Responsiveness and other psychometric properties of the Yale-Brown Obsessive-Compulsive Scale Severity Scale-Second Edition in a Dutch clinical sample.

The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used clinician-rated interview to assess the presence and severity of obsessive-compulsive disorder (OCD). The scale is revised (Y-BOCS-II) to overcome several psychometric limitations, for example by extending the scoring for better discrimination within higher severity levels. The aim of the present study was to examine the responsiveness and other psychometric properties of the Y-BOCS-II Severity Scale in a Dutch clinical sample. The Y-BOCS-II is translated into Dutch and administered to 110 patients seeking therapy for OCD. This was done twice, before and after treatment. The original Y-BOCS was simultaneously rated. Self-report measures regarding depression, symptom severity and OCD symptoms were assessed. The Y-BOCS-II has a good internal consistency (Cronbach's α = 0.84), test-retest (intraclass correlation coefficient [ICC] = 0.89) and interrater reliability (ICC = 0.98). The construct validity proved to be modest to good. The responsiveness over time was in favour of the Y-BOCS-II, compared with the Y-BOCS-I, particularly in the moderate-severely affected OCD patients. The Y-BOCS-II Severity Scale is a reliable and valid instrument for accurately assessing the severity of OCD symptoms and for measuring treatment-induced change. This second version also has clinical and psychometric advantages over the Y-BOCS-I. When these findings are sufficiently replicated, use of the Y-BOCS-II as the new common standard seems recommendable.

Proof of Principle: Is a Pre-treatment Behavior Approach Test a Potential Predictor for Response to Intensive Residential Treatment in Patients With Treatment Refractory Obsessive Compulsive Disorder?

Patients with severe and treatment refractory obsessive compulsive disorder (OCD) are usually referred to a specialized center for intensive residential treatment (IRT), consisting of exposure and response prevention (EX/RP), pharmacotherapy and additional therapies. About 50% of the patients does not respond to IRT. Currently we are not able to predict treatment response. If we were to have predictive tools, we could personify treatment at an earlier stage. Recent studies show that early adherence and willingness to EX/RP and low avoidance during EX/RP measured during treatment were associated with treatment response. In this observational study willingness and ability of patients with severe and treatment refractory OCD (N = 58) is conceptualized by a behavioral measurement, measured before the start of 12 weeks of IRT, using a Behavior Approach Test (BAT), as opposed to relying on self-report measurements. A medium or strong association between pre-treatment performance on the BAT and treatment response would justify next steps to test the BAT as a predictive tool for IRT. Results of regression analyses showed that there is a significant association between the performance on the BAT and change in OCD symptom severity after IRT. However, the effect-size is too small to use the BAT in its current form as predictor in clinical practice. The principle of the association between pre-treatment behaviorally measured willingness and ability to fully engage in EX/RP, and treatment response has now been proven. To ultimately design a predictive tool, future research is needed to refine a behavioral measurement of pre-treatment willingness and ability.

Use of videotaped personal compulsions to enhance motivation in obsessive-compulsive disorder.

BACKGROUND: Watching videotaped personal compulsions together with a therapist might enhance the effect of cognitive-behavioural therapy in obsessive-compulsive disorder (OCD) but little is known about how patients experience this.AimsTo performed a qualitative study that describes how watching these videos influences motivation for treatment and whether patients report any adverse events. METHOD: In this qualitative study, data were gathered in semi-structured interviews with 24 patients with OCD. The transcripts were coded by two researchers. They used a combination of open and thematic coding and discrepancies in coding were discussed. RESULTS: The experience of watching videos with personal compulsions helped patients to realise that these compulsions are aberrant and irrational. Patients report increased motivation to resist their OCD and to adhere to therapy. No adverse events were reported. CONCLUSIONS: Videos with personal compulsions create more awareness in patients with OCD that compulsions are irrational, leading to enhanced motivation for treatment.Declaration of interestNone.

Examining the factor structure of the self-report Yale-Brown Obsessive Compulsive Scale Symptom Checklist.

Obsessive-compulsive symptom dimensions are important in studies about the pathogenesis and treatment of obsessive-compulsive disorder. More than 30 factor analytic studies using the Yale-Brown Obsessive Compulsive Scale Symptom Checklist (Y-BOCS-SC) interview version have been published. However, a drawback of the Y-BOCS-SC interview is that it is time-consuming for the clinician. Baer's self-report version of the Y-BOCS-SC could be a less time-consuming alternative. The purpose of this study was to examine the factor structure of Baer's self-report Y-BOCS-SC. In a sample of 286 patients, we performed two factor analyses, one using categories and one using items of the Y-BOCS-SC. Using category-level data, we identified four factors; when using items we identified six factors. Symptom dimensions for contamination/cleaning, symmetry/repeating/counting/ordering and hoarding were found in both analyses. The impulsive aggression, pathological doubt, sexual, religious somatic and checking categories formed one factor in the analysis using category-level data and divided into three factors using item-level data. These factors correspond with studies using the interview version and support our hypothesis that the self-report version of the Y-BOCS-SC could be an alternative for the interview version.

Chronic obsessive-compulsive disorder: prognostic factors.

BACKGROUND: The course of illness in obsessive-compulsive disorder (OCD) varies significantly between patients. Little is known about factors predicting a chronic course of illness. The aim of this study is to identify factors involved in inducing and in maintaining chronicity in OCD. METHODS: The present study is embedded within the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, an ongoing multicenter naturalistic cohort study designed to identify predictors of long-term course and outcome in OCD. For this study, 270 subjects with a current diagnosis of OCD were included. Chronicity status at 2-year follow-up was regressed on a selection of baseline predictors related to OCD, to comorbidity and to stress and support. RESULTS: Psychotrauma [odds ratio (OR) 1.98, confidence interval (CI) 1.22-3.22, p = 0.006], recent negative life events (OR 1.42, CI 1.01-2.01, p = 0.043), and presence of a partner (OR 0.28, CI 0.09-0.85, p = 0.025) influenced the risk of becoming chronic. Longer illness duration (OR 1.46, CI 1.08-1.96, p = 0.013) and higher illness severity (OR 1.09, CI 1.03-1.16, p = 0.003) increased the risk of remaining chronic. CONCLUSIONS: External influences increase the risk of becoming chronic, whereas the factors involved in maintaining chronicity are illness-related. As the latter are potentially difficult to modify, treatment should be devoted to prevent chronicity from occurring in the first place. Therapeutic strategies aimed at alleviating stress and at boosting social support might aid in achieving this goal.

Presence and Predictive Value of Obsessive-Compulsive Symptoms in Anxiety and Depressive Disorders.

OBJECTIVE: Obsessive-compulsive symptoms (OCS) co-occur frequently with anxiety and depressive disorders, but the nature of their relationship and their impact on severity of anxiety and depressive disorders is poorly understood. In a large sample of patients with anxiety and depressive disorders, we assessed the frequency of OCS, defined as a Young Adult Self-Report Scale-obsessive-compulsive symptoms score >7. The associations between OCS and severity of anxiety and/or depressive disorders were examined, and it was investigated whether OCS predict onset, relapse, and persistence of anxiety and depressive disorders. METHODS: Data were obtained from the third (at 2-year follow-up) and fourth wave (at 4-year follow-up) of data collection in the Netherlands Study of Anxiety and Depression cohort, including 469 healthy controls, 909 participants with a remitted disorder, and 747 participants with a current anxiety and/or depressive disorder. RESULTS: OCS were present in 23.6% of the total sample, most notably in those with current combined anxiety and depressive disorders. In patients with a current disorder, OCS were associated with severity of this disorder. Moreover, OCS predicted (1) first onset of anxiety and/or depressive disorders in healthy controls (odds ratio [OR], 5.79; 95% confidence interval [CI], 1.15 to 29.14), (2) relapse in those with remitted anxiety and/or depressive disorders (OR, 2.31; 95% CI, 1.55 to 3.46), and (3) persistence in patients with the combination of current anxiety and depressive disorders (OR, 4.42; 95% CI, 2.54 to 7.70) within the 2-year follow-up period Conclusions: OCS are closely related to both the presence and severity of anxiety and depressive disorders and affect their course trajectories. Hence, OCS might be regarded as a course specifier signaling unfavorable outcomes. This specifier may be useful in clinical care to adapt and intensify treatment in individual patients.

No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia: A Double-Blind, Randomized Controlled Trial.

PURPOSE/BACKGROUND: D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the effectiveness of adding 125 mg of DCS to exposure therapy (before or directly after the first 6 treatment sessions) in patients with panic disorder with agoraphobia and (2) the effectiveness of DCS augmentation preceding exposure relative to DCS augmentation directly postexposure. METHODS/PROCEDURES: Fifty-seven patients were allocated to 1 of 3 medication conditions (placebo and pre-exposure and postexposure DCS) as an addition to 6 exposure sessions within a 12-session exposure and response prevention protocol. The primary outcome measure was the mean score on the "alone" subscale of the Mobility Inventory (MI). FINDINGS/RESULTS: No differences were found in treatment outcome between DCS and placebo, administered either pre-exposure or postexposure therapy, although at 3-month follow-up, the DCS postexposure group compared with DCS pre-exposure, exhibited greater symptom reduction on the MI-alone subscale. Ancillary analyses in specific subgroups (responders vs nonresponders, early vs late responders, severely vs mildly affected patients) did not reveal any between-group DCS versus placebo differences. Finally, the study did not find an effect of DCS relative to placebo to be specific for successful exposure sessions. IMPLICATIONS/CONCLUSIONS: This study does not find an effect of augmentation with DCS in patients with severe panic disorder and agoraphobia administered either pretreatment or directly posttreatment sessions. Moreover, no preferential effects are revealed in specific subgroups nor in successful exposure sessions. Yet, a small effect of DCS administration postexposure therapy cannot be ruled out, given the relatively small sample size of this study.

Borderline or Schizotypal? Differential Psychodynamic Assessment in Severe Personality Disorders.

Considerable overlap in symptoms between patients with borderline personality disorder (BPD) and schizotypal personality disorder (STPD) complicates personality diagnostics. Yet very little is known about the level of psychodynamic functioning of both personality disorders. Psychodynamic assessment procedures may specify personality characteristics relevant for differential diagnosis and treatment planning. In this cross-sectional study we explored the differences and similarities in level of personality functioning and psychodynamic features of patients with severe BPD or STPD. In total, 25 patients with BPD and 13 patients with STPD were compared regarding their level of personality functioning (General Assessment of Personality Disorder), current quasipsychotic features (Schizotypal Personality Questionnaire), and psychodynamic functioning [Developmental Profile (DP) interview and Developmental Profile Inventory (DPI) questionnaire]. Both groups of patients showed equally severe impairments in the level of personality functioning and the presence of current quasipsychotic features. As assessed by the DP interview, significant differential psychodynamic patterns were found on the primitive levels of functioning. Moreover, subjects with BPD had significantly higher scores on the adaptive developmental levels. However, the self-questionnaire DPI was not able to elucidate all of these differences. In conclusion, our study found significant differences in psychodynamic functioning between patients with BPD and STPD as assessed with the DP interview. In complicated diagnostic cases, personality assessment by psychodynamic interviewing can enhance subtle but essential differentiation between BPD and STPD.

Inference-Based Approach versus Cognitive Behavioral Therapy in the Treatment of Obsessive-Compulsive Disorder with Poor Insight: A 24-Session Randomized Controlled Trial.

OBJECTIVE: Obsessive-compulsive disorder (OCD) with poor insight has severe consequences for patients; nonetheless, no randomized controlled trial has ever been performed to evaluate the effectiveness of any treatment specifically for poor-insight OCD. A new psychotherapy for OCD, the inference-based approach (IBA), targets insight in OCD by strengthening normal sensory-driven reality testing. The goal of the present study is to compare the effectiveness of this new treatment to the effectiveness of cognitive behavior therapy (CBT) for patients with OCD with poor insight. METHOD: A randomized controlled trial was conducted, in which 90 patients with OCD with poor insight received either 24 CBT sessions or 24 IBA sessions. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcome measures were level of insight, anxiety and depressive symptoms, and quality of life. Mixed-effects models were used to determine the treatment effect. RESULTS: In both conditions, a significant OCD symptom reduction was reached, but no condition effects were established. Post hoc, in a small subgroup of patients with the worst insight (n = 23), it was found that the patients treated with the IBA reached a significantly higher OCD symptom reduction than the patients treated with CBT [estimated marginal mean = -7.77, t(219.45) = -2.4, p = 0.017]. CONCLUSION: Patients with OCD with poor insight improve significantly after psychological treatment. The results of this study suggest that both CBT and the IBA are effective treatments for OCD with poor insight. The IBA might be more promising than CBT for patients with more extreme poor insight.

The relationship between adverse childhood experiences and symptom severity, chronicity, and comorbidity in patients with obsessive-compulsive disorder.

BACKGROUND: Studies on the relationship between adverse childhood experiences (ACEs) and obsessive-compulsive disorder (OCD) symptom severity are scarce. Available studies leave a considerable degree of uncertainty. The present study examines the relationship between ACEs and symptom severity, chronicity, and comorbidity in a sample of patients with OCD. METHOD: Baseline data of the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, in which 382 referred patients with DSM-IV-diagnosed OCD participated, were analyzed. ACEs (physical abuse, sexual abuse, witnessing interparental violence, maternal dysfunction, paternal dysfunction, and early separation from a parent) were measured using a structured interview. Data were collected between September 2005 and November 2009. RESULTS: None of the ACEs were related to OCD symptom severity or chronicity, nor was there a dose-response relationship between ACEs and OCD severity or chronicity, but results of linear regression analysis revealed that ACEs were related to comorbidity in patients with OCD (P < .001), in particular to comorbid affective disorders (P < .01), substance use disorders (P < .01), and eating disorders (P < .01), but not to comorbid anxiety disorders. CONCLUSIONS: Results of the study suggest that unlike in other psychiatric disorders, ACEs play no significant role in symptom severity and chronicity of OCD. This study was the first to reveal evidence for a relationship between ACEs and comorbidity in patients with OCD. Conclusions about trauma-relatedness of OCD based on studies finding higher trauma rates or severity among patients with OCD than among healthy controls, should be critically reconsidered, since presence of comorbidity might account for these differences.

Obsessive-compulsive disorder; chronic versus non-chronic symptoms.

OBJECTIVE: Understanding chronicity in OCD is hampered by contradictory findings arising from dissimilar definitions of chronic OCD. The purpose of this study was to investigate the magnitude of chronicity in OCD and to examine if chronic OCD is critically different from non-chronic OCD, using a chronicity definition that reflects empirical findings. METHOD: Baseline data of the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, in which 379 OCD patients participated, were analyzed. Chronic OCD was defined as "continuous presence of at least moderately severe OCD symptoms during at least two years", and was assessed retrospectively using a Life-Chart Interview. RESULTS: Application of the chronicity criterion resulted in two groups with highly distinguishable course patterns. The majority of the sample (61.7%) reported a chronic course. Patients with a chronic course reported significantly more severe OCD symptoms, more illness burden, more comorbidity, an earlier OCD onset and more contamination and washing - and symmetry and ordering symptoms. Multivariable logistic regression analysis revealed that chronic OCD was independently associated with more OCD-subtypes (p<0.001), contamination and washing symptoms (p<0.001), earlier OCD onset (p=0.05) and higher severity of compulsions (p<.01). LIMITATIONS: The findings are based on a cross-sectional survey. Furthermore course was assessed retrospectively, implying the possibility of overestimation of persistence and severity of symptoms. CONCLUSION: Chronicity is the rule rather than the exception in OCD in clinical samples. Chronic OCD is critically different from non-chronic OCD. Further attempts to break down the heterogeneity of OCD in homogeneous course subtypes should be made to allow for a more precise determination of the pathogenesis of OCD and better treatment.

The association between CYP2D6 genotype and switching antipsychotic medication to clozapine.

PURPOSE: Genetic variation in the cytochrome P450 2D6 (CYP2D6) enzyme is responsible for interindividual differences in the metabolism of many antipsychotic drugs, but the clinical relevance of polymorphisms in CYP2D6 for response to antipsychotic treatment is relatively unknown. In the Netherlands, clozapine is prescribed only when patients are non-responsive to or intolerant of at least two different antipsychotics. The aim of our study was to determine the association of the CYP2D6 genotype with switching to clozapine, which served as a surrogate outcome marker for treatment response to antipsychotics. METHODS: CYP2D6 genotype was assessed in patients who had been switched to clozapine and compared with antipsychotic users whose treatment regimen included no more than two different antipsychotic drugs and no clozapine. We also performed the analysis in patients who only used CYP2D6-dependent antipsychotics. RESULTS: A total of 528 patients were included in the study (222 cases, 306 controls). No statistically significant differences were found in the distribution of the polymorphisms among the case and control groups, both in all patients and in only those patients using CYP2D6-dependent antipsychotics. However, a trend was observed, suggesting an inverse association between CYP2D6 genotype and the switch to clozapine. (9.5 vs. 5.1 % poor metabolisers and 1.3 vs. 2.6 % ultrarapid metabolisers in cases vs. controls, respectively). CONCLUSIONS: Although the results of our study suggest that the CYP2D6 phenotype is not a major determining factor for patients to be switched to clozapine treatment, larger studies are warranted with a focus on the clinical consequences of the CYP2D6 ultrarapid metaboliser and poor metaboliser phenotypes.

Clinical relevance of comorbidity in obsessive compulsive disorder: the Netherlands OCD Association study.

BACKGROUND: This study describes lifetime and current rates of comorbidity, its onset and its consequences in a large clinical sample of patients with obsessive compulsive disorder (OCD). A wide range of risk factors and clinical characteristics were also examined to determine whether pure OCD is different from OCD with current comorbidity. Finally, the temporal sequencing of the disorders was examined. METHOD: Data were obtained from the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. A sample of 382 participants with current OCD (during the past month) was evaluated. RESULTS: Current comorbidity occurred in 55% of patients with OCD, while 78% suffered from lifetime comorbidity. Comorbidity is associated with more severe OCD, anxiety and depressive symptoms and more negative consequences on daily life. Multiple comorbid disorders often precede OCD and influence both its course and severity. Childhood trauma and neuroticism are vulnerability factors for the development of multiple comorbid disorders in OCD. LIMITATIONS: It should be noted that causal inferences about the association between risk factors and OCD are precluded since our results were based on cross-sectional data. CONCLUSION: (Multiple) comorbidity in OCD is clinically relevant since it is associated with a specific pattern of vulnerability, with greater chronicity, with more severe OCD and more negative consequences on daily life. This indicates that the diagnosis and treatment of all comorbid disorders is clinically relevant, and clinicians should be especially aware of multiple disorders in cases of childhood trauma and high levels of neuroticism. Primary OCD has a different developmental and comorbidity pattern compared to secondary OCD.

The Netherlands Obsessive Compulsive Disorder Association (NOCDA) study: design and rationale of a longitudinal naturalistic study of the course of OCD and clinical characteristics of the sample at baseline.

In half of Obsessive Compulsive Disorder (OCD) patients the disorder runs a chronic course despite treatment. The factors determining this unfavourable outcome remain unknown. The Netherlands Obsessive Compulsive Disorder Association (NOCDA) study is a multicentre naturalistic cohort study of the biological, psychological and social determinants of chronicity in a clinical sample. Recruitment of OCD patients took place in mental health organizations. Its design is a six-year longitudinal cohort study among a representative clinical sample of 419 OCD patients. All five measurements within this six-year period involved validated semi-structured interviews and self-report questionnaires which gathered information on the severity of OCD and its co-morbidity as well as information on general wellbeing, quality of life, daily activities, medical consumption and key psychological and social factors. The baseline measurements also include DNA and blood sampling and data on demographic and personality variables. The current paper presents the design and rationale of the study, as well as data on baseline sample characteristics. Demographic characteristics and co-morbidity ratings in the NOCDA sample closely resemble other OCD study samples. Lifetime co-morbid Axis I disorders are present in the majority of OCD patients, with high current and lifetime co-morbidity ratings for affective disorders (23.4% and 63.7%, respectively) and anxiety disorders other than OCD (36% current and 46.5% lifetime).

Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive comorbidity and "double" comorbidity (i.e. anxiety and depressive comorbidity). METHODS: Data were obtained from the Netherlands Study of Anxiety and Depression (NESDA). A sample of 1004 participants with a current anxiety disorder was evaluated. RESULTS: As compared with single anxiety, anxiety-anxiety comorbidity was associated with higher severity, greater chronicity and more treatment. Anxiety-anxiety comorbidity was associated with an earlier age of onset and a more chronic course compared with anxiety-depressive comorbidity, while anxiety-depressive comorbidity was associated with more severe symptoms and more impaired functioning than anxiety-anxiety comorbidity. "Double" comorbidity was associated with higher severity, greater chronicity, more treatment and increased disability. Sociodemographic and vulnerability factors were comparable among the four groups. Limitations A prospective design would be more appropriate to study the outcome. In this study no distinction was made between whether depression or anxiety disorder preceded the current anxiety disorder. CONCLUSIONS: It is clinical relevant to diagnose and treat comorbidity among anxiety disorders as it is associated with higher severity and more chronicity. Whereas anxiety-anxiety comorbidity has an earlier age of onset and a more chronic course, anxiety-depressive comorbidity leads to more treatment and impaired functioning. "Double" comorbidity leads to even more severity, chronicity and impairment functioning compared with both anxiety-anxiety and anxiety-depressive comorbidity.

Polymorphisms of the LEP, LEPR and HTR2C gene: obesity and BMI change in patients using antipsychotic medication in a naturalistic setting.

UNLABELLED: Weight gain is a frequently occurring serious somatic adverse effect of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. OBJECTIVES: To determine whether LEPR Q223R, LEP -2548G/A and HTR2C -759C/T polymorphisms are associated with obesity and weight change in patients using atypical antipsychotic drugs. METHODS: A longitudinal study design was used in a naturalistic setting. The study population included 141 patients, all of whom were using an atypical antipsychotic drug. The body mass index was measured twice. Primary outcome measures were obesity at the moment of first measurement and body mass index change during treatment. Determinants were the LEPR Q223R (rs1137101), the LEP -2548G/A SNP (rs7799039) and the HTR2C -759C/T (rs3813929) polymorphisms. RESULTS: Of the 141 included patients, 35 (24.8%) were obese. In females, presence of the LEPR 223R allele was associated with an increased risk of obesity (47.6 vs 17.6%; p = 0.03). In males this association was not found. None of the SNPs were significantly associated with weight change during treatment. CONCLUSIONS: The LEPR Q223R polymorphism may be a risk factor for obesity in women with a psychotic disorder treated with atypical antipsychotic drugs. This is in line with earlier findings of our group.

Paroxetine augmentation in patients with generalised social anxiety disorder, non-responsive to mirtazapine or placebo.

OBJECTIVES: The aim of the study was to investigate if combination of mirtazapine with paroxetine causes a greater therapeutic effect and less sexual side effects than paroxetine monotherapy in social anxiety disorder (SAD). METHODS: Twenty one patients with generalised SAD, non-responsive to a 12 week trial with mirtazapine and 22 patients, non-responsive to placebo received paroxetine (20-40 mg) in addition to their double-blind treatment with mirtazapine or placebo for another 12 weeks. The Liebowitz Social Anxiety Scale (LSAS) and the Clinical Global Impression-Improvement (CGI-I) scale were used to measure efficacy. Sexual functioning was assessed by the Arizona Sexual Experiences Scale (ASEX). RESULTS: Both treatments showed a significant LSAS reduction and their response rates (based on LSAS reduction ≥ 40% and CGI-I ≤ 2) were similar (paroxetine and mirtazapine: 52.4%, paroxetine and placebo: 59.1%). Sexual dysfunction (based on ASEX ≥ 19) was found in half of patients treated with paroxetine and placebo, and in 38% of patients treated with paroxetine and mirtazapine. CONCLUSION: The present study did not find support for a greater efficacy of combination pharmacotherapy in SAD, however results suggest that combination of paroxetine with mirtazapine might cause less sexual dysfunction than treatment with paroxetine alone.

Combined HTR2C-LEP genotype as a determinant of obesity in patients using antipsychotic medication.

Obesity is one of the most serious common somatic adverse effects of atypical antipsychotic agents. Genetic factors partly determine the individual patients risk of developing obesity during treatment. As weight-regulating mechanisms, such as the leptinergic and serotonergic system, may be interdependent, genetic polymorphisms in these systems also may show interactions. To determine whether combined HTR2CLEP genotype or HTR2C-LEPR genotype are associated with obesity in patients using atypical antipsychotic drugs, a cross-sectional study design was used. The study population included 200 patients aged between 18 and 65 years of age, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. Primary outcome measure was presence of obesity (body mass index, >30). Determinants were the combined (HTR2C -759C/T-LEPR Q223R), (HTR2C -759C/T-LEP -2548G/A, (HTR2C rs1414334-LEPR Q223R) and (HTR2C rs1414334-LEP -2548G/A) genotypes. Of the 200 included patients, 61 (31%) were obese. In patients without the HTR2C -759T allele, presence of the LEP -2548G allele was associated with obesity (odds ratio, 2.88; 95% confidence interval, 1.05-7.95). The results of the other analyses showed some nonsignificant trends. The combined (HTR2C -759C/TYLEP -2548G/A) genotype may be a determinant of obesity in patients during treatment with atypical antipsychotic drugs.

Mirtazapine in generalized social anxiety disorder: a randomized, double-blind, placebo-controlled study.

This study is aimed at investigating the efficacy and tolerability of mirtazapine in a generalized social anxiety disorder. Sixty patients with generalized social anxiety disorder were randomly allocated to receive mirtazapine (30-45 mg/day) (n= 30) or placebo (n= 30) for 12 weeks in a double-blind study design. Primary efficacy was assessed by the Liebowitz Social Anxiety Scale (LSAS) and response to treatment was defined as a reduction of 40% on the LSAS and an improvement on the Clinical Global Impression scale of 'much or very much improved'. An intent-to-treat analysis showed no difference between mirtazapine and placebo on the absolute LSAS scores with a mean decrease of 13.5 +/- 16.9 and 11.2 +/- 17.8 respectively, and on the number of responders, 13 and 13%, respectively. In conclusion, mirtazapine (30-45 mg/day) failed to be effective in the generalized social anxiety disorder.