Tobacco smoke is known to affect plasma levels of some drugs, including the antipsychotic clozapine. The effects of suddenly stopping smoking on patients who take clozapine can be severe, as plasma concentrations are expected to rapidly rise, potentially leading to toxicity. A ban on smoking at South London and the Maudsley NHS Foundation Trust (SLaM) was implemented in 2014, and this was expected to affect the plasma concentrations of clozapine for inpatients at the time. This study aimed to determine whether plasma concentrations of clozapine were affected, and additionally, in line with observations from other authors, whether levels of reported violence would also be affected.
The smoking habits of all patients at SLaM who smoked and were prescribed clozapine were recorded both before and after the ban. The Glasgow Antipsychotic Side Effect Scale for Clozapine (GASS-C) scale was used to evaluate side-effect burden. Clozapine doses and plasma concentrations were also collected.
In total, 31 patients were included in this study. The mean clozapine dose before the ban was 502 mg/day, and this did not change significantly after the ban. Similarly, there were no significant changes in clozapine or norclozapine plasma concentrations, or in GASS-C scores. There was no change in the amount of tobacco patients reported smoking before or after the ban. A modest but statistically significant reduction in violent incidences was observed.
Our data suggest that a ban on smoking for patients taking clozapine on open wards at inpatient hospital sites had little impact on clozapine plasma concentrations, because patients continued to smoke tobacco if allowed to leave. Smoking bans may result in a reduction in violent incidences.
Asenapine is a second-generation antipsychotic approved in Europe for treating moderate-to-severe manic episodes in adults affected by type I bipolar disorder (BD-I). We aimed to compare its efficacy in psychiatric inpatients with BD-I, with or without substance use disorder (SUD).
We administered flexible asenapine doses ranging from 5–20 mg/day to 119 voluntarily hospitalized patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) BD-I diagnosis, with or without SUD. Patients were assessed with clinician-rated questionnaires [i.e. Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Global Assessment of Functioning (GAF)]. Assessments were carried out at baseline (T0, prior to treatment), and 3 (T1), 7 (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF.
Patients improved on all scales (p < 0.001) across all timepoints, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Patients without comorbid SUD showed greater reductions in BPRS scores at T2 and T3, greater reduction in YMRS scores at T3, and lower HARS scores at all timepoints. HDRS scores did not differ between the two groups at any timepoint. However, the reduction in HARS scores in the comorbid group was stronger than in the BD-I only group, albeit not significantly. Side effects were few and mild-to-moderate.
The open-label design and the relatively short observation period may expose to both type I and type II statistical errors (false positive and false negatives). Asenapine showed effectiveness and safety in hospitalized BD-I patients. Its effect was stronger in patients without comorbid SUD.
The negative symptoms of schizophrenia are generally harder to recognize, more difficult to treat than positive symptoms, and have a significant impact on patient functioning and overall outcomes. Treatment with aripiprazole may be associated with benefits on negative symptoms and functioning given its partial agonism to the dopamine D2 receptor. The aim of this subanalysis was to explore the impact of flexibly dosed, long-acting paliperidone palmitate once monthly (PP1M) on negative and depressive symptoms, disorganized thoughts, anxiety, extrapyramidal symptoms, and patient functioning in nonacute adult patients with schizophrenia previously unsuccessfully treated with oral aripiprazole monotherapy.
Post-hoc subanalysis of 46 nonacute but symptomatic patients enrolled in a prospective, interventional, single-arm, multicenter, open-label 6-month study.
At endpoint, improvements of >= 20% and >= 50% in the Positive and Negative Syndrome Scale (PANSS) total score were observed in 52.2% and 21.7% of patients, respectively. Significant and clinically relevant improvements were observed at endpoint in mean (standard deviation [SD]) PANSS negative subscale score (–3.0 (5.0); p < 0.0001) and in the PANSS Marder factor scores for negative symptoms (–2.9 (5.4); p = 0.0006), disorganized thoughts (–2.8 (4.3); p < 0.0001) and anxiety/depression (–1.8 (3.9); p = 0.0031). Patient functioning assessed by mean (SD) Personal and Social Performance scale (3.9 (13.2); p = 0.0409), Mini International Classification of Functioning rating for Activity and Participation Disorders in Psychological Illnesses total scores (–2.9 (7.1); p = 0.0079), and Extrapyramidal Symptom Rating Scale scores (–0.6 (3.4); p = 0.0456) improved significantly at endpoint. PP1M was well tolerated with no new safety signals.
Six-month treatment with flexibly dosed PP1M was associated with significant and clinically relevant improvements in negative and depressive symptoms, disorganized thoughts, functioning, and extrapyramidal symptoms in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral aripiprazole.
In March 2015, pipotiazine palmitate depot antipsychotic was globally withdrawn due to the shortage of its active ingredient. Thus, all patients receiving this medication had to be switched to an alternative antipsychotic drug. In this study we set to evaluate the process of switching away from pipotiazine palmitate within our clinical service, and its impact on hospitalization.
Demographic and clinical data on patients who were receiving pipotiazine palmitate in Northamptonshire at the time of its withdrawal were anonymously extracted from their electronic records and analyzed using descriptive statistics.
A total of 17 patients were switched away from pipotiazine palmitate at the time of its withdrawal, all of whom had a prior history of nonadherence with oral treatment. A total of 14 patients were switched to another depot antipsychotic drug, while three patients chose an oral alternative which they subsequently discontinued resulting in relapse and hospitalization. There was a five-fold increase in mean hospitalization among patients who completed a year after the switch.
Switching away from pipotiazine palmitate was associated with significant clinical deterioration in patients who switched to an oral antipsychotic, whereas most patients who switched to another depot treatment maintained stability. Clinicians should exercise caution when switching patients with schizophrenia away from depot antipsychotic drugs, especially in cases of patients with a history of treatment nonadherence who prefer to switch to oral antipsychotics.
The objectives of this study were to investigate the dose of lamotrigine when prescribed with an enzyme inhibitor or enzyme inducer in patients discharged from a mental health trust and to determine the corresponding lamotrigine plasma concentrations and the factors that may affect these.
All patients discharged on lamotrigine between October 2007 and September 2012 were identified using the pharmacy dispensing database. We recorded demographic details, lamotrigine dose and plasma levels and coprescribed medication.
During the designated period, 187 patients were discharged on lamotrigine of whom 117 had their plasma levels recorded. The mean lamotrigine daily dose was 226.1 mg (range 12.5–800 mg) and the mean plasma level 5.9 mg/l (range 0.8–18.1 mg/l). Gender, ethnicity, diagnosis and smoking status had no significant effect on dose or plasma levels. Patients taking an enzyme-inducing drug (n = 6) had significantly lower plasma levels [mean (SD) 3.40 (1.54) mg/l] than those not taking enzyme inducers [n = 111; 6.03 (3.13) mg/l; p = 0.043]. Patients taking an enzyme-inhibiting drug (n = 23) had significantly higher levels [7.47 (3.99) mg/l] than those not taking an inhibitor [n = 94; 5.52 (2.75) mg/l; p = 0.035]. No significant difference was found between the doses of lamotrigine in patients taking an enzyme inhibitor and those not taking one (p = 0.376). No significant difference was found between the doses of lamotrigine in patients taking an enzyme-inducing drug and those not taking any (p = 0.574).
Current dosing recommendations indicate that lamotrigine doses should be halved in individuals taking enzyme inhibitors and doubled in those on enzyme inducers. In our survey these recommendations were rarely followed with the consequence that patients received too high or too low a dose of lamotrigine, respectively.
The study aimed to determine the prevalence, pattern and correlates of antipsychotic polypharmacy (APP) among outpatients with schizophrenia attending a tertiary psychiatric facility in Nigeria.
A cross-sectional study of 250 patients with schizophrenia attending the outpatient clinic of a regional tertiary psychiatric facility in Nigeria was undertaken. They were administered a sociodemographic questionnaire, the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Liverpool University Side Effects Rating Scale (LUNSERS).
Of the 250 subjects interviewed, 176 (70.4%) were on APP. APP was significantly associated with higher prescribed chlorpromazine equivalent doses of antipsychotics (p < 0.001), increased frequency of dosing (p < 0.001), negative symptoms (p < 0.01), poorer functioning (p = 0.04) and greater side-effect burden (p = 0.04).
The APP rate reported from this study is high. Clinicians should be mindful of its impact on dosage and side-effect profiles as APP use is associated with negative symptoms and poor psychosocial functioning.
The aim of this study was to describe dosing patterns and medication adherence among bipolar patients who initiated lurasidone in a real-world setting.
Adult bipolar patients who initiated lurasidone between 1 November 2010 and 31 December 2012 (index period) with 6-month pre- and post-index continuous enrollment were identified from the IMS RWD Adjudicated Claims US database. Patients were grouped by starting lurasidone daily dose: 20 mg (7.1%), 40 mg (62.2%), 60–80 mg (28.7%), and 120–160 mg (2.1%). Patient characteristics were compared across doses using Cochran–Armitage trend tests. Multivariable ordinal logistic regression assessed the association between initial lurasidone dose and patient characteristics. Medication adherence was measured using medication possession ratio (MPR).
Of 1114 adult bipolar patients (mean age 40.6 years, 70.6% female), 90% initiated lurasidone at 40 mg or 80 mg/day (mean 51.9 mg/day). Of these, 16.2% initiated lurasidone as monotherapy. Mean lurasidone maintenance dose was 55.2 mg/day and mean MPR was 0.53 [standard deviation (SD) = 0.34] over the 6-month follow up. Substance use, hyperglycemia, obesity, and prior antipsychotic use were associated with higher initial lurasidone doses (p < 0.05). Odds of a 20 mg/day increase in initial lurasidone dose was 1.6-times higher for patients with substance use [95% confidence interval (CI): 1.16–2.24], 2.6-times higher with hyperglycemia problems (95% CI: 1.15–5.83), 1.7-times higher with obesity (95% CI: 1.05–2.60), and 1.3 (95% CI: 1.01–1.78) and 1.8-times higher (95% CI: 1.17–2.86) with prior use of second- and first-generation antipsychotics, respectively.
This real-world analysis of bipolar patients indicated that 40 mg or 80 mg/day were the most common starting doses of lurasidone. A majority of patients used concomitant psychiatric medications (polypharmacy). Higher doses of lurasidone were prescribed to patients with comorbidities or prior antipsychotic use. Adherence to lurasidone was comparable to or better than antipsychotic adherence reported in bipolar disorder literature.
Many patients with schizophrenia have low medication adherence. There is, however, no objective assessment scale that can be used by nurses or caregiver specialists. The Nursing Assessment of Medication Acceptance (NAMA) was developed to assess patients’ medication adherence. The aim of this study was to examine the validity and reliability of the NAMA in patients with schizophrenia.
A total of 121 Japanese patients with schizophrenia were enrolled. All patients underwent evaluation using the NAMA and the Drug Attitude Inventory (DAI-10). Reliability was investigated using a test-retest method and a parallel-test method. To determine the test-retest reliability of the NAMA, we tested 101 schizophrenia patients twice, with the second assessment 2–4 weeks after the date of the first assessment. For validity verification, standard-related validity and the degree of concordance with the DAI-10 scores were measured.
The Cronbach’s alpha value of the NAMA in schizophrenia was 0.88. The test-retest correlation coefficients were all between 0.53–0.74. The total scores and all subscores for the NAMA were significantly correlated, and the NAMA total scores were significantly correlated with the DAI-10 total scores.
The NAMA shows good reliability and validity in measuring medication adherence in schizophrenia.
Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia and so this may contribute to the cognitive impairments of schizophrenic patients. Because such deficits do not respond to neuroleptic treatment, different approaches have been done by acetylcholinesterase inhibitors (AChEIs). The objective of the present assessment was to evaluate the safety and clinical effects of rivastigmine, as an adjunctive drug, on the clinical symptoms of schizophrenia.
A total of 46 patients with a diagnosis of schizophrenia entered into a 12-week, double-blind, clinical trial for random assignment to rivastigmine or placebo, as adjuvant to their current antipsychotic medication. Positive and Negative Symptom Scale (PANSS) and Mini Mental State Examination (MMSE) had been used as the primary outcome measures. Clinical Global Impressions- Improvement (CGI-I) Scale and Extrapyramidal Symptom Rating Scale (ESRS) had been used as the secondary measures. Treatment efficacy was evaluated by a Student’s t test and repeated-measures analysis of variance (ANOVA). Statistical significance was defined as a two-sided p value <= 0.05. Cohen’s standard (d) and correlation measures of effect size (r) had been calculated for comparing baseline to endpoint changes.
According to the findings, except for significant enhancement of MMSE by rivastigmine (p < 0.001), no significant improvement in PANSS (negative symptoms), PANSS (positive symptoms), and PANSS (general psychopathology) was evident in the target group. Also, except for significant improvement of CGI-I by rivastigmine in intragroup analysis, no significant effectiveness was evident in between-group analysis or repeated-measures ANOVA. ESRS, also, did not show any significant alteration in either group. Effect size (ES) analysis showed a large improvement in MMSE by rivastigmine.
According to the findings, while rivastigmine could not induce significant improvement of positive and negative symptoms of schizophrenia, it caused significant enhancement of cognitive function in this group of patients.
Olanzapine is a well established treatment for schizophrenia. The olanzapine pamoate depot (long-acting injectable) formulation improves compliance and clinical trials have shown it to be effective. However, there are no previously published reports evaluating olanzapine depot in violent patients with schizophrenia in the community. We evaluated the clinical efficacy of olanzapine depot, its effect on violence, hospitalization and incarceration in community patients with schizophrenia and prior history of serious violence.
This was a retrospective service evaluation in a community forensic psychiatry service where patients had schizophrenia spectrum disorder and a significant history of violence. Treatment resistance, substance use disorders and antisocial personality disorder were common. Nine deidentified patient records were audited for 12 months pre and 12 months post olanzapine depot initiation to identify any clinical changes, breaches of (legislated) psychiatric treatment orders, hospital admission days, days incarcerated and emergency presentations.
Community forensic psychiatric patients treated with olanzapine depot showed an improvement in psychotic symptoms (p = 0.008) with overall decreases in violence, supported by reductions in hospitalization days (p = 0.018) and days incarcerated (p = 0.043). Several patients had reduced psychiatric treatment order breaches and emergency presentations.
Community forensic psychiatric patients with schizophrenia responded to olanzapine depot with decreased violence and reduced hostility. A depot antipsychotic medication that reduces violence and improves engagement has significant implications for greater effective community management of forensic patients with schizophrenia.
The objective of this study was to investigate the concordance in attitudes of psychiatrists towards the doses of antipsychotics given to stable outpatients with schizophrenia and to examine the psychiatrists’ estimates of equally potent doses of haloperidol and olanzapine.
We asked all 22 doctors serving at the psychiatry department of Jönköping County Hospital if they considered the combined dose of antipsychotics for 20 individual patients to be ‘low’, ‘medium’ or ‘high’. We also asked each doctor to state the dose of haloperidol that they considered to be clinically equivalent to 20 mg/day of olanzapine.
The inter-rater reliability (Krippendorff’s alpha (α)) was 0.50, and the mean estimated dose haloperidol considered clinically equivalent to 20 mg/day of olanzapine was 4.45 mg/day.
The inter-rater reliability (Krippendorff’s α) was low, suggesting lack of agreement. The dose of antipsychotics given to a patient might thus be more influenced by which doctor they meet than the severity of the disease. The respondents in this study considered a mean dose of 4.45 mg/day of haloperidol to be clinically equivalent to 20 mg/day of olanzapine. This is a considerably lower dose than was determined by an international consensus study of antipsychotic dosing, and more in line with the available PET studies measuring central dopamine receptor blockage of optimal clinical doses.
Antidepressants are the first line treatment for moderate to severe major depressive disorder (MDD) in perinatal and general populations. However, there appears to be paucity of evidence around antidepressant use in women with postpartum depression or anxiety. Selection of an appropriate antidepressant is crucial in promoting efficacy, optimizing tolerability, and managing comorbid anxiety or depression. Our aim was to investigate the treatment effect and tolerability profile of desvenlafaxine, and to examine the functionality of women with postpartum depression or anxiety after desvenlafaxine treatment.
Fifteen postpartum women with depression or anxiety completed this 12-week prospective pilot study with a flexible dose of desvenlafaxine (50–100 mg). Participants were recruited at a tertiary care level program. Measures of depression (Montgomery–Åsberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAM-A), worry (Penn State Worry Questionnaire, PSWQ) and functional impairment (Sheehan Disability Scale, SDS) were completed at baseline, 8 weeks, and 12 weeks.
In the intention-to-treat analysis (n = 17), the majority of women responded to medication (88.2%, n = 15), and reached remission of depressive (82.4%, n = 14) and anxiety symptoms (82.4%, n = 14). Remission of depression was achieved in a mean of 6.9 weeks [standard deviation (SD) = 3.01] at a mean dose of 71 mg/day (SD = 25.7). Significant decreases were observed on PSWQ worry scores (p < 0.0001) and SDS scores for social (p < 0.0001) and family life impairment (p < 0.0001). The medication was generally well tolerated.
The results of our prospective pilot study suggest that treatment with desvenlafaxine of postpartum mothers with depression or anxiety can lead to symptom remission and restoration of functionality.
The treatment of sleep disorders in Alzheimer’s disease (AD) may be quite challenging in elderly patients because of drug side effects or interactions and comorbid local or systemic diseases. Here, we report a patient with AD, who was suffering from severe insomnia and depression. We ordered agomelatine for the treatment of insomnia in this patient, and it was quite helpful not only for insomnia but also for depression and for the cognitive symptoms related with dementia. Our aim was to share these observations for similar patients.
Correct identification of alcohol as a contributor to, or comorbidity of, many psychiatric diseases requires health professionals to be competent and confident to take an accurate alcohol history. Being able to estimate (or calculate) the alcohol content in commonly consumed drinks is a prerequisite for quantifying levels of alcohol consumption. The aim of this study was to assess this ability in medical and nursing students.
A cross-sectional survey of 891 medical and nursing students across different years of training was conducted. Students were asked the alcohol content of 10 different alcoholic drinks by seeing a slide of the drink (with picture, volume and percentage of alcohol by volume) for 30 s.
Overall, the mean number of correctly estimated drinks (out of the 10 tested) was 2.4, increasing to just over 3 if a 10% margin of error was used. Wine and premium strength beers were underestimated by over 50% of students. Those who drank alcohol themselves, or who were further on in their clinical training, did better on the task, but overall the levels remained low.
Knowledge of, or the ability to work out, the alcohol content of commonly consumed drinks is poor, and further research is needed to understand the reasons for this and the impact this may have on the likelihood to undertake screening or initiate treatment.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child’s development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA® to the same dose of generic Novo-methylphenidate ER-C®.
Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II).
Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study.
Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.
The objective of the study was to use routinely collected data on vitamin D levels of adolescents detained in a secure psychiatric hospital to see if this at-risk group for vitamin D deficiency do in fact have low vitamin D levels.
Vitamin D blood levels were collated from clinical records of inpatients admitted to Bluebird House, a medium secure adolescent unit, since 2012. Corresponding data were gathered to include gender, ethnic status and age. Blood levels were assessed on admission to the unit and after treatment with vitamin D supplementation, if indicated.
Only 3 out of the 35 patients (8.6%) had adequate vitamin D levels (serum 25-hydroxyvitamin D [25-OHD] > 50 nmol/l). A total of 23 patients (65.7%) had levels consistent with deficiency (25-OHD < 30 nmol/l) with the remaining 9 patients (25.7%) showing levels indicating possible deficiency (25-OHD 30–50 nmol/l.
Vitamin D levels were low in our sample of young people admitted to a secure psychiatric hospital. This is the first published study of vitamin D levels in a secure adolescent psychiatric hospital. The results point to the need for routine prescription of vitamin D to adolescents held in secure conditions such as hospitals, secure children’s homes and youth offender institutes.
The objective of this study was to evaluate the prevalence and severity of clozapine-induced hypersalivation, and assess the impact hypersalivation has on global functioning.
Participants attending a dedicated clozapine clinic were invited to undertake a structured interview regarding their experiences of clozapine-induced hypersalivation. Two psychometric instruments to measure hypersalivation, the Nocturnal Hypersalivation Rating Scale and the Drooling Severity and Frequency Scale were used.
Clozapine-induced hypersalivation was experienced by 92% of participants, with nocturnal hypersalivation more prevalent compared to daytime hypersalivation (85% versus 48%). Daytime drooling was severe in 18% of cases and was present on a frequent or constant basis for 20% of individuals. Hypersalivation had at least a moderate impact on the quality of life of 15% of study participants.
Clozapine-induced hypersalivation is the most prevalent adverse effect experienced by patients treated with clozapine and negatively impacts on quality of life, particularly if daytime drooling is present. The development of further strategies to ameliorate this adverse effect is required given the demonstrated lack of success to date in managing this condition.
Black people are over represented in mental health services and prescribing of antipsychotics differs by race in some countries. Our previous UK research into the prescribing of antipsychotics in large, multicentre studies found no important differences for black and white patients. However, we received several comments challenging our findings. We wanted to test the validity of these anecdotes by devising two case vignettes that differed only by race and asking prescribers to choose antipsychotic treatment.
A case study was sent to all medical prescribers in the South London and Maudsley NHS Trust. Half of the prescribers for each grade of staff were sent the case study where the ethnicity of the patient was white and the other half where the ethnicity was black. Participants were asked to describe what they would prescribe for the patient. Outcomes were total percentage maximum dose, high dose, type of antipsychotic, route of administration and antipsychotic polypharmacy.
We received 123 completed case studies and demographic data forms from prescribers. There were no differences in percentage maximum dose, high dose, type, route and number of antipsychotics prescribed by case study ethnicity.
Prescribing for UK black and white patients is broadly similar when tested in clinical and theoretical studies.
The objective of this study was to compare patients’ attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI).
A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale.
The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication.
Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including medication tolerability; assessment of side effects, efficacy and quality of life made by blinded raters; and additional objective side-effect data including changes in weight and key blood parameters.
Background: Oral olanzapine is a well-established treatment for patients suffering from schizophrenia. Advantages of depot olanzapine may include improved compliance. However, it is expensive, causes metabolic side effects, and carries a risk of postinjection syndrome. Clinical trials have shown olanzapine pamoate to be effective, but further work is needed in this area. This study was a retrospective service evaluation, carried out in a high-security hospital, where the majority of patients have complex, treatment resistant schizophrenia spectrum disorder and a very high propensity for violence. Compliance is a significant problem, both in the high-security setting and on discharge. There has been no previous published work that the authors are aware of evaluating the effects of olanzapine pamoate in this subgroup of patients.
Methods: The aim of the study was to evaluate the clinical efficacy of olanzapine pamoate, its effect on violence as well as its side effects, in a high-security setting for the first time. Anonymized patient records were used to identify the main outcome measure and clinical global improvement, and to ascertain secondary outcome measures which included seclusion hours, risk of violence and side effects. Metabolic parameters and number of incidents were also recorded. Eight patients were treated with olanzapine pamoate.
Results: Six showed an improvement in symptoms, with an associated decrease in violence and number of incidents. Four showed an associated decrease in seclusion hours. Two showed an increase in body mass index and two showed an increase in glucose.
Conclusions: The findings of this study are important in showing that all patients who responded to olanzapine pamoate also showed a decrease in violent behaviour. The potential anti-aggression effects of olanzapine pamoate may represent a very promising area for further work. A depot antipsychotic medication that reduces violence could have significant implications for management of high-security patients.
Background: Clozapine has been used to good effect in the treatment of adults with borderline personality disorder, but there is scant evidence of it being used in an adolescent population with these difficulties.
Methods: Clozapine was trialled in an adolescent with a clinical presentation consistent with an emerging borderline personality disorder.
Results: There was a large reduction in the number of incidents involving abuse to staff, or harm to self, in the 8 weeks after commencing clozapine therapy, compared with the 8 weeks prior, and also a large reduction in the number of episodes of the use of seclusion in the 13 weeks after commencing clozapine therapy, compared with the 13 weeks prior. The young person was also able to be reintegrated in to the ward environment once established on clozapine therapy, which had not been possible full-time, for a whole year prior.
Conclusions: Although limited by involving just one adolescent, this very preliminary data does nonetheless suggest that clozapine may have a role in treating adolescents with emerging borderline personality disorder when other treatment options have been exhausted.
Objective: Mixed-depressive features imply an occult bipolarity and might be linked to resistance to antidepressant therapy and a higher risk of suicide. Currently, there is no consensus about or any clinical guidelines available for this ill-defined clinical entity. The aim of this study was to assess the effectiveness, safety, and tolerability of mood stabilizers, such as valproate, for adjuvant therapy in patients suspected of having mixed-depressive features.
Methods: This retrospective observational study reviewed medical records of psychiatric outpatients attended by the author from 2008 to 2013. Patients who presented with inadequately treated, long-lasting atypical depressive- and/or anxiety-spectrum symptoms, and who started adjuvant valproate therapy for the first time in their course of treatment, were identified. Patient demographics, clinical profiles, treatment responses, and treatment-emergent adverse events (AEs) were examined in detail.
Results: A total of 22 patients (7 men and 15 women) ranging in age between 25 and 78 years were treated with valproate 100–1250 mg/day and observed for 3–60 months. The majority exhibited much or moderate improvement, and only four showed a limited response. During follow up, 12 continued adjuvant valproate, 3 were intermittent users, and 3 quit after no apparent response; 4 experienced an aggravation of symptoms after discontinuation but were stabilized soon after reinstitution. AEs were reported by 12 patients and 4 stopped valproate for intolerability despite improvement.
Conclusion: Adjuvant valproate therapy seems to be a promising approach to treating patients who manifest atypical neurotic or mood disorders with subthreshold bipolarity at a dosage around the lower end of that used to treat full-syndromal bipolar disorders.
Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent data suggesting therapeutic utility in treating depressive illnesses. This review explores their pharmacodynamic actions and the current limited data on their clinic effectiveness. These drugs appear to exert their psychedelic effects through their agonist or partial agonist activity at the serotonergic 5-HT2A receptor, though they also have affinity for other metabotropic serotonin receptors. Hallucinogen binding affects a wide range of intracellular signalling pathways, the precise nature of which remains incompletely understood. They alter the serotonergic tone of brainstem raphe nuclei that project through the brain; they interact with receptors in the prefrontal cortex altering connectivity patterns and intracellular functioning; and they disrupt inhibitory control of sensory input via the thalamus to the cortex. The serotonergic system has long been implicated in anxiety and depressive disorders, and is a major target of most existing antidepressants. Classical hallucinogens alter the functioning of this system, but not in the same way current medications do: whilst there are identified receptors and neurotransmitter pathways through which hallucinogens could therein produce therapeutic effects, the neurobiology of this remains speculative at this time. There is currently an extremely limited but growing literature on hallucinogen safety and clinical application. The drugs appear well tolerated by healthy controls and clinical populations, and the rapid tolerance to repeated administration might reduce the possibility of dependency. Clinical trials reported over the past decade have generally shown positive therapeutic potential, but they are notably few in number. Legislative policy has had a freezing effect on evaluation of these compounds, a better understanding of which might improve our knowledge of the processes involved in consciousness, the neuropathology of depression, and potentially open up new pharmacological therapies.
Background: Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatments for major depressive disorders (MDD). It has been reported, however, that 30–40% of patients with MDD who received SSRIs failed to respond to treatment. Use of lithium (Li) to augment SSRIs seems to be the most common strategy in such cases. It was recently demonstrated that atypical antipsychotics are effective augmentation agents in MDD. Here, we present a randomized controlled study that compared augmentation with Li, olanzapine (OLA) or aripiprazole (ARI) in paroxetine-refractory patients with MDD.
Methods: Participants were 30 patients who met Diagnostic and Statistical Manual of Mental Disorders IV criteria for MDD and refractory to paroxetine treatment. Treatment with Li, OLA or ARI was added to paroxetine in a randomized protocol for 4 weeks. We defined the patients whose scores on the Hamilton Rating Scale for Depression decreased 50% or more as responders.
Results: Two patients dropped out because of adverse effects. Response rates to Li, OLA or ARI augmentation were 4/10 (40%), 3/10 (30%) and 4/10 (40%), respectively. In addition, Li, OLA and ARI did not influence plasma paroxetine concentrations.
Conclusions: We concluded that OLA or ARI could be used as alternatives to Li as options for patients who do not respond to paroxetine treatment.
Objectives: Clozapine is the most efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by intolerability. Sinus tachycardia is a common adverse event associated with clozapine use, which may lead to the premature discontinuation of clozapine. Traditionally, β blockers are used to treat clozapine-associated tachycardia, though problems with intolerability and ineffectiveness can limit their utility.
Methods: In this article, we present two cases of patients with treatment-resistant schizophrenia who developed symptomatic tachycardia associated with clozapine therapy.
Results: We demonstrate that the novel heart rate controlling agent ivabradine can be effectively and safely used to control the heart rate and to allow for continued treatment with clozapine.
Conclusion: This is the first report in the literature demonstrating that ivabradine appears to be a well tolerated agent, which should be considered as a symptomatic treatment of clozapine-induced tachycardia if the use of a β blocker fails due to a lack of response or intolerability.
Objectives: There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.
Methods: This was a 12-week rater-blind placebo-controlled study. A total of 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) and Abnormal Involuntary Movement Scale (AIMS).
Results: Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with treatment as usual (TAU) on PANSS total score, although this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
Conclusions: Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with TAU. This study has led to a larger Stanley Medical Research Institute (SMRI)-funded, double-blind, randomized control trial.
Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling.
We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an ‘outlier’ manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.
Objective: To assess the cognitive effects of sertindole and olanzapine in patients diagnosed with schizophrenia. Cognition was the primary outcome of the study.
Method: This was a 12-week double-blinded randomized clinical controlled trial. Participants were randomized to either 16–24 mg of sertindole or 10–20 mg of olanzapine.
Results: The study had a low recruitment rate (N = 9) and was terminated before the expected number of patients was reached. No significant differences between groups were found at study end on any of the 32 cognitive subtests. A simple sign test did not show any of the comparator drugs trending towards being superior on the majority of tests. Mean change on Positive and Negative Syndrome Scale (PANSS) total and PANSS subscales from baseline to end of study were not significantly different between treatment groups. Similar results on cognition and PANSS was seen on completers and last observation carried forward analysis.
Conclusion: In this study we did not find any significant differences between sertindole or olanzapine on PANSS subscales or neurocognitive tests in a population consisting of patients diagnosed with schizophrenia.
Objective: This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated elderly patients with schizophrenia at 2 hours postdose.
Methods: The subjects were 23 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and laboratory tests.
Results: The mean reduction from baseline on the PANSS-EC total score, the PANSS total score and the ACES score were significantly greater in the IM olanzapine injection group than in the IM haloperidol injection group. The mean changes from baseline on the AIMS score, the BARS score and the DIEPSS total score were significantly better in the IM olanzapine injection group than in the IM haloperidol injection group. No serious adverse events such as paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive dyskinesia occurred between the two groups.
Conclusion: The results of this study suggest the possibility that agitated elderly patients may result in superior efficacy and safety after IM olanzapine without serious adverse events in comparison with IM haloperidol.
Temperature dysregulation is an infrequent but previously documented adverse effect of antipsychotic medications. The majority of documented cases involve durations of hypothermia of less than 24 h. We present the case of a patient on therapeutic olanzapine for bipolar disease with dehydration from gastroenteritis leading to acute kidney injury in the setting of stage III chronic kidney disease, who presented with severe hypothermia of 31.2°C (88.2°F). He required active rewarming in the intensive care unit for a total of 9 days. This is the second case report of prolonged hypothermia from olanzapine in the setting of kidney disease. Clinicians should be aware that patients with renal dysfunction may be at increased risk for prolonged hypothermia from olanzapine.
Objective: Depression is one of the most common psychiatric disorders in the world. Lifetime prevalence is 15% among men and 25% among women. Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and monoamine oxidase inhibitor antidepressants are often used for depression, with their own side effects. This study was carried out since little information on sexual dysfunction due to these medications is available in Iran.
Methods: This observational cross-sectional study included 100 patients attending a university or private psychiatry clinic who, after an interview based on Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria, were considered depressed. These patients had no history of depression, sexual dysfunction or use of psychiatric medications. Sexual functioning of patients was evaluated at the start of the study, and after 2, 4 and 8 weeks of treatment. Data were evaluated using SPSS software and t and 2 tests.
Results: A total of 75% of patients reported sexual dysfunction: 66.7% of men and 79.7% of women. A total of 74.1% of patients on fluvoxamine, 100% on fluoxetine, 75% on sertraline, 71.4% on citalopram and 100% on paroxetine reported sexual dysfunction. The most frequent sexual dysfunction was difficulty with orgasm, which affected 41.17% of women and 33.33% of men.
Conclusion: The incidence of sexual dysfunction among users of SSRIs was highest in patients on fluvoxamine, but this was not statistically significant. Minimization of sexual side effects should be an essential consideration when prescribing antidepressants.
The increasing use of antipsychotics (APs) to treat pediatric psychiatric conditions has led to concerns over the long-term tolerability of these drugs. While the risk of cardiometabolic abnormalities has received most of the attention, preclinical and clinical studies provide preliminary evidence that APs can adversely impact bone metabolism. This would be most concerning in children and adolescents as suboptimal bone accrual during development may lead to increased fracture risk later in life. However, the potential mechanisms of action through which APs may impact bone turnover and, consequently, bone mineral content are not clear. Emerging data suggest that the skeletal effects of APs are complex, with APs directly and indirectly impacting bone cells through modulation of multiple signaling pathways, including those involving dopamine D2, serotonin, adrenergic, and prolactin receptors, as well as by affecting gonadotropins. Determining the action of APs on skeletal development is further complicated by polypharmacy. In children and adolescents, APs are frequently coprescribed with psychostimulants and selective serotonin reuptake inhibitors, which have also been linked to changes in bone metabolism. This review discusses the mechanisms by which APs may influence bone metabolism. Also covered are preclinical and pediatric findings concerning the impact of APs on bone turnover. However, the dearth of clinical information despite the potential public health significance of this issue underscores the need for further studies. The review ends with a call for clinicians to be vigilant about promoting optimal overall health in chronically ill youth with psychopathology, particularly when pharmacotherapy is unavoidable.
With the exception of fluoxetine, all selective serotonin reuptake inhibitors (SSRIs) commonly cause hyperprolactinemia through presynaptic mechanisms indirectly via 5-hydroxytryptamine (5-HT)-mediated inhibition of tuberoinfundibular dopaminergic neurons. However, there is little insight regarding the mechanisms by which fluoxetine causes hyperprolactinemia via the postsynaptic pathway. In this text, analysis of five spontaneously reported clinical cases of hyperprolactinemia resulting in overt symptoms of amenorrhea with or without galactorrhea, were scrupulously analyzed after meticulously correlating relevant literature and an attempt was made to explore the putative postsynaptic pathway of fluoxetine inducing hyperprolactinemia. Hypothetically, serotonin regulates prolactin release either by increasing oxytocin (OT) level via direct stimulation of vasoactitive intestinal protein (VIP) or indirectly through stimulation of GABAergic neurons. The pharmacodynamic exception and pharmacokinetic aspect of fluoxetine are highlighted to address the regulation of prolactin release via serotonergic pathway, either directly through stimulation of prolactin releasing factors (PRFs) VIP and OT via 5-HT2A receptors predominantly on PVN (neurosecretory magnocellular cell) or through induction of 5-HT1A-mediated direct and indirect GABAergic actions. Prospective molecular and pharmacogenetic studies are warranted to visualize how fluoxetine regulate neuroendocrine system and cause adverse consequences, which in turn may explore new ways of approach of drug development by targeting the respective metabolic pathways to mitigate these adverse impacts.
Clozapine (Denzapine) is a treatment for resistant schizophrenia. Among the serious but rare side effects of clozapine are agranulocytosis and priapism. We hereby present the case of a 30-year-old man with a diagnosis of schizophrenia who has spent nearly 12 years of his adult life on various psychiatric in-patient units including open wards, secure units, psychiatric intensive care units and rehab wards. Diagnosed at the age of 15, he only responded to clozapine at the age of 18. Whilst being on clozapine he developed priapism in June 2010 and needed emergency surgical treatment in the form of surgical decompression. He again responded only to clozapine and fortunately he did not redevelop priapism; however, he was readmitted in February 2011 due to relapse, and he remained resistant to other antipsychotics. He was rechallenged with clozapine and recovered, but unfortunately redeveloped priapism which required emergency surgical and medical intervention (goserline acetate and tinzaperin injection). In order to relieve the recurrent priapism, he agreed to continue clozapine and goserline acetate injection. This decision was made by the patient in a compos mentis state. As far as we are aware, this is the first time goserline acetate has been reported as a successful treatment for clozapine-induced priapism.
Background:Lithium has been used in the fields of rheumatology and psychiatry since the 1800s and it is now generally considered to be a gold standard treatment for bipolar disorders. However, lithium is known to have significant side effects and requires close serum level monitoring to ensure levels remain within the therapeutic range to minimize the risk of serious adverse effects or toxicity. This article reviews the monitoring of lithium and reports on the implementation of a regional lithium register and database within Norfolk.
Methods: Recorded blood results from the Norfolk lithium database were extracted for the first full year of operation across the region, 2005/6, and from the most recent full year 2011/12. The number of lithium monitoring tests, U&Es and thyroid function tests conducted on all people registered on the database were compared between the two sample years.
Results: In 2005/6 there were a significant number of people not receiving the recommended number of four or more serum lithium test per year (68.3%) and the majority of people had two or three tests (62%). By 2011/12 this had noticeably increased with the majority of patients having four or more tests per year (68.5%) and the number having only two or three tests reducing dramatically (26.4%).
Conclusion: Improved rates of lithium testing and monitoring have been demonstrated since the introduction of the Norfolk database helping to achieve national targets. Consequently, the chances of adverse events from insufficient monitoring have been minimized.
Prior reports suggest that clozapine can markedly reduce aggression and self-injurious behavior in patients with borderline personality disorder (BPD). We present a series of four patients with BPD and persistent self-injurious behavior treated with clozapine at a state psychiatric hospital. After treatment with clozapine these patients ceased self-injurious behaviors and aggression, and no longer required intensive levels of observation or restrictive procedures. All were successfully discharged from the hospital soon after initiation of clozapine. Clozapine appears to be efficacious in the management of chronic suicidality, self-injurious behaviors and aggression in patients with severe BPD.
Clozapine is regarded as a second-line and in some cases last-line antipsychotic known for its common life-threatening side effects like of agranulocytosis, constipation and cardiomyopathies, but rarely haematemesis. We report a case of severe haemetemesis in a chronic schizophrenic patient managed with clozapine. The patient was a 46-year-old male being managed for chronic schizophrenia with treatment resistance who developed sudden severe haematemesis following commencement of clozapine for 6 weeks. The patient had 1.1 l of blood transfusion. The relevant literature is reviewed. Clozapine can be associated with a life-threatening haematemesis. Psychiatrists and other medical specialists need to be alert to the fatality of clozapine-induced haematemesis in the treatment of psychiatric disorders.
Background: The current guidelines dictate that clozapine should be stopped following the emergence of neutropenia. Various alternative approaches have been tried in the past, among them one rarely used alternative being to continue treatment with clozapine with coprescription of granulocyte colony-stimulating factor (G-CSF).
Aim and method: In this case series we aim to describe the treatment and progress of a number of patients in a secure psychiatric hospital in the UK. These patients were restarted on clozapine in combination with G-CSF, in spite of previous neutropenia associated with clozapine treatment.
Discussion and conclusion: We hope that this case series will raise the profile of a potentially effective alternative to discontinuing clozapine after neutropenia.