Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery—no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups.

Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the “Remission in Schizophrenia Working Group” criteria and TR on adaptations of the “Treatment Response and Resistance in Psychosis” (TRRIP) working group criteria.

97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects.

The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

To investigate the relationship between lean muscle mass and treatment response in treatment-resistant late-life depression (TR-LLD). We hypothesized that lower lean muscle mass would be associated with older age, higher physical comorbidities, higher depressive symptom severity, and poorer treatment response.

Secondary analysis of a randomized, placebo-controlled trial.

Three academic hospitals in the United States and Canada.

Adults aged 60+ years with major depressive disorder who did not remit following open treatment with venlafaxine extended-release (XR) (n = 178).

We estimated lean muscle mass using dual-energy X-ray absorptiometry (DEXA) scans prior to and following randomized treatment with aripiprazole or placebo added to venlafaxine XR. Multivariate regressions estimated influence of demographic and clinical factors on baseline lean muscle mass, and whether baseline lean muscle mass was associated with treatment response, adjusted for treatment arm.

Low lean muscle mass was present in 22 (12.4%) participants. Older age and female sex, but not depressive symptom severity, were independently associated with lower lean muscle mass at baseline. Marital status, baseline depressive symptom severity, and treatment group were associated with improvement of depressive symptoms in the randomized treatment phase. Baseline lean muscle mass was not associated with improvement, regardless of treatment group.

As expected, older age and female sex were associated with lower lean muscle mass in TR-LLD. However, contrary to prior results in LLD, lean muscle mass was not associated with depression severity or outcome. This suggests that aripiprazole augmentation may be useful for TR-LLD, even in the presence of anomalous body composition.

clinicaltrials.gov Identifier: NCT00892047.

This study aimed to evaluate the retinal nerve fibre layer changes among different group of patients with schizophrenia and compare it with healthy controls by using swept-source optical coherence tomography.

Patients with first-episode schizophrenia (n = 21) in remission (n = 35) or with treatment-resistant schizophrenia (TRS) (n = 35) and 36 healthy controls were evaluated for retinal thickness.

Patients with psychotic illnesses had significantly lower sub-foveal choroidal thickness (effect size 0.84–0.86), when compared to the healthy controls. When patients with first-episode schizophrenia were compared with patients with TRS, TRS patients had significant lower sub-foveal choroidal thickness (left eye) when the various confounders (such as age, gender, duration of treatment, smoking, current medications, body mass index, waist circumference, blood pressure, fasting glucose, HbA1c, presence or absence of metabolic syndrome) were taken into account. When the patients with TRS were compared with healthy controls, initially significant differences were observed for the macular volume (left and right) and the ganglion cell thickness (right eye) but these differences disappeared after controlling for the various covariates.

Compared to healthy controls, patients with schizophrenia, psychotic illnesses have thinning of the retina, especially in the sub-foveal choroidal thickness.

The response to antipsychotic treatment in patients with schizophrenia varies from 14 to 34% in first episodes, and from 45 to 61% in more chronic patients. Nevertheless, the concept of treatment resistant schizophrenia (TRS) is still a matter of great controversy. Recently, an international group of experts has developed the TRRIP criteria to define treatment resistant schizophrenia (TRS), including an ultra-resistance category for clozapine resistant patients. Up till now, there is a scarcity of epidemiological data of TRS with TRRIP criteria.

This study attempts to identify the population diagnosed of schizophrenia that fulfils the minima TRRIP criteria for TRS in our mental health catchment area.

A descriptive and retrospective study has been developed on the patients diagnosed of schizophrenia (ICD.10, F.20) in the catchment area of the Mental Health Service at Jerez Hospital between 2018 and 2019. TRRIP criteria were applied for two independent researchers and, in case of disagreement, consensus was reached by using the LEAD procedure.

The total number of ICD-10 schizophrenic patients identified was 590, from a population of 456.752 in 2019. A group of these, 206 patients (35%) qualified as TRS according to the minima TRRIP criteria, 50% were positive subtype and the rest the negative one. 46.8% were treated with clozapine.

Consensus criteria of TRS minimise the heterogeneity of epidemiological data in literature. Our data suggest a prevalence rate of TRS lower than that of similar studies. Accordingly, a comprehensive understanding of this population would undoubtedly contribute to improve preventive and therapeutic strategies.

No significant relationships.

Obsessive Compulsive Disorder (OCD) and Tic Disorder (TD) are two highly disabling, comorbid and difficult-to-treat conditions. DSM-5 acknowledged a new “tic-related” specifier for OCD, i.e., Obsessive-Compulsive Tic-related Disorder (OCTD), which may show poor treatment response.

The aim of the present study was to evaluate rates and clinical correlates of response, remission and resistance to treatment in a large multicentre sample of OCD patients with versus without tics.

398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from ten psychiatric departments across Italy. Treatment response profiles in the whole sample were analysed comparing the rates of response, remission and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to highlight possible treatment response related factors.

Later ages of onset of TD and OCD were found in the remission group. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts were associated to the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement.

While remission was related to 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. These findings suggest a worse profile of treatment response for patients with OCTD.

No significant relationships.

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.

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.

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.

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.

Treatment-resistant schizophrenia (TRS) represents a major clinical issue, characterized by worse psychopathological outcome, a more disrupted neurobiological substrate and higher healthcare costs. Cognitive impairment is a core feature of schizophrenia, strongly associated with patients’ functional outcome. Different studies showed that TRS patients exhibit poorer neurocognitive performance, particularly on verbal domains. To date Cognitive Remediation Therapy (CRT) represents the best available tool for treating cognitive deficits in schizophrenia. However, CRT outcomes are highly heterogeneous and significant treatment predictors are still lacking.

To investigate possible differences of CRT outcome among patients with schizophrenia, stratified according to antipsychotic response (TRSs vs. first-line responders - FLRs).

150 patients with schizophrenia, (95 FLRs, 55 TRSs) were assessed for neurocognition with BACS and WCST at baseline and after CRT. General Linear Models (GLMs) were performed to investigate possible differences between groups on basal cognition and CRT outcome (Cohen’s d Effect Size).

At baseline, GLMs showed significant differences in Verbal Memory (F=4,66; p=0,03) and WCST–executive functions (F=5,59; p=0,02), both worse in TRS group. Effecr Sizes of CRT outcome resulted significantly different in domains of Verbal Memory (F=4,68; p=0,03) and WCST–executive functions (F=4,62; p=0,03), with greater improvements among TRS patients.

This is the first study to indicate treatment-resistance as a possible predictor of CRT outcome in schizophrenia. Moreover, we observed that CRT resulted able to fill the cognitive gap between treatment groups. Thus, these results further highlight the importance of early cognitive interventions in order to reduce the neuropsychological and functional burden associated with the disease, especially for TRS patients.

No significant relationships.

It has been suggested that individual differences in temperament could be involved in the (non-)response to antidepressant (AD) treatment. However, how neurobiological processes such as brain glucose metabolism may relate to personality features in the treatment-resistant depressed (TRD) state remains largely unclear.

To examine how brainstem metabolism in the TRD state may predict Cloninger's temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), and Reward Dependence (RD), we collected 18fluorodeoxyglucose positron emission tomography (18FDG PET) scans in 40 AD-free TRD patients. All participants were assessed with the Temperament and Character Inventory (TCI). We applied a multiple kernel learning (MKL) regression to predict the HA, NS, and RD from brainstem metabolic activity, the origin of respectively serotonergic, dopaminergic, and noradrenergic neurotransmitter (NT) systems.

The MKL model was able to significantly predict RD but not HA and NS from the brainstem metabolic activity. The MKL pattern regression model identified increased metabolic activity in the pontine nuclei and locus coeruleus, the medial reticular formation, the dorsal/median raphe, and the ventral tegmental area that contributed to the predictions of RD.

The MKL algorithm identified a likely metabolic marker in the brainstem for RD in major depression. Although 18FDG PET does not investigate specific NT systems, the predictive value of brainstem glucose metabolism on RD scores however indicates that this temperament dimension in the TRD state could be mediated by different monoaminergic systems, all involved in higher order reward-related behavior.

Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.

This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.

Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.

A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.

Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.

While the efficacy of repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) is well established, the debate is still open in relation to bipolar depression and to a possible different effectiveness of high vs. low stimulation. The present study was aimed to assess and compare the efficacy and tolerability of different protocols of augmentative rTMS in a sample of patients with current Major Depressive Episode (MDE), poor drug response/treatment resistance and a diagnosis of MDD or bipolar disorder.

Thirty-three patients were recruited in a 4-week, blind-rater, rTMS trial and randomised to the following three groups of stimulation: (1) (n = 10) right dorsolateral prefrontal cortex (DLPFC) 1 HZ, 110% of the motor threshold (MT), 420 stimuli/day; (2) (n = 10) right DLPFC, 1 Hz, 110% MT, 900 stimuli/day; (3) (n = 13) left DLPFC, 10 Hz, 80% MT, 750 stimuli/day.

Twenty-nine patients completed the treatment, showing a significant reduction of primary outcome measures (HAM-D, MADRS and CGI-S total scores: t = 8.1, P < 0.001; t = 8.6, P < 0.001; t = 4.6, P < 0.001 respectively). No significant differences in terms of efficacy and tolerability were found between high vs. low frequency and between unipolar and bipolar patients. Side effects were reported by 21% of the sample. One of the 4 dropouts was caused by a hypomanic switch.

Augmentative rTMS appeared to be effective and well tolerated for the acute treatment of unipolar and bipolar depression with features of poor drug response/treatment resistance, showing a comparable effectiveness profile between protocols of high and low frequency stimulation.