ABSTRACT
BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.
ABSTRACT
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.
Subject(s)
Emergency Medical Services , Mental Disorders , Crisis Intervention , Hermeneutics , Humans , PoliceABSTRACT
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.
Subject(s)
Antipsychotic Agents/administration & dosage , Polypharmacy , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Adolescent , Adult , Aged , Education, Medical, Continuing/methods , Feedback , Follow-Up Studies , Guideline Adherence , Humans , Inpatients , Middle Aged , Outcome Assessment, Health Care , Physicians/standards , Practice Patterns, Physicians'/standards , Psychotic Disorders/drug therapy , Young AdultABSTRACT
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.
Subject(s)
Emergency Medical Services , Nurses , Ambulances , Humans , Qualitative ResearchABSTRACT
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 June 2017.
Subject(s)
Antipsychotic Agents/administration & dosage , Psychotic Disorders/drug therapy , Adolescent , Adult , Antipsychotic Agents/standards , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multicenter Studies as Topic , Practice Guidelines as Topic , Pragmatic Clinical Trials as Topic , Psychotic Disorders/diagnosis , Quality of Life , Remission Induction/methods , Severity of Illness Index , Single-Blind Method , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Many patients with psychotic disorders have persistent paranoid ideation and avoid social situations because of suspiciousness and anxiety. We investigated the effects of virtual-reality-based cognitive behavioural therapy (VR-CBT) on paranoid thoughts and social participation. METHODS: In this randomised controlled trial at seven Dutch mental health centres, outpatients aged 18-65 years with a DSM-IV-diagnosed psychotic disorder and paranoid ideation in the past month were randomly assigned (1:1) via block randomisation to VR-CBT (in addition to treatment as usual) or the waiting list control group (treatment as usual). VR-CBT consisted of 16 individual therapy sessions (each 1 h long). Assessments were done at baseline, after treatment (ie, 3 months from baseline), and at a 6 month follow-up visit. The primary outcome was social participation, which we operationalised as the amount of time spent with other people, momentary paranoia, perceived social threat, and momentary anxiety. Analysis was by intention to treat. This trial was retrospectively registered with ISRCTN, number 12929657. FINDINGS: Between April 1, 2014, and Dec 31, 2015, 116 patients with a psychotic disorder were randomly assigned, 58 to the VR-CBT group and 58 to the waiting list control group. Compared with the control, VR-CBT did not significantly increase the amount of time spent with other people at the post-treatment assessment. Momentary paranoid ideation (b=-0·331 [95% CI -0·432 to -0·230], p<0·0001; effect size -1·49) and momentary anxiety (-0·288 [-0·438 to -0·1394]; p=0·0002; -0·75) were significantly reduced in the VR-CBT group compared with the control group at the post-treatment assessment, and these improvements were maintained at the follow-up assessment. Safety behaviour and social cognition problems were mediators of change in paranoid ideation. No adverse events were reported relating to the therapy or assessments. INTERPRETATION: Our results suggest that the addition of VR-CBT to standard treatment can reduce paranoid ideation and momentary anxiety in patients with a psychotic disorder. FUNDING: Fonds NutsOhra, Stichting tot Steun VCVGZ.
Subject(s)
Cognitive Behavioral Therapy , Paranoid Behavior/therapy , Psychotic Disorders/therapy , Social Isolation , Virtual Reality , Adolescent , Adult , Aged , Cognitive Behavioral Therapy/methods , Female , Humans , Male , Middle Aged , Paranoid Behavior/psychology , Psychiatric Status Rating Scales , Single-Blind Method , Social Participation , Treatment Outcome , Young AdultABSTRACT
PURPOSE: To explore the lived experiences of patients with a psychotic or bipolar disorder and their families with emergency care during the first contact with a mobile crisis team. METHODS: Open individual interviews were held with ten patients and ten family members. Content data-analysis was conducted. FINDINGS: Communication and cooperation was difficult in several cases. Personal crisis plans were not always used. Stigma was felt, especially when police-assistance was needed. A calm, understanding attitude was appreciated. PRACTICE IMPLICATIONS: Focus explicitly on communication with the patient, despite the acute condition, enhances the chance of cooperation. Taking time for contact is important.
Subject(s)
Communication , Crisis Intervention , Emergency Services, Psychiatric/organization & administration , Family/psychology , Bipolar Disorder/therapy , Hospitalization , Humans , Mental Health Services/organization & administration , Patient Care Team/organization & administration , Professional-Family Relations , Psychotic Disorders/therapyABSTRACT
To date, only few studies have examined the impact of medication on social cognition and none have examined the effects of aripiprazole in this respect. The goal of this 8-week, randomized, multicenter, open-label study was to examine the effects of aripiprazole and risperidone on social cognition and neurocognition in individuals with schizophrenia. Eighty schizophrenia patients (DSM-IV-TR) aged 16-50 years were administered multiple computerized measures of social cognition and neurocognition including reaction times at baseline and the end of week 8. Social functioning was mapped with the Social Functioning scale and Quality of Life scale. The study ran from June 2005 to March 2011. Scores on social cognitive and neurocognitive tests improved with both treatments, as did reaction time. There were few differences between the two antipsychotics on (social) cognitive test-scores. The aripiprazole group performed better (more correct items) on symbol substitution (P=.003). Aripiprazole was also superior to risperidone on reaction time for emotional working memory and working memory (P=.006 and P=.023, respectively). Improvements on these tests were correlated with social functioning. In conclusion, aripiprazole and risperidone showed a similar impact on social cognitive test-scores. However, aripiprazole treatment produced a greater effect on patients' processing speed compared to risperidone, with these improvements being associated with concurrent improvements in social functioning. Further research on the long-term effects of aripiprazole on cognition is warranted.
Subject(s)
Aripiprazole/therapeutic use , Dopamine Agonists/therapeutic use , Dopamine Antagonists/therapeutic use , Emotional Intelligence/drug effects , Risperidone/therapeutic use , Schizophrenia/drug therapy , Social Behavior Disorders/prevention & control , Adolescent , Adult , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Aripiprazole/administration & dosage , Aripiprazole/adverse effects , Diagnostic and Statistical Manual of Mental Disorders , Dopamine Agonists/administration & dosage , Dopamine Agonists/adverse effects , Dopamine Antagonists/administration & dosage , Dopamine Antagonists/adverse effects , Drug Monitoring , Female , Humans , Male , Memory, Short-Term/drug effects , Middle Aged , Netherlands , Patient Dropouts , Reaction Time/drug effects , Recognition, Psychology/drug effects , Risperidone/administration & dosage , Risperidone/adverse effects , Schizophrenia/physiopathology , Social Behavior Disorders/etiology , Young AdultABSTRACT
OBJECTIVE: The purpose of this study was to review the scientific evidence for neurobiological rationale, efficacy, tolerability and cost effectiveness of antipsychotic polypharmacy (APP). DATA SOURCES: A systematic literature search of Medline, Embase, Ovid and the Cochrane Database of Systematic Reviews until April 2012 was carried out. RESULTS: Theories behind APP have only modest pre-clinical and clinical evidence. We found limited statistical evidence supporting modest efficacy of APP in patients with psychotic symptoms refractory to clozapine. APP is associated with increased mortality, metabolic syndrome, decreased cognitive functioning, high dose prescription and non-adherence. It brings up extra costs, lacking evidence for cost-effectiveness. CONCLUSIONS: Pre-clinical studies underpinning neurobiological hypotheses in APP are lacking. Evidence supporting efficacy of APP is limited with modest beneficial clinical relevance. APP is associated with several serious adverse effects and increased health costs. In the absence of more convincing pre-clinical support and clinical evidence we advise adherence to existing guidelines and limiting combinations of antipsychotics (in consideration with other pharmacotherapeutic, somatic and psychotherapeutic options) to patients with clozapine-refractory psychosis in well-evaluated individual trials that might need 10 weeks or more.
Subject(s)
Antipsychotic Agents/therapeutic use , Brain/drug effects , Evidence-Based Medicine , Neurons/drug effects , Polypharmacy , Psychotic Disorders/drug therapy , Animals , Antipsychotic Agents/adverse effects , Antipsychotic Agents/economics , Brain/metabolism , Cost-Benefit Analysis , Drug Costs , Drug Resistance , Health Care Costs , Humans , Neurons/metabolism , Psychotic Disorders/economics , Psychotic Disorders/metabolismSubject(s)
Drug Therapy, Combination , Mental Disorders/drug therapy , Psychiatry , Psychotropic Drugs/therapeutic use , Adult , Anxiety/drug therapy , Depressive Disorder, Major/drug therapy , Female , Guidelines as Topic , Humans , Male , Mental Disorders/psychology , Middle Aged , Psychotic Disorders/drug therapy , Psychotic Disorders/psychology , Schizophrenia/drug therapySubject(s)
Bipolar Disorder/etiology , Prefrontal Cortex/physiology , Stress Disorders, Post-Traumatic/therapy , Transcranial Magnetic Stimulation/adverse effects , Comorbidity , Depressive Disorder, Major/epidemiology , Humans , Patient Selection , Randomized Controlled Trials as Topic , Stress Disorders, Post-Traumatic/epidemiology , Transcranial Magnetic Stimulation/therapeutic useABSTRACT
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.
Subject(s)
Antidepressive Agents/therapeutic use , Bipolar Disorder/drug therapy , Adult , Aged , Anticonvulsants/therapeutic use , Bipolar Disorder/psychology , Double-Blind Method , Female , Humans , Lithium/therapeutic use , Male , Middle Aged , Placebos , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Risk Assessment , Treatment OutcomeABSTRACT
BACKGROUND: The atypical antipsychotic agent risperidone has beneficial effects on mood in patients with schizophrenia. This study aimed to assess whether risperidone produced typical antidepressant-like effects in the polysomnogram of healthy subjects and in depressed patients unresponsive to antidepressant medication. METHOD: We measured the effect of a single dose of risperidone (1 mg) on the polysomnogram of 8 healthy volunteers in a placebo-controlled, double-blind, crossover design. We also measured the effects of open-label risperidone treatment (0.5-1.0 mg daily) on the polysomnogram of 8 patients meeting DSM-IV criteria for major depressive disorder who had received therapeutic doses of an antidepressant with an unsatisfactory response. Sleep was recorded at baseline and following 2 weeks of risperidone addition. RESULTS: In the healthy volunteers, risperidone significantly decreased rapid eye movement (REM) sleep (p =.04). After 2 weeks of risperidone treatment, depressed patients had significantly less wake (p =.02) and REM sleep (p =.02). Scores on depression rating scales for the depressed patients showed a significant decline (p <.05). CONCLUSION: Risperidone administration decreases REM sleep in both healthy volunteers and medication-resistant depressed patients, an action characteristic of conventional antidepressant medication. In depressed patients, risperidone also decreased wake. The utility of risperidone as an augmentation agent in depressed patients merits controlled study.
Subject(s)
Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Depressive Disorder/drug therapy , Risperidone/therapeutic use , Sleep, REM/drug effects , Wakefulness/drug effects , Administration, Oral , Adult , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/pharmacology , Cross-Over Studies , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Personality Inventory , Placebos , Polysomnography/drug effects , Psychiatric Status Rating Scales , Risperidone/administration & dosage , Risperidone/pharmacology , Treatment OutcomeABSTRACT
UNLABELLED: 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.
Subject(s)
Dexfenfluramine/pharmacology , Saccades/drug effects , Serotonin Receptor Agonists/pharmacology , Serotonin/physiology , Adolescent , Adult , Cross-Over Studies , Dexfenfluramine/pharmacokinetics , Dose-Response Relationship, Drug , Double-Blind Method , Electroencephalography , Hallucinogens , Humans , Male , N-Methyl-3,4-methylenedioxyamphetamine , Norfenfluramine/metabolism , Serotonin Receptor Agonists/pharmacokinetics , Substance-Related Disorders/physiopathologyABSTRACT
RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.
Subject(s)
Amino Acids, Branched-Chain/pharmacology , Dopamine/metabolism , Prolactin/blood , Recognition, Psychology/drug effects , Space Perception/drug effects , Adult , Amino Acids, Branched-Chain/administration & dosage , Amino Acids, Branched-Chain/blood , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Pattern Recognition, Visual/drug effects , Phenylalanine/metabolism , Prolactin/drug effects , Time Factors , Tryptophan/blood , Tyrosine/metabolismABSTRACT
Single-dose administration of 5-hydroxytryptophan (5-HTP) is regularly used as a challenge test of the serotonergic system. The use of 5-HTP has been limited by an apparent small window between the occurrence of neuroendocrine endpoints and the occurrence of side effects. Therefore, many dosing strategies have been tried with and without concurrent administration of carbidopa, a peripheral inhibitor of the decarboxylation from 5-HTP to serotonin. The aim of the current study was to assess the relation between pharmacokinetics and pharmacodynamics of 5-HTP. Twelve healthy male volunteers were included in a placebo-controlled, randomized, four-way crossover, double-blind, single-dose investigation of oral 5-HTP with or without coadministration of carbidopa. The four dose regimens were placebo, 5-HTP 100 mg, 5-HTP 200 mg, and 5-HTP 100 mg with coadministration of carbidopa 100 mg and 50 mg at 3 hours before and 3 hours after the administration of 5-HTP, respectively. The last regimen resulted in a doubling of the elimination half-life, an apparent clearance at least 14 times smaller, and a 15.4 times greater area under the curve compared with 5-HTP 100 mg without carbidopa. Furthermore, it was the only regimen to induce a significant change in cortisol and prolactin. It did not induce any change in subjective psychologic symptoms or cardiovascular parameters, but it was the only regimen to induce some nausea in three participants. The authors conclude that this regimen of 5-HTP 100 mg plus carbidopa is a relatively simple, effective, and tolerable challenge of the presynaptic serotonergic system. Further increase of the dose of 5-HTP might improve the size of the effect on endpoints as long as the tolerability remains good.
Subject(s)
5-Hydroxytryptophan , Hydrocortisone/blood , Prolactin/blood , Receptors, Presynaptic/drug effects , Receptors, Serotonin/drug effects , 5-Hydroxytryptophan/administration & dosage , 5-Hydroxytryptophan/adverse effects , 5-Hydroxytryptophan/pharmacokinetics , Adult , Adverse Drug Reaction Reporting Systems , Carbidopa/administration & dosage , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Male , Metabolic Clearance Rate , Receptors, Presynaptic/physiology , Receptors, Serotonin/physiologyABSTRACT
The valid measurement of the concentration of serotonin (5-HT) in blood plasma is important when using the platelet as a model for the serotonergic neuron. The assay is hampered by the release of 5-HT by (residual) platelets during the preparation for assay. We developed an isopycnic method that separates cells gently and completely from plasma by centrifuging a diluted Percoll density-gradient to which whole blood was added. In this study this method was compared with the usual differential centrifugation method. The isopycnic method on average resulted in nine times lower levels of plasma 5-HT. This difference was linearly related to the number of residual platelets in plasma after differential centrifuging. The proportion of intra-individual variation decreased three-fold. Therefore, the use of a Percoll density-gradient may lead to a more precise and more accurate estimate of the level of plasma 5-HT. Copyright 2000 John Wiley & Sons, Ltd.