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

Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness

Stress-related psychiatric disorders across the life spa

The Additional Effect of Individualized Prescriber-Focused Feedback on General Guideline Instruction in Reducing Antipsychotic Polypharmacy in Inpatients

PURPOSE/BACKGROUND: Antipsychotic polypharmacy (APP) is the concurrent use of more than one antipsychotic by a patient. Multiple antipsychotics are often prescribed, although all relevant guidelines discourage this practice. These recommendations are based on a lack of evidence for effectiveness and an increased risk of serious adverse events with APP. Studies on the effects of educational interventions targeted at physicians have demonstrated inconclusive results. Moreover, it is unclear how individualized these interventions need to be. In this study, we aimed to assess the effect of a general intervention and the additional impact of an individualized, prescriber-focused intervention on guidelines adherence, that is, the prescription of APP. METHODS/PROCEDURES: We conducted a 36-month 2-step serial intervention study with 4 stages of 9 months each (baseline, general intervention, addition of an individualized intervention, and follow-up) including all 20 inpatient units of one regional mental health organization. The primary outcome was the proportion of patients with regular prescriptions for APP ≥30 consecutive days across all patients with a prescription of at least one antipsychotic. The secondary outcome was the proportion of patient days on APP over the total number of patient days on at least one antipsychotic. FINDINGS/RESULTS: The general intervention was ineffective on both outcome measures. Addition of an individualized intervention decreased the proportion of patients with prescriptions for episodes of persistent APP significantly by 49.6%. The proportion of patient days on APP significantly decreased by 35.4%. IMPLICATIONS/CONCLUSIONS: In contrast to a general intervention, the addition of an individualized intervention was effective in improving adherence to guidelines with respect to APP prescription in inpatients

Experiences of Dutch ambulance nurses in emergency care for patients with acute manic and/or psychotic symptoms: A qualitative study

PURPOSE: To explore the experiences of ambulance nurses in emergency care of patients with acute manic and/or psychotic symptoms. METHODS: In this qualitative study, 14 interviews were conducted and analyzed using thematic analysis according to Braun and Clarke (2006). FINDINGS: Psychiatric emergency care causes stress and uncomfortable feelings for ambulance nurses due to a lack of information on the patients, being alone with the patient in a small place and the unpredictability of the situation. PRACTICE IMPLICATIONS: More information about the specific patient, education, and good collaboration with other professionals could improve care

Antidepressants for bipolar depression: a systematic review of randomized, controlled trials.

OBJECTIVE: This study reviewed the evidence from randomized, controlled trials on the efficacy and safety of antidepressants in the short-term treatment of bipolar depression. METHOD: The authors performed a systematic review and meta-analysis of randomized, controlled trials. They searched the Cochrane Collaboration Depression, Anxiety, and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE, EMBASE, CINAHL, PsycLIT, PSYNDEX, and LILACS. The main outcome measures were the proportion of patients who clinically responded to treatment and the rate of switching to mania. RESULTS: Twelve randomized trials were included, with a total of 1,088 randomly assigned patients. Five trials compared one or more antidepressants with placebo: 75% of these patients were receiving a concurrent mood stabilizer or an atypical antipsychotic. Antidepressants were more effective than placebo. Antidepressants did not induce more switching to mania (the event rate for antidepressants was 3.8% and for placebo, it was 4.7%). Six trials allowed comparison between two antidepressants. The rate of switching for tricyclic antidepressants was 10%, and for all other antidepressants combined, it was 3.2%. CONCLUSIONS: Antidepressants are effective in the short-term treatment of bipolar depression. The trial data do not suggest that switching is a common early complication of treatment with antidepressants. It may be prudent to use a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor rather than a tricyclic antidepressant as first-line treatment. Given the limited evidence, there is a compelling need for further studies with longer follow-up periods and careful definition and follow-up of emerging mania and partial remission

Plasma interleukin-1, tumor necrosis factor and hypothalamic-pituitary-adrenal axis responses during migraine attacks

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Emergency care to 'persons with confused behavior': Lived experiences of, and collaboration between, police and members of a mobile crisis team - A hermeneutic-phenomenological study

BACKGROUND: Police officers and members of a mobile crisis team (MCT) are the two actors who respond to nuisance in Dutch society related to 'persons with confused behavior' and serious violent incidents. Their collaboration creates tension and dissatisfaction about roles and responsibilities. AIM: To explore the lived experiences of, and collaboration between, police officers and members of a MCT. METHODS: A hermeneutic-phenomenological study with unstructured in-depth interviews of eight police officers and eight members of a MCT. FINDINGS: The main findings in this study are that in the emergency care of 'persons with confused behavior' two very different professions are forced to work together, and that this collaboration is quite challenging. It becomes clear that different visions and expectations cause frustration in the collaboration. Police want the participation of the MCT as soon as possible after they are called in. The MCT wants to be easily accessible for police and can identify the great diversity of problems adequately but cannot solve all problems. There are shortcomings in adequate follow-up care provided by other health-care facilities. CONCLUSION: It turns out that it is extremely important for police officers that members of the MCT explain to them why a crisis assessment has a certain outcome. The exposed frictions and stagnation in the collaboration should be discussed openly as part of the process in order to acknowledge this and resolve it together. A recently started project called 'street triage', in which the police and MCT work together as one team and give a joint response, seems to remove a lot of the friction and stagnation. Further studies are needed to explore the effects of street triage by testing the validity of the hypothesis that street triage can close the gap between the two professions

Saccadic peak velocity and EEG as end-points for a serotonergic challenge test.

We previously reported that a single dose of the serotonin receptor agonist meta-chlorophenylpiperazine increased the peak velocity of saccadic eye movements and decreased low-frequency electroencephalographic activity. METHODS: We administered a single dose of the serotonin releaser dexfenfluramine in a double blind, placebo controlled randomised cross-over design and measured saccadic eye movements and EEG every hour up to 6 h. Subjects were 62 males (18-30 years) with a history of no, moderate or heavy use of ecstasy tablets. RESULTS: Dexfenfluramine increased saccadic peak velocity and decreased alpha, delta and theta electroencephalographic activity, the latter predominantly in heavy users of ecstasy. CONCLUSIONS: This study supports the idea that saccadic peak velocity and EEG can be useful endpoints of a serotonergic challenge. This could be an important anatomical extension of these end-points, which until now were limited to the effect on hypothalamic serotonergic projections

Cognitive performance and serotonergic function in users of ecstasy.

Item does not contain fulltextRATIONALE: () 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns. OBJECTIVE: We investigated, in humans, the relation between past use of ecstasy and cognitive performance as well as serotonergic function. Methods: Two groups of 21 males with moderate and heavy recreational use of MDMA, respectively, and a control group of 20 males without use of MDMA were compared. All were from the same subculture. Reaction time, direct recall, and recognition were assessed. Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled, crossover challenge with dexfenfluramine. RESULTS: Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users. Release of cortisol but not of prolactin after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls. Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy, psychosocial profiles and use of other drugs did not explain the differences found between the groups. CONCLUSIONS: These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals