Medications are commonly used to treat co-occurring psychopathology in persons with borderline personality disorder (BPD)

To systematically review and integrate the evidence of medications for treatment of co-occurring psychopathology in people with BPD, and explore the role of comorbidities.

Building on the current Cochrane review of medications in BPD, an update literature search was done in March 2024. We followed the methods of this Cochrane review, but scrutinised all identified placebo-controlled trials post hoc for reporting of non BPD-specific (‘co-occurring’) psychopathology, and explored treatment effects in subgroups of samples with and without defined co-occurring disorders. GRADE ratings were done to assess the evidence certainty.

Twenty-two trials were available for quantitative analyses. For antipsychotics, we found very-low-certainty evidence (VLCE) of an effect on depressive symptoms (standardised mean difference (SMD) −0.22, P = 0.04), and low-certainty evidence (LCE) of an effect on psychotic–dissociative symptoms (SMD −0.28, P = 0.007). There was evidence of effects of anticonvulsants on depressive (SMD −0.44, P = 0.02; LCE) and anxious symptoms (SMD −1.11, P < 0.00001; VLCE). For antidepressants, no significant findings were observed (VLCE). Exploratory subgroup analyses indicated a greater effect of antipsychotics in samples including participants with co-occurring substance use disorders on psychotic–dissociative symptoms (P = 0.001).

Our findings, based on VLCE and LCE only, do not support the use of pharmacological interventions in people with BPD to target co-occurring psychopathology. Overall, the current evidence does not support differential treatment effects in persons with versus without defined comorbidities. Medications should be used cautiously to target co-occurring psychopathology.

Psychotic disorders are highly heritable, yet the evidence is less clear for subclinical psychosis expression, such as psychotic experiences (PEs). We examined if PEs in parents were associated with PEs in offspring.

As part of the Danish general population Lolland-Falster Health Study, families with youths aged 11–17 years were included. Both children and parents reported PEs according to the Psychotic Like Experiences Questionnaire, counting only ‘definite’ PEs. Parents additionally reported depressive symptoms, anxiety, and mental wellbeing. The associations between parental and child PEs were estimated using generalized estimating equations with an exchangeable correlation structure to account for the clustering of observations within families, adjusting for sociodemographic characteristics.

Altogether, 984 youths (mean age 14.3 years [s.d. 2.0]), 700 mothers, and 496 fathers from 766 households completed PEs-questionnaires. Offspring of parents with PEs were at an increased risk of reporting PEs themselves (mothers: adjusted risk ratio (aRR) 2.42, 95% CI 1.73–3.38; fathers: aRR 2.25, 95% CI 1.42–3.59). Other maternal problems (depression, anxiety, and poor mental well-being), but not paternal problems, were also associated with offspring PEs. In multivariate models adjusting for parental problems, PEs, but not other parental problems, were robustly associated with offspring PEs (mothers: aRR 2.25, 95% CI 1.60–3.19; fathers: aRR 2.44, 95% CI 1.50–3.96).

The current findings add novel evidence suggesting that specific psychosis vulnerability in families is expressed at the lower end of the psychosis continuum, underlining the importance of assessing youths’ needs based on psychosis vulnerability broadly within the family systems.

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.

A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD).

To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely.

We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition.

Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) −0.54, P = 0.006; psychosocial functioning: SMD −0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P < 0.0007; suicide-related outcomes: risk ratio 0.10, P < 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD −0.66, P = 0.002; psychosocial functioning: SMD −0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference −8.49, P < 0.00001), manual-assisted cognitive therapy (self-harm: mean difference −3.03, P = 0.03; suicide-related outcomes: SMD −0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD −0.48, P = 0.002).

There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings.

To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics.

FEP (N = 191) were recruited from in- and outpatient services 1997–2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15–65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale.

CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms.

Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has been shown to have a statistically and clinically significant anti-depressant effect. The present pilot study was carried out to investigate if right prefrontal low-frequency rTMS as an add-on to electroconvulsive therapy (ECT) accelerates the anti-depressant effect and reduces cognitive side effects.

In this randomised, controlled, double-blind study, thirty-five patients with major depression were allocated to ECT+placebo or ECT+low-frequency right prefrontal rTMS. The severity of depression was evaluated during the course using the Hamilton scale for depression (the 17-item as well as the 6-item scale) and the major depression inventory (MDI). Furthermore, neuropsychological assessment of cognitive function was carried out.

The study revealed no significant difference between the two groups for any of the outcomes, but with a visible trend to lower scores for MDI after treatment in the placebo group. The negative impact of ECT on neurocognitive functions was short-lived, and scores on logical memory were significantly improved compared to baseline 4 weeks after last treatment. The ECT-rTMS group revealed generally less impairment of cognitive functions than the ECT-placebo group.

The addition of low-frequency rTMS as an add-on to ECT treatment did not result in an accelerated response. On the contrary, the results suggest that low-frequency rTMS could inhibit the anti-depressant effect of ECT.

Information about the cost-effectiveness of early intervention programmes for first-episode psychosis is limited.

To evaluate the cost-effectiveness of an intensive early-intervention programme (called OPUS) (trial registration NCT00157313) consisting of enriched assertive community treatment, psychoeducational family treatment and social skills training for individuals with first-episode psychosis compared with standard treatment.

An incremental cost-effectiveness analysis of a randomised controlled trial, adopting a public sector perspective was undertaken.

The mean total costs of OPUS over 5 years (€123683, s.e. = 8970) were not significantly different from that of standard treatment (€148751, s.e. = 13073). At 2-year follow-up the mean Global Assessment of Functioning (GAF) score in the OPUS group (55.16, s.d. = 15.15) was significantly higher than in standard treatment group (51.13, s.d. = 15.92). However, the mean GAF did not differ significantly between the groups at 5-year follow-up (55.35 (s.d. = 18.28) and 54.16 (s.d. = 18.41), respectively). Cost-effectiveness planes based on non-parametric bootstrapping showed that OPUS was less costly and more effective in 70% of the replications. For a willingness-to-pay up to €50000 the probability that OPUS was cost-effective was more than 80%.

The incremental cost-effectiveness analysis showed that there was a high probability of OPUS being cost-effective compared with standard treatment.

There is highly replicated positive correlation between longer duration of untreated psychosis and poorer outcome

To study the effect of early intervention in first psychosis on one-year outcome using an historical quasi-experimental design

We compare the outcome of two samples of first-episode psychosis from the same healthcare district at different time periods. The historical control sample was assessed during 19931994, before the establishment of a system for early detection of psychosis. The experimental sample is the early detection sample in the Early Treatment and Intervention in Psychosis study assessed during 1997–2000

At 1-year follow-up, the early detection group was younger, had a smaller fraction of individuals with schizophrenia, had less severe negative and general symptoms and had more friends in the past year than the historical control group. No differences were found in clinical course (remission, relapse, continuously psychotic) or positive symptoms, but more patients in the early detection sample were treated as outpatients without hospitalisation

Early detection of schizophrenia in one healthcare sector is associated with less severe deterioration at 1 year

It is unclear whether an early detection programme increases or decreases the number of patients with a long duration of untreated psychosis (DUP), and whether these differ from other patients with a long DUP.

To investigate whether the number and characteristics of patients with a long DUP in the early detection programme differ from those with along DUP in the non-earlydetection programme.

We compared the number and characteristics of patients with a DUP $2 years in an early detection area and a non-early detection area.

The early detection programme recruited slightly fewer patients with a long DUP than the non-early detection programme. The patients in the early detection programme had lower PANSS scores, but more frequently had a deteriorating course of premorbid social functioning.

An early detection programme does not seem to drain a pool of previously undetected patients with a long DUP. The patients in the early detection programme seem to have a lower symptom level at baseline and to have had a deteriorating premorbid social course.

Early detection programmes aim to reduce the duration of untreated psychosis (DUP) by public education and by prompt access to treatment via active outreach detection teams.

To determine whether those with first-episode psychosis in an early detection healthcare area with existing referral channels differ from those who access care via detection teams.

Those with first-episode psychosis recruited via detection teams were compared with those accessing treatment via conventional channels, at baseline and after 3 months of acute treatment.

Patients recruited via detection teams are younger males with a longer DUP a less dramatic symptom picture and better functioning; however they recover more slowly, and have more symptoms at 3-month follow-up.

After establishing low threshold active case-seeking detection teams, we found clear differences between those patients entering treatment via detection teams v. those obtaining treatment via the usual channels. Such profiling may be informative for early detection service development.

Knowledge about premorbid development in psychosis can shed light upon theories about aetiology and schizophrenic heterogeneity, and form a basis for early detection initiatives.

To identify and validate patterns of premorbid functioning in first-episode psychosis.

The Premorbid Adjustment Scale was used to examine 335 patients.

Social and academic function constituted fairly independent dimensions. Cluster analysis identified groups varying both in level and course. Patients with a stable social course compared with a deteriorating one had a shorter duration of untreated psychosis, were older, had more friends and less negative symptoms. Good childhood academic function correlated with more education, more meaningful activities and better working memory. Patients with a stable academic course were older at admission.

Patterns of premorbid development suggest both neuro-developmental and neuroregressive pathways to illness.