The potential efficacy of various antiepileptic drugs in the treatment of Panic Disorder (PD) with (PDA) or without Agoraphobia has been studied in clinical trials, though not as yet that of lamotrigine (LTG).

We administered LTG to four outpatients with PDA according to DSM-IV-TR criteria, as an augmentation therapy (three patients with chronic and severe agoraphobia) or monotherapy (one drug-naïve patient with first-onset PD and moderate agoraphobia). LTG was titrated up to 200 mg/day within a 6-week period and remained at that dosage for another eight weeks. The patients were clinically monitored every week, while standard psychometric evaluations were completed at baseline and after the end of the trial.

The patient under LTG monotherapy exhibited a complete remission of his panic attacks and a significant improvement in agoraphobic avoidances and other outcome measures. Some improvement was evident after the clinical trial in one more patient who exhibited a complete remission of her spontaneous panic attacks and in another patient who exhibited reductions in both her anxiety levels and PD-related cognitions.

Although anecdotal and thus in need of replication in well-designed large studies, our preliminary findings suggest that LTG as monotherapy (at 200 mg/day) might improve significantly PDA symptomatology in a proportion of drug-naïve patients with recent-onset PD and moderate agoraphobia, while LTG as augmentation agent (at 200 mg/day) might improve at least some aspects of the clinical psychopathology of PD patients with chronic and severe agoraphobia.

Preliminary studies providing evidence of the neuroprotective effect of SSRIs in patients with Multiple Sclerosis (MS) by improving the metabolic function of axons. The aim of this, open label, randomized, controlled, one year follow-up prospective study was to investigate the effect of escitalopram in the prevention of relapses in women with MS.

Forty eight ambulating women with relapsing-remitting MS were randomly assigned to receive 10 mg of escitalopram per day (e-group, N=24) or to continued the study without medication as a control group (c-group, N=24). Neurological examination was performed, by the same neurologist, at baseline and at every regular (4 weeks) and additional visit after a suspect exacerbation.

During the study period 55 exacerbations occurred in 33/48 (68.7%) of the patients, and these were confirmed by the study neurologist. E- group patients’ present a mean of 0.8 (SD=0.8) and c-group patients’ a mean of 1.4 (SD=1.0) exacerbations per year. Patients treated with escitalopram present a statistically significant reduction in the mean number of MS relapses respect to the previous year (paired t-test, df=23, t=4.9, p< .001). There was no significant difference between the mean number of MS relapses during the year of the study and the previous year in c-group (paired t-test, df=23, t=-0.68, NS). The cumulative risk for relapse was 2.9 times higher for the controls than for escitalopram-treated patients (95% CI= 1.7- 5.1, p< .001).

This study provides evidence that escitalopram tends to decrease MS disease activity in women with MS.

Both tricyclic antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase QTc interval to a moderate extent (10-20 msec). Moreover, electroconvulsive therapy (ECT) also increases patients’ propensity to arrhythmias. Finally, females are more prone than males to both drug-induced QTc prolongation and torsades-de-pointes. Thus, the combination of all the above treatments raises serious safety concerns. We investigated the safety of the co-administration of ECT with a tricyclic-ziprasidone-quetiapine combination with respect to QTc interval in six female patients with severe major depression resistant to pharmacotherapy.

Each patient underwent a series of 10-11 sessions of bilateral ECT. QTc intervals were calculated at baseline and several times up to 10 min after seizures cessation in a total of 63 patients/ECT sessions.

A small initial decrease of QTc after the administration of pre-ECT medications was followed by its steady statistically non-significant increase during the first 20 sec after seizure cessation. Thereafter, a steady larger and statistically significant decrease of QTc emerged during the ensuing 21-50 sec interval. Finally, this decrease was gradually reversed within the following 2 min approximately with return of QTc interval to stable baseline levels.

Overall, QTc interval changes remained within normal limits (fixed at 470 msec in women), without the occurrence of any cardiac adverse events, especially severe arrhythmias such as torsades-de-pointes. Our findings suggest that the co-administration of these treatments might be safe, at least with respect to QTc interval changes.

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.

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). Pearson's (r) or Spearman's (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.

The FQ score was significantly correlated with HDRS (r=0.406, p< 0.001) and age at onset (r=-0.281, p=0.02). In the multiple regression model, HDRS and age at onset turned out as significant independent predictors of the FQ score, with standardised beta coefficients of 0.419 (p< 0.001) and -0.3 (p=0.006), respectively (R2=0.255).

The severity of fatigue in female patients with major depression is independently correlated with earlier age at illness onset.

There is a substantial body of evidence that cognitive deficits in schizophrenia and bipolar disorder persist after the subsidence of active symptoms. The aim of the study was to assess and compare the cognitive functioning of patients with clinically stable schizophrenia and bipolar disorder.

Attention, memory, verbal learning ability, visuospatial ability, executive functions and social cognition were assessed in 21 patients with schizophrenia in remission, 23 euthymic bipolar-I patients, and 27 normal controls, using WAIS - Vocabulary, Block design, and Digit span, Stroop Test, Babcock Story Recall Test, Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (Trails A and B), Wisconsin Card Sorting Test (WCST), and Faux Pas Recognition Test. The three groups were matched for gender, age and education. One-way ANOVA with post hoc Bonferroni corrections was used for the between groups comparisons.

Both bipolar disorder and schizophrenia patients were significantly impaired on tests of working memory, learning abilities, and executive functions compared to control subjects. Patients with schizophrenia performed significantly worse than patients with bipolar disorder on attention and verbal memory tasks, whereas the latter performed worse than normal controls on visuospatial ability tasks.

Table 1

Comparison of neuropsychological function

Our results indicate that stable schizophrenia and euthymic bipolar disorder exhibit different but overlapping profiles of cognitive impairment.

Transcranial magnetic stimulation (TMS) is a novel treatment for patients with depressive disorder. TMS is a noninvasive method to excite neurons in the brain: weak electric currents are induced in the tissue by rapidly changing magnetic fields. We report two cases suffering from pharmacoresistant depression and the efficacy of TMS in their treatment.

The first case was a 45-year-old male Caucasian patient suffering from unipolar depression and the second case was a 53-year-old female Caucasian patient suffering from bipolar depression.

The patients were under treatment with SSRI, SNRI, NASSA (one medicine or combination of them) without any or minor improvement.

So TMS sessions were performed daily in both patients for a period of one month.

A marked reduction of depressive symptoms was demonstrated in both patients. Thus, TMS sessions may help the pharmacoresistant depression by minimizing physical and subjective discomfort. Furthermore TMS appears to be safer and better tolerated than many others medicines or electroconvulsive therapy. Further studies are needed in order to investigate the effect of TMS in resistant depression

A significant number of patients suffering from a mood disorder gain weight either due to the medication side effect and/or the lack of exercise. Binge Eating disorder has a high comorbidity with mood disorders. Both disorders have been found separately to have a high negative impact ob the patients quality of life

The aim of the study was to investigate the possible impact of binge eating symptomatology in the quality of life of obese patients suffering from a mood disorder.

We approached 117 obese patients treated for mood disorder (unipolar and/or bipolar). All patients were recruited from a free of charge anti-obesity program specifically designed for mental patients that have gained weight. Each participant filled in the WHO Quality of Life Brief Scale (WHOQOL-Bref), a questionnaire on Binge Eating symptomatology based on DSM-IV research criteria, the General Health Questionnaire (GHQ) and the Social Physique Anxiety Scale (SPAS).

According to DSM-IV criteria 40 patients were suffering from Binge Eating Disorder. The comparison between Binge Eating and non Binge Eating group (t-test) showed that the former group had higher SPAS measurements (p=0.007) and lower WHOQOL-Bref measurements in the psychological (p=0.01) and physical (p=0.006) domains. All other measurements as well as age, body mass index and gender did not show any statistical significant difference between the two groups.

The presence of Binge Eating symptomatology might worsen patients quality of life especially when they are already carrying the burden of a mood disorder and obesity.

Patients with psychotic or mood disorders often undergo electroconvulsive therapy (ECT) while receiving antipsychotic and/or other pharmacological agents. Paliperidone (PLP) -a benzisoxazole derivative and the principal active metabolite of risperidone- is a second-generation antipsychotic which has been developed in an osmotic controlled-release oral-delivery system. Thus the peak-through fluctuations of its concentration in plasma are minimized, with consequently decreased incidence of side-effects. To the best of our knowledge, there are, as yet, no reports on the safety of ECT-PLP co-administration.

Nine female inpatients suffering from affective disorders (N=7) or schizophrenia (N=2) underwent ECT while receiving PLP (3-12 mg/d). Patients’ regimen included other psychotropic medications as well (mainly antidepressants and/or antipsychotics). All patients were monitored closely for recovery time, post-ictal delirium, cardiological and EEG status for at least one hour after each ECT session. In addition to their clinical evaluation, patients’ cognitive -especially memory- functioning was regularly assessed by the Mini Mental State Examination. Overall, patients underwent 83 sessions of bilateral ECT.

ECT-PLP combination was well tolerated and even in cases where cognitive side-effects were of moderate severity (three cases; all were also receiving venlafaxine), they were transient.

Although anecdotal and thus in need of replication in well-designed large studies, our preliminary findings suggest that ECT and PLP can be safely combined whenever both indicated.

The high comorbidity of depression in patients with diabetes mellitus type 2 has been established.

The association between Obsessive Compulsive Disorder (OCD) and diabetes mellitus type 2 is poorly understood.

The aim of the present study was to assess the degree in which diabetes mellitus type 2 is accompanied by OCD.

131 diabetic patients, 55 female and 76 male were randomly enrolled and during the first assessment was administered in all participants the Zung Self Rating Scale (ZUNG) and the Maudsley O-C Inventory Questionnaire (MOCI). After one year, while an intensive effort to improve the patients’ metabolic profile was performed, the diabetic patients that were initially uncontrolled (n = 31) were re-evaluated by the same psychometric tools. From those 31 patients 10 had managed to control their metabolic profile.

MOCI and the sub-scale of slowness are statistically related with the diabetic profile (controlled-uncontrolled), with uncontrolled patients scoring significantly higher on the overall MOCI score and the factor of slowness of MOCI scale (p = 0.028). Regarding the association between the values of Glycosylated Haemoglobin (HbA1c) and the scores of MOCI it was found that they were significantly positively correlated in overall scores (p = 0,028) and in the subscale of slowness (p = 0,028). The analysis revealed a positive association between depression (p = 0.004) and obsessive compulsive disorder symptomatology (p < 0.001) and thepatient’s metabolic profile.

Diabetes mellitus type 2 is associated with obsessive compulsive disorder symptomatology and depression. Improvements in glycaemic control were found to decrease the severity of the symptoms.

We reported that the non-specific 5HT agonist m-chlorophenylpiperazine (mCPP) and the SSRI fluoxetine (FLX) both cause acute persistence increases in the rewarded alternation (RA) model of OCD. Chronic pretreatment with either substance or their combined subclinical doses protects from this ‘pathogenic’ effect, so mCPP and fluoxetine exhibit cross-tolerance and synergy.

Using specific 5HT2A and 5HT2C receptor antagonists we investigated whether these receptors participate in a common mechanism of action mediating the acute mCPP/fluoxetine effect in our model.

Naïve, male Wistars were used. Drugs used (intraperitoneally): FLX (10mg/kg), mCPP (2.5mg/kg), M100907 (5HT2A antagonist, 0.03mg/kg), SB242084 (5HT2C antagonist, 0.5mg/kg), vehicle. Experiments included a drug-free training/baseline phase in T-maze RA (group-matching for spontaneous persistence: SP).

Experiment 1: Effects of M100907, SB242084, vehicle were assessed on 3 matched low SP and 3 high SP groups.

Experiment 2: the acute effect of FLX, mCPP and saline were examined on RA in 3 SP-matched groups.

Experiment 3: Effects of Vehicle+FLX, M100900+FLX, SB242084+FLX and Vehicle were examined on RA, in 4 SP-matched groups.

Experiment 4: Correspondingly for mCPP.

Experiment 1: Neither M100907 nor SB242084 affected high or low SP.

Experiment 2 replicated the pathogenic effects of FLX/mCPP.

Experiment 3: Neither M100907 nor SB242084 affected the pathogenic effect of FLX.

Experiment 4: in contrast, SB242084 (but not M100907) significantly reduced the pathogenic mCPP effect.

The acute pathogenic action of mCPP, but not of FLX, involves 5HT2C but not 5HT2A receptors. the similar acute action of mCPP and FLX on persistence cannot be attributed to 5HT2 mediation.

In the rewarded alternation model of obsessive compulsive disorder (OCD), the serotonin agonist m-chlorophenylpiperazine (mCPP) increases persistent behaviour, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI-fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increases, counteracted by mCPP pretreatment.

This study

1. a. further explores the apparent cross-tolerance between fluoxetine and mCPP and

2. b. extends the model by investigating its sensitivity to dopaminergic manipulations (D2,3 agonism - quinpirole).

In both experiments, baseline and drug testing was carried out under daily T-maze alternation training.

Matched group (n=8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration):

1. 1. saline,

2. 2. low-dose fluoxetine (2.5mg/kg),

3. 3. low-dose mCPP (0.5mg/kg) or

4. 4. combined fluoxetine+mCPP.

One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10mg/kg), the other with high-dose mCPP (2.5mg/kg).

One group (n=12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg).

Quinpirole significantly increased directional persistence after 13 administration days.

These results establish the sensitivity of the rewarded alternation OCD model to D2,3receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

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.

A Medline search for all studies dealing with quetiapine induced hypothyroidism was carried out from January 1997 to June 2008.

Published literature on quetiapine's 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.

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.

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.

Two case reports.

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.

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.

Children abduction by one parent and their transport refers to a foreign country is a gradually increasing phenomenon worldwide as well as Greece. Data from the Greek Ministry of Justice show that the frequency of such incidences is up to one a day (360/year). Some but not all of these cases come to the attention of the International Social Services (Division of Greece).

Records of fifty (50) cases of inter family abduction were obtained. These were cases that took place during the year 2003. These records were studied and analysed. The majority of cases concerned abductions within the European Union. Permission from the Personal Data Protection service was obtained before the research.

It was found that fathers were predominantly the abductors (60%). Based on the medical records of the parents, the abductor had established psychopathology (fathers 51,1%; mothers 48,5%). The abducting fathers made significant use of violence (50%) compared to the mother abductors (20%). The legal procedures that ensued the abductions were particularly prolonged: The trial period until the reach of a verdict took an average of 3 years.

In the cases of children abduction by a parent, there is high correlation between the action and the psychopathology of the abductor. The need for establishment of services appropriate to face this multidisciplinary problem is imminent. The long time each case takes to be resolved has obvious implications for the mental health of the children and the parents involved.

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.

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. Pearson's 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.

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< 0.05). F1, F2 and F4 turned out to be significant predictors of FQ in the multiple regression, with standardised beta coefficients of 0.291, 0.290 and 0.278 (p< 0.05), respectively.

Depressed mood, somatic anxiety, middle and late insomnia correlate independently with the severity of fatigue reported by patients with major depression.

To measure Anxiety, Depression and Qol in IBD patients through psychometric tools and correlate these results with the presence or absence of the inducible form of Heat Shock Protein 70 (HSP70i) in the histologic examination of the same patients. The HSPs are cellular proteins with ubiquitus presence in humans, known to exert cytoprotecive functions when induced under conditions of cellular stress ( heat, hypoxia, etc as well as psychophysiological stress).

The study was conducted between 2005 and 2008 in two general state hospitals in the broader area of Athens, Greece.

59 IBD patients hospitalized for the endoscopic investigation of a possible relapse of their disease participated in the study(37 UC, 21 CD, 1 Intermediate Colitis).

A cross-sectional study was conducted through administration of the inventories and the comparison of their values with the presence of HSP70i in the histologic examination of each patient.

1. a. WHOQOL-BREF;

2. b. Zung Depression Scale;

3. c. STAI (State Trait Anxiety Inventory);

4. d. Нospital Anxiety Depression Scale;

5. e. SPA-810 Antigen for HSP70i (Stressgen, Canada).

The X2 distribution for nominal data showed that the presence of the inducible form of HSP70 in the lymphoid tissue, the neutrophiles and the monocytes of IBD patients’ histologic examination is not the same (not homogeneous) regarding depression, anxiety and quality of life, suggesting its possible psychosomatic character (X2>6.635,d.f.=1,p< 0.01).

Depression is the most frequent psychiatric disorder encountered in patients with Multiple Sclerosis (MS), with a life-time prevalence of approximately 50%. INF-beta (INF-β) shows beneficial effect on the course of MS. Although it has been suggested that interferons may be associated to depression, the validity and the nature of this relationship remain unclear regarding INF-β. The objective of this study is to review the scientific literature in order to elucidate the relationship between depression and INF-β therapy.

This systematic review was based on Medline, Embase and, PsycLIT literature searches (through January 2005), supplemented by bibliographical citations in identified papers.

The majority of studies ruled out a correlation between INF-β1a/1b and depression in MS patients. However, patients with a recent history of depression may be at higher risk for depression particularly in the early phase of treatment (first 6 months), even if they are not depressed at the initiation of medication. There is an association between depressive symptoms and discontinuation of INF therapy but INF-β does not seem to be associated with suicide attempts. Treating patient-reported depression increases adherence to treatment.

Clinicians should not refrain from including patients with MS in INF-β treatment programs, even those with depression in the past or at the present time. Screening, monitoring, and early antidepressant treatment is necessary to optimize IFN therapy for the majority of patients with MS.