Alert for the efficiency of the clozapina, in high doses, in refractory mania to pharmacological treatment.

Review of literature relevant after the description of a clinical case example.

Description of a clinical case: Woman 30 years, ethnicity african, with bipolar disease type 1, with 12 years of evolution, and 11 treatments with around 1 year duration. Specifics took place with medication, such as intolerance to mood stabilizers, including lithium and valproate. Last inpatient care, with 5 months, it was for outbreak manic characterized by huge dysphoria and easy irritability with aggressiveness. There were administered antipsychotics, in high doses, and attempted electroconvulsive therapy, without success. Clinical remission has been achieved by the gradual increase of clozapina, in accordance with the patient tolerance, until 1400 mg daily without occurrence of agranulocytosis. The only intercurrence was a epileptic seizure, controlled with phenytoin.

Refractory mania is treated with clozapina in high doses, which must be administered according to the patient tolerance and clinical improvement. The risk of agranulocytosis (1-3%) is low, and is the only formal indication to suspend the treatment. The extensive metabolizers do not respond to conventional doses of psychotropic substances, they need larger doses and are more frequent in african people.

Lack of patient compliance in a general psychiatric ambulatory causes delays in diagnosing as well as in patient treatment efficacy.

a 30 year old patient underwent a psychiatric treatment which lasted two yaers. He was treated with a combination of psychopharmacs and psychotheraphy.

The patient contacted a psychiatrist for the first time exhibiting the following symptoms: loss of will and interests, weight gain, lowered general mood, avoidance of social contacts. A depressive episode was diagnosed and and antidepressive was introduced to his therapy (fluvoxamine). He did not comply to the therapy assigned nor he attended his scheduled examination.

His medicamentous therapy was intensified (fluoxamine, alprazolam, promazine). After six months, the patient returned in company with his family, and his non-compliance with the therapy was revealed.

After a sucessfful therapy an improvement in his mental state was noticed. During the last year, he was regular at his examinations and medication, with psychotherapy once a week.

Patient compliance is a prerequisite for diagnosing and a successful treatment. Combined treatment methods (psychopharmacotherapy, psychotherapy) with an adherend patient guarantee a good remission.

A partial solved issues in the treatment of Bipolar Disorder (BD) is depressive episode if is rapid cycling. Often, antidepressant monotherapy increases the risk of switching into mania/hypomania. Using quetiapine XR in these cases may help to avoid these disease burdens.

To estimate the clinical efficacy and acceptability, in rapid cycling depressive episode of quetiapine XR.

34 yrs. woman, Bipolar Disorder-Depressive Episode, rapid cycling (DSM-IV), scores YMRS=10 and HAMD-17=32 at baseline.

Depression (HAMD-17), mania (YMRS), CGI-S, CGI-I, side effects and relapse (follow-up: 12 month). The patient has a history of 12 yrs. of BD with 5 depressive and 6 manic episodes. Last year depressive episodes were 3 manic and 1 depressive episodes.

After 4 weeks, of treatment with quetiapine XR 300mg/day in the evening, the depressive scores improved 75%, sleep became normal, no co-medication was needed. The patient continued to receive quetiapine XR and assessments were performed monthly. The follow-up priod demonstrated no relapses (depressive or manic).

1. In this case of Bipolar Disorder-rapid cycling, the treatment of depressive episode quetiapine XR-300mg/day was effective and well tolerated; no switch in manic or hippomanic was noticed.

Chronic diabetics at some point gives up their vigilance in the sugar control. Many of them end up with intractable diabetic feet with limb losses incurring health budget, enormous morbidity and mortality.

300 patients who presented with diabetic feet been interviewed and noticed that ‘few weeks or months prior to their start of symptoms a major change in the treatment mechanism happens which lead to catastrophic complications of Diabetes’. They do not qualify according to DSM IV classification to be called MDE. But can be called Dysthymia. Surgical, Medical, Vascular and Psychiatric units in an Australian Hospital have been involved in these interviews (a simple questionnaire). Personal audit in two countries (Fiji Islands & Bangladesh) where Diabetes is pretty alarming in number have been included in the data.

Diabetic patients over time develop Dysthymia when they feel hopeless about control of their illness. Often they are overwhelmed by thoughts of long-term complications like retinopathy, neuropathy that they give up hope that they could combat its complications. Diabetic educators should be involved during their early stage of their illness before complications set in and should be trained to pick up dysthymic signs and symptoms for prompt referral for early psychological and psychiatric intervention.

:

• • Diabetic feet are preventable.

• • Early psychiatric assessment is helpful.

• • Preventive steps are cost effective.

• • Should Psychiatry Department have a role in the multidisciplinary management team of Diabetes?

To collect the opinions of a sample of Spanish psychiatrists and their patients about the acceptability, preference and adherence to treatment of mirtazapine orally disintegrating tablets in relation to mirtazapine conventional tablets.

It was carried out an on-line survey recruiting a total of 422 psychiatrists who responded to a questionnaire of 14 closed questions. Fieldwork for this project was conducted out between January and March 2009.

The 422 psychiatrists who responded to the present survey had an average age of 45. 54% of them were men and 46% were women. The scope of activity of the participants (multiple choice possible) was: 27.5% hospital, 68% mental health center, 27% private practice and 6% other kind of activity. The 42.5% of visited patients suffered major depression and concomitant chronic organic disease.

When prescribing an antidepressant, psychiatrists of the sample did not usually take account the patient preferences: 26% did not and 33% asked the patient “in less than 50% of the time.”

The doctors emphasized that mirtazapine orally disintegrating tablets was more convenience for the patient (94%), support for better compliance (91%), had a pleasant taste (87%) and had patient preference (86%) among the main issues that took into account when they opting for that drug formulation.

The change from mirtazapine conventional tablets to mirtazapine orally disintegrating tablets did not caused any problem for 70% of doctors.

Differences in galenic presentations of the same drug should lead significant perceived differences in clinical practice, by doctors and their patients

To estimate the prevalence of depressive symptoms in patients affected by subclinical hypothyroidism by means of Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS); to assess which depressive symptoms are prevalent in our population, with references to the factorialization of HAM-D by Cleary and Guy (1977); to verify whether levothyroxine replacement therapy alone can induce total remission of depressive symptoms.

The study enrolled 63 patients affected by subclinical hypothyroidism undergoing follow-up at the endocrinology service of San Paolo Hospital in Milan. All patients underwent an evaluation by means of HAM-D and MADRS scales and serum TSH, free T4, free T3, TPO-Ab and Tg-Ab levels were measured.

We estimated a prevalence of depressive symptoms in our population of 63.5%. Concerning the qualitative assessment of psychiatric disturbances in the population we considered, our results showed that the most frequent symptoms were part of four factors, according to the Cleary and Guy factorialization of HAM-D: these factors are representative of anxiety and somatisation (factor I), cognitive impairment disturbances (factor III), psychomotor retardation (factor V) and sleep disorders (factor VI). Levothyroxine replacement therapy alone wasn’t effective in inducing total remission of depressive symptoms.

This study suggests the importance of a psychiatric evaluation in patients affected by subclinical hypothyroidism.

Behavioural addictions (BAs) can be understood as disorders characterized by repetitive occurrence of impulsive and uncontrolled behaviours. Very few studies have investigated their association with mood disorders. The present study was undertaken to determine the prevalence of the main behavioural addictions in a sample of bipolar outpatients in euthymic phase or stabilised by medications and to investigate the role of impulsivity and temperamental and character dimensions.

One-hundred-fifty-eight Bipolar Disorder (BD) (DSM-IV) outpatients were assessed with tests designed to screen the main behavioural addictions: pathological gambling (SOGS), compulsive shopping (CBS), sexual (SAST), internet (IAD), work (WART) and physical exercise (EAI) addictions. TCI-R and BIS-11 were administered to investigate impulsivity and personality dimensions mainly associated with BAs. The clinical sample has been compared with 200 matched healthy control subjects.

In bipolar patients, 33% presented at least one BA respect to the 13% of controls. Significantly higher scores at the scales for pathological gambling (p< .001), compulsive buying (p< .05), sexual (p< .001) and work addictions (p< .05) have been found. Self-Directness (p=.007) and Cooperativeness (p=.014) scores were significantly lower while impulsivity level was significantly higher (p=.007) in bipolar patients with BA than those without BA.

To our knowledge, this is the first study investigating the prevalence of behavioural addictions in BD showing a significant association of these disorders. BAs are more frequent in bipolar patients than in healthy controls and are related to higher impulsivity levels and character immaturity.

We have randomly divide patients into control group(N=45) without antidepressants, and experimental groups in accordance with applied antidepressants: clomipramine(N=48), fluoxetine (N=49), sertraline (N=51), escitalopram (N=49), mirtazepine (N=45), and tianeptine (N=52). We have used HAMD for estimation of depression, QOL scale for quality of life, and UPDRS subscales I(behaviour and mood) and II(daily activities) for PD symptoms at pretrial, and after 3 months scores in all groups. Data were processed with SPSS for Windows.

There is no statistical significance in pretrial scores between groups. After 3 months there is: significant increase in control and significant discrease(p=0.000) of HAMD scores in all experimental groups, in favour of antidepressant with higher mediana(escitalopram 9; sertralin 8; tianeptin 6;clompramin 3; mirtazapin 3;fluoxetine 1; control -2); significant increase of QOL scores in favour of antidepressant with higher mediana(escitalopram 1.24; sertraline 1.12; tianeptine 0.65; clomipramine 0.40; mirtazapine 0.27; fluoxetine 0.27), and significant difference in UPDRS II pretrial and after 3 months subscores(p=0.016), in favour of escitalopram.

All tested antidepressant are efficient in reducing HAMD score, but only escitalopram,sertraline,and tianeptine improved HAMD, QOL, UPDRS I, and II scores without side effects.

Determine levels of folic acid and vitamin B12 in a sample of depressed patients in the first visit to mental health center.

Demonstrate a high prevalence of folate and vitamin B12 deficiency in this group of patients and the relation with the depression and treatment resistant.

The sample was all the patients with a diagnosis of unipolar depression, who were derivated by general practitioner (GP) between January and June 2009 to Vallecas Villa Mental Health Center in Madrid. The sample was 82 patients, they were between 20 and 86 years old. In 62 cases the GP derivated the patients because resistant to treatment, and in 20 cases were naive-treatment. In the first visit folate serum and vitamin B12 were measured.

69 patients present low levels of folate (84,14%), and 4 low levels of vitamin B12 (4,87%). The mean of folate was 2,2 ng/ml in low-serum folate sample and the mean of vitamin B12 was 93 pg/ml in low vitamin B2 sample. 90,80% (56) of the resistant-treatment group presents low folate serum, in the naive sample was 65% (13).

In our sample depression is associated to a very high prevalence of folate deficiency. The highest prevalence appeared in the resistant-treatment group, so it could be a factor that influence in the persistent depressive symptoms, and poor antidepressant response.

Treatment of BDII may place the physician in difficulty because of the treatment resistence.

2 male patients 48 and 52 years old diagnosed with BDII (according to DSM IV) lastest episode, major depressive episode, with a poor or partial response to long-term treatment with antidepressant, mood stabilizer and sometimes antipsychotic drugs during the presence of psychotic symptoms.

During last year their treatment was: Paroxetine 40mg/ 2x day and Lamotrigine 150mg/day. Because of the lack of response the treatment was changed as follows:

Remove of lamotrigine; decrease of paroxetine to 20 mg; adding Aripiprazole 15 mg.

BPRS, HAMD and CGI-severity were used to evaluate their symptoms and gravity.

After 2 weeks of treatment significant improvement was noticed. This includes depressive and psychotic symptoms, sleep, anxiety and cognitive symptoms. Increase of professional performance.

After using this combination, they started psychosocial rehabilitation program. Since September 2007 their situation is stabile and there have not been noticed recurrences.

Favorable clinical results were noticed to both patients, with no noticeable adverse side effects. Aripiprazole combined with Paroxetine has improved depressive and psychotic symptoms of these patients with bipolar depression.

Our findings suggest that Aripiprazole - Paroxetine is a safe and tolerable combination; however, control trials are needed to validate our findings.

Bipolar disorder begins during adolescence but often escapes diagnosis at this time because episodes are misinterpreted with other psychiatric disorders. Lithium, carbamazepine, valproate, and other drugs are used for the treatment of acute episodes and maintain treatment of bipolar disorders.

To compare the efficacy of Valproate vs. Lithium in the long-term treatment of patients with subtypes of bipolar disorders.

120 patients with more than two episodes of BD (according to DSM-IV) in a longitudinal, comparative and randomized clinical trial, for 2 years (104 weeks) divided in two equal parallel-groups with open label pre-randomized phase. Primary outcome measure was time to relapse/recurrence of any mood episodes. Survival analyses (Kaplan-Mayer and Cox Proportional Hazard) were used for statistical analysis.

Cumulative survival for valproate's group was S(104)=0.3570, (35.70% and lithium's group S(104)=0.3136, (31,36%). Valporate is superior to lithium for the treatment of non classic BD I (Log Rank 0.0309, p=0.0100). Valproate prolongs median survival time with 11±9 and mean survival time to 7±4 weeks more than lithium. Treatment with lithium has 20.4% higher relative risk for relapse/recurrence than treatment with valproate Vp (β = 0.186, p = 0.434). Valproate is superior for the treatment of BD with psychiatric comorbidity (Log Rank =0.0007. p=0.0026).

We found that valproate is significantly more effective than lithium in prophylactic treatment of bipolar I disorders in non-classic subtype and in bipolar disorder with psychiatric comorbidity.

Recurrent depression could be considered as a stumbling block for the individuals during their active period of life. Beside the global functionality, recurrent depression could affect negatively academic skills of depressed subjects that will result in considerable higher indirect costs of the disorder. Our main objective was to reveal the clinical and non clinical factors correlated with academic impairment in subjects with recurrent depression.

We performed a longitudinal retrospective study on 248 patients admitted in our Clinic for Recurrent depressive disorder during 2001 - 2005. Two control samples were done, one with Bipolar affective disorder (N=44) and other with Persistent delusional disorder (N=59).

From 90 depressed subjects who were employed at the onset of psychiatric disorder, 56 (62.2%) became retired and another 6 (6.6%) became unemployed. Despite the treatability of recurrent depression the negative outcome on academic skills was similar to that occurring in both control groups that traditionally are considered as being more disabling. The clinical factors that concurred to the worsening of academic status were the more advancing age at the onset and actual moment of recurrent depression (p=0.006 and p=0.012 respectively), along with longer total duration of recurrent depression (p< 0.001), the absolute total number of depressive episodes and psychiatric hospitalizations (p=0.001).

Recurrent depression has a significant negative outcome on academic skills. The disabling character of recurrent depression could be caused by its high chronicity along with high recurrent pattern of clinical evolution.

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.

517 patients with a diagnosis of major depressive disorder were evaluated in the period January to December 2008 in First Psychiatry Clinic of Tirgu Mures. The data obtained were entered into computer, processed and were compared statistically with data from literature.

380 of the 517 patients suffer from one or more psychosomatic diseases. The majority patients with depressive mood disorders and psychosomatic illness associated were between 50 and 59 years old. The incidence of these diseases is more common in female sex. 75% of all patients hospitalized for these diseases are women. The most common disease associated with depression was hypertension. It is followed by coronary artery disease, gastrointestinal disorders, hypothyroidism, type 2 diabetes mellitus and duodenal ulcer. The most common gastrointestinal disorders were chronic gastrointestinal, chronic recto colitis and gastro duodenal ulcer.

Depression is one of the most common disease for which patients are presented in specialty medical practices and psychiatric hospitals. Frequently, the psychiatric disorder is associated with some psychosomatic diseases that can decrease compliance of these patients and worsen long-term prognosis of the psychiatric disease.

Low testosterone levels in men are associated with the metabolic syndrome (MetS) as well as with depressive symptoms, low vitality and sexual dysfunction.

To assess the effects of testosterone administration on these subjective symptoms, which have not extensively been studied in hypogonadal men with the MetS.

In a randomized, placebo-controlled, double-blind, phase III trial, 184 men suffering from both the MetS and hypogonadism were included. They were treated for 30 weeks with either parenteral testosterone undecanoate (TU; 1000 mg IM testosterone undecanoate, at baseline, and after 6 and 18 weeks; Nebido®) or placebo injections. 105 (92.9%) men receiving TU and 65 (91.5%) receiving placebo completed the 30 week trial. The Beck Depression Inventory (BDI), Aging Males’ Symptoms (AMS) scale, and International Index of Erectile Function 5-item (IIEF-5) scale at baseline, 18 and 30 weeks were analysed using multilevel analysis.

The mean age was 52.1 years (range: 35-69), with a mean body mass index of 35.5 kg/m2 (SD 6.7), and a mean total testosterone level of 8.0 nmol/L (SD 4.0). There were significant improvements in BDI (mean difference vs. placebo after 30 weeks: -2.5 points; 95% confidence interval [CI]: -0.9;-4.1; P=0.003), AMS (-7.4 points; 95% CI: -4.3;-10.5; P< 0.001), and IIEF-5 (+3.1 points; 95% CI: +1.8;+4.4; P< 0.001). The effects were strongest in men with baseline total testosterone levels < 7.7 mmol/L.

TU administration may improve depressive symptoms, aging male symptoms and sexual dysfunction in hypogonadal men with the MetS.

To conduct a subgroup analysis of the efficacy of adjunctive aripiprazole as treatment in patients with major depressive disorder (MDD) who demonstrated an inadequate response to standard antidepressant therapy (ADT).

Data were pooled from three identical, short-term, double-blind, placebo-controlled studies (CN138-139, CN138-163, CN138-165) with an 8-week phase of placebo plus ADT and a 6-week double-blind phase with ADT plus adjunctive placebo or aripiprazole. Only MDD patients without psychotic features were eligible for entry. The primary efficacy endpoint was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind phase. Subgroup analyses of the primary efficacy endpoint were performed for age, race, ethnicity, MADRS response, number and choice of previous ADTs, episode duration, and use of selective serotonin re-uptake inhibitors (SSRI).

Compared with the adjunctive placebo group, adjunctive aripiprazole was associated with greater reductions in MADRS total score in all subgroups. Mean change in MADRS total score ranged from -10.71 to -5.89 with adjunctive aripiprazole and -7.57 to -4.10 with adjunctive placebo. No statistically significant treatment-by-subgroup interaction effects were observed for any subgroup except gender (p=0.039). This difference is, however, primarily because of results from study CN138-139 results; consistent results between men and women were reported in CN138-163 and CN138-165.

Pooled data indicate that in patient populations with similar baseline characteristics, treatment with adjunctive aripiprazole and ADT is efficacious in improving the symptoms of MDD in subgroups of patients having an inadequate response to ADT.

To evaluate the efficacy of aripiprazole as adjunctive treatment in patients with major depressive disorder (MDD) without psychotic features and an inadequate response to standard antidepressant therapy (ADT).

Data were collected from three identical, short-term, double-blind, placebo-controlled studies (CN138-139, CN138-163, CN138-165). After a single-blind prospective phase with placebo plus ADT, patients with inadequate response were randomized to 6-weeks’ treatment with adjunctive aripiprazole or placebo. The primary efficacy endpoint was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) total score during the double-blind phase. Secondary endpoints were response (≥50% reduction in MADRS total score), remission (MADRS total score ≤10 and ≥50% reduction in MADRS total score), and mean change in Hamilton Depression Rating Scale (HAM-D17) total score.

In all three studies, adjunctive aripiprazole was associated with a significantly greater reduction in MADRS total score than adjunctive placebo, with a treatment difference ranging between -3.73 and -2.84 (p≤0.001 in each study). Response and remission rates with adjunctive aripiprazole (32.4-46.6% and 25.4-36.8%, respectively) were also significantly higher than with adjunctive placebo (17.4-26.6% [p< 0.05 in each study] and 15.2-18.9% [p< 0.05 in each study]). Mean change in HAM-D17 total score ranged from -7.64 to -6.77 with adjunctive aripiprazole and from -5.12 to -4.41 with adjunctive placebo (p< 0.001 for each study).

Results of the three studies indicate that treatment with adjunctive aripiprazole and ADT is effective in improving the symptoms of MDD in patients who have had an inadequate response to ADT.

Suicide is a multicausal phenomenon posing a great challenge to medicine and society, yet we still have limited knowledge concerning underlying biochemical, neuroanatomical and genetic factors. Research increasingly points to a role of the serotonergic system, both on the level of suicidal behavior, and such behavioural traits which may serve as important intermedier endophenotypes in suicide research. Although results are conflicting, several studies described an association between the 5-HTTLPR polymorphism and suicide, as well as this polymorphism and certain aggressive traits. Impulsive aggression is also thought to play a major contributory role in suicide. The aim of our research was to investigate the association between the 5-HTTLPR and aggressive traits in depressive patients carrying a higher risk for suicide and healthy controls.

137 major depressive and 164 healthy controls women were recruited. Participants completed the Buss-Durkee Hostility Inventory and were genotyped for 5-HTTLPR. Association of aggressive traits and indeces with 5-HTTLPR genotype in the two groups were analysed using ANCOVA.

Diagnosis and 5-HTTLPR genotype showed a significant association with aggressive traits. The pattern of association was different in the depressed and control groups. The strongest interaction effect between genotype and diagnosis was observable in case of Resentment.

We found a significant association between 5-HTTLPR and several aggressive traits. In case of depressive patients the association was more marked. In depressed women the 5-HTTLPR shows a stronger association with aggressive traits related to aggression turned inward, which may play a role in the background of suicide.

The issue whether the clinical characteristics of unipolar psychotic major depression (PMD) vary according to the age of onset remains still unclear. In this study we assess comparatively the clinical characteristics of young early-onset (n=30), elderly early-onset (n=34) and elderly late-onset (n=35) psychotic depressives.

Ninety-nine inpatients suffering from DSM IV unipolar PMD were assessed on the basis of SCID IV, HRSD and a physical impairment rating scale.

The elderly late-onset patients suffered from overall more severe depression compared to both categories of early-onset ones, more gastrointestinal symptoms compared to young early-onset patients and more psychic anxiety compared to elderly early-onset patients. Moreover, they expressed significantly more frequently delusions of somatic content and had higher scores on the HRSD item of hypochondriasis than their young early-onset counterparts. The group of elderly early-onset PMD patients was found to hold an intermediate position between the young early-onset and elderly late-onset PMD patients with regard to hypochondriacal ideation, gastrointestinal symptoms and delusions of somatic, guilt and paranoid content.

The findings of the present study suggest considerable differences between young, elderly early-onset and elderly late-onset PMD patients with respect to their clinical features.