Somatic monitoring of patients with mood and anxiety disorders:Problem definition, implementation and further explorations

Patients with a severe mental illness die 13 to 30 year earlier than the general population. This is often caused by an unhealthy lifestyle along with the psychiatric disease, but also by side effects of medication. Therefore, it is important to look at physical complaints and medication use in psychiatric patients too. In this thesis it is shown that there is quite a lot to be gained there. By regular physical examination, blood tests and medication interviews, the risks can be better mapped and decreased and health care can be improved. In the north of the Netherlands, a system was developed, in which psychiatric patients are regularly monitored during their outpatient treatment: ‘Monitoring Outcomes of psychiatric Pharmacotherapy’ (MOPHAR). MOPHAR is a new method to improve standard care of individual patients and also research on the physical effects of medication use. The first results show that with MOPHAR, mental health care professionals of GGZ Drenthe gain better insight into the physical health of their patients. Furthermore, almost half of the patients turn out to have metabolic syndrome, a risk factor for cardiovascular disease. Thanks to the information, patients can be treated to minimize this risk. In the last part of the thesis, some individual measurements were investigated in more detail, such as the heart scan. We investigated with which patients it seems useful to make a heart scan around the start of antidepressants, to prevent severe cardiac arrhythmia. Using this kind of research, measurements in MOPHAR can be further improved and adjusted to individual patients

Rosiglitazone is a superior bronchodilator compared to chloroquine and beta-adrenoceptor agonists in mouse lung slices

BACKGROUND: Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor agonist efficacy was limited or impaired in mouse small airways within lung slices. METHODS: Relaxation to RGZ and CQ was assessed following submaximal methacholine (MCh) pre-contraction, in slices treated overnight with either RGZ, CQ or albuterol (ALB) (to induce β-adrenoceptor desensitization), and in slices treated with caffeine/ryanodine in which contraction is associated with increases in Ca(2+) sensitivity in the absence of contractile agonist-induced Ca(2+) oscillations. Furthermore, the effects of RGZ, CQ, ALB and isoproterenol (ISO) on the initiation and development of methacholine-induced contraction were also compared. RESULTS: RGZ and CQ, but not ALB or ISO, elicited complete relaxation with increasing MCh pre-contraction and maintained their potency and efficacy following β-adrenoceptor desensitization. RGZ, CQ and ALB maintained efficacy following overnight incubation with RGZ or CQ. Relaxation responses to all dilators were generally maintained but delayed after caffeine/ryanodine. Pre-treatment with RGZ, but not CQ, ALB or ISO, reduced MCh potency. CONCLUSIONS: This study demonstrates the superior effectiveness of RGZ in comparison to CQ and β-adrenoceptor agonists as a dilator of mouse small airways. Further investigation of the mechanisms underlying the relatively greater efficacy of RGZ under these conditions are warranted and should be extended to include studies in human asthmatic airways

Monitoring of somatic parameters at outpatient departments for mood and anxiety disorders

INTRODUCTION: Somatic complications account for the majority of the 13-30 years shortened life expectancy in psychiatric patients compared to the general population. The study aim was to assess to which extent patients visiting outpatient departments for mood and anxiety disorders were monitored for relevant somatic comorbidities and (adverse) effects of psychotropic drugs-more specifically a) metabolic parameters, b) lithium safety and c) ECGs-during their treatment. METHODS: We performed a retrospective clinical records review and cross-sectional analysis to assess the extent of somatic monitoring at four outpatient departments for mood and anxiety disorders in The Netherlands. We consecutively recruited adult patients visiting a participating outpatient department between March and November 2014. The primary outcome was percentage of patients without monitoring measurements. Secondary outcomes were number of measurements per parameter per patient per year and time from start of treatment to first measurement. RESULTS: We included 324 outpatients, of whom 60.2% were female. Most patients were treated for depressive disorders (39.8%), anxiety disorders (16.7%) or bipolar or related disorders (11.7%) and 198 patients (61.1%) used at least one psychotropic drug. For 186 patients (57.4%), no monitoring records were recorded (median treatment period 7.3 months, range 0-55.6). The median number of measurements per parameter per year since the start of outpatient treatment for patients with monitoring measurements was 0.31 (range 0.0-12.9). The median time to first monitoring measurement per parameter for patients with monitoring measurements was 3.8 months (range 0.0-50.7). DISCUSSION: Somatic monitoring in outpatients with mood and anxiety disorders is not routine clinical practice. Monitoring practices need to be improved to prevent psychiatric outpatients from undetected somatic complications

Modification of the association between paroxetine serum concentration and SERT-occupancy by ABCB1 (P-glycoprotein) polymorphisms in major depressive disorder

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) exert substantial variability in effectiveness in patients with major depressive disorder (MDD), with up to 50-60% not achieving adequate response. Elucidating pharmacokinetic factors that explain this variability is important to increase treatment effectiveness. OBJECTIVES: To examine potential modification of the relationship between paroxetine serum concentration (PSC) and serotonin transporter (SERT)-occupancy by single nucleotide polymorphisms (SNPs) of the ABCB1 gene, coding for the P-glycoprotein (P-gp) pump, in MDD patients. To investigate the relationship between ABCB1 SNPs and clinical response. METHODS: Patients had MDD and received paroxetine 20 mg/day. We measured PSC after 6 weeks. We quantified SERT-occupancy with SPECT imaging (n = 38) and measured 17-item Hamilton Depression Rating Scale (HDRS17)-scores at baseline and after 6 wee

Design and methods of the 'monitoring outcomes of psychiatric pharmacotherapy' (MOPHAR) monitoring program - a study protocol

BACKGROUND: At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner. Structural support for data collection and follow-up tests seems essential for improvement of monitoring practices in psychiatric outpatients. The implementation of a structured somatic monitoring program as part of routine clinical practice, as we describe in this study protocol, may be a solution. METHODS: In order to address these issues, we developed the innovative program 'Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR)'. MOPHAR is an infrastructure for implementation of standardized routine outcome monitoring (ROM; including standardized monitoring of treatment effect), monitoring of adverse psychotropic medication effects in psychiatric outpatients, encompassing both somatic adverse effects (e.g. metabolic disturbances) and subjective adverse effects (e.g. sedation or sexual side effects) and medication reconciliation. DISCUSSION: In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program is feasible and beneficial for patients in any MHS organisation. This paper describes the objectives, target population, setting and the composition and roles of the treatment team. It also indicates what measurements are performed at which time points during outpatient treatment in the MOPHAR monitoring program, as well as the research aspects of this project. TRIAL REGISTRATION: MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014. ( NL4779 )

Somatic monitoring of patients with mood and anxiety disorders: Problem definition, implementation and further explorations

Patients with a severe mental illness die 13 to 30 year earlier than the general population. This is often caused by an unhealthy lifestyle along with the psychiatric disease, but also by side effects of medication. Therefore, it is important to look at physical complaints and medication use in psychiatric patients too. In this thesis it is shown that there is quite a lot to be gained there. By regular physical examination, blood tests and medication interviews, the risks can be better mapped and decreased and health care can be improved. In the north of the Netherlands, a system was developed, in which psychiatric patients are regularly monitored during their outpatient treatment: ‘Monitoring Outcomes of psychiatric Pharmacotherapy’ (MOPHAR). MOPHAR is a new method to improve standard care of individual patients and also research on the physical effects of medication use. The first results show that with MOPHAR, mental health care professionals of GGZ Drenthe gain better insight into the physical health of their patients. Furthermore, almost half of the patients turn out to have metabolic syndrome, a risk factor for cardiovascular disease. Thanks to the information, patients can be treated to minimize this risk. In the last part of the thesis, some individual measurements were investigated in more detail, such as the heart scan. We investigated with which patients it seems useful to make a heart scan around the start of antidepressants, to prevent severe cardiac arrhythmia. Using this kind of research, measurements in MOPHAR can be further improved and adjusted to individual patients