Psychometric evaluation of the Fatigue Severity Scale in patients with major depression.

PURPOSE: This study aimed to investigate the psychometric properties of the Fatigue Severity Scale (FSS), a widely used unidimensional fatigue measure, in patients with major depression. METHODS: Subjects included were 72 patients with major depressive disorder, diagnosed with the DSM-IV based M.I.N.I. 5.0.0., without comorbid fatigue-associated conditions and Hamilton Depression Rating Scale (HDRS) scores ≥ 17 as well as 40 sex- and age-matched healthy controls. The FSS was administered to patients on two time points separated by a 1-week interval and to controls. The vitality subscale of the 36-item Short Form Health Survey (SF-36vit) and a visual analogue fatigue scale (VASF) were also administered. RESULTS: A total of 79.2% of patients vs. 15% of controls were fatigue cases according to the M.I.N.I. fatigue/energy loss item. The distribution of FSS scores was negatively skewed in the patient group, demonstrating a ceiling effect. The FSS presented satisfactory test-retest reliability (intraclass correlation coefficient 0.993), internal consistency (Cronbach's α coefficient 0.947), concurrent validity (correlations with SF-36vit, VASF and HDRS were -0.52, 0.73 and 0.32, respectively) and discriminative validity between patients and controls. Factor analysis demonstrated a unidimensional structure. The optimal FSS cutoff score for clinically significant fatigue was 5.4 against the presence of fatigue/energy loss according to the M.I.N.I. as a 'gold standard'. CONCLUSION: When administered to patients with major depression, the FSS was shown to have satisfactory psychometric properties with the exception of a ceiling effect, which may pose limitations to its use in this population.

The Fatigue Questionnaire: Standardization in patients with major depression.

Fatigue measures have not been specifically standardized in depressed patients. This study aimed to investigate the reliability and validity of the 14-item Fatigue Questionnaire (FQ), a widely used multidimensional fatigue measure, in patients with major depression without comorbid fatigue-associated conditions. Subjects included were 81 patients with Major Depressive Disorder and Hamilton Depression Rating Scale (HDRS) scores > or = 15 without conditions associated with prominent fatigue and 40 sex- and age-matched healthy controls. The vitality subscale of the 36-item Short-Form Health Survey (SF-36vit) and a visual analogue fatigue scale (VASF) served as standards of reference for reported fatigue. The FQ presented satisfactory internal consistency (Cronbach's alpha coefficient 0.924), test-retest reliability (intraclass correlation coefficient 0.978), discriminant validity (between patients and controls) and concurrent validity (correlations with the SF-36vit and the VASF were -0.469 and 0.477, respectively). Factor analysis showed a two-factor structure (physical and mental fatigue), i.e. a structure similar to the one originally proposed. However, items 3 ('sleepiness'), 4 ('difficulty starting things') and 14 ('loss of interest') did not load on the factor expected. With these items removed, the derived 11-item version of the scale was shown to be a 'purer' measure of fatigue in depressed patients, independent of the severity of depression and comorbid sleepiness.

Can quetiapine-induced hypothyroidism be reversible without quetiapine discontinuation?

Recent clinical trials and case reports have recorded dose-related thyroid function test abnormalities during quetiapine treatment usually requiring drug discontinuation or initiation of thyroid replacement therapy. The authors highlight the potential reversibility of quetiapine-induced hypothyroidism without quetiapine discontinuation in 2 in-patients (a 51-year-old schizophrenic woman and a 46-year-old bipolar man) to which quetiapine (300 and 350 mg/d, respectively) was administered. Both patients had a negative personal and family history of thyroid dysfunction. Significant decreases in T4/free T4 levels and a marked elevation in thyroid-stimulating hormone level were recorded without any clinical signs of hypothyroidism 3 weeks after quetiapine initiation. Antithyroid antibody titers remained within reference range. Thyroid function tests returned to normal 6 weeks after quetiapine initiation, although quetiapine was continued at the same daily dose without thyroid replacement therapy. These are the first cases reporting spontaneous resolution of quetiapine-induced hypothyroidism without quetiapine discontinuation. We suggest careful thyroid monitoring for patients initiating quetiapine. However, physicians can wait in cases of quetiapine-induced hypothyroidism if a close laboratory monitoring is available because thyroid dysregulation may soon resolve.

Isotretinoin and psychopathology: a review.

Isotretinoin, a synthetic oral retinoid that is used against severe nodulocystic acne, has been associated with various psychiatric side effects such as depression, suicidality and psychotic symptoms. A great number of reports on its effects have been published since its introduction into the market. However, a causal relationship has not been established and the link between isotretinoin use and psychiatric events remains controversial. The present paper reviews the available evidence regarding the association of isotretinoin and psychiatric side effects. All published material reporting psychiatric side effects following isotretinoin treatment, including case reports, case series, reports from adverse drug event reporting systems, prospective surveys and retrospective case-control studies, are presented. In addition, the neurobiology of the retinoids and possible biological mechanisms that may lead to psychopathology are described.

Sleep disturbances in relation to fatigue in major depression.

OBJECTIVE: This study aimed to investigate the independent correlations of subjective sleep disturbances (insomnia and daytime sleepiness) with the severity of fatigue in patients with major depression. METHODS: Eighty-one currently depressed patients (70 females and 11 males), aged between 23 and 65 years, with a DSM-IV diagnosis of major depressive disorder were studied. Patients with physical diseases or other conditions associated with prominent fatigue were excluded. The 17-item Hamilton Depression Rating Scale (HDRS), the Athens Insomnia Scale (AIS), and the Epworth Sleepiness Scale (ESS) were used for the cross-sectional assessment of the severity of depression, insomnia, and sleepiness, respectively. Severity of fatigue was measured with the Fatigue Severity Scale (FSS). Pearson's and Spearman's coefficients were used in bivariate correlations between FSS score and the independent variables (age, gender, inpatient/outpatient status, HDRS score, AIS total score, AIS individual item scores, and ESS score). A stepwise multiple regression analysis was then performed, with FSS score as the dependent variable. RESULTS: The severity of fatigue was significantly correlated with female sex, HDRS score, AIS total score, awakenings during the night (AIS item 2), compromised sleep quality (AIS item 5), and ESS score. Sleep quality (AIS item 5) and daytime sleepiness (ESS) were the only significant predictors of the severity of fatigue in the multiple regression analysis. CONCLUSIONS: Both sleep quality and daytime sleepiness correlate independently with fatigue severity, as measured with the FSS, in patients with major depression. The FSS does not appear to be a 'pure' measure of fatigue in depressed patients, a finding with potential implications for the choice of appropriate fatigue measures in this population.

Association of physical and social anhedonia with depression in the acute phase of schizophrenia.

BACKGROUND/AIMS: Researchers have shown interest in the association between anhedonia and depression in schizophrenia. The aim of the current study was to investigate the relationship between physical and social anhedonia with depression in a sample of inpatients with schizophrenia in the acute phase of their illness. METHODS: Sixty-two patients with acute schizophrenia consecutively admitted at the Eginition Hospital, Department of Psychiatry, University of Athens were assessed using the revised Physical Anhedonia Scale, the revised Social Anhedonia Scale and the Calgary Depression Scale for Schizophrenia. RESULTS: The Calgary Depression Scale for Schizophrenia score correlated with both physical anhedonia and social anhedonia ratings. The revised Social Anhedonia Scale score significantly correlated to self-depreciation, guilty ideas of reference, pathological guilt, early wakening, suicidality and observed depression. The revised Physical Anhedonia Scale score significantly correlated with depressive mood, self-depreciation, pathological guilt and observed depression. Self-depreciation, pathological guilt and observed depression were correlated with both social and physical anhedonia. CONCLUSION: Depression in schizophrenia and anhedonia may overlap, and it could therefore be difficult to clinically differentiate them, especially in acute schizophrenia patients.

Refractory psychosis and prominent cognitive deficits in a patient with mega-cisterna magna.

We present a case of refractory psychosis with prominent cognitive deficits in a patient with 'mega-cisterna magna', a congenital defect within the 'Dandy-Walker Complex' continuum. The 21-year-old female had a 3-year history of refractory psychotic symptoms despite adequate antipsychotic treatment. CT and MRI scans disclosed 'mega-cisterna magna'. Thorough neuropsychological testing recorded extensive deficits. Treatment with amisulpride 1200 mg/day resulted in a 30% decrease in PANSS score within 2 months. Then galantamine 8 mg/day was added and PANSS score decreased further by 27% within 2 weeks. Cognitive and social functioning was overall much improved. The effect was sustained in a 24 months follow-up. It is postulated that even a less extended cerebellar lesion, such as mega-cisterna magna, can be associated with psychosis, and in some cases with treatment refractoriness or cognitive dysfunction. Adjuvant galantamine may improve cognitive and psychosocial functioning in these patients.

Risperidone augmentation of clozapine: a critical review.

OBJECTIVE: Atypical antipsychotics are frequently used as augmentation agents in clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most studied as a clozapine (CLZ) adjunct. The aim of this study is to critically review all published studies regarding the efficacy and safety of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients. METHODS: A MEDLINE search from January 1988 to June 2005 was conducted. Identified papers were examined against several clinical, pharmacological and methodological parameters. RESULTS: A total of 15 studies were found (2 randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs)) comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years). Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6 mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was reported for 37 patients (43%). A lower RIS dosage and a longer duration of the trial seemed to be associated with a better outcome. Main side effects reported were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and hypersalivation (5.8%). CONCLUSIONS: Existing evidence encourages the use of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.

Concurrent administration of clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia.

OBJECTIVE: The aim of this article is to critically review all published studies regarding the efficacy and safety of the concurrent administration of clozapine (CLZ) and electroconvulsive therapy (ECT) in CLZ-resistant schizophrenic or schizoaffective patients. METHOD: A MEDLINE search from January 1980 to July 2005 was conducted. RESULTS: One open-label trial and 6 case studies were located, comprising 21 schizophrenic and 1 schizo affective patients (12 men and 10 women) with a mean age of 41.9 years. The duration and dosage of CLZ monotherapy before ECT were reported at least 12 weeks and 300 mg/d, respectively, in 10 patients (45.4%). Plasma CLZ levels before ECT were assessed in 12 patients (54.5%), in which only 7 (31.8%) were reported to be higher than 350 ng/mL. The CLZ dosage during ECT ranged from 200 to 900 mg/d (mean, 518.2 +/- 203.3 mg/d). The number of ECT sessions ranged from 2 to 20 (mean, 11.5 +/- 5.4). Application of electrodes was unilateral in 7 patients, bilateral in 10 patients, and mixed in 2 patients. Sixteen patients (72.7%) showed marked improvement whereas 6 patients (27.3%) had moderate, minimal, or no improvement. No predictors of outcome could be isolated. Side effects reported by 5 patients (22.7%) were nausea, tachycardia, hypertension, memory problems, and confusion. Ten patients (45.4%) relapsed during follow-up. Substantial improvement persisted beyond 4 months in only 5 patients (22.7%). CONCLUSION: Preliminary evidence exists for the safety and short-term efficacy of the concurrent administration of CLZ and ECT in CLZ-resistant schizophrenic or schizoaffective patients.

Physical anhedonia in the acute phase of schizophrenia.

BACKGROUND: The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. METHOD: Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS), the Positive and Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side-Effects (EPSE), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed. RESULTS: Both positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved. CONCLUSION: According to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology.

Randomized controlled augmentation trials in clozapine-resistant schizophrenic patients: a critical review.

Approximately 40-70% of treatment-resistant schizophrenic patients fail to benefit from clozapine monotherapy or are partial responders. During the last years several clozapine adjunctive agents have come into clinical practice. This study aims to critically review all published randomized, double-blind, placebo-controlled clinical trials (RCTs) regarding the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic or schizoaffective patients. A MEDLINE search for RCTs on clozapine adjunctive agents published from January 1980 to February 2004 was conducted. All identified papers were critically reviewed and examined against several methodological features as well as clinical and pharmacological parameters. Eleven trials including 270 patients, partial or non-responders to clozapine, assessed the efficacy of sulpiride, lithium, lamotrigine, fluoxetine, glycine, d-serine, d-cycloserine and ethyl-eicosapentanoate (E-EPA) as clozapine adjuncts. There were eight parallel-group and three crossover trials. The inclusion criteria varied widely. The duration as well as the dosage of clozapine monotherapy were reported adequate in only one trial. Plasma clozapine levels were assessed in only three trials. Main side-effects reported were hypersalivation, sedation, diarrhea, nausea, hyperprolactinaemia. The outcome favored clozapine augmentation with sulpiride, lamotrigine and E-EPA. Lithium was shown to benefit only schizoaffective patients. However, the methodological shortcomings of trials analyzed limit the impact of evidence provided.

Case studies of adjunctive agents in clozapine-resistant schizophrenic patients.

Approximately 40%-70% of neuroleptic-resistant schizophrenic patients are nonresponders even to clozapine. Several clozapine augmentation strategies have come into clinical practice, although often without evidence-based support. This study aims to critically review all the reported case studies regarding the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic or schizoaffective patients. All published case studies examining the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic patients were searched for in the MEDLINE database from January 1980 to February 2004. Case studies regarding ECT as a clozapine augmentation strategy were not included in our study. All the included papers were critically reviewed and examined against a set of clinical and pharmacological parameters, outcome measures, and reported side effects. Fifteen case studies regarding the efficacy and safety of sulpiride, risperidone, olanzapine, lithium, lamotrigine, fluvoxamine, and bromocriptine as clozapine adjuncts were found. A total of 33 schizophrenic or schizoaffective patients were included. Of the 15 studies, 8 were associated with risperidone. The duration and dosage of previous clozapine monotherapy was adequate for 16 patients. Plasma clozapine level was assessed for only 7 patients. Outcome measures were used for only 11 patients. The outcome was positive in 13 studies. Combined treatments were generally well tolerated, and side effects never resulted in discontinuation of treatment. Most case studies favor the use of risperidone as an adjunctive agent in clozapine-resistant schizophrenic or schizoaffective patients. However, small numbers of patients and other methodological shortcomings limit the impact of evidence provided.

Suicidal ideation in inpatients with acute schizophrenia.

OBJECTIVE: Schizophrenia has been associated with a high rate of suicide. This study investigates the prevalence of suicidal ideation in a population of inpatients with acute schizophrenia, together with the clinical parameters associated with suicidal thoughts. METHOD: We assessed 93 schizophrenia patients. We matched subjects for age and sex and compared subjects with and without suicidal thoughts. We performed stepwise multiple regression analysis to assess the association between specific clinical symptoms and suicidal ideation. RESULTS: Of the patients, 20.4% reported suicidal thoughts during the last 15 days. Severity of depressive symptoms, motor retardation, guilt feelings, pathological guilt, and self-depreciation predicted the patients' suicidal ideation. CONCLUSIONS: Suicidal thoughts are frequent among inpatients with acute schizophrenia. Prevention of suicidal behaviour should include helping patients improve their self-esteem and reducing depression and guilt feelings.