Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis.

BACKGROUND: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression. METHODS: This comprehensive systematic review and meta-analysis of observational studies on pramipexole-antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint. RESULTS: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8-69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects. CONCLUSIONS: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression.

Serotonin reuptake inhibitor-cognitive behavioural therapy-second generation antipsychotic combination for severe treatment-resistant obsessive-compulsive disorder. A prospective observational study.

INTRODUCTION: Six in ten patients with obsessive-compulsive disorder (OCD) do not respond to the first-line treatments with serotonin reuptake inhibitor (SRI) or cognitive behavioural therapy including exposure and response prevention (CBT/ERP), and several do not respond to second-line treatments, i.e., SRI-second generation antipsychotic (SGA) or SRI-CBT/ERP augmentation. Evidence on third-line treatments is inconsistent. OBJECTIVE: We investigated the 1-year response to SRI-CBT/ERP-SGA combination in patients with severe treatment-resistant OCD, who failed to respond to SRI and to SRI-SGA or SRI-CBT/ERP augmentation. METHODS: Twenty-eight patients were consecutively recruited and treated with SRI (drug(s) and doses previously administered), SGA (risperidone median dosage 1 mg/day in 14 cases, aripiprazole median dosage 3 mg/day in 14 cases) and CBT/ERP (median hours 32.5). Exclusion criteria: mental retardation and organic brain syndrome. RESULTS: The mean Y-BOCS total score reduction at 12 months was 28.2%, 60.7% of patients improved, 46.4% partially responded, 32.1% responded, and 28.6% remitted. Patients previously resistant to SRI-SGA and SRI-CBT/ERP did not significantly differ in the rates of improvement, partial response, response and remission. CONCLUSIONS: This study suggests that SRI-SGA-CBT/ERP combination could be useful for severe treatment-resistant OCD. Small sample size is a limitation.Key pointsUp to 6 in 10 patients with OCD do not respond to first line treatments (CBT/ERP or SRIs) and several to second-line treatments (SRI-SGA or SRI CBT/ERP augmentation).In our study, patients with OCD resistant to the first and the second line treatment improved (61%), partially responded (46%), responded (32%), or remitted (29%) combining SRI, SGA and CBT/ERP.In our patients the SRI-SGA-CBT/ERP augmentation improved working/school, social and family impairment.SRI-SGA-CBT/ERP augmentation is easier to use than other treatments for severe treatment-resistant OCD.

Assessing response, remission, and treatment resistance in patients with obsessive-compulsive disorder with and without tic disorders: results from a multicenter study.

BACKGROUND: Highlighting the relationship between obsessive-compulsive disorder (OCD) and tic disorder (TD), two highly disabling, comorbid, and difficult-to-treat conditions, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) acknowledged a new "tic-related" specifier for OCD, ie, obsessive-compulsive tic-related disorder (OCTD). As patients with OCTD may frequently show poor treatment response, the aim of this multicenter study was to investigate rates and clinical correlates of response, remission, and treatment resistance in a large multicenter sample of OCD patients with versus without tics. METHODS: A sample of 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from 10 different psychiatric departments across Italy. For the purpose of the study, treatment response profiles in the whole sample were analyzed comparing the rates of response, remission, and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to identify possible factors associated with treatment response. RESULTS: The remission group was associated with later ages of onset of TD and OCD. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts emerged in the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement. CONCLUSIONS: Although remission was associated with later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response with a significant impairment in quality of life for both patients and their caregivers, suggesting a worse profile of treatment response for patients with OCTD.

What Is the Impact of COVID-19 Pandemic on Patients with Pre-Existing Mood or Anxiety Disorder? An Observational Prospective Study.

Background and Objectives: This observational prospective study aims to examine the psychological and psychopathological impact of the pandemic stress on patients with pre-existing mood, anxiety and obsessive-compulsive disorders. Materials and Methods: The study includes 386 consecutive patients recruited from 10 March to 30 June 2020 among those being treated at the Institute of Psychopathology in Rome (Italy) with an age ≥18 years and meeting DSM-5 criteria for major depressive disorder (MDD) (35.2%), bipolar I (BD-I) (21.5%) or II (BD-II) (28.8%) disorder, obsessive-compulsive disorder (OCD) (7.5%), panic disorder (PD) (7.0%) or social anxiety (SA). A total of 34.2% had lifetime comorbid Axis I disorders and 15.3% had alcohol/drug abuse disorders. Using a semi-structured interview, we investigated if the impact of COVID-19 stress for patients has been similar, higher or lower than that of their family and friends and, for patients with relapse/symptoms worsening, if there was a relationship between the clinical condition worsening and the pandemic stress. Results: Compared with that experienced by their family members and friends, the psychological impact of pandemic stress was similar in 52.1% of the sample, better in 37.1% and worse in 10.8%. In 21 patients (5.4%), the stress triggered a recurrence or worsened the symptoms. Patients with OCD had a higher rate of worsening due to pandemic stress compared to patients with MDD (p = 0.033), although, overall, the χ2 test was not significant among primary diagnoses (χ2 = 8.368; p = 0.057). Conclusions: The psychological and psychopathological consequences of COVID-19 stress in our outpatients were very modest. The continuity of care offered during the lockdown could explain the results.

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.

Cognitive-behavioural therapy for obsessive-compulsive disorder co-occurring with psychosis: Systematic review of evidence.

AIM: To review available evidence on the use of cognitive behavioural therapy (CBT) for treating obsessive compulsive disorder co-occurring with psychosis. METHODS: In this paper we present a detailed and comprehensive review of the current literature focusing on CBT treatment of obsessive compulsive disorder (OCD) co-occurring with schizophrenia or schizoaffective disorder. We identified relevant literature published between 2001 and May 2016 through MEDLINE/PubMed search using as search string ("obsessive compulsive disorders" or "obsessive compulsive symptoms") and ("schizophrenia" or "schizoaffective disorder" or "psychosis") and ("cognitive behavioural therapy"). Other citations of interest were further identified from references reported in the accessed articles. The search was limited to studies written in English and carried out in adult patients. A total of 9 studies, 8 case reports and 1 case series, were found. RESULTS: The reviewed evidence indicates that CBT is: (1) safe, i.e., does not worsen psychotic symptoms; (2) well accepted, with a discontinuation rate quite similar to that reported for patients with OCD without psychosis comorbidity; (3) effective, with a symptom reduction quite similar to that reported for patients with OCD without psychosis and for SRIs treatment of OCD co-occurring with psychosis; and (4) effective in patients with OCD induced by second-generation antipsychotic as well as in patients with OCD not induced by second-generation antipsychotic. Alcohol/substance use disorder comorbidity and OCD onset preceding that of SCH/SA was predictors of poor outcome. These results are derived only by additional studies with adequate sample size. CONCLUSION: Our results support the use of CBT for OCD in patients with psychosis.