Concomitant Psychotropic Drugs Research Articles

Treatment patterns of antidepressants in children and adolescents in Scandinavia.

The aim of this study was to examine variations in use of antidepressants among children and adolescents in the three Scandinavian countries (Sweden, Norway, and Denmark). We identified new users of antidepressants (5-17years) during 2007-2018 and described the annual incidence rate, treatment duration, concomitant psychotropic drug use, and the clinical setting of the prescribing physician (in Sweden and Denmark). Incident use of antidepressants increased by a factor 1.9 in Sweden, 1.3 in Norway and decreased by a factor 0.6 in Denmark during the study period. In Sweden, 58% of antidepressant users were covered by a prescription 12months after initiation compared to 40% in Norway and 49% in Denmark. Also, 34% of Swedish antidepressant users were in continuous treatment after 12months compared to 26% in Norway and 31% in Denmark. Concomitant use of other psychotropics was more common in Sweden (57%) than in Norway (37%) and Denmark (27%). During 2007-2018, clinicians from psychiatry settings initiated 75% of antidepressant treatments in Sweden, while this was the case for 50% of prescriptions in Denmark, although the proportion increased over time. The number of new antidepressant users is high and still rising in Sweden compared to Norway and Denmark. Swedish antidepressant users are more likely to use other psychotropics and to be covered by an antidepressant prescription after one year. Most antidepressants in Sweden are prescribed by physicians within psychiatric settings suggesting that they are based on specialized psychiatric evaluation.

Polypharmacy in children and adolescents initiating antipsychotic drug in 2008–2016: a nationwide register study

Objective The use of antipsychotics in children and adolescents has increased rapidly. Little is known about psychotropic polypharmacy in children and adolescent initiating an antipsychotic drug. Thus, we investigated the frequency and predictors of polypharmacy during the first year of antipsychotic use in Finnish children and adolescents. Methods Between 2008 and 2016, 14 848 individuals aged 1–17 years initiating risperidone, quetiapine, aripiprazole, or olanzapine treatment were identified from Finnish Prescription Registry. Data on psychotropic drug prescriptions prior to and during antipsychotic treatment were collected. Associations between predictors and polypharmacy were analyzed with regression models. Results During the study period polypharmacy occurred in 44.9% of the new antipsychotic users, being more frequent in girls (55.5%) than in boys (44.5%, p < 0.001). The two most frequent concomitant psychotropic drug classes were antidepressants (66.2%) and psychostimulants/atomoxetine (30.8%). Adolescents aged 13–15 and 16–17 years, and girls showed an increased risk of polypharmacy during antipsychotic treatment (OR 2.37 [95% CI 1.91–2.92], OR 2.39 [95% CI 1.92–2.98], and OR 1.64 [95% CI 1.51–1.78], respectively). The use of psychostimulants/atomoxetine or antidepressants prior to initiation of antipsychotic treatment was strongly associated with polypharmacy during antipsychotic treatment (OR 8.39 [95% CI 7.49–9.41], OR 3.02 [95% CI 2.75–3.31]). Conclusions Polypharmacy was common in children and adolescents initiating antipsychotic treatment. Prior use of psychostimulants/atomoxetine and antidepressants increased the risk of polypharmacy. The use of antipsychotics was mainly off-label, thus, the risks of concomitant use of antipsychotics with other psychotropic drugs should be carefully weighed.

Trends in Prescribing Antipsychotics for Children and Adolescents in Japan: A Descriptive Epidemiological Study Using a Large-Scale Pharmacy Dataset.

Little is known about antipsychotic prescription patterns among children and adolescents in Japan, particularly in outpatient settings. We investigated the prevalence and trends of antipsychotic prescription for outpatients aged ≤ 17years receiving a first antipsychotic prescription from 2006 to 2012 based on a large-scale dispensation dataset. Measurements included age, sex, department of diagnosis and treatment, type of prescription (monotherapy or polytherapy), antipsychotic dosage, and concomitant psychotropic drugs. Of the 10,511 patients, 65.1% were aged 13-17years, and 52.9% were males. Second-generation antipsychotic monotherapy prescriptions increased from 53.8% in 2006 to 78.3% in 2012. Risperidone was the most frequently prescribed antipsychotic, followed by aripiprazole and olanzapine. Approximately 25.0% of patients were prescribed an initial dose less than recommended. Second-generation antipsychotic monotherapy is currently the most frequent prescription pattern among outpatients aged ≤ 17years receiving an initial antipsychotic prescription.

Predicting Serum Levels of Lithium-Treated Patients: A Supervised Machine Learning Approach.

Routine monitoring of lithium levels is common clinical practice. This is because the lithium prediction strategies available developed by previous studies are still limited due to insufficient prediction performance. Thus, we used machine learning approaches to predict lithium concentration in a large real-world dataset. Real-world data from multicenter electronic medical records were used in different machine learning algorithms to predict: (1) whether the serum level was 0.6–1.2 mmol/L or 0.0–0.6 mmol/L (binary prediction), and (2) its concentration value (continuous prediction). We developed models from 1505 samples through 5-fold cross-validation and used 204 independent samples to test their performance by evaluating their accuracy. Moreover, we ranked the most important clinical features in different models and reconstructed three reduced models with fewer clinical features. For binary and continuous predictions, the average accuracy of these models was 0.70–0.73 and 0.68–0.75, respectively. Seven features were listed as important features related to serum lithium levels of 0.6–1.2 mmol/L or higher lithium concentration, namely older age, lower systolic blood pressure, higher daily and last doses of lithium prescription, concomitant psychotropic drugs with valproic acid and -pine drugs, and comorbid substance-related disorders. After reducing the features in the three new predictive models, the binary or continuous models still had an average accuracy of 0.67–0.74. Machine learning processes complex clinical data and provides a potential tool for predicting lithium concentration. This may help in clinical decision-making and reduce the frequency of serum level monitoring.

Risk factors for early-phase clozapine discontinuation: A nested case-control study.

Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction. We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction. Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction. Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia.

Reducing Psychotropic Drug Use in Nursing Homes in Belgium: An Implementation Study for the Roll-Out of a Practice Improvement Initiative.

Psychotropic drug use is high in nursing homes in Belgium. A practice improvement initiative (including education, professional support and the transition towards person-centred care) achieved significant reductions in psychotropic drug use. The initiative outline was transcribed into a general intervention template, and consequently implemented in five nursing homes (in mixed locations and with a mixed character) in preparation for a future broader roll-out in Belgium. The impact of the intervention on the use of psychotropic drugs in these five nursing homes is reported in this paper. The general intervention template was fitted into the individual nursing home setting. Education for the nursing home personnel on psychotropic drugs and non-pharmacological alternatives, as well as details for a transition to person-centred care was provided. Psychotropic drug use was recorded using a dynamic cohort study design with cross-sectional observations (November 2016-November 2017). At baseline, participants' (n = 677) mean age was 85.6years (range 54-109years), with 72.6% female. Mean medication intake was 8.5 (range 1-22), predominantly central nervous system drugs (Anatomic Therapeutic Chemical classification N, 88.8%). Long-term (> 3months) psychotropic drug use (62.0%) and concomitant psychotropic drug use (31.5% taking two or more medications) were high. After 12months, the prevalence of long-term psychotropic drug use decreased significantly (from 62.0 to 52.9%, p < 0.001), likewise the combined use of psychotropic drugs (from 31.5 to 24.0%, p = 0.001). The decrease in the prevalence of antidepressant and hypnosedative use was significant (respectively, from 32.2 to 23.4%, p < 0.001, and from 35.3 to 28.7%, p = 0.006) in contrast to antipsychotic use (from 17.1 to 15.9%, p = 0.522). The stand-alone adaptation of the previously reported initiative using a general template was possible. This intervention resulted in a significant decrease in psychotropic drug use (predominantly hypnosedatives and antidepressants) among nursing home residents after 12months.

S201. RELATION BETWEEN PSYCHOTROPIC DRUGS AND SEIZURE THRESHOLD IN ELECTROCONVULSIVE THERAPY

BackgroundElectroconvulsive therapy (ECT) is the most popular way to stimulate brain for achieving therapeutic effects. The therapeutic effect of ECT results from the induction of a generalized seizure. The minimal amount of electrical energy needed to induce seizures is known as the seizure threshold (ST). It is commonly believed that treatment efficacy is related to stimulus dose relative to ST, but higher stimuli usually also increase unwanted side effects. Therefore, ST is an important issue in conducting ECT. Most patients including schizophrenics undergoing ECT take concomitant psychotropic drugs, but little information is available on how these drugs affect ST. Our study aimed to analyze the relationship between ST and psychotropic drugs in patients treated with ECT.MethodsWe retrospectively reviewed the medical charts of 43 patients who received ECT at Korea University Guro Hospital between February 2009 and June 2015. Patients with a history of seizure disorders or other medical emergent conditions were excluded. A total of fifty-eight subjects received ECT during the study period. Patients were excluded if treatment was aborted due to side effects or any other reasons before the 10th session (n=12) because we intended to investigate the ST shift during the course of consecutive ECT sessions. We included 43 subjects in the final data analysis. Patients’ psychiatric disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R) by at least two experienced psychiatrists. ECT was administrated with concurrent antipsychotics and antidepressants.67.4 percent of subjects were diagnosed as schizophrenia and 20.9 percent of subjects were diagnosed as major depressive disorder. We used stepwise multivariate correlation analyses for examining the associations between ST and psychotropic drugs. Data are presented as initial ST, the difference in ST between the first and 10th sessions (ΔST10th), and the mean difference in ST between the first and last sessions (mean ΔSTlast). We used chlorpromazine-equivalent dose for antipsychotics and fluoxetine-equivalent dose for antidepressants.ResultsOf the 43 patients included in the study, 20 were male, and the other 23 were female. The mean age of all participants was 41.44 years (SD=15.89). Patients were taking the following antipsychotics and antidepressants: clozapine (n=6), amisulpride (n=9), aripiprazole (n=5), olanzapine (n=18), risperidone (n=1), quetiapine (n=20), haloperidol (n=1), paliperidone (n=5), chlorpromazine (n=1), blonanserin (n=1), escitalopram (n=7), sertraline (n=1), mirtazapine (n=2), duloxetine (n=1), venlafaxine (n=3), amitriptyline (n=1), trazodone (n=1), bupropion (n=1). Participants took an average of 1.91 (SD=1.02, range 0–5) different psychotropic drugs during ECT. The mean number of types of antipsychotics and antidepressants used were 1.53 (SD=0.74, range 0–3) and 0.37 (SD=0.76, range 0–4), respectively. Multivariate regression analyses showed positive correlations between initial ST and the total chlorpromazine-equivalent dose of antipsychotics (β = 0.363, p < 0.05). The total fluoxetine-equivalent dose of antidepressants was positively correlated to ΔST10th (β = 0.486, p < 0.05) and mean ΔSTlast (β = 0.472, p < 0.01).DiscussionOur study elucidated possible effects of psychotropic drugs on ST in patients undergoing ECT. We revealed that larger doses of antipsychotics are associated with higher initial ST, whereas higher doses of antidepressants are associated with stronger shifts of ST during the course of treatment. We believe that our findings provide a basis for creating safer and more efficient ECT protocols.

A retrospective examination of subjective symptoms and objective urodynamic findings in patients with multiple sclerosis and non-neurogenic LUTS: Focus on concomitant psychotropic drug treatment

Introduction-Aims: The aim of the study was to assess the potential contribution of lower urinary tract symptoms to psychotropic drug use, in neurological and non-neurological patients. Material-Method: The study consisted of Multiple Sclerosis (MS) patients ( n =150), and a control group of patients with lower urinary tract symptoms (LUTS), refractory to initial medical treatment (n =187). Results: Between men and women with MS, statistically significant differences were observed only in the symptom of stress urinary incontinence (women), and reported voiding symptoms (men). With regard to the objective urodynamic parameters, a statistically significant difference was only observed at the maximum detrusor pressure and the detrusor pressure at maximum flow rate. Detrusor overactivity was the only statistically significantly different urodynamic parameter between women with MS, under, or without undergoing psychotropic drug treatment. In the comparative analysis between MS and non-neurological patients, both as a whole, or divided into sex-based subgroups, no aggravating urodynamic parameter was identified, so as to justify psychotropic drug treatment. Conclusions: In both MS and refractory (r-LUTS) patients, female gender appears to constitute an independent predisposing factor for antidepressant drug treatment. No aggravating urodynamic observation was identified, so as to justify psychotropic drug treatment in neurological and other patients. Eισαγωγή-Στόχοι: Στόχος της μeλέτης ήταν να eκτιμηθeί η πιθανή συμβολή των συμπτωμάτων της κατώτeρης ουροφόρου οδού στην χρήση ψυχοτρόπων φαρμάκων, σe νeυρολογικούς και μη νeυρολογικούς ασθeνeίς. Υλικό-Μέθοδος: Η μeλέτη πeριeλάμβανe ασθeνeίς μe σκλήρυνση κατά πλάκας (MS) ( n =150) και ομάδα eλέγχου ασθeνών μe συμπτώματα κατώτeρης ουροφόρου οδού (LUTS), ανθeκτικά στην αρχική θeραπeία ( n =187). Αποτeλέσματα: Μeταξύ ανδρών και γυναικών μe ΣΚΠ, παρατηρήθηκαν στατιστικά σημαντικές διαφορές μόνο στο σύμπτωμα της ακράτeιας ούρων κατά την προσπάθeια (γυναίκeς), και στα αναφeρόμeνα συμπτώματα ούρησης (άνδρeς). Όσον αφορά τις αντικeιμeνικές ουροδυναμικές παραμέτρους, παρατηρήθηκe στατιστικά σημαντική διαφορά μόνο στη μέγιστη πίeση του eξωστήρα και στην πίeση του eξωστήρα στο μέγιστο ρυθμό ροής. Η υπeρλeιτουργία του eξωστήρα ήταν η μόνη στατιστικά σημαντική διαφορeτική ουροδυναμική παράμeτρος μeταξύ των γυναικών μe ΣΚΠ, υπό και δίχως ψυχοτρόπο αγωγή. Στη συγκριτική ανάλυση μeταξύ μη νeυρολογικών ασθeνών και ασθeνών μe ΣΚΠ, και οι δύο ομάδeς στο σύνολό τους ή χωρισμένeς σe υποομάδeς μe βάση το φύλο, δeν προσδιορίστηκe καμία eπιβαρυντική ουροδυναμική παράμeτρος, ώστe να δικαιολογeίται η θeραπeία μe ψυχοτρόπα φάρμακα. Συμπeράσματα: Στους ασθeνeίς μe ΣΚΠ αλλά και στους ασθeνeίς μe ανθeκτικά συμπτώματα κατώτeρης ουροφόρου οδού (r-LUTS), το γυναικeίο φύλο φαίνeται να αποτeλeί έναν ανeξάρτητο παράγοντα προδιάθeσης για θeραπeία μe αντικαταθλιπτικά φάρμακα. Δeν διαπιστώθηκe κάποια παρατήρηση eπιβαρυντικής ουροδυναμικής, έτσι ώστe να δικαιολογeίται η θeραπeία μe ψυχοτρόπα φάρμακα σe νeυρολογικούς και άλλους ασθeνeίς.

A Comparison of Lamotrigine or Sodium Valproate on the Efficacy in Alzheimer’s disease with Behavioral and Psychological Symptoms of Dementia: A Retrospective Open-Label Study Running Title: Efficacy of Anticonvulsants for BPSD

Aim: We compared the clinical efficacy and subsequent changes in dosages of concomitantly used psychotropic drugs with lamotrigine and sodium valproate therapy in Alzheimer’s disease (AD) with Behavioral and Psychological Symptoms on Dementia (BPSD). Methods: This study was a 16-week, retrospective, open-label study. The 45 subjects were inpatients. The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the neuropsychiatric inventory (NPI) and cognitive function was assessed using the mini-mental examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. Results: Although the mean changes from baseline NPI scores and the two NPI subscales (agitation and irritability) decreased both in the lamotrigine therapy group and in the sodium valproate therapy group, no significant difference was found between the two groups. The mean decrease in diazepam-equivalent dose from baseline was significantly greater in the lamotrigine therapy group than that in the sodium valproate therapy group (p < 0.05). Furthermore, in the sodium valproate therapy group, the occurrence rates of somnolence, body tilt, and dizziness were all 30%. Conclusions: The results of this study suggested that while the administration of lamotrigine or sodium valproate might be effective in patients with severe AD with BPSD, special attention is required when using sodium valproate on a daily basis.

Management Issues During Pregnancy in Women With Bipolar Disorder

Back to table of contents Previous article Next article Communications and UpdatesFull AccessManagement Issues During Pregnancy in Women With Bipolar DisorderVerinder Sharma, M.B.B.S., and Christina Sommerdyk, M.Sc.Verinder SharmaSearch for more papers by this author, M.B.B.S., and Christina SommerdykSearch for more papers by this author, M.Sc.Published Online:1 Mar 2014https://doi.org/10.1176/appi.ajp.2014.13111493AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We read with interest the article by Clark et al. (1) on lamotrigine dosing in pregnant patients with bipolar I disorder. The authors report on the use of lamotrigine in eight patients with bipolar disorder, six of whom received concomitant psychotropic drugs including four women who were taking antidepressant drugs. Dosage adjustments of lamotrigine were made in response to hypomanic, manic, or depressive symptoms. It is not clear whether the dosages of concomitant psychotropic drugs remained the same during pregnancy. Of the three women requiring a dosage increase to manage symptoms, two were also taking antidepressants that can increase the recurrence of bipolar mood episodes both during and after pregnancy (2). There are no data suggesting that monitoring serum levels with corresponding adjustments to lamotrigine dosing will protect against antidepressant-led mood instability. Interestingly, the authors did not report a correlation between lamotrigine concentration and scores on rating scales for depression and mania. Thus, the conclusion that women with bipolar disorder who are treated with lamotrigine experience an increase in symptoms as a result of declining concentrations of this drug is not justified.While lamotrigine has a role in the management of bipolar disorder during pregnancy, no data on its effectiveness in the prevention of postpartum mood episodes are currently available. Moreover, lamotrigine is generally not recommended for the acute treatment of mania (3).Finally, the statement that pregnancy is a vulnerable period for recurrence of mood episodes is true for women treated at tertiary care centers with complex and often comorbid disorders and women who discontinue mood-stabilizing drugs. However, evidence from studies using nonclinical samples, retrospective studies, and studies on psychiatric hospitalization rates is suggestive of a positive effect of pregnancy on bipolar disorder (4).From the Departments of Psychiatry and Obstetrics & Gynecology, University of Western Ontario, London, Ontario, Canada; the Perinatal Clinic, London Health Sciences Centre, London, Ontario; and Regional Mental Health Care, London, Ontario.Professor Sharma has received grant support from, participated on scientific advisory boards for, or served on the speakers’ bureaus of AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Janssen, Lundbeck, the Ontario Mental Health Foundation, Pfizer, Servier, and the Stanley Foundation. Ms. Sommerdyk reports no financial relationships with commercial interests.References1 Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL: Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry 2013; 170:1240–1247Link, Google Scholar2 Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen LS: Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry 2007; 164:1817–1824Link, Google Scholar3 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O’Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord 2013; 15:1–44Crossref, Medline, Google Scholar4 Sharma V, Pope CJ: Pregnancy and bipolar disorder: a systematic review. J Clin Psychiatry 2012; 73:1447–1455Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byRisk of Medication Exposures in Pregnancy and Lactation26 May 2021 Volume 171Issue 3 March 2014Pages 370-371 Metrics PDF download History Accepted 1 January 2014 Published online 1 March 2014 Published in print 1 March 2014

The influence and changes in the dosages of concomitantly used psychotropic drugs associated with the discontinuation of donepezil in severe Alzheimer’s disease with behavioral and psychological symptoms on dementia: a preliminary open-label trial

We investigated the influence on behavioral and psychological symptoms on dementia (BPSD) and the changes in the dosages of concomitant psychotropic drugs associated with the discontinuation of donepezil in patients with severe Alzheimer's disease (AD) who developed BPSD during donepezil therapy. The subjects were 44 inpatients who had been diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the Neuropsychiatric Inventory (NPI) and cognitive function was assessed using the Mini Mental Examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. Significant decreases were found in the donepezil treatment discontinuation group in the following NPI total score and two NPI subscales (agitation and irritability), but no significant differences were seen between the donepezil treatment discontinuation group and the control group. Furthermore, the mean changes from baseline in the risperidone equivalent dose and the diazepam equivalent dose were hardly changed in the donepezil treatment discontinuation group. The results of this study suggest that the discontinuation of donepezil treatment in patients with AD with BPSD may afford superior efficacy and may make it possible to not increase the dosage of other psychotropic drugs.

Combination Pharmacotherapy for Psychiatric Disorders in Children and Adolescents: Prevalence, Efficacy, Risks and Research Needs

Polypharmacy, defined as the concomitant use of two or more psychotropic drugs, has become increasingly common in the paediatric and adolescent population over the past two decades. Combining psychotropic drugs leads to possible increases in benefits, but also in risks, particularly given the potential for psychotropic drug interactions. Despite the increasing use of concomitant therapy in children and adolescents, there is very little evidence from controlled clinical trials to provide guidance for prescribers. Even while acknowledging the small evidence base, clinical practice guidelines from eminent medical organizations are either relatively silent on or tend to support the use of concomitant treatments more enthusiastically than the evidence would warrant, so that practice and guidance are running ahead of the science. Our narrative review shows that the published evidence for efficacy and safety of concomitant psychotropic drugs in children and adolescents is scanty. A comprehensive search located 37 studies published over the last decade, of which 18 were randomized controlled trials (RCTs). These focused mainly on stimulants, central sympatholytics (such as clonidine), antipsychotics and 'mood stabilizers'. While several small, often methodologically weak, RCTs demonstrated statistically significant advantages for dual pharmacotherapy over monotherapy, only adding central sympatholytics to stimulants for treating attention-deficit hyperactivity disorder (ADHD) symptoms was supported by substantial studies with an effect size large enough to suggest clinical importance. Non-randomized studies tended to have results that supported concomitant treatment, but all have design-related problems that decrease the reliability of the results. Two studies that specifically examined tolerability of combination pharmacotherapy compared with monotherapy showed significant increases in adverse effects, both subjective and objective, and other studies confirmed a statistically significant increase in adverse effects, including sedation and self-harm. Given the extent of combination therapy occurring, particularly in conditions such as ADHD, and the ambiguous evidence for benefit with clear evidence of harm, we propose that further research should be carried out as a matter of urgency. Until such a time, the attitude to combination pharmacotherapy should be conservative, and combining psychotropic medications should be considered as an 'n of 1' trial to be closely monitored.

Clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy in Alzheimer's disease with behavioral and psychological symptoms on dementia.

We investigated the clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy in Alzheimer's disease (AD) with behavioral and psychological symptoms on dementia (BPSD). The subjects were 38 inpatients who had been diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the neuropsychiatric inventory (NPI) and cognitive function was assessed using the mini-mental examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. SIGNIFICANT DECREASES WERE FOUND IN THE MEMANTINE THERAPY GROUP IN THE FOLLOWING NPI TOTAL SCORE AND FIVE NPI SUBSCALES: delusions, hallucinations, agitation, irritability, and aberrant motor behavior, but no significant differences were seen between the memantine therapy group and the control group. Furthermore, the memantine therapy group allowed the dosage of the psychotropic drugs to be significantly reduced compared with the control group. The results of this study suggest that the administration of memantine to patients with AD with BPSD may afford superior efficacy and may also make it possible to reduce the risperidone equivalent dose, the diazepam equivalent dose and the dosage of the psychotropic drugs.

Regional variaton on the presentation of Alzheimer subjects in memory clinics within Europe: Data from the ICTUS study

To describe the European variation of Alzheimer disease (AD) patients regarding clinical and socio-demographic features, co-morbidities, drug treatment and psychosocial care. 1379 mild to moderate AD subjects of the ICTUS study recruited in academic memory clinics from 12 European countries were analyzed. The cohort was clustered into four geographical regions according to the WHO-classification of European countries. Clinical outcomes were MMSE, ADAScog, NPI, ADL / IADL, and Zarit caregiver burden, socio-demographic variables, drug-treatment, co-morbidities, living arrangements and care status. Northern patients showed the mildest severity of dementia (MMSE: 21.6 ± 3.7, p < 0.001) and the lowest rate of concomitant psychotropic drug treatment (24.3%, p < 0.001). They also appeared to be healthier than Europe's rest. Western subjects were diagnosed earlier (0.5 ± 0.9 month, p < 0.001) with dementia than the other European subjects, received the highest rate of formal care (45.0%, p < 0.001) and most frequently antidementia drugs (60.4%, p < 0.001). Southern subjects had the shortest education time (5.6 ± 4.0, p < 0.001) in Europe and the most severe cognitive decline in MMSE: 19.8 ± 4.0, p < 0.001 and ADAScog: 24.2 ± 9.6, p < 0.001. They received less antidementia drug treatment (37.6%; p < 0.001) than the others and lived more often together with their caregivers (74.4%, p < 0.001). Southern area had the highest caregiver burden (22.6 ± 15.2, p = 0.049).Eastern AD subjects received more concomitant psychopharmacological drugs (68.6%, p < 0.001) than the other Europeans. Their caregivers were more often different (18.6%, p < 0.001) from spouse or offspring. Caregiver burden was lower (18.7 ± 12.4, p = 0.049) than in other clusters. Nearly all subjects received only informal care (95.7%, p < 0.001). They were affected more by co-morbidities. The data show various differences in socio-demographic and clinical characteristics and management between AD patients from 4 European geographical regions. The presentation and management of AD in Europe appears to differ according European regions, probably affected by cultural factors and health politics. These data are important for the conductance of clinical trials as well as health policy makers.

Psychotropic Drug Use among Icelandic Children: A Nationwide Population-Based Study

The aim of this study was to investigate psychotropic drug use among children in Iceland between 2003 and 2007. A nationwide population-based drug use study covering the total pediatric population (ages 0-17) in Iceland. Information was obtained from the National Medicines Registry to calculate prevalence of use by year and psychotropic drug group; incidence by year, psychotropic drug group, child's age and sex, and medical specialty of prescriber; the most commonly used psychotropic chemical substances, off-label and unlicensed use and concomitant psychotropic drug use. The overall prevalence of psychotropic drug use was 48.7 per 1000 Icelandic children in 2007. Stimulants and antidepressants increased in prevalence from 2003 to 2007 and were the two most prevalent psychotropic drug groups, respectively, 28.4 and 23.4 per 1000 children in 2007. A statistically significant trend of declining prevalence (p = 0.00013) and incidence (p = 0.0018) of antidepressant use occurred during the study period. Out of 21,986 psychotropic drugs dispensed in 2007, 25.4% were used off-label. With reference to reports from other European countries, the results indicate extensive psychotropic drug use among children in Iceland between 2003 and 2007. Further scrutiny is needed to assess the rationale behind this widespread use.

Factors Associated with Concomitant Psychotropic Drug Use in the Treatment of Major Depression: A STAR*D Report

Concomitant psychotropic medication (CPM) treatment is common in persons with major depression (MDD). However, relationships with patient characteristics and response to treatment are unclear. Participants with nonpsychotic MDD (N=2682) were treated with citalopram, 20-60 mg/day. Sociodemographic, clinical, and treatment outcome characteristics were compared between those using CPMs at study entry or during up to 14 weeks of citalopram treatment, and non-users. About 35% of participants used a CPM. Insomnia was the predominant indication (70.3%). CPM users were more likely to be seen in primary care settings (69.3% versus 30.7%), be white, of non-Hispanic ethnicity, married, and have a higher income, private insurance, and certain comorbid disorders. CPM users had greater depressive severity, poorer physical and mental functioning, and poorer quality of life than non-users. Response and remission rates were also lower. CPM users were more likely to achieve >50 mg/day of citalopram, to report greater side effect intensity, and to have serious adverse events, but less likely to be intolerant of citalopram. CPMs are associated with greater illness burden, more Axis I comorbidities (especially anxiety disorders), and lower treatment effectiveness. This suggests that CPM use may identify a more difficult to treat population that needs more aggressive treatment.

The use of benzodiazpines and related drugs amongst older people in Sweden: Associated factors and concomitant use of other psychotropics

To determine the factors associated with use of benzodiazepines and benzodiazepine related drugs (BZDs/BZDRDs) in a nationwide population of older people. We analyzed data on age, sex, type of residential area (urban/rural), and dispensed drugs for people aged > or = 75 years registered in the Swedish Prescribed Drug Register from October to December 2005 (n = 731,105; corresponds to 91% of the domain population). Multivariate logistic regression analysis was used for analyzing whether age, sex, type of residential area, number of other drugs, and concomitant psychotropic drug use was associated with use of BZDs/BZDRDs. > or =1 BZDs/BZDRDs and > or =2 BZDs/BZDRDs were used by 25% and 5% of the study population, respectively. The most commonly used BZDs/BZDRDs were zopiclone, zolpidem, oxazepam, flunitrazepam, and diazepam. The probability of use BZDs/BZDRDs increased with age, female gender, living in an urban area, use of many other drugs, and concomitant use of other psychotropics, particularly antidepressants. In the comparisons of different BZDs/BZDRDs (n = 179,632), the medium-acting BZDs were associated with higher age, female gender, and use of other psychotropics, whereas BZDRDs showed the opposite pattern. Also, the two BZDRDs zopiclone and zolpidem showed different patterns regarding age, sex, and use of other drugs. One in four of the elderly used one or more BZD/BZDRD, which should be prescribed cautiously and with the recognition of the potentially negative effects. There were differences in patterns of use for different BZDs/BZDRDs, even within the same drug class. Hence, large study populations are needed for future research of individual BZDs/BZDRDs.

How expensive is antipsychotic polypharmacy? Experience from five US state Medicaid programs

ABSTRACTObjective: To characterize healthcare costs associated with antipsychotic polypharmacy and to investigate predictors of high-cost patients.Methods: A retrospective cohort study using Medicaid claims data from California, Nebraska, Oregon, Utah, and Wyoming evaluated 55 383 fee-for-service patients with antipsychotic prescriptions between 1998 and 2002. Polypharmacy was defined as initiating multiple antipsychotic drugs or concomitant antipsychotic therapy (≥ 60 days). Healthcare costs (drug and non-drug) were summed for 365 days following index antipsychotic claim. Adjusted mean costs were compared to antipsychotic monotherapy. Logistic regression was performed to identify predictors of high-cost patients (top quintile) with regard to patient age, gender, race/ethnicity, mental disorders, hospitalization, index antipsychotic, concomitant psychotropic drugs, and polypharmacy.Results: The average annual prevalence of antipsychotic polypharmacy was 6%. 70–80% of total healthcare expenditures for polypharmacy patients were drug-related. Polypharmacy was associated with significantly higher drug expenditures ($1716–2079) in the year following drug initiation than monotherapy even after adjusting for case mix and index antipsychotic ( p < 0.05). Differences in non-drug expenditures versus monotherapy were smaller and varied by state ranging from a $77 increase in California ( p < 0.001) to a $211 savings in Utah ( p = 0.02). In California, polypharmacy alone (OR = 2.69; 95% CI: 2.30–3.16) or in combination with concomitant psychotropics (OR = 6.26; 95% CI: 5.51–7.11) was associated with greater likelihood of being a high-cost patient than monotherapy.Conclusions: Cost savings from limiting antipsychotic polypharmacy could be significant. Caution must be taken in ensuring reductions in polypharmacy do not lead to unintended consequences or shift care to more costly alternatives. Study limitations, including the known shortcomings of claims data and differences across state Medicaid programs, should be considered when interpreting the results of this or any multi-state study.

Dissociation as a Predictor of Cognitive Behavior Therapy Outcome in Patients with Obsessive-Compulsive Disorder

Background: Previous studies have found a strong association between dissociation and obsessive-compulsive disorder (OCD). The purpose of the present study was to evaluate whether dissociation is a predictor of cognitive behavior therapy (CBT) outcome in patients with OCD. Methods: Fifty-two patients with OCD were assessed using the Dissociative Experience Scale (DES), the Yale-Brown Obsessive-Compulsive Scale and the Beck Depression Inventory. CBT lasted on average 9.5 weeks and included exposure therapy. Results: Patients who dropped out due to noncompliance had higher baseline DES scores and depression scores compared to the 43 patients (83%) who completed the study. Significant OCD symptom reduction at posttreatment was observed in study completers with a large effect size (d = 1.7). More severe OCD symptoms at posttreatment were associated with higher DES scores at baseline, and treatment nonresponders had significantly higher baseline DES scores compared to responders. These associations with outcome were mainly due to the DES subfactor absorption-imaginative involvement. In regression analyses, higher absorption-imaginative involvement scores at baseline predicted poorer CBT outcome, even after controlling for depressive symptoms, comorbid axis I disorders and concomitant psychotropic drugs. Conclusions: Results from this preliminary study suggest that higher levels of dissociation (particularly absorption-imaginative involvement) in patients with OCD might predict poorer CBT outcome. If our results can be replicated, treatment outcome might be improved by additional interventions for those patients with OCD who indicate high levels of dissociation, for example by using interventions aimed at improving coping with emotionally stressful situations.

Table of Contents

The Brown University Geriatric Psychopharmacology UpdateVolume 9, Issue 10 p. 1-8 Table of Contents First published: 27 September 2005 https://doi.org/10.1002/gpu.20005AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Severe Neuroleptic Sensitivity Common in Parkinson's Disease Can Rivastigimine Reduce Concomitant Psychotropic Drug Use in AD Patients? A Possible Case of Drug-Induced Pancreatitis Inappropriate Drug Prescribing in Older Veterans Geriatric Depression and Antidepressant Response CX717 May Reverse Effects of Sleep Deprivation and Possibly Benefit AD Patients Moderate Hyperinsulinemia May Raise Risk of AD in Non-Diabetics Worsening Delusions and Hallucinations Following Memantine Treatment Personalized Medicine through Genetic Testing Volume9, Issue10October 2005Pages 1-8 RelatedInformation