P. Ferentinos

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 and10 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.

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.

The Measurement of Fatigue in Depression

instruments such as the Medical Outcomes Study Short-Form 36 (SF-36), the General Health Questionnaire (GHQ), the Symptom Distress Checklist (SCL-90) and the Profile of Mood States (POMS). Specific fatigue instruments were used in only 10 studies to assess fatigue in patients with major depression [3–12] and in 1 study including 13 patients with dysthymia [13] . A total of 694 patients suffering from major depression (n = 681) or dysthymia (n = 13) were included. Of these studies, 6 were trials concerning the efficacy of modafinil as an adjunctive treatment in major depression [6, 8–12] . The fatigue instruments used were: Fatigue Severity Scale (FSS) in 7 studies [4–6, 8–10, 12] , Brief Fatigue Inventory (BFI) in 2 [7, 12] , Fatigue Questionnaire (FQ) in 1 [3] , Fatigue Assessment Instrument (FAI) in 1 [13] and Fatigue Scale Inventory (FSI) in 1 study [11] . FSS was the instrument most often used to assess fatigue severity in depressed patients. Validation data were provided in only 1 study using FAI to assess fatigue in a group of 13 patients with dysthymia [13] . There were no studies presenting standardisation data for any fatigue instrument in patients with major depression. In conclusion fatigue in patients with depression is understudied. Fatigue inFatigue is a frequent, albeit non-specific symptom encountered in various clinical settings. It is considered as a core symptom of major depression and the main residual symptom persisting after treatment interventions [1, 2] . Although fatigue is difficult to define and conceptualise, various self-report fatigue measures have been used to assess its severity and/or prevalence, especially in patients with physical diseases. We sought to review the specific instruments used to measure fatigue in depressed patients without co-morbid fatiguing diseases and to search for fatigue measures standardised for depressed patients. We searched the MEDLINE, EMBASE and PsycINFO databases for papers published from January 1980 to December 2005, studying fatigue in patients with major depression and/or dysthymia without co-morbid physical diseases associated with fatigue. The identified papers were screened for the fatigue measures used and critically reviewed. The key words used were: ‘major depression’, ‘dysthymia’, ‘fatigue’, ‘scale’, ‘measure’ and ‘instrument’. In the majority of studies found, fatigue was indirectly and briefly assessed by means of specific items or subscales of broader general health or psychopathology instruments. These included generic Received: November 28, 2005 Accepted aftrer revision: February 13, 2006 Published online: January 11, 2007

Predicting insomnia in medical wards: the effect of anxiety, depression and admission diagnosis

OBJECTIVE Insomnia is frequently underrecognized in medical wards; therefore, we assessed the prevalence and explored medical and psychological variables associated with insomnia. METHOD The Athens Insomnia Scale and the Hospital Anxiety and Depression Scale (HADS) were completed in 235 inpatients along with demographic data, admission diagnosis, lifetime psychiatric diagnosis and prescribed psychotropics. RESULTS The overall insomnia prevalence was 37%. Logistic regression showed that HADS anxiety and depression cases and patients with infections were more likely to have insomnia (OR 24.2, 6.1 and 5.4, respectively). CONCLUSIONS Patients with depressive and mainly anxiety symptoms are more likely to experience insomnia in medical wards. Patients with infections are also likely to have insomnia, independently of depressive and anxiety symptoms, and appropriate interventions should be applied.

P03-10 Quetiapine and hypothyroidism: A literature review

Objective Recently, there is an interest on the possible association between quetiapine and hypothyroidism. The aim of this study is to critically review all the reported cases in the international literature. Methods A Medline search for all studies dealing with quetiapine induced hypothyroidism was carried out from January 1997 to June 2008. Results Published literature on quetiapines impact on thyroid function consists of 1 double-blind study, 1 observational study, 2 open studies, 3 case reports and data from the product monograph. A study on elderly psychotic patients revealed only small decreases in T4 levels, while another one in adolescents show trends for decrease in T4 and a marked increase in TSH. An observational study of thyroid function in patients treated with quetiapine and other antipsychotics, found a decrease in T4 with no changes in TSH and T3 and another one only slight increases in TSH. In the case reports all patients excibited clinical hypothyroidism. In one case there was a positive history for hypothyroidism, while in another one the patient had experienced lithium induced hypothyroidism in the past. According to quetiapine manufacturer 0.4% of the patients experienced TSH increases with half of them requiring thyroid replacement treatment. In studies, where quetiapine was adjunct to lithium or divalproate, 12% of patients had elevated TSH levels. Conclusion We suggest a careful thyroid monitoring for patients initiating quetiapine, since hypothyroidism may emerge and masquerade psychopathologic manifestations. However, there is an open question whether thyroid dysfunction is a permanent or reversible condition.

Temperament Profile Interacts with Proximal Sleep Disturbance in Predicting Suicidal Intent

Introduction Cyclothymic-depressive-anxious-irritable (CDAI) temperament has been linked to increased suicidal risk. Sleep disturbance and short self-reported sleep duration have been associated with suicidal ideation and behavior independently of a current major depressive episode (MDE). Objectives This cross-sectional study in consecutive hospitalized suicide attempters aimed to investigate the interplay of temperament with proximal sleep disturbance in predicting suicide intent. Methods Depression severity was measured with Major Depression Inventory, whereby DSM-IV-TR diagnosis of current MDE was derived. Temporally proximal sleep disturbance (during ≥2 weeks preceding the attempt) was assessed with Athens Insomnia Scale (AIS); average night sleep duration (ANSD) was also self-reported. Suicidal intent was recorded with Becks Suicide Intent Scale (BSIS). Attempters’ temperament profile was investigated with TEMPS-A self-report questionnaire. A two-step cluster analysis of TEMPS-A subscales mean scores was performed. BSIS was sequentially regressed on AIS and ANSD along with their interactions with temperament clusters after adjusting for clinicodemographic variables and current MDE. Results 114 subjects (57.9% females), aged 16-87 (44.1±17.7) years were included. 50% reported previous attempts. 38.6% were currently depressed. 62.3% suffered from insomnia (AIS score ≥6); 42.1% slept ≤5 hours per night on average. Cluster analysis identified a CDAI group and a non-CDAI one. In multiple regressions, BSIS was independently associated with current MDE, CDAI temperament profile, AIS (beta=0.43, p=0.004) and ANSD (beta=-0.40, p=0.002). Significant interactions of temperament cluster with AIS (p=0.017) and ANSD (p=0.011) were recorded. Conclusions Temperament profile interacts with proximal insomnia and short self-reported sleep duration in predicting suicidal intent in recent attempters.

P01-35 - Fatigue in female patients with major depression: the effect of age at onset

Objectives This study aimed to investigate the independent correlation of the severity of fatigue in female patients with Major Depressive Disorder (MDD) with age at illness onset. Methods We studied 70 female patients (34 inpatients), aged 23-65 years (mean 48.2±10.6 years), with MDD as assessed with the M.I.N.I. version 5.0.0. All patients were currently in a Major Depressive Episode, with a 17-item Hamilton Depression Rating Scale (HDRS) score ≥17, and free of major fatigue-associated conditions. Reported fatigue was assessed with the 14-item Fatigue Questionnaire (FQ). Pearsons (r) or Spearmans (rho) correlations between FQ, age, inpatient status, HDRS and age at onset were calculated. A multiple regression analysis was then performed, with FQ as the dependent variable. Results The FQ score was significantly correlated with HDRS (r=0.406, p 2 =0.255). Conclusions The severity of fatigue in female patients with major depression is independently correlated with earlier age at illness onset.

P03-09 Can quetiapine induced hypothyroidism be reversible?

Objective Quetiapine induced hypothyroidism is a rare side effect requiring either drug discontinuation or initiation of thyroid replacement therapy. We highlight the potential reversibility of quetiapine induced hypothyroidism in two such cases. Methods Two case reports. Results Case 1.Quetiapine (200mg/day) was initiated to a psychotic female patient due to exaggeration of positive symptomatology. Although her thyroid function tests (TFTs) upon admission were normal after a month significant decreases in T3 and T4 level and an elevation in TSH was observed. 45 days later the TFT returned to normal, although she remained on quetiapine. Case 2. Quetiapine (300mg/daily) was prescribed to a bipolar male patient due to a mixed affective episode with a very good response. Despite his normal admission TFTs, three weeks later a decrease in total T4 and a marked increase in TSH was observed .45 days later, although no measures were taken, TFTs returned within reference range. Conclusions These are the first cases reporting reversibility of quetiapine induced hypothyroidism. TFTs alterations are dose related, relatively slight and linked to a positive history of thyroid abnormality. Our patients did not fulfil any of these criteria. Besides, hypothyroidism resolved although the antipsychotic therapy was continued and no thyroid replacement therapy was given. We suggest a careful thyroid monitoring for patients initiating quetiapine. However, physicians should wait in cases of thyroid dysfunction, since thyroid dysregulation may soon be resolved.

P01-252 Depressive symptoms as predictors of the severity of fatigue in major depression

Objective Fatigue in patients with major depression is understudied, although highly prominent. The objective of this study was to investigate the independent correlation of various depressive symptoms with the severity of fatigue in major depression. Methods Eighty-one patients (70 female/11 male, 40 inpatients/41 outpatients), aged 23-65 years (mean 48.6±10.6), with a DSM-IV main diagnosis of Major Depressive Disorder (М.Ι.Ν.Ι. 5.0.0.) and currently in a Major Depressive Episode [17-item Hamilton Depression Rating Scale (HDRS) score ≥15], were studied. Patients with physical diseases or other fatigue-related conditions were excluded. The 14-item Fatigue Questionnaire (FQ) was used for the assessment of reported fatigue. Factor analysis of all HDRS items was performed. Pearsons correlations between the derived regression factor scores and the FQ score were calculated. Age, gender, and factor scores that significantly correlated with the FQ score entered a multiple regression analysis, with the FQ score as the dependent variable. Results Factor analysis of HDRS items indicated a 6-factor structure (F1 ‘depressed mood’, F2 ‘middle/late insomnia and somatic anxiety’, F3 ‘anorexia/ weight loss’, F4 ‘general somatic symptoms’, F5 ‘anxiety/hypochondriasis’, F6 ‘early insomnia’). Only factors F1 (items 1,3,7,8), F2 (items 5,6,11) and F4 (items 13,14,17) were significantly correlated with the FQ score (p Conclusions Depressed mood, somatic anxiety, middle and late insomnia correlate independently with the severity of fatigue reported by patients with major depression.