A significant number of women experience mental ill health related to the major brain gonadal hormone shifts that occur in their midlife. There is poor understanding and management of the complex mental ill health issues, with the biological brain hormone changes receiving little formal attention. The current treatment advice is to manage this special type of mental ill health in the same way that all mental ill health is managed. This leads to poor outcomes for women and their families. Many women leave the workforce earlier than expected due to menopause-related depression and anxiety, with subsequent loss of salary and superannuation. Others describe being unable to adequately parent or maintain meaningful relationships - all ending in a poor quality of life. We are a large and diverse group of national and international clinicians, lived experience and social community advocates, all working together to innovate the current approaches available for women with menopausal mental ill health. Above all, true innovation is only possible when the woman with lived experience of menopause is front and centre of this debate.

Impact of irritability: a 2-year observational study of outpatients with bipolar I or schizoaffective disorder.

OBJECTIVES: Many people experience irritability when manic, hypomanic, or depressed, yet its impact on illness severity and quality of life in bipolar and schizoaffective disorders is poorly understood. This study aimed to examine the relationship between irritability and symptom burden, functioning, quality of life, social support, suicidality, and overall illness severity in a naturalistic cohort of people with bipolar I or schizoaffective disorder. METHODS: We used data from 239 adult outpatients with bipolar I or schizoaffective disorder in the Bipolar Comprehensive Outcomes Study (BCOS) - a non-interventional observational study with a 2-year follow-up period. Baseline demographic and clinical characteristics of participants with and without irritability were compared. A mixed-model repeated measures analysis was conducted to examine the longitudinal effect of irritability on clinical and quality-of-life variables over follow-up using significant baseline variables. RESULTS: At baseline, 54% of participants were irritable. Baseline irritability was associated with illness severity, mania, depression, psychotic symptoms, suicidality, poor functioning, and quality of life, but not diagnosis (schizoaffective/bipolar disorder). Participants with irritability were less likely to have a partner and perceived less adequate social support. On average, over follow-up, those with irritability reported more symptoms, functional impairment, and suicidality. Furthermore, the effects of irritability could not be fully explained by illness severity. CONCLUSIONS: Irritability was associated with more negative symptomatic, functional, and quality-of-life outcomes and suicidality. The identification, monitoring, and targeted treatment of irritability may be worth considering, to enhance health and wellbeing outcomes for adults with bipolar and schizoaffective disorders.

Demonstrating the effectiveness of less restrictive care pathways for the management of patients treated with clozapine.

OBJECTIVE: The purpose of this study was to measure the effectiveness of two alternative care pathways for managing patients treated with clozapine. METHOD: Medical records for 90 clozapine patients managed via three care pathways were audited for a 24 month period (30 per group). The three care pathways established to manage patients prescribed clozapine include: (1) remaining in public mental health service case management; (2) transitioning to general practitioner-mental health service shared care; or (3) transitioning to private psychiatry sole care. Demographic, illness, medication compliance, service utilisation and performance on clinical outcome measures were collected in the 12 months prior to and following transition. RESULTS: Across both the private psychiatry and general practitioner (GP) shared care transitioned groups, only one patient had a psychiatric hospital admission in the 12 months following transition, and transitioned patients also had fewer mental health service clinician contacts. Good medication compliance, better skills of daily living, lower levels of illicit substance abuse and a lower intensity of case management history were seen in transitioned patients. CONCLUSIONS: Transitioning appropriate patients taking clozapine to less intensive care pathways like private psychiatrists and GP shared care can be effectively achieved if appropriate supports are in place for both the clinicians and their patients.

Treatment and outcomes of an Australian cohort of outpatients with bipolar I or schizoaffective disorder over twenty-four months: implications for clinical practice.

BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with 'real-world' treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication. METHODS: Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale - Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data. RESULTS: On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts. CONCLUSIONS: Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Transitioning patients taking clozapine from the public to private/GP shared-care setting: barriers and criteria.

OBJECTIVE: The aim of this study was to explore the barriers to transitioning patients taking clozapine from the public to private psychiatrist or general practitioner (GP) shared-care setting, as well as the criteria used by staff to identify patients suitable for transitioning. METHOD: The experience of clinicians managing people taking clozapine was explored through circulation of a feedback questionnaire. The clozapine transition questionnaire (CTQ) was developed as the primary measure following extensive consultation with clinical staff with expertise in clozapine treatment. A total of 215 clinicians were sent questionnaires (60 community mental health service staff, 120 private psychiatrists registered to prescribe clozapine, and 35 GPs from the Bayside Health clozapine GP shared-care programme), with overall 80 (46.2%) returned. RESULTS: Over 64% of participants had managed patients who had been transitioned from public to private psychiatrist or GP shared-care settings. Around half of these said that it was a 'worthwhile treatment option' and that 'it went smoothly' and 'the patient was satisfied'. The most significant barriers to successful transitioning were the cost of private service, the patient's level of disorganization, and the need for ongoing care coordination. The most important criteria for transitioning patients was compliance with medication, ability to independently attend appointments and access appropriate pharmacies to receive medication, and willingness to transition out of the public system. CONCLUSIONS: Transitioning suitable public psychiatric patients taking clozapine into private psychiatrist/GP shared-care offers an important model to improve the efficiency and effectiveness of care, but requires careful planning, preparation, and monitoring to ensure sustained success.

A prospective study of the impact of smoking on outcomes in bipolar and schizoaffective disorder.

BACKGROUND: Tobacco smoking is more prevalent among people with mental illnesses, including bipolar disorder, than in the general community. Most data are cross-sectional, and there are no prospective trials examining the relationship of smoking to outcome in bipolar disorder. The impact of tobacco smoking on mental health outcomes was investigated in a 24-month, naturalistic, longitudinal study of 240 people with bipolar disorder or schizoaffective disorder. METHOD: Participants were interviewed and data recorded by trained study clinicians at 9 interviews during the study period. RESULTS: Comparisons were made between participants who smoked daily (n = 122) and the remaining study participants (n = 117). During the 24-month study period, the daily smokers had poorer scores on the Clinical Global Impressions-Depression (P = .034) and Clinical Global Impressions-Overall Bipolar (P = .026) scales and had lengthier stays in hospital (P = .012), compared with nonsmokers. LIMITATIONS: Smoking status was determined by self-report. Nicotine dependence was not measured. CONCLUSION: These findings suggest that smoking is associated with poorer mental health outcomes in bipolar and schizoaffective disorder.

The cost of relapse in schizophrenia and schizoaffective disorder.

OBJECTIVE: The aim of this study was to quantify the costs and resource utilization associated with a relapse of schizophrenia or schizoaffective disorder. METHODS: The study comprised a retrospective audit of data from 200 patients diagnosed with schizophrenia or schizoaffective disorder who were admitted to hospital for a relapse of their disorder in two mental health services in Australia between 1 June 2001 and 31 May 2002. Resource use and costing data were collected for 12 months before and 12 months after the hospitalization. RESULTS: There was an increase in contacts per month and associated outpatient costs after the index admission which persisted for the full 12 month data collection period (total of AUD $637). There was also a total increase in hospital costs but this did not persist beyond the first 2 months of the follow-up period and is likely explained by the index admission. CONCLUSIONS: Increased healthcare resource utilization and costs results from relapse in patients with schizophrenia or schizoaffective disorder. An increase in service use and costs persist for a considerable time period after an episode of relapse.

The Bipolar Comprehensive Outcomes Study (BCOS): baseline findings of an Australian cohort study.

BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, observational study of participants with bipolar I or schizoaffective disorder examining clinical, functional, and economic outcomes associated with naturalistic treatment. METHODS: Participants prescribed mood stabilisers were assessed using various measures, including the Young Mania Rating Scale (YMRS), 21-item Hamilton Depression Rating scale (HAMD21), Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), and the EuroQol instrument (EQ-5D). RESULTS: 240 participants were recruited from two sites. On average, participants were 41.8+/-12.7 years of age (mean+/-SD), 58.3% were female, and 73.3% had a diagnosis of bipolar I disorder at study entry. The majority of participants were moderately ill, with an average CGI-BP Overall score of 3.8+/-1.3. Most participants had subthreshold mania and depression symptoms, indicated by HAMD21 Total 13.4+/-8.6, CGI-BP Depression 3.2+/-1.3, YMRS Total 8.2+/-8.5 and CGI-BP Mania 3.0+/-1.6 average scores. For bipolar participants, 94.6% of hospitalisations for psychiatric treatment in the past 3 months were single admissions (vs. 65.2% for schizoaffective participants, p=.002). Bipolar participants rated their overall health state higher (EQ-5D scores: 68.2+/-18.8 vs. 61.6+/-22.7, p=.023), had a higher mean weekly wage ($500-$999, 21.3% vs. 6.3%), lower unemployment (22.2% vs. 48.4%), and higher romantic relationship status (47.1% vs. 26.6%). LIMITATIONS: The observational design and small sample size may have limited the causal relationships and generalisability within the current findings. CONCLUSIONS: Participants were characterised by social and occupational dysfunction at entry, but schizoaffective participants appeared to be more severely affected. Effective treatment is required to address both clinical and functional impairment.

A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression.

OBJECTIVE: High-frequency left-side repetitive transcranial magnetic stimulation (rTMS) and low-frequency stimulation to the right prefrontal cortex have both been shown to have antidepressant effects, but doubts remain about the magnitude of previously demonstrated treatment effects. The authors evaluated sequentially combined high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex for treatment-resistant depression. METHOD: The authors conducted a 6-week double-blind, randomized, sham-controlled trial in 50 patients with treatment-resistant depression. Three trains of low-frequency rTMS to the right prefrontal cortex of 140 seconds' duration at 1 Hz were applied daily, followed immediately by 15 trains of 5 seconds' duration of high-frequency left-side rTMS at 10 Hz. Sham stimulation was applied with the coil angled at 45 degrees from the scalp, resting on the side of one wing of the coil. The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale. RESULTS: There was a significantly greater response to active than sham stimulation at 2 weeks and across the full duration of the study. A significant proportion of the study group receiving active treatment met response (11 of 25 [44%]) or remission (nine of 25 [36%]) criteria by study end compared to the sham stimulation group (two of 25 [8%] and none of 25 respectively). CONCLUSIONS: Sequentially applying both high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex, has substantial treatment efficacy in patients with treatment-resistant major depression. The treatment response accumulates to a clinically meaningful level over 4 to 6 weeks of active treatment.

A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder.

We tested and compared the use of two adjunctive hormonal agents, tamoxifen and medroxyprogesterone acetate (MPA), for the treatment of acute mania or hypomania. A total of 13 women with acute Bipolar Affective Disorder in the manic or hypomanic phase were recruited from a clinical population to participate in this 28-day, three-arm, double blind, placebo-controlled study. The women who received tamoxifen exhibited significant improvement in symptoms of mania from baseline to final assessment compared with the placebo group. The MPA group improved more than the placebo group. Further exploration of tamoxifen as a useful adjunct in the treatment of acute manic symptoms in women with Bipolar Affective Disorder is warranted.

The treatment of recurring auditory hallucinations in schizophrenia with rTMS.

BACKGROUND: Auditory hallucinations are a common and disabling problem for many patients with schizophrenia and often fail to respond to optimal antipsychotic therapy. Repetitive transcranial magnetic stimulation (rTMS) has recently been trialled as an alternative treatment option for these patients. These studies have generally been positive, but treatment has only been provided for short periods of time and little is known about the longer-term impact of TMS on the course of hallucinations. METHOD: We describe two cases in which rTMS was provided to patients upon relapse of hallucinations following initial successful rTMS treatment in a clinical trial. RESULTS: A repeat course of rTMS resulted in a marked improvement in the symptoms experienced by these two patients. CONCLUSIONS: rTMS appears to have potential as a long-term treatment for patients with auditory hallucinations, but requires ongoing systematic investigation.

A study of the effects of lorazepam and dextromethorphan on the response to cortical 1 Hz repetitive transcranial magnetic stimulation.

We studied the effects of lorazepam and dextromethorphan on the responses to 1 Hz repetitive transcranial magnetic stimulation applied to the left human motor cortex. Lorazepam, dextromethorphan or placebo was administered to 45 normal controls in a double-blind fashion 2.5 h before the repetitive transcranial magnetic stimulation procedure. Motor cortical excitability was measured with single transcranial magnetic stimulation pulses before and after 15 min of 1 Hz repetitive transcranial magnetic stimulation applied at supra-threshold intensity. 1 Hz repetitive transcranial magnetic stimulation resulted in a decrease in motor cortical excitability in the placebo group but not in the groups taking lorazepam or dextromethorphan. These results suggest that cortical responses to 1 Hz repetitive transcranial magnetic stimulation are dependent on activity at both gamma-aminobutyric acid and N-methyl-D-asparate receptor systems.

Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial.

BACKGROUND: High-frequency left-sided repetitive transcranial magnetic stimulation (HFL-TMS) has been shown to have antidepressant effects in double-blind trials. Low-frequency stimulation to the right prefrontal cortex (LFR-TMS) has also shown promise, although it has not been assessed in treatment-resistant depression and its effects have not been compared with those of HFL-TMS. OBJECTIVE: To prospectively evaluate the efficacy of HFL-TMS and LFR-TMS in treatment-resistant depression and compared with a sham-treated control group. DESIGN: A double-blind, randomized, sham-controlled trial. SETTING: Two general psychiatric services. PARTICIPANTS: Sixty patients with treatment-resistant depression who had failed to respond to therapy with multiple antidepressant medications were divided into 3 groups of 20 that did not differ in age, sex, or any clinical variables. All patients completed the double-blind phase of the study. INTERVENTIONS: Twenty 5-second HFL-TMS trains at 10 Hz and five 60-second LFR-TMS trains at 1 Hz were applied daily. Sham stimulation was applied with the coil angled at 45 degrees from the scalp, resting on the side of one wing of the coil. Main Outcome Measure Score on the Montgomery-Asberg Depression Rating Scale. RESULTS: There was a significant difference in response among the 3 groups (F56,2 = 6.2), with a significant difference between the HFL-TMS and sham groups and between the LFR-TMS and sham groups (P<.005 for all) but not between the 2 treatment groups. Baseline psychomotor agitation predicted successful response to treatment. CONCLUSIONS: Both HFL-TMS and LFR-TMS have treatment efficacy in patients with medication-resistant major depression. Treatment for at least 4 weeks is necessary for clinically meaningful benefits to be achieved. Treatment with LFR-TMS may prove to be an appropriate initial repetitive TMS strategy in depression taking into account safety, tolerability, and efficacy considerations.

Impact of Cannabis Use on Long-Term Remission in Bipolar I and Schizoaffective Disorder.

OBJECTIVE: To investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders. METHODS: The 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months. RESULTS: Of the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group. CONCLUSION: Cannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders.

Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia.

BACKGROUND: Schizophrenia may be characterized by abnormal plastic modulation in cortical neuronal circuits. Activation of premotor cortex using repetitive transcranial magnetic stimulation (rTMS) produces suppression of cortical excitability in primary motor cortex. We hypothesized that premotor rTMS would cause less suppression of motor cortical excitability in patients with schizophrenia than in control subjects. METHODS: Twelve patients diagnosed with schizophrenia and twelve healthy control subjects underwent subthreshold rTMS to the premotor area in a 15-min conditioning train. Measurements of primary motor cortical excitability (motor evoked potential; MEP), the resting motor threshold (RMT), and cortical inhibition (CI) were taken before and after the rTMS. RESULTS: There was no difference in RMT between groups at baseline, although the patient group had less CI than the control group at baseline. Following rTMS, the change in both MEP size and RMT between groups was significant. After rTMS, MEP size was suppressed in the control group and increased in the patient group, whereas RMT increased in the normal control group and decreased in the patient group. CONCLUSIONS: Patients with schizophrenia demonstrate abnormal brain responses to rTMS applied to the premotor cortex that appear to relate to reduced motor cortical inhibition.

Reduced plastic brain responses in schizophrenia: a transcranial magnetic stimulation study.

BACKGROUND: Abnormalities in brain plasticity, possibly related to abnormal cortical inhibition (CI), have been proposed to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation (TMS) provides a dynamic method for non-invasive study of plastic processes in the human brain. We aimed to determine whether patients with schizophrenia would exhibit an abnormal response to repetitive TMS (rTMS) applied to the motor cortex and whether this would relate to deficient cortical inhibition. METHODS: Measures of motor cortical excitability and cortical inhibition were made before and after a single 15-min train of 1-Hz rTMS applied to the motor cortex in medicated and unmedicated patients with schizophrenia as well as healthy controls. RESULTS: All three groups had equal motor cortical excitability prior to rTMS, although both patient groups had a shorter cortical silent period (CSP) and less cortical inhibition than the control group. Cortical excitability, as assessed by motor threshold levels, did not reduce in both medicated and unmedicated patients in response to rTMS as was seen in the control group. Significant differences were also seen between the groups in response to the rTMS for motor-evoked potential (MEP) size and cortical silent period duration. CONCLUSIONS: Both medicated and medication free patients with schizophrenia demonstrated reduced brain responses to rTMS and deficits in cortical inhibition.

A confirmatory factor analytic evaluation of the pentagonal PANSS model.

The positive and negative syndrome scale (PANSS) is widely used in psychiatric research. Reflecting this common use, considerable attention has been applied to the psychometric properties of this instrument. However, despite the publication of numerous studies and analyses, it remains uncertain how best data from the PANSS should be analysed to best model the symptoms of schizophrenia. A resolution to these concerns seemed to be offered following the publication in 1997 of a large multisite factor analysis that produced the 'pentagonal model', which has subsequently been included in the 2000 revision of the PANSS user manual. However, to date, an independent confirmatory analysis of this model has not yet been published. The aim of this study was to test this model in a new independent sample with confirmatory factor analysis (CFA). Independent confirmation of the fit of the model is required to ensure that its implementation is informed by confirmation of its psychometric properties. CFA was performed in a sample of 347 subjects with schizophrenia. The analysis found that the model had inadequate goodness of fit. The use of the pentagonal model has similar difficulties as earlier models and more research is required to ascertain the optimal method for measuring symptom dimensions in research and clinical settings.

Motor cortical excitability and clinical response to rTMS in depression.

BACKGROUND: The relationship between frontal lobe activity in the left and right hemispheres and the pathophysiology of depression remains unclear. In addition, it is uncertain whether levels of frontal or motor cortical excitability relate to clinical response to treatment modalities. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to predict the response to treatment with repetitive TMS (rTMS) applied to the left or right prefrontal cortex. METHODS: Motor thresholds, cortical excitability and cortical inhibition (CI) were assessed prior to a trial of rTMS in patients with treatment resistant depression. RESULTS: There was no consistent pattern of differences in hemispheric activity, although there was a relationship between the degree of psychopathology and cortical excitability (right hemisphere) and an inverse relationship between inhibitory activity and clinical response (left hemisphere). CONCLUSIONS: The study does not support a simple model of laterality in motor cortical excitability in depression. The TMS measures used in this study appear to be of limited use in the prediction of clinical response to rTMS.

A transcranial magnetic stimulation study of abnormal cortical inhibition in schizophrenia.

Previous research suggests that patients with schizophrenia demonstrate deficits in a range of parameters of motor cortical and cognitive inhibition. I-wave facilitation and long-interval cortical inhibition (LICI) are two paired pulse transcranial magnetic stimulation paradigms that appear to assess aspects of cortical inhibitory function that have not previously been assessed in this patient group. Eighteen patients with schizophrenia (nine medication-free) were compared with eight control subjects. We assessed resting motor threshold (RMT) levels, LICI and I-wave facilitation. RMT levels did not differ between the three groups. There was a significant overall difference in I-wave facilitation levels. Both patient groups as compared with the control group showed increased facilitation. There were no differences between the groups in the measure of LICI. Patients with schizophrenia appear to have increased I-wave facilitation. Increased I-wave facilitation suggests deficient function of cortical inhibitory GABAergic activity. This is consistent with previous research that has found deficient cortical inhibition in patients with schizophrenia.

A longitudinal study of patient- and observer-rated quality of life in schizophrenia.

Patient-rated life satisfaction and observer-rated quality of life (ORQOL) appear to have different determinants in patients with schizophrenia, although most studies conducted to date have used cross-sectional methods or related clinical dimensions at one time point with quality of life (QOL) measured at another. The aim of this study was to investigate the relationship between changes in patient-rated QOL (PRQOL) and ORQOL over time and changes in clinical variables. Two hundred and thirty-one patients taking part in the Schizophrenia Care Assessment Program (SCAP) study at Dandenong in Australia were included in this analysis. Subjective ratings of several domains of social functioning and life satisfaction were taken from the SCAP instrument and comparisons made with data from the QOL Scale rated by research staff, as well as several psychopathology measures. Changes in these scores over 1 year were correlated to investigate relationships between measures. Weak correlations were seen between changes in PRQOL and ORQOL domains. Patient-rated domains related most closely to depressive symptoms (Montgomery-Asberg Depression Rating Scale scores) whereas observer-rated domains related to both negative symptoms and depressive symptoms. Positive psychotic symptoms had little effect on either domain. Longitudinal data appear to confirm that PRQOL and ORQOL are not closely related and may have differing determinants in patients with schizophrenia. They should be considered as separate and complementary outcome variables and utilized accordingly.