Impact of Ramadan fasting on medical and psychiatric health.

Ramadan is a religious month dedicated to prayer, fasting and feasting. Recently, there has been an increased interest among healthcare providers regarding possible health-related complications as a consequence of religious fasting such as that seen during Ramadan. In , a 34-year-old female patient with a diagnosis of schizoaffective disorder, depressive type, was admitted for inpatient hospitalization to an inpatient psychiatric hospital in Buffalo, New York. The earliest date of initial diagnosis is unclear; however, the patient reports an increase in symptoms during her early twenties. Upon admission, the patient was continued on haloperidol, lithium and fluphenazine decanoate which had been initiated prior to this admission. Medication administration and meal times were adjusted to accommodate her observance of Ramadan. Despite efforts to mitigate the potential impact, the patient complained of dizziness and weakness following initiation and titration of clozapine. Due to psychiatric exacerbation, inpatient hospitalization and continuous monitoring, clozapine titration occurred quickly. Upon admission, the patient's blood pressure was 137/85 mmHg, which decreased to a low of 87/58 mmHg as her clozapine dose was increased, leaving the patient requesting bedrest due to significant dizziness and weakness. On the 21st day of Ramadan, the patient broke her fast due to substantial adverse effects. Five days after breaking her fast, the patient's blood pressure increased and returned to baseline. Individuals participating in Ramadan tend to have disrupted sleep cycles, including nocturnal sleep reduction and broken sleep patterns, which can impact overall health. Additional health-related complications that have been reported include dehydration and changes in blood glucose, blood pressure, lipid panel, body weight and exacerbation of psychiatric symptoms. These adverse effects can result in serious complications in fasting individuals with acute medical and psychiatric illness. Clozapine was initiated and rapidly titrated during the patient's observance of Ramadan. She exhibited signs and symptoms of hypotension, which were also subjectively reported by the patient. The significant drop in blood pressure while fasting, and rapid increase once the fast was broken, confirm that medication changes implemented during religious fasting, such as that seen during Ramadan, can increase a patient's risk of serious adverse effects.

The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.

Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.

BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.

Metabolic monitoring for youths initiating use of second-generation antipsychotics, 2003-2011.

OBJECTIVE: In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years. METHODS: Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis. RESULTS: The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern. CONCLUSIONS: The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

Intentional overdose of azathioprine in a patient with systemic lupus erythematosus.

A 14-year-old girl with systemic lupus erythematosus presented with a mixed overdose of paracetamol, ibuprofen and azathioprine (1500 mg) following a deliberate self-harm attempt. The patient was admitted and monitored. No adverse effects were observed. A review of the literature showed very few reported azathioprine overdoses. Lupus patients are at risk of developing low mood and depression (and related self-harm including overdose of medication). This can be as a consequence of the disease process itself or in reaction to the stresses of living with a chronic disease, which are perhaps particularly acute in some adolescents with the disease. An intentional overdose in a patient with lupus is clearly a cry for help and should be appropriately managed. Counselling of young people and their parents about possible mood disorders is an important part of the management of this chronic disease. Despite the theoretical risk of significant myelosuppression as well as other potential adverse effects, azathioprine in acute overdose seems to be generally well tolerated.

Complexities of personalized medicine: how genes, drug-drug interactions, dosing schedules, and other factors can combine to produce clinically meaningful differences in a drug's effect.

Given increased knowledge from molecular biology and pharmacology, it is apparent that multiple factors can interact to produce clinically meaningful differences in a drug's effect in specific individuals (i.e., personalized medicine). This topic is discussed in this column using iloperidone as an example. The variables discussed include dose, dosing schedule, genes, drug-drug interactions, and other medical factors. How such variables can combine to alter a drug's effect is illustrated with a case example and the results of a thorough QTc study of iloperidone.

Mortality and its determinants in people with psychotic disorder.

OBJECTIVE: We investigated mortality and its determinants in people with psychotic disorder. METHODS: A nationally representative two-stage cluster sample of 8028 persons aged 30 years or older from Finland was selected for a comprehensive health survey conducted from 2000 to 2001. Participants were screened for psychotic disorder, and screen-positive persons were invited for a Structured Clinical Interview for DSM-IV. The diagnostic assessment of DSM-IV psychotic disorders was based on the Structured Clinical Interview for DSM-IV, case records from mental health treatments, or both. Mortality was followed up until September 2009 and analyzed using Cox proportional hazards model. RESULTS: People with schizophrenia (hazard ratio [HR] = 3.03; 95% confidence interval [CI] = 1.93-4.77) and other nonaffective psychoses (HR = 1.84; 95% CI = 1.17-2.91) had elevated mortality risk, whereas people with affective psychoses did not (HR = 0.61; 95% CI = 0.24-1.55). Antipsychotic medication use was associated with increased mortality (HR = 2.34; 95% CI = 1.86-2.96). There was an interaction between antipsychotic medication use and the presence of a psychotic disorder: antipsychotic medication use was only associated with elevated mortality in persons who were using antipsychotics and did not have primary psychotic disorder. In persons with psychotic disorder, mortality was predicted by smoking and Type 2 diabetes at baseline survey. CONCLUSIONS: Schizophrenia and nonaffective psychoses are associated with increased mortality risk, whereas affective psychoses are not. Antipsychotic medication use increases mortality risk in older people without primary psychotic disorder, but not in individuals with schizophrenia. Smoking and Type 2 diabetes are important predictors of elevated mortality risk in persons with psychotic disorder.

A young woman presenting with psychotic and mood symptoms from anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis: an emerging diagnosis.

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis, first characterized in 2005, is a neurological disease with prominent psychiatric features that frequently involves the consultation of psychiatrists. Since its discovery, the rate of diagnosis of new cases has increased rapidly and several epidemiological studies now confirm that NMDA-R encephalitis may be as common as many other prominent infectious etiologies of encephalitis. We describe a case of a young woman presenting initially with psychotic and mood symptoms who was found to have anti-NMDA-R encephalitis. We further provide details of her treatment and prolonged recovery process after hospital discharge with a review of the literature and discussion of the epidemiology, symptomology, diagnosis, and management of both the neurologic and psychiatric manifestations of this condition. Last, we contextualize the importance of anti-NMDA-R encephalitis for psychiatrists, highlighting the role for psychiatrists in establishing the initial diagnosis as well as in providing ongoing psychiatric care.

[Malignant neuroleptic syndrome associated with amisulpride]. / Malignes neuroleptisches Syndrom durch Amisulprid.

Malignant neuroleptic syndrome (MNS) is a rare side effect of antipsychotic medications but means a serious and life-threatening complication. The risk of MNS seems to be lower for second generation antipsychotics (SGA). We report the 9-month history of a 42-year-old female patient whose antipsychotic medication was switched to 800 mg per day of amisulpride. Two weeks after discharge she suffered muscular pain, stiffness, weakness of the legs, rigor, and fever. After attending our outpatient department and being diagnosed, she was transferred to the neurological intensive unit, where the creatine kinase (CK) level was measured at 160,000 U/l. Furthermore extensive rhabdomyolysis accompanied by a compartment syndrome was seen. Surgical intervention was necessary for the latter. The patient was then retransferred to the psychiatric department after treatment with lorazepam and withdrawal of antipsychotic medications. In addition a therapy with valproate sodium was conducted. Long-term high levels of CK and abnormalities in the electromyogram led to the hypothesis of myopathy as a possible risk factor, but a final diagnostic classification was not feasible. This report describes the appearance of a MNS as a consequence of SGA therapy, discusses risk factors and therapy options, and shows the 9-month course.

Development of a comprehensive measure to assess clinical issues in dual diagnosis patients: The Substance Use Event Survey for Severe Mental Illness.

This paper provides a description of The Substance Use Event Survey for Severe Mental Illness (SUESS), a brief (20-30 min) interview that assesses clinical issues and domains that are relevant patients with substance use disorders and severe mental illness. First, we discuss the need for a new clinical measure for dual diagnosis patients, as well as our process of creating domains and items and developing the content of the assessment. Second, we provide a first look at the performance of the SUESS in a large sample of dually diagnosed patients from several large scale studies, including how patients responded to the instrument and their ability to complete the items. Third, we present initial reliability data on the SUESS. Finally, we include some initial validity data, including comparison of the self-report of substance use questions to urinalysis results, and verification of the service use information from medical record review. The SUESS appears to be a useful assessment that is tolerated and understood by dual diagnosis patients, and shows good preliminary reliability and validity.

Topiramate for acute affective episodes in bipolar disorder.

BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Retrospective and open-label trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder. There is a need to clarify the evidence available in the form of randomised controlled trials for its use in bipolar disorder. OBJECTIVES: To review the evidence for the efficacy and acceptability of topiramate in the treatment of acute mood episodes in bipolar disorder. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group search strategy was used. The following databases were searched:The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), September 2003;The Cochrane Controlled Clinical Trials Register (CCCTR), September 2003;EMBASE (1980 to December 2003);MEDLINE (1966 to December 2003);LILACS;PsycLIT;Psyndex.Reference lists of relevant papers and major textbooks of mood disorder. Handsearches (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials which compared topiramate with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder. Participants were patients with bipolar disorder and were males and females of all ages. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean difference was used for continuously distributed outcomes. MAIN RESULTS: One randomised controlled trial met the inclusion criteria for the review, a comparison between topiramate and bupropion sustained release (SR) in the adjunctive treatment of depressed patients with bipolar disorder. However, the trial had several limitations in methodology and in the description of data. Its data regarding efficacy required clarification before it could be analysed according to the protocol of this systematic review. From the limited data available, topiramate had efficacy similar to bupropion SR in the adjunctive treatment of bipolar depression. Both groups of subjects suffered a high drop-out rate. There was no significant difference between the topiramate and the bupropion treated groups in those dropping out for any reason (relative risk 1.60, 95% confidence interval 0.65 to 3.96). There was no significant difference in those withdrawing from the study due to adverse effects (relative risk 1.50, 95% confidence interval 0.51 to 4.43). Although the data on weight loss were not analysed formally, weight loss was marked in the topiramate treated group. Several unpublished trials have been identified and data from these trials may be included in future reviews. AUTHORS' CONCLUSIONS: There is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness, either in monotherapy or as an adjunctive treatment.

Clozapine toxicity associated with smoking cessation: case report.

We report on a 28-year-old white woman with chronic psychotic-affective illness who abruptly stopped her decade-long habit of heavy daily cigarette smoking while maintained on clozapine at 450 mg/d. Within several days, she developed dry mouth, muscle spasms, dizziness, and blurred vision with dilated and sluggish pupils, with worsening sedation and confusion. Her combined serum concentration of clozapine + norclozapine was 2.5 microg/mL, compared with levels of about 600 ng/mL at daily doses of 350 mg at other times while smoking. Reducing the dose of clozapine led to rapid alleviation of these symptoms. Additional experience with and without smoking in this case further documented the effect of smoking to decrease circulating levels of clozapine. These observations add to the conclusion that cigarette smoke can increase clearance of many drugs, calling for special caution during treatment with potentially toxic substances and dose reduction in anticipation of smoking cessation.

An 8-week open-label trial of a 6-day course of mifepristone for the treatment of psychotic depression.

OBJECTIVE: Several investigations suggest that mifepristone leads to the rapid amelioration of psychotic depression. However, these studies were of short duration (1 week or less) and included subjects who were taking other psychotropic medications. The goals of this study were to extend these findings by conducting an 8-week trial of mifepristone for subjects with psychotic depression who were taking no concomitant psychiatric medications. METHOD: Twenty subjects with a DSM-IV major depressive episode with psychotic features (for convenience we use the term psychotic depression) taking no psychotropic medications were given a 6-day course of mifepristone and followed as inpatients for a total of 8 weeks. Nonblinded ratings using the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) were performed at baseline and at the end of weeks 1, 4, and 8. The Brief Psychiatric Rating Scale (BPRS) was also administered at baseline and after weeks 4 and 8. Subjects were recruited between February 2003 and December 2003. RESULTS: Significant improvements in HAM-D and CGI scores were shown after 1 week and between weeks 1 and 4 but not between weeks 4 and 8. BPRS scores improved significantly after week 4, while the improvement in BPRS scores between weeks 4 and 8 was of borderline significance. CONCLUSION: Mifepristone appears to be a useful intervention for psychotic depression, leading to significant improvements even after a 1-week course of administration. Issues related to its optimal dosing and to prediction of response are discussed, as are the implications of lack of a placebo group and the use of nonblinded ratings in the present study.

Variables associated with high olanzapine dosing in a state hospital.

BACKGROUND: Olanzapine has a U.S. Food and Drug Administration-approved dosing range of 10 to 20 mg/day but is often used at doses exceeding this range. Olanzapine is largely metabolized by cytochrome P450 (CYP) 1A2. Smoking, which induces CYP1A2, is expected to increase clearance of olanzapine by 40%; however, dosage adjustment in smokers is not currently recommended. Additionally, female gender is expected to reduce clearance by 30%. Many institutions target high-dose olanzapine prescribers in an effort to reduce unnecessary drug costs. However, factors such as smoking or gender may necessitate increased doses. METHOD: A retrospective review of all patients receiving olanzapine during an inpatient stay at a state psychiatric hospital in Kentucky during 2001 was conducted. Demographic information and smoking status were collected for all patients. Olanzapine doses of > 20 mg/day were considered high doses. RESULTS: Nine percent (48/522) of olanzapine patients were prescribed high doses. The percentages were similar in women and men (10% vs. 9%, p =.69) and in smokers and nonsmokers (9% vs. 9%, p =.82). Moreover, the mean maximum olanzapine dose was also similar in men and women (15.4 +/- 7.2 vs. 14.9 +/- 7.3 mg/day, p =.51). The odds of receiving a high dose of olanzapine were increased 2.1 for patients with a schizophrenia spectrum diagnosis (DSM-IV schizophrenia or other psychotic disorder). The odds of receiving a high dose of olanzapine were increased with each incremental increase in length of stay (intermediate length of stay [8-60 days], OR = 5.6; long-term length of stay [> 60 days], OR = 12.0, relative to acute length of stay [< 8 days]). CONCLUSIONS: Neither gender nor smoking status was associated with receiving a high dose of olanzapine. The association of increased length of stay with high dose suggests that treatment resistance may be an important factor in receiving high daily doses of olanzapine.

Orientações ao pediatra sobre o manejo das drogas psicoativas e antiepilépticas / Use of psychoactive and antiepileptic drugs: guidelines for pediatricians

OBJETIVO: Revisar as indicações e o manejo clínico das drogas psicoativas e antiepilépticas na infância e adolescência. FONTES DE DADOS: Estudo baseado em revisão de literatura. Os autores organizam, de acordo com os quadros patológicos, uma rotina para o manejo dos psicofármacos e das drogas antiepilépticas na infância e na adolescência. SíNTESE DOS DADOS: Indicação clínica, dosagem terapêutica e efeitos colaterais dos psicofármacos e drogas antiepilépticas são descritos. O uso de psicofármacos na infância e adolescência está se tornando mais freqüente, com a disponibilidade de novos medicamentos e com o crescimento do conhecimento sobre diagnóstico de transtornos emocionais nessa faixa etária. CONCLUSÕES: O manejo dos psicofármacos e drogas antiepilépticas na faixa etária pediátrica requer amplo conhecimento da farmacocinética dos mesmos, assim como de seus efeitos colaterais deletérios. A escolha do fármaco adequado é determinante no sucesso terapêutico.

Conventional antipsychotic prescription in unipolar depression, I: an audit and recommendations for practice.

BACKGROUND: Despite narrow indications for conventional antipsychotics in depression, recent reports confirm a suspicion that they are widely prescribed in nonpsychotic depressive conditions. METHOD: Data from the case notes of over 510 patients with unipolar depression (unvalidated clinical diagnoses) were collected between June 1997 and January 1998 from community and acute units in 1 National Health Service (NHS) Trust. The aim of this audit was to assess the extent and pattern of antipsychotic prescription in this sample. RESULTS: More than a quarter (N = 138) of the sample (N = 494) were currently prescribed an antipsychotic; 40% of these received an antipsychotic without any recognized indication. The mean time on antipsychotic therapy was 3 years. Patients on antipsychotic therapy were, on average, taking twice as many total medications as those not on antipsychotic therapy. Patients with psychotic depression were taking an average of nearly twice the antipsychotic dose of nonpsychotic patients. CONCLUSION: Current clinical guidelines commend careful antidepressant choice in preference to polypharmacy. A number of drug choices for specific depressive presentations are summarized from recent sources.