Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology.

OBJECTIVE: Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants' pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment. METHODS: In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants' blood concentrations and psychometric assessments were collected at five time points. Antidepressants' cord blood concentrations were assessed at birth. RESULTS: Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants' concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6. CONCLUSIONS: Pregnancy modulates cytochrome activity and drugs' pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.

Intensive Neurofeedback Protocol: An Alpha Training to Improve Sleep Quality and Stress Modulation in Health Care Professionals During the Covid-19 Pandemic. A Pilot Study.

Objective: health care workers (HCWs) represent a vulnerable group in the COVID-19 pandemic, given the exposure to greater risk and higher levels of work-related stress. Neurofeedback (NF) has shown to be effective in the treatment of stress-related symptoms. We aimed to assess the effectiveness of an alpha-increase NF protocol for the treatment of acute stress symptoms in HCWs exposed to the COVID-19 pandemic. Method: eighteen medical doctors on duty during the COVID-19 health emergency underwent an intensive NF alpha-increase protocol. The mean alpha wave values were recorded at the beginning (T0) and at the last day of stimulation (T1). Rapid Stress Assessment: Italian version; Copenhagen Burnout Inventory (CBI); Pittsburgh Sleep Quality Index (PSQI), and Brief-COPE were administered as psychometric assessment. Results: a significant increase in alpha wave values and a significant reduction of the PSQI scores from T0 to T1 were found. Conclusions: NF alpha-increase protocol showed promising results in terms of stress modulation, sleep quality improvement, and safety in a pilot sample of HCWs.

The Role of Lifestyle on Adherence to Treatment in a Sample of Patients with Unipolar and Bipolar Depression.

Introduction: Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence. The aim of the present study is to assess potential differences in terms of clinical and lifestyle features related to adherence to treatment in a sample of patients with unipolar and bipolar depression. Methods: One hundred and eight patients with a diagnosis of unipolar or bipolar depressive episode were recruited from January 2021 to October 2022. Adherence to psychopharmacological treatment was assessed using the clinician rating scale. Descriptive and association analyses were performed to compare subgroups based on adherence to treatment. Results: Lower levels of adherence to treatment were associated with fewer years of education, work impairment, manic prevalent polarity lifetime, and greater comorbidity with alcohol and drug abuse. The majority of patients with positive adherence did not report any hospitalization and involuntary commitment lifetime. Conclusions: Patients with a positive treatment adherence showed significant differences in terms of lifestyle and clinical features compared to non-adherent patients. Our results may help to identify patients more likely to have poor medication adherence, which seem to lead to a worse disease course and quality of life.

Staging models applied in a sample of patients with bipolar disorder: Results from a retrospective cohort study.

BACKGROUND: Bipolar Disorder (BD) is a life-long illness with compelling evidence of progression. Although different staging models have been proposed to evaluate its course, clinical data remain limited. The aim of the present study was to retrospectively assess applicability of available staging approaches and their pattern of progression in a sample of bipolar patients. METHODS: In a naturalistic sample of 100 BD patients, retrospective assessment of clinical stages was performed at four time points over 10 years, according to four staging models. Staging progression with potential associations between stages and unfavourable illness characteristics were analyzed. RESULTS: A pattern of stage worsening emerged for each model, with a significant increase at every time point. Greater stage increases emerged in patients with lower educational level, age at first elevated episode ≤35 years, duration of illness ≤25 years, and duration of untreated illness ≤5 years. Lower stage values were associated with BD II, no psychiatric hospitalization, depressive onset and predominant polarity, ≤three lifetime episodes, age at first mood stabilizer >40 years, duration of illness ≤25 years, and engaged/employed status. Higher stage values were associated with lower age at first elevated episode and mood stabilizing treatment instead. LIMITATIONS: Naturalistic and retrospective design, recruitment at a 2nd level specialistic clinic. CONCLUSIONS: Reported findings support the progressive nature of BD and the application of staging models for early intervention, suggesting a conceptualization of a standardized approach to better characterize patients, predict their clinical course, and deliver tailored treatment options.

A preliminary investigation of Cyberchondria and its correlates in a clinical sample of patients with obsessive-compulsive disorder, anxiety and depressive disorders attending a tertiary psychiatric clinic.

Objectives. This cross-sectional study aimed to investigate the frequency and presentation of cyberchondria (CYB) in patients with obsessive-compulsive disorder (OCD), anxiety disorders (ADs), and major depression disorder (MDD).Methods. Seventy-seven patients (OCD:25, ADs:26, MDD:26) referred to a tertiary psychiatry outpatient clinic and 27 healthy controls (HCs) were included. A 'working' definition of CYB was used to measure CYB frequency. CYB severity was measured with the Cyberchondria Severity Scale (CSS).Results. CYB as currently defined was present in just 1.3% of the combined patients' sample. Using a broader definition (omitting the disability criterion), we found a higher distribution (OCD:12%, ADs:19.2%, MDD:15.4%, HCs:3.7%) and greater CYB symptom severity. Patients with OCD (63.3 ± 18.9) and ADs (63.3 ± 25.9) showed a higher CYB severity, compared with HCs (48.4 ± 9.9, p<.05). In the combined patients' sample, a positive correlation was found between the CSS scores and measures of health anxiety or hypochondriasis. Higher CYB symptom severity emerged in patients with a positive family history of psychiatric disorders and in those prescribed benzodiazepines or mood-stabilisers.Conclusion. CYB represents a common transdiagnostic syndrome in patients with OCD, ADs, and MDD with a spectrum of severity and indicates a variable burden of illness, supporting the need for specific clinical considerations and interventions.Key pointsCyberchondria (CYB) represents a common transdiagnostic syndrome in patients with obsessive-compulsive disorder, anxiety, and depressive disorders.CYB's frequency as a syndrome of compulsive online health searches associated with an increased anxiety and distress was reported in 10-20% patients.Health anxiety/hypochondriasis showed a strong correlation with CYB.Patients with a positive family history of psychiatric disorders and those prescribed benzodiazepines or mood-stabilisers showed higher CYB symptom severity.Considering the spread of Internet use for health-related information, additional studies investigating CYB in clinical samples are encouraged.

Suicidal ideation and suicidal attempts in patients with obsessive-compulsive tic-related disorder vs obsessive-compulsive disorder: results of a multicenter Italian study.

BACKGROUND: Obsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD. METHODS: Three hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA). RESULTS: No differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups. CONCLUSIONS: Patients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.

Correlation between pharmacokinetics and pharmacogenetics of Selective Serotonin Reuptake Inhibitors and Selective Serotonin and Noradrenaline Reuptake Inhibitors and maternal and neonatal outcomes: Results from a naturalistic study in patients with affective disorders.

OBJECTIVE: Some studies have linked the use of selective serotonin reuptake inhibitors and selective serotonin and noradrenaline reuptake inhibitors (SSRIs/SNRIs) to the risk of perinatal complications. This study explored the relationship between pharmacokinetics and pharmacogenetics, SSRIs/SNRIs tolerability and effectiveness and maternal and newborn outcomes. METHODS: Fifty-five pregnant women with Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnoses of affective disorders, treated with SSRIs/SNRIs, were recruited and, during the third trimester, their blood samples were collected for pharmacokinetic and pharmacogenetic analyses. Plasma levels and metabolic phenotypes were then related to different obstetrical and maternal outcomes. RESULTS: The pharmacokinetic data were more stable for Sertraline, Citalopram, and Escitalopram compared to other molecules (p = 0.009). The occurrence of postnatal adaptation syndrome onset was associated with higher plasma levels for Sertraline (median at delivery: 16.7 vs. 10.5 ng/ml), but not for fluoxetine and venlafaxine. Finally, the subgroup within range plasma concentrations had less blood loss than the below range subgroup (p = 0.030). CONCLUSIONS: Plasma levels of Sertraline, Citalopram and Escitalopram were more frequently in range in late pregnancy when compared to other drugs. Drug plasma concentrations do not strictly correlate with worse perinatal outcomes, but with possible differences between the different drugs.

Effectiveness, tolerability, and dropout rates of vortioxetine in comorbid depression: A naturalistic study.

OBJECTIVE: Vortioxetine is a novel antidepressant whose safety, tolerability, and therapeutic action have been supported by several studies. The present naturalistic study aimed to characterize its effectiveness, tolerability, and dropout rate in the real world. METHODS: Total sample consisted of 66 outpatients with major depressive episode, treated with vortioxetine, whose clinical variables were evaluated over three time points. RESULTS: Most common primary diagnoses were major depressive disorder (45.5%) and bipolar disorder (33.4%), with an overall comorbidity rate of 48.5% and concomitant medications in the 89.4%. The mean vortioxetine daily dosage was 12.90 ± 5.65 mg. Effectiveness of vortioxetine through a significant improvement on specific psychometric scales emerged, while only a nonsignificant trend of association between higher dosage and effectiveness was found. In the total sample, 51.5% were classified as responders and 36.4% as remitters. Two-thirds of subjects did not report side effects, while in the remaining patients, gastrointestinal ones were the most frequent (72.7%). Almost two-thirds of the sample could complete the follow-up, while 36.4% dropped out; the main reasons for dropout were side effects (37.5%) and lack of efficacy (29.2%). CONCLUSIONS: Larger sample studies are warranted to better characterize vortioxetine effectiveness and tolerability in the real world.

Duration of untreated illness and depression severity are associated with cognitive impairment in mood disorders.

Introduction: In this study we estimated the rate and the trajectory of cognitive impairment in a naturalistic sample of outpatients with major depressive disorder (MDD) and bipolar disorder (BD) and its correlation with different variables.Materials and methods: An overall sample of 109 outpatients with MDD or BD was assessed for multiple clinical variables, including duration of untreated illness (DUI), and tested using the Montreal Cognitive Assessment (MoCA) during Major Depressive Episodes (MDE) and after remission. Correlations between MoCA scores and the clinical variables were then computed.Results: About 50% of patients with MDD and BD showed mild cognitive impairment during MDE. Improvement of cognitive function between depression and remission was significant, even though residual symptoms were observed especially in the most impaired patients. Of note, cognitive performance during depression was negatively associated with depression severity and DUI.Discussion: Present findings confirm available evidence about patterns of cognitive impairment in mood disorders, in terms of prevalence and persistence beyond remission in most severe cases. Moreover, a longer DUI was associated with worse cognitive performance during depression, and consequently with poorer outcome, underlining the importance of prompt treatment of these disorders also in light of a cognitive perspective.KeypointsAlthough distinct entities, unipolar and bipolar depression determine similar patterns of cognitive impairment in terms of severity and types of altered domains.Depression (but not anxiety) severity is associated with cognitive performance in depression.Prolonged duration of untreated illness is associated with more severe cognitive impairment during depression, particularly but not specifically in bipolar disorder.

Using network analysis to explore cognitive domains in patients with unipolar versus bipolar depression: a prospective naturalistic study.

OBJECTIVE: Despite growing evidence in the field of cognitive function in mood disorders, the neurocognitive profiles of patients with unipolar and bipolar depression still need further characterization. In this study, we applied network analysis, hypothesizing this approach could highlight differences between major depressive disorder (MDD) and bipolar disorder (BD) from a cognitive perspective. METHODS: The cognitive performance of 109 patients (72 unipolar and 37 bipolar depressed outpatients) was assessed through the Montreal Cognitive Assessment (MoCA), and a series of clinical variables were collected. Differences in cognitive performance between MDD and BD patients were tested using non-parametric tests. Moreover, a network graph representing MoCA domains as nodes and Spearman's rho correlation coefficients between the domains as edges was constructed for each group. RESULTS: The presence of mild cognitive impairment was observed in both MDD and BD patients during depression. No statistical significant difference was found between the two groups in terms of overall cognitive performance and across single domains. Nonetheless, network analytic metrics demonstrated different roles of memory and executive dysfunction in MDD versus BD patients: in particular, MDD network was more densely interconnected than BD network, and memory was the node with the highest betweenness and closeness centrality in MDD, while executive function was more central in BD. CONCLUSIONS: From a network analytic perspective, memory impairment displays a central role in the cognitive impairment of patients with unipolar depression, whereas executive dysfunction appears to be more central in bipolar depression. Further research is warranted to confirm our results.

Clinical features and patterns of psychopharmacological prescription in bipolar patients with vs without anxiety disorders at onset.

AIM: Up to just over half of bipolar disorder (BD) patients report at least one-lifetime anxiety disorder (AD). In some, anxiety represents the earliest psychiatric manifestation, prior to any mood episode. We sought to investigate prevalence of AD subtypes as first psychiatric manifestations and AD's relations with duration of untreated illness (DUI) and treatment among BD outpatients. METHODS: We recruited patients referred to the Centre for the Treatment of Depressive Disorders in Milan, diagnosed with BD-I, BD-II, BD not otherwise specified (BD-NOS) and cyclothymia according to Diagnostic and Statistical Manual fourth edition-text revision criteria. Several clinical characteristics were assessed through retrospective chart review and/or direct patient interviews. Based on presence/absence of an AD at psychiatric onset, eligible subjects were stratified into two groups (A+ and A-) and clinical features were compared between these groups and between BD subtypes. RESULTS: We analysed 260 BD patients (77 BD-I, 122 BD-II, 45 BD-NOS and 16 cyclothymia). An AD was the first psychiatric manifestation in 69 patients (26.5%). BD-II and BD-NOS more frequently had an AD at psychiatric onset, with panic disorder being the most common AD. Among A+ vs A-, age at BD onset was younger, duration of untreated BD illness (DUI) was longer, and a mood stabilizer/antipsychotic was less often prescribed at psychiatric onset. CONCLUSIONS: Considering BD in its longitudinal course, over one in four BD patients presenting with an AD at psychiatric onset belatedly access adequate treatment, with subsequent prolonged DUI and prospective worse outcome compared to patients with a mood episode at psychiatric onset.

Anxiety disorders anticipate the diagnosis of bipolar disorder in comorbid patients: Findings from an Italian tertiary clinic.

BACKGROUND: Studies indicate bipolar disorder (BD) syndromal symptoms are commonly preceded by sub-syndromal BD symptoms, dysregulated sleep, irritability, and anxiety. We aimed to evaluate prevalence and clinical correlates of anxiety disorders (ADs) at BD onset in outpatients with versus without at least one AD at BD onset. METHODS: 246 bipolar spectrum outpatients, according to the text revision of the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM- IV-TR), attending Sacco University Hospital in Milan, were recruited and their onset and clinical features assessed retrospectively. Patients were stratified into those with versus without an AD at BD onset (w/A and wo/A), according to a semi-structured clinical interview to provide diagnoses according to (DSM- IV-TR). RESULTS: 29% of patients reported being w/A, among whom Panic Disorder (PD, in 55.6%) was the most frequent AD, and first AD occurred approximately 4 years before BD diagnosis. Patients w/A versus wo/A had higher (p < 0.05) rates of BDII and first mood episode being depression versus elevation (mania/hypomania), and lifetime rates of separation anxiety disorder, substance poly-abuse and benzodiazepine abuse. In contrast, patients wo/A had higher lifetime rates of alcohol and illicit drug use. CONCLUSION: In this naturalistic sample, ADs, in particular PD, preceded BD in almost 1/3 of BD outpatients, and had distinctive clinical correlates. Further investigation into relationships between BD and AD at onset may enhance early BD diagnosis and treatment.

Alexithymia and Psychopathology in Patients Suffering From Inflammatory Bowel Disease: Arising Differences and Correlations to Tailoring Therapeutic Strategies.

Comorbidity with anxiety or depression is common in patients with Inflammatory Bowel Disease (IBD) as Crohn Disease (CD) and Ulcerative Colitis (UC). Data suggest that the cognitive construct of alexithymia has high prevalence in people suffering from anxiety and mood disorders and even in people with IBD. Most studies have investigated mainly anxiety and depression, considering IBD population as a homogeneous group of patients. Little evidence shows the impact of alexithymia on the course of IBD. We evaluated a broad spectrum of psychopathological symptoms and alexithymia levels in a group of outpatients affected by IBD in clinical remission, comparing CD and UC and investigating the relationship with clinical and socio-demographic variables. One hundred and seventy IBD outpatients were screened by using the Hospital Anxiety Depression Scale (HADS), the Self-report Symptom Inventory-90-Revised (SCL-90-R) and the Toronto Alexithymia Scale (TAS-20). A high prevalence of anxious and depressive symptoms (42.35 and 25.8% respectively) together with alexithymia (31.76%) was confirmed. CD patients experienced high levels of depression (HADS Depression 35.2% p = 0.034; SCL-90-R mean 1.39 p < 0.001), somatisation (SCL-90-R mean 1.04 p < 0.001), obsessive-compulsive symptoms (SCL-90-R mean 1.2 p < 0.001), and global severity (SCL-90-R mean 1.15 p < 0.001). There is no statistical difference in the prevalence of alexithymia in both subpopulations. The levels of alexithymia are correlated to the levels of anxiety (HADS Anxiety rs = 0.516 p < 0.001), depression (HADS Depression rs = 0.556 p < 0.001; SCL-90-R rs = 0.274 p = 0.001), somatisation (SCL-90-R rs = 0.229 p = 0.005), obsessive-compulsive symptoms (SCL-90-R rs = 0.362 p < 0.001), and global severity (SCL-90-R rs = 0.265 p = 0.001). Furthermore, alexithymia is associated with a delay of diagnosis of IBD, poly-therapies and greater IBD extension. Older age, female gender, greater IBD extension, surgery, and delay of diagnosis seem to be related to a high prevalence of psychopathological symptoms such as anxiety, depression, somatisation, and obsessive-compulsive symptoms. Psychopathological symptoms and high levels of alexithymia are frequent in IBD patients and seem to be related to a high risk of poor clinical outcome. CD patients could be considered at higher risk of mental comorbidity. A more comprehensive psychiatric assessment, including alexithymia, and an integrated treatment of underlying conditions, must be taken into account in order to improve the global prognosis of the disease.

Personality disorders in addiction outpatients: prevalence and effects on psychosocial functioning.

AIM: To evaluate the prevalence of personality disorders (PDs) in the outpatients attending an addiction service, with particular attention to the effects of PDs on social and occupational functioning and on the intensity of treatment required. DESIGN: A cross-sectional epidemiological study with the assessment of 320 outpatients, through SCID-II (Structured Clinical Interview for DSM-IV Axis II PDs), SOGS (South Oaks Gambling Screen), and questionnaire extracted from EuropASI. RESULTS: The percentage prevalence of PDs was 62.2% (confidence interval at 95% (95% CI): 57-68). PDs were positively associated with placement in an addiction treatment community (odds ratio (OR) = 2.98, CI = 1.77-5.03), having received lifetime treatment at the mental health center (MHC) (OR = 3.67, CI = 1.67-8.07) or having attempted suicide (OR = 2.30, CI = 1.05-5.02). Furthermore, PDs were related to a reduced probability of keeping a job (OR = 0.54, CI = 0.31-0.95) or starting a family (OR = 0.51, CI = 0.30-0.87). CONCLUSION: Axis II comorbidity occurs in 62% of addiction outpatients and has substantial effects on social and occupational functioning as well as on treatment programs.

Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial.

AIM: Patients with panic disorder (PD) might be sensitive to the stimulating effects of selective serotonin reuptake inhibitors (SSRI), thus requiring low dosages at treatment initiation. The aim of the present study was to assess eventual differences in terms of effectiveness and tolerability between a slow up-titration with paroxetine and a standard one. METHODS: In an open randomized, multicenter, primary-care study, 60 patients (44 women and 16 men) with PD with or without agoraphobia were enrolled and randomized to receive a slow up-titration with paroxetine (increments of 2.5 mg/day every 2 days) or a standard one (increments of 10 mg/day every week) up to a maximum daily dose of 20 mg. Repeated-measures anova on sub-items scores of the Panic Attack Anticipatory Anxiety Scale (PAAS) and Dosage Record and Treatment Emergent Symptom Scale (DOTES), respectively, used as outcome measures of effectiveness and tolerability, were performed. Significance level was set at 0.05 and it was not corrected. RESULTS: anova showed no differences between the two treatments in terms of effectiveness and tolerability. Post hoc analysis found only one significant difference in the intensity of spontaneous panic attacks (Panic and Anticipatory Anxiety Scale) in the first 9 days of treatment between the two treatment groups, which was that this item was less intense in the slow-titration group (treatment effect: F = 4.89, P = 0.03, effect size = 0.1). CONCLUSION: Present findings suggest only a small superiority for a slow up-titration regimen of paroxetine compared to a standard one in the first 9 days of treatment but no differences at end-point.

Impairment in psychosocial functioning associated with dysthymic disorder in the NESARC study.

BACKGROUND: Chronic depression is associated with impaired functioning. The National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC) is a representative sample (N=43,093) of the United States non-institutionalized population aged 18years and older. We hypothesized that individuals with chronic low-grade depression, dysthymic disorder, would have more impaired functioning than individuals with acute major depression or the general population. METHOD: Diagnoses were generated by the NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). The dysthymic disorder (DD) sample (N=328) consisted of DD diagnosis without current MDD. The dysthymic group was not chosen on the basis of alcohol use or abuse. Individuals with MDD with duration ≦24months, without lifetime DD constituted the acute depression (AD) sample (N=712). All other respondents were classified as general population (GP) (N=42,052). Past year functioning was assessed by Supplemental Social Security Income (SSI), employment, and Medicaid statuses. Past month functioning was assessed by Short-form 12-Item Health Survey (SF-12), with scores for social functioning, role emotional functioning, and mental health, using odds ratios. RESULTS: Over the past year, compared to AD, persons with DD were less likely to work full-time (36.2% vs. 44%; OR=0.70, CI=.54,.92) and more often received SSI (13.9% vs. 4.5%; OR=3.4, CI=2.0,5.9) and Medicaid (20.2% vs. 13%; OR=1.7 , CI=1.1,2.6). Dysthymics reported accomplishing less over the past month due to emotional problems, and that emotional or physical problems interfered with social activities. Relative to GP, respondents with DD were more likely to receive SSI (13.9% vs. 2.9%; OR=4.6, CI 3.4,6.2) and Medicaid (20.2% vs. 5.9%; OR=2.9, CI 2.0,4.1). Compared to GP, dysthymics reported accomplishing less due to emotional problems, and that emotional or physical problems interfered with social activities and work functioning. CONCLUSIONS: DD-associated psychosocial impairment in the community setting comprises a significant public health burden.

Short-term intravenous citalopram augmentation in partial/nonresponders with major depression: a randomized placebo-controlled study.

Approximately 30-45% of patients with major depressive episode (MDE) do not fully respond to standard recommended treatments and further strategies of intervention, including pharmacological augmentation, have been proposed for these patients. This study was aimed to evaluate the efficacy of short-term, low-dose (10 mg/day) intravenous (i.v.) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders, 4th edition, text revision criteria MDE and partial or no response to oral SSRIs were selected and randomly assigned to citalopram (n=18) or to placebo (n=18) i.v. augmentation. The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs. Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale total scores, administered daily with blind-raters conditions, were done. With regard to the Hamilton Depression Rating Scale total scores, a significant time effect (F=42.02, P<0.0001) and timextreatment effect (F=21.17, P<0.0001) were found in favor of citalopram. Similar results were obtained from the analysis on Montgomery-Asberg Depression Rating Scale total scores: time effect (F=50.07, P<0.0001), timextreatment effect (F=19.91, P<0.0001), and treatment effect (F=4.07, P=0.05). Even though referred to a small sample, the present findings seem to suggest that short-term, low-dose, i.v. citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs. Further controlled studies performed with double-blind conditions are warranted to confirm the present results.

Novel 5'-regulatory region polymorphisms of the 5-HT2C receptor gene: association study with panic disorder.

Candidate genes for association studies in panic disorder are often selected on the basis of molecular mechanisms of drugs utilized in challenge tests such as m-chlorophenylpiperazine (mCPP), a non-selective 5-HT2C receptor agonist. Two novel, adjacent polymorphisms [(GT)12-18 and (CT)4-5] in the 5'-regulatory region of the X-chromosomal 5-HT2C receptor gene have recently been reported. We determined the allele frequency of long vs. short polymorphism haplotypes in a German and an Italian sample (combined n = 211) of panic disorder patients (DSM-III-R) and compared it with allele frequencies in two ethnically matched control samples (combined n = 226). In the German sample, a comparison of female genotypes containing the short haplotype vs. female genotypes containing only long haplotypes showed a significant difference (p = 0.01, ?2 analysis). In the Italian sample, however, this observation could not be replicated (p = 0.54, ?2 analysis). This argues against a major role for these promoter-associated 5-HT2C receptor gene length polymorphisms in the aetiopathogenesis of panic disorder.