Treatment-resistant OCD: Pharmacotherapies in adults

Serotonin reuptake inhibitor (SRI) medications are well established as first-line pharmacotherapeutic treatment for Obsessive-Compulsive Disorder (OCD). However, despite the excellent safety profile and demonstrated ef-ficacy of these medications, a substantial proportion of individuals with OCD fail to attain sufficient benefit from SRIs. In this narrative review, we discuss clinical features of OCD that have been associated with poorer response to SRIs, and we present pharmacotherapeutic interventions that have been explored as augmenting or alternative treatments for treatment-resistant OCD. We additionally highlight non-SRI interventions for OCD that are currently under investigation. Pharmacotherapeutic interventions were identified via expert consensus. To assess the evidence base for in-dividual pharmacotherapies, targeted searches for relevant English-language publications were performed on standard biomedical research databases, including MEDLINE. Information relevant to ongoing registered clinical trials in OCD was obtained by search of ClinicalTrials.gov. Pharmacotherapies are grouped for review in accordance with the general principles of Neuroscience-based Nomenclature (NbN). Clinical features of OCD that may suggest poorer response to SRI treatment include early age of onset, severity of illness, duration of untreated illness, and the presence of symmetry/ordering or hoarding-related symptoms. Based on evolving pathophysiologic models of OCD, diverse agents engaging serotonin, dopamine, norepi-nephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Medications with dopamine antagonist activity remain the most robustly evidence-based of augmenting in-terventions, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Interventions targeting glutamatergic and anti-inflammatory pathways are less well evidenced, but may offer more favorable benefit to risk profiles. Ongoing research should explore whether specific in-terventions may benefit individuals with particular features of treatment-resistant OCD

How is COVID-19 affecting patients with obsessive-compulsive disorder? A longitudinal study on the initial phase of the pandemic in a Spanish cohort

Background: Although the consequences of the COVID-19 pandemic on emotional health are evident, little is known about its impact on patients with obsessive-compulsive disorder (OCD). Methods: One hundred and twenty-seven patients with OCD who attended a specialist OCD Clinic in Barcelona, Spain, were assessed by phone from April 27 to May 25, 2020, during the early phase of the pandemic, using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured interview that collected clinical and sociodemographic information. Results were compared with those for 237 healthy controls from the same geographic area who completed an online survey. Results: Although 65.3% of the patients with OCD described a worsening of their symptoms, only 31.4% had Y-BOCS scores that increased >25%. The risk of getting infected by SARS-CoV2 was reported as a new obsession by 44.8%, but this only became the main obsessive concern in approximately 10% of the patients. Suicide-related thoughts were more frequent among the OCD cohort than among healthy controls. The presence of prepandemic depression, higher Y-BOCS scores, contamination/washing symptoms, and lower perceived social support all predicted a significantly increased risk of OCD worsening. Conclusions: Most patients with OCD appear to be capable of coping with the emotional stress of the COVID-19 outbreak and its consequences during the initial phase of the pandemic. Nevertheless, the current crisis constitutes a risk factor for a significant worsening of symptoms and suicidal ideation. Action is needed to ensure effective and individualized follow-up care for patients with OCD in the COVID-19 era

Late onset eating disorders in Spain: clinical characteristics and therapeutic implications

OBJECTIVE: The literature on later age of onset (LAO) in women with eating disorders is scarce. We compared the severity of eating disorders, eating disorder subtype, and personality profiles in a clinical sample of consecutively assessed women with eating disorders with later age of onset (LAO, > = 25 years) to women with typical age of onset (TAO, <25 years). METHOD: All eating disorder patients met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria and were admitted to the Eating Disorder Unit of the University Hospital of Bellvitge in Barcelona, Spain. Ninety-six patients were classified as LAO and 759 as TAO. ASSESSMENT: Measures included the Eating Attitude Test-40 (EAT-40), Eating Disorders Inventory-2 (EDI-2), Bulimic Investigatory Test Edinburgh (BITE), Symptom Checklist Revised (SCL-90-R), and the Temperament and Character Inventory-Revised (TCI-R), as well as other clinical and psychopathological indices. RESULTS: LAO individuals reported significantly fewer weekly vomiting episodes, fewer self-harming behaviours, less drug abuse, and lower scores on the BITE symptoms, the EDI-2 drive for thinness, and the TCI-R harm avoidance scales than TAO individuals. Conversely, the LAO group reported more current and premorbid obesity than the TAO group. CONCLUSION: LAO eating disorder patients in this sample presented with milder symptomatology and less extreme personality traits. Premorbid obesity may be more relevant to LAO than TAO eating disorders and should be routinely assessed and considered when planning treatment

First manic/hypomanic episode in obsessive-compulsive disorder patients treated with antidepressants: a systematic review

High doses of antidepressants, particularly clomipramine and selective serotonin reuptake inhibitors (SSRIs), are the well-established treatment for obsessive-compulsive disorder (OCD), but manic/hypomanic episodes are potential adverse events associated with this treatment. A systematic literature review was performed on manic/ hypomanic episodes in non-bipolar OCD patients. Clinical, sociodemographic and antidepressant characteristics during the manic/hypomanic switch were extracted using descriptive statistics. Data were obtained from 20 case reports and case series. Switching episodes mostly appeared in the first 12 weeks after antidepressant initiation and took place more frequently during SSRI use (mostly fluoxetine) in 64.3% of cases. Clomipramine and SSRI use differed non-significantly between the switching episodes that appeared during the first 12 weeks of antidepressant treatment and the episodes that appeared beyond 12 weeks. Switching episodes emerging before 12 weeks were associated with a lower defined daily dose of antidepressants than episodes emerging after 12 weeks. These findings suggest that there are two independent characteristics involved in manic/hypomanic switch in OCD: a) they appeared most frequently with SSRI use (fluoxetine) regardless of the time of it use, and b) episodes appeared in the first 12 weeks after SSRI or clomipramine initiation had a lower dose of antidepressant than episodes appeared after 12 weeks

The Role of Sleep Quality, Trait Anxiety and Hypothalamic-Pituitary-Adrenal Axis Measures in Cognitive Abilities of Healthy Individuals

Sleep plays a crucial role in cognitive processes. Sleep and wake memory consolidation seem to be regulated by glucocorticoids, pointing out the potential role of the hypothalamic-pituitary-adrenal (HPA) axis in the relationship between sleep quality and cognitive abilities. Trait anxiety is another factor that is likely to moderate the relationship between sleep and cognition, because poorer sleep quality and subtle HPA axis abnormalities have been reported in people with high trait anxiety. The current study aimed to explore whether HPA axis activity or trait anxiety moderate the relationship between sleep quality and cognitive abilities in healthy individuals. We studied 203 healthy individuals. We measured verbal and visual memory, working memory, processing speed, attention and executive function. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Trait anxiety was assessed with the State-Trait Anxiety Inventory. HPA axis measures included the cortisol awakening response (CAR), diurnal cortisol slope and cortisol levels during the day. Multiple linear regression analyses explored the relationship between sleep quality and cognition and tested potential moderating effects by HPA axis measures and trait anxiety. Poor sleep quality was associated with poorer performance in memory, processing speed and executive function tasks. In people with poorer sleep quality, a blunted CAR was associated with poorer verbal and visual memory and executive functions, and higher cortisol levels during the day were associated with poorer processing speed. Trait anxiety was a moderator of visual memory and executive functioning. These results suggest that subtle abnormalities in the HPA axis and higher trait anxiety contribute to the relationship between lower sleep quality and poorer cognitive functioning in healthy individuals

BDNF genetic variants and methylation: effects on cognition in major depressive disorder

Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples

Treatment outcome of patients with comorbid type 1 diabetes and eating disorders

Background: Co-morbidity between Type 1 Diabetes Mellitus (T1DM) and eating disorders (ED) has been previously described; however the effect of this illness on the outcomes for conventional ED treatments has not been previously investigated. This study aims to compare clinical, psychopathological and personality features between two samples of ED individuals: those with comorbid T1DM and those without (No-DM); and to identify differences in treatment outcomes between the groups. Methods: This study compares treatment outcome, dropouts, ED psychopathology and personality characteristics for 20 individuals with ED and T1DM and 20 ED patients without diabetes, matched for diagnostic and treatment type. Results: The study found higher dropout rates from therapy in individuals with T1DM and worse treatment outcome in spite of having no significant differences in eating disorder psychopathology, although individuals with T1DM report misusing insulin. Conclusions: The low levels of motivation to change, and insulin abuse in T1DM patients, may suggest that treatment for patients with ED and T1DM should consider the individual's personality and role of insulin abuse when determining the appropriate intervention

Childhood Maltreatment and Its Interaction with Hypothalamic–Pituitary–Adrenal Axis Activity and the Remission Status of Major Depression: Effects on Functionality and Quality of Life

Relationships among childhood maltreatment (CM), hypothalamic-pituitary-adrenal (HPA) axis disturbances, major depressive disorder (MDD), poor functionality, and lower quality of life (QoL) in adulthood have been described. We aimed to study the roles of the remission status of depression and HPA axis function in the relationships between CM and functionality and QoL. Ninety-seven patients with MDD and 97 healthy controls were included. The cortisol awakening response, cortisol suppression ratio in the dexamethasone suppression test, and diurnal cortisol slope were assessed. Participants completed measures of psychopathology, CM, functionality, and QoL. Multiple linear regression analyses were performed to study the relationships between CM and functionality and QoL. Only non-remitted MDD patients showed lower functionality and QoL than controls, indicating that depressive symptoms may partly predict functionality and QoL. Cortisol measures did not differ between remitted and non-remitted patients. Although neither HPA axis measures nor depression remission status were consistently associated with functionality or QoL, these factors moderated the effects of CM on functionality and QoL. In conclusion, subtle neurobiological dysfunctions in stress-related systems could help to explain diminished functionality and QoL in individuals with CM and MDD and contribute to the persistence of these impairments even after the remission of depressive symptoms

Sex-specific association between the cortisol awakening response and obsessive-compulsive symptoms in healthy individuals

Background: Previous studies have shown associations between obsessive-compulsive disorder (OCD) and hypothalamic-pituitary-adrenal axis activity (HPA). We aimed to investigate the association between obsessive-compulsive (OC) symptoms and HPA axis functionality in a non-clinical sample and to explore whether there are sex differences in this relationship. Methods: One hundred eighty-three healthy individuals without any psychiatric diagnosis (80 men, 103 women; mean age 41.3 ± 17.9 years) were recruited from the general population. The Obsessive-Compulsive Inventory Revised (OCI-R) was used to assess OC symptoms. State-trait anxiety, perceived stress, and stressful life events were also assessed. Saliva cortisol levels were determined at 6 time points (awakening, 30 and 60 min post-awakening, 10:00 a.m., 23:00 p.m. and 10:00 a.m. the following day of 0.25 mg dexamethasone intake [that occurred at 23:00 p.m.]). Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope, and cortisol suppression ratio after dexamethasone (DSTR). Multiple linear regression analyses were used to explore the association between OC symptoms and HPA axis measures while adjusting for covariates. Our main analyses were focused on OCI-R total score, but we also explored associations with specific OC symptom dimensions. Results: No significant differences were observed between males and females in OC symptoms, anxiety measures, stress, or cortisol measures. In the multiple linear regression analyses between overall OC symptoms and HPA axis measures, a female sex by OC symptoms significant interaction (standardized beta = − 0.322; p = 0.023) for the CAR (but not cortisol diurnal slope nor DSTR) was found. Regarding specific symptom dimensions, two other sex interactions were found: a blunted CAR was associated with obsessing symptoms in women, whereas a more flattened diurnal cortisol slope was associated with ordering symptoms in men. Conclusions: There are sex differences in the association between OC symptoms and HPA axis measures in healthy individuals

Respuesta de la hormona de crecimiento al factor liberador de la misma en pacientes con depresiones, con o sin alucinaciones, así como en controles sanos

Se analizan las respuestas de la hormona del crecimiento (GH) a los factores liberadores de la hormona de crecimiento (GHRH) en 53 pacientes que, según la clasificación DSM-III-R, presentaban los criterios de episodio depresivo mayor con melancolía (24 con depresión no alucinatoria y 23 alucinatoria) respecto a las correspondientes a 19 controles sanos. No se hallaron diferencias significativas en la GH basal entre controles y pacientes, presentaran éstos una depresión alucinatoria o no. Globalmente, el grupo con depresión mostraba una respuesta significativamente menor a la hallada en los controles. Esta diferencia se constató a todos los niveles de la curva de respuesta de la GH frente a la GHRH. De la misma forma el área bajo la curva es también menor Al comparar los tres grupos (controles, depresión con o sin alucinación) se evidenció que únicamente los pacientes con depresión no alucinatoria se asociaban a una menor área bajo la curva significativa y a valores inferiores, a los +60, +90y +120 min., respecto a los controles. La única diferencia significativa entre los dos grupos de pacientes depresivos era que entre el grupo con depresión no alucinatoria existía un retraso en la aparición del pico de máxima respuesta, así como una respuesta más prolongada