Oral isotretinoin is presently regarded as the drug of choice for the treatment of severe and recalcitrant acne.

Although its use has been associated with various psychiatric side effects, the casual relationship between these manifestations and oral isotretinoin still remains in dispute.

The purpose of this study was to investigate the incidence of psychopathological reactions in patients with severe acne orally treated with isotretinoin.

Seventy-two (72) patients with severe acne and thirty-six (36) healthy volunteers acne enrolled in the study from January 2003 and August 2009. Acne patients were allocated either to oral isotretinoin (1mg/kg/day) (N=36) or to topical treatment (N=36). All patients and controls were separately interviewed by two psychiatrists before and 1, 3 and 6 months after onset of treatment. Their psychological status was evaluated using SCID-I, SCID-II (DSM-IV) and Hamilton Scale for Depression and Anxiety.

A statistical significant increase in the incidence of depression, mood and/or anxiety disorders was observed in the group of isotretinoin-treated acne patients as compared to the group of those topically treated and to healthy controls. No association between development of symptoms of mental disorder and duration of treatment with isotretinoin was detected.

In view of the above findings it seems reasonable to suggest that oral isotretinoin may be capable of causing anxiety and/or depressive or other mood disorders in patients with severe acne. Close psychiatric monitoring should be included in the investigations that are routinely performed throughout oral isotretinoin treatment of these patients.

The rate of manifestation of depressive episodes can vary appreciably. The complete development of a depressive episode may be very rapid, taking less than one hour or be very slow, taking up to one month. Altough this clinical observation suggests different neurobiological pathomechanisms, the onset speed of depressive episodes in different affective disorders has not been investigated systematically up to now. The objective of this study was to establish the onset speed of depressive episodes in patients with a history of at least one depressive episode and to compare the onset speed in unipolar with that in bipolar affective disorders.

A group of 96 inpatients was investigated consecutively using the structured patient interview “Onset of Depression Inventory” (ODI). In 76 patients, there was a unipolar depressive disorder and 20 patients suffered from a bipolar depressive disorder.

The onset speed of the current depressive episode in patients with effective disorders correlated significantly with the onset speed of the previous depressive episodes (p < 0.001). Furthermore, there was a significant difference in the onset of the depressive episodes between unipolar and bipolar affective disorders (p < 0.001). In 55% of patients with a bipolar disorder, the depressive episode was manifested within one week whereas this was the case in only 22,37% of the patients with a unipolar affective disorder.

The rate of manifestation of depressive episodes differs between unipolar and bipolar disorders. The clinical observation reported here can support the diagnostic appraisal of depressive episodes.

Considering the effects of the level of social support and self-esteem as risk factors in the onset and continuation of depression, the purpose of the current study (in addition to studying the demographic items of depression) was to investigate the correlation between depression and level of social support and self-esteem in Iranian university students studying non medical majors.

The study was a cross-sectional descriptive-analytic research carried out on the students of Ferdowsi University of Mashhad in 2006. Self administered questionnaires on socio-demographic information (age, gender, marital status, and educational level), Eysenk self-esteem scale, Beck Depression Inventory and Cassidy social support scale were randomly given out to students who were selected by multi stage randomized sampling. The data were analyzed using SPSS version 14 using the χ2-test.

1200 students responded to the anonymous questionnaires. A total of 57.2% of the participants had depression (36.3% mild, 14.4% moderate and 6.5% severe). Depression was significantly higher in males, singles and in 25-29-year-old students. Results showed that 9.4%, 18.3% and 72.3% of the participants reported low, moderate and high levels of social support respectively. 1.8% and 6.3% of the participants reported low and moderate levels of self-esteem respectively; while 91.9% reported high levels of self-esteem.

Depression has a higher rate in non-medical university students of Iran than general population. Levels of social support and self-esteem were negatively associated with frequency of depression.

Mixed Bipolar patients are those who have co-existing depressive symptoms during mania. These patients are supposed to have a worse evolution.

The objective of this study was to compare the long-term outcomes of patients who had at least one mixed episode with those who experienced only pure manic episodes.

169 outpatients diagnosed of Bipolar I disorder and treated at least during two years were included. 120 patients (71%) complited the follow-up over 10 years. Baseline demographic and clinical variables were included.

The patients with mixed episodes (37%) had a significantly younger mean age at onset comparing with those with manic episodes (25.3 years vs. 30.8 years; p=0.025) they also had more previous mood- incongruent psychotic symptoms χ2= 6.77, p=0.034), more number of hospitalizations (OR= 1.36, 95% CI = 1.14; -1.63; p< 0.001), and more number of episodes (OR= 1.21, 95% CI = 1.10-1.31; p< 0.001). There were no significant differences relating to depressive episodes, alcohol use, drug abuse, suicidal behaviour and suicide attempts.

Age at onset differed significantly between the mixed episode and pure mania groups, with mixed episode patients having a younger age of onset. This is interesting as one of the major results of the study we have found that age at onset mediates some of the factors classically related to outcome in mixed episodes like alcohol abuse and suicide attempts. However, independently of age at onset, these patients represent a especially severe type of bipolar disorder.

To evaluate the long-term tolerability and effectiveness of aripiprazole adjunctive to lithium or valproate in bipolar mania.

Completers of a 6-week double-blind comparison of adjunctive aripiprazole versus placebo in bipolar mania partially responsive to monotherapy were followed up over 46-weeks on open-label aripiprazole plus lithium (ARI+LI) or valproate (ARI+VAL).

283 (ARI+LI n=108; ARI+VAL n=175) patients entered and 146 (ARI+LI n=55; ARI+VAL n=91) completed the 46-week extension. Safety results for both combinations were consistent with the known tolerability profile of aripiprazole, lithium and valproate. No clinically significant changes in lipids or glucose were observed with either ARI+LI or ARI+VAL. Mean (SE) weight change from double-blind endpoint to Week 46 (LOCF) was 2.3 (0.6) kg with ARI+LI and 2.0 (0.4) kg with ARI+VAL. Temporal analysis of the time of first onset of adverse events showed that akathisia and insomnia tended to occur early in treatment, with few new cases in patients previously treated with aripiprazole during the 6-week study.

Significant improvements from baseline in YMRS total score and MADRS total score were sustained over the 52 weeks with both ARI+LI and ARI+VAL treatment.

Long-term aripiprazole adjunctive to lithium/valproate in bipolar mania was safe and well-tolerated. Improvements in manic and depressive symptoms observed during the first 6 weeks of treatment were maintained.

To determine the efficacy of QTP in patients with bipolar I disorder with mixed symptoms.

Data from 2 phase III studies (D1447C00126 and D1447C00127) were pooled. Unlike previous analyses of these studies, mixed events were analyzed separately. Patients received QTP (400-800 mg/d)+Li/DVP to achieve ≥12 weeks of clinical stability followed by double-blind treatment with QTP (400-800 mg/d)+Li/DVP or PBO+Li/DVP for up to 104 weeks. Primary endpoint was time to first mood event post-randomization.

1326 patients were included in the ITT population. Relative to PBO, QTP significantly increased time to recurrence of mixed events (P< 0.0001). 445 ITT patients had a most recent mixed episode at study entry. In these patients, mood events were reported by fewer patients on QTP+Li/DVP (21.0%) than on PBO+Li/DVP (53.9%). These events included mixed (6.4% vs 22.1%), pure manic (5.0% vs 13.3%), and pure depressed events (9.6% vs 18.6%). Time to recurrence of mood events was significantly longer for patients on QTP+Li/DVP than for those on PBO+Li/DVP for mixed (HR, 0.23, 95% CI, 0.13-0.42, P< 0.0001), pure manic (HR, 0.30, 95% CI, 0.15-0.60, P=0.0007), and pure depressed events (HR, 0.38, 95% CI, 0.22-0.64, P=0.0003). No new safety concerns were noted.

In stable patients with bipolar I disorder, QTP+Li/DVP significantly increased: a) time to recurrence of mood events compared with PBO in patients with mixed symptoms at study entry; and b) time to occurrence of mixed mood events in patients with any mood episode at study entry.

Supported by funding from AstraZeneca Pharmaceuticals.

Combined data are presented from 2 long-term studies (D1447C00126; D1447C00127) of QTP in combination with Li or DVP in the prevention of mood events in bipolar I disorder. Data from Li and DVP treatment groups are analyzed separately to determine the added benefit of QTP.

Patients received QTP (400-800 mg/d)+Li/DVP to achieve ≥12 weeks of clinical stability followed by double-blind treatment with QTP (400-800 mg/d)+Li/DVP or PBO+Li/DVP for up to 104 weeks. Li or DVP treatment was openly assigned at the discretion of the investigator. Primary endpoint was time to first mood event post-randomization.

1326 patients were included in the ITT population. In both Li and DVP groups, the risk of recurrence of any mood event was significantly reduced following treatment with QTP relative to placebo (HR, 0.32, 95% CI, 0.24-0.44 and HR, 0.28, 95% CI, 0.21-0.37; for Li and DVP, respectively; P< 0.0001 for both). This trend was repeated for risk of recurrence of mania and depression events (P< 0.0001 vs placebo). Comparison of QTP+Li versus QTP+DVP groups revealed no differences in the risk of recurrence of mood, mania, or depression events. Safety data were generally consistent with the recognized safety profiles of QTP, Li, and DVP.

In stable patients with bipolar I disorder, treatment with QTP, in combination with either Li or DVP, resulted in similar significant increases in the time to recurrence of a mood event (mania or depression) compared with placebo, regardless of Li or DVP co-treatment.

Supported funding from AstraZeneca Pharmaceuticals.

To evaluate the extent of hypomanic symptoms in patients presenting with a current major depressive episode (MDE) and to identify characteristics differentiating patients with hypomanic symptoms from those with pure unipolar depression, using the HCL-32 self-assessment tool.

This cross-sectional diagnostic study was performed in eighteen countries. Community- and hospital- based psychiatrists included consecutively all consulting adult patients with a diagnosis of MDE and completed a questionnaire on sociodemographic variables, diagnosis, medical history, treatment and comorbid psychiatric disorders. Each patient completed the Hypomania Self-Rating Scale (HCL-32 R2), and those scoring ≥14 were assigned a diagnosis of bipolar disorder. The frequency of study variables in the bipolar disorder (BD) and unipolar depression subgroups were compared.

A total of 5635 patients were included. Overall, 1645(39%) had received a diagnosis of BD, 703(16%) fulfilled DSM-IV-TR criteria for BD and 2942(54%) scored ≥14 on the HCL-32. Patients scoring ≥14 on the HCL-32 were significantly more likely to have experienced a mood switch in response to antidepressants (OR:3.4), a family history of bipolarity (OR:2.4), comorbid substance abuse (OR:2.1) or borderline personality disorder (OR:1.7) and current mixed-state symptoms (OR:1.5).

In patients with DSM-IV MDE self-assessed, hypomanic symptoms were present in 54% of patients, whereas only 16% fulfilled DSM-IV criteria for bipolar disorder. However, these patients presented features recognised to be associated with bipolar disorder. The presence of bipolarity in patients presenting with a major depressive disorder may be frequent and use of this questionnaire would contribute to improve awareness and prompt better diagnosis.

Dysregulation of motivation and altered processing of reward represent important diagnostic criteria of bipolar disorder and have been proposed as a trait marker of the disorder. Until now, only few studies investigated the processing of reward and learning through reward and punishment in euthymic bipolar patients (BP).

Two studies were conducted to investigate mechanisms of reward learning and processing in euthymic BP and healthy individuals (HC).

In the first study, 23 euthymic BP, 15 remitted patients with Major depression (MD) and 16 HC participated in an associative learning task, assessing the efficiency of contingency learning as well as the preference to learn through positive or negative feedback. In the second study, a probabilistic reversal learning task was conducted during functional magnetic resonance imaging. Here, the neural correlates of reward and punishment were assessed in 22 euthymic BP and 21 HC.

We observed no group differences for the efficiency of contingency learning. However, euthymic BP with a manic episode prior to remission learned better from positive feedback whereas euthymic BP with a depressed episode prior to remission and remitted MD patients learned better from negative feedback. HC did not show such preferences in learning. In addition, bipolar patients exhibited increased orbitofrontal and parahippocampal activity in response to reward but no differences in response to punishment.

Interestingly, the last episode seems to differentially affect emotional and learning processes during euthymia. On a neural level, euthymic BP seem to be more sensitive to reward than healthy individuals.

Mefloquine is being used as malaria prevention by Plasmodium Falciparum in chloroquine-resistant zones. We describe a woman who developed a manic episode with psychotic symptoms during mefloquine treatment.

The case describes a 26-year-old Spanish woman who had been working in Mali for the last six months and had started antimalarial prevention with mefloquine. In Mali, the clinical picture had a sudden debut and she related: excessive happiness, incapacity to sleep, and megalomania (she believed to have special powers and to be the mother of all the children). She was admitted in a hospital in Mali for seven days and received treatment with haloperidol and chlorpromazine. Then, she was repatriated to Spain without treatment and she continued suffering the same symptoms. After 15 days, she went to our hospital and she was admitted. Treatment started with risperidone (up to 6 mg/day) and clonazepam (up to 1.5 mg/day). At admission Young Mania Rating Scale (YMRS) was 25 points. Physical examination and complementary tests were normal, and was orientated as a manic episode with psychotic symptoms secondary to mefloquine. She had a quick symptomatic improvement (after 7 days of treatment YMRS was 5 points) and was discharged after 15 days.

Mefloquine more frequent adverse neuropsychiatric effects are: dizziness, vivid dreams and insomnia. Others are confusion, and auditory hallucinations. Side effects are dose dependent. Psychotic symptoms are frequently auto-limited when mefloquine is suppressed but treatment with atypical antipsychotics is often needed. MDR1/ABCB1 polymorphisms may play a role in neuropsychiatric side effects.

Estimate efficacy of the escitalopram in treatment of disability and impairment in social, professional and family life in patients with MDD.

This prospective clinical study included 110 patients with MDD diagnosed by ICD-10 criteria for MDD, who are randomly divided into control (40 patients) and experimental group (70 patients). Antidepressants were tested, for 6 months in hospital and outpatients conditions, according to specially designed protocol, which included Hamilton Depression Rating Scale (HAMD) and Sheehan Disability Scale (SDS). Control group was treated with mianserine (30-90 mg/24h) and experimental group was treated with escitalopram (10-20 mg/24h).

Escitalopram therapy influenced on HAMD score with high statistical significance vs. Mianserine, p=0.000. Escitalopram therapy improves all SDS scores after 6 months in comparison to Mianserine therapy with high statistical significance in Social life p=0.000, Family life/home responsibilities p=0.000, Days lost p=0.036 and Days unproductive p=0.003. Percentage of adverse effects is significantly lower in Escitalopram (10.76%) than in Mianserine (26.67%) group.

Escitalopram has significantly better efficacy in treatment of MDD and disability and impairment in MDD patients comparing to Mianserine, with significantly lower adverse effects rate.

Social anxiety disorder (SAD) is characterized by anxiety in situations in which one may be evaluated or be in focus of attention by others. Functional neuroimaging studies revealed hyperactivity of the amygdala in response to social cues like faces in patients with SAD. To date, little is known about the neuroarchitecture of SAD. We hypothesized structural alterations in white matter regions projecting to or from the amygdala such as the uncinate fasciculus.

Diffusion tensor imaging (DTI) was applied in 26 patients with SAD and 24 healthy controls (HC). White matter integrity was assessed by fractional anisotropy (FA), a measure of fiber coherence and integrity. In addition, individual scores of trait anxiety were correlated voxel-wise with FA values.

Patients with SAD showed reduced global mean FA across the whole brain and locally in regions near the left amygdala, thalamus, cerebellum, cingulate cortex/corpus callosum, and in the corticospinal tract. Furthermore, trait anxiety correlated negatively with FA in a similar region as in the group comparison near the left amygdala, probably representing the left uncinate fasciculus.

Reduced white matter integrity in patients with SAD was found globally as well as locally in different brain regions. The region near the left amygdala/uncinate fasciculus was the only one yielding significance in both the FA group comparison and voxel-wise correlation with trait anxiety. This points to a functional role of this fiber tract in anxiety and emotion regulation, for instance in top-down inhibition of the amygdala by the frontal cortex.

There is evidence that the antioxidant enzyme glyoxalase-1 (Glx-1) may play a role in anxiety-related behaviour. However, discordant findings between Glx-1 expression and anxiety-related behaviour have been observed in animal models. Because no data are available on the relation between Glx-1 mRNA expression and human anxiety so far, we investigated the expression of Glx-1 mRNA in peripheral red blood cells in relation to cholecystokinin-tetrapeptide (CCK-4) induced anxiety in healthy subjects.

Twenty-three healthy subjects underwent challenge with CCK-4. Glx-1 mRNA expression was assessed by quantitative real-time polymerase chain reaction prior to CCK-4 injection. Baseline anxiety was assessed with the State-Trait-Anxiety-Inventory (STAI) and panic response was measured with the Panic Symptom Scale (PSS).

CCK-4 elicited a marked anxiety response accompanied by a significant increase in heart rate. Glx-1 mRNA expression correlated significantly with severity of CCK-4 induced anxiety. In contrast, Glx-1 activity did not correlate with state or trait anxiety.

The positive correlation between Glx-1 mRNA expression and CCK-4 induced panic severity suggests that Glx-1 is involved into the acute anxiety response to CCK-4. Our preliminary findings support preclinical findings and point towards a role of Glx-1 for human anxiety.

Biomarkers for psychiatric disorders are critical for patient stratification, premorbid diagnosis and personalized treatment. Our aim is to identify protein biomarkers for anxiety disorders by comparing the synaptic proteomes of a well-established mouse model of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior.

We have compared protein expression levels using 15N metabolic labeling and quantitative proteomics. Mice were metabolically labeled through feeding with a 15N-enriched diet. Synaptosomes from unlabeled HAB and LAB mice were then compared with synaptosomes from 15N labeled NAB mice by quantitative mass spectrometry. Protein expression differences were validated with Western blots, enzymatic assays and in silico pathway analysis.

We have identified numerous protein expression differences between HAB and LAB synaptosome proteomes. We observed alterations in energy metabolism pathways such as the Krebs cycle as well as in mitochondrial function. Furthermore, we detected changes in transport and phosphorylation processes.

We present an accurate proteomics platform for biomarker discovery in psychiatric disorders. We identified candidate biomarkers and pathways involved in anxiety pathophysiology. Our data provide the basis for the establishment of a biomarker panel that will shed light on anxiety pathophysiology and can be applied for optimal therapeutic intervention.

Selective serotonin re-uptake inhibitors (SSRI), such as escitalopram, are currently the pharmacological treatment of choice for patients suffering from panic disorder.

Serotonergic modulation of experimental panic in healthy human volunteers by such medication, however, has not been investigated as yet.

We intended to study the effects of chronic treatment with the SSRI escitalopram on the panic response to a cholecystokinin-tetrapeptide (CCK-4) challenge.

In a double-blind, placebo-controlled, randomized, within subject cross-over design thirty healthy young men, 15 each with the long/long or short/short genotype for the serotonin transporter linked polymorphic region (5-HTTLPR), were pre-treated with 10 mg/d of escitalopram for 6 weeks and then challenged with 50 μg of the panicogen CCK-4. Primary outcome measure was the increase of Acute Panic Inventory ratings by CCK-4.

A significant treatment by genotype effect on the increases of Acute Panic Inventory ratings emerged. CCK-4 panic was significantly more pronounced in the short/short genotype subjects under escitalopram versus placebo pre-treatment. Contrary to our expectation, no inhibitory effect of escitalopram upon panic symptoms elicited by CCK-4 could be demonstrated in healthy men.

Our findings do not support the usefulness of this panic model for proof-of-concept studies in volunteer translational research, at least concerning serotonergic agents.

(Supported by a grant from Deutsche Forschungsgemeinschaft (DFG), Ke 595/7-1)

Findings about dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S) in patients with post-traumatic stress disorder (PTSD) have been inconsistent and confusing.

Although its impact on the regulation of the hypothalamic-pituitary-adrenocortical axis has been demonstrated, the potential effect of severe childhood adverse events has not been considered regarding DHEA and DHEA-S data in PTSD.

We investigated whether a history of severe childhood traumatisation affects these steroids in PTSD patients.

33 patients with chronic PTSD (15 with and 18 without sexual and/or severe physical abuse before age 12) were studied in a combined low dose dexamethasone/corticotropin-releasing hormone (CRH) test. Mean pre-CRH levels of both plasma DHEA and DHEA-S were significantly increased in the subgroup with childhood abuse, the respective ratios with plasma cortisol were significantly lower. In the entire population of PTSD patients significant amounts of the variation of these parameters could be explained by childhood trauma history.

Further studies are needed to clarify the potential role of DHEA and DHEA-S as biomarkers for severe early adverse events in patients suffering from PTSD and in other stress-related disorders.

The DSM-IV indicates severity of social phobia (SP) by the “generalized subtype”, when “most social situations” are feared. This specifier refers to the number of feared social situations, perhaps ignoring quantitative differences. We therefore compared specific and interaction-related vs. performance-related social fears according to clinical (age of onset, avoidance, impairment, comorbidities) and vulnerability characteristics (behavioural inhibition (BI), parental psychopathology and rearing).

Six social situations and SP along with their clinical characteristics were assessed using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI) in a population-based sample of N=3,021 14-24 year olds. BI and parental rearing were assessed using self-report questionnaires. Parental psychopathology was assessed directly in parents via DIA-X/M-CIDI, supplemented by offsprings’ family-history reports.

Isolated social fears were rare, except for fear of taking tests and public speaking. The majority reported to fear two or more social situations. Compared to isolated fears of either interaction or performance situations, their co-occurrence was associated with lower age of onset, severe avoidance and impairment, more comorbid anxiety and depressive disorders. All social fears (in particular interaction-related fears) were associated with higher BI. Associations with parental psychopathology and unfavourable rearing were less consistent, albeit strongest for interaction-related fears.

Interaction-related fears may represent a more familial form of SP, while performance-related fears might be less impairing and originate from non-familial factors. The DSM-IV specifier of SP may overlook these differences when individuals with predominantly interaction-related fears are categorized as generalized SP-cases. Findings suggest considering alternative specifiers for SP in future diagnostic systems.

Depersonalization (DP) is a common and complex clinical phenomenon in neurology and psychiatry. It is defined as an experience in which the individual feels a sense of unreality and detachment from him/herself. Prevalence and clinical correlates of dissociative symptoms in general, and DP in particular have been associated to panic disorder (Hunter et al., 2004). Moreover, DP has been associated with certain personality traits, specifically “harm-avoidant” temperament dimension, immature defenses, and overconnection and disconnection cognitive schemata (Simeon et al., 2002).

To investigate the prevalence of DP syndrome in panic disorder and its relationship with personality.

One-hundred-four consecutive adult patients with panic disorder were assessed with the Semi- Structured Clinical Interview for DSM-IV-Axis I and II. All participants were evaluated with the Cambridge Depersonalization Scale (Sierra and Berrios, 2000) and the Cloninger Temperament and Character Inventory. The severity of panic disorder was measured with the Panic and Agoraphobia Scale.

Seventeen patients (16.3%) had a DP syndrome. There were not socio-demographic differences between both groups with and without DP syndrome. Patients with DP syndrome showed a higher score in “self-transcendence” character dimension (p< .001), higher prevalence of personality disorders (p=.007) and greater severity of panic disorder (p=.007). A logistic regression analysis showed that severity of panic disorder (p=.031) and higher “self-transcendence” personality dimension (p=.019) predicts DP syndrome in panic disorder patients. The Hosmer-Lemeshow test showed the goodness-of-fit of the model.

The study confirms the association of DP syndrome with panic disorder and their relationship with “self-transcendence” personality dimension.

To elucidate the consequences of broadening DSM-IV criteria for generalized anxiety disorder (GAD), we examined the evolution of GAD symptoms in two groups of newly diagnosed patients; one group according to DSM-IV criteria and the other, according to broader criteria.

Multicentre, prospective and observational study conducted in outpatient psychiatric clinics. Patients with GAD according to DSM-IV criteria and subjects with anxiety symptoms fulfilling broader criteria were compared. Broadening criteria was considered 1-month of excessive or non-excessive worry and only 2 associated symptoms listed on DSM-IV for GAD. Socio-demographic data, medical history and functional outcome measures were collected three times during a 6-month period.

3,549 patients were systematically recruited; 12.8% excluded because not fulfilling inclusion criteria, 1,815 patients in DSM-IV group (DG) and 1,264 in broad group (BG). Both groups were similar on their sociodemographic characteristics at baseline and most patients (about 80%), even newly diagnosed were exposed previously to pharmacological therapies (mainly benzodiazepines) of their anxiety symptoms. As a result of treatment at psychiatric clinics, the percentage of patients without symptoms of anxiety as per HAM-A scale were 49.0% and 58.0%, respectively at the 6 month visit (p=0.261). Similarly, responder rate (≥ 50% reduction of baseline scoring) were, respectively, 59.7% and 67.7% (p=0.103). Improvement in MADRS scores were observed in both group to a similar extent; 12.1 and 12.5 points average reduction respectively (p=0.264).

Broadening of GAD criteria could lead to earlier diagnosis that will benefit patients by starting appropriate treatment sooner.

To analyse the consequences of broadening DSM-IV criteria for generalized anxiety disorder (GAD) on the utilization of health care resources and corresponding costs.

Multicentre, prospective and observational study conducted in outpatient psychiatric clinics selected at random and weighted by geographical density of population. Patients with GAD according to DSM-IV criteria and subjects with anxiety symptoms fulfilling broader criteria were compared. Broadening criteria was considered 1-month of excessive or non-excessive worry and only 2 associated symptoms listed on DSM-IV for GAD. Socio-demographic data, medical history and health care resources and corresponding costs were recorded during a 6-month period.

A total of 3,549 patients were systematically recruited; 12.8% excluded because not fulfilling inclusion criteria, 1,815 patients in DSM-IV criteria group (DG) and 1,264 in broad criteria group (BG). Both groups were similar on their sociodemographic characteristics at baseline. Type of treatments prescribed at psychiatric clinics during the study were similar in frequency; anti-depressives (77.0% in DG vs. 75.3% in BG, ns), benzodiazepines (71.5% vs. 67.2% respectively, ns), and anti-convulsants (72.1% vs. 67.0% respectively, ns). Health care resources utilization were statistically reduced to a similar extent in both groups as a consequences of treatments yielding to a cost-of-illness in the 6-month period of 1,196 (1,158) and 1,112 (874), respectively; p=0.304.

In a large sample of subjects, broadening of GAD criteria could lead to earlier diagnosis that would not be associated necessarily to an increase in health care resources utilization or costs to the National Health System.