Acute effects of lithium augmentation on the kidney in geriatric compared with non-geriatric patients with treatment-resistant depression.

INTRODUCTION: Lithium augmentation (LA) of antidepressants is a first-line therapy option for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients mostly because of the fear of kidney toxicity. The purpose of this study is to investigate estimated glomerular filtration rate (eGFR) changes and number of acute kidney injuries (AKI) using LA in geriatric compared with non-geriatric patients. METHODS: In a prospective multicenter cohort study, eGFR changes were measured in 201 patients with unipolar depression (nage≥65years  = 29; nage<65years  = 172) at baseline and over 2-6 weeks of LA. We used linear mixed models to investigate changes in eGFR upon LA and assessed the number of AKIs, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: Both age groups showed a significant eGFR decline over the course of treatment with lower eGFR in geriatric patients. The lithium serum level (interpretable as "effect of LA") had a significant effect on eGFR decline. Both effects (age group and lithium serum level) on eGFR decline did not influence each other, meaning the effect of LA on eGFR decline did not differ between age groups. Two AKIs were observed in the geriatric age group when serum lithium levels exceeded the therapeutic range of >0.8 mmol/L. CONCLUSION: This is the first study investigating eGFR change and AKI upon LA for TRD in geriatric compared with non-geriatric patients. Our data suggest that LA, as an effective treatment option in geriatric patients, should be closely monitored to avoid AKIs.

Promoting stigma coping and empowerment in patients with schizophrenia and depression: results of a cluster-RCT.

There is a need for interventions supporting patients with mental health conditions in coping with stigma and discrimination. A psycho-educational group therapy module to promote stigma coping and empowerment (STEM) was developed and tested for efficacy in patients with schizophrenia or depression. 30 clinical centers participated in a cluster-randomized clinical trial, representing a broad spectrum of mental health care settings: in-patient (acute treatment, rehabilitation), out-patient, and day-hospitals. As randomized, patients in the intervention group clusters/centers received an illness-specific eight sessions standard psychoeducational group therapy plus three specific sessions on stigma coping and empowerment ('STEM'). In the control group clusters the same standard psychoeducational group therapy was extended to 11 sessions followed by one booster session in both conditions. In total, N = 462 patients were included in the analysis (N = 117 with schizophrenia spectrum disorders, ICD-10 F2x; N = 345 with depression, ICD-10 F31.3-F31.5, F32-F34, and F43.2). Clinical and stigma-related measures were assessed before and directly after treatment, as well as after 6 weeks, 6 months, and 12 months (M12). Primary outcome was improvement in quality of life (QoL) assessed with the WHO-QOL-BREF between pre-assessment and M12 analyzed by mixed models and adjusted for pre-treatment differences. Overall, QoL and secondary outcome measures (symptoms, functioning, compliance, internalized stigma, self-esteem, empowerment) improved significantly, but there was no significant difference between intervention and control group. The short STEM module has proven its practicability as an add-on in different settings in routine mental health care. The overall increase in empowerment in both, schizophrenia and depression, indicates patients' treatment benefit. However, factors contributing to improvement need to be explored.The study has been registered in the following trial registers. ClinicalTrials.gov: https://register.clinicaltrials.gov/ Registration number: NCT01655368. DRKS: https://www.drks.de/drks_web/ Registration number: DRKS00004217.

Attentional dysfunction in abstinent long-term cannabis users with and without schizophrenia.

Long-term cannabis use may confer cognitive deficits and increased risk of psychosis. However, the relationship between cannabis use and schizophrenia is complex. In particular, little is known about the effects of chronic cannabis use on the attention-related electric brain response in schizophrenia. We investigated auditory novelty and oddball P300 evoked potentials in a mixed sample of first-episode and chronic schizophrenic patients and healthy controls with (SZCA, n = 20; COCA, n = 20, abstinence ≥28 days) or without (SZ, n = 20; CO, n = 20) chronic cannabis use. Duration of regular cannabis use was 8.3 ± 5.6 (SZCA) and 9.1 ± 7.1 (COCA) years. In general, schizophrenic patients showed reduced P300 amplitudes. Cannabis use was associated with both a reduced early and late left-hemispheric novelty P300. There was a significant 'diagnosis × cannabis' interaction for the left-hemispheric late novelty P300 in that cannabis use was associated with a reduced amplitude in the otherwise healthy but not in the schizophrenic group compared with their relative control groups (corrected p < 0.02; p > 0.9, respectively). The left-hemispheric late novelty P300 in the otherwise healthy cannabis group correlated inversely with amount and duration of cannabis use (r = -0.50, p = 0.024; r = -0.57, p = 0.009, respectively). Our study confirms attentional deficits with chronic cannabis use. However, cannabis use may lead to different cognitive sequelae in patients with schizophrenia and in healthy controls, possibly reflecting preexisting alterations in the endocannabinoid system in schizophrenia.

Treatment response of lithium augmentation in geriatric compared to non-geriatric patients with treatment-resistant depression.

BACKGROUND: Lithium augmentation (LA) of antidepressants is an effective strategy for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients. The purpose of this study was to investigate treatment response of LA in geriatric compared to non-geriatric patients. METHOD: In a prospective multicenter cohort study, severity of depression was measured weekly in 167 patients with unipolar depression (nage≥65years = 22; nage<65years = 145) at baseline and over at least four weeks of LA. RESULTS: Geriatric patients showed a significantly better response to LA compared to non-geriatric patients (Hazard Ratio = 1.91; p = 0.04). LIMITATIONS: An important limitation of our study is the lack of a control group of LA and the missing evaluation of side effects in both groups. CONCLUSIONS: This is the first study investigating the efficacy of LA for TRD in geriatric compared to non-geriatric patients. Our data suggest that LA is an effective treatment option in geriatric patients that clinicians might consider more frequently and earlier on in the course of treatment.

Opposing Effects of Cannabis Use on Late Auditory Repetition Suppression in Schizophrenia Patients and Healthy Control Subjects.

BACKGROUND: Chronic cannabis use may cause neurocognitive deficits and increase the risk of psychosis. Nevertheless, the effects of cannabis use on neurocognitive functioning in schizophrenia have remained largely unspecified. METHODS: Here, we studied repetition suppression of auditory event-related responses in a paired-stimulus design in a mixed sample of schizophrenia patients (n = 34) and healthy control subjects (n = 45) with chronic heavy cannabis use and schizophrenia patients (n = 33) and healthy control subjects (n = 61) without cannabis use. RESULTS: Repeated measures analysis yielded an overall significant reduction of P50 amplitude between first and second stimulus (p < .02), which was not different between the groups, a reduction of N100 amplitude, which was different for schizophrenia patients compared with healthy control subjects independent of cannabis use (p < .02), and a significant interaction between diagnosis and chronic cannabis use on the reduction of the P200 amplitude (p < .001). While chronic cannabis use was related with increased P200 suppression ratios in control subjects (with chronic cannabis use: 0.55 ± 0.04; without chronic cannabis use: 0.40 ± 0.03; p < .02), the reverse effect was found in schizophrenia (with chronic cannabis use: 0.36 ± 0.05; without chronic cannabis use: 0.54 ± 0.05; p < .02). This result remained significant after inclusion of potential confounders. Total lifetime cannabis use showed a significant correlation with the P200 suppression ratio in otherwise healthy control subjects (r = .28, p < .007). By contrast, the duration of time since last cannabis use was significantly correlated with the P200 suppression ratio in schizophrenia patients (r = .42, p < .002). CONCLUSIONS: In aggregate, these diverging effects of chronic cannabis use on P200 repetition suppression may suggest underlying alterations in the endocannabinoid system in schizophrenia.