The course of depressive symptoms and prescribing patterns of antidepressants in schizophrenia in a one-year follow-up study

AbstractBackgroundAntidepressants are frequently prescribed in patients with psychotic disorders, but little is known about their effects in routine clinical practice. The objective was to investigate the prescribing patterns of antidepressants in relation to the course of depressive symptoms in patients with psychotic disorders.MethodsA cohort of 214 Dutch patients with psychotic disorders received two assessments of somatic and psychiatric health, including a clinician-rated screening for depressive symptoms, as part of annual routine outcome monitoring.ResultsDepressive symptoms were prevalent among 43% (93) of the patients. Antidepressants were prescribed for 40% (86) of the patients and the majority 83% (71) continued this therapy after one year. Multivariable analysis showed that patients with more severe psychopathology had a higher risk to develop depressive symptoms the following year (OR [95% CI]=0.953 [0.912–0.995]). For patients with depressive symptoms at baseline, polypharmacy was a potential risk factor to keep having depressive symptoms (OR [95% CI]=1.593 [1.123–2.261]). Antidepressant use was not an independent predictor in both analyses.ConclusionsRoutine outcome monitoring in patients with psychotic disorders revealed a high prevalence of depressive symptoms. Antidepressants were frequently prescribed and continued in routine clinical practice

Altered emotional experiences attributed to antipsychotic medications - A potential link with estimated dopamine D-2 receptor occupancy

Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D-2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their anti psychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients' relatively low dose range, altered emotional experiences did not appear to relate to the level of D-2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033-2.015]); possibly due to higher D-2 receptor occupancies as estimated by dose equivalents. (C) 2016 Published by Elsevier Ireland Ltd

The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913)

<p>Abstract</p> <p>Background</p> <p>The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC), which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone) (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]).</p> <p>Method</p> <p>This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX). This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper.</p> <p>Results</p> <p>A total of 555 patients were randomised to receive aripiprazole (n = 284) or SOC (n = 271). Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC). Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS) at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p < 0.001).</p> <p>Conclusion</p> <p>The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.</p

Neurobiological Divergence of the Positive and Negative Schizophrenia Subtypes Identified on a New Factor Structure of Psychopathology Using Non-negative Factorization:An International Machine Learning Study

ObjectiveDisentangling psychopathological heterogeneity in schizophrenia is challenging and previous results remain inconclusive. We employed advanced machine-learning to identify a stable and generalizable factorization of the “Positive and Negative Syndrome Scale (PANSS)”, and used it to identify psychopathological subtypes as well as their neurobiological differentiations.MethodsPANSS data from the Pharmacotherapy Monitoring and Outcome Survey cohort (1545 patients, 586 followed up after 1.35±0.70 years) were used for learning the factor-structure by an orthonormal projective non-negative factorization. An international sample, pooled from nine medical centers across Europe, USA, and Asia (490 patients), was used for validation. Patients were clustered into psychopathological subtypes based on the identified factor-structure, and the neurobiological divergence between the subtypes was assessed by classification analysis on functional MRI connectivity patterns.ResultsA four-factor structure representing negative, positive, affective, and cognitive symptoms was identified as the most stable and generalizable representation of psychopathology. It showed higher internal consistency than the original PANSS subscales and previously proposed factor-models. Based on this representation, the positive-negative dichotomy was confirmed as the (only) robust psychopathological subtypes, and these subtypes were longitudinally stable in about 80% of the repeatedly assessed patients. Finally, the individual subtype could be predicted with good accuracy from functional connectivity profiles of the ventro-medial frontal cortex, temporoparietal junction, and precuneus.ConclusionsMachine-learning applied to multi-site data with cross-validation yielded a factorization generalizable across populations and medical systems. Together with subtyping and the demonstrated ability to predict subtype membership from neuroimaging data, this work further disentangles the heterogeneity in schizophrenia

The Effect of Chronic Antipsychotic Drug on Hypothalamic Expression of Neural Nitric Oxide Synthase and Dopamine D2 Receptor in the Male Rat

Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect. It has been demonstrated that both neuronal nitric oxide (nNOS) and dopamine D2 receptor (DRD2) in the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) of the hypothalamus have important roles in the regulation of sexual behaviour. We investigated the influences of 21 days’ antipsychotic drug administration on expression of nNOS and DRD2 in the rat hypothalamus. Haloperidol (0.5 mg/kg/day i.p.) significantly decreased nNOS integrated optical density in a sub-nucleus of the MPOA, medial preoptic nucleus (MPN), and decreased the nNOS integrated optical density and cell density in another sub-nucleus of the MPOA, anterodorsal preoptic nucleus (ADP). Risperidone (0.25 mg/kg) inhibited the nNOS integrated optical density in the ADP. nNOS mRNA and protein in the MPOA but not the PVN was also significantly decreased by haloperidol. Haloperidol and risperidone increased DRD2 mRNA and protein expression in both the MPOA and the PVN. Quetiapine (20 mg/kg/day i.p.) did not influence the expression of nNOS and DRD2 in either the MPOA or the PVN. These findings indicate that hypothalamic nNOS and DRD2 are affected to different extents by chronic administration of risperidone and haloperidol, but are unaffected by quetiapine. These central effects might play a role in sexual dysfunction induced by certain antipsychotic drugs

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 J

The specificity of neurological signs in schizophrenia:a review

This review examines the extent to which neurological signs are more prevalent in schizophrenia patients, compared to mood-disorder patients and healthy subjects, and whether there is a pattern in any of the differences that may be found. We included 17 studies and calculated the weighted mean prevalence of 30 neurological signs. The prevalence of most signs appears to be si,significantly different between schizophrenia patients and normal controls, but there are fewer differences between schizophrenia and mood-disorder patients. Several signs - poor stereognosis and rhythm tapping - are even more prevalent in mood-disorder patients than in schizophrenia patients. Only lack of extinction, dysdiadochokinesia, poor tandem walk, finger-thumb-opposition and articulation are significantly more prevalent in schizophrenia compared to mood-disorder patients. Impaired motor coordination seems most specific to schizophrenia. The discriminating power of motor sequencing still needs to be studied. So far, there is no evidence of a clearly interpretable pattern of neurological signs distinguishing schizophrenia patients from mood-disorder patients. (C) 2000 Elsevier Science B.V. All rights reserved