Predictors of medication adherence in patients with schizophrenia and bipolar disorder.

OBJECTIVE: To investigate potential risk factors for medication non-adherence in patients with schizophrenia and bipolar disorder. METHOD: A total of 255 patients underwent clinical assessments, neurocognitive testing and blood sampling. The patients were divided into groups of 'No', 'Partial' or 'Full' adherence. Relationships to different risk factors were analyzed. RESULTS: In schizophrenia, use of illicit substances, alcohol and poor insight were related to worse adherence. Schizophrenia patients with No adherence did better on tests of executive functioning, verbal learning and memory and had higher IQ than patients with better adherence. There were higher levels of autonomic side effects in the non-adherence group, but body mass index was lower in the Partial adherence group than in the Full adherence group. In the bipolar disorder patients, there was an association between the use of illicit substances and alcohol and poor adherence. We found no relationship between adherence behavior and neurocognition in the bipolar disorder group. CONCLUSION: Substance use is an important risk factor for non-adherence in patients with schizophrenia and bipolar disorder. Poor insight is also a risk factor in schizophrenia. The results suggest that cognitive dysfunction is not a risk factor for non-adherence in these diagnostic groups.

Early detection of psychosis: positive effects on 5-year outcome.

BACKGROUND: During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long-term outcome. This study reports the effects of reducing DUP on 5-year course and outcome. METHOD: During 1997-2000 a total of 281 consecutive patients aged >17 years with first episode non-affective psychosis were recruited, of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) programme with public information campaigns and low-threshold psychosis detection teams was established in one healthcare area (ED-area), but not in a comparable area (no-ED area). Both areas ran equivalent treatment programmes during the first 2 years and need-adapted treatment thereafter. RESULTS: At the start of treatment, ED-patients had shorter DUP and less symptoms than no-ED-patients. There were no significant differences in treatment (psychotherapy and medication) for the 5 years. Mixed-effects modelling showed better scores for the ED group on the Positive and Negative Syndrome Scale negative, depressive and cognitive factors and for global assessment of functioning for social functioning at 5-year follow-up. The ED group also had more contacts with friends. Regression analysis did not find that these differences could be explained by confounders. CONCLUSIONS: Early treatment had positive effects on clinical and functional status at 5-year follow-up in first episode psychosis.

Opposite relationships between cannabis use and neurocognitive functioning in bipolar disorder and schizophrenia.

BACKGROUND: Cannabis use is associated with altered neurocognitive functioning in severe mental disorders, but data are still inconclusive and there are no studies of bipolar disorder. The aim of this study was to investigate the association between cannabis use and neurocognition in bipolar disorder compared with schizophrenia in a naturalistic setting. METHOD: A total of 133 patients with bipolar disorder and 140 patients with schizophrenia underwent neuropsychological assessments and clinical characterization including measures of substance use. Relationships between cannabis users and neurocognitive function were explored in the two diagnostic groups. Possible interactions between diagnosis and cannabis use were investigated, and findings were controlled for possible confounders. RESULTS: In bipolar disorder subjects, cannabis use was associated with better neurocognitive function, but the opposite was the case for the schizophrenia subjects. There was a statistically significant interaction effect of diagnosis and cannabis use on focused attention (p=0.019), executive functioning (verbal fluency--set shifting) (p=0.009), logical memory-learning (p=0.007) and on logical memory-recall (p=0.004). These differences in neurocognitive function could not be explained by putative confounders. CONCLUSIONS: The findings suggest that cannabis use may be related to improved neurocognition in bipolar disorder and compromised neurocognition in schizophrenia. The results need to be replicated in independent samples, and may suggest different underlying disease mechanisms in the two disorders.

Early identification of non-remission in first-episode psychosis in a two-year outcome study.

OBJECTIVE: To identify predictors of non-remission in first-episode, non-affective psychosis. METHOD: During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. RESULTS: One hundred and twenty-nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non-remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non-remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two-year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non-remission at 3 months, but only DUP predicted at 2 years. CONCLUSION: Long DUP predicted both 3 month and 2-year non-remission rates in first-episode psychosis.

A 2-year follow-up of involuntary admission's influence upon adherence and outcome in first-episode psychosis.

OBJECTIVE: To see, if voluntary admission for treatment in first-episode psychosis results in better adherence to treatment and more favourable outcome than involuntary admission. METHOD: We compared consecutively first-admitted, hospitalised patients from a voluntary (n = 91) with an involuntary (n = 126) group as to psychopathology and functioning using Positive and Negative Syndrome Scale and Global Assessment of Functioning Scales at baseline, after 3 months and at 2 year follow-up. Moreover, duration of supportive psychotherapy, medication and number of hospitalisations during the 2 years were measured. RESULTS: More women than men were admitted involuntarily. Voluntary patients had less psychopathology and better functioning than involuntary patients at baseline. No significant difference as to duration of psychotherapy and medication between groups was found. No significant difference was found as to psychopathology and functioning between voluntarily and involuntarily admitted patients at follow-up. CONCLUSION: Legal admission status per se did not seem to influence treatment adherence and outcome.

Are multi family groups appropriate for patients with first episode psychosis? A 5-year naturalistic follow-up study.

OBJECTIVE: To compare outcome over 5 years for patients who participated in multi family groups (MFGs) to those who refused or were not offered participation. METHOD: Of 301 first episode psychotic patients aged 15-65 years, 147 participated in MFGs. Outcome was measured by drop-out rates, positive and negative syndrome scale (PANSS) symptom scores, and duration of psychotic episodes during the follow-up period. RESULTS: Multi family group participants had a significantly lower drop-out rates at 5-year follow-up than patients who did not participate. However, the MFG participants had significantly less improvement in PANSS positive and excitative symptoms and had significantly longer duration of psychotic symptoms during the follow-up period. CONCLUSION: Multi family groups appear to increase the chance of retaining patients in a follow-up study, but adjustment of the programme may be necessary with first episode psychosis patients to meet their needs better.

Baseline profiles of adolescent vs. adult-onset first-episode psychosis in an early detection program.

OBJECTIVE: Psychotic disorders often start in adolescence. We aim to investigate premorbid and baseline differences characterizing patients with an onset of psychosis in adolescence versus adulthood. METHOD: We compare first-episode, DSM-IV non-affective psychosis with onset before (n = 43) and after (n = 189) 18 years on duration of untreated psychosis (DUP), level of symptoms, suicidal behaviour, and other baseline clinical and demographic characteristics. RESULTS: Adolescent onset patients had poorer premorbid functioning, a longer DUP, higher suicidality, and more depressive symptoms. They also had better cognition, fewer psychotic symptoms, and were more likely to be treated on an out-patient basis. CONCLUSION: Adolescents with first-episode psychosis may have a slower and more silent, i.e. insidious onset, and are at risk of experiencing longer treatment delays than adults. They fit the description of what used to be labeled process (versus reactive) schizophrenia.

Illicit drug use in patients with psychotic disorders compared with that in the general population: a cross-sectional study.

OBJECTIVE: Prevalence estimates of illicit drug use in psychotic disorders vary between studies, and only a few studies compared prevalence estimates with those in the general population. METHOD: Cross-sectional study comparing 148 stable-phase patients with schizophrenia or bipolar disorder with 329 representative general citizens of Oslo. A total of 849 patients from the same hospital department in the same time period constituted a patient reference group. RESULTS: Lifetime illicit drug use was 44% higher (P < 0.001) in study patients than in the general population sample; while lifetime use of amphetamine/cocaine was 160% higher (P < 0.001). No differences were found between user groups for sociodemographic characteristics. CONCLUSION: Patients with psychotic disorders in stable phase had a markedly higher lifetime use of any illicit substance, especially amphetamine/cocaine, than the general population. They also seemed to use drugs more periodically. The same sociodemographic characteristics were associated with increased illicit drug use in both groups.

The level of illicit drug use is related to symptoms and premorbid functioning in severe mental illness.

OBJECTIVE: There is conflicting data on drug abuse and outcome in severe mental illness. This study aims to investigate if the amount of illicit psychoactive drug use is related to symptom load or premorbid functioning across diagnosis in patients with severe mental illness. METHOD: Symptom load, sociodemographic status, premorbid functioning and the level of use of illicit psychoactive drugs were assessed in 423 subjects with schizophrenia or bipolar disorder in a cross-sectional study. RESULTS: High amount of illicit drug use was associated with poorer premorbid academic functioning. In schizophrenia, there was a significant positive association between amount of drug use and severity of psychiatric symptoms. The association between symptom load and drug use was significant after controlling for premorbid functioning. CONCLUSION: The results suggest a direct association between the quantity of current drug use and more severe symptoms in schizophrenia. Poor premorbid functioning was related to high amount of use, but did not explain the difference in symptom load.

Insight, symptoms and neurocognition in bipolar I patients.

BACKGROUND: Level of insight and its relationship to clinical variables and neurocognitive functions was assessed in bipolar I patients. METHODS: Verbal memory, executive functioning, sustained attention, general intelligence and other neurocognitive functions were compared between 37 chronic in- and outpatients and 31 matched normal controls. Detailed psychiatric interviews were completed to define the level of symptomatology and psychosocial functioning. Insight was assessed by the Scale to Assess Unawareness of Mental Disorder (SUMD). RESULTS: Seventy percent of the patients were classified as having impaired insight. Prevalence of impaired insight was 47% and 94% in remitted and symptomatic patients, respectively. Symptomatic patients scored significantly below remitted patients on insight and neurocognition. Illness and symptom unawareness were related to overall level of symptoms, measures of memory, conceptual ability and right hand psychomotor speed and accuracy. Misattribution of symptoms and signs was correlated to visuomotor speed and visuospatial performance in addition to affective symptoms and thought disturbance. CONCLUSIONS: Our findings support the hypothesis that impaired insight and other neurocognitive dysfunctions were present in a large percentage of cases among symptomatic as well as remitted bipolar patients. This may be of clinical relevance and raises important questions about the course and outcome of the illness.

Long-acting risperidone in stable patients with schizoaffective disorder.

Oral and long-acting risperidone has been shown to be effective for acute and maintenance treatment of patients with schizoaffective disorders. The present analysis investigated the efficacy and tolerability of direct transition from other antipsychotics to risperidone long-acting injectable in patients with schizoaffective disorder. Patients aged > or = 18 years with schizoaffective disorder (DSM-IV), who required a change of medication, received risperidone long-acting injectable 25 mg (increased to 37.5 or 50 mg, if necessary) every 2 weeks for 6 months. The analysis included 249 patients (47% male; mean age 43 years), of whom 74% completed the 6-month study. Mean scores for the total Positive and Negative Syndrome Scale (PANSS) and all three subscales were significantly reduced from baseline to week 4 (p < 0.001), with further improvements until treatment endpoint. Significant improvements from baseline to endpoint were seen in the mood symptom domains of anxiety/depression (10.4+/-4.1 vs 8.7+/-3.9) and uncontrolled hostility/excitement (7.6+/-3.6 vs 6.9+/-3.8). Mean Global Assessment of Function (GAF) score improved significantly from 59.4+/-15.6 at baseline to 66.4+/-17.7 (p < 0.001) at endpoint. Of 87 patients hospitalized at baseline, 67% were discharged at endpoint. Both quality of life (SF-36) and satisfaction with treatment were improved significantly at endpoint. Total ESRS scores fell progressively throughout the study, and the reduction was already statistically significant (p < 0.001) at 4 weeks. Small but statistically significant (p < 0.001) mean shifts of 1.8% were seen in body weight and Body Mass Index (BMI). Patients with schizoaffective disorder derived several benefits from a change to risperidone long-acting injectable, including reductions in psychiatric symptoms (particularly the mood symptom domains) and a reduction in the severity of drug-induced neurological movement disorders.

Measuring quality of life in first-episode psychosis.

Quality of life (QoL) measures are increasingly recognized as necessary parts of outcome assessments in psychosis. The present paper is a comprehensive study of patients with first-episode psychosis where QoL is measured by the commonly used Lehman Quality of Life Interview (L-QoLI). The aim is to examine if the L-QoLI maintain its original structure when used in a group of patients with first-episode psychosis, and to investigate what determines global subjective QoL with a specific emphasis on premorbid adjustment, duration of untreated psychosis (DUP) and clinical symptoms. The study indicates that the psychometric properties of the L-QoLI do not change significantly when used in first-episode samples. The patients report subjective and objective QoL in the fair to good range, with only a moderate association between the objective and subjective measures. Poor global satisfaction is predicted by being single, abusing drugs, being depressed, having a diagnosis of psychotic affective disorder, having poor premorbid social adjustment and DUP over 10 weeks. The study supports the notion that patients with first-episode psychosis construct QoL in the same way as other groups, and that longer durations of compromised function at this stage produces poor satisfaction with life rather than a downward readjustment of expectations.

Shortened duration of untreated first episode of psychosis: changes in patient characteristics at treatment.

OBJECTIVE: This study examined whether duration of untreated psychosis can be shortened in patients with first episodes of DSM-IV schizophrenia spectrum disorders and whether shorted duration alters patient appearance at treatment. METHOD: Two study groups were ascertained in the same Norwegian health care sector: one from 1993-1994 with usual detection methods and one from 1997-1998 with early detection strategies that included education about psychosis. RESULTS: Patients with early detection had a shorter median duration of untreated psychosis by 21.5 weeks than patients with usual detection. The number with psychosis was greater in the early detection group; the number with schizophrenia was less. Early detection patients had more substance abuse and were younger, better adjusted premorbidly, and less ill. CONCLUSIONS: Early detection can shorten duration of untreated psychosis and help more patients when they are less severely ill. Given the devastation of psychosis, this is a significant treatment advance.

Androgen replacement and quality of life in patients treated for bilateral testicular cancer.

Gonadal hormones and quality of life (QL) were assessed in bilaterally orchiectomized patients with testicular cancer who received intramuscular androgen replacement (ARP). 43 patients were to have serum analyses of testosterone LH, FSH and SHBG, preferably performed at the end of the interval between two intramuscular injections. They also completed a QL questionnaire consisting of the EORTC QLQ-C30, GHQ-28, IES and PAIS (sexuality). 17 of 31 evaluable patients had subnormal testosterone levels, and 9 highly elevated LH. Blood levels indicating hypogonadism were more often observed in the 25 patients whose ARP was scheduled at > or = 3 week intervals than in the 18 patients with < or = 2 weeks between ARP injections. A total of 11 patients reported hot flushes. The patients' QL was similar to that of a control group. However, 8 (20%) patients were 'cases' according to GHQ-28/IES, independent of their hormone levels. Current standard intramuscular ARP is not optimal in approximately 1/3 of the patients who have undergone bilateral orchiectomy for testicular cancer, particularly if scheduled at > or = 3 week intervals. Schedules for ARP have to be improved. In spite of intermittent hypogonadism most patients are psychosocially and sexually well adjusted to their health situation.

Sex-sensitive cognitive performance in untreated patients with early onset gender identity disorder.

BACKGROUND: We explored whether the cognitive performance of gender identity disorder patients (GID) was comparable to that of their biological sex or skewed towards that of their gender identity. METHOD: We tested four potentially sex-sensitive cognitive factors (rotation, visualization, perception, and verbalization) as well as two neutral factors (logic and arithmetic) in GID patients from Norway (GID-N, n = 33) or the USA (GID-US, n = 19) and in a control group (C, n = 29). The testing was undertaken prior to cross sex hormone treatment. Four-way ANOVA was applied in the final analysis of the cognitive performance and its dependency on different predictors (age, biological sex, education, group). RESULTS: In both GID groups as well as in the control group (C) males excelled in visualization and rotation, also when controlling for potential confounders (biological sex, group, age and education). No female advantage was detected. Furthermore, no interaction between biological sex and group assignment was revealed in the samples. CONCLUSION: In this study the cognitive pattern of GID patients is consistent with that of their biological sex and not that of their gender identity.

Early detection strategies for untreated first-episode psychosis.

Some studies in first-episode schizophrenia correlate shorter duration of untreated psychosis (DUP) with better prognosis, suggesting that timing of treatment may be important. A three-site prospective clinical trial in Norway and Denmark is underway to investigate the effect of the timing of treatment in first-episode psychosis. One health care sector (Rogaland, Norway) is experimental and has developed an early detection (ED) system to reduce DUP. Two other sectors (Ullevål, Norway, and Roskilde, Denmark) are comparison sectors and rely on existing detection and referral systems for first-episode cases. The study ultimately will compare early detected with usual detected patients. This paper describes the study's major independent intervention variable, i.e. a comprehensive education and detection system to change DUP in first onset psychosis. System variables and first results from the four-year inclusion period (1997-2000) are described. It includes targeted information towards the general public, health professionals and schools, and ED teams to recruit appropriate patients into treatment as soon as possible. This plus easy access to psychiatric services via ED teams systematically changed referral patterns of first-episode schizophrenia. DUP was reduced by 1.5 years (mean) from before the time the ED system was instituted (to 0.5 years). The ED strategies appear to be effective and to influence directly the community's help-seeking behaviour.

Internal consistency of the Seasonal Pattern Assessment Questionnaire (SPAQ).

We examined the consistency reliability of the widely used Seasonal Pattern Assessment Questionnaire (SPAQ). In total, 587 questionnaires from a random sample of the general population were analysed. The 6 items of the Seasonality Scale Index (SSI) correlated fairly well, and consequently this scale proved to have a high internal consistency (alpha = 0.82). Items from the SSI that measure seasonal variations in sleep and weight were consistent with other SPAQ scales that also measure these dimensions. Since the questionnaires analysed were from an epidemiological study, the high consistency reliability shows that the symptoms probed for by the SSI, tend to cluster in susceptible individuals in the general population.

Unawareness of illness in chronic schizophrenia and its relationship to structural brain measures and neuropsychological tests.

The present study seeks to elucidate the relationship between unawareness of illness in schizophrenia and frontal lobe dysfunction, in addition to investigating the relationship between lack of insight and sociodemographic and clinical variables. Twenty-one medicated schizophrenic patients, recruited from in- and out-patient wards at Ullevâl Hospital, underwent the Scale to Assess Unawareness of Mental Disorder (SUMD), neuropsychological testing, psychiatric symptom ratings and neuroimaging procedures (CT). Also, 21 matched normal controls were neuropsychologically tested. CT data were assessed blindly by two experienced neuroradiologists, according to the degree of ventricular enlargement and/or sulcal widening, and an assessment of localisation of atrophy was made. Unawareness of illness was correlated with neuropsychological measures related to executive functioning, but not with other neuropsychological measures. Five patients showed slight frontal atrophy, while two showed moderate frontal atrophy. The remaining 13 patients did not show signs of frontal lobe atrophy. Frontal lobe atrophy documented by structural brain measures was associated with poor insight in schizophrenia. Furthermore, Anergia (BPRS), GAF score and 'undifferentiated' sub-diagnosis correlated with SUMD scores. Unawareness of illness in schizophrenia may be related to frontal lobe deficit. Also, awareness of illness may not be related to general psychopathology, but rather to specific aspects.

Depression during pregnancy and after delivery: a repeated measurement study.

The aim of this study was to examine the risk of depression in the postpartum period (first four months after delivery) as compared to the remaining postnatal year and the pregnancy period. All postpartum women from two municipalities in Norway were included in a questionnaire study of mental health (n = 416). Over 50% of the women (n = 259) answered an identical questionnaire at an additional time either before or after the postpartum period. The level of depression was measured by the Edinburgh Postnatal Depression Scale (EPDS) and the Hopkins Symptom Check List-25 items (SCL-25). The point prevalence of depression (EPDS> or =10) in the first four months postpartum did not differ significantly as compared to other time periods during pregnancy and the postnatal year. This finding remained also after controlling for other risk factors of depression; high score on the life event scale, prior depression and poor partner relationship. There was a non-significant trend of lower prevalence of depression during early pregnancy and after the first eight postnatal months. In conclusion, our findings suggest that the first four months postpartum were not distinguished by higher depression prevalence as compared to other time periods during pregnancy and the first postnatal year.

Early identification and treatment of schizophrenia: conceptual and ethical considerations.

To identify and start treatment of schizophrenic patients at an early stage has been a matter of growing interest in recent years (Alanen 1994; Birchwood 1992; Docherty et al. 1978; Falloon 1992; Lieberman et al. 1993). However, we are not aware of any controlled study definitively concluding that early treatment of schizophrenia is favorable. Many researchers discuss the topic, for example, regarding outcome and prognosis (Falloon 1992) or treatment response (Alanen 1994; Lieberman et al. 1993). In this article we take a closer look at the idea of early treatment of schizophrenia by analyzing the concept of early schizophrenia/early psychosis at an epistemological level and discuss related ethical problems.